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  • CLASSES

    Serotonin-Dopamine Antagonist (SDA) Antipsychotics

    BOXED WARNING

    Dementia, geriatric, stroke

    Older adult patients have not been shown to be more susceptible to the actions of oral ziprasidone than other adults in clinical studies. However, given the greater incidence of concomitant chronic illness and other conditions in this population, geriatric patients should generally be started on lower doses followed with careful dosage titration, and observed closely. Intramuscular ziprasidone injections have not been evaluated in geriatric patients. Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients. In April 2005 the FDA mandated that all manufacturers of atypical antipsychotics include a boxed warning to the labeling indicating that increased death rates (1.6 to 1.7 times that of placebo) have been noted in this patient population receiving atypical antipsychotics. Death typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). Of 17 placebo controlled trials (n = 5,106) performed with olanzapine, aripiprazole, risperidone, or quetiapine in elderly patients with dementia-related psychosis, 15 showed numerical increases in mortality in the drug-treated group compared to the placebo-treated patients. Additionally, In June 2008, FDA required manufacturers of conventional antipsychotics to also add a boxed warning to their product labeling regarding an increased risk of death in elderly patients with dementia. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. In addition, avoidance of ziprasidone is recommended in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: Parkinson's disease (symptom exacerbation), delirium (possible new-onset or worsening delirium), and dementia (adverse CNS effects). There is an increased risk of stroke and greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics, and the Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. The Panel recommends avoiding antipsychotics in elderly patients with a history of falls or fractures, unless safer alternatives are not available, since antipsychotics can cause ataxia, impaired psychomotor function, syncope, and additional falls; if an antipsychotic must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and that meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. There is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. Therefore, identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic. To initiate antipsychotic therapy, behavioral symptoms must be a danger to self or others and are either 1) due to mania or psychosis or 2) the plan of care includes documentation of attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less with evaluation and documentation within 7 days which identifies and addresses contributors/causes. For acute conditions persisting beyond 7 days, pertinent non-pharmacologic interventions must be attempted, unless clinically contraindicated, and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment, and include monitoring that ensures the behavioral symptoms are not due to a treatable or correctable medical condition, are not due to correctable environmental or treatable psychological stressors alone, and provides clearly documented evidence of persistence. The LTCF must evaluate the appropriateness of the antipsychotic during or within 2 weeks of admission for a newly admitted resident on an antipsychotic. In all cases, the lowest possible dose and shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, rationale for use, and potential adverse effects (e.g., anticholinergic effects, neurological symptoms, metabolic syndrome, cardiac effects). Antipsychotics are subject to periodic review for effectiveness, necessity, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    DEA CLASS

    Rx

    DESCRIPTION

    Dopamine and serotonin antagonist 'atypical' antipsychotic; approved for schizophrenia, bipolar mania, and maintenance treatment of bipolar disorder; lower incidence of EPS than traditional agents; associated with QTc interval prolongation; do not use with other drugs that cause QT prolongation; increased risk of death in elderly patients treated for dementia-related psychosis.

    COMMON BRAND NAMES

    Geodon

    HOW SUPPLIED

    Geodon Intramuscular Inj Pwd F/Sol: 20mg
    Geodon/Ziprasidone/Ziprasidone Hydrochloride Oral Cap: 20mg, 40mg, 60mg, 80mg

    DOSAGE & INDICATIONS

    For the treatment of schizophrenia.
    Oral dosage
    Adults

    Initially, 20 mg PO twice daily with food. Increase as needed at intervals of 2 days or more. Ordinarily observe patient for several weeks before upward dosage adjustment. Usual Max: 80 mg PO twice per day. Periodically reassess to determine the need for maintenance treatment and the appropriate dosage.

    For the treatment of bipolar disorder (bipolar I disorder), including monotherapy treatment of mania or mixed episodes and as an adjunct to lithium or valproate in maintenance therapy.
    Oral dosage
    Adults

    FOR ACUTE MANIA OR MIXED EPISODES AS MONOTHERAPY: Initially, 40 mg PO twice daily with food. On day 2 of treatment, increase to 60 or 80 mg PO twice a day. Thereafter, adjust dose based on tolerability and efficacy within the range 40 to 80 mg PO twice a day. In flexible-dose clinical trials, the mean daily dose administered was approximately 120 mg/day. Clinical trial results, based on the Mania Rating Scale, demonstrated that patients improved with ziprasidone (vs. placebo) by the second day and reached statistical significance by day 21. At endpoint, the reduction in scores was -12.4 and -7.8 for ziprasidone- and placebo-treated groups, respectively. Trials lasted for only 3 weeks, although it is generally agreed that longer-term therapy is required for maintenance of bipolar disorder. MAINTENANCE TREATMENT AS AN ADJUNCT TO LITHIUM OR VALPROATE: Continue at the same dose on which the patient was initially stabilized, within the range of 40 to 80 mg PO twice daily. Efficacy of ziprasidone as an adjunct to lithium or valproate was established in one maintenance trial in adult patients. Periodically re-evaluate the need for continued treatment.

    For the treatment of acute agitation associated with schizophrenia or other psychiatric illness† associated with acute agitation.
    Intramuscular dosage (injection solution; Geodon injection)
    Adults

    10 to 20 mg IM per dose. Doses of 10 mg IM may be given every 2 hours as needed; doses of 20 mg IM may be administered every 4 hours as needed. Max: 40 mg/day IM. Do not administer IM dosage for more than 3 consecutive days. Convert to oral therapy as soon as possible if long term treatment is indicated. There is no experience in administering IM ziprasidone to patients already receiving oral ziprasidone; co-administration is NOT recommended. A reduction in anxiety usually occurs within 15 minutes of an IM dose, with improvement sustained for 4 hours or more after administration. An open-label, pilot study suggests the transition from IM to oral dosing on days 4 to 5 of treatment is well tolerated; no EPS symptoms, acute dystonia, or serious adverse events were reported. While FDA-approved for use in acute agitation due to schizophrenia, use for patients with other acute agitation (i.e., schizoaffective or bipolar disorder) is common in acute settings. Newer antipsychotics which have shown efficacy in treating acute agitation secondary to psychiatric disorders are preferential in emergency use to conventional antipsychotics.

    Geriatric Adults†

    Not FDA approved, safety and efficacy have not been established in controlled clinical trials. Off-label use has been reported in the literature, using the same dosing as for younger adults: 10 to 20 mg IM per dose. Doses of 10 mg IM may be given every 2 hours as needed; doses of 20 mg IM may be administered every 4 hours as needed. Max: 40 mg/day IM. Do not give via IM route for more than 3 consecutive days. Convert to oral therapy as soon as possible if long term treatment is indicated. There is no experience in administering IM ziprasidone to patients already receiving oral ziprasidone and co-use is NOT recommended. Newer antipsychotics which have shown efficacy in treating acute agitation secondary to psychiatric disorders are preferential in emergency use to conventional antipsychotics.

    Children† and Adolescents† 12 years and older

    Not FDA approved, safety and efficacy have not been established in controlled clinical trials. Data are limited; controlled studies are needed. Off-label use has been reported as effective but is reserved for when non-pharmacologic treatment fails or oral treatment is refused. Suggested dosing: 10 mg IM per dose (12 to 16 years), and 10 mg to 20 mg IM per dose (more than 16 years). Sedation appears to be common. Convert to oral therapy as soon as possible if long term treatment is indicated.

    For the treatment of Tourette's syndrome†.
    Oral dosage
    Children and Adolescents 7 years and older

    Initially, 5 mg PO once daily for 3 days, increased thereafter in divided doses as tolerated. Max: 20 mg PO twice daily. At the end of a 56-day pilot study (n = 28), the mean daily dose of ziprasidone was 28.2 +/- 9.6 mg/day (0.64 +/- 0.24 mg/kg/day).

    For the treatment of severe behavioral or psychological symptoms of dementia† (BPSD)†.
    Oral dosage
    Geriatric Adults

    Dosage not established. According to the Agency for Healthcare Research and Quality (AHRQ) atypical antipsychotic review in 2011, ziprasidone had not been studied as an off-label treatment for behavioral disturbances associated with dementia. Antipsychotics are not FDA-approved for the treatment of behavioral problems associated with dementia and the labeling of all antipsychotics contains a boxed warning noting an increased risk of death in geriatric patients being treated for behavioral problems associated with dementia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. Specific criteria for treatment must be met, and adherence to daily dose thresholds for each antipsychotic is required, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. No OBRA Max ziprasidone dosing guidance is available due to lack of safety and efficacy data in these patients. For all antipsychotics, the facility must attempt a gradual dose reduction (GDR) in 2 separate quarters, at least 1 month apart, within the first year of admission to the facility or after the facility has initiated an antipsychotic, unless clinically contraindicated. After the first year, a GDR must be attempted annually unless clinically contraindicated. The GDR may be considered clinically contraindicated if the target symptoms returned or worsened after the most recent GDR attempt within the facility and the physician has documented justification for why attempting additional dose reductions at that time would likely impair the resident's function or increase distressed behavior.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    160 mg/day PO or 40 mg/day IM.

    Geriatric

    160 mg/day PO. 40 mg/day IM is suggested from off-label use.

    Adolescents

    More than 16 years: 40 mg/day PO per Tourette's off-label use. 20 mg/dose IM for acute agitation off-label use has been suggested.
    13 to 16 years: 40 mg/day PO per Tourette's off-label use. 10 mg/dose IM for acute agitation off-label use has been suggested.

    Children

    12 years: 40 mg/day PO per Tourette's off-label use. 10 mg/dose IM for acute agitation off-label use has been suggested.
    7 to 11 years: 40 mg/day PO per Tourette's off-label use. Safety and efficacy have not been established for IM dosing.
    6 years or less: Safety and efficacy have not been established.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    The AUC and half-life of ziprasidone have been increased after oral administration in those with cirrhosis; however, the manufacturer does not require oral dosage adjustments in patients with hepatic impairment. Intramuscular ziprasidone has not been evaluated in patients with hepatic dysfunction.

    Renal Impairment

    Dosage adjustments are not required in patients with renal impairment; however, intramuscular ziprasidone has not been systematically evaluated in patients with renal impairment. Because the cyclodextrin excipient in the intramuscular formulation is cleared by renal filtration, this dosage form should be administered with caution to patients with impaired renal function.
     
    Intermittent hemodialysis
    Ziprasidone is not removed by hemodialysis.

    ADMINISTRATION

    Oral Administration

    Ziprasidone capsules should be administered whole, given with plenty of fluid and at roughly the same times each day. Administer with food to ensure adequate absorption.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution affords a colorless to pale pink color upon dilution.

    Intramuscular Administration

    For administration by the intramuscular (IM) route only; do not administer intravenously. Do not mix with other drugs (i.e., in the same syringe).
    Ziprasidone injection requires reconstitution prior to administration.
     
    Reconstitution instructions:
    Using aseptic technique, add 1.2 ml of Sterile Water for Injection, USP to the single-dose vial and shake vigorously until all the drug is dissolved. The resulting solution contains ziprasidone 20 mg/ml. The solution contains no preservative or bacteriostatic agents; therefore, any remaining solution from a partially used vial should be discarded.
    Do not mix with any other medicinal products or solvents other than Sterile Water for Injection (SWI).
    Following reconstitution, the unused vial can be stored, protected from light, for up to 24 hours at 15—30 degrees C (59—86 degrees F). Alternatively, may store for up to 7 days refrigerated and protected from light at 2—8 degrees C (36—46 degrees F).
     
    Intramuscular (IM) injection:
    Inject ziprasidone slowly and deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh). Aspirate prior to injection to avoid injection into a blood vessel. If possible, keep patient in a recumbent position for at least 30 minutes following injection to minimize any potential hypotensive effects.

    STORAGE

    Geodon:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Serious rash

    Ziprasidone is contraindicated in those with hypersensitivity to ziprasidone or any of its ingredients. Ziprasidone has been associated with serious rash and related cutaneous conditions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a rare but potentially fatal syndrome characterized by symptoms such as rash, fever, lymphadenopathy, eosinophilia, and organ involvement. Other severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, have been reported with ziprasidone exposure. Severe cutaneous adverse reactions are sometimes fatal. Discontinue ziprasidone immediately if severe cutaneous adverse reactions or DRESS are suspected. Patients should be advised to promptly report symptoms of rash, swollen lymph nodes and/or fever.

    Agranulocytosis, leukopenia, neutropenia

    Hematologic effects including leukopenia, neutropenia, and agranulocytosis have been associated with antipsychotic use. A history of drug-induced leukopenia or neutropenia or a pre-existing low white blood cell (WBC) count may increase the likelihood of developing hematologic effects during treatment with an antipsychotic medication like ziprasidone. Patients with a history of clinically significant low WBC count or drug-induced leukopenia/neutropenia should have frequent assessment of complete blood count (CBC) with differential during the first few months of treatment. Discontinuation of ziprasidone should be considered if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Patients with clinically significant neutropenia should be closely monitored for fever and infection, and appropriate medical intervention should be instituted if necessary. Ziprasidone should be discontinued in patients with severe neutropenia (ANC less than 1,000/mm3); ongoing medical care is recommended until the symptoms resolve.

    Acute myocardial infarction, alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, cerebrovascular disease, coronary artery disease, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, hypovolemia, long QT syndrome, malnutrition, myocardial infarction, orthostatic hypotension, QT prolongation, thyroid disease, torsade de pointes

    Clinical trial data indicate that ziprasidone causes QT prolongation; therefore, the drug is contraindicated in patients with a known history of QT prolongation (including congenital long QT syndrome). Ziprasidone is also contraindicated in patients with a recent acute myocardial infarction or uncompensated heart failure. Torsade de pointes has rarely been reported during post-marketing use of the drug. Given the potential for QT prolongation, ziprasidone is contraindicated for use with other drugs that cause QT prolongation. Use ziprasidone with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Baseline magnesium and potassium levels are recommended for high-risk patients, with periodic monitoring as clinically indicated. Females, elderly patients, patients with diabetes, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation. Ziprasidone should be discontinued in any patient with persistent QT interval measurements greater than 500 msec. Prescribers should evaluate symptoms of dizziness, syncope, or palpitations that occur with ziprasidone treatment. Ziprasidone may induce tachycardia and/or orthostatic hypotension and may potentiate hypotension caused by hypovolemia, the presence of antihypertensive drugs, or a dehydrated state. Orthostatic hypotension or syncope is most likely to occur during the dosage titration phase. Therefore, a low initial dosage should be used, followed by gradual dosage titration, in patients with potential risk factors for hypotension. Orthostatic hypotension could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate orthostasis. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Due to the potential orthostatic effects of ziprasidone, caution is recommended in patients with cerebrovascular disease.

    Renal failure, renal impairment

    Ziprasidone is not extensively excreted by the kidney. However, intramuscular ziprasidone injections have not been evaluated in patients with renal impairment or renal failure and the cyclodextrin excipient in the injection is cleared by renal filtration; the injection should be administered with caution to patients with impaired renal function.

    Tardive dyskinesia

    Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Periodic evaluation for movement disorders is recommended (e.g., AIMS). Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the initiation of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotics differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotics administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief periods at low doses or may even arise after drug discontinuation. The syndrome may remit, partially or completely, if the antipsychotic is withdrawn. Antipsychotics may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, ziprasidone should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotics, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic therapy, the smallest dose and the shortest duration producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear, ziprasidone discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

    Ambient temperature increase, dehydration, hyperthermia, hypothermia, strenuous exercise

    Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving ziprasidone should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration). A less frequently described alteration in thermoregulatory processes reported with both conventional and atypical antipsychotics is hypothermia. Thermoregulation is multi-factorial; however, the dopaminergic system appears to have a primary role, and serotonin may also have modulatory activity (5-HT2a receptors). Most cases of hypothermia associated with antipsychotics have occurred in conjunction with other potential precipitating factors such as hypothyroidism, sepsis, organic brain injury, or environmental temperature. Hypothermia appears to occur more frequently during initiation of antipsychotic therapy or after dose increases.

    Hepatic disease

    Ziprasidone is extensively metabolized in the liver. An increase in AUC and half-life has been observed in patients with cirrhosis. Although specific guidelines for dosage adjustments in those with hepatic disease have not been recommended, initiate therapy with caution and titrate upward slowly while monitoring liver function tests (LFTs). Intramuscular ziprasidone injections have not been evaluated in patients with impaired liver function.

    CNS depression, coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion

    Ziprasidone has the potential to impair cognitive and motor skills. The sedative effects of ziprasidone may be most evident in the initial days of treatment. Patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness, until they know how ziprasidone affects their cognition. Somnolence from antipsychotic use could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate somnolence. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Because ziprasidone may cause CNS depression, it is not recommended for use in those with severe CNS depression. Given the primary CNS effects of ziprasidone, caution should be used during coadministration with other CNS depressants and alcohol. Ethanol ingestion may further impair cognitive and motor skills and patients should be advised to avoid use of alcoholic beverages.

    Dysphagia

    Patients with dysphagia or those at risk for aspiration pneumonia should be closely monitored while receiving ziprasidone. The use of antipsychotics has been associated with esophageal dysmotility and aspiration of gastric contents which may increase the incidence of aspiration pneumonia in certain patient populations, such as patients with advanced Alzheimer's disease.

    Diabetes mellitus, hyperglycemia, obesity

    Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. There have been a few cases of hyperglycemia and diabetes reported during treatment with ziprasidone; however, no reports of diabetes mellitus requiring emergency treatment have been reported. It is not known if this lower incidence of reports is due to a lower risk with ziprasidone, due to fewer patients treated with ziprasidone, or some other cause. In epidemiological studies and case reports, atypical antipsychotics have been associated with elevations in blood glucose, decreased insulin sensitivity, and precipitation or unmasking of diabetes mellitus in susceptible patients (see Adverse Reactions). Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available. Patients with pre-existing diabetes mellitus should monitor their blood glucose levels and watch for signs of excessive urination, thirst, weakness and hunger while taking atypical antipsychotics. Additionally, the clinician should regularly monitor the patient for worsening of glucose control. Patients with risk factors for diabetes, such as obesity or a family history of diabetes should undergo fasting glucose testing at baseline and periodically throughout treatment. Patients developing signs or symptoms suggestive of diabetes while receiving an atypical antipsychotic should be tested for diabetes. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.

    Seizure disorder, seizures

    The manufacturer reports that during pre-marketing studies, 0.4% of ziprasidone-treated patients developed seizures, however, confounding factors may have contributed to the occurrence of seizures in many of these cases. Ziprasidone should be used cautiously in those patients with a history of seizure disorder or with conditions that potentially lower the seizure threshold. The continuation of adequate anticonvulsant therapy should prevent an increase in seizure frequency during ziprasidone treatment. If ziprasidone therapy is needed, it should be initiated with a low dosage and titrated upward slowly to the desired clinical effect.

    Suicidal ideation

    Suicidal ideation is inherent in schizophrenia. Ziprasidone should be used with caution in these patients because of the possibility of suicide. Close monitoring of the schizophrenic patient is essential during the initial stages of therapy. Ziprasidone should be prescribed in the smallest quantity consistent with good management in order to reduce the risk of overdose.

    Neurological disease, Parkinson's disease

    Antipsychotics can cause motor and sensory instability, which may lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with diseases (e.g., neurological disease), conditions, or concurrent medication use that could exacerbate motor and sensory instability. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Ziprasidone should be used cautiously in patients with Parkinson's disease. Central blockade of dopamine (D2) receptors may dramatically worsen the extrapyramidal symptoms of Parkinson's disease. If treatment with an antipsychotic is indicated, however, atypical antipsychotics (like ziprasidone) are preferable to conventional antipsychotics due to a lower likelihood of symptom exacerbation from extrapyramidal effects.

    Dementia, geriatric, stroke

    Older adult patients have not been shown to be more susceptible to the actions of oral ziprasidone than other adults in clinical studies. However, given the greater incidence of concomitant chronic illness and other conditions in this population, geriatric patients should generally be started on lower doses followed with careful dosage titration, and observed closely. Intramuscular ziprasidone injections have not been evaluated in geriatric patients. Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients. In April 2005 the FDA mandated that all manufacturers of atypical antipsychotics include a boxed warning to the labeling indicating that increased death rates (1.6 to 1.7 times that of placebo) have been noted in this patient population receiving atypical antipsychotics. Death typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). Of 17 placebo controlled trials (n = 5,106) performed with olanzapine, aripiprazole, risperidone, or quetiapine in elderly patients with dementia-related psychosis, 15 showed numerical increases in mortality in the drug-treated group compared to the placebo-treated patients. Additionally, In June 2008, FDA required manufacturers of conventional antipsychotics to also add a boxed warning to their product labeling regarding an increased risk of death in elderly patients with dementia. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. In addition, avoidance of ziprasidone is recommended in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: Parkinson's disease (symptom exacerbation), delirium (possible new-onset or worsening delirium), and dementia (adverse CNS effects). There is an increased risk of stroke and greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics, and the Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. The Panel recommends avoiding antipsychotics in elderly patients with a history of falls or fractures, unless safer alternatives are not available, since antipsychotics can cause ataxia, impaired psychomotor function, syncope, and additional falls; if an antipsychotic must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and that meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. There is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. Therefore, identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic. To initiate antipsychotic therapy, behavioral symptoms must be a danger to self or others and are either 1) due to mania or psychosis or 2) the plan of care includes documentation of attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less with evaluation and documentation within 7 days which identifies and addresses contributors/causes. For acute conditions persisting beyond 7 days, pertinent non-pharmacologic interventions must be attempted, unless clinically contraindicated, and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment, and include monitoring that ensures the behavioral symptoms are not due to a treatable or correctable medical condition, are not due to correctable environmental or treatable psychological stressors alone, and provides clearly documented evidence of persistence. The LTCF must evaluate the appropriateness of the antipsychotic during or within 2 weeks of admission for a newly admitted resident on an antipsychotic. In all cases, the lowest possible dose and shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, rationale for use, and potential adverse effects (e.g., anticholinergic effects, neurological symptoms, metabolic syndrome, cardiac effects). Antipsychotics are subject to periodic review for effectiveness, necessity, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    Sunlight (UV) exposure

    Photosensitivity reactions (1%) have been reported during clinical trials with ziprasidone. Patients should be warned either to keep out of the sun or to use effective sunscreens (SPF 15+) on exposed areas of the body. Patients should avoid undue sunlight (UV) exposure and the use of tanning beds.

    Breast cancer, hyperprolactinemia, infertility

    Similar to other antipsychotics, ziprasidone can cause hyperprolactinemia, likely due to central dopamine D2 antagonism.Although endocrine disturbances such as galactorrhea, amenorrhea, gynecomastia, impotence and infertility have been reported with prolactin-elevating compounds, the clinical significance of elevated serum prolactin levels is unknown for most patients. Chronic hyperprolactinemia when associated with hypogonadism may lead to decreased bone density (osteopenia). Some human breast cancers may be prolactin-dependent and therefore most antipsychotics should be used cautiously in those who have a history of breast cancer; mammary gland neoplasia was noted in mice during animal studies of ziprasidone, but not in rats and the clinical implications for humans are unclear.

    Neonates, pregnancy, pregnancy testing

    Ziprasidone should be used during pregnancy only if the benefits outweigh the potential risks to the fetus. Although the effects in pregnant women are unknown, animals studies indicate that ziprasidone may cause fetal structural abnormalities, decreased fetal weight, delayed skeletal ossification, and decreased postnatal survival. Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity and have ranged from self-limited to those requiring intensive care unit support and prolonged hospitalization. Neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal should be carefully monitored. The knowledge about long-term neurobehavioral effects in offspring is limited for all antipsychotic agents and requires further investigation. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. The National Pregnancy Registry for Psychiatric Medications is dedicated to evaluating the safety of psychiatric medications that may be taken by women during pregnancy to treat a wide range of mood, anxiety, or psychiatric disorders. The primary goal of this Registry is to determine the frequency of major malformations, such as heart defects, cleft lip, or neural tube defects, in babies exposed to various psychiatric drugs during pregnancy. While the research concentrates on atypical antipsychotics and antidepressant use, pregnant women using other psychiatric medications are encouraged to register. For more information, contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by phone 1-866-961-2388. It is not known if antipsychotics, through their effect on prolactin, would affect labor or obstetric delivery.

    Breast-feeding

    According to the manufacturer, it is not known if ziprasidone or its metabolites are excreted in breast milk and it is recommended that women receiving ziprasidone should not breast-feed. However, in one case report, the use of ziprasidone 160 mg/day for one week resulted in a milk to plasma ratio of 0.06 and a relative infant dose of 1.2%. In a separate case, no adverse effects on the growth and development occurred in one nursing infant after maternal use of ziprasidone 40 mg/day for 6 months during breast-feeding. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. There is very limited experience with ziprasidone during breast-feeding; other agents may be preferred especially while nursing a newborn or preterm infant. Alternate medications for consideration include atypical agents such as olanzapine or quetiapine. Data related to the safety of antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children, infants

    Safety and efficacy of ziprasidone use in children and adolescents under the age of 18 years have not been established. Limited data exist regarding the off-label use of oral ziprasidone in pediatric patients 7 years of age or older, and the use of IM ziprasidone for acute agitation secondary to psychiatric disorders in adolescents. Routine cardiovascular monitoring has been suggested for any children receiving certain psychotropic medications due to the potential of these agents to produce adverse cardiac effects. Monitor the electrocardiogram (ECG) in children taking ziprasidone. Avoid use of this drug in children who have known cardiac conduction defects or congenital heart disease (i.e. congenital long QT syndrome). There is no known use of ziprasidone in infants. Additionally, adverse effects have been reported after delivery in newborns exposed to antipsychotics during the third trimester; these effects have varied in severity ranging from self-limited to requiring intensive care unit stays and prolonged hospitalization.

    Abrupt discontinuation

    Abrupt discontinuation of ziprasidone is not recommended, unless required by the patient's medical condition. Otherwise discontinuation should usually occur via a gradual 1—2 week reduction in dosage. Patients should be carefully observed for the recurrence of psychotic symptoms during drug discontinuation.

    Priapism

    Drugs with alpha-adrenergic blocking effects have been reported to induce priapism. One case of priapism was reported during pre-marketing evaluation of ziprasidone. Priapism requires medical treatment and severe cases may require surgical intervention. Advise male patients to seek medical intervention if they experience a prolonged or painful erection lasting more than 4 hours. The patient should call their healthcare provider or go to the nearest emergency room right away if this occurs.

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 3.0-6.0
    bradycardia / Rapid / 0-2.0
    exfoliative dermatitis / Delayed / 0.1-1.0
    muscle paralysis / Delayed / 0.1-1.0
    atrial fibrillation / Early / 0.1-1.0
    seizures / Delayed / 0.4-0.4
    myocarditis / Delayed / 0-0.1
    torticollis / Delayed / 0-0.1
    hematemesis / Delayed / 0-0.1
    AV block / Early / 0-0.1
    stroke / Early / 0-0.1
    pulmonary embolism / Delayed / 0-0.1
    laryngospasm / Rapid / 0-0.1
    oliguria / Early / 0-0.1
    keratitis / Delayed / 0-0.1
    ocular hemorrhage / Delayed / 0-0.1
    keratoconjunctivitis / Early / 0-0.1
    hyperkalemia / Delayed / 0-0.1
    akinesia / Delayed / 1.0
    tardive dyskinesia / Delayed / 1.0
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    pericarditis / Delayed / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    neuroleptic malignant syndrome / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known

    Moderate

    akathisia / Delayed / 0-10.0
    constipation / Delayed / 0-9.0
    chest pain (unspecified) / Early / 3.0-3.0
    sinus tachycardia / Rapid / 2.0-2.0
    dysphagia / Delayed / 0.1-2.0
    atopic dermatitis / Delayed / 0.1-1.0
    eosinophilia / Delayed / 0.1-1.0
    lymphadenopathy / Delayed / 0.1-1.0
    contact dermatitis / Delayed / 0.1-1.0
    psychosis / Early / 0-1.0
    angina / Early / 0.1-1.0
    peripheral vasodilation / Rapid / 0-1.0
    galactorrhea / Delayed / 0.1-1.0
    priapism / Early / 0-1.0
    ejaculation dysfunction / Delayed / 0.1-1.0
    impotence (erectile dysfunction) / Delayed / 0.1-1.0
    hematuria / Delayed / 0.1-1.0
    urinary retention / Early / 0.1-1.0
    glycosuria / Early / 0.1-1.0
    blepharitis / Early / 0.1-1.0
    conjunctivitis / Delayed / 0.1-1.0
    photophobia / Early / 0.1-1.0
    cataracts / Delayed / 0.1-1.0
    synovitis / Delayed / 0.1-1.0
    hyperglycemia / Delayed / 0.1-1.0
    leukopenia / Delayed / 0.1-1.0
    anemia / Delayed / 0.1-1.0
    hypokalemia / Delayed / 0.1-1.0
    dehydration / Delayed / 0.1-1.0
    elevated hepatic enzymes / Delayed / 0.1-1.0
    peripheral edema / Delayed / 0.1-1.0
    hepatitis / Delayed / 0-0.1
    trismus / Delayed / 0-0.1
    myoclonia / Delayed / 0-0.1
    nystagmus / Delayed / 0-0.1
    hyperreflexia / Delayed / 0-0.1
    melena / Delayed / 0-0.1
    phlebitis / Rapid / 0-0.1
    bundle-branch block / Early / 0-0.1
    hemoptysis / Delayed / 0-0.1
    vaginal bleeding / Delayed / 0-0.1
    myopathy / Delayed / 0-0.1
    lymphocytosis / Delayed / 0-0.1
    thrombocytopenia / Delayed / 0-0.1
    polycythemia / Delayed / 0-0.1
    hypothyroidism / Delayed / 0-0.1
    hyperthyroidism / Delayed / 0-0.1
    hyperuricemia / Delayed / 0-0.1
    hypomagnesemia / Delayed / 0-0.1
    gout / Delayed / 0-0.1
    hypocalcemia / Delayed / 0-0.1
    hypochloremia / Delayed / 0-0.1
    hyperchloremia / Delayed / 0-0.1
    hypoglycemia / Early / 0-0.1
    hyponatremia / Delayed / 0-0.1
    hepatomegaly / Delayed / 0-0.1
    steatosis / Delayed / 0-0.1
    jaundice / Delayed / 0-0.1
    dyskinesia / Delayed / 1.0
    choreoathetosis / Delayed / 1.0
    pseudoparkinsonism / Delayed / 1.0
    dystonic reaction / Delayed / 1.0
    hypertonia / Delayed / 1.0
    delirium / Early / 1.0
    hostility / Early / 1.0
    amnesia / Delayed / 1.0
    confusion / Early / 1.0
    hypotonia / Delayed / 1.0
    ataxia / Delayed / 1.0
    peripheral neuropathy / Delayed / 1.0
    withdrawal / Early / 1.0
    orthostatic hypotension / Delayed / 1.0
    hypertension / Early / 1.0
    dyspnea / Early / 1.0
    dysarthria / Delayed / 1.0
    flank pain / Delayed / 1.0
    bullous rash / Early / Incidence not known
    pneumonitis / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    mania / Early / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known
    urinary incontinence / Early / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known

    Mild

    drowsiness / Early / 8.0-31.0
    insomnia / Early / 0-30.0
    weight gain / Delayed / 2.4-20.0
    headache / Early / 3.0-18.0
    dizziness / Early / 3.0-16.0
    nausea / Early / 4.0-12.0
    injection site reaction / Rapid / 7.0-9.0
    dyspepsia / Early / 1.0-8.0
    infection / Delayed / 0.1-8.0
    asthenia / Delayed / 2.0-6.0
    rash / Early / 3.0-5.0
    anxiety / Delayed / 0-5.0
    vomiting / Early / 0-5.0
    xerostomia / Early / 0-5.0
    diarrhea / Early / 0-5.0
    hypersalivation / Early / 4.0-4.0
    rhinitis / Early / 0-4.0
    pharyngitis / Delayed / 3.0-3.0
    cough / Delayed / 3.0-3.0
    hyperhidrosis / Delayed / 0-2.0
    agitation / Early / 0-2.0
    paresthesias / Delayed / 0-2.0
    anorexia / Delayed / 0-2.0
    dysmenorrhea / Delayed / 0-2.0
    maculopapular rash / Early / 0.1-1.0
    vesicular rash / Delayed / 0.1-1.0
    alopecia / Delayed / 0.1-1.0
    urticaria / Rapid / 0.1-1.0
    amenorrhea / Delayed / 0.1-1.0
    orgasm dysfunction / Delayed / 0.1-1.0
    epistaxis / Delayed / 0.1-1.0
    menorrhagia / Delayed / 0.1-1.0
    polyuria / Early / 0.1-1.0
    xerophthalmia / Early / 0.1-1.0
    back pain / Delayed / 0-1.0
    leukocytosis / Delayed / 0.1-1.0
    ecchymosis / Delayed / 0.1-1.0
    tinnitus / Delayed / 0.1-1.0
    polydipsia / Early / 0.1-1.0
    gynecomastia / Delayed / 0-0.1
    nocturia / Early / 0-0.1
    tremor / Early / 1.0
    hyperkinesis / Delayed / 1.0
    vertigo / Early / 1.0
    abdominal pain / Early / 1.0
    photosensitivity / Delayed / 1.0
    influenza / Delayed / 1.0
    fever / Early / 1.0
    diplopia / Early / 1.0
    myalgia / Early / 1.0
    chills / Rapid / 1.0
    syncope / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including abarelix.
    Acarbose: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Acetaminophen; Butalbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Acetaminophen; Butalbital; Caffeine: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including dihydrocodeine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Acetaminophen; Codeine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Drugs that can cause CNS depression, including dichloralphenazone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness if used concomitantly with atypical antipsychotics.
    Acetaminophen; Diphenhydramine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Acetaminophen; Hydrocodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including oxycodone.
    Acetaminophen; Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Acetaminophen; Propoxyphene: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including propoxyphene.
    Acetaminophen; Tramadol: (Moderate) Concurrent use of tramadol and ziprasidone should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and ziprasidone.
    Albiglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
    Alfentanil: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including alfentanil.
    Alfuzosin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including alfuzosin.
    Aliskiren; Amlodipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Alogliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alogliptin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alogliptin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alpha-glucosidase Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alprazolam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Amiloride: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amiloride; Hydrochlorothiazide, HCTZ: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amiodarone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including amiodarone.
    Amitriptyline: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Amitriptyline; Chlordiazepoxide: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Amlodipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amlodipine; Atorvastatin: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amlodipine; Benazepril: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amlodipine; Olmesartan: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amlodipine; Telmisartan: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amlodipine; Valsartan: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Amobarbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Amoxapine: (Moderate) Use caution during co-administration of amoxapine and ziprasidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
    Amoxicillin; Clarithromycin; Lansoprazole: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including clarithromycin.
    Amoxicillin; Clarithromycin; Omeprazole: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including clarithromycin.
    Amphetamine: (Major) Ziprasidone should be used cautiously with drugs that are known to lower seizure threshold such as amphetamine or dextroamphetamine. Also, ziprasidone has a risk for QT prolongation, and amphetamines can potentially sensitize the myocardium.
    Amphetamine; Dextroamphetamine Salts: (Major) Ziprasidone should be used cautiously with drugs that are known to lower seizure threshold such as amphetamine or dextroamphetamine. Also, ziprasidone has a risk for QT prolongation, and amphetamines can potentially sensitize the myocardium.
    Amphetamine; Dextroamphetamine: (Major) Ziprasidone should be used cautiously with drugs that are known to lower seizure threshold such as amphetamine or dextroamphetamine. Also, ziprasidone has a risk for QT prolongation, and amphetamines can potentially sensitize the myocardium.
    Anagrelide: (Severe) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs.
    Angiotensin II receptor antagonists: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Angiotensin-converting enzyme inhibitors: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Apalutamide: (Moderate) Monitor for decreased efficacy of ziprasidone if coadministration with apalutamide is necessary. Ziprasidone is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ziprasidone exposure by 35%.
    Apomorphine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including apomorphine.
    Aprepitant, Fosaprepitant: (Major) Use caution if ziprasidone and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ziprasidone-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ziprasidone is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ziprasidone. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aripiprazole: (Severe) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Because of the potential for QT prolongation and torsade de pointes (TdP), concurrent use of ziprasidone and aripiprazole is contraindicated.
    Arsenic Trioxide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including arsenic trioxide.
    Artemether; Lumefantrine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including artemether; lumefantrine.
    Articaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine, and possibly of other adrenergic agonists, can be blocked during concurrent administration of ziprasidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with alpha-1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension.
    Asenapine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of asenapine, the drug can cause QT prolongation; therefore, use with ziprasidone is contraindicated. In addition, coadministration of ziprasidone with atypical agents may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures .Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including dihydrocodeine.
    Aspirin, ASA; Carisoprodol: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including carisoprodol.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including carisoprodol. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Aspirin, ASA; Oxycodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including oxycodone.
    Atazanavir: (Major) Avoid coadministration when possible. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of ziprasidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and ziprasidone. Downward dosage adjustment of ziprasidone may be necessary.
    Atazanavir; Cobicistat: (Major) Avoid coadministration when possible. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of ziprasidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and ziprasidone. Downward dosage adjustment of ziprasidone may be necessary. (Moderate) The plasma concentrations of ziprasidone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ziprasidone is a CYP3A4 substrate.
    Atomoxetine: (Severe) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including atomoxetine.
    Atropine; Difenoxin: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including diphenoxylate/difenoxin.
    Atropine; Diphenoxylate: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including diphenoxylate/difenoxin.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Azithromycin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including azithromycin.
    Baclofen: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including baclofen.
    Barbiturates: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Bedaquiline: (Severe) Due to the potential for torsade de pointes (TdP), concurrent use of ziprasidone with bedaquiline is contraindicated. Prolongation of the QT interval is known to occur with both drugs, and coadministration may result in additive QT prolongation.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Belladonna; Opium: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including opium.
    Benzodiazepines: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Benzphetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Bepridil: (Severe) Bepridil is associated with a well-established risk of QT prolongation and torsades de pointes and is contraindicated for use with drugs that prolong the QT interval due to the risk of TdP, including ziprasidone.
    Beta-adrenergic blockers: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Beta-agonists: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Severe) Potential QT prolongation has been reported in limited case reports with metronidazole. Because of the potential for TdP, use of ziprasidone with metronidazole is contraindicated.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Severe) Potential QT prolongation has been reported in limited case reports with metronidazole. Because of the potential for TdP, use of ziprasidone with metronidazole is contraindicated.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering ziprasidone with boceprevir due to an increased potential for ziprasidone-related adverse events. If ziprasidone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ziprasidone. Ziprasidone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ziprasidone plasma concentrations.
    Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as ziprasidone. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
    Bromocriptine: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine. Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
    Brompheniramine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Brompheniramine; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Buprenorphine: (Severe) Due to the potential for QT prolongation and/or torsades de pointes (TdP), use of ziprasidone with buprenorphine is contraindicated. Both buprenorphine and ziprasidone have been associated with QT prolongation and have a possible risk of TdP. Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Buprenorphine; Naloxone: (Severe) Due to the potential for QT prolongation and/or torsades de pointes (TdP), use of ziprasidone with buprenorphine is contraindicated. Both buprenorphine and ziprasidone have been associated with QT prolongation and have a possible risk of TdP. Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
    Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
    Buspirone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Butabarbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Butorphanol: (Moderate) Concomitant use of butorphanol with other central nervous system (CNS) depressants, such as ziprasidone, can potentiate the effects of butorphanol and may lead to additive CNS or respiratory depression. Prior to concurrent use of butorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, a reduced dosage of butorphanol and/or ziprasidone may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
    Cabergoline: (Major) The prolactin-lowering effect of cabergoline may be antagonized by antipsychotic medications that increase prolactin levels. In addition, cabergoline, which is a dopamine agonist, may diminish the effectiveness of dopamine antagonists such as the antipsychotics. In general, however, atypical antipsychotics like ziprasidone are less likely to interfere with these therapies than traditional antipsychotic agents.
    Canagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Canagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Capsaicin; Metaxalone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including metaxalone.
    Carbamazepine: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone. Decreased anticonvulsant efficacy is a possibility when some antipsychotic or antidepressant agents are administered to patients with a seizure disorder, because some of these drugs lower the seizure threshold. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with ziprasidone.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbidopa; Levodopa: (Major) Antipsychotic agents may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain. In general, however, the 'atypical antipsychotics' are less likely to interfere with these therapies than traditional antipsychotic agents (e.g., phenothiazines). Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments. In general, experts consider quetiapine the atypical antipsychotic of choice in Parkinson's patients due to a lower incidence of extrapyramidal symptoms, although the choice of antipsychotic medication must always be made on a case-by-case decision.
    Carbidopa; Levodopa; Entacapone: (Major) Antipsychotic agents may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain. In general, however, the 'atypical antipsychotics' are less likely to interfere with these therapies than traditional antipsychotic agents (e.g., phenothiazines). Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments. In general, experts consider quetiapine the atypical antipsychotic of choice in Parkinson's patients due to a lower incidence of extrapyramidal symptoms, although the choice of antipsychotic medication must always be made on a case-by-case decision. (Major) Atypical antipsychotics are central dopamine antagonists and may inhibit the clinical response to antiparkinsonian agents with dopamine agonist properties by blocking dopamine receptors in the brain. Due to the CNS depressant effects of atypical antipsychotics, additive drowsiness may occur with Parkinson's treatments like entacapone or tolcapone. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents.
    Carbinoxamine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Carbinoxamine; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Carbinoxamine; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Carisoprodol: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including carisoprodol.
    Ceritinib: (Major) Avoid coadministration of ceritinib with ziprasidone due to an increased risk of QT prolongation and torsade de pointes (TdP). If coadministration cannot be avoided, conduct periodic monitoring with electrocardiograms (ECGs) and electrolytes. Concentration-dependent QT prolongation has been reported with ceritinib. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Cetrorelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs including cetrorelix.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Chlorcyclizine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Chlordiazepoxide: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Chlordiazepoxide; Clidinium: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Chloroquine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including chloroquine.
    Chlorpheniramine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Chlorpheniramine; Codeine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Chlorpheniramine; Dextromethorphan: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including dihydrocodeine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including dihydrocodeine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Chlorpheniramine; Hydrocodone: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Chlorpheniramine; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Chlorpromazine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Because chlorpromazine has an established risk of QT prolongation and TdP, concurrent use with ziprasidone should be considered contraindicated. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Chlorthalidone; Clonidine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Chlorzoxazone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including chlorzoxazone.
    Ciprofloxacin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including ciprofloxacin.
    Cisapride: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including cisapride.
    Citalopram: (Severe) Because citalopram is associated with a dose-dependent QT prolongation and ziprasidone has an established association with QT prolongation and torsade de pointes, concurrent use of ziprasidone and citalopram is considered contraindicated. Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with drugs that are dopamine antagonists such as ziprasidone. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving ziprasidone and citalopram should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Clarithromycin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including clarithromycin.
    Class IA Antiarrhythmics: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including Class IA antiarrhythmics.
    Clemastine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Clobazam: (Moderate) Benzodiazepines such as clobazam should be combined cautiously with antipsychotics because of the potential for additive CNS depressant effects, and reduced effectiveness of clobazam as an anticonvulsant due to the possible lowering of the seizure threshold by antipsychotics.
    Clomipramine: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Clonazepam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Clonidine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Clorazepate: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Clozapine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. At elevated serum concentrations, clozapine may produce clinically significant prolongation of the QTc interval and is contraindicated with ziprasidone. In addition, coadministration of ziprasidone with atypical agents may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Cobicistat: (Moderate) The plasma concentrations of ziprasidone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ziprasidone is a CYP3A4 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of ziprasidone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ziprasidone is a CYP3A4 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of ziprasidone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ziprasidone is a CYP3A4 substrate.
    Codeine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Codeine; Guaifenesin: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Codeine; Phenylephrine; Promethazine: (Severe) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and ziprasidone is considered contraindicated. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    Codeine; Promethazine: (Severe) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and ziprasidone is considered contraindicated. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including codeine.
    COMT inhibitors: (Major) Atypical antipsychotics are central dopamine antagonists and may inhibit the clinical response to antiparkinsonian agents with dopamine agonist properties by blocking dopamine receptors in the brain. Due to the CNS depressant effects of atypical antipsychotics, additive drowsiness may occur with Parkinson's treatments like entacapone or tolcapone. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents.
    Conivaptan: (Major) According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as ziprasidone, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with ziprasidone. Treatment with ziprasidone may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Crizotinib: (Major) Concomitant use of ziprasidone and crizotinib should be avoided due to a potential for additive QT prolongation; ziprasidone plasma concentrations may also increase. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Crizotinib has been associated with concentration-dependent QT prolongation.
    Cyclobenzaprine: (Severe) Cyclobenzaprine is structurally similar to tricyclic antidepressants. Tricyclic antidepressants have been reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). Cyclobenzaprine is associated with a possible risk of QT prolongation and torsades de pointes (TdP), particularly in the event of acute overdose. Because of the potential for TdP, use of ziprasidone with cyclobenzaprine is contraindicated.
    Cyproheptadine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Danazol: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of ziprasidone. Patients receiving ziprasidone should be closely monitored for toxicity if danazol is added to therapy.
    Dantrolene: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including dantrolene.
    Dapagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Dapagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Dapagliflozin; Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Darunavir: (Major) The plasma concentrations of ziprasidone may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while ziprasidone is a CYP3A4 substrate.
    Darunavir; Cobicistat: (Major) The plasma concentrations of ziprasidone may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while ziprasidone is a CYP3A4 substrate. (Moderate) The plasma concentrations of ziprasidone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ziprasidone is a CYP3A4 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) Concurrent use of ziprasidone and ritonavir is contraindicated due to the risk of QT prolongation. Ritonavir has been associated with QT prolongation. Ziprasidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes. Per the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs.
    Dasatinib: (Major) Concomitant use of ziprasidone and dasatinib should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Daunorubicin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including daunorubicin.
    Degarelix: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including degarelix.
    Desipramine: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Deutetrabenazine: (Major) Concomitant use of ziprasidone and deutetrabenazine should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Clinically relevant QTc prolongation may occur with deutetrabenazine. Additionally, deutetrabenazine is a reversible, dopamine-depleting drug, and ziprasidone is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as ziprasidone, may have additive effects and worsen drowsiness or sedation.
    Dexchlorpheniramine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Dexmethylphenidate: (Moderate) Atypical antipsychotics and dexmethylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Dexmethylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of dexmethylphenidate.
    Dextroamphetamine: (Major) Ziprasidone should be used cautiously with drugs that are known to lower seizure threshold such as amphetamine or dextroamphetamine. Also, ziprasidone has a risk for QT prolongation, and amphetamines can potentially sensitize the myocardium.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Dextromethorphan; Promethazine: (Severe) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and ziprasidone is considered contraindicated.
    Dextromethorphan; Quinidine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including Class IA antiarrhythmics.
    Diazepam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including dihydrocodeine.
    Diltiazem: (Major) Diltiazem may reduce ziprasidone metabolism via inhibition of CYP3A4 isoenzymes. In addition, additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Dimenhydrinate: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Diphenhydramine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Diphenhydramine; Ibuprofen: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Diphenhydramine; Naproxen: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Diphenhydramine; Phenylephrine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Disopyramide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including Class IA antiarrhythmics.
    Dofetilide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including dofetilide.
    Dolasetron: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including dolasetron.
    Dolutegravir; Rilpivirine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including rilpivirine.
    Donepezil: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Therefore, concurrent use of ziprasidone and donepezil is contraindicated.
    Donepezil; Memantine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Therefore, concurrent use of ziprasidone and donepezil is contraindicated.
    Dopamine: (Moderate) The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of ziprasidone.
    Doxazosin: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Doxepin: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Doxorubicin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including doxorubicin.
    Doxylamine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Doxylamine; Pyridoxine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Dronabinol, THC: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Dronedarone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including dronedarone.
    Droperidol: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including droperidol.
    Dulaglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Efavirenz: (Severe) Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including efavirenz.
    Efavirenz; Emtricitabine; Tenofovir: (Severe) Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including efavirenz.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Severe) Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including efavirenz.
    Elbasvir; Grazoprevir: (Major) Administering ziprasidone with grazoprevir may result in elevated ziprasidone plasma concentrations. Ziprasidone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: (Severe) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Because of the potential for torsades de pointes (TdP), use of ziprasidone with eliglustat is contraindicated.
    Empagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Empagliflozin; Linagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Empagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including rilpivirine.
    Enalapril; Felodipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Encorafenib: (Major) Avoid coadministration of encorafenib and ziprasidone due to the potential for additive QT prolongation. Encorafenib is associated with dose-dependent prolongation of the QT interval. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors.
    Enflurane: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including enflurane.
    Entacapone: (Major) Atypical antipsychotics are central dopamine antagonists and may inhibit the clinical response to antiparkinsonian agents with dopamine agonist properties by blocking dopamine receptors in the brain. Due to the CNS depressant effects of atypical antipsychotics, additive drowsiness may occur with Parkinson's treatments like entacapone or tolcapone. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents.
    Epinephrine: (Major) The alpha-adrenergic effects of epinephrine, and possibly of other adrenergic agonists, can be blocked during concurrent administration of ziprasidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with alpha-1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension.
    Epirubicin: (Severe) Acute cardiotoxicity can occur during the administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Because of the potential for torsades de pointes (TdP), use of ziprasidone with epirubicin is contraindicated.
    Eplerenone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Epoprostenol: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Eribulin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including eribulin.
    Ertugliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ertugliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ertugliflozin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Erythromycin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including erythromycin.
    Erythromycin; Sulfisoxazole: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including erythromycin.
    Escitalopram: (Severe) Because of the potential for QT prolongation and torsade de pointes (TdP), concurrent use of ziprasidone and escitalopram is contraindicated.
    Eslicarbazepine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with eslicarbazepine.
    Estazolam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
    Ethanol: (Moderate) Alcohol may potentiate the CNS effects of the atypical antipsychotics, which have the potential to cause increased sedation, or to impair judgment, thinking, or motor skills. Patients should be appropriately cautioned.
    Ethotoin: (Major) Hydantoins may induce hepatic microsomal enzymes, leading to increased clearance of ziprasidone. Some antipsychotics may also increase CNS depression and also may lower the seizure threshold, producing a pharmacodynamic interaction with anticonvulsants. Adequate dosages of the anticonvulsant should be continued when an antipsychotic drug is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either drug.
    Exenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ezogabine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including ezogabine.
    Felodipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Fentanyl: (Major) Concomitant use of opiate agonists with ziprasidone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with ziprasidone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking ziprasidone, use a lower initial dose of the opiate and titrate to clinical response. If ziprasidone is prescribed for a patient taking an opiate agonist, use a lower initial dose of ziprasidone and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Fingolimod: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including fingolimod.
    Flecainide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including flecainide.
    Fluconazole: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including fluconazole.
    Fluoxetine: (Severe) Fluoxetine is contraindicated for use with ziprasidone. Both ziprasidone and fluoxetine are associated with a risk for QT prolongation and torsade de pointes (TdP). In addition, the metabolite of fluoxetine is a moderate CYP3A4 inhibitor and may decrease the clearance of CYP3A4 substrates such as ziprasidone. Decreased metabolism of ziprasidone may lead to clinically important adverse reactions such as extrapyramidal symptoms or QT prolongation.
    Fluoxetine; Olanzapine: (Severe) Coadministration of ziprasidone and olanzapine is contraindicated due to the potential for QT prolongation and torsade de pointes. In addition, coadministration of ziprasidone with olanzapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. (Severe) Fluoxetine is contraindicated for use with ziprasidone. Both ziprasidone and fluoxetine are associated with a risk for QT prolongation and torsade de pointes (TdP). In addition, the metabolite of fluoxetine is a moderate CYP3A4 inhibitor and may decrease the clearance of CYP3A4 substrates such as ziprasidone. Decreased metabolism of ziprasidone may lead to clinically important adverse reactions such as extrapyramidal symptoms or QT prolongation.
    Fluphenazine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Fluphenazine is associated with a possible risk for QT prolongation and TdP based on varying levels of documentation and is contraindicated with ziprasidone.
    Flurazepam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Fluvoxamine: (Major) Concomitant use of ziprasidone and fluvoxamine should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. In addition, fluvoxamine is a moderate CYP3A4 inhibitor and may decrease the clearance of CYP3A4 substrates such as ziprasidone. Decreased metabolism of ziprasidone may lead to adverse reactions, such as extrapyramidal symptoms or QT prolongation.
    Food: (Major) It is recommended that patients avoid the use of marijuana, by any route, if they are treated for a psychiatric history, including psychosis and bipolar disorder, as the cannabinoids (the psychoactive ingredients, such as THC) in marijuana can produce psychotoxic effects and may exacerbate psychiatric disorders. A high frequency of use and use of products with high-potency of THC are potential risk factors for psychiatric effects. Additionally, additive CNS effects, such as sedation or CNS depression are possible. Clinical studies suggest that cannabis use may reduce the efficacy of some antipsychotic drugs. In addition, several cannabinoids in marijuana appear to influence the activity of CYP enzymes and P-glycoprotein, which may alter the concentrations of antipsychotics and influence either safety or efficacy, For example, the smoking of marijuana influences the metabolism of some medications in a manner similar to tobacco by inducing CYP1A2.
    Foscarnet: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsade de pointes including foscarnet.
    Fosphenytoin: (Major) Hydantoins may induce hepatic microsomal enzymes, leading to increased clearance of ziprasidone. Some antipsychotics may also increase CNS depression and also may lower the seizure threshold, producing a pharmacodynamic interaction with anticonvulsants. Adequate dosages of the anticonvulsant should be continued when an antipsychotic drug is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either drug.
    Ganirelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to ganirelix, a gonadotropin-releasing hormone (GnRH) analog.
    Gemifloxacin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including gemifloxacin.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with ziprasidone due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors.
    Glipizide; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glyburide; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Goserelin: (Severe) Goserelin use is contraindicated with ziprasidone, due to the risk for QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (tdP). Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Granisetron: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including granisetron.
    Guaifenesin; Hydrocodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Guanabenz: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Guanfacine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Halofantrine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including halofantrine.
    Haloperidol: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Haloperidol is associated with a possible risk for QT prolongation and TdP based on varying levels of documentation and is contraindicated with ziprasidone. In addition, coadministration of ziprasidone with haloperidol may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Halothane: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including halothane.
    Histrelin: (Major) Avoid concomitant use of ziprasidone and histrelin due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Androgen deprivation therapy (e.g., histrelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Homatropine; Hydrocodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Hydantoins: (Major) Hydantoins may induce hepatic microsomal enzymes, leading to increased clearance of ziprasidone. Some antipsychotics may also increase CNS depression and also may lower the seizure threshold, producing a pharmacodynamic interaction with anticonvulsants. Adequate dosages of the anticonvulsant should be continued when an antipsychotic drug is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either drug.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Hydrochlorothiazide, HCTZ; Triamterene: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Hydrocodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Hydrocodone; Ibuprofen: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Hydrocodone; Phenylephrine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Hydrocodone; Pseudoephedrine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydrocodone.
    Hydromorphone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including hydromorphone.
    Hydroxychloroquine: (Severe) Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In a study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for TdP including hydroxychloroquine.
    Hydroxyzine: (Severe) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including hydroxyzine.
    Ibuprofen; Oxycodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including oxycodone.
    Ibutilide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including ibutilide.
    Idarubicin: (Severe) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Because of the potential for torsades de pointes (TdP), use of ziprasidone with idarubicin is contraindicated.
    Idelalisib: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ziprasidone, a CYP3A substrate, as ziprasidone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of iloperidone, the drug can cause QT prolongation; therefore, use with ziprasidone is contraindicated. In addition, coadministration of ziprasidone with atypical agents may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Iloprost: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Imatinib: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme system. The concurrent use of ziprasidone with CYP3A4 inhibitors, such as imatinib, may lead to decreased metabolism of ziprasidone.
    Imipramine: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Incretin Mimetics: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with ziprasidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP.
    Insulin Degludec; Liraglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Insulin Glargine; Lixisenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Insulins: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with ziprasidone may result in increased serum concentrations of ziprasidone. Ziprasidone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as extrapyramidal symptoms and CNS effects, are advised if these drugs are used together.
    Isocarboxazid: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Isoflurane: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including isoflurane.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4, such as rifampin. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone.
    Isoniazid, INH; Rifampin: (Moderate) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4, such as rifampin. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone.
    Isradipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Itraconazole: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Itraconazole has been associated with prolongation of the QT interval. Therefore, concurrent use of ziprasidone and itraconazole is contraindicated.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and ziprasidone concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as ziprasidone, can increase ziprasidone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Kava Kava, Piper methysticum: (Major) Patients who are taking atypical antipsychotics should only use kava kava with prescriber approval and close monitoring. Additive sedation and CNS effects are possible, and inhibition of antipsychotic metabolism may occur. In addition, kava kava has been reported to inhibit many CYP isozymes (i.e., CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A9/11) and important pharmacokinetic interactions with CNS-active agents that undergo oxidative metabolism via these CYP isozymes are possible. Atypical antipsychotics are metabolized by various CYP isoenzymes and it is not yet documented if pharmacokinetic interactions occur with kava kava. At least 1 case report of a potential clinically significant interaction with kava kava and an atypical antipsychotic has been reported.
    Ketoconazole: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ketoconazole has been associated with prolongation of the QT interval. Also, ziprasidone is partially metabolized via CYP3A4. The concurrent use of ziprasidone with ketoconazole, a potent CYP3A4 inhibitor, causes a 35 to 40% increase in the AUC and Cmax of ziprasidone. While the inhibition of ziprasidone metabolism did not further increase the QTc interval above the administration of ziprasidone alone in this study, some patients might experience such side effects.
    Lapatinib: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including lapatinib.
    Lenvatinib: (Severe) Because of the potential for torsades de pointes (TdP), use of ziprasidone with lenvatinib is contraindicated. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ziprasidone; monitor for potential reduction in efficacy. Ziprasidone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ziprasidone; monitor for potential reduction in efficacy. Ziprasidone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) An increase in the plasma concentration of ziprasidone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Ziprasidone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent use of ziprasidone with a strong CYP3A4 inhibitor increased the AUC and Cmax of ziprasidone by 35% to 40%.
    Leuprolide: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of ziprasidone with leuprolide is contraindicated. Additionally, antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Leuprolide; Norethindrone: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of ziprasidone with leuprolide is contraindicated. Additionally, antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Levodopa: (Major) Antipsychotic agents may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain. In general, however, the 'atypical antipsychotics' are less likely to interfere with these therapies than traditional antipsychotic agents (e.g., phenothiazines). Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments. In general, experts consider quetiapine the atypical antipsychotic of choice in Parkinson's patients due to a lower incidence of extrapyramidal symptoms, although the choice of antipsychotic medication must always be made on a case-by-case decision.
    Levofloxacin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including levofloxacin.
    Levomethadyl: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including levomethadyl.
    Levorphanol: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including levorphanol.
    Linagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Linagliptin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Liraglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Lithium: (Severe) Lithium has been associated with QT prolongation. Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including lithium. Additionally, some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is advisable to monitor patients for neurotoxicity during co-administration. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. Early case reports described an encephalopathic syndrome consisting of delirium, tremulousness, dyskinesia, seizures, leukocytosis, weakness, hyperpyrexia, confusion, extrapyramidal symptoms, elevations in laboratory values (e.g., liver function tests, blood urea nitrogen, fasting blood sugar) and, in some cases, irreversible brain damage, during use of lithium and conventional antipsychotics, particularly haloperidol. Subsequent rare reports of NMS or NMS-like reactions have been described during co-administration of lithium and atypical antipsychotics (e.g., aripiprazole, risperidone, olanzapine, clozapine). Following resolution of NMS, there are isolated instances of re-emergence of symptoms following re-initiation of lithium as monotherapy. Lithium may be a risk factor for antipsychotic-induced NMS; however, this hypothesis has not been confirmed. In many reported cases, confounding factors have been present (e.g., previous history of NMS, high dose therapy). The ability of antipsychotics alone to precipitate NMS and the rarity of the condition further complicate assessment of lithium as a risk factor.
    Lixisenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Lofexidine: (Major) Avoid coadministration of lofexidine with ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Monitor ECG if coadministration cannot be avoided. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors.
    Lomefloxacin: (Moderate) Lomefloxacin has been associated with QT prolongation and infrequent cases of arrhythmia. Other medications which may prolong the QT interval, such as ziprasidone, should be used cautiously when given concurrently with lomefloxacin.
    Loop diuretics: (Minor) Monitor of potassium and magnesium levels when loop diuretics are used during ziprasidone therapy. The risk of QT prolongation from ziprasidone is increased in the presence of hypokalemia or hypomagnesemia.
    Loperamide: (Severe) Due to the potential for QT prolongation and/or torsades de pointes (TdP), use of ziprasidone with loperamide is contraindicated. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Loperamide; Simethicone: (Severe) Due to the potential for QT prolongation and/or torsades de pointes (TdP), use of ziprasidone with loperamide is contraindicated. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Lopinavir; Ritonavir: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including lopinavir; ritonavir. (Severe) Concurrent use of ziprasidone and ritonavir is contraindicated due to the risk of QT prolongation. Ritonavir has been associated with QT prolongation. Ziprasidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes. Per the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs.
    Lorazepam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Loxapine: (Major) Caution is advisable during concurrent use of loxapine and other antipsychotics. Loxapine use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Luliconazole: (Moderate) Theoretically, luliconazole may increase the side effects of ziprasidone, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of ziprasidone, such as QT prolongation, CNS effects, and extrapyramidal symptoms. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of ziprasidone. If used together, monitor the patient closely for antipsychotic efficacy; dosage increases should be based on clinical evaluation. Ziprasidone is primarily metabolized by CYP3A, and lumacaftor is a strong CYP3A inducer. Coadministration of ziprasidone with carbamazepine (200 mg twice daily for 21 days), another strong CYP3A inducer, resulted in a 35% decrease in AUC of ziprasidone.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and ziprasidone concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as ziprasidone, can increase ziprasidone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Lurasidone: (Major) Lurasidone administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The risk of these adverse effects may be increased during concurrent use of lurasidone with other antipsychotics. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Maprotiline: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including maprotiline.
    Meclizine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Mefloquine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including mefloquine.
    Meglitinides: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Meperidine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including meperidine.
    Meperidine; Promethazine: (Severe) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and ziprasidone is considered contraindicated. (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including meperidine.
    Mephobarbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including antipsychotics.
    Mesoridazine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Therefore, concurrent use of ziprasidone and mesoridazine is contraindicated. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Metaxalone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including metaxalone.
    Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Methadone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including methadone.
    Methamphetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Methocarbamol: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including methocarbamol.
    Methohexital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Methoxsalen: (Moderate) Medications that may cause additive photosensitization when used with ziprasidone include methoxsalen. Patients should limit sunlight and ultra-violet exposure whenever possible, and use proper UV precautions to protect the skin.
    Methyldopa: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Methylphenidate: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
    Metoclopramide: (Severe) Concomitant use of metoclopramide and antipsychotics is contraindicated by the manufacturer of metoclopramide as the risk of extrapyramidal effects may be increased. Both metoclopramide and antipsychotics antagonize dopamine receptors, which can increase the risk of extrapyramidal effects, including tardive dyskinesia or other dystonic reactions. Additionally, because both antipsychotics and metoclopramide can cause sedation, seizures, or increased prolactin levels, it is possible that the risk of these effects may be increased during concurrent use.
    Metronidazole: (Severe) Potential QT prolongation has been reported in limited case reports with metronidazole. Because of the potential for TdP, use of ziprasidone with metronidazole is contraindicated.
    Midazolam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Midostaurin: (Severe) Concomitant use of midostaurin and ziprasidone is contraindicated; both drugs have been reported to increase the QT interval and the risk of torsade de pointes (TdP) may be increased. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Clinical trial data indicate that ziprasidone also causes QT prolongation; TdP has been reported during postmarketing use. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Mifepristone: (Severe) Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsade de pointes (TdP) including mifepristone. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP. Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage.
    Miglitol: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Mirtazapine: (Major) Concomitant use of ziprasidone and mirtazapine should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Mitotane: (Major) Use caution if mitotane and ziprasidone are used concomitantly, and monitor for decreased efficacy of ziprasidone and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and ziprasidone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of ziprasidone. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone. Additionally, mitotane can cause sedation, lethargy, vertigo, and other CNS adverse reactions; additive CNS effects may occur initially when mitotane is given concurrently with ziprasidone.
    Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), or anticholinergic effects (e.g., constipation, xerostomia) may occur. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Monoamine oxidase inhibitors: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Morphine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including morphine.
    Morphine; Naltrexone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including morphine.
    Moxifloxacin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including moxifloxacin.
    Nabilone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Nafarelin: (Moderate) Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Nalbuphine: (Moderate) Drugs that can cause CNS depression such as nalbuphine, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Nateglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Nefazodone: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme system. Decreased metabolism of ziprasidone may lead to clinically important side effects. Drugs having the potential to decrease the elimination of ziprasidone via inhibition of CYP3A4 include nefazodone.
    Nelfinavir: (Moderate) Nelfinavir may inhibit the metabolism of other substrates of cytochrome P450 3A4 such as ziprasidone.
    Nicardipine: (Major) Nicardipine is a weak inhibitor of CYP3A4 isoenzymes. Co-administration with nicardipine may lead to an increase in serum levels of ziprasidone, a CYP3A4 substrate.
    Nifedipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Nilotinib: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including nilotinib.
    Nimodipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Nisoldipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold, such as ziprasidone, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Norfloxacin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including norfloxacin.
    Nortriptyline: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Octreotide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including octreotide.
    Ofloxacin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including ofloxacin.
    Olanzapine: (Severe) Coadministration of ziprasidone and olanzapine is contraindicated due to the potential for QT prolongation and torsade de pointes. In addition, coadministration of ziprasidone with olanzapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Ombitasvir; Paritaprevir; Ritonavir: (Severe) Concurrent use of ziprasidone and ritonavir is contraindicated due to the risk of QT prolongation. Ritonavir has been associated with QT prolongation. Ziprasidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes. Per the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs.
    Ondansetron: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including ondansetron.
    Oritavancin: (Moderate) Ziprasidone is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of ziprasidone may be reduced if these drugs are administered concurrently.
    Orphenadrine: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including orphenadrine.
    Osimertinib: (Major) Concomitant use of ziprasidone and osimertinib should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib.
    Oxaliplatin: (Major) Concomitant use of ziprasidone and oxaliplatin should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Oxazepam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Oxycodone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including oxycodone.
    Oxymorphone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including oxymorphone.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Clinical trial data indicate that ziprasidone causes QT prolongation. There are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. If concurrent use is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. Coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Panobinostat: (Severe) Because of the potential for torsade de pointes (TdP), use of ziprasidone with panobinostat is contraindicated. QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs.
    Paroxetine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with drugs that are dopamine antagonists such as ziprasidone. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving ziprasidone and an SSRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Pasireotide: (Severe) Because of the potential for torsades de pointes (TdP), use of pasireotide and ziprasidone is contraindicated. Coadministration of pasireotide and drugs that prolong the QT interval may have additive effects on the prolongation of the QT interval. According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP. Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Pazopanib: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including pazopanib.
    Pentamidine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including pentamidine.
    Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Pentazocine; Naloxone: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Pentobarbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Pergolide: (Major) Pergolide is a potent dopamine-receptor agonist. Antipsychotic agents may inhibit the clinical antiparkinsonian response to pergolide by blocking dopamine receptors in the brain. In general, the atypical antipsychotics are less likely to interfere with antiparkinsons treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to pergolide.
    Perindopril; Amlodipine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Perphenazine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Perphenazine is associated with a possible risk for QT prolongation and TdP based on varying levels of documentation and is contraindicated with ziprasidone. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Perphenazine; Amitriptyline: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Perphenazine is associated with a possible risk for QT prolongation and TdP based on varying levels of documentation and is contraindicated with ziprasidone. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Phenelzine: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Phenobarbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Phenoxybenzamine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Phentolamine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Phenylephrine; Promethazine: (Severe) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and ziprasidone is considered contraindicated.
    Phenytoin: (Major) Hydantoins may induce hepatic microsomal enzymes, leading to increased clearance of ziprasidone. Some antipsychotics may also increase CNS depression and also may lower the seizure threshold, producing a pharmacodynamic interaction with anticonvulsants. Adequate dosages of the anticonvulsant should be continued when an antipsychotic drug is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either drug.
    Pimavanserin: (Severe) Due to the potential for QT prolongation and/or torsades de pointes (TdP), use of ziprasidone with pimavanserin is contraindicated. Pimavanserin causes QT prolonging effects that may be additive to those of ziprasidone. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Pimozide: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Therefore, concurrent use of ziprasidone and pimozide is contraindicated. In addition, coadministration of ziprasidone with pimozide may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Porfimer: (Moderate) Medications that may cause additive photosensitization when used with ziprasidone include porfimer. Patients should limit sunlight and ultra-violet exposure whenever possible, and use proper UV precautions to protect the skin.
    Posaconazole: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including posaconazole.
    Potassium-sparing diuretics: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Pramipexole: (Major) Pramipexole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of pramipexole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Pramlintide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Prazosin: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Prilocaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine, and possibly of other adrenergic agonists, can be blocked during concurrent administration of ziprasidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with alpha-1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension.
    Primaquine: (Severe) Primaquine has the potential to prolong the QT interval. Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including primaquine.
    Primidone: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Procainamide: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including Class IA antiarrhythmics.
    Prochlorperazine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Prochlorperazine is associated with a possible risk for QT prolongation and TdP based on varying levels of documentation and is contraindicated with ziprasidone. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Promethazine: (Severe) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and ziprasidone is considered contraindicated.
    Propafenone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including propafenone.
    Propoxyphene: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including propoxyphene.
    Protriptyline: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Quazepam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Quetiapine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of quetiapine, the drug can cause QT prolongation; therefore, use with ziprasidone is contraindicated. In addition, coadministration of ziprasidone with atypical agents may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Quinidine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including Class IA antiarrhythmics.
    Quinine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including quinine.
    Ranolazine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including ranolazine.
    Rasagiline: (Moderate) Atypical antipsychotics may reduce the beneficial effects of rasagiline by blocking dopamine. Additive CNS effects are possible; advise against engaging in tasks requiring mental alertness until the effects of the drug combination are known to the patient. Monoamine oxidase type B inhibitors increase the availability of central dopamine. Antipsychotics may induce pseudoparkinisonism (e.g., shuffling gait, tremor), thereby exacerbating Parkinson's disease symptoms. In addition, dopaminergic medications, including rasagiline, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Atypical antipsychotics may exacerbate sedation or hypotension.
    Regadenoson: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including regadenoson.
    Remifentanil: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including remifentanil.
    Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Reserpine: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Ribociclib: (Severe) Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsade de pointes (TdP) including ribociclib. Systemic exposure of ziprasidone may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ziprasidone has also been associated with a possible risk for QT prolongation and TdP. Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and ziprasidone is a CYP3A4 substrate.
    Ribociclib; Letrozole: (Severe) Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsade de pointes (TdP) including ribociclib. Systemic exposure of ziprasidone may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ziprasidone has also been associated with a possible risk for QT prolongation and TdP. Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and ziprasidone is a CYP3A4 substrate.
    Rifabutin: (Moderate) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4, such as rifabutin. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone.
    Rifampin: (Moderate) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4, such as rifampin. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone.
    Rilpivirine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including rilpivirine.
    Risperidone: (Major) The benefits and risks of combining antipsychotics should be considered prior to treatment initiation. Both ziprasidone and risperidone have been associated with a possible risk for QT prolongation and torsade de pointes. In addition, coadministration of antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited.
    Ritonavir: (Severe) Concurrent use of ziprasidone and ritonavir is contraindicated due to the risk of QT prolongation. Ritonavir has been associated with QT prolongation. Ziprasidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes. Per the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs.
    Romidepsin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including romidepsin.
    Ropinirole: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Rotigotine: (Moderate) Rotigotine is a dopamine-receptor agonist. Dopamine-receptor antagonists, including atypical antipsychotics, should generally be avoided when possible because they may antagonize the effects of rotigotine. In general, atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotics. Use only if the benefit of the drug outweighs the risk of decreased therapeutic response to rotigotine or other treatments. Monitor for an altered clinical response to drug therapy and for additive CNS effects if used together.
    Safinamide: (Moderate) Atypical antipsychotics may reduce the beneficial effects of safinamide by blocking dopamine. Additive CNS effects are possible; advise against engaging in tasks requiring mental alertness until the effects of the combination are known. Monoamine oxidase type B inhibitors increase the availability of central dopamine. Antipsychotics may induce pseudoparkinism (e.g., shuffling gait, tremor), thereby exacerbating Parkinson's disease symptoms. In addition, dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Atypical antipsychotics may exacerbate sedation or hypotension.
    Saquinavir: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect within the contraindications or boxed warnings of the official labeling, such as with saquinavir boosted with ritonavir. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes. Ziprasidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes; however, substantial data are currently lacking to establish causality in association with torsade de pointes. Additionally, saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4 and may reduce the metabolism of ziprasidone, resulting in elevated ziprasidone serum concentrations and potential for QT prolongation.
    Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Secobarbital: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Selegiline: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Semaglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sertraline: (Major) Concomitant use of ziprasidone and sertraline should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. There have been postmarketing reports of QT prolongation and TdP during treatment with sertraline and the manufacturer of sertraline recommends avoiding concurrent use with drugs known to prolong the QTc interval.
    Sevoflurane: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including sevoflurane.
    SGLT2 Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sibutramine: (Major) Caution and close monitoring should be observed when administering sibutramine with drugs that are dopamine antagonists such as the atypical antipsychotics. Monitor for CNS depression, changes in mood or behavior, and for other drug-related adverse reactions. Sibutramine has not been systematically evaluated in combination with antipsychotic medications. Sibutramine is a serotonin reuptake inhibitor that also inhibits norepinephrine and dopamine reuptake. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Simeprevir: (Major) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of ziprasidone, which is a CYP3A4 substrate. Monitor patients for adverse effects of ziprasidone, such as QT prolongation, CNS effects, and extrapyramidal symptoms.
    Simvastatin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that are known to induce Antidiuretic Hormone Secretion (SIADH), such as antipsychotics, as these drugs may increase the risk of water retention and/or electrolyte imbalance.
    Solifenacin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including solifenacin.
    Sorafenib: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including sorafenib.
    Sotalol: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including sotalol.
    Sparfloxacin: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes and is contraindicated in combination with other drugs that prolong the QT interval, such as sparfloxacin.
    Spironolactone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Sufentanil: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including sufentanil.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). QT prolongation resulting in ventricular tachycardia and TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Because of the potential for TdP, concurrent use is contraindicated.
    Sulfonylureas: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sunitinib: (Major) Concomitant use of ziprasidone and sunitinib should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Tacrolimus: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including tacrolimus.
    Tamoxifen: (Major) Avoid coadministration of tamoxifen with ziprasidone due to an increased risk of QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Telaprevir: (Major) Close clinical monitoring is advised when administering ziprasidone with telaprevir due to an increased potential for ziprasidone-related adverse events. If ziprasidone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ziprasidone. Ziprasidone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ziprasidone plasma concentrations.
    Telavancin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including telavancin.
    Telithromycin: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including telithromycin.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and ziprasidone is necessary, as the systemic exposure of ziprasidone may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of ziprasidone; consider increasing the dose of ziprasidone if necessary. Ziprasidone is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temazepam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Terazosin: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Terfenadine: (Severe) Use is contraindicated due to the potential risk for QT prolongation and torsade de pointes (TdP). Terfenadine is associated with a well-established risk for QT prolongation and TdP and should not be administered with other drugs with a known association with QT prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP and is contraindicated in combination with other drugs that prolong the QT interval, such as terfenadine.
    Tetrabenazine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including tetrabenazine.
    Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and ziprasidone concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as ziprasidone, can increase ziprasidone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Thiazide diuretics: (Minor) Monitor potassium and magnesium levels when thiazide diuretics are used during ziprasidone therapy. The risk of QT prolongation from ziprasidone is increased in the presence of hypokalemia or hypomagnesemia.
    Thiazolidinediones: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Thiopental: (Major) Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with inducers of CYP3A4 including barbiturates. Additive CNS depressant effects are also possible when ziprasidone is used concurrently with barbiturates.
    Thioridazine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Therefore, concurrent use of ziprasidone and thioridazine is contraindicated. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Thiothixene: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Tizanidine: (Severe) Given the potential for QT prolongation, ziprasidone is contraindicated for use with tizanidine. Tizanidine administration may result in QT prolongation. Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Tolcapone: (Major) Atypical antipsychotics are central dopamine antagonists and may inhibit the clinical response to antiparkinsonian agents with dopamine agonist properties by blocking dopamine receptors in the brain. Due to the CNS depressant effects of atypical antipsychotics, additive drowsiness may occur with Parkinson's treatments like entacapone or tolcapone. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents.
    Tolterodine: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including tolterodine.
    Toremifene: (Severe) Concomitant use of ziprasidone and toremifene is contraindicated due to the risk of additive QT prolongation. The administration of toremifene with agents that have demonstrated QT prolongation should be avoided; the labeling has a boxed warning regarding QT prolongation. If such an agent is necessary, it is recommended that therapy with toremifene be interrupted. If interruption of toremifene is not possible, patients who require treatment with a drug that prolongs QT should be closely monitored for prolongation of the QT interval, including ECG monitoring. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Toremifene has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
    Tramadol: (Moderate) Concurrent use of tramadol and ziprasidone should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and ziprasidone.
    Trandolapril; Verapamil: (Major) Verapamil may reduce ziprasidone metabolism via inhibition of CYP3A4 isoenzymes.
    Tranylcypromine: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Trazodone: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. According to the manufacturer of ziprasidone, the drug is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Therefore, concurrent use of ziprasidone and trazodone is contraindicated. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of TdP.
    Treprostinil: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Triamterene: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Triazolam: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant.
    Tricyclic antidepressants: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Trifluoperazine: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Trifluoperazine is associated with a possible risk for QT prolongation and TdP based on varying levels of documentation and is contraindicated with ziprasidone. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Trimipramine: (Severe) Ziprasidone should be avoided for concurrent use with other drugs that may be associated with QT prolongation, considering an assessment of the level of probability for drug-induced QT prolongation and torsades de pointes and individual patient risk factors for torsades de pointes. Drugs which have been reported to prolong the QT interval include tricyclic antidepressants.
    Triprolidine: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
    Triptorelin: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes. Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of ziprasidone with triptorelin is contraindicated.
    Vandetanib: (Severe) Concurrent use of vandetanib and ziprasidone is contraindicated. Vandetanib can prolong the QT interval in a concentration-dependent manner, and torsade de pointe (TdP) and sudden death have been reported. Because ziprasidone may cause QT prolongation, the manufacturer contraindicates use with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs, which includes vandetanib. Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Vardenafil: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including vardenafil.
    Vasodilators: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
    Vemurafenib: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including vemurafenib.
    Venlafaxine: (Severe) Venlafaxine is contraindicated for use with ziprasidone. Venlafaxine is associated with a possible risk of QT prolongation and ziprasidone has an established risk of QT prolongation and torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine.
    Verapamil: (Major) Verapamil may reduce ziprasidone metabolism via inhibition of CYP3A4 isoenzymes.
    Verteporfin: (Moderate) Medications that may cause additive photosensitization when used with ziprasidone include verteporfin. Patients should limit sunlight and ultra-violet exposure whenever possible, and use proper UV precautions to protect the skin.
    Voriconazole: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for TdP including voriconazole.
    Vorinostat: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including vorinostat.
    Zaleplon: (Moderate) Additive CNS-depressant effects may occur with the atypical antipsychotics and zaleplon. In addition, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of CNS depressants than with zaleplon alone. In premarketing studies, zaleplon potentiated the CNS effects of a phenothiazine antipsychotic for at least 2 to 4 hours. Other antipsychotics may also have additive CNS effects with zaleplon.
    Zolpidem: (Moderate) Additive CNS-depressant effects may occur with the atypical antipsychotics and zolpidem. In addition, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of zolpidem and other CNS depressants than with zolpidem alone.
    Zonisamide: (Moderate) Zonisamide may cause decreased sweating (oligohidrosis), elevated body temperature (hyperthermia), heat intolerance, or heat stroke. The manufacturer recommends caution in using concurrent drug therapies that may predispose patients to heat-related disorders such as antipsychotics. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if zonisamide is used with any of these agents.

    PREGNANCY AND LACTATION

    Pregnancy

    According to the manufacturer, it is not known if ziprasidone or its metabolites are excreted in breast milk and it is recommended that women receiving ziprasidone should not breast-feed. However, in one case report, the use of ziprasidone 160 mg/day for one week resulted in a milk to plasma ratio of 0.06 and a relative infant dose of 1.2%. In a separate case, no adverse effects on the growth and development occurred in one nursing infant after maternal use of ziprasidone 40 mg/day for 6 months during breast-feeding. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. There is very limited experience with ziprasidone during breast-feeding; other agents may be preferred especially while nursing a newborn or preterm infant. Alternate medications for consideration include atypical agents such as olanzapine or quetiapine. Data related to the safety of antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Ziprasidone is considered an atypical antipsychotic. The efficacy of ziprasidone in schizophrenia is primarily attributable to dopamine (i.e, D2) and serotonin (specifically 5HT2A) receptor antagonism. Several characteristics of the drug are likely responsible for its antidepressant effects including 5HT1A agonism, 5HT1D antagonism, and serotonin/norepinephrine reuptake inhibition. Blockade of alpha-1 receptors likely accounts for the orthostatic hypotension that may occur. Ziprasidone has a high in vitro binding affinity for several sites including other dopamine (i.e., D3) and other serotonin (5HT2C) receptors. Cholinergic receptor binding is negligible. Ziprasidone exhibits a lower H1-receptor binding affinity than most other atypicals, which contributes to its more favorable effect on weight gain than clozapine, olanzapine, and risperidone.Clinically, the blockade of D2 receptors in the mesolimbic area of the brain is thought to reduce hallucinations and delusions. Extrapyramidal symptoms (EPS) and cognitive deficits are thought to occur from dopamine blockade in the nigrostriatal and mesocortical pathways, respectively. D2-antagonism in the tuberoinfundibular tract of the brain is likely responsible for the hyperprolactinemia that may occur with antipsychotic administration. Traditional antipsychotics block dopamine nonselectively in all four pathways of the brain and have little to no effect on serotonin functioning; thus, positive symptoms of schizophrenia are typically well controlled while negative symptoms are inadequately treated. In addition, EPS and increased cognitive deficits from traditional antipsychotics may further diminish the overall effectiveness of the drugs. Atypical antipsychotics are distinguishable from traditional agents by characteristics such as a high ratio of serotonin-to-dopamine receptor affinity, and/or D2 receptor specificity in the limbic region of the brain. Affinity for other dopamine receptor subtypes (i.e., D3, D4) may also contribute to the effectiveness of some atypicals. The resulting clinical effects include an improvement in negative symptom efficacy and a reduction in the incidence of EPS. Some data indicate that the likelihood of developing tardive dyskinesia (TD) is reduced with atypicals versus traditional antipsychotics.

    PHARMACOKINETICS

    Ziprasidone is administered orally or intramuscularly (IM). After administration, it is > 99% protein bound to plasma proteins, primarily to albumin and a-1-acid glycoprotein. However, it does not displace other highly-protein bound drugs and is not displaced by other drugs.
     
    Ziprasidone undergoes extensive metabolism (66%) in the liver via reduction primarily by chemical reduction by glutathione as well as enzymatic reduction by aldehyde oxidase with subsequent methylation mediated through thiol methyltransferase. One-third of the drug is cleared via oxidation. Oxidation occurs primarily through hepatic cytochrome P450 isoenzyme CYP3A4; metabolism via CYP1A2 is a lesser contributor. Four major metabolites have been identified including benzisothiazole sulphoxide, benzisothiazole sulphone, ziprasidone sulphoxide, and S-methyldihydroziprasidone. Ziprasidone does not appear to affect metabolism of other drugs cleared via hepatic CYP450 isoenzymes. The drug's mean terminal half-life is roughly 7 hours. Less than 1% and 4% of the parent compound is excreted unchanged in the urine and feces, respectively. The drug is primarily excreted as metabolites in the feces (66%), with 20% of an administered dose excreted in the urine.
     
    Affected cytochrome P450 isoenzymes and drug transporters: None
    In vitro studies revealed little potential for ziprasidone to interfere with the metabolism of drugs cleared primarily by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.

    Oral Route

    Orally administered ziprasidone has a bioavailability of about 60% when administered with food. Administration with food increases absorption up to two-fold, so the dosage should be administered with food. Peak plasma concentrations occur in 6—8 hours; steady state concentrations are achieved within 1 to 3 days of oral dosing.

    Intramuscular Route

    Intramuscularly administered ziprasidone has a bioavailability of 100%. Peak serum concentrations typically occur at approximately 60 minutes post-dose or earlier and the mean half-life ranges from 2—5 hours. Exposure increases in a dose-related manner and following 3 days of IM dosing, little accumulation is observed.