MELATONIN

Posology Jet-lag in adults The recommended dose is 2 mg (2 ml) daily for a maximum of 5 days. The dose may be increased to 5 mg (5 ml) daily if the initial dose does not adequately alleviate symptoms. The dose that adequately alleviates symptoms should be taken for the shortest period.

The first dose should be taken on arrival at destination at the habitual bedtime. Due to the potential for incorrectly timed intake of melatonin to have no effect, or an adverse effect, on re-synchronisation following jet-lag, Melatonin 1 mg/ml oral solution should not be taken before 20:00 hr or after 04:00 hr at destination.

Melatonin 1 mg/ml oral solution may be taken for a maximum of 16 treatment periods per year. Sleep onset insomnia in children and adolescents aged 6-17 years with ADHD Treatment should be initiated by physicians experienced in ADHD and/or paediatric sleep medicine.

Recommended starting dose is 1-2 mg (1-2 ml) 30-60 minutes before bedtime. The dose of melatonin can be increased by 1 mg (1 ml) every week until effect up to a maximum 5 mg (5 ml) per day, independent of age. The lowest effective dose that controls symptoms should be given.

There is limited data available for up to 3 years of treatment. After at least 3 months of treatment, the physician should evaluate the treatment effect and consider discontinuing the treatment if no clinically relevant treatment effect is seen.

The patient should be monitored at regular intervals (at least every 6 months) to check that Melatonin 1 mg/ml oral solution is still the most appropriate treatment. During ongoing treatment, especially if the treatment effect is uncertain, discontinuation attempts should be done regularly at least once per year.

If insomnia has occurred during treatment with ADHD medication, dose adjustment or change of the treatment should be considered. Special populations Elderly Caution should be exercised in the elderly population due to greater variability in plasma melatonin concentrations in this age group and potential for morning drowsiness.

2). Renal impairment There is only limited experience of administered melatonin in patients with renal impairment. Caution should be exercised if melatonin is used by patients with renal impairment. 2). Hepatic impairment There is no experience regarding the use of administered melatonin in patients with hepatic impairment.

Summary of the safety profile Melatonin causes few and no serious adverse reactions in the short term, up to three months. Drowsiness/sleepiness, headache, and dizziness/disorientation are the most frequently report adverse effects when melatonin is taken on a short-term basis to treat jet-lag.

Drowsiness, headache, dizziness, and nausea are also the adverse effects reported most frequently when typical clinical doses of melatonin have been taken for periods of several days to several weeks by healthy persons and patients.

There is limited documentation of long-term treatment with melatonin. Tabulated risks of adverse reactions In the table below all adverse reactions are listed according to organ class and frequency.

Frequencies are defined as:

Very common (≥1/10); Common (≥100 to <1/10); Uncommon (≥1/1000 to <1/100); Rare (≥1/10 000 to <1/1000); Very rare (<1/10000); Not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

System Organ Class Frequency Adverse Events Infections and infestations Rare Herpes Zoster Blood and lymphatic system Rare Leukopenia, thrombocytopenia disorders Immune system disorders Not known Hypersensitivity reaction Rare Hypertriglyceridaemia, hypocalcaemia, hyponatraemiaMetabolism and nutrition disorders Not known Hyperglycaemia Uncommon Irritability, nervousness, restlessness, insomnia, abnormal dreams, nightmares, anxiety Psychiatric disorders Rare Mood altered, aggression, agitation, crying, stress symptoms, disorientation, early morning awakening, libido increased, depressed mood, depression Common Headache, somnolence Uncommon Migraine, lethargy, psychomotor hyperactivity, dizziness Rare Syncope (fainting), memory impairment, disturbance in attention, dreamy state, restless legs syndrome, poor quality sleep, paraesthesia Nervous system disorders Not known Drowsiness, sedation Eye disorders Rare Visual acuity reduced, vision blurred, lacrimation increased Ear and labyrinth disorders Rare Vertigo positional, vertigo Cardiac disorders Rare Angina pectoris, palpitations Uncommon Hypertension Vascular disorders Rare Hot flushes Uncommon Abdominal pain, abdominal pain upper, dyspepsia, oral ulcers, dry mouth, nausea Gastrointestinal disorders Rare Gastroesophageal reflux disease, gastrointestinal disorder, oral mucosal blistering, tongue ulceration, gastrointestinal upset, vomiting, bowel sounds abnormal, flatulence, salivary hypersecretion, halitosis, abdominal discomfort, gastric disorder, gastritis Hepatobiliary disorders Uncommon Hyperbilirubinaemia Uncommon Dermatitis, night sweats, pruritus, rash, pruritus generalised, dry skin Rare Eczema, erythema, hand dermatitis, psoriasis, rash generalised, rash pruritic, nail disorder Skin and subcutaneous tissue disorders Not known Angioedema, oedema of mouth, tongue oedema Uncommon Pain in extremity Musculoskeletal and connective tissue disorders Rare Arthritis, muscle spasms, neck pain, night cramps Renal and urinary disorders Uncommon Glycosuria, proteinuria Rare Polyuria, haematuria, nocturia Uncommon Menopausal symptoms Rare Priapism, prostatitis Reproductive system and breast disorders Not known Galactorrhea Uncommon Malaise, chest painGeneral disorders and administration site conditions Rare Fatigue, pain, thirst Uncommon Liver function test abnormal, weight increased Investigations Rare Hepatic enzyme increased, blood electrolytes abnormal, laboratory test abnormal Pediatric population In the paediatric population, a low frequency of generally mild side effects have been reported.

Elderly Caution should be exercised in treatment of the elderly due to the potential for greater variability in plasma levels and of sensitivity to the effects of melatonin in this age group. Cautious dose titration is therefore recommended in the elderly.

g. epileptic patients). Caution should be exercised when prescribing to patients with epilepsy and/or with multiple neurological defects and/or with concomitant medications that could increase seizure frequency. Auto-immune diseases Occasional case reports have described exacerbation of an autoimmune disease in patients taking melatonin.

There are no data regarding use of melatonin in patients with autoimmune diseases. Melatonin 1 mg/ml oral solution is not recommended in patients with autoimmune diseases. Drowsiness Melatonin can cause drowsiness. Melatonin 1 mg/ml oral solution should be used with caution if the effects of drowsiness are likely to be associated with a risk to patient safety.

Food interaction Limited data suggest that melatonin taken in close proximity to ingestion of carbohydrate-rich meals may impair blood glucose control for several hours. Melatonin should be taken at least 2 hours before and at least 2 hours after a meal; ideally at least 3 hours after meal by persons with significantly impaired glucose tolerance or diabetes.

Renal and hepatic impairment Only limited data are available on the safety and efficiency of melatonin in patients with renal impairment or hepatic impairment. Melatonin 1 mg/ml oral solution is not recommended for use in patients suffering from severe renal impairment or moderate or severe hepatic impairment.

5) The patient should be closely monitored or switched to an alternative anti-coagulant, during melatonin use. Switching between formulations Caution may be taken when switching between melatonin products. Paediatric population (under 6 years of age) Melatonin 1 mg/ml oral solution is not recommended for use in children younger than 6 years of age.

1.