Levomepromazine

BRAND NAMES

• Nozinan

• Levoprome

• Hirnamin

• Generic: Levomepromazine / Methotrimeprazine

MECHANISM OF ACTION

Levomepromazine works mainly by blocking dopamine D2 receptors, which helps reduce psychotic symptoms and agitation. It also blocks histamine H1 receptors causing sedation and antiemetic effects, muscarinic receptors leading to anticholinergic effects like dry mouth and constipation, and alpha-1 adrenergic receptors which can cause orthostatic hypotension. Together, these actions give it strong antipsychotic, sedative, and anti-nausea properties.

PHARMACOKINETICS

Absorption

Levomepromazine is well absorbed after oral administration, but it undergoes significant first-pass metabolism in the liver, which reduces its systemic bioavailability. Peak plasma concentrations are usually reached within a few hours after dosing, and absorption can be influenced by food intake and individual variability in gastrointestinal uptake.

Distribution

Levomepromazine has a large volume of distribution (Vd), typically reported in the range of ~10–30 L/kg, reflecting extensive tissue binding and high lipophilicity. It readily distributes into the brain and other highly perfused tissues, and it is also highly protein-bound in plasma (often >90%), which contributes to prolonged tissue retention and a relatively long duration of action.

Metabolism

Levomepromazine is extensively metabolized in the liver, mainly through cytochrome P450 (CYP) enzymes, especially oxidation and demethylation pathways. It is converted into several active and inactive metabolites, some of which may contribute to its prolonged sedative effects. Because of this extensive hepatic metabolism, its clearance can vary significantly between individuals and may be affected by liver function and drug interactions.

Elimination

Levomepromazine is extensively metabolized in the liver, mainly through cytochrome P450 (CYP) enzymes, especially oxidation and demethylation pathways. It is converted into several active and inactive metabolites, some of which may contribute to its prolonged sedative effects. Because of this extensive hepatic metabolism, its clearance can vary significantly between individuals and may be affected by liver function and drug interactions.

PHARMACODYNAMICS

Levomepromazine works by blocking multiple receptors in the brain and body, mainly dopamine D2 receptors, which helps reduce psychosis and agitation. It also blocks histamine H1 receptors causing strong sedation, muscarinic receptors leading to anticholinergic effects, and alpha-1 adrenergic receptors resulting in low blood pressure. These combined actions give it antipsychotic, antiemetic, and sedative properties.

ADMINISTRATION

Levomepromazine is given mainly by oral route in tablet or liquid form for routine use. In acute or palliative care situations, it can also be administered by intramuscular or subcutaneous injection for faster effect. The dose is usually started low and adjusted carefully because of its strong sedative and blood pressure–lowering effects.

DOSAGE AND STRENGTH

Levomepromazine dosing varies by indication and patient condition. For oral use, common tablet strengths are 25 mg, 50 mg, and 100 mg, and typical daily doses range from 25–300 mg/day in divided doses for psychiatric indications. In palliative care or for sedation/antiemetic use, much lower doses are used, often 6.25–25 mg every 4–8 hours as needed. For intramuscular or subcutaneous use, doses are generally lower and individualized, depending on severity of symptoms and patient response.

DRUG INTERACTIONS

Levomepromazine has important drug interactions due to its strong sedative and receptor-blocking effects:

• CNS depressants (benzodiazepines, opioids, alcohol) → increased sedation, respiratory depression risk

• Anticholinergic drugs → additive effects like dry mouth, constipation, confusion

• Antihypertensives → enhanced hypotension due to alpha-1 blockade

FOOD INTERACTIONS

Levomepromazine has no major food interactions. It can be taken with or without food, although food may slightly delay absorption. Alcohol should be avoided because it can significantly increase sedation and dizziness.

CONTRAINDICATIONS

Levomepromazine is contraindicated in patients with hypersensitivity to phenothiazines, severe CNS depression or coma, and significant bone marrow suppression. It should also be avoided in pheochromocytoma and in patients with serious cardiac disease or prolonged QT interval due to risk of hypotension and arrhythmias.

SIDE EFFECTS

• Sedation / drowsiness

• Dizziness

• Dry mouth

• Constipation

• Blurred vision

• Orthostatic hypotension

• Weight gain

OVER DOSE

Levomepromazine overdose causes severe sedation, low blood pressure, confusion, and breathing problems. It may also lead to anticholinergic effects and dangerous heart rhythm changes, requiring urgent medical care.

TOXICITY

Levomepromazine toxicity causes severe sedation, low blood pressure, confusion, breathing depression, and anticholinergic effects like dry mouth and urinary retention. It can also lead to dangerous heart rhythm problems such as QT prolongation, requiring urgent supportive medical care and monitoring.