Circadin 2mg

Curated from: Sire – Men’s Health Clinic

Circadin® 2mg

Important Safety Information

Circadin®

Disclaimer: The information provided on this page is not a substitute for professional medical advice, diagnosis, or treatment. If you have any questions or concerns about your health, please talk to a doctor.

What does Circadin® contain?

The active ingredient in Circadin prolonged release tablets is melatonin.

Circadin prolonged release tablets also contain the excipients: ammonio methacrylate copolymer, calcium hydrogen phosphate, lactose, colloidal anhydrous silica, purified talc and magnesium stearate.

What is melatonin?

Melatonin is a naturally occurring hormone produced by the pineal gland and is structurally related to serotonin. Physiologically, melatonin secretion increases soon after the onset of darkness, peaks at 2-4 am and diminishes during the second half of the night. Melatonin is associated with the control of circadian rhythms and entrainment to the light-dark cycle. It is also associated with a hypnotic effect and increased propensity for sleep.

How does Circadin work?

Because of the role of melatonin in sleep and circadian rhythm regulation, and the age related decrease in endogenous melatonin production, melatonin may effectively improve sleep quality particularly in patients who are over 55 with primary insomnia.

How should I take Circadin?

Oral use. Tablets should be swallowed whole to maintain prolonged release properties. Crushing or chewing should not be used to facilitate swallowing. 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.

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Contraindications

Circadin prolonged release tablets are contraindicated in patients with a known hypersensitivity to any ingredient of the product (see WHAT DOES CIRCADIN CONTAIN?)

Precautions

Drowsiness

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.

Effects on ability to drive and operate machinery

Circadin has moderate influence on the ability to drive and use machines. Nevertheless, patients should avoid engaging in hazardous activities (such as driving or operating machinery) after taking Circadin.

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.

Excipients

The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the LAPP lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Effects on fertility

No significant effects on fertility or reproductive performance were observed in rats given oral melatonin prior to mating through to early gestation at doses over 900-fold the recommended clinical dose, based on body surface area.

Use in pregnancy

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.

Use in lactation

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.

Paediatric use

The safety and efficacy of Circadin in children aged 0 to 18 years has not yet been established. No data are available.

Use in the elderly

Melatonin metabolism is known to decline with age. Across a range of doses, higher AUC and Cmax levels have been reported in older subjects compared to younger subjects, reflecting the lower metabolism of melatonin in the elderly.

Renal insufficiency

The effect of any stage of renal insufficiency on melatonin pharmacokinetics has not been studied. Caution should be used when melatonin is administered to such patients.

Hepatic impairment

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.

Carcinogenicity

An oral lifetime carcinogenicity study with melatonin in rats showed an increased incidence of thyroid follicular cell adenomas in males at doses around 700-fold the recommended clinical dose, based on body surface area. No neoplastic tissue histopathology was examined at lower doses and therefore the no-effect dose could not be determined. These effects were associated with liver enzyme induction in this species and are unlikely to be relevant to humans.

Genotoxicity

Results from a standard battery of in vitro and in vivo assays showed no evidence of a genotoxic potential for melatonin.

Interactions with other medicines

Tell your healthcare provider if you take any of the following because these drugs interact with Circadin.

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

Pharmacokinetic interactions

Hepatic enzymes

Melatonin has been observed to induce CYP3A in vitro at supra-therapeutic concentrations. The clinical relevance of the finding is unknown. If induction occurs, plasma concentrations of concomitantly administered drugs can be reduced.

Melatonin does not appear to induce CYP1A enzymes in vitro at supra[1]therapeutic concentrations. Therefore, interactions between melatonin and other active substances as a consequence of melatonin’s effect on CYP1A enzymes are not likely to be significant.

Melatonin’s metabolism is mainly mediated by CYP1A enzymes. Therefore, interactions between melatonin and other active substances as a consequence of their effect on CYP1A enzymes is possible:

Quinolones – CYP1A2 inhibitors such as quinolones may give rise to increased melatonin exposure.

Carbamazepine and rifampicin – CYP1A2 inducers such as carbamazepine and rifampicin may give rise to reduced plasma concentrations of melatonin.

Fluvoxamine – Caution should be exercised in patients on fluvoxamine, which increases melatonin levels (17-fold higher AUC and 12-fold higher serum Cmax) by inhibiting its metabolism by hepatic cytochrome P450 (CYP) isozymes CYP1A2 and CYP2C19. The combination should be avoided.

5- or 8-methoxypsoralen – Caution should be exercised in patients on 5- or 8- methoxypsoralen (5 and 8-MOP), which increases melatonin levels by inhibiting its metabolism.

Cimetidine – Coadministration of Circadin with cimetidine resulted in a 1.7 fold increase in exposure to melatonin with no change in the exposure to cimetidine. Caution should be exercised in patients on cimetidine, a CYP2D inhibitor which increases plasma melatonin levels by inhibiting its metabolism. Cigarette smoking – Cigarette smoking may decrease melatonin levels due to induction of CYP1A2. Oestrogens – Caution should be exercised in patients on oestrogens (e.g. contraceptives or hormone replacement therapy), which increase melatonin levels by inhibiting its metabolism by CYP1A1 and CYP1A2.

Other – There is a large amount of data in the literature regarding the effect of adrenergic agonists/antagonists, opiate agonists/antagonists, antidepressant medicinal products, prostaglandin inhibitors, benzodiazepines, tryptophan and alcohol, on endogenous melatonin secretion. Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

Pharmacodynamic interactions

Alcohol

Alcohol should not be taken with Circadin, because it reduces the effectiveness of Circadin on sleep. The prolonged release characteristics of Circadin may be altered by alcohol, resulting in immediate release of melatonin.

Hypnotics

Circadin may enhance the sedative properties of benzodiazepines and non-benzodiazepine hypnotics, such as zalepon, zolpidem and zopiclone. In a clinical trial, there was clear evidence for a transitory pharmacodynamic interaction between Circadin and zolpidem one hour following co-dosing. Concomitant administration resulted in increased impairment of attention, memory and co-ordination compared to zolpidem alone.

Thioridazine and imipramine

Circadin has been co-administered in studies with thioridazine and imipramine, active substances which affect the central nervous system. No clinically significant pharmacokinetic interactions were found in each case. However, Circadin co-administration resulted in increased feelings of tranquility and difficulty in performing tasks compared to imipramine alone, and increased feelings of “muzzy-headedness” compared to thioridazine alone.

Effect on laboratory tests

No information is available on the effect of melatonin on laboratory tests.

Circadin Side Effects

The most common adverse reactions were headache, nasopharyngitis, back pain, and arthralgia, which were common, by MedDRA definition, in both the Circadin and placebo treated groups.

Tell your healthcare provider if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of Circadin®. For more information, ask your healthcare provider or pharmacist, or see the full Prescribing Information for Circadin®.

Talk to your doctor for medical advice about side effects.

What happens if I overdose?

Several cases of overdose have been reported post-marketing. Somnolence was the most reported adverse event. Most were mild to moderate in severity.

If overdose occurs, drowsiness is to be expected. Clearance of the active substance is expected within 12 hours after ingestion.

Always check with a healthcare professional for advice.

Storage Conditions

Store below 25ºC. Protect from light