MELATONIN - Oral

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.

Notes

Date

August 28, 2018

Proper name(s), Common name(s), Source material(s)

Table 1. Proper name(s), Common name(s), Source material(s)
Proper name(s) Common name(s) Source material(s)
Common name(s) Preparation(s)
  • N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide
  • N-Acetyl-5-methoxytryptamine
  • Melatonin
  • Pineal hormone

Melatonin

Synthetic

References: Proper names: O' Neil et al. 2013, Martindale 2012, Buscemi et al. 2004; Common name: O' Neil et al. 2013, Buscemi et al. 2004; Source material: O' Neil et al. 2013.

Route of Administration

Oral (Buscemi et al. 2004)

Dosage Form(s)

This monograph excludes foods or food-like dosage forms as indicated in the Compendium of Monographs Guidance Document.

Acceptable dosage forms for the age category listed in this monograph and specified route of administration are indicated in the Compendium of Monographs Guidance Document.

Use(s) or Purpose(s)

The following combined use(s) or purpose(s) is/are also acceptable:

Dose(s)

Subpopulation(s)

Adults 18 years and older (IOM 2004)

Quantity(ies)

All uses except jet lag

0.1-10 milligrams of melatonin, per day (Brzezinski et al. 2005; IOM 2004; Andrade et al. 2001; Kayumov et al. 2001; Koda-Kimble 2001; Smits et al. 2001; Zhdanova et al. 2001; Citera et al. 2000; Shamir et al. 2000; Brusco et al. 1999; Jean-Louis et al. 1999; Matsumoto 1999; Dolberg et al. 1998; Lewy et al. 1998; Attenburrow et al. 1996; Garfinkel 1995; Haimov et al. 1995; Tzischinsky and Lavie 1994; Dollins et al. 1993; Dahlitz et al. 1991; James et al. 1987).

Jet lag

0.5-10 milligrams of melatonin, per day (Brown et al. 2009; Herxheimer and Petrie 2009; Suhner et al. 1998a).

Direction(s) for use

All uses except jet lag

Take once a day, at or before bedtime (Murray et al. 2006; Kayumov et al. 2001; Zhdanoya et al. 2001).

Jet lag

Take once a day at bedtime, while travelling, and at destination until adapted to the new time zone/or daily pattern (Brown et al. 2009; Herxheimer and Petrie 2009).

Duration(s) of Use

All products

Consult a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 4 weeks (Buscemi et al. 2004; IOM 2004).

Risk Information

Caution(s) and warning(s)

All uses except jet lag

Consult your health care practitioner/health care provider/health care professional/doctor/ physician if sleeplessness persists for more than 4 weeks (chronic insomnia) (Buscemi et al. 2004; IOM 2004; Dipiro et al. 2002).

All uses

Contraindication(s)

Known adverse reaction(s)

Stop use if allergy occurs or if you experience headache, confusion, or nausea (Herxheimer and Petrie 2009).

Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database (NHPID) and must meet the limitations outlined in the database.

Storage conditions

No statement required.

Specifications

References Cited

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Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford I.  Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Medicine Reviews 2005;9:41-50.

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Cagnacci A, Arangino S, Renzi A, Paoletti AM, Melis GB, Cagnacci P, Volpe A.  Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clinical Endocrinology (Oxford) 2001a;54(3):339-46.

Cagnacci A, Arangino S, Angiolucci M, Melis GB, Facchinetti F, Malmusi S, Volpe A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clinical Endocrinology 2001b;54:261-266.

Calvo JR, Guerrero JM, Osuna C, Molinero P, Carrillo-Vico A. Melatonin triggers Crohn’s disease symptoms. Journal of Pineal Research 2002;32(4):277-278.

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Citera G, Arias MA, Maldonado-Cocco JA, Lazaro MA, Rosemffet MG, Brusco LI, Scheines EJ, Cardinalli DP.  The effect of melatonin in patients with fibromyalgia: a pilot study. Clinical Rheumatology 2000;19(1):9-13.

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Lewy AJ, Bauer VK, Cutler NL, Sack RL.  Melatonin treatment of winter depression: a pilot study. Psychiatry Research 1998;77(1):57-61.

Lissoni P, Barni S, Mandalà M, Ardizzoia A, Paolorossi F, Vaghi M, Longarini R, Malugani F, Tancini G. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. European Journal of Cancer 1999;35(12):1688-1692.

Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. British Journal of Clinical Pharmacology 2000;49:423427.

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Matsumoto M.  The hypnotic effects of melatonin treatment on diurnal sleep in humans. Psychiatry and Clinical Neurosciences 1999;53(2):243-5. 

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Petrie K, Dawson AG, Thompson L, Brook R.  A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biological Psychiatry 1993;33(7): 526-30. 

Petrie K, Conaglen JV, Thompson L, Chamberlain K.  Effect of melatonin on jet lag after long haul flights. British Medical Journal 1989;298(6675):705-7.

Sack RL, Brandes RW, Kendall AR, Lewy AJ.  Entrainment of free-running circadian rhythms by melatonin in blind people. New England Journal of Medicine 2000;343 (15):1070-7.

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Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, Zisapel N.  Melatonin improves sleep quality of patients with chronic schizophrenia. Journal of Clinical Psychiatry 2000;61(5):373-7.

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Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA.  Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. Journal of Child Neurology 2001;16(2):86-92.

Suhner A, Schlagenhauf P, Johnson R, Tschopp A, Steffen R.  Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiology International 1998a;15(6):655-6.

Suhner A, Schlagenhauf P, Tschopp A, Hauri-Bionda R, Friedrich-Koch A, Steffen R.  Impact of melatonin on driving performance. Journal of Travel Medicine 1998b;5(1):7-13.

Sutherland ER, Martin RJ, Ellison MC, Kraft M. Immunomodulatory effects of melatonin in asthma. American Journal of respiratory and critical care medicine 2002;166:1055-1061.

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References Reviewed

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