Melatonin

New Zealand - English - Medsafe (Medicines Safety Authority)

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Active ingredient:
Melatonin 2 mg
Available from:
Generic Partners (NZ) Limited
Dosage:
2 mg
Pharmaceutical form:
Modified release tablet
Composition:
Active: Melatonin 2 mg Excipient: Calcium hydrogen phosphate dihydrate Colloidal silicon dioxide Lactose monohydrate Magnesium stearate Methacrylic acid copolymer Purified talc
Prescription type:
Prescription
Therapeutic indications:
Indicated as a monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients aged 55 years and over.
Product summary:
Package - Contents - Shelf Life: Blister pack, PVC/PVDC/Al in outer cardboard carton - 7 tablets - 36 months from date of manufacture stored at or below 25°C protect from light - Blister pack, Al/Al in outer cardboard carton - 7 tablets - 36 months from date of manufacture stored at or below 25°C protect from light - Blister pack, PVC/PVDC/Al in outer cardboard carton - 21 tablets - 36 months from date of manufacture stored at or below 25°C protect from light - Blister pack, Al/Al in outer cardboard carton - 21 tablets - 36 months from date of manufacture stored at or below 25°C protect from light - Blister pack, PVC/PVDC/Al in outer cardboard carton - 30 tablets - 36 months from date of manufacture stored at or below 25°C protect from light - Blister pack, Al/Al in outer cardboard carton - 30 tablets - 36 months from date of manufacture stored at or below 25°C protect from light
Authorization number:
TT50-10536
Authorization date:
2018-11-26

NEW ZEALAND DATA SHEET

1

PRODUCT NAME

MELATONIN (Generic Partners) Prolonged Release Tablets Melatonin 2 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 2mg of melatonin.

MELATONIN (Generic Partners) contains lactose monohydrate.

For the full list of excipients, see Section 6.1 List of excipients.

3

PHARMACEUTICAL FORM

MELATONIN (Generic Partners) 2 mg prolonged release tablets: White to off-white, round, biconvex

tablets

4

CLINICAL PARTICULARS

4.1

T

HERAPEUTIC INDICATIONS

Monotherapy for the short-term treatment of primary insomnia characterized by poor quality of

sleep in patients who are aged 55 or over.

4.2

D

OSE AND METHOD OF ADMINISTRATION

Oral use. Tablets should be swallowed whole.

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.

Paediatric Use

Melatonin is not recommended for use in children and adolescents below 18 years of age due to

insufficient data on safety and efficacy.

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 Melatonin 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, Melatonin is not recommended

for use in patients with hepatic impairment.

4.3

C

ONTRAINDICATIONS

Melatonin prolonged release tablets are contraindicated in patients with a known hypersensitivity to

any ingredient of the product (see section 6.1 List of Excipients).

4.4

S

PECIAL WARNINGS AND PRECAUTIONS FOR USE

Drowsiness

Melatonin 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.

Autoimmune Diseases

No clinical data exist concerning the use of Melatonin in individuals with autoimmune diseases.

Therefore, Melatonin 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.

Use in the elderly

Melatonin metabolism is known to decline with age. Across a range of doses, higher AUC and C

levels have been reported in older subjects compared to younger subjects, reflecting the lower

metabolism of melatonin in the elderly.

Paediatric use

Melatonin is not recommended for use in children and adolescents below 18 years of age due to

insufficient data on safety and efficacy.

Effects on laboratory tests

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

4.5

I

NTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS

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 medicines can be reduced.

Melatonin does not appear to induce CYP1A enzymes in vitro at supra-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 C

) 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 Melatonin 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 Melatonin or vice

versa has not been studied.

Pharmacodynamic Interactions

Alcohol

Alcohol should not be taken with Melatonin, because it reduces the effectiveness of Melatonin on

sleep. The prolonged release characteristics of Melatonin may be altered by alcohol, resulting in

immediate release of melatonin.

Hypnotics

Melatonin 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 Melatonin 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

Melatonin 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, Melatonin co-administration resulted in increased feelings of

tranquillity and difficulty in performing tasks compared to imipramine alone, and increased feelings

of “muzzy-headedness” compared to thioridazine alone.

4.6

F

ERTILITY

,

PREGNANCY AND LACTATION

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 – Pregnancy Category B3

No significant effects on embryofoetal development were observed in rats given oral melatonin

during the period of organogenesis at doses over 900 - fold the recommended clinical dose, based

on body surface area.

No clinical data on exposed pregnancies are available. In view of the lack of clinical data, use in

pregnant women and by women intended to become pregnant is not recommended.

Use in lactation.

Maternal transfer of exogenous melatonin to the foetus via the placenta or milk has been

demonstrated in several animal species including rats, hamsters, goats, monkeys and cows. A slight

reduction in post-natal growth, viability and development was found in rats given oral melatonin

during gestation through weaning at doses over 900 - fold the recommended clinical dose, based on

body surface area; the no-effect dose was over 250 - fold the clinical dose.

Endogenous melatonin has been detected in human breast milk, thus exogenous melatonin is likely

excreted into human milk. The effects of melatonin on the nursing infant have not been established.

Therefore, breast-feeding is not recommended in women under treatment with melatonin.

4.7

E

FFECTS ON ABILITY TO DRIVE AND USE MACHINES

Melatonin has negligible 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

Melatonin.

4.8

U

NDESIRABLE EFFECTS

In clinical trials (in which a total of 1931 patients were taking Melatonin and 1642 patients were

taking placebo), 48.8% of patients receiving Melatonin reported an adverse reaction compared with

37.8% taking placebo. Comparing the rate of patients with adverse reactions per 100 patient weeks,

the rate was higher for placebo than Melatonin (5.743 – placebo vs. 3.013 Melatonin). The most

common adverse reactions were headache, nasopharyngitis, back pain, and arthralgia, which were

common, by MedDRA definition, in both the Melatonin and placebo treated groups. In the

Melatonin group, there were 72 cases (2.9% of the safety population) of adverse events leading to

discontinuation of the patient. In the placebo group there were 62 cases (4.0% of the safety

population) of adverse events leading to discontinuation of the patient.

Overall Adverse Experience for adverse events occurring with a frequency ≥ 1%

Body System/Adverse

Experience

Melatonin %

(N=1931)

Placebo %

(N=1642)

Gastrointestinal disorders

Abdominal Pain

Abdominal Pain upper

Constipation

Diarrhoea

Nausea

Vomiting

General Disorders and administration site conditions

Asthenia

Infections and infestations

Influenza

Lower respiratory tract

infections

Nasopharyngitis

Pharyngitis

Upper respiratory tract

infection

Urinary tract infection

Musculoskeletal and connective tissue disorder

Arthralgia

Back Pain

Muscle cramp

Neck pain

Pain in extremity

Nervous system disorders

Dizziness

Headache

Migraine

Psychiatric disorders

Anxiety

Respiratory, thoracic and mediastinal disorder

Cough

Pharyngolaryngeal pain

Rhinitis

The adverse reactions in the table below were reported in clinical trials and were defined as

possibly, probably or definitely related to treatment. A total of 9.5% of subjects receiving Melatonin

reported an adverse reaction compared with 7.4% of subjects taking placebo. Only those adverse

events occurring in subjects at an equivalent or greater rate than placebo have been included.

Within each frequency grouping, undesirable effects are presented in order of decreasing

seriousness.

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 established from the available

data).

Adverse events related to treatment occurring with a frequency < 1%

System Organ Class

Uncommon

Rare

Not Known

Infections and

Infestations

Herpes zoster

Blood and Lymphatic

System Disorders

Leukopenia,

Thrombocytopenia

Cardiac Disorders

Angina pectoris

Palpitations

Immune System

Disorders

Hypersensitivity

reaction

Metabolism and

Nutrition Disorders

Hypertriglyceridaemia

Hypocalcaemia

Hyponatraemia

Psychiatric Disorders

Irritability,

Nervousness,

Restlessness,

Insomnia,

Abnormal

dreams, Anxiety,

Nightmares

Mood altered,

Aggression, Agitation,

Crying, Stress

symptoms,

Disorientation, Early

morning awakening,

Libido increased,

Depressed mood,

Depression

Nervous System

Disorders

Migraine Lethargy

Psychomotor

hyperactivity,

Dizziness,

Somnolence,

Headache

Syncope, Memory

impairment,

Disturbance in

attention, Dreamy

state, Restless legs

syndrome, Poor

quality sleep,

Paresthesia

Eye Disorders

Visual acuity reduced,

Vision blurred,

Lacrimation increased

Ear and Labyrinth

Disorders

Vertigo positional,

Vertigo

Vascular Disorders

Hypertension

Hot flush

Gastrointestinal

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

Hepatobiliary

Disorders

Hyperbilirubinaemia

Skin and

Subcutaneous Tissue

Disorders

Dermatitis, Night

sweats, Pruritus, Rash,

Pruritus generalised,

Dry skin

Eczema, Erythema,

Hand dermatitis,

Psoriasis, Rash

generalised, Rash

pruritic, Nail disorder

Angioedema, Oedema

of mouth, Tongue

oedema

Musculoskeletal and

Connective Tissue

Disorders

Pain in extremity

Arthritis, Muscle

spasm, Neck pain,

Night cramps

Reproductive System

and Breast Disorders

Menopausal

symptoms

Priapism, Prostatitis

Galactorrhoea

General Disorders and

Administration Site

Conditions

Asthenia, Chest pain

Fatigue, Pain, Thirst

Renal and Urinary

Disorders

Glycosuria,

Proteinuria

Polyuria, Haematuria,

Nocturia

Investigations

Liver function test

abnormal, Weight

increased

Hepatic enzyme

increased, Blood

electrolytes abnormal,

Laboratory test

abnormal

Post-Marketing Data

Psychiatric Disorders: Nightmares

Reporting suspected adverse effects

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are

asked to report any suspected adverse reactions at http://nzphvc.otago.ac.nz/reporting/

4.9

O

VERDOSE

In general, the main therapy for all overdoses is supportive and symptomatic care.

Symptoms

No case of overdose has been reported. Melatonin has been administered at 5 mg daily doses in

clinical trials over 12 months without significantly changing the nature of the adverse reactions

reported.

Administration of daily doses of up to 300 mg of melatonin without causing clinically significant

adverse reactions have been reported in the literature.

If overdose occurs, drowsiness is to be expected.

Treatment

Clearance of the active substance is expected within 12 hours after ingestion. No special treatment

is required

For information on the management of overdose, contact the National Poisons Centre on 0800

POISON (0800 764766).

5

PHARMACOLOGICAL PROPERTIES

5.1

P

HARMACODYNAMIC PROPERTIES

Chemical structure

Chemical name:

N-[2-(5-Methoxyindol-3-yl)ethyl]acetamide. Melatonin is a slightly off

white, odourless crystalline powder.

Molecular weight:

232.27

pKa:

12.3 – 12.7

CAS number

73-31-4

Pharmacotherapeutic group: Melatonin Receptor Agonists, ATC code: N05CH01

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.

Mechanism of action

The activity of melatonin at the MT1 MT2 receptors is believed to contribute to its sleep-

promoting properties via their distinct actions on the circadian clock. The MT1 receptors are

thought to inhibit neuronal firing, while the MT2 receptors have been implicated in the phase-

shifting response.

Rationale for Use

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.

Clinical trials

Three Phase 3 studies and a sleep laboratory study were considered pivotal. These studies enrolled

patients with primary insomnia who were aged at least 55 years. Patients suffering from severe

neurological, psychiatric or neurosurgical diseases or taking CNS medications including

benzodiazepines or other hypnotic agents were excluded.

The primary assessment tool was the Leeds Sleep Evaluation Questionnaire (LSEQ), comprising 10

self-rated 100 mm-line analogue questions concerning aspects of sleep and early morning

behaviour. The LSEQ measures ease of getting to sleep (GTS), quality of sleep (QOS), ease of waking

from sleep (AFS) and behaviour following wakefulness (BFW). The primary outcome variable in the

pivotal clinical trials was QOS, or a combination on QOS and BFW, where a patient had to show a

clinically relevant improvement on both QOS and BFW. Time to onset of sleep and duration of sleep

were measured objectively only in a polysomnography study. Efficacy of Melatonin in combination

with other hypnotic agents has not been assessed.

In a polysomnographic (PSG) study (N = 40; 20 Melatonin, 20 placebo) with a run-in of 2 weeks

(single-blind with placebo treatment), followed by a treatment period of 3 weeks (double-blind,

placebo-controlled, parallel group design) and a 3-week withdrawal period, time to onset of sleep

was shortened significantly by 9 minutes compared to placebo. A statistically significant difference

favouring Melatonin was seen for total duration of time awake prior to sleep onset (approximate

change from 10 to 11 minutes for Melatonin and from 21 to 20 minutes for placebo). There were no

modifications of sleep architecture and no effect on REM sleep duration by Melatonin. Modifications

in diurnal functioning did not occur with Melatonin 2 mg. Melatonin did not prolong the duration of

sleep significantly compared to placebo.

In the outpatient studies patients who failed to meet the inclusion criteria at the end of the run- in

period due to the instability of their disorder (16% of the total population) were not included in the

efficacy analysis.

In an outpatient study (Neurim VII: N = 170; 82 Melatonin, 88 placebo) with two week run in

baseline period with placebo, a randomised, double blind, placebo controlled, parallel group

treatment period of 3 weeks and two week withdrawal period with placebo, the primary efficacy

endpoint was Quality of Sleep (QOS). The rate of patients who showed a clinically significant

improvement in both quality of sleep and morning alertness was 47% in the Melatonin group as

compared to 27% in the placebo group. There was a mean difference of approximately 6 mm in

quality of sleep and approximately 9 mm in morning alertness, both favouring Melatonin compared

to placebo. Sleep variables gradually returned to baseline with no rebound, no increase in adverse

events and no increase in withdrawal symptoms.

In a second outpatient study (N = 334; 169 Melatonin, 165 placebo) with two week run in baseline

period with placebo and a randomised, double blind, placebo controlled, parallel group treatment

period of 3 weeks, the rate of patients who showed a clinically significant improvement in both

quality of sleep and morning alertness was 26% in the Melatonin group as compared to 15% in the

placebo group. Melatonin shortened patients’ reported time to onset of sleep by 24.3 minutes vs

12.9 minutes with placebo. In addition, patients’ self- reported quality of sleep, number of

awakenings and morning alertness significantly improved with Melatonin compared to placebo.

Quality of life was improved significantly with Melatonin 2 mg compared to placebo.

A third study involved more than 600 patients over 55, over 400 of whom were on Melatonin

treatment for up to 6 months. Patients given Melatonin demonstrated a difference from placebo in

mean change from baseline in subjective sleep latency, assessed using a sleep diary, of -7.8 minutes

after 3 weeks (p = 0.014). Small differences in sleep latency were generally maintained over 13

weeks of placebo-controlled treatment.

The percentage of patients showing both remission of insomnia (PSQI of < 6) and a clinically relevant

improvement of 10% in quality of life scores (WHO-5 index) increased from 16.7% (cf. 10.6%

placebo, p = 0.044) at week 3 to 25.8% at week 13 (cf. 15.7% placebo, p =0.0006).

This study also examined the effect of Melatonin on sleep latency in younger subjects with primary

insomnia and low excretion of melatonin. Clinically significant effects on sleep latency were not

demonstrated in these patients.

Long Term Safety

The safety profile both during 3 weeks and during the 26 week periods was comparable to placebo

with no withdrawal and rebound effects.

In an open study where 96 subjects completed 12 months treatment with Melatonin no tolerance,

rebound or withdrawal effects were reported.

5.2

P

HARMACOKINETIC PROPERTIES

Absorption

The absolute bioavailability of melatonin from Melatonin has not been assessed. Other oral

formulations of melatonin have an absolute bioavailability in the region of 15% but this is highly

variable with high first-pass metabolism. The relative bioavailability of melatonin from Melatonin is

comparable to that of an oral melatonin solution.

Data from other formulations of melatonin indicate that the absorption of orally ingested melatonin

is complete in adults and may be decreased by up to 50% in the elderly. The kinetics of melatonin is

linear over the range of 2 - 8 mg as obtained from published results using a formulation other than

Melatonin.

Bioavailability as assessed from other oral formulations of melatonin is in the order of 15%. There is

a significant first pass effect with an estimated first pass metabolism of 85% as assess from other

oral formulations of melatonin. T

occurs after 2.6 hours in a fed state. The rate of melatonin

absorption following Melatonin 2 mg oral administration is affected by food. The presence of food

delayed the absorption of the melatonin resulting in a later T

= 2.6 h versus T

= 1.6 h). C

and AUC levels were not affected by food.

Distribution

The in vitro plasma protein binding of melatonin is approximately 60%. Melatonin is mainly bound to

albumin, alpha1-acid glycoprotein and high density lipoprotein. The binding to the other serum

proteins is insignificant. The melatonin binding was constant over the range of the studied

concentrations in serum. Literature data indicates that melatonin is distributed in all body fluids and

is accessible at all tissues.

Metabolism

Experimental data suggest that isoenzymes CYP1A1, CYP1A2 and possibly CYP2C19 of the

cytochrome P450 system are involved in melatonin metabolism. The principal metabolite is 6-

sulphatoxy-melatonin (6-S-MT), which is inactive. The site of biotransformation is the liver. The

excretion of the metabolite is completed within 12 hours after ingestion.

Excretion

Terminal half-life (t½) is 3.5 - 4 hours. Elimination is by renal excretion of metabolites, 89% as

sulphated and glucoronide conjugates of 6-hydroxymeltonin and 2% is excreted as melatonin

(unchanged medicine).

Gender

A 3 - 4-fold increase in C

is apparent for women compared to men. A five-fold variability in C

between different members of the same sex has also been observed.

However, no pharmacodynamic differences between males and females were found despite

differences in blood levels.

Elderly

Melatonin metabolism is known to decline with age. Across a range of doses, higher AUC and C

levels have been reported in older subjects compared to younger subjects, reflecting the lower

metabolism of melatonin in the elderly. C

levels around 500 pg/ml in adults (18 - 45) versus 1200

pg/ml in the elderly (55 - 65); AUC levels around 3,000 pg*h/mL in adults versus 6000 pg*h/mL in

the elderly.

Renal Impairment

Melatonin did not accumulate after repeated dosing with Melatonin. This finding is compatible with

the short half-life of melatonin in humans.

The levels assessed in the blood of patients at 23:00 (2 hours after administration) following 1 and 3

weeks of daily administration were 411.4 ± 56.5 and 432.00 ± 83.2 pg/ml respectively, and are

similar to those found in healthy volunteers following a single dose of Melatonin 2 mg.

Hepatic Impairment

The liver is the primary site of melatonin metabolism and therefore, hepatic impairment results in

higher endogenous melatonin levels.

Plasma melatonin levels in patients with cirrhosis were significantly increased during daylight hours.

Patients had a significantly decreased total excretion of 6-sulfatoxymelatonin compared with

controls.

5.3

P

RECLINICAL SAFETY DATA

Genotoxicity

Results from a standard battery of in vitro and in vivo assays showed no evidence of a genotoxic

potential for melatonin.

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.

6

PHARMACEUTICAL PARTICULARS

6.1

L

IST OF EXCIPIENTS

Melatonin prolonged release tablets also contain the excipients: Ammonio methacrylate copolymer,

calcium hydrogen phosphate, lactose monohydrate, colloidal anhydrous silica, purified talc and

magnesium stearate.

6.2

I

NCOMPATIBILITIES

This medicine must not be mixed with other medicines.

6.3

S

HELF LIFE

36 months

6.4

S

PECIAL PRECAUTIONS FOR STORAGE

Store below 25ºC. Protect from light.

6.5

N

ATURE AND CONTENTS OF CONTAINER

PVC/PVDC/Al or Alu/Alu Blister packs of 7, 21, 30 tablets

6.6

S

PECIAL PRECAUTIONS FOR DISPOSAL

<

AND OTHER HANDLING

>

Any unused medicine or waste material should be disposed of in accordance with local

requirements.

6.7

P

HYSICOCHEMICAL PROPERTIES

7

MEDICINE SCHEDULE

Prescription Medicine

8

SPONSOR

Generic Partners (NZ) Limited

84 Halesowen Avenue

Mount Eden

Auckland, 1041

New Zealand

Contact number: +64 3 4779 669

9

DATE OF FIRST APPROVAL

26 August 2019

10

DATE OF REVISION OF THE TEXT

26 August 2019

S

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