Note: ECG should be performed at baseline and periodically thereafter, especially during dosage adjustment.
Delusional infestation (also called delusional parasitosis) (alternative agent) (off-label):
Note: Reserve for those who cannot access or tolerate preferred options due to tolerability issues with pimozide (Suh 2024).
Oral: Initial: 0.5 to 2 mg once daily. Increase dose based on response and tolerability in 1 mg increments every 2 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). If therapy requires exceeding dose of 4 mg/day, CYP2D6 geno-/phenotyping should be performed. 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).
Tourette syndrome (alternative agent):
Note: The American Academy of Neurology comprehensive systematic review of the treatment of tics in people with Tourette syndrome and chronic tic disorders concluded there is low confidence that pimozide is superior to placebo at reducing tics (AAN [Pringsheim 2019]).
Oral: Initial: 1 to 2 mg/day once daily at bedtime or 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). If therapy requires exceeding dose of 4 mg/day, CYP2D6 geno-/phenotyping should be performed (Shapiro 1989; manufacturer labeling).
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 2022).
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.
ECG changes: QTc prolongation >0.52 seconds or >25% above baseline: Decrease dose.
Note: Avoid use (Ref).
(For additional information see "Pimozide: Pediatric drug information")
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Constipation, xerostomia
Genitourinary: Erectile dysfunction
Nervous system: Akathisia, akinesia, asthenia, behavioral changes, drowsiness, hypertonia, sedated state
Ophthalmic: Decreased accommodation, visual disturbance
1% to 10%:
Cardiovascular: ECG abnormality (including appearance of U waves on ECG, flattened T wave on ECG, inversion T wave on ECG, notching of T wave on ECG, and prolonged QT interval on ECG)
Dermatologic: Skin rash
Endocrine & metabolic: Increased thirst
Gastrointestinal: Diarrhea, dysgeusia, dysphagia, increased appetite, sialorrhea
Nervous system: Abnormal dreams, headache, insomnia, nervousness, speech disturbance, tremor, writing difficulty (handwriting change)
Neuromuscular & skeletal: Hyperkinetic muscle activity, muscle rigidity, myalgia, stooped posture, torticollis
Ophthalmic: Photophobia
Frequency not defined:
Cardiovascular: Chest pain, hypertension, hypotension, orthostatic hypotension, palpitations, syncope, tachycardia
Dermatologic: Diaphoresis, skin irritation
Endocrine & metabolic: Decreased libido, weight gain, weight loss
Gastrointestinal: Anorexia, gastrointestinal distress, nausea, vomiting
Genitourinary: Nocturia, urinary frequency
Nervous system: Dizziness, excitement, parkinsonism
Neuromuscular & skeletal: Dyskinesia
Ophthalmic: Blurred vision, cataract, periorbital edema
Postmarketing:
Endocrine & metabolic: Hyponatremia, polydipsia (Landry 1992)
Gastrointestinal: Gingival hyperplasia
Genitourinary: Urinary incontinence (Shapiro 1981)
Hematologic & oncologic: Hemolytic anemia
Nervous system: Depression (Landry 1992), extrapyramidal reaction (including dystonia, hyperreflexia, oculogyric crisis, opisthotonos, pseudoparkinsonism, tardive dyskinesia) (Ernst 1993), neuroleptic malignant syndrome, seizure
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 syndrome is causing tics; treatment of simple tics or tics other than Tourette syndrome.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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; concurrent use with serotonin reuptake inhibitors (eg, sertraline, paroxetine, citalopram, escitalopram).
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: ay 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 low likelihood of cholinergic blockade.
• 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 (eg, 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: Older adults 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 older adults 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, alcohol use disorder, or concurrent therapy with medications that 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 1 mg, 2 mg
Yes
Tablets (Pimozide Oral)
1 mg (per each): $1.83
2 mg (per each): $2.44
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 2 mg, 4 mg
Oral: May be administered without regard to meals; preferable to administer dose at bedtime.
Tourette syndrome: Suppression of severe motor and phonic tics in patients with Tourette syndrome who have failed to respond satisfactorily to standard treatment. Note: The American Academy of Neurology comprehensive systematic review of the treatment of tics in people with Tourette syndrome and chronic tic disorders concluded there is low confidence that pimozide is superior to placebo at reducing tics (AAN [Pringsheim 2019]).
Delusional infestation (also called delusional parasitosis)
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia. Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. 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. Use of antipsychotics may be appropriate for labeled indications including schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive therapy in major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).
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]).
Substrate of CYP1A2 (minor), CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents With Seizure Threshold Lowering Potential: May enhance the adverse/toxic effect of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Aldesleukin: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). 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
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
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
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
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. 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
Bulevirtide: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
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: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. 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
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
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
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
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
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
Dinutuximab Beta: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Donepezil: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
Elranatamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Epcoritamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
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
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
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). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification
Galantamine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Givinostat: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Glofitamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
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
Huperzine A: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
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
Itraconazole: May increase the serum concentration of Pimozide. Risk X: Avoid combination
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. 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
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
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
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: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Mosunetuzumab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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
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
Pacritinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Paliperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
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
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. 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
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
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
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
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
Ritlecitinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Rivastigmine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
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
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
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. 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
Talquetamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Teclistamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Treosulfan: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Triptorelin: Hyperprolactinemic Agents may diminish the therapeutic effect of Triptorelin. Risk X: Avoid combination
Trofinetide: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
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
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. 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.
It is not known if pimozide is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Frequency of Antipsychotic Monitoring in Pimozidea,b | ||
---|---|---|
Monitoring parameter |
Frequency of monitoring |
Comments |
a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected adverse reactions) in addition to the timeline. | ||
b ADA 2004; APA [Keepers 2020]; Landi 2005; Seppala 2018; manufacturer's labeling. | ||
c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. | ||
d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; and past or current EPS. | ||
e Cardiac risk factors include congenital long QT syndrome, structural or functional cardiac disease, bradycardia, family history of sudden cardiac death. | ||
Adherence |
Every visit |
|
Blood chemistries (electrolytes, renal function, liver function, TSH) |
As clinically indicated |
|
CBC |
As clinically indicated |
Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia. |
CYP2D6 genotyping or phenotyping |
At baseline, to establish dose |
|
ECG |
As clinically indicated |
Check after significant dose increase or new QTc-prolonging medication if there are cardiac risk factors.e |
Extrapyramidal symptoms |
Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high risk.c |
|
Fall risk |
As clinically indicated |
Evaluate regularly in patients ≥60 years of age. |
Fasting plasma glucose/HbA1c |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
Lipid panel |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow lipid guidelines. |
Mental status and alertness |
Every visit |
|
Metabolic syndrome history |
Annually |
Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease. |
Ocular exam |
As clinically indicated |
Particularly important for those taking thioridazine or chlorpromazine, or those with diabetes and other conditions that impact sight. |
Prolactin |
Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported. |
Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function. |
Tardive dyskinesia |
Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high risk.d |
|
Vital signs (BP, orthostatics, temperature, pulse, signs of infection) |
As clinically indicated |
|
Weight/Height/BMI |
Every visit for first 6 months, then quarterly |
Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. |
Timing of serum samples: Draw trough just before next dose (Hiemke 2018).
Therapeutic reference range: 15 to 20 ng/mL (SI: 32.55 to 43.4 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations; however, therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).
Laboratory alert level: 20 ng/mL (SI: 43.4 nmol/L) (Hiemke 2018).
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
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