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Levomepromazine (methotrimeprazine) (United States: Not available): Drug information

Levomepromazine (methotrimeprazine) (United States: Not available): Drug information
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For additional information see "Levomepromazine (methotrimeprazine) (United States: Not available): Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: Canada
  • Methoprazine;
  • Nozinan
Pharmacologic Category
  • Analgesic, Nonopioid;
  • Antimanic Agent;
  • First Generation (Typical) Antipsychotic
Dosing: Adult

Note: Patients receiving parenteral therapy should be switched to oral therapy as soon as possible. If pronounced sedation occurs, administer smaller doses during the day and higher doses at night.

Anxiety

Anxiety: Oral: Initial: 6 to 25 mg/day in 3 divided doses with meals; may increase based on response and tolerability.

Bipolar disorder

Bipolar disorder:

IM: 25 mg, 3 or 4 times per day.

Oral: Initial: 50 to 75 mg/day in 2 or 3 divided doses; may increase based on response and tolerability. Patients requiring higher initial doses (100 to 200 mg/day in divided doses) should remain in bed for the first few days of therapy. Doses ≥1 g/day may be needed in some patients with psychosis.

Insomnia

Insomnia:

Note: Limit long-term use (>4 weeks) to cases for which nonpharmacologic treatments are not available or not effective and benefits are felt to outweigh risks (Ref).

Oral: Single dose of 10 to 25 mg at bedtime.

IM: Single dose of 25 mg at bedtime.

SUBQ (off-label route): Palliative care:

Continuous infusion: 6.25 to 250 mg/day in sterile water or NS (via syringe pump) (Ref).

Bolus administration: Median dose: 6.25 mg/day (range: 3.12 to 25 mg/day) administered as 1 to 2 divided doses (Ref).

Nausea/vomiting

Nausea/vomiting:

IM: 25 mg, 3 or 4 times per day.

Oral: Initial: 6 to 25 mg/day in 3 divided doses with meals; may increase based on response and tolerability.

SUBQ (off-label route): Palliative care:

Continuous infusion: 6.25 to 250 mg/day in sterile water or NS (via syringe pump) (Ref).

Bolus administration: Median dose: 6.25 mg/day (range: 3.12 to 25 mg/day) administered as 1 to 2 divided doses (Ref).

Pain

Pain:

IM: 25 mg, 3 or 4 times per day. For postoperative adjunctive analgesia: 10 to 25 mg every 8 hours (equivalent to oral dose of 20 to 40 mg); consider additional dose reduction if administered in combination with narcotics.

Oral:

Mild conditions: Initial: 6 to 25 mg/day in 3 divided doses with meals; may increase based on response and tolerability.

Severe conditions: Initial: 50 to 75 mg/day in 2 or 3 divided doses; may increase based on response and tolerability. Patients requiring higher initial doses (100 to 200 mg/day in divided doses) should remain in bed for the first few days of therapy.

Schizophrenia

Schizophrenia:

IM: 25 mg, 3 or 4 times per day.

Oral: Initial: 50 to 75 mg/day in 2 or 3 divided doses; may increase based on response and tolerability. Patients requiring higher initial doses (100 to 200 mg/day in divided doses) should remain in bed for the first few days of therapy. Doses ≥1 g/day may be needed in some patients with psychosis.

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 (Ref).

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 with schizophrenia 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 (Ref). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. Avoid parenteral use in patients with renal impairment.

Dosing: Liver Impairment: Adult

Use is contraindicated.

Dosing: Older Adult

Note: Avoid for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. If used, consider deprescribing attempts to assess continued need and/or lowest effective dose. Of note: use in certain indications may be appropriate (eg, schizophrenia, bipolar disorder) (Ref).

Refer to adult dosing. Dosages in the lower range of recommended adult dosing are generally sufficient with late-onset schizophrenia. Titrate dosage slowly and monitor carefully (Ref).

Dosing: Pediatric

Note: Patients receiving parenteral therapy should be switched to oral therapy as soon as possible. If pronounced sedation occurs, administer smaller doses during the day and higher doses at night.

Insomnia, nausea/vomiting, pain, psychotic disorders

Insomnia, nausea/vomiting, pain, psychotic disorders (ie, schizophrenia and/or manic-depressive syndromes):

Children and Adolescents:

Oral: 0.25 mg/kg/day in 2 to 3 divided doses; may titrate to effect (maximum dose for children <12 years of age: 40 mg/day). Note: May also be used for anxiety/tension disorders.

Parenteral:

IM: 0.0625 to 0.125 mg/kg/day as a single dose or in several divided doses.

IV: Palliative care: 0.0625 mg/kg in D5W 250 mL infused slowly at a rate of 20 to 40 drops/minute.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Liver Impairment: Pediatric

Use is contraindicated.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reactions listed are based on reports for other agents in this same pharmacologic class, and may not be specifically reported for methotrimeprazine.

Postmarketing:

Cardiovascular: Atrioventricular block, cardiac arrhythmia (including atrial arrhythmia, cardiac fibrillation, tachycardia, ventricular arrhythmia, ventricular tachycardia), deep vein thrombosis, ECG changes (depression of ST segment on ECG, prolonged QT interval on ECG, T-wave changes, U-wave changes), orthostatic hypotension, pulmonary embolism, torsades de pointes, venous thromboembolism

Dermatologic: Dyschromia, skin photosensitivity, skin rash, Stevens-Johnson syndrome (Moubayed 2017), urticaria

Endocrine & metabolic: Amenorrhea, change in libido, decreased glucose tolerance, diabetic ketoacidosis, galactorrhea not associated with childbirth, gynecomastia, hyperglycemia, hyperprolactinemia, hyponatremia, menstrual disease, SIADH, weight gain

Gastrointestinal: Constipation, necrotizing enterocolitis, paralytic ileus, xerostomia

Genitourinary: Ejaculatory disorder (including inhibited ejaculation), lactation, priapism, urinary retention

Hematologic & oncologic: Agranulocytosis (Ananth 1970), eosinophilia, granulocytopenia, immune thrombocytopenia, leukopenia, neutropenia, thrombocytopenia

Hepatic: Abnormal hepatic function tests, cholestatic jaundice, hepatic injury

Hypersensitivity: Angioedema, hypersensitivity reaction

Local: Irritation at injection site (Moubayed 2017), skin ulceration at injection site (Moubayed 2017)

Nervous system: Anxiety, apathy, confusion, delirium, disruption of body temperature regulation, dizziness, drowsiness, extrapyramidal reaction (including akathisia, akinesia [with or without hypertonia], dystonia ([oculogyric crisis, spasmodic torticollis, trismus], hyperkinetic muscle activity, neuromuscular excitability, parkinsonism), insomnia, mood changes, neonatal withdrawal, neuroleptic malignant syndrome (Hayashida 2013), seizure, withdrawal syndrome (with abrupt discontinuation of high dose therapy; including gastritis, nausea, tremor, and vomiting)

Neuromuscular & skeletal: Tardive dyskinesia

Ophthalmic: Accommodation disturbance, cataract (Kim 2010), deposits on or around the surface of the eye (brownish deposits due to accumulation of the drug) (Kim 2010), myopia (Kashani 2005)

Respiratory: Nasal congestion, respiratory depression

Contraindications

Hypersensitivity to methotrimeprazine, phenothiazines, or any component of the formulation; hepatic disease; hematologic disorders (blood dyscrasia); coma or CNS depression due to ethanol, hypnotics, analgesics, or opioids.

Injection: Additional contraindications: Bone marrow depression; brain damage; pheochromocytoma; circulatory collapse/severe hypotension or severe heart disorders; myasthenia gravis; regional or spinal anesthesia; patients at risk of closed-angle glaucoma or urinary retention related to urethroprostatic disorders; history of agranulocytosis; concomitant use of neuroleptics (eg, dopaminergics); pediatric patients <1 year of age.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines. QT prolongation has been reported rarely with use.

• Anticholinergic effects: Phenothiazines may cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); therefore, they should be used with caution in patients with decreased gastrointestinal motility, urinary retention, benign prostatic hyperplasia, xerostomia, glaucoma, or visual problems.

• Blood dyscrasias: Agranulocytosis, neutropenia, and granulocytopenia have been reported with use of antipsychotics. Monitor for any signs of infection and obtain CBC if symptoms (eg, fever, sore throat) evident.

• 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, 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 of age (Herzig 2017; Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and probably 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.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability (Landi 2005; Seppala 2018).

• GI effects: Paralytic ileus may occur and should be treated as an emergency. Fatal necrotizing enterocolitis (rare) has been reported.

• Hyperglycemia: Hyperglycemia or glucose intolerance has been reported with use; diabetic ketoacidosis has been observed in patients without a prior history of hyperglycemia. Assess glucose prior to initiating therapy and periodically thereafter; patients with diabetes or those at risk for diabetes should be monitored for loss of glucose control during therapy.

• Hyperprolactinemia: Antipsychotic use has been associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown (APA [Keepers 2020]; Pollack 1993; Wang 2002). Prolonged hyperprolactinemia in association with hypogonadism may result in decreased bone mineral density in females and males.

• Neuroleptic malignant syndrome: May be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability. Discontinue use immediately for signs/symptoms of NMS and treat appropriately.

• Ocular effects: Antipsychotic use has been associated with pigmentary retinopathy, and lenticular and corneal deposits, particularly with prolonged therapy (Oshika 1995).

• Orthostatic hypotension: May cause orthostatic hypotension, particularly following parenteral administration or with high dosages; use with caution in patients at risk of hypotension or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Patients should remain in bed for the first few days following initiation of parenteral therapy or with high oral doses.

• Photosensitivity: May cause photosensitization; avoid prolonged exposure to sunlight and use high SPF sunscreen.

• Priapism: Rare cases of priapism have been reported with use; effects appear to be independent of dose and duration of therapy.

• Temperature regulation: Antipsychotic use has been associated with impaired core body temperature regulation; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects (Kerwin 2004; Kwok 2005; Martinez 2002).

• Venous thromboembolism: Cases of venous thromboembolism (some fatal) have been reported; use with caution in patients at risk for thromboembolism.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease. Dose reductions may be necessary when initiating therapy. Avoid use in patients with heart failure.

• Dementia: [Canadian Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared to those treated with placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. An increased risk of cerebrovascular events including stroke has been observed with atypical antipsychotic use in elderly patients with dementia; risk with methotrimeprazine has not been established but cannot be ruled out. Methotrimeprazine is not indicated for the treatment of dementia or dementia-related psychosis in elderly patients.

• Hypothyroidism: Avoid use in patients with hypothyroidism.

• Parkinson disease: Avoid use in patients with Parkinson disease.

• Prostatic hypertrophy: Avoid use in patients with prostatic hypertrophy.

• Respiratory disease: Use with caution in patients with respiratory disease (eg, severe asthma, emphysema) due to potential for CNS depression effects.

• Seizure disorder: Use with caution in patients with seizure disorders; appropriate antiseizure therapy should be administered. Phenothiazines may lower seizure threshold.

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). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).

Product Availability

Not available in the US

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Nozinan: 25 mg/mL (1 mL) [contains sodium sulfite]

Tablet, Oral:

Generic: 2 mg, 5 mg, 25 mg, 50 mg

Administration: Adult

Oral: Administer with meals.

Injection may be administered parenterally by slow IV infusion at a rate of 20 to 40 drops/minute, deep IM injection, subcutaneously (off-label route) as bolus injection (Ref), or as continuous infusion over 24 hours (Ref). Patients should remain lying down for ≥1 hour (to reduce risk of hypotension).

For intermittent dosing, may administer smaller doses during day and higher doses at night if pronounced sedation occurs.

Administration: Pediatric

IM: May be administered by deep IM injection into a large muscle. May administer smaller doses during day and higher doses at night if pronounced sedation occurs.

IV: Palliative care: May be administered by slow IV infusion at a rate of 20 to 40 drops/minute.

Use: Labeled Indications

Note: Not approved in the United States.

Anxiety (tablet only): Treatment of conditions associated with anxiety.

Bipolar disorder: Treatment of bipolar disorder.

Insomnia: Management of insomnia, including for sedation in palliative care settings.

Nausea/vomiting: Management of nausea and vomiting.

Pain: Management of pain, including pain caused by neuralgia, cancer, or muscular discomforts, and as adjunct to general anesthesia (pre- and postoperatively).

Schizophrenia: Treatment of schizophrenia and psychotic disorders.

Medication Safety Issues
Safety concerns:

ALERT: Canadian Boxed Warning: Health Canada-approved labeling includes a boxed warning. See "Warnings/Precautions" section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling.

Older Adult: High-Risk Medication:

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 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]).

Antipsychotics are identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) for treatment of sleep disorder. Some disease states of concern include dementia, parkinsonism, recurrent falls, dysphagia, QTc prolongation, and coronary, cerebral, or peripheral vascular disease (O’Mahony 2023).

Metabolism/Transport Effects

Substrate of CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

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.

Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor

Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Agents with Clinically Relevant Anticholinergic Effects: May increase anticholinergic effects of Methotrimeprazine. Risk C: Monitor

Agents With Seizure Threshold Lowering Potential: May increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Alcohol (Ethyl): May increase adverse/toxic effects of Methotrimeprazine. Specifically, CNS depressant effects may be increased. Management: Avoid alcohol in patients treated with methotrimeprazine. Risk X: Avoid

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor

Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid

Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor

Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor

Amisulpride (Oral): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Antacids: May decrease absorption of Antipsychotic Agents (Phenothiazines). Risk C: Monitor

Anti-Parkinson Agents (Dopamine Agonist): Methotrimeprazine may decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may decrease therapeutic effects of Methotrimeprazine. Risk X: Avoid

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor

ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor

Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Benzgalantamine-Galantamine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor

Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor

Beta-Blockers: Antipsychotic Agents (Phenothiazines) may increase hypotensive effects of Beta-Blockers. Beta-Blockers may decrease metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease metabolism of Beta-Blockers. Risk C: Monitor

Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor

Blonanserin: CNS Depressants may increase CNS depressant effects 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

Bornaprine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, tardive dyskinesia symptoms may be potentiated. Risk C: Monitor

Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromopride: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects 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

BuPROPion: May increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cabergoline: May decrease therapeutic effects of Antipsychotic Agents. Risk X: Avoid

Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects 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 increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid

CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider Therapy Modification

CNS Depressants: May increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects 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

Daridorexant: May increase CNS depressant effects 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

Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor

DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects 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

Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may increase adverse/toxic effects of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor

Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Donepezil: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects 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

Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor

Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor

Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid

Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor

Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Guanethidine: Antipsychotic Agents may decrease therapeutic effects of Guanethidine. Risk C: Monitor

Huperzine A: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor

HydrOXYzine: May increase CNS depressant effects 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 increase adverse/toxic effects 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 increase adverse/toxic effects 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 increase adverse/toxic effects 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 (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lemborexant: May increase CNS depressant effects 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

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid

Lithium: May increase neurotoxic effects of Antipsychotic Agents. Lithium may decrease serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor

Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: Antipsychotic Agents may decrease therapeutic effects of Metergoline. Metergoline may decrease therapeutic effects of Antipsychotic Agents. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor

Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor

Metoclopramide: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

MetyroSINE: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor

Monoamine Oxidase Inhibitors: May increase adverse/toxic effects of Methotrimeprazine. Specifically, monoamine oxidase inhibitors may enhance dopamine blockade, possible increasing the risk for neuroleptic malignant syndrome. Methotrimeprazine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects 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

Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor

OxyCODONE: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Paraldehyde. Risk X: Avoid

Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor

Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid

Piribedil: Antipsychotic Agents may decrease therapeutic effects of Piribedil. Piribedil may decrease therapeutic effects 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

Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor

Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid

Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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

Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid

Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Products Containing Ethanol: Methotrimeprazine may increase CNS depressant effects of Products Containing Ethanol. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid

Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor

Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Quinagolide: Antipsychotic Agents may decrease therapeutic effects of Quinagolide. Risk C: Monitor

QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor

Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid

Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects 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

Saquinavir: Antipsychotic Agents (Phenothiazines) may increase arrhythmogenic effects of Saquinavir. Risk X: Avoid

Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects 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

Serotonergic Agents (High Risk): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor

Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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

Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid

Sulpiride: Antipsychotic Agents may increase adverse/toxic effects of Sulpiride. Risk X: Avoid

Suvorexant: CNS Depressants may increase CNS depressant effects 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

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor

Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid

Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor

Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor

Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor

Zolpidem: CNS Depressants may increase CNS depressant effects 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

Zuranolone: May increase CNS depressant effects 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

Reproductive Considerations

Hyperprolactinemia associated with methotrimeprazine may lead to impaired fertility in women. Limited data suggest that methotrimeprazine may also be associated with impaired fertility in men.

If treatment with an antipsychotic is needed in a woman planning a pregnancy, other agents are preferred (Larsen 2015).

Pregnancy Considerations

Information related to use in pregnancy is limited (Callaghan 1966; DeKornfeld 1964; Heazell 2005). 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. Delayed meconium passage, abdominal bloating, and initial feeding difficulties due to the atropinic properties of the phenothiazines may also occur.

If treatment with an antipsychotic is initiated during pregnancy, use of other agents is preferred (Larsen 2015). Methotrimeprazine is not one of the treatments recommended for nausea and vomiting associated with pregnancy (Campbell 2016).

Breastfeeding Considerations

Methotrimeprazine is present in breast milk.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of exposure to the infant and the benefits of treatment to the mother. If treatment with an antipsychotic is needed in a breastfeeding woman, other agents are preferred (Larsen 2015).

Monitoring Parameters

Frequency of Antipsychotic Monitoring in Methotrimeprazinea,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.

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

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.

Mechanism of Action

Aliphatic phenothiazine that antagonizes D1 and D2 dopamine receptor subtypes; also binds alpha-1, alpha-2, serotonin (5-HT1 and 5-HT2), and muscarinic (M1 and M2) receptors (Lal 1993)

Pharmacokinetics (Adult Data Unless Noted)

Onset of action:

Anxiety/tension: Injection: 1 hour (Nozinan datasheet, Sanofi Aventis New Zealand limited 2010).

Bipolar disorder, acute mania: Oral: Initial effects may be observed within days of treatment with continued improvements over 1 to 2 weeks (Goikolea 2013; Tohen 2000; Welten 2016).

Schizophrenia: Oral: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).

Duration: 2 to 4 hours (Nozinan datasheet, Sanofi Aventis New Zealand limited 2010)

Distribution: Vd: 23 to 42 L/kg (Dahl 1976)

Bioavailability: 50% (Dahl 1976)

Time to peak, serum: IM: 0.5 to 1.5 hours; Oral: 1 to 3 hours (Nozinan datasheet, Sanofi Aventis New Zealand limited 2010)

Half-life elimination: 15 to 30 hours (Dahl 1976)

Excretion: Urine; feces (Nozinan datasheet, Sanofi Aventis New Zealand limited 2010)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Detenler | Levomepromazin Cevallos | Levomepromazina cevallos | Levomepromazina lepret | Levomepromazina luar | Levomepromazina Vannier | Meprozin | Nozinan | Sunonix | Togrel;
  • (AT) Austria: Nozinan;
  • (BE) Belgium: Nozinan;
  • (BG) Bulgaria: Levomepromazin | Nosinan | Tisercin;
  • (BR) Brazil: Levozine | Maleato de levomepromazina | Meprozin | Neozine;
  • (CH) Switzerland: Minozinan | Nozinan;
  • (CL) Chile: Sinogan;
  • (CO) Colombia: Levomepromazina | Sinogan;
  • (CZ) Czech Republic: Levomepromazin orion | Tisercin;
  • (DE) Germany: Levium | Levomepromazin neuraxpharm | Neurocil | Tisercin Ucb;
  • (EC) Ecuador: Lepromax | Levomepromazina | Sinogan;
  • (EE) Estonia: Levozin | Nozinan | Tisercin;
  • (ES) Spain: Sinogan;
  • (FI) Finland: Levomepromazine orion | Levozin | Nozinan;
  • (FR) France: Nozinan;
  • (GB) United Kingdom: Levinan | Levomepromazin | Levomepromazine | Levorol | Nozinan | Veractil;
  • (GR) Greece: Nozinan;
  • (HR) Croatia: Nozinan;
  • (HU) Hungary: Tisercin | Tisercinetta;
  • (ID) Indonesia: Nozinan;
  • (IE) Ireland: Levium | Nozinan;
  • (IL) Israel: Methozane | Nozinan | Ronexine;
  • (IT) Italy: Nozinan;
  • (JO) Jordan: Nozinan;
  • (JP) Japan: Hirnamin | Levaru | Levomepromazine | Levonormal | Levotomin | Procrazine | Sofmin | Sofmin amel;
  • (KR) Korea, Republic of: Tisercin;
  • (LB) Lebanon: Minozinan | Nozinan;
  • (LT) Lithuania: Levomepromazin | Milezin | Nozinan | Tisercin;
  • (LU) Luxembourg: Nozinan;
  • (LV) Latvia: Levomepromazin | Milezin | Tisercin;
  • (MA) Morocco: Nozinan;
  • (MX) Mexico: Fangerol | Levomepromazina | Rensed | Sinogan | Ziprolev;
  • (NL) Netherlands: Levomepromazin | Levomepromazine | Nozinan;
  • (NO) Norway: Levomepromazin | Levomepromazine orion | Methoprazine | Neurocil | Nozinan | Veractil;
  • (NZ) New Zealand: Nozinan;
  • (PE) Peru: Lepromax | Levomepromazin | Levomepromazina | Sinogan;
  • (PH) Philippines: Nozinan;
  • (PL) Poland: Levomepromazin | Lewomezin | Milezin | Nozinan | Tisercin;
  • (PT) Portugal: Nozinan;
  • (PY) Paraguay: Lasina | Levomepromazina rospaw | Levomepromazina whelp | Nozinan | Relaxan;
  • (RU) Russian Federation: Tisercin;
  • (SE) Sweden: Levomepromazine orion | Nozinan;
  • (SI) Slovenia: Nozinan;
  • (SK) Slovakia: Tisercin;
  • (TN) Tunisia: Levomepromazine | Nozinan;
  • (TW) Taiwan: Hirmazine | Hirnamin | Levohalte;
  • (UA) Ukraine: Tisercin;
  • (UY) Uruguay: Levomepromazina | Mesozina | Nidrane | Noranat | Nozinan;
  • (VE) Venezuela, Bolivarian Republic of: Sinogan
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