A fixed-dose combination (FDC) of a synthetic melatonin receptor agonist (Melatonin) and a non-benzodiazepine Z-drug hypnotic (Zolpidem). This combination is designed to address both the circadian rhythm dysregulation and the GABA-A receptor-mediated sleep initiation deficit in insomnia. Melatonin helps regulate the sleep-wake cycle, while Zolpidem provides rapid-onset sedation. The FDC is intended for short-term management of severe, transient insomnia where monotherapy is insufficient, though its use as an FDC is controversial and not a first-line standard globally.
Adult: One tablet (Melatonin 3mg + Zolpidem 5mg) orally, immediately before bedtime. Must ensure a full 7-8 hours of dedicated sleep time after ingestion. Not to be taken with or immediately after a meal.
Note: Take IMMEDIATELY before going to bed. Tablet should be swallowed whole with a glass of water. Must be taken only when the patient can commit to a full night's sleep (7-8 hours) to avoid residual drowsiness and complex sleep behaviors. Should not be taken with or immediately after a heavy, high-fat meal as it delays absorption and reduces efficacy.
The combination exerts a dual mechanism: Zolpidem is a selective agonist at the benzodiazepine-1 (BZ1 or ω1) receptor subtype, which is a part of the GABA-A receptor chloride channel macromolecular complex. This enhances GABAergic inhibitory neurotransmission, leading to sedative, anxiolytic, and muscle relaxant effects, with predominant sedative action at low doses. Melatonin acts as an agonist at MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN) of the hypothalamus. MT1 receptor activation promotes sleepiness, while MT2 receptor involvement helps in phase-shifting the circadian clock, thereby synchronizing the sleep-wake cycle.
Pregnancy: Category C (US FDA). Not recommended. Zolpidem crosses placenta. Limited human data; animal studies show toxicity. Risk of neonatal flaccidity, respiratory depression, withdrawal symptoms. Use only if potential benefit justifies potential fetal risk.
Driving: STRICTLY NOT ADVISED. The drug impairs alertness, motor coordination, and reaction time the next day. Patients must not drive, operate machinery, or perform hazardous tasks for at least 8 hours after ingestion, and until they are sure they are not impaired.
| CNS Depressants (Alcohol, Opioids, Benzodiazepines, Antipsychotics, Antihistamines) | Additive CNS depression, profound sedation, respiratory depression, risk of death. | Major |
| Potent CYP3A4 Inhibitors (Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Markedly increases Zolpidem plasma levels, increasing toxicity risk. Contraindicated in hepatic impairment. | Major |
| CYP3A4 Inducers (Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Decreases Zolpidem plasma levels, reducing efficacy. | Moderate |
| CYP1A2 Inhibitors (Fluvoxamine, Ciprofloxacin) | Increases Melatonin plasma levels. | Moderate |
| Antihypertensives | Enhanced hypotensive effect. | Moderate |
| SSRIs/SNRIs (e.g., Fluoxetine, Sertraline) | Potential pharmacodynamic interaction increasing CNS effects; rare risk of serotonin syndrome (theoretical with melatonin). | Moderate |
Same composition (Melatonin (3mg) + Zolpidem (5mg)), different brands: