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):

  • Helping people who feel anxious or stressed, and have problems like nervous system issues or personality changes, or feeling emotionally upset because of physical problems.

• Insomnia:

  • Helping people sleep better and managing when they need to feel calmer or sleepier.

• Nausea and vomiting:

  • Helping people feel better when they have the urge to vomit or actually vomit.

• Pain:

  • Helping people feel less pain, whether it's from nerve problems, cancer, or during surgery, both before and after the operation.

• Psychiatric disorders:

  • Helping people with mental health issues like schizophrenia, senile psychosis (which occurs in older adults), and manic-depressive syndrome (also known as bipolar disorder).

Levomepromazine (Methoprazine) Dose in Adults:

Note:

• If patients are getting treatment through injections, switch them to taking medicine by mouth as soon as possible.
• If they become very sleepy, give them smaller doses during the day and larger 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:

  • Start with 6 to 25 milligrams per day, divided into 3 doses with meals.
  • The dose can be adjusted as needed to achieve the desired effect.

• Insomnia:

  • Usually, just one dose of 10 to 25 milligrams at bedtime is enough.

• Severe conditions (eg, psychosis, severe pain):

  • Start with 50 to 75 milligrams per day, split into 2 or 3 doses.

  • The dose can be adjusted as needed. If patients need higher starting doses (100 to 200 milligrams per day split into doses), they should stay in bed for the first few days of treatment.

  • Some patients with psychosis may require doses of 1 gram per day or more.

Injection Levomepromazine (Methoprazine):

In the treatment of insomnia, nausea/vomiting, pain, and psychotic disorders such as schizophrenia, senile psychosis, and manic-depressive syndromes:

• Intramuscular (IM) injection: 75 to 100 milligrams per day, divided into 3 to 4 doses.

For managing postoperative pain:

• Intramuscular (IM) injection: 10 to 25 milligrams three times a day (equivalent to an oral dose of 20 to 40 milligrams).

For palliative care, such as for relieving vomiting, sedation, or pain, either through continuous infusion or bolus administration:

• Continuous infusion: 25 to 250 milligrams per day diluted in sterile water or normal saline, administered via a syringe pump.

Bolus administration:

• Median dose of 6.25 milligrams per day (range: 3.12 to 25 milligrams per day), given as 1 to 2 divided doses.

Levomepromazine (Methoprazine) Dose in Childrens:

Note:

• Switch patients from receiving injections to taking medication by mouth right away.

• If they become very sleepy, give them smaller doses during the day and larger doses at night.

Oral Levomepromazine (Methoprazine):

For children and adolescents with anxiety/tension disorders, insomnia, nausea/vomiting, pain, and psychotic disorders like schizophrenia and manic-depressive syndromes:

• The initial dose is 25 milligrams per kilogram of body weight per day, divided into 2 to 3 doses.
• The dose can be adjusted as needed to achieve the desired effect.
• The maximum dose for children under 12 years old is 40 milligrams per day.

Injection Levomepromazine (Methoprazine):

For children and adolescents with insomnia, nausea & vomiting, pain, and psychotic disorders like schizophrenia and manic-depressive syndromes:

• Intramuscular (IM) injection: A single dose of 0.0625 to 0.125 milligrams per kilogram of body weight per day, given as a one-time dose or split into several doses throughout the day.
• Intravenous (IV) infusion for palliative care: A dose of 0.0625 milligrams per kilogram of body weight in a 250 milliliter solution of D5W (5% dextrose in water), administered slowly at a rate of 20 to 40 drops per minute.

Pregnancy Risk Category: N (Not defined)

• When antipsychotic medications are used throughout the third trimester of pregnancy, infants may exhibit abnormal muscle movements and withdrawal symptoms after birth.

• These symptoms can include agitation, feeding difficulties, weak or stiff muscles, breathing problems, sleepiness, and tremors. These symptoms may improve on their own or require hospitalization.

• Women taking methotrimeprazine may experience impaired fertility due to increased levels of prolactin hormone.

• Limited data also suggest that methotrimeprazine could affect fertility in men.

Use of levomepromazine while breastfeeding

• Breast milk may contain small amounts of methotrimeprazine.

• When deciding whether to continue or discontinue breastfeeding while undergoing therapy, it's crucial to weigh the risks to the infant against the benefits to the mother.

• Consulting with a healthcare provider can help make an informed decision that takes into account both the mother's needs and the baby's well-being.

Levomepromazine (Methoprazine) Dose in Kidney Disease:

• It's important to note that the manufacturer's labeling does not specify any dosage modifications.
• Therefore, it's advised to use the medication cautiously and to follow the prescribed dosage guidelines closely.
• Always consult with a healthcare professional for guidance on appropriate dosing and any necessary adjustments based on individual circumstances.

Levomepromazine (Methoprazine) Dose in Liver disease:

• The use of the medication is not recommended and is considered contraindicated.
• This means that it is advised against due to potential risks or adverse effects.
• It's crucial to heed this warning and avoid using the medication in such cases.
• Always consult with a healthcare professional for alternative treatment options.

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):

• The use of this medication is contraindicated in individuals with:

• Hypersensitivity to phenothiazines, methotrimeprazine, or any other ingredient in the formulation.
• Hepatic (liver) disease.
• Hematologic disorders (blood dyscrasia).
• Coma or central nervous system (CNS) depression caused by ethanol, hypnotics, analgesics, or opioids.

• In these cases, the medication should not be used due to potential risks or adverse effects.

• It's essential to consult with a healthcare professional for alternative treatment options.

Injection:Additional contraindications:

• The use of this medication is contraindicated in individuals with:

• Brain damage.
• Pheochromocytoma (a type of tumor of the adrenal gland).
• Circulatory collapse/severe hypotension (low blood pressure) or severe heart conditions.
• Anesthesia for the spine or regional area.

• In these cases, the medication should not be used due to potential risks or adverse effects.

• It's crucial to consult with a healthcare professional for alternative treatment options.

Warnings and precautions

• Modified cardiac conduction

  • This medication could potentially alter cardiac conduction, which refers to how electrical signals travel through the heart.

  • Therapeutic doses of phenothiazines, the class of medication that includes methotrimeprazine, have been known to cause life-threatening irregular heart rhythms (arrhythmias).

  • Although rare, there have been reports of QT prolongation associated with this medication.

  • QT prolongation is a condition where the time it takes for the heart to recharge between beats is lengthened, which can increase the risk of arrhythmias and other heart-related issues.

• Anticholinergic effects

  • Phenothiazines, including methotrimeprazine, can lead to anticholinergic reactions, which may include symptoms like constipation, dry mouth (xerostomia), blurred vision, and difficulty urinating (urinary retention).

  • Individuals with conditions such as reduced gastrointestinal motility (slowed digestion), urinary retention (common in benign prostatic hyperplasia or BPH), dry mouth, or visual impairments should avoid using phenothiazines due to the potential exacerbation of these symptoms.

• Blood dyscrasias

  • Antipsychotic medications have been associated with conditions like granulocytosis (an increase in a type of white blood cell) and neutropenia (a decrease in a type of white blood cell).

  • Before beginning therapy with these medications, it's important to obtain a complete blood count (CBC) test.

  • Continual monitoring of the CBC should occur periodically throughout the treatment period, with particular focus during the initial three months.

  • Patients with blood disorders (blood dyscrasias) are advised against using this product due to the potential risks involved. It's essential to discuss any concerns or findings with a healthcare provider.

• Depression in the CNS:

  • Central nervous system (CNS) depression caused by this medication can result in mental or physical impairment.

  • It's crucial to inform patients about activities that require mental alertness, such as operating machinery or driving a vehicle.This precaution helps ensure their safety and the safety of others while taking the medication.

• Esophageal dysmotility/aspiration

  • The use of antipsychotic medications has been associated with an increased risk of aspiration (inhalation of food or liquid into the lungs), esophageal dysmotility (problems with the movement of food through the esophagus), and a higher risk with advancing age.

  • Patients who are at a high risk of aspiration pneumonia, such as those with Alzheimer's disease, should be treated with caution, particularly those who are over 75 years old.

  • It's important to consider these factors when prescribing antipsychotic medications to older patients or those with conditions that may increase the risk of aspiration pneumonia.

• Extrapyramidal symptoms

  • Extrapyramidal symptoms (EPS) associated with antipsychotic use can include conditions like pseudo-parkinsonism (similar to Parkinson's disease) and acute dystonic reactions (abnormal muscle contractions).

  • Factors such as higher doses of antipsychotics, the use of conventional antipsychotics, being male, and younger age can increase the risk of developing dystonia (and potentially other EPS).

  • Several factors can make individuals more vulnerable to tardive dyskinesia, a condition characterized by involuntary, repetitive movements.

  • These factors include older age, female gender, postmenopausal status, and the presence of Parkinson's disease symptoms.

  • If you experience symptoms of tardive dyskinesia, it may be appropriate to consider discontinuing therapy with antipsychotic medications.

  • It's essential to discuss any concerns or symptoms with a healthcare provider to determine the best course of action.

• Hyperglycemia

  • The use of this medication has been linked to hyperglycemia (high blood sugar) and glucose intolerance (difficulty processing sugar).

  • In some cases, diabetic ketoacidosis, a serious complication of diabetes, has been observed in patients who did not previously have high blood sugar levels.

  • Before initiating therapy with this medication, it's important to test blood glucose levels. Monitoring should continue periodically throughout treatment.

  • Patients with diabetes and those at high risk should be closely monitored for any changes in glucose control.

  • This includes individuals with a history of diabetes or those with risk factors for developing diabetes.

  • Regular monitoring helps to detect any changes in blood sugar levels promptly.

• Hyperprolactinemia

  • The use of antipsychotic medications has been associated with hyperprolactinemia, a condition characterized by high levels of prolactin hormone in the blood.

  • The clinical significance of hyperprolactinemia for individuals with breast cancer or other tumors that depend on prolactin remains unclear.

  • However, hypogonadism (reduced function of the gonads) and prolonged hyperprolactinemia can lead to decreased bone mineral density in both males and females.

  • This reduction in bone density may increase the risk of osteoporosis and fractures.

  • Therefore, it's important for healthcare providers to monitor bone health in patients receiving antipsychotic treatment, particularly those experiencing prolonged hyperprolactinemia or hypogonadism.

• Neuroleptic malignant Syndrome (NMS).

  • This medication can be used in conjunction with the monitoring of Neuroleptic Malignant Syndrome (NMS).

  • NMS is a serious condition that can occur as a side effect of antipsychotic medications.

  • Patients should be monitored for symptoms of autonomic instability (such as changes in blood pressure and heart rate), fever, muscle rigidity, and alterations in mental status.

  • If any signs or symptoms of NMS are observed, it is important to discontinue the medication immediately and seek medical advice from a doctor.

  • NMS requires prompt medical attention and intervention.

• Ocular effects

  • Long-term use of antipsychotic therapy has been associated with certain eye-related side effects, including pigmentary retinopathy (changes in the retina causing visual disturbances) and the formation of deposits in the lens (lenticular deposits) or cornea (corneal deposits).

  • These effects can potentially affect vision and eye health over time.

  • It's important for individuals on long-term antipsychotic therapy to undergo regular eye examinations to monitor for any changes in vision or eye health.

  • If any concerns or symptoms arise, it's essential to discuss them with a healthcare provider promptly.

• Orthostatic hypotension

  • Orthostatic hypotension, a drop in blood pressure upon standing, may occur after receiving the medication through injections, particularly with high doses.

  • Patients at high risk for hypotension, such as those with cardiovascular or cerebrovascular disease, should be cautious when using this medication.

  • For the initial days after starting treatment with injections or high-dose oral therapy, patients should remain in bed to minimize the risk of orthostatic hypotension and associated complications.

• Priapism

  • Rare cases of priapism, a prolonged and painful erection unrelated to sexual stimulation, have been reported with the use of this medication.

  • Interestingly, these effects do not appear to be associated with the duration or dose of therapy.

  • Priapism is a serious medical condition that requires immediate medical attention.

  • If you experience an erection lasting longer than four hours, seek emergency medical care promptly to prevent potential complications.

• Temperature regulation

  • The use of antipsychotic medications has been associated with impaired regulation of core body temperature.

  • It's important to exercise caution when exposed to heat, engaging in strenuous exercise, experiencing dehydration, or taking medications with anticholinergic effects (which can interfere with sweating and heat regulation).

  • These factors can increase the risk of heat-related complications, such as heat stroke or heat exhaustion.

  • It's essential to stay hydrated, avoid excessive heat exposure, and be mindful of any symptoms of overheating, such as dizziness, weakness, or confusion.

  • If you experience any concerning symptoms, seek medical attention promptly.

• Venous thromboembolism

  • There have been reported cases of venous hemorrhage, including some that were fatal, associated with the use of this medication.

  • Patients who are at a high risk for thromboembolism (the formation of blood clots) should receive careful monitoring and care when using this medication.

  • Thromboembolism is a serious condition that can lead to potentially life-threatening complications such as heart attack or stroke.

  • It's important for healthcare providers to assess each patient's individual risk factors for thromboembolism and to closely monitor for any signs or symptoms of this condition during treatment with this medication.

  • Prompt medical attention should be sought if any concerning symptoms arise.

• Cardiovascular disease

  • Patients with heart disease should approach the use of this medication cautiously due to the potential risk of exacerbating their condition.

  • When initiating therapy with this medication, it may be necessary to start with lower doses and gradually increase them as tolerated.

  • This cautious approach helps minimize the risk of adverse effects, especially in patients with pre-existing heart conditions.

  • Regular monitoring and close supervision by a healthcare provider are essential for patients with heart disease to ensure the medication is well-tolerated and effective while minimizing any potential risks to cardiovascular health.

• Dementia

  • Antipsychotic medications increase the risk of death in elderly patients with dementia-related psychosis.

  • The majority of these deaths are due to cardiovascular diseases, such as heart failure or sudden death, and infectious diseases like pneumonia.

  • Atypical antipsychotics, when used in dementia patients aged over 65, have been associated with an increased risk of cerebrovascular accidents (CVAs), such as strokes.

  • While methotrimeprazine is not specifically known to pose this risk, it cannot be ruled out entirely.

  • Therefore, methotrimeprazine should not be used to treat dementia-related psychosis in elderly patients.

  • It's crucial to consider alternative treatment options and to prioritize patient safety when managing symptoms in this population.

• Hepatic impairment

  • The use of methotrimeprazine is contraindicated in individuals with hepatic (liver) disease.

  • This means that it is not recommended to use this medication in patients with liver problems due to potential risks or adverse effects.

  • It's important for healthcare providers to consider alternative treatment options for individuals with hepatic disease to avoid potential complications.

• Respiratory disease

  • Patients with severe asthma or emphysema should approach the use of methotrimeprazine cautiously due to the potential risk of central nervous system (CNS) depression.

  • CNS depression refers to a decrease in brain activity, which can lead to symptoms such as drowsiness, confusion, and slowed breathing.

  • In patients with severe asthma or emphysema, CNS depression can exacerbate respiratory issues and potentially lead to respiratory failure.

  • Therefore, it's essential for healthcare providers to carefully assess the risks and benefits of using methotrimeprazine in patients with severe asthma or emphysema and to closely monitor them for any signs of CNS depression or respiratory compromise during treatment.

• Seizure disorder

  • Patients with seizure disorders should be treated cautiously when using methotrimeprazine due to the potential for lowering the seizure threshold.

  • Lowering the seizure threshold means that there is an increased risk of experiencing seizures or convulsions.

  • Therefore, it's crucial for healthcare providers to carefully assess the risks and benefits of using methotrimeprazine in patients with seizure disorders.

  • Additionally, patients with seizure disorders should receive appropriate anticonvulsant treatment to help control their seizures effectively.

  • Close monitoring for any changes in seizure frequency or severity is essential during treatment with methotrimeprazine.

  • If seizures occur or worsen, adjustments to the treatment plan may be necessary.

Monitoring parameters:

• During treatment with methotrimeprazine, patients should undergo regular monitoring to assess various aspects of their health. This monitoring may include:

• Mental status evaluation: Assessing changes in mood, cognition, and behavior.
• Vital signs: Monitoring blood pressure, heart rate, temperature, and respiratory rate as needed.
• Body mass index (BMI): Evaluating weight and height to determine BMI, which can indicate changes in weight over time.
• Liver function tests: Performing baseline tests before starting treatment and periodically thereafter to monitor liver health.
• Complete blood count (CBC): Obtaining baseline values and monitoring during the initial 2-3 months of therapy, then regularly thereafter to check for any abnormalities.
• Plasma glucose: Testing glucose levels in patients with or at risk of diabetes to monitor for hyperglycemia.
• Abnormal Involuntary Movement Scale (AIMS): Assessing for any abnormal movements or involuntary muscle contractions.
• Extrapyramidal symptoms (EPS): Monitoring for symptoms such as tremors, muscle stiffness, or involuntary movements.
• Electrocardiogram (ECG): Conducting ECG tests if clinically indicated to evaluate cardiac function and detect any abnormalities.

• Regular and comprehensive monitoring helps healthcare providers to detect any potential adverse effects or changes in health status promptly, allowing for timely intervention or adjustments to the treatment plan as needed.

Schizophrenia (additional monitoring recommendations):

• Regular monitoring of various parameters is essential during treatment with methotrimeprazine to ensure patient safety and detect any potential adverse effects. Here's a summary of the recommended monitoring schedule:

• Body mass index (BMI) and waist measurement:

  • Baseline assessment.
  • At every visit for the first 6 months.
  • Quarterly with a stable antipsychotic dose.

• Electrolytes:

  • Annually and as clinically indicated.

• Hemoglobin A1c (HbA1c) and fasting plasma glucose:

  • Baseline assessment.
  • Then yearly.
  • Repeat 4 months after starting antipsychotic in patients with diabetes risk factors or if gaining weight, then yearly.

• Fasting lipid panel:

  • Baseline assessment.
  • Repeat after two years if LDL levels are normal.
  • Repeat after six months if LDL levels are greater than 130 mg/dL.

• Menstrual cycle, libido, galactorrhea development, erectile, and ejaculatory function changes:

  • Baseline assessment.
  • Monthly for 3 months after initiation, then yearly.

• Parkinsonian symptoms or unusual involuntary motions:

  • Baseline assessment.
  • Repeat weekly until the dose is stabilized 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.

• Following this monitoring schedule helps healthcare providers to assess treatment efficacy, detect potential adverse effects, and adjust the treatment plan as needed to ensure optimal patient outcomes.

How to administer Levomepromazine (Methoprazine)?

• For oral administration:

• Take the medication with you.

• For injection:

• Parenteral administration options include slow intravenous injection at a rate of 20-40 drops per minute, deep intramuscular injection, or subcutaneous injection (off-label route).
• Injection can be given as bolus injections or as a continuous infusion for up to 24 hours.
• If you experience significant sedation, consider administering lower doses during the day and higher doses at night for intermittent dosing.

Mechanism of action of Levomepromazine (Methoprazine):

• Methotrimeprazine is an antagonist of D1 and D2 dopamine subtypes with an aliphatic phenothiazine structure. Additionally, it binds to serotonin (5HT-1 and 5-HT-2), alpha-1 and alpha-2, and muscarinic receptors (M-1 & M-2).

  Here are some pharmacokinetic details:

• Onset of action:

  • Injection: 1 hour

• Duration:

  • 2 to 4 hours

• Bioavailability:

  • 50%

• Time to peak serum concentration:

  • Intramuscular (IM): 0.5 to 1.5 hours
  • Oral: 1 to 3 hours

• Half-life elimination:

  • 15 to 30 hours

• Excretion:

  • Primarily through urine
  • Also through 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.