Skip to content
ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Melatonin Receptor Agonist — Hypnotic Pregnancy: §4.6, verbatim: 'For melatonin, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). In view of the lack of clinical data, use in pregnant women and by women intending to become pregnant is not recommended.' Breastfeeding: 'Endogenous melatonin was measured in human breast milk thus exogenous melatonin is probably secreted into human milk. There are data in animal models including rodents, sheep, bovine and primates that indicate maternal transfer of melatonin to the foetus via the placenta or in the milk. Therefore, breast-feeding is not recommended in women under treatment with melatonin.'

Melatonin

Brand names: Circadin (2mg modified-release — licensed), Slenyto (paediatric), Various OTC preparations (unlicensed in UK)

Melatonin is a pineal hormone analogue used orally as a hypnotic, licensed for short-term treatment of primary insomnia in older adults and used (often as modified-release preparations) for sleep-onset disorders in children with neurodevelopmental conditions and for circadian rhythm sleep disorders.

Adult dose

Dose: 2 mg once daily
Route: Oral. §4.2, verbatim: 'Oral use. Tablets should be swallowed whole to maintain prolonged release properties. Crushing or chewing should not be used to facilitate swallowing.'
Frequency: Once daily, 1-2 hours before bedtime and after food
§4.2, verbatim and complete: 'The recommended dose is 2 mg once daily, 1-2 hours before bedtime and after food. This dosage may be continued for up to thirteen weeks.' This is the only regimen the SPC states — there is no titration step and no higher dose in the label. || DURATION, NOT A DOSE CEILING: the 'up to thirteen weeks' limit is a limit on how long the dose may be continued, so it is recorded here and deliberately kept out of maxDose, which is reserved for an absolute ceiling on the amount given. NO MAXIMUM DOSE IS STATED ANYWHERE IN §4.2, so maxDose is left empty rather than inferred from the recommended dose. || SCOPE: §4.1 was not fetched, so this draft does not restate the licensed indication or any licensed lower age limit for the product; the dose above is simply the product's own recommended dose. || Interaction cautions from §4.5 that bear on dosing: fluvoxamine 'increases melatonin levels (by 17-fold higher AUC and a 12-fold higher serum C max)... The combination should be avoided'; caution also with 5- or 8-methoxypsoralen, cimetidine, oestrogens (contraceptive or HRT) and CYP1A2 inhibitors such as quinolones, all of which increase melatonin exposure; CYP1A2 inducers such as carbamazepine and rifampicin 'may give rise to reduced plasma concentrations of melatonin'; and 'Cigarette smoking may decrease melatonin levels due to induction of CYP1A2.'

Dose adjustments

Renal

§4.2, verbatim: 'The effect of any stage of renal impairment on melatonin pharmacokinetics has not been studied. Caution should be used when melatonin is administered to such patients.' No numeric dose adjustment is given.

Hepatic

§4.2, verbatim: 'There is no experience of the use of Circadin in patients with liver impairment. Published data demonstrates markedly elevated endogenous melatonin levels during daytime hours due to decreased clearance in patients with hepatic impairment. Therefore, Circadin is not recommended for use in patients with hepatic impairment.' No dose adjustment is given because use is not recommended.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • §4.3, and the only contraindication this SPC lists, verbatim: 'Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.'
  • NOT a contraindication but a §4.4 precaution — autoimmune diseases: 'No clinical data exist concerning the use of Circadin in individuals with autoimmune diseases. Therefore, Circadin is not recommended for use in patients with autoimmune diseases.'
  • NOT a contraindication but a §4.4 excipient restriction — 'Circadin contains lactose. Patients with rare hereditary problems of galactose intolerance, the LAPP lactase deficiency or glucose-galactose malabsorption should not take this medicine.'
  • NOT a contraindication but a §4.2 population statement — 'The safety and efficacy of Circadin in children aged 0 to 18 years has not yet been established. Other pharmaceutical forms/strengths may be more appropriate for administration to this population.' This is why paedDose is null on this page
  • NOT a contraindication but a §4.5 combination to avoid — fluvoxamine, which raises melatonin AUC 17-fold; 'The combination should be avoided.' Alcohol should not be taken with the product 'because it reduces the' effectiveness (§4.5, sentence truncated at the source-fetch limit)

Side effects

  • Overall rates, §4.8: in clinical trials of 1,931 patients on Circadin versus 1,642 on placebo, '48.8% of patients receiving Circadin reported an adverse reaction compared with 37.8% taking placebo', though the rate per 100 patient-weeks was higher for placebo (5.743) than Circadin (3.013). Most common reactions were headache, nasopharyngitis, back pain and arthralgia — common in both the Circadin and placebo groups
  • Uncommon (≥1/1,000 to <1/100), §4.8 table — irritability, nervousness, restlessness, insomnia, abnormal dreams, nightmares, anxiety; migraine, headache, lethargy, psychomotor hyperactivity, dizziness, somnolence; abdominal pain, abdominal pain upper, dyspepsia, mouth ulceration, dry mouth, nausea; hyperbilirubinaemia; dermatitis, night sweats, pruritus, rash, pruritus generalised, dry skin; hypertension
  • Rare (≥1/10,000 to <1/1,000), §4.8 table — herpes zoster; leukopenia, thrombocytopenia; hypersensitivity reaction; hypertriglyceridaemia, hypocalcaemia, hyponatraemia; mood altered, aggression, agitation, crying, stress symptoms, disorientation, early morning awakening, libido increased, depressed mood, depression; syncope, memory impairment, disturbance in attention, dreamy state, restless legs syndrome, poor quality sleep, paraesthesia; visual acuity reduced, vision blurred, lacrimation increased; vertigo and positional vertigo; angina pectoris, palpitations; hot flush; gastro-oesophageal reflux disease, oral mucosal blistering, tongue ulceration, vomiting, flatulence, salivary hypersecretion, halitosis, gastritis; eczema, erythema, hand dermatitis
  • Drowsiness — §4.4, verbatim: 'Circadin may cause drowsiness. Therefore the product should be used with caution if the effects of drowsiness are likely to be associated with a risk to safety.'
  • This side-effect list may be incomplete — check the full SPC.

Monitoring

  • Duration of treatment — §4.2 states the dose 'may be continued for up to thirteen weeks'; treatment length is the explicit thing to keep under review
  • Daytime drowsiness and any safety-critical activity — §4.4: use with caution 'if the effects of drowsiness are likely to be associated with a risk to safety'
  • Review concomitant CYP1A2 medication and smoking status, both of which move melatonin exposure substantially in either direction (§4.5)
  • No laboratory or blood monitoring schedule is specified in any fetched section — none is asserted here

Clinical monograph

How it works

It activates MT1 and MT2 melatonin receptors in the suprachiasmatic nucleus, reinforcing the endogenous circadian signal that promotes sleep onset and entrains the sleep-wake cycle.

Prescribing in practice

  • Brands and formulations are not interchangeable (immediate- versus modified-release behave differently), so prescribe by brand and avoid switching without intent.
  • It may cause daytime drowsiness; warn about driving and operating machinery, particularly when first started.
  • Caution and dose review are needed in hepatic impairment and with potent CYP1A2 inhibitors such as fluvoxamine, which markedly raise melatonin levels.

Monitoring

No routine laboratory monitoring is required; review clinical response to sleep and continued need periodically rather than continuing indefinitely.

Counselling the patient

  • Take shortly before bedtime and avoid alcohol, which reduces its effectiveness.
  • Swallow modified-release tablets whole unless a specific formulation is licensed to be dispersed.
  • Use alongside good sleep hygiene rather than as a sole measure.

Evidence & guidelines

NICE supports time-limited melatonin in defined groups such as older adults with insomnia and children with neurodevelopmental sleep problems, with regular review of ongoing need.

Reference: NICE NG215 (Insomnia); NICE TA739 (Slenyto for ASD/SMS); Circadin SPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Drugs
Pathways