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  • CLASSES

    First Generation Antipsychotics

    BOXED WARNING

    Dementia, geriatric, stroke

    Geriatric patients may be more susceptible to the actions and adverse effects of conventional antipsychotics, including tardive dyskinesia, dystonias, orthostatic hypotension, anticholinergic effects, and a risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not FDA-approved for the treatment of dementia-related psychosis in geriatric patients. A boxed warning in the label of all antipsychotics outlines the significantly increased incidence of cerebrovascular events (e.g., stroke, transient ischemic attack), including fatal events, reported in the elderly with dementia-related psychosis receiving antipsychotics compared to placebo. Two population-based, retrospective cohort studies evaluated the risk of death in elderly patients with dementia receiving conventional antipsychotics. One of the studies found that those receiving atypical antipsychotics had an increase in mortality compared to the placebo group and that those receiving conventional antipsychotics had a marginally higher risk of death compared to the atypical antipsychotic group. Investigators from a separate study reported that the risk of death (all-cause mortality) in the conventional antipsychotic group was comparable to and possibly greater than the risk of death in the atypical antipsychotic group. Deaths due to cancer and cardiac disease carried the highest relative risk. 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. Avoid use in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: lower urinary tract symptoms/benign prostatic hyperplasia in men (decreased urinary flow, urinary retention), 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 a 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 Beers Panel recommends avoiding antipsychotics in elderly patients with a history of falls or fractures, unless safer alternatives are not available, as antipsychotics can cause ataxia, impaired psychomotor function, syncope, and additional falls. If an antipsychotic must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement 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, the patient must be a danger to self or others and 1) symptoms 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, 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 that there is 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 the shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, the 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

    Antipsychotic drug structurally similar to phenothiazines; 5 mg PO equivalent to 100 mg chlorpromazine; increased risk of death in elderly patients treated for dementia-related psychosis.

    COMMON BRAND NAMES

    Navane

    HOW SUPPLIED

    Navane/Thiothixene Oral Cap: 1mg, 2mg, 5mg, 10mg

    DOSAGE & INDICATIONS

    For the treatment of schizophrenia.
    Oral dosage
    Adults

    Initially, 2 mg PO 3 times daily or 5 mg PO twice daily, depending on severity of the condition. Increase dosage gradually based upon response and tolerability. In general, a lower initial dosage and slower titration are advisable in geriatric or debilitated patients. The usual optimal dosage is in the range of 20 to 30 mg/day PO given in divided doses, but doses up to 60 mg/day may be necessary for severe conditions. Exceeding 60 mg/day rarely increases the beneficial response. For maintenance therapy, the lowest effective dosage should be used. A single daily dose may be used if desired.

    Children and Adolescents 12 to 17 years

    Initially, 2 mg PO 3 times daily or 5 mg PO twice daily, depending on the severity of the condition. Increase dosage gradually based upon response and tolerability. The usual optimal dosage is in the range of 20 to 30 mg/day PO given in divided doses, but doses up to 60 mg/day may be necessary for severe conditions. Exceeding 60 mg/day rarely increases the beneficial response. For maintenance therapy, the lowest effective dosage should be used. A single daily dose may be used if desired.

    Children 5 to 11 years†

    Data are very limited. In children, weight-based dosing is often used. A dose of 0.25 mg/kg/day PO, given in divided doses, has been suggested as an effective dose. In 1 small clinical trial of 10 boys (ages 5 to 15 years) with a diagnosis of autism, schizophrenia, or organic psychosis and inadequate response to prior treatment, the efficacy of thiothixene was compared to placebo alone followed by trihexyphenidyl alone during a run-in period. After the run-in period, trihexyphenidyl was continued as a prophylactic for extrapyramidal symptoms. Thiothixene was initiated at 1 mg/day PO and titrated to response and tolerability. Maximum tolerated dose range: 6 to 60 mg/day (mean 27 mg/day); optimum daily dose ranged from 6 to 30 mg/day (mean 14 mg/day). Analysis of the psychiatric rating scale for children showed significant improvement over both placebo and trihexyphenidyl monotherapy for the following symptoms: quantity and quality of motor activity, quantity of speech, thought content, social relationships, mood, anger, feeding, attention disorder, and emotional unresponsiveness.

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

    Initially, 1 to 2 mg PO once or twice per day. May gradually increase every 4 to 7 days by 1 to 2 mg/day as needed and tolerated. The dosage may range from 2 to 30 mg/day given in 1 to 3 divided doses. Antipsychotics are not FDA-approved for this indication, 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 residents with dementia-related behavioral symptoms. OBRA Max: 7 mg/day PO in residents meeting the OBRA criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. In addition, 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

    60 mg/day PO. Debilitated patients require lower dosages.

    Geriatric

    60 mg/day PO. Debilitated patients require lower dosages.

    Adolescents

    60 mg/day PO. Debilitated patients require lower dosages.

    Children

    Children 12 years of age: 60 mg/day PO. Debilitated patients require lower dosages.
    Children < 12 years: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available but decreased drug metabolism may occur. Patients who develop jaundice secondary to thiothixene use should have therapy discontinued.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. 
     
    Intermittent hemodialysis
    Thiothixene is not removed by hemodialysis.

    ADMINISTRATION

    Oral Administration

    May administer oral dosage forms with or without food. If stomach upset or nausea occur, take with food.

    Oral Solid Formulations

    Capsules:
    Administer orally as prescribed.

    STORAGE

    Navane:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Thyroid disease

    Thiothixene should be used with extreme caution in patients with thyroid disease such as thyrotoxicosis or hyperthyroidism. Antipsychotic agents can cause extremely severe extrapyramidal symptoms such as dystonias or rigidity. Laryngospasm can prevent breathing and could be life-threatening.

    Hypocalcemia

    Patients with hypocalcemia may be at an increased risk for having dystonic reactions, so thiothixene should be used with caution in this patient population.

    Cardiac disease, hypotension, orthostatic hypotension, syncope

    Rarely, thiothixene can cause hypotension or precipitate angina; therefore, it should be used with extreme caution in patients with cardiac disease. Hypotension induced by thiothixene may be additive with other hypotensive agents and may result in orthostasis or syncope. 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.

    Neonates, pregnancy, pregnancy testing

    Studies of thiothixene in human pregnancy have not been performed; therefore, thiothixene should be used during pregnancy only when the expected benefits outweigh the potential risks to the mother and fetus. It is likely that thiothixene crosses the placenta. Animal studies and clinical experience have not demonstrated teratogenic effects; however, decreased conception rates and litter size, as well as an increase in resorption rates have been observed in rats and rabbits. 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

    Although no breast-feeding recommendations are available from the manufacturer of thiothixene, related antipsychotics such as phenothiazines are excreted into human breast milk. Therefore, thiothixene should be avoided during breast-feeding if clinically possible. Thiothixene may induce hyperprolactinemia and galactorrhea, and thus may interfere with proper lactation. 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; however, alternate medications for consideration include atypical agents such as olanzapine or quetiapine. Data regarding the safety of atypical 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 ingested drug, healthcare providers are encouraged to report adverse effects to the FDA.

    Brain tumor, Reye's syndrome

    Severe adverse CNS reactions induced by thiothixene may appear similar to neurologic symptoms of CNS disorders such as encephalitis, Reye's syndrome, encephalopathy, meningitis, brain tumor, and tetanus. The drug can suppress the symptoms of these disorders, if they are present.

    Hepatic disease

    Patients with a history of hepatic encephalopathy secondary to cirrhosis may be at an increased risk for potentiation of the CNS effects of thiothixene. Although preexisting hepatic disease does not appear to increase the probability of jaundice occurring in patients receiving antipsychotic agents, thiothixene should be used with caution in this patient population.

    Children, infants

    The use of thiothixene in children under 12 years of age is not recommended because safe conditions for its use have not been established. Children with acute illnesses, including varicella-zoster infections, CNS infections, measles, gastroenteritis, or dehydration, can be more susceptible to developing extrapyramidal symptoms, particularly dystonias with thiothixene use. There is no known indication for the use of thiothixene in infants. Additionally, adverse effects have been reported after delivery in newborns and infants 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.

    Agranulocytosis, hematological disease, leukopenia, neutropenia

    Thiothixene should be used with caution in patients with hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis have been associated with antipsychotic use. A history of drug-induced leukopenia or neutropenia or pre-existing low white blood cell (WBC) count may increase the likelihood of developing hematologic effects during treatment with an antipsychotic medication. Patients with a history of clinically significant low WBC count or drug-induced leukopenia/neutropenia should have frequent complete blood count (CBC) assessments during the first few months of treatment. Discontinuation of the antipsychotic 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. Thiothixene should be discontinued in patients with severe neutropenia (ANC < 1000/mm3); ongoing medical care is recommended until the symptoms resolve.

    Seizure disorder

    Patients receiving anticonvulsant agents or who have a history of seizures, epilepsy, or EEG abnormalities should be carefully monitored during therapy with thiothixene due to its potential lowering of seizure threshold. Adequate anticonvulsant therapy should prevent an increase in seizure frequency during treatment with thiothixene. High doses and large changes in dose of thiothixene should be avoided in patients with a known seizure disorder.

    Glaucoma

    The anticholinergic effects of thiothixene or concomitant antiparkinsonian agent can worsen angle closure glaucoma, so they should be used with caution in patients with preexisting angle closure glaucoma.

    Prostatic hypertrophy, urinary retention

    Thiothixene should be used cautiously in patients with prostatic hypertrophy because the anticholinergic effects of thiothixene or concomitant antiparkinsonian agent can worsen urinary retention.

    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. Thiothixene should be used with caution in patients with Parkinson's disease, as blockade of dopamine receptors centrally by thiothixene may worsen patient symptoms.

    Dementia, geriatric, stroke

    Geriatric patients may be more susceptible to the actions and adverse effects of conventional antipsychotics, including tardive dyskinesia, dystonias, orthostatic hypotension, anticholinergic effects, and a risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not FDA-approved for the treatment of dementia-related psychosis in geriatric patients. A boxed warning in the label of all antipsychotics outlines the significantly increased incidence of cerebrovascular events (e.g., stroke, transient ischemic attack), including fatal events, reported in the elderly with dementia-related psychosis receiving antipsychotics compared to placebo. Two population-based, retrospective cohort studies evaluated the risk of death in elderly patients with dementia receiving conventional antipsychotics. One of the studies found that those receiving atypical antipsychotics had an increase in mortality compared to the placebo group and that those receiving conventional antipsychotics had a marginally higher risk of death compared to the atypical antipsychotic group. Investigators from a separate study reported that the risk of death (all-cause mortality) in the conventional antipsychotic group was comparable to and possibly greater than the risk of death in the atypical antipsychotic group. Deaths due to cancer and cardiac disease carried the highest relative risk. 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. Avoid use in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: lower urinary tract symptoms/benign prostatic hyperplasia in men (decreased urinary flow, urinary retention), 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 a 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 Beers Panel recommends avoiding antipsychotics in elderly patients with a history of falls or fractures, unless safer alternatives are not available, as antipsychotics can cause ataxia, impaired psychomotor function, syncope, and additional falls. If an antipsychotic must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement 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, the patient must be a danger to self or others and 1) symptoms 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, 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 that there is 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 the shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, the 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.

    Breast cancer

    Antipsychotics, such as thiothixene, stimulate the release of prolactin and should be used extremely cautiously in patients who have a history of breast cancer.

    Tobacco smoking

    Tobacco smoking can induce hepatic metabolism and reduce plasma concentrations of thiothixene compared with those of nonsmokers receiving the same dose. Dosage adjustments may be required in patients who start or stop smoking while receiving phenothiazines.

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

    Thiothixene is contraindicated in patients with central nervous system depression (CNS depression) due to any cause and coma.Thiothixene can cause somnolence. Somnolence 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. Patients receiving thiothixene should be advised to avoid driving or operating machinery until the effects of the drug are known. Given the primary CNS effects of thiothixene, 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.

    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 thiothixene 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.

    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, thiothixene 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, thiothixene discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

    Dysphagia

    Patients with dysphagia or who are at risk for aspiration should be closely monitored while receiving thiothixene. Antipsychotics have been associated with esophageal dysmotility and aspiration of gastric contents, which may increase the incidence of aspiration pneumonia in susceptible patient populations, such as those with severe Alzheimer's disease.[54413]

    ADVERSE REACTIONS

    Severe

    neuroleptic malignant syndrome / Delayed / Incidence not known
    tardive dyskinesia / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    retinopathy / Delayed / Incidence not known
    corneal opacification / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    asphyxia / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    stroke / Early / Incidence not known
    water intoxication / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known

    Moderate

    blurred vision / Early / 1.0-10.0
    constipation / Delayed / 1.0-10.0
    hypotension / Rapid / 1.0-10.0
    leukopenia / Delayed / 0-1.0
    orthostatic hypotension / Delayed / 0-1.0
    pseudoparkinsonism / Delayed / 10.0
    dystonic reaction / Delayed / 10.0
    akathisia / Delayed / 10.0
    hallucinations / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known
    ejaculation dysfunction / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    hypoglycemia / Early / Incidence not known
    hyperthermia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known

    Mild

    nausea / Early / 1.0-10.0
    leukocytosis / Delayed / 0-1.0
    vomiting / Early / 0-1.0
    xerostomia / Early / 10.0
    weight gain / Delayed / 10.0
    appetite stimulation / Delayed / 10.0
    restlessness / Early / Incidence not known
    insomnia / Early / Incidence not known
    agitation / Early / Incidence not known
    fatigue / Early / Incidence not known
    dizziness / Early / Incidence not known
    drowsiness / Early / Incidence not known
    weakness / Early / Incidence not known
    nasal congestion / Early / Incidence not known
    fever / Early / Incidence not known
    purpura / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    photosensitivity / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    rash / Early / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    hypersalivation / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    syncope / Early / Incidence not known
    mastalgia / Delayed / Incidence not known
    amenorrhea / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    breast enlargement / Delayed / Incidence not known
    libido decrease / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    hypothermia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Acetaminophen; Butalbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Acetaminophen; Codeine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) The CNS depressant effects of dichloralphenazone can be potentiated by other CNS depressants including thiothixene. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Acetaminophen; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Pentazocine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as pentazocine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Tramadol: (Major) Concurrent use of tramadol and thiothixene should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. In addition, in vitro data suggest that thiothixene is a weak CYP2D6 inhibitor and has the potential to decrease the metabolism of CYP2D6 substrates such as tramadol. Although the full pharmacologic impact of increased tramadol exposure is unknown, close monitoring for serious adverse effects, such as seizures, is advisable. In addition, serotonin syndrome may occur during use of tramadol with medications that impair its metabolism. 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. Because the analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), CYP2D6 inhibition by thiothixene may alter the analgesic response to tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and thiothixene.
    Acrivastine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Alfentanil: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Aliskiren: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Aliskiren; Amlodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Aliskiren; Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Alpha-blockers: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amantadine: (Moderate) It appears that amantadine potentiates the actions of dopamine. Since thiothixene is a dopamine antagonist, it should be avoided when possible in patients with Parkinson's disease who require amantadine therapy. If these drugs are used together, use caution. The anticholinergic actions of thiothixene and amantadine can be additive and may include constipation, dizziness, difficulty with urination, drowsiness, dry mouth and eyes, changes in vision, fast or irregular heartbeat, or confusion.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with thiothixene and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Thiothixene may increase the risk of seizures.
    Amiloride: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Aminolevulinic Acid: (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving phenothiazines should avoid ultra-violet (UV) exposure whenever possible.
    Amiodarone: (Severe) Amiodarone prolongs the QT interval and could lead to additive orthostatic hypotension and/or prolonged QT syndrome and torsade de pointes when combined with thiothixene and use should be done with caution and close monitoring, if not avoided.
    Amitriptyline: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Amitriptyline; Chlordiazepoxide: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Amlodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amlodipine; Atorvastatin: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amlodipine; Benazepril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amlodipine; Olmesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amlodipine; Telmisartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amlodipine; Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Amobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Amoxapine: (Moderate) Use caution during co-administration of amoxapine and thiothixene. 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.
    Amphetamine; Dextroamphetamine Salts: (Major) Concurrent use of antipsychotics, such as thiothixene, 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.
    Angiotensin II receptor antagonists: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Angiotensin-converting enzyme inhibitors: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Anticholinergics: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
    Apomorphine: (Major) Concomitant use of thiothixene and dopamine agonists (e.g., pergolide, pramipexole, or ropinirole) is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to dopamine agonists. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    Aripiprazole: (Major) Caution is advisable during concurrent use of aripiprazole with other CNS depressants such as thiothixene. 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. 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.
    Articaine; Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
    Asenapine: (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 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.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Aspirin, ASA; Carisoprodol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Atenolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Atenolol; Chlorthalidone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as phenobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including thiothixene.
    Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including thiothixene.
    Azilsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Azilsartan; Chlorthalidone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Baclofen: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as phenobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Belladonna; Opium: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Benazepril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Bendroflumethiazide; Nadolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with thiothixene may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with thiothixene 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 benzhydrocodone is initiated in a patient taking thiothixene, reduce initial dosage and titrate to clinical response. If thiothixene is initiated a patient taking an opioid agonist, use a lower initial dose of thiothixene and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Benzodiazepines: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Benzphetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, 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.
    Betaxolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Bisoprolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as thiothixene. 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. 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.
    Bromocriptine: (Major) Avoid concurrent use of thiothixene and bromocriptine when possible. Thiothixene is noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by thiothixene persists with chronic administration. However, bromocriptine does not appear to interfere with the antipsychotic effects of thiothixene if it is added to a stable neuroleptic regimen.
    Brompheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Brompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Bumetanide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    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 thiothixene can increase the risk for sedation.
    Butabarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as butabarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Butorphanol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as butorphanol. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Cabergoline: (Major) Due to antagonistic mechanisms of action, thiothixene may limit the ability of cabergoline to lower serum prolactin concentrations. The combination should be avoided where possible. However, cabergoline does not appear to interfere with the antipsychotic effects of thiothixene if it is added to a stable neuroleptic regimen.
    Calcium Carbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    Calcium Carbonate; Risedronate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    Calcium Carbonate; Simethicone: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    Calcium-channel blockers: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Candesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and thiothixene. CNS depressants can potentiate the effects of cannabidiol.
    Capsaicin; Metaxalone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Captopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Carbamazepine: (Major) Thiothixene, when used concomitantly with carbamazepine, can increase CNS depression and lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; monitor for loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant. In addition, carbamazepine is a potent inducer of the cytochrome P-450 mixed-function hepatic oxidase system, and can reduce plasma concentrations of thiothixene to undetectable levels. If thiothixene and carbamazepine must be used together, then dosage adjustments of thiothixene may be required.
    Carbetapentane; Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Carbetapentane; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Carbetapentane; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Carbidopa; Levodopa: (Major) Concomitant use of thiothixene and levodopa is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to levodopa. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    Carbidopa; Levodopa; Entacapone: (Major) Concomitant use of thiothixene and levodopa is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to levodopa. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy. (Major) Thiothixene may inhibit the clinical antiparkinsonian response to COMT inhibitors like entacapone and tolcapone by blocking dopamine receptors in the brain. In addition, COMT inhibitors and thiothixene should be given together cautiously due to the possibility of additive sedation. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to levodopa or other treatments. The use of older neuroleptics should generally not be necessary given the data indicating that parkinson's related psychosis can generally be safely and effectively treated by newer antipsychotics without a worsening of extrapyramidal symptoms.
    Carbinoxamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Carbinoxamine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Carbinoxamine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Cariprazine: (Major) Avoid use of these drugs together due to duplicative therapeutic effects and additive risks for drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. Cariprazine, like other antipsychotics, has the potential to impair judgment, thinking, or motor skills. The use of cariprazine with other antipsychotic agents, such as thiothixene, would be expected to have additive risks for pharmacologic effects and adverse reactions. 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 combined use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Carisoprodol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Carteolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Carvedilol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with thiothixene should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with thiothixene should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetrorelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia including thiothixene should not be administered concomitantly with cetrorelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Charcoal: (Major) The absorption of thiothixene is reduced when coadministered with activated charcoal. Concomitant administration is not recommended, however, coadministration with activated charcoal may be appropriate in certain overdose situations.
    Chlophedianol; Dexbrompheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Chlorcyclizine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Chlorothiazide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Chlorpheniramine; Codeine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Chlorpheniramine; Hydrocodone: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Chlorpromazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Chlorthalidone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Chlorthalidone; Clonidine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Chlorzoxazone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Clemastine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Clevidipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Clobazam: (Major) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects which may be potentiated during concurrent use of conventional antipsychotics including thiothixene. Antipsychotics may lower the seizure threshold and reduce the effectiveness of clobazam as an anticonvulsant.
    Clomipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Clonidine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Clozapine: (Major) Co-administration of clozapine with thiothixene may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Codeine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Codeine; Guaifenesin: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Codeine; Phenylephrine; Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Codeine; Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    COMT inhibitors: (Major) Thiothixene may inhibit the clinical antiparkinsonian response to COMT inhibitors like entacapone and tolcapone by blocking dopamine receptors in the brain. In addition, COMT inhibitors and thiothixene should be given together cautiously due to the possibility of additive sedation. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to levodopa or other treatments. The use of older neuroleptics should generally not be necessary given the data indicating that parkinson's related psychosis can generally be safely and effectively treated by newer antipsychotics without a worsening of extrapyramidal symptoms.
    Cyclizine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Cyclobenzaprine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Cyproheptadine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Dantrolene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Desipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Deutetrabenazine: (Major) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and thiothixene is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as thiothixene, may have additive effects and worsen drowsiness or sedation.
    Dexchlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Dexmethylphenidate: (Major) Antipsychotics, such as thiothixene, and dexmethylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Therefore, concurrent use should generally be avoided. 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.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Dextromethorphan; Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Diazoxide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Diltiazem: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Dimenhydrinate: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Diphenhydramine; Ibuprofen: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Diphenhydramine; Naproxen: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    dopamine agonists: (Major) Concomitant use of thiothixene and dopamine agonists (e.g., pergolide, pramipexole, or ropinirole) is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to dopamine agonists. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    Dopamine: (Moderate) The vasoconstrictive properties of dopamine infusion can be decreased by the alpha-adrenergic blocking effect of thiothixene. Because the alpha-blocking effect of thiothixene is weak, a significant interaction is unlikely.
    Doxepin: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Doxorubicin: (Major) In vitro, thiothixene is a mild CYP2D6 inhibitor; doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of thiothixene and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Doxylamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Dronabinol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as dronabinol. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Eliglustat: (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of thiothixene and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Thiothixene is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as thiothixene, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
    Enalapril, Enalaprilat: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Enalapril; Felodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Enflurane: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Entacapone: (Major) Thiothixene may inhibit the clinical antiparkinsonian response to COMT inhibitors like entacapone and tolcapone by blocking dopamine receptors in the brain. In addition, COMT inhibitors and thiothixene should be given together cautiously due to the possibility of additive sedation. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to levodopa or other treatments. The use of older neuroleptics should generally not be necessary given the data indicating that parkinson's related psychosis can generally be safely and effectively treated by newer antipsychotics without a worsening of extrapyramidal symptoms.
    Ephedrine: (Major) The alpha-adrenergic effects of adrenergic agonists like ephedrine, can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal,' which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
    Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
    Eplerenone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Epoprostenol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Eprosartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Esketamine: (Moderate) Closely monitor patients receiving esketamine and thiothixene for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Esmolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as thiothixene, 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).
    Ethacrynic Acid: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Ethanol: (Major) Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.
    Ethosuximide: (Moderate) Concomitant use of ethosuximide with thiothixene can lower the seizure threshold and reduce the effectiveness of ethosuximide as an anticonvulsant. Additive CNS effects, such as drowsiness, may also occur.
    Etomidate: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Felodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Fenoldopam: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Fentanyl: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Fluoxetine; Olanzapine: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene 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.
    Fluphenazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Fosinopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Fospropofol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Furosemide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Ganirelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, including thiothixene, should not be administered concomitantly with ganirelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    General anesthetics: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Goserelin: (Major) Avoid coadministration of goserelin with thiothixene due to the risk of reduced efficacy of goserelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Guanabenz: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. In addition, thiothixene can antagonize the pharmacologic actions of guanethidine. Both guanethidine and guanadrel should be avoided in patients receiving thiothixene.
    Guanfacine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. In addition, thiothixene can antagonize the pharmacologic actions of guanethidine. Both guanethidine and guanadrel should be avoided in patients receiving thiothixene.
    Haloperidol: (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.
    Halothane: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Histrelin: (Major) Avoid coadministration of histrelin with thiothixene due to the risk of reduced efficacy of histrelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydantoins: (Major) Thiothixene, when used concomitantly with various anticonvulsants can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant.
    Hydralazine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. Concurrent administration of thiothixene and methyldopa has been reported to cause dementia in some cases. The clinical importance of this interaction has not been established.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Hydrocodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydromorphone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydroxyzine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Iloperidone: (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.
    Iloprost: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Imipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Indapamide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Iohexol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, 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.
    Iopamidol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, 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.
    Iopromide: (Major) Use of medications that lower the seizure threshold, such as thiothixene, 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.
    Ioversol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, 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.
    Irbesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Isocarboxazid: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
    Isoflurane: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
    Isoniazid, INH; Rifampin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
    Isosulfan Blue: (Major) Use of medications that lower the seizure threshold, such as thiothixene, 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.
    Isradipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Kava Kava, Piper methysticum: (Major) The German Commission E warns that any substances that act on the CNS, including psychotropic agents such as thiothixene, may interact with kava kava. While the interactions can be pharmacodynamic in nature, 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 also possible.
    Ketamine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Labetalol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Leuprolide: (Major) Avoid coadministration of leuprolide with thiothixene due to the risk of reduced efficacy of leuprolide. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with thiothixene due to the risk of reduced efficacy of leuprolide. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with thiothixene should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Levodopa: (Major) Concomitant use of thiothixene and levodopa is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to levodopa. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    Levorphanol: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Lisdexamfetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, 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.
    Lisinopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Lithium: (Moderate) It is advisable to monitor patients for neurotoxicity during co-administration of lithium and thiothixene. Although conventional antipsychotics are considered a treatment option as adjuncts to mood stabilizers such as lithium, neuroleptic malignant syndrome (NMS) and extrapyramidal effects have been observed occasionally during concurrent use. 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., 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.
    Lofexidine: (Moderate) Monitor for excessive sedation during concurrent use of lofexidine and thiothixene. Lofexidine can potentiate the effects of CNS depressants, including thiothixene.
    Loop diuretics: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Losartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    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.
    Lurasidone: (Major) Similar to other antipsychotics, 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.
    Meclizine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Meperidine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Meperidine; Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Mephobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as mephobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Meprobamate: (Moderate) Coadministration of meprobamate and thiothixene may result in additive CNS depressant effects.
    Mesoridazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Metaxalone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Methadone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Methamphetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, 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.
    Methohexital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as methohexital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Methyclothiazide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Methyldopa: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. Concurrent administration of thiothixene and methyldopa has been reported to cause dementia in some cases. The clinical importance of this interaction has not been established.
    Methylphenidate: (Moderate) Antipsychotics, such as thiothixene, 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.
    Metolazone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Metoprolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Metyrosine: (Moderate) Because it also blocks central dopamine receptors, metyrosine, should be avoided or used cautiously in patients receiving thiothixene to minimize the risk of additive adverse CNS effects.
    Minoxidil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Moexipril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    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. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
    Monoamine oxidase inhibitors: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
    Morphine: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Morphine; Naltrexone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Nabilone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as nabilone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Nadolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Nalbuphine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as nalbuphine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with thiothixene. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as thiothixene, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with thiothixene. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as thiothixene, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Nicardipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Nifedipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Nimodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Nisoldipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Nitroprusside: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold, such as thiothixene, 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.
    Norepinephrine: (Major) The alpha-adrenergic effects of adrenergic agonists like norepinephrine, can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal,' which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
    Nortriptyline: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as thiothixene. Therapeutic monitoring is recommended with coadministration.
    Olanzapine: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene 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.
    Olmesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Omeprazole; Sodium Bicarbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    Opiate Agonists: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Orphenadrine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Oxycodone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Oxymorphone: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Paliperidone: (Major) Coadministration of antipsychotics, including paliperidone and thiothixene, should be avoided if possible. Coadministration may increase the risk of adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and 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.
    Pemoline: (Major) Concurrent use of antipsychotics, such as thiothixene, and pemoline should generally be avoided. Antipsychotics and stimulants may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. The pharmacology of pemoline is poorly understood, but the drug may block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of pemoline.
    Penbutolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Pentazocine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as pentazocine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Pentazocine; Naloxone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as pentazocine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Pentobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as pentobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Pergolide: (Major) Concomitant use of thiothixene and dopamine agonists (e.g., pergolide, pramipexole, or ropinirole) is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to dopamine agonists. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    Perindopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Perindopril; Amlodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Perphenazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Perphenazine; Amitriptyline: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Phenelzine: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
    Phenobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as phenobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Phenothiazines: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Phenylephrine; Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
    Photosensitizing agents (topical): (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving phenothiazines should avoid ultra-violet (UV) exposure whenever possible.
    Photosensitizing agents: (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving thiothixene should avoid ultra-violet (UV) exposure whenever possible.
    Pimozide: (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.
    Pindolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Porfimer: (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving thiothixene should avoid ultra-violet (UV) exposure whenever possible.
    Potassium-sparing diuretics: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Pramipexole: (Major) Concomitant use of thiothixene and dopamine agonists (e.g., pergolide, pramipexole, or ropinirole) is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to dopamine agonists. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    Prilocaine; Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
    Primidone: (Moderate) Barbiturates such as primidone may have additive CNS depressant effects, such as sedation, with thiothixene. Antipsychotics, such as thiothixene, may lower the seizure threshold, resulting in an exacerbation of symptoms in patients with a seizure disorder. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Prochlorperazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Propafenone: (Major) Propafenone prolongs the QT interval. Combined use with thiothixene could lead to additive orthostatic hypotension and/or prolonged QT syndrome and torsade de pointes. If concomitant use unavoidable, use together with caution and close monitoring.
    Propofol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Propoxyphene: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Propranolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Protriptyline: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Quetiapine: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene 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.
    Quinapril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Ramipril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Rasagiline: (Moderate) The significance of an interaction between monoamine oxidase inhibitors, such as rasagiline, and antipsychotics, such as thiothixene, is unclear. While some drug references warn of the potential for additive sedative, hypotensive, and anticholinergic effects, clinical data are very limited. Low potency agents such as chlorpromazine and thioridazine have been suggested to be more problematic than high potency agents such as haloperidol or thiothixene. Nevertheless, thiothixene and rasagiline should be used together cautiously.
    Remifentanil: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Reserpine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Rifabutin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
    Rifampin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
    Rifamycins: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
    Rifapentine: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
    Risperidone: (Major) Co-administration of risperidone with thiothixene 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.
    Ropinirole: (Major) Concomitant use of thiothixene and dopamine agonists (e.g., pergolide, pramipexole, or ropinirole) is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to dopamine agonists. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    Rotigotine: (Major) Avoid use together unless the benefits outweigh potential for reduced medication efficacy. Rotigotine is a dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., thiothixene), should be avoided concurrently because they may antagonize the effects of rotigotine. Monitor for an altered clinical response to drug therapy and for additive CNS effects if used together.
    Sacubitril; Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Secobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as secobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
    Sedating H1-blockers: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Selegiline: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
    Sevoflurane: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Skeletal Muscle Relaxants: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Sodium Bicarbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    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: (Moderate) Additive anticholinergic effects may be seen when thiothixene is used concomitantly with other drugs having anticholinergic activity such as solifenacin. Monitor for anticholinergic-related adverse effects such as constipation, blurred vision, and urinary retention during concurrent use.
    Spironolactone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Sufentanil: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include thiothixene. Prior to concurrent use of an opiate 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Telmisartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tetrabenazine: (Major) Concurrent use of thiothixene and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Thalidomide: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
    Thiazide diuretics: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Thiethylperazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Thiopental: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as thiopental. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Thioridazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Tizanidine: (Moderate) Concurrent use of tizanidine and antipsychotics like thiothixene can cause additive CNS depression.
    Tolcapone: (Major) Thiothixene may inhibit the clinical antiparkinsonian response to COMT inhibitors like entacapone and tolcapone by blocking dopamine receptors in the brain. In addition, COMT inhibitors and thiothixene should be given together cautiously due to the possibility of additive sedation. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to levodopa or other treatments. The use of older neuroleptics should generally not be necessary given the data indicating that parkinson's related psychosis can generally be safely and effectively treated by newer antipsychotics without a worsening of extrapyramidal symptoms.
    Torsemide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tramadol: (Major) Concurrent use of tramadol and thiothixene should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. In addition, in vitro data suggest that thiothixene is a weak CYP2D6 inhibitor and has the potential to decrease the metabolism of CYP2D6 substrates such as tramadol. Although the full pharmacologic impact of increased tramadol exposure is unknown, close monitoring for serious adverse effects, such as seizures, is advisable. In addition, serotonin syndrome may occur during use of tramadol with medications that impair its metabolism. 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. Because the analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), CYP2D6 inhibition by thiothixene may alter the analgesic response to tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and thiothixene.
    Trandolapril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Trandolapril; Verapamil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tranylcypromine: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
    Trazodone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as trazodone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Treprostinil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Triamterene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tricyclic antidepressants: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Trifluoperazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine 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 phenothiazines 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. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Trimipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
    Triprolidine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Triptorelin: (Major) Avoid coadministration of triptorelin with thiothixene due to the risk of reduced efficacy of triptorelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Trospium: (Moderate) Additive anticholinergic effects may be seen when thiothixene is used concomitantly with other drugs having anticholinergic activity such as trospium. Monitor for anticholinergic-related adverse effects such as constipation, blurred vision, and urinary retention during concurrent use.
    Valproic Acid, Divalproex Sodium: (Major) Thiothixene, when used concomitantly with various anticonvulsants, such as valproic acid, can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant.
    Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Vasodilators: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Verapamil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Verteporfin: (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving thiothixene should avoid ultra-violet (UV) exposure whenever possible.
    Vigabatrin: (Major) Vigabatrin should not be used with thiothixene, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Zaleplon: (Moderate) Coadministration of zaleplon and antipsychotics like thiothixene can result in additive CNS depressant effects. In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours. A similar interaction may occur with other antipsychotics.
    Ziprasidone: (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.
    Zolpidem: (Moderate) Zolpidem and thiothixene may have cumulative effects on CNS depression when administered concurrently and they should be used together with caution. 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

    Although no breast-feeding recommendations are available from the manufacturer of thiothixene, related antipsychotics such as phenothiazines are excreted into human breast milk. Therefore, thiothixene should be avoided during breast-feeding if clinically possible. Thiothixene may induce hyperprolactinemia and galactorrhea, and thus may interfere with proper lactation. 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; however, alternate medications for consideration include atypical agents such as olanzapine or quetiapine. Data regarding the safety of atypical 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 ingested drug, healthcare providers are encouraged to report adverse effects to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Thiothixene blocks postsynaptic dopamine receptors in the mesolimbic system and increases dopamine turnover by blockade of the D2 somatodendritic autoreceptor. After approximately 12 weeks of chronic therapy, depolarization blockade of dopamine tracts occurs. The decrease in dopamine neurotransmission has been found to correlate with the antipsychotic effects. This D2 blockade is also responsible for the potent extrapyramidal effects observed with this drug. Dopamine blockade in the chemoreceptor trigger zone accounts for the antiemetic effects. Thiothixene possesses weak anticholinergic and alpha-adrenergic receptor blocking effects. Blockade of alpha1-adrenergic receptors produces sedation; muscle relaxation; and cardiovascular effects such as hypotension, reflex tachycardia, and minor changes in ECG patterns.

    PHARMACOKINETICS

    Thiothixene is administered orally and intramuscularly. Distribution is extensive, and the drug can be detected in the body for several weeks after use. Metabolism takes place in the liver, but large amounts of drug are excreted with metabolites in the feces, via the bile. Profound increases in clearance of thiothixene can be observed in the presence of carbamazepine. The elimination is biphasic, with an initial half-life of 3.4 hours and a terminal half-life of 34 hours.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP1A2
    Data from a small retrospective study indicated that smokers had a higher clearance of thiothixene than non-smokers, suggesting that CYP1A2 may be involved in the metabolism of the drug. In addition, the daily dose of thiothixene was an average of 45% higher in the smoking group than the non-smoking group. In the same study, use with CYP1A2 enzyme-inducing drugs, including carbamazepine and phenytoin, also resulted in a significant increase in clearance. Thiothixene has been shown to weakly inhibit CYP2D6 in vitro.

    Oral Route

    Following oral administration, thiothixene is rapidly and well absorbed. Peak concentrations occur 1—3 hours following a dose.