RISPERDAL CONSTA (risperidone microspheres)

There are 2 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Iomeprol/Neuroleptics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Neuroleptics may lower seizure threshold.(1) CLINICAL EFFECTS: Use of iomeprol in a patient receiving a neuroleptic may increase the risk of seizure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of iomeprol states that neuroleptics should be discontinued 48 hours before iomeprol use. Treatment with a neuroleptic should not be resumed until 24 hours post-procedure.(1) DISCUSSION: Because neuroleptics may lower seizure threshold, neuroleptics should be discontinued 48 hours before iomeprol use. Treatment with a neuroleptic should not be resumed until 24 hours post-procedure.(1)	IOMERON 350
Selected CYP2D6 Substrates/Mavorixafor SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Mavorixafor is a strong inhibitor of CYP2D6 and is expected to inhibit the metabolism of agents through this pathway.(1) CLINICAL EFFECTS: Concurrent use of mavorixafor may result in elevated levels of and toxicity from agents metabolized by CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2) PATIENT MANAGEMENT: The US manufacturer of mavorixafor states concurrent use with CYP2D6 substrate that are highly dependent on CYP2D6 metabolism is contraindicated.(1) The US manufacturer of doxepin states if concurrent use of doxepin and strong CYP2D6 inhibitors such as mavorixafor is warranted, monitor doxepin plasma concentrations and reduce the doxepin dose based on doxepin plasma concentrations.(5) DISCUSSION: Mavorixafor (400 mg) increased dextromethorphan (CYP2D6 substrate) maximum concentration (Cmax) and area-under-curve (AUC) by 6-fold and 9-fold, respectively.(1) Selected CYP2D6 substrates linked to this monograph include: aripiprazole, brexpiprazole, desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, fenfluramine, metoclopramide, methoxyphenamine, metoprolol, mexiletine, nebivolol, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, venlafaxine, and yohimbine.	XOLREMDI

Drug contraindication overview.

*Known hypersensitivity to either risperidone or paliperidone (metabolite of risperidone) or to any of the excipients in the risperidone formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported.

Adverse reaction overview.

The most frequent adverse effects of oral risperidone reported in >=5% of patients who received the drug in clinical trials and with an incidence of at least twice that of those receiving placebo were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain. The most frequent adverse effects of IM risperidone in patients with schizophrenia (>=5%) were headache, parkinsonism, dizziness, akathisia, fatigue, constipation, dyspepsia, sedation, weight increase, pain in extremity, and dry mouth. The most frequent adverse effects of IM risperidone in patients with bipolar disorder were weight increase (5% in monotherapy trial) and tremor and parkinsonism (>=10% in adjunctive therapy trial).

The most frequent adverse effects of subcutaneous risperidone (Uzedy(R)) reported in >=5% of patients who received the drug in clinical trials and with an incidence greater than placebo were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain. The most frequent injection site reactions with subcutaneous risperidone (Uzedy(R)) (>=5% and greater than placebo) were pruritus and nodule. The most frequent adverse effects of subcutaneous risperidone (Perseris(R)) reported in >=5% of patients who received the drug in clinical trials and with an incidence of at least twice that of those receiving placebo were increased weight, sedation/somnolence, and musculoskeletal pain.

Safety and efficacy of risperidone for IM or subcutaneous administration have not been established in pediatric patients. Safety and efficacy of oral risperidone for the treatment of schizophrenia in adolescents 13-17 years of age were demonstrated in 2 short-term clinical trials in 417 patients. Efficacy and safety of oral risperidone for the treatment of acute manic or mixed episodes associated with bipolar I disorder in children and adolescents 10-17 years of age were demonstrated in a 3-week, placebo-controlled study in 169 patients.

The safety and efficacy of oral risperidone in children younger than 13 years of age with schizophrenia or younger than 10 years of age with bipolar I disorder have not been established. Efficacy and safety of oral risperidone in the treatment of irritability associated with autistic disorder have been evaluated in 3 placebo-controlled trials in pediatric patients 5 to 17 years of age. In clinical trials in 1885 children and adolescents treated with risperidone, 2 patients (0.1%) reportedly developed tardive dyskinesia, which resolved upon discontinuance of therapy.

Weight gain has been observed in children and adolescents during treatment with oral risperidone; clinical monitoring of weight is recommended during treatment. Somnolence frequently occurred in placebo-controlled trials of oral risperidone in pediatric patients with autistic disorder. Most cases were mild to moderate in severity, occurred early during therapy (peak incidence during the first 2 weeks of therapy), and were transient (median duration of 16 days).

Somnolence also was the most common adverse effect in clinical trials in children and adolescents with bipolar disorder as well as in schizophrenia clinical trials in adolescents; as in the autistic disorder trials, somnolence usually occurred early during therapy and was transient. Pediatric patients experiencing persistent somnolence may benefit from a change in dosage regimen. Oral risperidone has been shown to elevate prolactin concentrations in children and adolescents as well as adults.

In double-blind, placebo-controlled trials of up to 8 weeks' duration in children and adolescents 5-17 years of age, 49% of oral risperidone-treated patients had elevated prolactin concentrations compared with 2% of those receiving placebo. Similarly, in placebo-controlled trials in children and adolescents 10-17 years of age with bipolar disorder or adolescents 13-17 years of age with schizophrenia, 82-87% of risperidone-treated patients had elevated prolactin concentrations compared with 3-7% of placebo recipients. Increases in prolactin concentrations were dose dependent and generally greater in female than male patients across indications.

In clinical trials conducted in 1885 children and adolescents, galactorrhea and gynecomastia reportedly occurred in 0.8 and 2.3%, respectively, of oral risperidone-treated patients. The manufacturers state that the long-term effects of oral risperidone on growth and sexual maturation have not been fully evaluated in children and adolescents.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None