Levomethadon (Levomethadone Hydrochloride)

• Levomethadone is an opioid analgesic indicated for conditions that require strong pain control or opioid substitution.
• Severe chronic pain: provides potent analgesia for patients with high‑intensity, long‑standing pain.
• Opioid dependence substitution therapy: reduces withdrawal symptoms and cravings in individuals with opioid use disorder.
• Cancer‑related pain: offers opioid analgesia for malignant disease‑associated pain.

• Levomethadone acts as a full agonist at the µ‑opioid receptor, producing analgesia and opioid substitution effects. It also inhibits the reuptake of norepinephrine and serotonin, enhancing descending inhibitory pain pathways. Metabolism occurs primarily via CYP3A4 and CYP2B6, leading to inactive metabolites that are excreted renally.

Levomethadone may cause a range of adverse reactions, from mild to severe.

Common Side Effects

• Constipation: reduced gastrointestinal motility.
• Nausea and vomiting: gastrointestinal upset.
• Drowsiness or sedation: central nervous system depression.
• Dry mouth: reduced salivary flow.
• Sweating: increased perspiration.
• Dizziness: light‑headed sensation.

Serious or Rare Side Effects

• Respiratory depression: markedly reduced breathing effort.
• Severe hypotension: dangerous drop in blood pressure.
• Cardiac arrhythmias: abnormal heart rhythm.
• Dependence or addiction: potential for misuse with prolonged use.

• Levomethadone requires careful monitoring due to its opioid nature and potential for serious adverse events.
• Assess respiratory function: monitor for signs of respiratory depression, especially after dose initiation or escalation.
• Evaluate liver function: adjust use in patients with hepatic impairment.
• Monitor for signs of dependence: watch for cravings, tolerance, or withdrawal.
• Avoid concomitant CNS depressants: limit use with benzodiazepines or alcohol.
• Adjust dose in renal impairment: consider reduced dosing in severe kidney disease.
• Store at ambient temperature: keep in the original container, protect from moisture and direct sunlight.

Levomethadone can interact with several drug classes, affecting safety and efficacy.

Major Interactions (Avoid)

• MAO inhibitors: risk of severe serotonin syndrome.
• Other central nervous system depressants (e.g., benzodiazepines, barbiturates): additive respiratory depression.
• CYP3A4 strong inhibitors (e.g., ketoconazole, clarithromycin): increased levomethadone plasma levels.

Moderate Interactions (Monitor Closely)

• CYP3A4 inducers (e.g., rifampin, carbamazepine): reduced efficacy.
• Serotonergic agents (e.g., SSRIs, SNRIs): potential for serotonin syndrome.
• Antihistamines and anticholinergics: may enhance sedation and anticholinergic effects.