Note: Slow titration is recommended to improve tolerability; use lowest effective dose. An ECG should be performed baseline and periodically thereafter, especially during dosage adjustment.
Tourette disorder, moderate to severe: Note: Due to potential cardiac toxicity, not recommended as first-line therapy; a trial of standard treatment is necessary before initiating a trial of pimozide therapy (Scahill 2006). Reliable dose-response data in patients younger than 12 years of age with Tourette disorder are lacking.
Children ≥2 years and Adolescents: Oral:
Weight-directed dosing: Initial: 0.05 mg/kg/dose once daily, preferably at bedtime; maximum initial dose: 1 mg/dose; may increase dose every third day if needed; maximum daily dose: 0.2 mg/kg/day not to exceed 10 mg/day; in active comparator trials in children ≥7 years old, reported mean effective dose: 2.4 to 3.4 mg/day (range: 1 to 6 mg/day) (Gilbert 2004; Sallee 1997).
Fixed dosing: 0.5 to 1 mg daily; usual daily dose range: 2 to 8 mg/day (AACAP [Murphy 2013])
Note: If therapy requires exceeding dose of 0.05 mg/kg/day, CYP2D6 geno-/phenotyping should be performed; CYP2D6 poor metabolizers should be dose titrated in ≥14-day increments and should not receive doses in excess of 0.05 mg/kg/day, up to 4 mg/day. This is based on a study of simulated multiple-dose pimozide exposures using pharmacokinetic parameters following a single dose in 32 healthy people; CYP2D6 poor metabolizers had higher pimozide exposure, which is a surrogate for arrhythmia risk; the study did not provide guidance for CYP2D6 intermediate or ultra-rapid metabolizers (Rogers 2012).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Children ≥2 years and Adolescents:
ECG changes: QTc prolongation >0.47 seconds or >25% above baseline: Do not increase dose further; consider a lower dose.
Neutropenia: Absolute neutrophil count <1,000/mm3: Discontinue pimozide; monitor CBC until recovery.
Neuroleptic malignant syndrome: Discontinue; monitor carefully if therapy is reinitiated.
Tardive dyskinesia signs/symptoms: Consider discontinuing therapy; a possible early sign of tardive dyskinesia is fine vermicular movement of the tongue; if this appears, and the medication is stopped, tardive dyskinesia may not develop.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
(For additional information see "Pimozide: Drug information")
Note: If therapy requires exceeding dose of 4 mg/day, CYP2D6 geno-/phenotyping should be performed.
Tourette disorder (alternative agent) (AAN [Pringsheim 2019]): Oral: Initial: 1 to 2 mg/day in divided doses, then increase dosage as needed every other day; maximum dose: 10 mg/day or 0.2 mg/kg/day (whichever is less).
Delusional infestation (also called delusional parasitosis) (off-label): Oral: Initial: 0.5 to 2 mg once daily. Increase dose based on response and tolerability in 1 mg increments every 3 to 7 days up to a usual dosage of 2 to 4 mg daily (doses up to 12 mg daily have been studied, however manufacturer labeling recommends a maximum dose of 10 mg/day or 0.2 mg/kg/day). Consider taper of therapy in decrements of ≥1 mg weekly after adequate relief of symptoms for 1 month; assess for return of symptoms and need for continued long-term treatment (Lorenzo 2004).
Dosage adjustment for CYP2D6 poor metabolizers: Increase dose based on response and tolerability at intervals ≥14 days; do not exceed 4 mg/day.
Discontinuation of therapy: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (APA [Keepers 2020]; Lambert 2007; Moncrieff 2020; Post 2020).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Cerovecki 2013; Remington 2005; Takeuchi 2017). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Stroup 2020).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustment provided in manufacturer’s labeling; use with caution.
There are no dosage adjustment provided in manufacturer’s labeling; use with caution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Orap: 1 mg [DSC], 2 mg [DSC]
Generic: 1 mg, 2 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Orap: 2 mg
Orap: 4 mg [contains fd&c blue #1 aluminum lake, tartrazine (fd&c yellow #5)]
Generic: 2 mg, 4 mg
Oral: May be administered without regard to meals; preferable to administer dose at bedtime.
Store at 25°C (77°F); excursion permitted to 15°C to 30°C (59°F to 86°F).
Suppression of severe motor and phonic (vocal) tics in patients with Tourette disorder who have failed to respond satisfactorily to standard treatment and whose daily life function and/or development is severely compromised by the presence of motor and phonic tics (FDA approved in ages ≥2 years and adults). Note: A trial of standard treatment is currently recommended before a trial of pimozide due to potential cardiac toxicity with pimozide therapy (Scahill 2006).
Beers Criteria: Antipsychotics are identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older due to an increased risk of cerebrovascular accidents (stroke) and a greater rate of cognitive decline and mortality in patients with dementia. Antipsychotics may be appropriate for schizophrenia, bipolar disorder, other mental health conditions or short-term use as antiemetic during chemotherapy but should be given in the lowest effective dose for the shortest duration possible. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2019]).
KIDs List: Dopamine antagonists, when used in pediatric patients <18 years of age, are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list; use should be avoided in infants and used with caution in children and adolescents due to risk of acute dystonia (dyskinesia) (strong recommendation; moderate quality of evidence) (PPA [Meyers 2020]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequencies as reported in adults (limited data) and/or children with Tourette's disorder.
>10%:
Central nervous system: Sedation (70%), akathisia (40%), drowsiness (35%; children: ≤25%), behavioral changes (22% to 25%), hypertonia (15%)
Gastrointestinal: Xerostomia (25%), constipation (20%)
Genitourinary: Impotence (15%)
Neuromuscular & skeletal: Akinesia (40%), weakness (14%)
Ophthalmic: Decreased accommodation (20%), visual disturbance (3% to 20%)
1% to 10%:
Cardiovascular: ECG abnormality (3%)
Central nervous system: Depression (10%), insomnia (10%), speech disturbance (10%), nervousness (5% to 6%), writing difficulty (handwriting change: 5%), headache (3% to 5%), abnormal dreams (3%)
Dermatologic: Skin rash (3%)
Endocrine & metabolic: Increased thirst (5%)
Gastrointestinal: Sialorrhea (6%), diarrhea (5%), dysgeusia (5%), increased appetite (5%), dysphagia (3%)
Neuromuscular & skeletal: Muscle rigidity (10%), stooped posture (10%), hyperkinesia (3%), myalgia (3%), torticollis (3%), tremor (3%)
Ophthalmic: Photophobia (5%)
Frequency not defined (some reported for disorders other than Tourette's disorder):
Cardiovascular: Chest pain, hypertension, hypotension, orthostatic hypotension, prolonged QT interval on ECG, syncope, tachycardia, ventricular arrhythmia
Central nervous system: Dizziness, excitement, drug-induced extrapyramidal reaction (dystonia, pseudoparkinsonism, tardive dyskinesia), neuroleptic malignant syndrome, palpitations, seizure
Dermatologic: Diaphoresis, skin irritation
Endocrine & metabolic: Decreased libido, hyponatremia, weight changes (gain/loss)
Gastrointestinal: Anorexia, gastrointestinal distress, nausea, vomiting
Genitourinary: Nocturia
Hematologic & oncologic: Hemolytic anemia
Ophthalmic: Blurred vision, cataract, periorbital edema
Renal: Polyuria
<1%, postmarketing, and/or case reports: Gingival hyperplasia
Hypersensitivity to pimozide or any component of the formulation; severe toxic CNS depression; coma; history of cardiac arrhythmias; congenital long QT syndrome; concurrent use with QTc-prolonging agents; hypokalemia or hypomagnesemia; concurrent use of drugs that are inhibitors of CYP3A4, including concurrent use of the azole antifungals itraconazole and ketoconazole, macrolide antibiotics (eg, clarithromycin or erythromycin [Note: The manufacturer lists azithromycin, dirithromycin, and troleandomycin in its list of contraindicated macrolides; however, azithromycin does not inhibit CYP3A4, but may interact with pimozide on the basis of QTc prolongation]), protease inhibitors (ie, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir), citalopram, escitalopram, nefazodone, sertraline, and other less potent inhibitors of CYP3A4 (eg, fluvoxamine, zileuton); concurrent use with strong CYP2D6 inhibitors (eg, paroxetine); concurrent use with medications that may cause motor or phonic tics (eg, amphetamines, methylphenidate, pemoline) until it is determined if medications or Tourette disorder is causing tics; treatment of simple tics or tics other than Tourette disorder
Canadian labeling: Additional contraindications (not in US labeling): Brain damage; depressive disorders; Parkinson disease; renal impairment; liver disorders; pheochromocytoma; blood dyscrasias; regional or spinal anesthesia; family history of congenital long QT syndrome; acquired long QT syndrome; clinically significant bradycardia
Concerns related to adverse effects:
• Altered cardiac conduction: May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics. Contraindicated in patients with underlying QT prolongation, in those taking medicines that prolong the QT interval, or cause polymorphic ventricular tachycardia; monitor ECG closely for dose-related QT effects. Sudden unexplained deaths have occurred in patients taking high doses (~1 mg/kg). ECG monitoring recommended periodically during therapy. Use caution with concomitant medication or conditions which cause hypokalemia or hypomagnesemia; correct hypokalemia or hypomagnesemia prior to initiation of therapy.
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. Relative to neuroleptics, pimozide has a high potency of cholinergic blockade (Yamamura 1976).
• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm3.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Esophageal dysmotility/Aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (ie, Alzheimer disease), particularly in patients >75 years (Herzig 2017; Maddalena 2004).
• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Keepers 2020]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.
• Hyperprolactinemia: Antipsychotics are associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.
• Neuroleptic malignant syndrome (NMS): Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability; may also be associated with increased CPK, myogloburia, and acute renal failure. Discontinue use; may recur upon rechallenge.
• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease.
• Dementia: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared with placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. The APA recommends giving preference to second generation antipsychotics over first-generation antipsychotics in elderly patients with dementia-related psychosis due to a potentially greater risk of harm relative to second-generation antipsychotics (APA [Reus 2016]). Pimozide is not approved for the treatment of dementia-related psychosis.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
Special populations:
• CYP2D6 poor metabolizers: Increased pimozide serum concentration and prolonged half-life are observed in CYP2D6 poor metabolizers; dose adjustment required
Other warnings/precautions:
• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradually taper antipsychotics to avoid physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013).
Pimozide may have a tumorigenic potential; a dose related increase in pituitary tumors was observed in studies of mice; full significance in humans is unknown; however, this finding should be considered when deciding to use pimozide chronically in a young patient. Limited information exists about the use of pimozide in children <12 years of age.
Substrate of CYP1A2 (minor), CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome may be increased. Risk X: Avoid combination
Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): May diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
Aprepitant: May increase the serum concentration of Pimozide. Risk X: Avoid combination
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Pimozide. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Pimozide. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Pimozide. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Pimozide. Risk X: Avoid combination
CYP3A4 Inhibitors (Weak): May increase the serum concentration of Pimozide. Risk X: Avoid combination
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy
Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fosaprepitant: May increase the serum concentration of Pimozide. The active metabolite aprepitant is likely responsible for this effect. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Pimozide. Risk X: Avoid combination
Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
Haloperidol: Pimozide may enhance the QTc-prolonging effect of Haloperidol. Risk X: Avoid combination
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Letermovir: May increase the serum concentration of Pimozide. Risk X: Avoid combination
Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Lofepramine: May enhance the arrhythmogenic effect of Pimozide. Risk X: Avoid combination
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Ondansetron: Pimozide may enhance the QTc-prolonging effect of Ondansetron. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Pentamidine (Systemic): Pimozide may enhance the QTc-prolonging effect of Pentamidine (Systemic). Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid combination
Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination
QT-prolonging Agents (Moderate Risk): Pimozide may enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rolapitant: May increase the serum concentration of Pimozide. Risk X: Avoid combination
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Pimozide. Risk X: Avoid combination
Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Spironolactone: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Treosulfan: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Pimozide serum concentration may be increased when taken with grapefruit juice due to CYP3A4 inhibition. Management: Avoid concurrent use with grapefruit juice.
Adverse events were observed in some animal reproduction studies. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.
ECG should be performed at baseline and periodically thereafter, especially during dosage adjustment; mental status; abnormal involuntary movement scale (AIMS), extrapyramidal symptoms (EPS) screening; CBC with differential (patients with a history of low WBC or drug-induced leukopenia or neutropenia; monitor frequently during first few months of therapy); additionally during therapy consider periodic assessment of: Vital signs, serum potassium, magnesium, sodium, renal and hepatic function, growth parameters (height, weight, BMI)
Pimozide, a diphenylbutylperidine conventional antipsychotic, is a potent centrally-acting dopamine-receptor antagonist resulting in its characteristic neuroleptic effects
Onset of action: Within 1 week; Maximum effect: 4 to 6 weeks
Duration of action: Variable
Absorption: ≥50%
Protein binding: 99%
Metabolism: Hepatic via N-dealkylation primarily by CYP3A4, but with contributions by CYP1A2 and CYP2D6; significant first-pass effect
Half-life elimination: Children 6 to 13 years (n=4): Mean ± SD: 66 ± 49 hours; Adults 23 to 39 years (n=7): Mean ± SD: 111 ± 57 hours (Sallee 1987)
Time to peak, serum: 6 to 8 hours; Range: 4 to 12 hours
Excretion: Urine
Tablets (Pimozide Oral)
1 mg (per each): $1.83
2 mg (per each): $2.44
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