Melatonin

§4.2 verbatim: '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.' §4.1 verbatim and in full: 'Circadin is indicated as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over.' NO MAXIMUM DOSE IS STATED — §4.2 gives a single fixed dose and sets no ceiling above it; its only limit is one of DURATION (up to thirteen weeks), which is not a dose ceiling and has therefore been left out of the maxDose field and recorded here and in the frequency instead. PAEDIATRIC — §4.2 verbatim: '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.' No paediatric dose is therefore published. 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.' 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.' DROWSINESS — §4.4: '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.' AUTOIMMUNE DISEASE — §4.4: '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.' LACTOSE — §4.4: contains lactose; patients with rare hereditary problems of galactose intolerance, the LAPP lactase deficiency or glucose-galactose malabsorption should not take this medicine. KEY INTERACTIONS from §4.5 (whose text sits inside the bundle's 'warnings' value, as eMC does not expose it as a separate section heading): fluvoxamine increases melatonin levels 17-fold (AUC) and 12-fold (serum Cmax) by inhibiting CYP1A2 and CYP2C19 — 'The combination should be avoided'; caution with 5- or 8-methoxypsoralen, cimetidine, oestrogens (contraceptives or HRT) and CYP1A2 inhibitors such as quinolones, all of which increase melatonin exposure; CYP1A2 inducers such as carbamazepine and rifampicin may reduce melatonin levels, as may cigarette smoking; 'Alcohol should not be taken with Circadin, because it reduces the effectiveness of Circadin on sleep'; 'Circadin may enhance the sedative properties of benzodiazepines and non-benzodiazepine hypnotics, such as zaleplon, zolpidem and zopiclone' — co-dosing with zolpidem increased impairment of attention, memory and co-ordination versus zolpidem alone. §4.5 also notes 'Interaction studies have only been performed in adults.' ⚠️ §4.8 OF THIS BUNDLE IS TRUNCATED AT THE SOURCE-FETCH LIMIT — the sideEffects list below is therefore incomplete.