Levomepromazine, Methotrimeprazine (Nozinan) - Uses, Dose, Side effects

Levomepromazine (Methoprazine) is a neuroleptic phenothiazine drug that is used to treat patients with agitation, psychosis, and mania.

Levomepromazine (Methoprazine) Uses:

  • Anxiety and tension (tablet only):

    • Treatment of conditions associated with anxiety and tension (eg, autonomic disturbances personality disturbances, emotional disorders secondary to physical conditions)
  • Insomnia:

    • Management of insomnia and sedation
  • Nausea and vomiting:

    • Management of nausea and vomiting
  • Pain:

    • Management of pain, including pain caused by neuralgia or cancer and as an adjunct to general anesthesia (pre- and postoperatively)
  • Psychiatric disorders:

    • Treatment of schizophrenia, senile psychosis, and manic-depressive syndromes

Levomepromazine (Methoprazine) Dose in Adults:

Note:

  • As quickly as feasible, patients taking parenteral therapy should convert to oral therapy.
  • If pronounced sedation occurs, administer smaller doses during the day and higher doses at night.

Oral Levomepromazine (Methoprazine):

Dose for treating Anxiety/ tension disorders, insomnia, nausea/vomiting, pain, psychotic disorders (ie, schizophrenia, senile psychosis, and/or manic-depressive syndromes):

  • Mild conditions:

    • Initial:
      • 6 to 25 mg/day in 3 divided doses with meals; may titrate to effect.
  • Insomnia:

    • Single-dose of 10 to 25 mg at bedtime is usually sufficient.
  • Severe conditions (eg, psychosis, severe pain):

    • Initial:
      • 50 to 75 mg/day in 2 or 3 divided doses; may titrate to effect.
      • 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 psychotic patients.

Injection Levomepromazine (Methoprazine):

Dose in the treatment of Insomnia, nausea/vomiting, pain, psychotic disorders (ie, schizophrenia, senile psychosis, and/or manic-depressive syndromes):

  • IM: 75 to 100 mg/day in 3 to 4 divided doses
    • Management of postoperative pain:

      • 10 to 25 mg TDS (equivalent to an oral dose of 20 to 40 mg).
    • SubQ (off-label route):

      • Palliative care (eg, antiemetic, sedative [at higher doses]):
    • Continuous infusion:

      • 25 to 250 mg/day in sterile water or NS (via syringe pump)
    • Bolus administration:

      • Median dose: 6.25 mg/day (range: 3.12 to 25 mg/day) administered as 1 to 2 divided doses

Levomepromazine (Methoprazine) Dose in Childrens:

Note:

  • Immediately transition patients receiving parenteral therapy to oral therapy.
  • If pronounced sedation occurs, administer smaller doses during the day and higher doses at night.

Oral Levomepromazine (Methoprazine):

Dose in the treatment of Anxiety/tension disorders, insomnia, nausea/vomiting, pain, psychotic disorders (ie, schizophrenia and/or manic-depressive syndromes):

  • Children and Adolescents:

    • 25 mg/kg/day in 2 to 3 divided doses
    • May titrate to effect
    • Maximum dose for children <12 years: 40 mg/day

Injection Levomepromazine (Methoprazine):

Dose in the treatment of Insomnia, nausea & vomiting, pain, psychotic disorders (ie, schizophrenia and/or manic-depressive syndromes):

  • Children and Adolescents:

    • IM: 0.0625 to 0.125 mg/kg/day as a stat 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

Pregnancy Risk Category: N (Not defined)

  • We have limited information about pregnancy.
  • When antipsychotics are taken throughout the third trimester of pregnancy, the infants may have aberrant muscle movements and withdrawal  symptoms.
  • Agitation, feeding issues, hypotonia, hypertonia, respiratory distress, somnolence, and tremor are all possible in a baby.
  • These symptoms could subside on their own or might necessitate hospitalisation.
  • Women may experience impaired fertility due to hyperprolactinemia when taking methotrimeprazine.
  • There are limited data suggesting that methotrimeprazine could also cause impaired fertility in men.

Use of levomepromazine while breastfeeding

  • Breast milk contains small amounts of methotrimeprazine.
  • When deciding whether to discontinue or continue breastfeeding during therapy, it is important to consider the risks to the infant as well as the benefits to the mother.

Levomepromazine (Methoprazine) Dose in Kidney Disease:

  • The manufacturer's labelling does not mention dosage modifications.
  • Use cautiously.

Levomepromazine (Methoprazine) Dose in Liver disease:

  • Use is contraindicated.

Side effects of Levomepromazine (Methoprazine):

  • Cardiovascular:

    • Orthostatic Hypotension
    • Pulmonary Embolism
    • Tachycardia
    • Venous Thromboembolism
  • Central Nervous System:

    • Disruption Of Body Temperature Regulation
    • Drowsiness; Drug-Induced Extrapyramidal Reaction (Including Akathisia, Dystonia, Parkinsonian-Like Syndrome, Tardive Dyskinesia)
    • Neuroleptic Malignant Syndrome (NMS)
    • Seizure
    • Headache
    • Dizziness
  • Dermatologic:

    • Diaphoresis
    • Skin Rash
  • Endocrine & Metabolic:

    • Menstrual Disease
    • Decreased Glucose Tolerance
    • Hyperglycemia
    • Weight Gain
    • Gynecomastia
    • Change In Libido
  • Gastrointestinal:

    • Vomiting
    • Intestinal Obstruction
    • Necrotizing Enterocolitis
    • Xerostomia
    • Nausea
    • Constipation
  • Genitourinary:

    • Urinary Incontinence
    • Priapism
    • Urinary Retention
    • Ejaculatory Disorder
  • Hematologic & Oncologic:

    • Leukopenia
    • Hemolytic Anemia
    • Pancytopenia
    • Immune Thrombocytopenia
    • Eosinophilia
  • Hepatic:

    • Hepatotoxicity
    • Cholestatic Jaundice
  • Renal:

    • Polyuria

Contraindications to Levomepromazine (Methoprazine):

  • Hypersensitivity to phenothiazines, methotrimeprazine, or any other ingredient in the formulation
  • Hepatic disease
  • Hematologic disorders (blood dyscrasia).
  • Coma or CNS Depression due to ethanol or hypnotics or analgesics or opioids

Injection:Additional contraindications:

  • Brain damage
  • Pheochromocytoma
  • Circulatory collapse/severe Hypotension or severe heart conditions
  • Anesthesia for the spine or regional area

Warnings and precautions

  • Modified cardiac conduction

    • Could cause alteration of cardiac conduction.
    • Therapeutic doses of phenothiazines have been shown to cause life-threatening arrhythmias.
    • Rarely has QT prolongation been reported.
  • Anticholinergic effects

    • Phenothiazines can cause anticholinergic reactions (constipation and xerostomia, blurred sight, urinary retention, etc.
    • Patients with reduced gastrointestinal motility, urinary retention (BPH), xerostomia or visual impairments should not use them.
  • Blood dyscrasias

    • Antipsychotics have been linked to granulocytosis and neutropenia.
    • Before you start therapy, get CBC. Then, continue to check it periodically throughout the therapy period, especially during the first three months.
    • Patients with blood dyscrasias are not recommended to use this product.
  • Depression in the CNS:

    • CNS depression can lead to mental or physical impairment.
    • It is crucial to inform patients about activities requiring mental awareness, including operating machinery or a vehicle.
  • Esophageal dysmotility/aspiration

    • Aspiration, esophageal dysmotility, and an age-related increase in risk have all been associated with antipsychotic usage.
    • Patients at high risk of aspiration pneumonia (ie Alzheimer's disease) should be treated with caution, especially patients over 75 years.
  • Extrapyramidal symptoms

    • Extrapyramidal symptoms (EPS) may include pseudo parkinsonism and acute dystonic reactions.
    • Higher doses of antipsychotics, conventional antipsychotics, men, and younger patients may increase the risk of dystonia (and possibly other EPS).
    • There are several factors that increase the vulnerability to tardive dyskinesia, including older age, female gender, postmenopausal status and Parkinson disease symptoms.
    • You may consider discontinuing therapy if you experience tardive dyskinesia symptoms.
  • Hyperglycemia

    • Use has been associated with hyperglycemia and glucose intolerance.
    • Diabetic ketoacidosis was observed in patients who had not previously experienced hyperglycemia.
    • Before starting therapy, test glucose and then again periodically.
    • Patients with diabetes and those at high risk should be closely monitored for any loss of glucose control.
  • Hyperprolactinemia

    • Hyperprolactinemia has been linked to antipsychotic use.
    • Hyperprolactinemia's clinical relevance for people with breast cancer or other prolactin-dependent tumours remains unknown,  nevertheless.
    • Hypogonadism and prolonged hyperprolactinemia may lead to decreased bone mineral density in males and females.
  • Neuroleptic malignant Syndrome (NMS).

    • Can be used in conjunction with the NMS 
    • Monitor to check for symptoms of autonomic instability, fever, muscle rigidity, and/or changes in mental status.
    • If you notice any signs or symptoms of NMS, stop using the medication immediately and consult your doctor.
  • Ocular effects

    • Long-term antipsychotic therapy has been linked to pigmentary retinopathy and lenticular or corneal deposits.
  • Orthostatic hypotension

    • Orthostatic hypotension may occur after parenteral administration, especially if the dosage is high.
    • Patients at high risk for hypotension and patients with transient hypotensive episodes (cardiovascular disease, cerebrovascular disease) should be cautious.
    • For the first few days after the introduction of parenteral or high-dose oral therapy, patients should be in bed.
  • Priapism

    • Rare cases of priapism were reported. The effects seem to be independent from the duration and dose of therapy.
  • Temperature regulation

    • The use of antipsychotics has been linked to impaired core temperature regulation.
    • Be careful with heat exposure, strenuous exercise, heat, dehydration, or concomitant anticholinergic medication.
  • Venous thromboembolism

    • There have been cases of venous hemorhage (some fatal).
    • Patients who are at a high risk for thromboembolism should get cautious care.
  • Cardiovascular disease

    • Patients with heart disease should be cautious.
    • It may be necessary to reduce doses when starting therapy.
  • Dementia

    • Antipsychotics increase the risk of death for dementia-related psychosis patients in their elderly years.
    • The majority of deaths were either from cardiovascular disease (eg heart failure, sudden death, etc.) or infectious diseases (eg pneumonia).
    • Atypical antipsychotics used in dementia patients aged over 65 have been linked to an increased risk of CVAs.
    • Methotrimeprazine is not known to pose a risk, but it cannot be excluded.
    • Methotrimeprazine should not be used to treat dementia in elderly patients.
  • Hepatic impairment

    • Contraindicated for hepatic disease
  • Respiratory disease

    • Patients with severe asthma or emphysema should be cautious as there is a risk of CNS depression.
  • Seizure disorder

    • Patients with seizure disorders should be treated cautiously
    • It is important to administer the appropriate anticonvulsant treatment.
    • The seizure threshold may be lower with phenothiazines.

Monitoring parameters:

  • Mental status
  • Vital signs (as clinically indicated)
  • BMI
  • Liver function tests (baseline and periodically thereafter)
  • CBC (baseline, during the first 2-3 months of therapy, and regularly thereafter)
  • Plasma glucose (patients with or at risk of diabetes)
  • Abnormal involuntary movement scale (AIMS)
  • Extrapyramidal symptoms (EPS)
  • ECG (if clinically indicated)

Schizophrenia (additional monitoring recommendations):

  • BMI and waist measurement (baseline; at every visit for the first 6 months; quarterly with stable antipsychotic dose)
  • Electrolytes (annually and as clinically indicated)
  • HbA/fasting plasma glucose (baseline, then yearly; in patients with diabetes risk factors or if gaining weight, repeat 4 months after starting  antipsychotic, then yearly)
  • Fasting lipid panel (baseline; repeat after two years if LDL levels are normal; after six months if LDL levels are greater than 130 mg/dL)
  • Menstrual cycle, libido, galactorrhea development, erectile, and ejaculatory function changes (baseline, monthly for 3 months after initiation and  then yearly)
  • Parkinsonian symptoms or unusual involuntary motions (baseline; repeat weekly until dose stabilised for at least 2 weeks after the introduction  and for 2 weeks after any significant dose increase)
  • Tardive dyskinesia (every six months; every three months for high-risk patients); visual alterations (inquire yearly)
  • Ocular examination (every year for people over 40; every two years for patients under 40).

How to administer Levomepromazine (Methoprazine)?

  • Oral:
    • Take with you.
  • Injection:
    • You can administer it parenterally with a slow intravenous injection at a rate between 20-40 drops per minute, deep IM, injection, or subcutaneously (off label route), as bolus injections or a continuous infusion for up to 24 hours.
  • You can administer lower doses during the day, and greater doses at night for intermittent dosing if you experience pronounced sedation.

Mechanism of action of Levomepromazine (Methoprazine):

  • An antagonist of D1 and D2 dopamine subtypes with aliphatic phenothiazine
  • It also binds serotonin (5HT-1 and 5-HT-2), alpha-1 and alpha-2, and muscarinic receptors (M-1 & M-2).

The onset of action:

  • Injection: 1 hour.

Duration:

  • 2 to 4 hours.

Bioavailability:

  • 50%

Time to peak, serum:

  • IM: 0.5 to 1.5 hours
  • Oral: 1 to 3 hours.

Half-life elimination:

  • 15 to 30 hours.

Excretion:

  • Urine
  • feces .

International Brands of Levomepromazine:

  • Methoprazine
  • NOVO-Meprazine
  • Nozinan
  • PMS-Methotrimeprazine
  • Detenler
  • Hirnamin
  • Levium
  • Levozin
  • Neozine
  • Neurocil
  • Nidrane
  • Nozinan
  • Ronexine
  • Sinogan
  • Tiscerin
  • Tisercin

Levomepromazine Brand Names in Pakistan:

No Brands Available in Pakistan.

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