Melatonin

Registered South African indications: 

• Primary insomnia characterised by poor quality of sleep

Contraindications

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of its excipients 
• Pregnancy
• Lactation

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredients or any of its excipients

Cautions 

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment 
• Hepatic impairment 
• Autoimmune disease
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: Prolonged release (PR) tab

South African registered indications and dosages

Primary insomnia characterised by poor quality of sleep
- Short-term up to 13 weeks treatment in patients who are aged 55 years or over

• Oral (PR tab): 2mg, once daily, 1-2hrs before bedtime and after food; Treatment duration: Up to 13 weeks

Method of administration: Tablets should be swallowed whole to maintain prolonged release properties. Crushing or chewing should not be used to facilitate swallowing

Efficacy in patients younger than 55 years has not been demonstrated

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Contraindicated
• Melatonin should not be used during pregnancy as safety has not been established

Recommendations in other jurisdictions

• Caution; not recommended
• 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. In view of the lack of clinical data, use in pregnant women and by women intending to become pregnant is not recommended

Breastfeeding

South African recommendations

• Contraindicated
• Melatonin should not be used during lactation as safety has not been established
• Endogenous melatonin was measured in breast milk thus exogenous melatonin is probably secreted into human milk
• Mothers on melatonin 2mg should not breastfeed their infants

Recommendations in other jurisdictions

• Caution; not recommended
• 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, breastfeeding is not recommended in women under treatment with melatonin

Renal Impairment

• Caution; no dose adjustment recommended 

Hepatic Impairment

• Caution; no dose adjustment recommended 

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

•  Permitted - No warnings 

Central Nervous System Disorders

• Migraine
• Headache
• Lethargy
• Psychomotor hyperactivity
• Dizziness
• Somnolence
• Syncope
• Memory impairment
• Disturbance in attention
• Fatigue 
• Restless legs syndrome
• Poor quality sleep
• Paraesthesia
• Irritability
• Nervousness
• Restlessness
• Insomnia
• Abnormal dreams
• Anxiety
• Altered mood
• Aggression
• Agitation
• Crying
• Stress symptoms
• Disorientation
• Early morning awakening
• Increased libido 
• Depressed mood

Cardiovascular Disorders

• Angina pectoris
• Palpitations
• Hypertension
• Hot flush
• Chest pain 

Gastrointestinal Disorders

• Abdominal pain
• Dyspepsia
• Mouth ulceration
• Dry mouth
• Nausea and vomiting 
• Gastro-oesophageal reflux disease
• Oral mucosal blistering
• Tongue ulceration
• Abnormal bowel sounds
• Flatulence
• Salivary hypersecretion
• Halitosis
• Abdominal discomfort
• Gastritis

Hepatobiliary Disorders

• Hyperbilirubinaemia
• Increased hepatic enzymes

Genitourinary Disorders

• Glycosuria
• Proteinuria
• Polyuria
• Haematuria
• Nocturia
• Menopausal symptoms
• Priapism
• Prostatitis

Endocrine and Metabolic Disorders

• Galactorrhoea
• Increased weight 
• Hypertriglyceridaemia
• Hypocalcaemia
• Hyponatraemia

Musculoskeletal Disorders

• Arthritis
• Muscle spasms
• Neck pain
• Night cramps
• Pain in extremity

Skin and Subcutaneous Tissue Disorders

• Dermatitis
• Night sweats
• Pruritus
• Rash
• Pruritus
• Dry skin
• Eczema
• Erythema
• Psoriasis
• Nail disorder
• Angioedema
• Mouth oedema
• Tongue oedema

Immune, Blood and Lymphatic System Disorders

• Herpes zoster
• Leukopenia
• Thrombocytopenia
• Hypersensitivity reaction

Sensory Disorders

• Decreased visual acuity
• Blurred vision
• Increased lacrimation 
• Positional vertigo

• CYP3A substrates 
• CYP1A substrates 
• Fluvoxamine
• 8-methoxypsoralen
• 5-methoxypsoralen
• Cimetidine
• Oestrogens
• CYP1A2 inhibitors
• CYP1A2 inducers
• Alcohol
• Benzodiazepines
• Zaleplon
• Zolpidem
• Zopiclone
• Thioridazine
• Imipramine
• Cigarette smoking
• Quinolones
• Carbamazepine

None routine 

Melatonin is a hormone that is produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm.

Tablet 2mg

• Circadin (Litha Pharma) originator