ADAFLEX AVA

Posology Jet lag in adults The standard dose of Melatonin AGB-Pharma tablets is 3 mg daily for a maximum of 5 days. 5 mg to 5 mg, may be gradually adjusted up to 5 mg for a maximum of 5 days, if symptoms are not sufficiently relieved by the standard dose.

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 (at local time). 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 AGB- Pharma tablets should not be taken before 20:00 hr or after 04:00 hr at destination.

g. 5). Melatonin AGB-Pharma may be taken for a maximum of 16 treatment periods per year. Insomnia in children and adolescents with ADHD Treatment should be initiated by physicians experienced in ADHD and/or paediatric sleep medicine. When treating insomnia in children and adolescents, melatonin should only be administered after other treatable causes of insomnia have been ruled out by appropriate specialist investigation and non- pharmacological measures have been insufficient.

5-2 mg once a day, 30-60 minutes before the desired bedtime. The dose of melatonin can be gradually increased every week until sufficient effect has been attained. The lowest effective dose should be sought. The maximum dose should not exceed 5 mg.

Limited data are available for up to 3 years of treatment. After at least 3 months of treatment, the physician should evaluate the treatment effect and consider stopping 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 AGB-Pharma is still the most appropriate treatment.

g. once per year. If the sleep disorder has started during treatment with medicinal products for ADHD, dose adjustment or switching to another product should be considered. 2). Caution should be exercised in treatment of significantly older patients and individual dosage is recommended.

Renal impairment There is only limited experience regarding the use of melatonin in patients with renal impairment. Caution is recommended when melatonin is administered to this patient population. 2). Hepatic impairment Limited data indicate that plasma clearance of melatonin is significantly reduced in patients with liver cirrhosis.

Summary of the safety profile Drowsiness/sleepiness, headache, and dizziness/disorientation are the most frequently reported adverse reactions when melatonin is taken on a short-term basis to treat jet lag and primary insomnia. Drowsiness, headache, dizziness, and nausea are also the adverse reactions 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.

Tabulated list of adverse reactions Adverse reactions in adults are listed according to MedDRA system organ class and presented within each frequency category according to the following: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).

System organ class Very comm on Commo n Uncommon Rare Not known (cannot be estimated from the available data) Infections and infestations Herpes zoster Blood and lymphatic system disorders Leukopenia, thrombocytopeni a Immune system disorders Hypersensiti vity reaction Metabolism and nutrition disorders Hypertriglycerid emia, hypocalcaemia, hyponatraemia Hyperglycae mia Psychiatric disorders Irritability, nervousness, restlessness, insomnia, abnormal dreams, nightmares, anxiety Mood altered, aggression, agitation, crying, stress symptoms, disorientation, early morning awakening, libido increased, depressed mood, depression Hallucinatio ns Nervous system disorders Headach e, somnole nce Migraine, lethargy, psychomotor hyperactivity, dizziness Syncope, memory impairment, disturbance in attention, Drowsiness, sedation System organ class Very comm on Commo n Uncommon Rare Not known (cannot be estimated from the available data) dreamy state, restless legs syndrome, poor quality sleep, paraesthesia Eye disorders Visual acuity reduced, vision blurred, lacrimation increased Ear and labyrinth disorders Vertigo positional, vertigo Cardiac disorders Angina pectoris, palpitations Vascular disorders Hypertension Hot flush Gastrointesti nal disorders Abdominal pain, abdominal pain upper, dyspepsia, mouth ulceration, dry mouth, nausea Gastro- oesophageal reflux disease, gastrointestinal disorder, oral mucosal blistering, tongue ulceration, gastrointestinal upset, vomiting, bowel sounds abnormal, flatulence, salivary hypersecretion, halitosis, abdominal discomfort, gastric disorder, gastritis Hepatobiliar y disorders Hyperbilirubin emia Skin and subcutaneou s tissue disorders Dermatitis, night sweats, pruritus, rash, pruritus Eczema, erythema, hand dermatitis, psoriasis, rash Angioedema , oedema of mouth, tongue System organ class Very comm on Commo n Uncommon Rare Not known (cannot be estimated from the available data) generalised, dry skin generalised, rash pruritic, nail disorder oedema Musculoskel etal and connective tissue disorders Pain in extremity Arthritis, muscle spasms, neck pain, night cramps Renal and urinary disorders Glycosuria, proteinuria Polyuria, haematuria, nocturia Reproductiv e system and breast disorders Menopausal symptoms Priapism, prostatitis Galactorrho ea General disorders and administrati on site conditions Asthenia, chest pain Fatigue, pain, thirst Investigatio ns Liver function test abnormal, weight increased Hepatic enzyme increased, blood electrolytes abnormal, laboratory test abnormal Paediatric population A low frequency of in general mild adverse reactions have been reported in the paediatric population.

Melatonin may cause drowsiness. Melatonin tablets should be used with caution if the effects of drowsiness are likely to be associated with a risk to patient safety. Elderly Exposure levels to melatonin after oral administration in young and moderately older adults are comparable.

It is unclear if significantly older persons are especially sensitive to exogenous melatonin. Caution should therefore be exercised in treatment of this age group and individual dosage is recommended. Immunological diseases Occasional case reports have described exacerbation of an autoimmune disease in patients taking melatonin.

There are no data regarding use of melatonin tablets in patients with autoimmune diseases. Melatonin tablets are not recommended in patients with autoimmune diseases. Epilepsy Melatonin has been reported to increase, decrease and have no effect on seizure frequency.

Because of the uncertainty of the effect of melatonin on epileptic seizures, some caution should be exercised for use in people with epilepsy. Impaired glucose tolerance Limited data suggest that melatonin taken in close proximity to ingestion of carbohydrate rich meals may impair blood glucose control for several hours.

Melatonin tablets 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. Excipients This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

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