Package leaflet: Information for the user

Syncropine 3 mg tablets, 5 mg tablets

melatonin
Please read all of this leaflet carefully before you take this medicine, as it contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are similar to yours, as it may be harmful.
If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
Contents of this leaflet

What Syncropine is and what it is used for
What you need to know before taking Syncropine
How to take Syncropine
Possible side effects
How to store Syncropine
Contents of the pack and other information

1. What Syncropine is and what it is used for

Syncropine contains the active substance melatonin, which belongs to a group of natural hormones produced by the body. Melatonin helps regulate the body's sleep-wake cycle.
Syncropine is used for:
The short-term treatment of jet lag in adults aged 18 years and over. Jet lag refers to the symptoms caused by time zone differences when travelling across multiple time zones (eastward or westward).
Insomnia with difficulty in falling asleep in children and adolescents (from 6 to 17 years) with attention deficit hyperactivity disorder (ADHD), in cases where a healthy sleep routine has not been sufficient.
Syncropine is particularly suitable for adult travellers crossing 5 or more time zones, especially eastward, who have previously experienced symptoms of jet lag during past travels.

2. What you need to know before taking Syncropine

Do not take Syncropine:
if you are allergic to melatonin or to any of the other ingredients of this medicine (listed in
section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking Syncropine if you have:
diabetes or impaired glucose tolerance, as this medicine may increase blood glucose levels
liver or kidney problems
an autoimmune disease (a condition in which the body is attacked by its own immune system)
epilepsy. Melatonin may increase the frequency of seizures in patients with epilepsy.
or if you are elderly.

Smoking may reduce the effectiveness of Syncropine, as components of tobacco smoke can promote the breakdown of melatonin by the liver.

Women of childbearing age should use effective contraception during treatment with Syncropine. For further details, see section "Pregnancy and breastfeeding". However, this medicine may be affected by certain contraceptives; see section “Other medicines and Syncropine” for more information.

Children and adolescents
This medicine is not recommended for children and adolescents under 18 years of age for the short-term treatment of jet lag. Do not administer this medicine to children under 6 years of age.

Syncropine with food and alcohol
It is recommended not to eat food 2 hours before or 2 hours after taking Syncropine. Do not drink alcohol before, during, or after taking Syncropine, as alcohol may reduce the effectiveness of melatonin.

Other medicines and Syncropine
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

Taking Syncropine together with the following medicines may affect how Syncropine or the other medicines work:

warfarin and other anticoagulants, e.g. dabigatran, rivaroxaban, apixaban and edoxaban (used to prevent blood clots). In such cases, more specific monitoring of INR (blood coagulation test) may be required
antidepressants, e.g. fluvoxamine, imipramine
ciprofloxacin, norfloxacin and rifampicin (used to treat bacterial infections)
carbamazepine and phenytoin (used to treat epilepsy)
5-methoxypsoralen or 8-methoxypsoralen (5-MOP or 8-MOP) (used to treat skin diseases such as psoriasis)
pain and anti-inflammatory medicines (non-steroidal anti-inflammatory drugs, e.g. acetylsalicylic acid and ibuprofen)
benzodiazepines and non-benzodiazepine hypnotics (medicines used to promote sleep such as zaleplon, zolpidem and zopiclone)
cimetidine for ulcers
verapamil (for heart conditions)
antihypertensives (nifedipine, beta-blockers)
thioridazine (for schizophrenia)
contraceptives containing ethinylestradiol and progestogens
hormone replacement therapy for menopausal symptoms.

Pregnancy and breastfeeding
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.

Contraception in women of childbearing age
Women of childbearing age should use effective contraceptive methods during treatment with Syncropine.
However, this medicine may be affected by certain contraceptives; for further information, see section “Other medicines and Syncropine”. Consult your doctor for advice on choosing contraception.

Pregnancy
Syncropine is not recommended during pregnancy. Melatonin crosses the placenta and there is insufficient information on the risks to the unborn child.

Breastfeeding
Syncropine is not recommended during breastfeeding. Melatonin is excreted in breast milk and a risk to the breastfed infant cannot be excluded.

Driving and using machines
Syncropine may cause drowsiness and reduce attention for several hours after taking it. Therefore, this medicine should not be taken before driving or operating machinery.

Syncropine contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially 'sodium-free'.

3. How to take Syncropine

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.

Adults with jet lag
The recommended standard dose is one 3 mg tablet once daily for up to 4 days.
Take the tablet at bedtime according to local time, starting on the day of arrival at your destination.
If the standard dose of 3 mg does not provide adequate relief from symptoms, you may take a 5 mg tablet instead of the 3 mg tablet. The 5 mg tablet must not be taken in addition to the 3 mg tablet (i.e. not on the same day), but a higher dose may be taken on subsequent days.
The maximum daily dose is 5 mg. The maximum duration of treatment is 4 days.
The timing of melatonin administration is important. The dose must be taken at bedtime (according to local time). Tablets must not be taken before 8:00 p.m. or after 4:00 a.m.

Children and adolescents aged 6 to 17 years with insomnia and difficulty falling asleep associated with ADHD
Treatment with melatonin should be titrated to the lowest effective dose. Syncropine may be used when the lowest effective dose has been established as 3 or 5 mg. The tablet should be taken 30–60 minutes before bedtime. The maximum daily dose is 5 mg.
Treatment should be regularly monitored by the doctor (frequency as determined by the doctor) to assess whether it remains appropriate.
The tablet may be crushed before administration and mixed with cold water.
It is recommended to avoid eating food 2 hours before or 2 hours after the time of taking Syncropine tablets.

If you take more Syncropine than you should
If you or your child has taken an excessive dose of this medicine, or if a child or adolescent has accidentally taken this medicine, always contact your doctor or hospital to assess potential risks and receive further instructions.
Taking a higher dose than the recommended daily dose may cause drowsiness.

If you forget to take Syncropine
If you forget to take a dose before going to bed and wake up during the night, you may take the missed dose provided it is before 4:00 a.m.
Do not take a double dose to make up for the missed dose.

If you stop taking Syncropine
No negative effects due to stopping or interrupting treatment are known. The use of Syncropine does not cause known withdrawal symptoms once treatment is discontinued. If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
If you experience any of the following serious side effects, stop taking Syncropine and contact your doctor immediately:
Uncommon (may affect up to 1 in 100 people):
chest pain
Rare (may affect up to 1 in 1,000 people):
loss of consciousness or fainting
severe chest pain due to angina
awareness of your heartbeat
depression
visual disturbances
disorientation
dizziness (giddiness or “spinning sensation”)
blood in the urine
reduction in the number of white blood cells in the blood
reduction in the number of platelets in the blood, increasing the risk of bleeding or bruising
psoriasis
Frequency not known (frequency cannot be estimated from the available data):
hypersensitivity reaction
skin swelling
If you experience any of the following non-serious side effects, contact your doctor and/or seek medical assistance:
Common (may affect up to 1 in 10 people):
headache
drowsiness
Uncommon (may affect up to 1 in 100 people):
irritability, nervousness, restlessness, anxiety
insomnia, abnormal dreams, nightmares
migraine, dizziness, nausea
lethargy (tiredness) and lack of energy, restlessness associated with hyperactivity
high blood pressure
abdominal pain, indigestion, mouth ulceration, dry mouth
changes in blood composition that may cause yellowing of the skin or eyes
skin inflammation, itching, rash, dry skin, night sweats
pain in the extremities
glucose excretion in urine, excess protein in urine
menopausal symptoms
weakness
weight gain
Rare (may affect up to 1 in 1,000 people):
Herpes zoster
low levels of calcium or sodium in the blood
elevated levels of fat molecules in the blood
mood changes, aggression, agitation associated with hyperactivity, crying spells, stress symptoms, early morning awakening, increased sex drive, depressed mood
memory impairment, attention disorders, dream-like state, restless legs syndrome, poor quality sleep, tingling sensation, hallucinations
blurred vision, eye tearing
dizziness when standing or sitting
hot flushes
acid reflux, gastric discomfort, blistering in the mouth, tongue ulceration, stomach ache, vomiting, abnormal abdominal sounds, intestinal gas, excessive salivation, bad breath, abdominal discomfort, inflammation of the stomach lining
eczema, rash, hand dermatitis, itchy rash, nail disorders
arthritis, muscle spasms, neck pain, nocturnal cramps
large volumes of urine, need to urinate during the night
prolonged – potentially painful – erection in the absence of sexual stimulation, prostate inflammation
fatigue, pain, thirst
increased liver enzymes, electrolyte abnormalities in the blood, and laboratory test abnormalities
Frequency not known (frequency cannot be estimated from the available data):
facial swelling, swelling of the mouth or tongue
abnormal milk secretion
hyperglycaemia

Additional side effects in children and adolescents
In children and adolescents, adverse reactions have been reported at a low frequency and are generally mild.
The most common side effects were headache, hyperactivity, dizziness and abdominal pain. No serious side effects have been observed.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Syncropine

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label, blister pack, and outer carton.
The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Keep the blister pack in the original packaging to protect the medicine from light.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Syncropine contains

The active substance is melatonin 3 mg or 5 mg.
The other ingredients are magnesium stearate (E470b), colloidal anhydrous silica (E551), microcrystalline cellulose (E460), sodium croscarmellose (E468).

Description of the appearance of Syncropine and contents of the pack
3 mg: White or almost white, round, biconvex tablets, approximately 6.0 x 2.5 mm in size.
5 mg: White or almost white, round, biconvex tablets, approximately 7.0 x 3.2 mm in size.
A notch is present on both sides. The notch is intended solely to facilitate swallowing and is not intended for dividing the tablet into equal doses.
Syncropine 3 mg and 5 mg tablets are available in cardboard packs containing transparent blisters made of polyvinyl chloride (PVC) and polyethylene (PE), coated with polyvinylidene chloride (PVDC), sealed with an aluminium (Al) foil.
Pack size: 30 tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Pierpaoli Exelyas srl
Corso Concordia 11, 20129, Milan,
Italy

Manufacturer
Orion Corporation Orion Pharma
Orionintie 1
FI-02200 Espoo, Finland
Orion Corporation Orion Pharma
Joensuunkatu 7
FI-24100 Salo, Finland

This medicinal product is authorised in the European Economic Area countries with the following names:
Italy: Syncropine
Finland: Syncropine