CONTRAINDICATIONS / PRECAUTIONS
Serious hypersensitivity reactions or anaphylaxis
Risperidone is contraindicated in patients with a known hypersensitivity to risperidone or paliperidone, or to any of the excipients in the risperidone formulation. There is a risk of serious hypersensitivity reactions or anaphylaxis. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been observed in patients treated with risperidone and in patients treated with paliperidone. Paliperidone is an active metabolite of risperidone; therefore, cross-sensitivity is likely.
CNS depression, coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion
Risperidone has the potential to impair cognitive and motor skills. The sedative effects of risperidone may be most evident in the initial days of treatment. Patients should be advised to use caution when engaging in activities requiring coordination and concentration, such as driving or operating machinery, until they know how this drug affects them. Somnolence due to antipsychotic use could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate somnolence. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. In general, avoid use in patients with significant CNS depression. Given the primary CNS effects of risperidone, 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.
Abrupt discontinuation
Abrupt discontinuation of antipsychotics is generally not advisable unless required by the patient's medical condition. Abrupt discontinuation of antipsychotics can be associated with withdrawal dyskinesias and recurrence of symptoms. Because of the strong alpha-adrenergic receptor blocking effects of risperidone, abrupt discontinuation may cause rebound anxiety, restlessness, sweating, tremors, abdominal pain, heart palpitations, headache, and increased blood pressure. During drug discontinuation, patients should be carefully observed for the recurrence of symptoms from the psychiatric disorder (e.g., schizophrenia, bipolar disorder) being treated. A drug withdrawal syndrome (unspecified) was reported during clinical trial evaluation of oral risperidone; however, the frequency is unknown and causality to the drug has not been established.
Tardive dyskinesia
Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Regular evaluation for movement disorders is recommended (e.g., AIMS, DISCUS). Factors associated with a greater susceptibility to tardive dyskinesia include an age above 55 years, female gender, white or African ethnicity, presence of a mood disorder, intellectual disability, CNS injury, prior or current akathisia, significant parkinsonism, or acute dystonic reaction. The rate of tardive dyskinesia in adults treated with a first generation antipsychotic appears to be at least 3 times that observed with second generation antipsychotics. In general, the risk of developing TD and the likelihood that it will become irreversible appears to increase with the duration of treatment and the cumulative dose. However, the syndrome can develop, although much less commonly, after relatively brief periods at low doses or may arise after drug discontinuation. Antipsychotics may suppress the signs and symptoms of tardive dyskinesia and thereby mask the underlying process; however, the syndrome may also remit partially or completely if the antipsychotic is withdrawn. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. If signs and symptoms of tardive dyskinesia appear, risperidone discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
Cardiac disease, cerebrovascular disease, heart failure, hypotension, hypovolemia, myocardial infarction, orthostatic hypotension, syncope
Secondary to alpha-blockade, risperidone can inhibit vasoconstriction and can produce vasodilation. The resultant drop in blood pressure through decreased peripheral resistance can precipitate orthostatic hypotension associated with dizziness, tachycardia, and, in some patients, syncope. This effect may especially occur during the initial dose-titration period. Limiting the initial risperidone dose and titration of the dosage according to recommended schedules can minimize the risk of orthostatic hypotension and syncope. Monitoring of orthostatic vital signs should be considered in patients for whom hypotension is of concern. 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. Patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider dose reduction if hypotension occurs. Use with particular caution in patients with known cardiac disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, or with conditions that would predispose patients to hypotension (e.g., dehydrated state or hypovolemia). Of note, heart failure and myocardial infarction may also increase the risk of prolonging the QT interval when using risperidone. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications.
Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, systemic lupus erythematosus (SLE)
Use risperidone with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, cerebrovascular disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Pooled data from controlled trials indicate there are no statistically significant differences in mean changes from baseline in ECG parameters including QT, corrected QT (QTc), and PR intervals when risperidone is compared to placebo. However, postmarketing reports of overdose indicate that QT prolongation and torsade de pointes (TdP) have occurred. Paliperidone, the active metabolite of risperidone, also modestly increases the QTc interval. One expert source considers risperidone to have a conditional risk for QT prolongation and TdP because there are reports of TdP in risperidone-treated patients who also have bradycardia, hypokalemia, hypomagnesemia, or are receiving other medications known to prolong the QT interval. Females, older adults 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. [59321]
Agranulocytosis, hematological disease, leukopenia, neutropenia
Risperidone should be used with caution in patients with a hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis (severe neutropenia) 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. Consider discontinuation of the antipsychotic if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Monitor patients with clinically significant neutropenia closely for fever and infection, and institute appropriate medical intervention if necessary. Discontinue risperidone in patients with severe neutropenia (ANC less than 1,000/mm3); provide ongoing medical care and follow the WBC count until neutropenia resolves.
Hyponatremia, seizure disorder, seizures
Patients with a history of seizures or with a known seizure disorder should be treated cautiously with risperidone. In clinical trials, oral risperidone was associated with seizures in 9 out of 2,607 adult patients (0.3%); 2 cases occurred in association with hyponatremia. Similarly, 5 out of 1,499 patients (0.3%) experienced seizures in premarketing testing of a long-acting injectable risperidone product. Seizures have also been reported during postmarketing use.
Renal failure, renal impairment
Because the active metabolite of risperidone is substantially excreted by the kidneys, the risk of toxicity is greater in patients with renal impairment, including renal failure. Reduced oral dosages are recommended for adult patients with severe renal impairment (CrCl less than 30 mL/minute). The manufacturers of the extended-release intramuscular injections (Risperdal Consta or Rykindo) and extended-release subcutaneous injections (Perseris or Uzedy) recommend careful titration with oral risperidone in patients with renal impairment before depot therapy is initiated.
Hepatic disease
Reduced oral dosages of risperidone are recommended for adults with significant hepatic disease (Child Pugh score 10 to 15). The manufacturers of the extended-release intramuscular injections (Risperdal Consta or Rykindo) and extended-release subcutaneous injections (Perseris or Uzedy) recommend careful titration with oral risperidone in patients with hepatic impairment before depot therapy is initiated.
Ambient temperature increase, anticholinergic medications, dehydration, hyperthermia, strenuous exercise
Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus and predispose patients to hyperthermia. Patients receiving risperidone should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, dehydration, or use of anticholinergic medications).
Dysphagia
Patients with dysphagia or who are at risk for aspiration should be closely monitored while receiving risperidone. Esophageal dysmotility and aspiration of gastric contents have been associated with antipsychotic use, which may increase the incidence of aspiration pneumonia in certain patient populations, such as those with advanced Alzheimer's disease.
Dementia with Lewy bodies, neurological disease, Parkinson's disease
Antipsychotics, including risperidone, 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, particularly in the older adult, those with neurological disease, conditions, or medications that could exacerbate these effects. Reassess fall risk recurrently for patients on long-term antipsychotic therapy. Patients with Parkinson's disease or dementia with Lewy Bodies can experience increased sensitivity to risperidone. Manifestations can include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with neuroleptic malignant syndrome.
Dementia, geriatric, stroke
Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric adults and use of risperidone should be avoided if possible due to an increase in morbidity and mortality in elderly adults with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. Lower initial dosages of risperidone are generally recommended for the geriatric adult, with careful titration, to minimize risks for orthostasis and hypotension. Monitor blood pressure and renal function. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in elderly patients except for treating schizophrenia, bipolar disorder, and nausea/vomiting during chemotherapy. The Beers panel recommends avoiding antipsychotics in geriatric patients with delirium, dementia, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in geriatrics with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored when risperidone is initiated and after dose changes. According to the federal Omnibus Budget Reconciliation Act (OBRA) regulations in residents of long-term care facilities, antipsychotic therapy should only be initiated in a patient with behavioral or psychological symptoms of dementia (BPSD) when the patient is a danger to self or others or has symptoms due to mania or psychosis. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Antipsychotics are subject to periodic review for effectiveness, medical necessity, gradual dose reduction (GDR), or rationale for continued use. Refer to the OBRA guidelines for complete information.
Phenylketonuria
Risperidone orally disintegrating tablets (e.g., Risperdal M-Tab ODT, others) contain aspartame, a source of phenylalanine. For example, Risperdal M-Tabs contain phenylalanine in the following quantities: each 4 mg ODT contains 0.84 mg phenylalanine; each 3 mg ODT contains 0.63 mg phenylalanine; each 2 mg ODT contains 0.42 mg phenylalanine; each 1 mg ODT contains 0.28 mg phenylalanine; and each 0.5 mg ODT contains 0.14 mg phenylalanine. Caution is advised in patients with phenylketonuria.
Diabetes mellitus, diabetic ketoacidosis, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperosmolar hyperglycemic state (HHS), hypertriglyceridemia, obesity
Atypical antipsychotics, including risperidone, have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk over time, including loss of blood glucose control, dyslipidemia, and weight gain. Use risperidone with caution in patients with pre-existing conditions such as obesity, pre-diabetes, established diabetes mellitus, or hyperlipidemia. All patients treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia (polydipsia, polyuria, polyphagia, weakness), worsening of glucose control, dyslipidemia, and weight gain. Evaluate weight gain against expected normal growth patterns in pediatric patients. Perform fasting blood glucose testing at the beginning of treatment in patients with risk factors for diabetes mellitus (e.g., obesity, family history). Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing. Hyperglycemia or diabetes was reported in rare instances during risperidone clinical trials. Hyperglycemia, in some cases associated with diabetic ketoacidosis or hyperosmolar hyperglycemic state (HHS) with coma or death, has been reported in patients treated with atypical antipsychotics. Hyperglycemia resolved in some cases when the antipsychotic was discontinued; however, some patients required continuation of antidiabetic agents despite discontinuation of the suspect drug. Metabolic changes in patients treated with atypical antipsychotics have also included dyslipidemias such as hypercholesterolemia and/or hypertriglyceridemia. Prior to initiating risperidone or shortly after that, obtain a fasting lipid profile. Periodic monitoring of serum lipids is recommended during long-term treatment. Inform all patients of the importance of maintaining a nutritionally balanced diet during treatment with an antipsychotic.
Priapism
Painful or prolonged penile erections (priapism) have been reported during postmarketing use of risperidone. Severe priapism may require surgical intervention. A patient should seek immediate medical attention right away if priapism occurs.
Breast cancer, hyperprolactinemia, infertility
Risperidone can cause hyperprolactinemia, likely due to central dopamine D2 receptor antagonism, and is associated with higher elevations in prolactin than many other antipsychotics. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Elevations in prolactin may result in infertility in either men or women, or other endocrine abnormalities in adults and pediatric patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both females and males. Close monitoring for adverse endocrine effects is advisable during use of risperidone. In animal studies, an increase in pituitary gland, mammary gland, and pancreatic islet cell neoplasia have been observed during administration of some antipsychotics, including risperidone, and may be mediated by prolactin. Although the clinical significance of these findings is unknown, some human breast cancers may be prolactin-dependent and therefore risperidone should be used cautiously in those who have a history of breast cancer. Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of antipsychotics and tumorigenesis in humans; however, the available evidence is considered too limited to be conclusive at this time.
Neonates, pregnancy, pregnancy testing
When considering the use of risperidone during pregnancy, the possibility of risperidone-related adverse outcomes in the fetus or neonate should be weighed against the risks of an untreated maternal psychiatric condition, which may include hospitalization, relapse, suicide, and increased adverse perinatal outcomes (e.g., pre-term birth). A prospective observational study of women (n = 6) treated with risperidone demonstrated placental passage of risperidone and its metabolite paliperidone. A retrospective cohort study from a Medicaid database of 9,258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. There was a small increase in major birth defects and cardiac malformations in a subgroup of 1,566 women exposed to risperidone during their first trimester of pregnancy; however, there is no mechanism of action to explain the increased malformation rate, and the overall available data from published epidemiologic studies of pregnant women exposed to atypical antipsychotics have not established a drug-associated risk of birth defects, miscarriages, or adverse maternal or fetal outcomes. There is a human case report of agenesis of the corpus callosum occurring in utero. 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. It is not known if antipsychotics, through their effect on prolactin, would affect labor or delivery. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to risperidone; information about the registry can be obtained at womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by calling 1-866-961-2388.
Breast-feeding
The developmental and health benefits of breast-feeding should be considered along with the clinical need for risperidone and any potential adverse effects on the breastfed child from risperidone or from the maternal underlying condition. Limited data from published literature reports the presence of risperidone and its metabolite, 9-hydroxyrisperidone, in human breast milk at relative infant dose ranging between 2.3% and 4.7% of the maternal weight-adjusted oral dosage. There are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to risperidone. There is no data on the effects of risperidone on milk production. Risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose of risperidone extended-release injection (Risperdal Consta), and the clinical significance on the breastfed infant is not known. Data related to the safety of antipsychotics during breast-feeding are limited. It may be prudent to continue an existing antipsychotic regimen if ongoing treatment is deemed necessary during breast-feeding, since there is considerable individual variation in antipsychotic response. Alternate medications for consideration include olanzapine or quetiapine. Regardless of the antipsychotic used, closely monitor the breastfed infant for excessive drowsiness, lethargy, developmental delays, and other side effects. Combination treatment with antipsychotics may increase the risk of these adverse events.
Suicidal ideation
Adverse psychiatric effects, including aggression and suicidal behaviors (e.g., suicidal ideation, suicide attempt), have occurred in pediatric patients receiving risperidone. Although causality to the drug has not been established, careful monitoring for changes in mood and behavior is advisable as well as prescribing risperidone in the smallest quantity consistent with good management in order to reduce the risk of overdose. Oral risperidone is indicated for use in children and adolescents 5 to 17 years of age dependent on the selected indications; safety and efficacy of extended-release risperidone depot injections are not established in pediatric patients.
DRUG INTERACTIONS
Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation including risperidone. Prescribers need to weigh the potential benefits and risks of abarelix use in patients that are taking drugs that can cause QT prolongation.
Acarbose: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Acebutolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of acebutolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving acebutolol concomitantly.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine 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 dihydrocodeine 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; Pyrilamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Drugs that can cause CNS depression, including dichloralphenazone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness if used concomitantly with atypical antipsychotics.
Acetaminophen; Diphenhydramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
Acrivastine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Adagrasib: (Major) Concomitant use of adagrasib and risperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Albiglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Alfentanil: (Moderate) Due to the sedative effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications including opiate agonists such as alfentanil.
Alfuzosin: (Moderate) Use risperidone and alfuzosin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Alfuzosin may prolong the QT interval in a dose-dependent manner.
Alogliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alogliptin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alpha-glucosidase Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alprazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics 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. Atypical antipsychotics may increase the risk of seizures.
Amiodarone: (Major) Concomitant use of risperidone and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with risperidone. Amisulpride causes dose- and concentration- dependent QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Amitriptyline: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Atorvastatin: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Benazepril: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Celecoxib: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Olmesartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Valsartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amobarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Amoxapine: (Moderate) Use caution during co-administration of amoxapine and risperidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include risperidone.
Angiotensin II receptor antagonists: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of angiotensin II receptor antagonists. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving angiotensin II receptor antagonists concomitantly.
Angiotensin-converting enzyme inhibitors: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Apalutamide: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer like apalutamide. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting apalutamide. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of apalutamide to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing apalutamide, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating apalutamide in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of apalutamide in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Apomorphine: (Moderate) Use risperidone and apomorphine together with caution due to a potential for additive QT prolongation and sedation. Also, risperidone and apomorphine may reduce the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
Aripiprazole: (Moderate) Use risperidone and aripiprazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Arsenic Trioxide: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include arsenic trioxide.
Artemether; Lumefantrine: (Major) Concomitant use of drugs with a possible risk of QT prolongation and torsade de pointes, including artemether; lumefantrine and risperidone, should be avoided if possible. Consider ECG monitoring if risperidone must be used with artemether; lumefantrine.
Articaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Asenapine: (Major) Avoid coadministration of risperidone and asenapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Asenapine has also been associated with QT prolongation.
Aspirin, ASA; Butalbital; Caffeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Atazanavir: (Major) Avoid coadministration of atazanavir and risperidone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of risperidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and risperidone.
Atazanavir; Cobicistat: (Major) Avoid coadministration of atazanavir and risperidone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of risperidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and risperidone. (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
Atenolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of atenolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving atenolol concomitantly.
Atenolol; Chlorthalidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of atenolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving atenolol concomitantly.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with risperidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Azithromycin: (Major) Concomitant use of risperidone and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Barbiturates: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with risperidone. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Belladonna; Opium: (Moderate) Additive CNS depression may occur if opiate agonists are used concomitantly with risperidone. The dose of one or both drugs should be reduced.
Bendroflumethiazide; Nadolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of nadolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nadolol concomitantly.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with risperidone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with risperidone 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 risperidone, reduce initial dosage and titrate to clinical response. If risperidone is initiated a patient taking an opioid agonist, use a lower initial dose of risperidone and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Betaxolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of betaxolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving betaxolol concomitantly.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bisoprolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of bisoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving bisoprolol concomitantly.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of bisoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving bisoprolol concomitantly.
Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as risperidone. 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.
Brimonidine; Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
Bromocriptine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Brompheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Bumetanide: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Bupivacaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of risperidone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Risperidone has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of risperidone and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine 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. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of risperidone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Risperidone has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of risperidone and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine 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. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Bupropion: (Major) Initiate risperidone at a reduced dose in patients receiving bupropion. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when bupropion is initiated or discontinued. An adjustment of the dose may be required. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Bupropion is a strong CYP2D6 inhibitor. Risperidone is a CYP2D6 substrate.
Bupropion; Naltrexone: (Major) Initiate risperidone at a reduced dose in patients receiving bupropion. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when bupropion is initiated or discontinued. An adjustment of the dose may be required. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Bupropion is a strong CYP2D6 inhibitor. Risperidone is a CYP2D6 substrate.
Buspirone: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant atypical antipsychotic and buspirone use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Butabarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Butalbital; Acetaminophen: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Butalbital; Acetaminophen; Caffeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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.
Butorphanol: (Moderate) Concomitant use of butorphanol with risperidone can potentiate the effects of butorphanol on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Cabergoline: (Moderate) Cabergoline should not be coadministered with risperidone due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of risperidone may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as risperidone.
Cabotegravir; Rilpivirine: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Calcium-channel blockers: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and risperidone. Concurrent use may result in additive CNS depression.
Carbamazepine: (Moderate) Carbamazepine may decrease risperidone plasma concentrations. A risperidone dosage increase may need to be considered. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Carbamazepine is an enzyme-inducing medication. Additive sedation or other CNS effects are also possible. When oral risperidone is given with an enzyme inducer, slowly titrate the risperidone dose upwards; do not exceed twice the patient's usual dose. Upon discontinuation of the enzyme inducer, the risperidone dose should be re-evaluated and decreased if necessary. For the long-acting intramuscular risperidone injection (Risperdal Consta), adult patients should be closely monitored for the first 4 to 8 weeks after initiation of an enzyme inducer. A dose increase, or additional oral risperidone, may need to be considered. Upon discontinuation of the enzyme inducer, the dosage of Risperdal Consta should be re-evaluated and decreased if necessary. Patients may need to be placed on a lower dose of Risperdal Consta 2 to 4 weeks before the planned discontinuation of an enzyme inducer to adjust for the expected increase in risperidone plasma concentrations. For patients receiving 25 mg of Risperdal Consta, it is recommended to maintain the 25 mg dose upon discontinuation of the enzyme inducer unless clinical judgment warrants lowering the dose to 12.5 mg or interrupting risperidone treatment. The efficacy of the 12.5 mg dose has not been evaluated in clinical trials. When initiating carbamazepine in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of carbamazepine in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Carbidopa; Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease. (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Carbinoxamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Carbinoxamine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Carbinoxamine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Cariprazine: (Moderate) The risk of adverse effects may be increased during concurrent use of cariprazine with other antipsychotics, such as risperidone. Similar to other antipsychotics, cariprazine administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, but the risk appears to be increased.
Carteolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of carteolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving carteolol concomitantly.
Carvedilol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of carvedilol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving carvedilol concomitantly.
Celecoxib; Tramadol: (Major) Concurrent use of tramadol and risperidone should be avoided if possible due to a possible increased risk of seizures. Seizures have been reported in patients receiving monotherapy with tramadol or antipsychotics at recommended doses. In addition, due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications such as tramadol.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and risperidone. Concurrent use may result in additive CNS depression.
Central-acting adrenergic agents: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ceritinib: (Major) Avoid coadministration of ceritinib with risperidone if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Reports of QT prolongation and torsade de pointes (TdP) during risperidone therapy are also noted by the manufacturer, primarily in the overdose setting.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Cetrorelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs including cetrorelix.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Chlorcyclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Chlordiazepoxide: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Chlordiazepoxide; Amitriptyline: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics. (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Chlordiazepoxide; Clidinium: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Chloroquine: (Major) Avoid coadministration of chloroquine with risperidone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Chlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dextromethorphan: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine 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 dihydrocodeine 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) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpromazine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include chlorpromazine. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Risperidone has been associated with a possible risk for QT prolongation and torsade de pointes (TdP); however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Because of the potential for TdP, use of cisapride with risperidone is contraindicated.
Citalopram: (Major) Concomitant use of risperidone and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Clemastine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Clevidipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Clobazam: (Moderate) Clobazam, a benzodiazepine, should be combined cautiously with atypical antipsychotics because of the potential for additive CNS depressant effects. Antipsychotics may also lower the seizure threshold, which might effect the efficacy of clobazam to treat seizures. Clobazam is a weak inducer of CYP3A4 and may reduce the efficacy of atypical antipsychotics that are significantly metabolized by CYP3A4; consult the atypical antipsychotic product labeling for clinical relevance.
Clofazimine: (Moderate) Concomitant use of clofazimine and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clomipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Clonazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Clorazepate: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Clozapine: (Moderate) Because both clozapine and risperidone have a possible risk for QT prolongation and/or torsade de pointes (TdP), caution is advisable during concurrent use. Reports of QT prolongation and TdP during risperidone therapy are noted primarily in the overdosage setting. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. If coadministration is required, the patient's underlying medical conditions and additional potential risk factors should be considered. Patients with known risk factors for cardiac disease or arrhythmia should be closely monitored. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, or seizures. Chronic administration of clozapine and risperidone may decrease the clearance of risperidone.
Cobicistat: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
Cocaine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsades de pointes and should be used cautiously in combination with other drugs that also prolong the QT interval, including local anesthetics.
Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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 codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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; Pseudoephedrine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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 codeine 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) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
COMT inhibitors: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Crizotinib: (Major) Avoid coadministration of crizotinib with risperidone due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Risperidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting.
Cyclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Cyproheptadine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dacomitinib: (Major) Initiate risperidone at a reduced dose in patients receiving dacomitinib as increased plasma concentrations of risperidone and toxicity may occur. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when dacomitinib is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
Dantrolene: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as antipsychotics, can increase CNS depression.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Darunavir: (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Darunavir; Cobicistat: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required. (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required. (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Dasatinib: (Moderate) Use dasatinib with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Degarelix: (Major) Avoid coadministration of degarelix with risperidone due to the risk of reduced efficacy of degarelix; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog. Additionally, risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Desipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Desvenlafaxine: (Major) Coadministration of risperidone, a CYP2D6 substrate, and desvenlafaxine, a CYP2D6 inhibitor, may increase plasma concentrations of risperidone. Clinical studies have shown desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at doses less than 100 mg/day; hence, per desvenlafaxine product labeling, CYP2D6 substrates can be dosed at the original level when desvenlafaxine doses are 100 mg or less or when desvenlafaxine is discontinued. For desvenlafaxine doses more than 400 mg, product labeling recommends to reduce the risperidone dose by one-half.
Deutetrabenazine: (Moderate) Use risperidone and deutetrabenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Monitor for excessive sedation and somnolence during coadministration of risperidone and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dextromethorphan; Bupropion: (Major) Initiate risperidone at a reduced dose in patients receiving bupropion. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when bupropion is initiated or discontinued. An adjustment of the dose may be required. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Bupropion is a strong CYP2D6 inhibitor. Risperidone is a CYP2D6 substrate.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Dextromethorphan; Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include risperidone.
Diazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diltiazem: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Dimenhydrinate: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Diphenhydramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenhydramine; Ibuprofen: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenhydramine; Naproxen: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenhydramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with risperidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Disopyramide: (Major) Risperidone should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Dofetilide: (Major) Coadministration of dofetilide and risperidone is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Dopamine: (Minor) The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone.
Dorzolamide; Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
Doxazosin: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Doxepin: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Doxylamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Doxylamine; Pyridoxine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dronabinol: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Dronedarone: (Contraindicated) Concomitant use of dronedarone with risperidone is contraindicated due to the potential risk of QT prolongation and torsade de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Risperidone has been associated with a possible risk of QT prolongation and/or TdP, primarily in the overdose setting. In addition, dronedarone is an inhibitor of CYP2D6. Risperidone is a substrate for CYP2D6. Concomitant use of dronedarone with risperidone may increase risperidone concentration and further increase the risk for adverse cardiac effects.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Efavirenz: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
Elbasvir; Grazoprevir: (Moderate) Administering risperidone with elbasvir; grazoprevir may result in elevated risperidone plasma concentrations. Risperidone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Moderate) Use risperidone and eliglustat together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Encainide: (Major) Since risperidone has a possible risk for QT prolongation and torsade de pointes, caution is advisable during concurrent use of other agents also known to have these effects, including encainide.
Encorafenib: (Major) Avoid coadministration of encorafenib and risperidone due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy have been reported, primarily in the overdosage setting.
Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Entrectinib: (Major) Avoid coadministration of entrectinib with risperidone due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Enzalutamide: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer like enzalutamide. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting enzalutamide. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of enzalutamide to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing enzalutamide, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating enzalutamide in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of enzalutamide in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Eplerenone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Epoprostenol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Eribulin: (Moderate) Monitor ECG if risperidone is coadministered with eribulin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eribulin has also been associated with QT prolongation.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Erythromycin: (Major) Concomitant use of risperidone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Moderate) Concomitant use of escitalopram and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Esketamine: (Major) Closely monitor patients receiving esketamine and risperidone 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) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of esmolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving esmolol concomitantly.
Estazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
Ethacrynic Acid: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethotoin: (Major) Because antipsychotics such as risperidone can lower the seizure threshold, the effectiveness of ethotoin as an anticonvulsant may be reduced. In addition, inducers of CYP3A4, such as ethotoin, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials.
Exenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Felodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and risperidone. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of fentanyl with other central nervous system (CNS) depressants such as risperidone can potentiate the effects of fentanyl and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of fentanyl 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 fentanyl 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.
Fingolimod: (Moderate) Monitor ECG continuously overnight in a medical facility after the first fingolimod dose if risperidone is coadministered due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of risperidone and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Moderate) Concomitant use of fluconazole and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Major) Initiate risperidone at a reduced dose in patients receiving fluoxetine as increased plasma concentrations of risperidone and toxicity may occur; additive QT prolongation is also possible. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when fluoxetine is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; fluoxetine is a potent CYP2D6 inhibitor. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation and TdP have also been reported in patients treated with fluoxetine.
Fluphenazine: (Moderate) Use risperidone and fluphenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Flurazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Fluvoxamine: (Moderate) Use risperidone and fluvoxamine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Major) Concomitant use of risperidone and fosamprenavir may result in altered risperidone plasma concentrations. Risperidone is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as risperidone. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Risperidone has also been associated with a possible risk for QT prolongation and TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosphenytoin: (Major) Because antipsychotics such as risperidone can lower the seizure threshold, the effectiveness of fosphenytoin may be reduced. In addition, potent inducers of CYP3A4, such as fosphenytoin, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Fostemsavir: (Moderate) Use risperidone and fostemsavir together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Furosemide: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. Furthermore, two of four placebo-controlled trials showed that elderly patients with dementia-related psychosis receiving the combination of risperidone and furosemide had a higher incidence of mortality than those receiving either agent alone. The mechanism for this adverse association is unknown. Caution should be exercised when the combined use of risperidone and furosemide is necessary in those with dementia-related psychosis.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and risperidone. Concomitant use of gabapentin with risperidone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Ganirelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to ganirelix, a gonadotropin-releasing hormone (GnRH) analog.
Gemifloxacin: (Moderate) Use risperidone and gemifloxacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and risperidone together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Gilteritinib: (Moderate) Use caution and closely monitor for additive QT prolongation if concurrent use of gilteritinib and risperidone is necessary. Gilteritinib has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) during risperidone therapy have primarily occurred in the overdosage setting.
Glasdegib: (Major) Avoid coadministration of glasdegib with risperidone due to the potential for additive QT prolongation. If coadministration cannot be avoided, consider the patient's underlying disease state(s) and additional potential risk factors. Monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Glimepiride; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Goserelin: (Major) Avoid coadministration of goserelin with risperidone due to the risk of reduced efficacy of goserelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
Granisetron: (Moderate) Use risperidone and granisetron together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with risperidone. Halogenated anesthetics can prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors.
Haloperidol: (Major) Caution is advisable when coadministering medications that have a possible risk of QT prolongation and torsade de pointes (TdP), including risperidone and haloperidol. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation than with routine oral dosing. Coadministration of haloperidol with risperidone may also 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.
Histrelin: (Major) Avoid coadministration of histrelin with risperidone due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydromorphone: (Moderate) Concomitant use of hydromorphone with other central nervous system (CNS) depressants can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include risperidone. Prior to concurrent use of hydromorphone 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 hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. 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.
Hydroxychloroquine: (Major) Concomitant use of risperidone and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Use risperidone and hydroxyzine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as risperidone. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Imipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with risperidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulins: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp like rifampin. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating rifampin in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of rifampin in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Isoniazid, INH; Rifampin: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp like rifampin. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating rifampin in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of rifampin in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Isradipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Itraconazole: (Moderate) Use risperidone and itraconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Itraconazole has also been associated with prolongation of the QT interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with risperidone due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and risperidone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Labetalol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of labetalol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving labetalol concomitantly.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with risperidone. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and risperidone. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) Avoid coadministration of lefamulin with risperidone as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with risperidone due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Risperidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting.
Leuprolide: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levamlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and risperidone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levorphanol: (Moderate) Concomitant use of levorphanol with other CNS depressants such as risperidone can potentiate the effects of levorphanol on respiration, blood pressure, and alertness. Severe hypotension, respiratory depression, profound sedation, or coma may occur. Prior to concurrent use of levorphanol 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. When concomitant treatment with levorphanol with another CNS depressant is necessary, reduce the dose of 1 or both drugs. The initial dose of levorphanol should be reduced by approximately 50% or more when levorphanol is used with another drug that may depress respiration.
Lidocaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Lithium: (Moderate) Use risperidone and lithium together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, it is advisable to monitor patients for neurotoxicity. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Lithium has also been associated with QT prolongation.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with risperidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Loperamide: (Moderate) Use risperidone and loperamide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Loperamide; Simethicone: (Moderate) Use risperidone and loperamide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with risperidone due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Lorazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Loxapine: (Major) Caution is advisable during concurrent use of loxapine and risperidone. 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 risperidone. 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.
Lumacaftor; Ivacaftor: (Major) Potent inducers of CYP3A4, such as lumacaftor, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed, up to double the patient's usual dose, during use of a 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. When planning discontinuation of a CYP3A4 inducer, a lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation to adjust for the expected increase in concentrations of risperidone and its active metabolite. For patients treated with Risperdal Consta 25 mg and discontinuing an inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials.
Lumacaftor; Ivacaftor: (Major) Potent inducers of CYP3A4, such as lumacaftor, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed, up to double the patient's usual dose, during use of a 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. When planning discontinuation of a CYP3A4 inducer, a lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation to adjust for the expected increase in concentrations of risperidone and its active metabolite. For patients treated with Risperdal Consta 25 mg and discontinuing an inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and risperidone, 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 antipsychotic combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
Lurasidone: (Moderate) Co-administration of risperidone with lurasidone 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.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as risperidone. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Risperidone has been associated with a possible risk for QT prolongation and torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Maprotiline: (Moderate) Use risperidone and maprotiline together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mecamylamine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Meclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meclizine. Additive drowsiness or other CNS effects may occur.
Mefloquine: (Moderate) Use risperidone and mefloquine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Meglitinides: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Meperidine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meperidine. Hypotension, respiratory and/or CNS depression can be additive if meperidine is used concomitantly with risperidone.
Meperidine; Promethazine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meperidine. Hypotension, respiratory and/or CNS depression can be additive if meperidine is used concomitantly with risperidone. (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including antipsychotics.
Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Methadone: (Major) Methadone has a known risk of QT prolongation and torsade de pointes (TdP) and a careful assessment of risks versus benefits should be performed before coadministration with drugs having a possible risk of QT prolongation and TdP such as risperidone. Methadone is particularly associated with an increased risk for QT prolongation and TdP at higher doses (e.g., 400 mg/day in adults). Concomitant use of CNS depressants, such as risperidone and methadone, can lead to additive CNS depression, hypotension, or coma. Prior to the use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, the patient's overall response to treatment, and the patient's use of alcohol or illicit drugs. In opioid-naive adults, initiate methadone at a dose of 2.5 mg every 12 hours in patients receiving other CNS depressants. Also consider using a lower dose of the CNS depressant.
Methohexital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Methylphenidate Derivatives: (Moderate) Monitor for extrapyramidal symptoms (EPS) with concomitant use of risperidone and methylphenidate derivatives. Postmarketing cases of extrapyramidal symptoms (dystonia and dyskinesia) have been reported in patients when there was a change in dosage of either medication (increase or decrease in dosage) as well as with the initiation or discontinuation of either or both medications.
Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
Metoprolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of metoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving metoprolol concomitantly.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of metoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving metoprolol concomitantly.
Metronidazole: (Moderate) Concomitant use of metronidazole and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Midostaurin: (Major) The concomitant use of midostaurin and risperidone may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram (ECG) monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Pooled data from controlled trials indicate there are no statistically significant differences in mean changes from baseline in ECG parameters including QT, QTc, and PR intervals when risperidone is compared to placebo. However, post-marketing reports of overdose indicate that QT prolongation and torsade de pointes have occurred.
Mifepristone: (Major) Concomitant use of risperidone and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Miglitol: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mitotane: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer like mitotane. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting mitotane. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of mitotane to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing mitotane, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating mitotane in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of mitotane in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Mobocertinib: (Major) Concomitant use of mobocertinib and risperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Molindone: (Major) Co-administration of risperidone with molindone 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.
Monoamine oxidase inhibitors: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of monoamine oxidase inhibitors (MAOIs) and risperidone due to the risk for additive hypotension and CNS depression.
Morphine: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include risperidone. Prior to concurrent use of morphine 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 a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
Morphine; Naltrexone: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include risperidone. Prior to concurrent use of morphine 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 a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
Moxifloxacin: (Major) Concurrent use of risperidone and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Moxifloxacin has been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Nabilone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Nadolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of nadolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nadolol concomitantly.
Nafarelin: (Moderate) Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
Nalbuphine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and nalbuphine. Concurrent use may result in additive CNS depression.
Nateglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Nebivolol: (Moderate) Risperidone may cause orthostatic hypotension and thus enhance the hypotensive effects of nebivolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nebivolol.
Nebivolol; Valsartan: (Moderate) Risperidone may cause orthostatic hypotension and thus enhance the hypotensive effects of nebivolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nebivolol.
Nicardipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Nifedipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and risperidone; significant prolongation of the QT interval may occur. If coadministration is required and the patient has risk factors for cardiac disease or arrhythmias, careful monitoring is recommended. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Nimodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Nirmatrelvir; Ritonavir: (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Nisoldipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold 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.
Nortriptyline: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Ofloxacin: (Moderate) Concomitant use of ofloxacin and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Use risperidone and olanzapine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Major) Initiate risperidone at a reduced dose in patients receiving fluoxetine as increased plasma concentrations of risperidone and toxicity may occur; additive QT prolongation is also possible. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when fluoxetine is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; fluoxetine is a potent CYP2D6 inhibitor. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation and TdP have also been reported in patients treated with fluoxetine. (Moderate) Use risperidone and olanzapine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Moderate) Use risperidone and olanzapine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Oliceridine: (Major) Concomitant use of oliceridine with risperidone may cause excessive sedation and somnolence. Limit the use of oliceridine with risperidone 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.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Ondansetron: (Major) Concomitant use of risperidone and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Opicapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with risperidone. Osilodrostat is associated with dose-dependent QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Osimertinib: (Major) Avoid coadministration of risperidone with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in risperidone-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Oxaliplatin: (Major) Closely monitor electrolytes and ECGs for QT prolongation if coadministration of risperidone with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
Oxazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Oxymorphone: (Moderate) Concomitant use of oxymorphone with other CNS depressants may produce additive CNS depressant effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants include risperidone. Prior to concurrent use of oxymorphone 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 a CNS depressant is used concurrently with oxymorphone, a reduced dosage of oxymorphone (1/3 to 1/2 of the usual dose) and/or the CNS depressant is recommended. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, it is recommended to use an initial dosage of 5 mg PO every 12 hours. Monitor for sedation or respiratory depression.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking risperidone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Pacritinib: (Major) Concomitant use of pacritinib and risperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Because paliperidone is the major active metabolite of risperidone, excessive paliperidone exposure is possible during concurrent use of the two drugs and coadministration is generally avoided. In addition, paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as risperidone. Coadministration of antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Panobinostat: (Major) The coadministration of panobinostat with risperidone should be avoided if possible; both agents have a possible risk for QT prolongation and torsade de pointes. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
Paroxetine: (Major) Initiate risperidone at a reduced dose in patients receiving paroxetine as increased plasma concentrations of risperidone and toxicity may occur. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when paroxetine is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; paroxetine is a strong CYP2D6 inhibitor. Daily dosing of paroxetine 20 mg PO in patients stabilized on risperidone (4 to 8 mg/day) increased mean plasma concentrations of risperidone roughly 4-fold, decreased 9-hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold. Other data suggest that daily administration of paroxetine increases plasma concentrations of risperidone 3- to 9-fold.
Pasireotide: (Moderate) Use risperidone and pasireotide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Both risperidone and pazopanib have been associated with a possible risk for QT prolongation and torsade de pointes; therefore, caution is advisable during coadministration. If concurrent treatment is required and the patient has risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
Penbutolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of penbutolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving penbutolol concomitantly.
Pentamidine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include pentamidine.
Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
Pentazocine; Naloxone: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
Pentobarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as risperidone.
Perindopril; Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Perphenazine: (Moderate) Use risperidone and perphenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Moderate) Use risperidone and perphenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Phenobarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Phenoxybenzamine: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Phentolamine: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Phenytoin: (Major) Because antipsychotics such as risperidone can lower the seizure threshold, the effectiveness of phenytoin as an anticonvulsant may be reduced. In addition, potent inducers of CYP3A4, such as phenytoin, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Consider the patient's underlying disease state(s) and additional potential risk factors if pimavanserin and risperidone coadministration cannot be avoided. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Pimozide: (Contraindicated) Risperidone has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Pindolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of pindolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving pindolol concomitantly.
Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pioglitazone; Glimepiride: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pioglitazone; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pitolisant: (Major) Avoid coadministration of pitolisant with risperidone as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking risperidone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Risperidone has been associated with a possible risk for QT prolongation and TdP, primarily in the overdose setting.
Posaconazole: (Moderate) Use risperidone and posaconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Posaconazole has also been associated with QT prolongation and rare cases of TdP.
Potassium-sparing diuretics: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Pramipexole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Pramlintide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Prazosin: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and risperidone. Concomitant use of pregabalin with risperidone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Primaquine: (Moderate) Use risperidone and primaquine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Primaquine has also been associated with QT prolongation.
Primidone: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Procainamide: (Major) Risperidone should be used cautiously and with close monitoring with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Prochlorperazine: (Moderate) Use risperidone and prochlorperazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Promethazine: (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Promethazine; Dextromethorphan: (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Promethazine; Phenylephrine: (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Propafenone: (Major) Concomitant use of risperidone and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propranolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of propranolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving propranolol concomitantly.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of propranolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving propranolol concomitantly.
Protriptyline: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Pseudoephedrine; Triprolidine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Pyrilamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Quazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Quetiapine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include quetiapine. Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Additionally, according to the manufacturer, no significant kinetic drug interactions were identified when quetiapine was coadministered with haloperidol or risperidone.
Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include risperidone.
Quinine: (Major) Concurrent use of quinine and risperidone should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is required and the patient has risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
Ranitidine: (Moderate) Although dosage adjustments are not necessary, patients receiving concurrent treatment with risperidone and ranitidine should be monitored for risperidone-induced side effects or extrapyramidal symptoms. Pharmacokinetic data indicate that increased exposure to risperidone and its active metabolite occurs during use of ranitidine. This interaction is thought to be the result of inhibition of CYP3A4, one of the isoenzymes responsible for the metabolism of risperidone.
Ranolazine: (Moderate) Use risperidone and ranolazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs concurrent use may result in additive QT prolongation.
Rasagiline: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or rasagiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rasagiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with rasagiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Relugolix: (Moderate) Use risperidone and relugolix together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Use risperidone and relugolix together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Remifentanil: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including remifentanil.
Remimazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ribociclib: (Major) Avoid coadministration of ribociclib with risperidone if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner and risperidone has also been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with risperidone if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner and risperidone has also been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Rifampin: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp like rifampin. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating rifampin in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of rifampin in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Rifapentine: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer like rifapentine. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating rifapentine in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of rifapentine in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Rilpivirine: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Ritonavir: (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Rolapitant: (Major) Coadministration of risperidone, a CYP2D6 substrate, and rolapitant, a CYP2D6 inhibitor, may increase plasma concentrations of risperidone. The inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. When oral risperidone is given with a CYP2D6 inhibitor, the dose of risperidone should be reduced; do not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting injection, the current adult dosage should be re-evaluated when a CYP2D6 inhibitor is initiated or discontinued. When initiation of a CYP2D6 inhibitor is considered, patients may be placed on a lower dose of injectable risperidone 2 to 4 weeks prior to initiation to adjust for the expected increase in risperidone plasma concentrations. For patients receiving a 25 mg dose, it is recommended to maintain the 25 mg dose upon initiation of the CYP2D6 inhibitor unless clinical judgment warrants lowering the dose to 12.5 mg or interrupting risperidone therapy. The efficacy of the 12.5 mg dose has not been evaluated in clinical trials. When injectable risperidone is initiated in patients already receiving a CYP2D6 inhibitor, a starting dose of 12.5 mg can be considered. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
Romidepsin: (Moderate) Monitor ECG and electrolytes if risperidone is coadministered with romidepsin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Romidepsin has also been reported to prolong the QT interval.
Ropinirole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Rotigotine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Safinamide: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Saquinavir: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. Avoid coadministration. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Secobarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Selegiline: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with risperidone is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Semaglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sertraline: (Moderate) Concomitant use of sertraline and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sibutramine: (Major) Caution and close monitoring should be observed when administering sibutramine with drugs that are dopamine antagonists such as the atypical antipsychotics. Monitor for CNS depression, changes in mood or behavior, and for other drug-related adverse reactions. Sibutramine has not been systematically evaluated in combination with antipsychotic medications. Sibutramine is a serotonin reuptake inhibitor that also inhibits norepinephrine and dopamine reuptake. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
Simvastatin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving risperidone due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Use risperidone and solifenacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with risperidone due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Concomitant use of sotalol and risperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
St. John's Wort, Hypericum perforatum: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer. St. John's wort is a strong inducer of CYP3A4; however, it should be noted that the amount of individual constituents in various St. John's wort products may alter the inhibitor or inducer effects, making drug interactions unpredictable. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of a strong CYP3A4 inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing a strong CYP3A4 inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
Stiripentol: (Major) Monitor for excessive sedation and somnolence during coadministration of stiripentol and risperidone. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Concomitant use of sufentanil with other CNS depressant, such as risperidone, can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects. A dose reduction of one or both drugs may be warranted.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sunitinib: (Moderate) Use risperidone and sunitinib together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Sunitinib can also prolong the QT interval.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and atypical antipsyhotics. Dosage adjustments of suvorexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with risperidone. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol 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 a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
Telavancin: (Moderate) Use risperidone and telavancin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Telavancin has also been associated with QT prolongation.
Telmisartan; Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Temazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Terazosin: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Terbinafine: (Major) Initiate risperidone at a reduced dose in patients receiving terbinafine as increased plasma concentrations of risperidone and toxicity may occur. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when terbinafine is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; terbinafine is a strong CYP2D6 inhibitor.
Tetrabenazine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as risperidone. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
Thiazide diuretics: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Thioridazine: (Contraindicated) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer primarily in the overdosage setting. However, due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of risperidone and thioridazine is considered contraindicated.
Thiothixene: (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.
Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
Tipranavir: (Major) Initiate risperidone at a reduced dose in patients receiving tipranavir as increased plasma concentrations of risperidone and toxicity may occur. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when tipranavir is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; tipranavir is a strong CYP2D6 inhibitor.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Tolcapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Tolterodine: (Moderate) Use risperidone and tolterodine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tolterodine has been