Zopiklon Mylan
SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
Zopiklon Mylan 5 mg Film-Coated Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5 mg of Zopiclone.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Film-Coated Tablet
White film coated round tablet, 7 mm in diameter, marked ‘Z05’ and ‘G’ on the other.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Temporary and transient sleep disturbances in adults. Supportive therapy of chronic sleep disturbances during a limited period of time in adults.
4.2 Posology and method of administration
Adults:
The normal initial dose is 5 mg of zopiclone. To be taken immediately before bedtime. Patients who do not respond to this dose should take 7.5 mg. The treatment should not exceed 4 weeks. Tablets should not be taken in the lying position as the absorption might be delayed.
Paediatric population
Zopiclone should not be used in children and adolescents less than 18 years. The safety and efficacy of zopiclone in children and adolescents aged less than 18 years have not been established.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Severe liver insufficiency, sleep apnoea and myasthenia gravis.
Special warnings and precautions for use
Special caution should be observed at impaired liver function, respiratory insufficiency and while treating elderly, patients with an impaired general condition or drug abusers. This is also the case at concomitant treatment with other psychotropic drugs. Concomitant use of alcohol should be avoided.
Sleep disturbances may be due to psychological or somatic diseases. Therefore, with reference to the above, sleep disturbances over a longer period of time should be investigated. Treatment with soporifics should be temporary or intermittent in order to reduce the risk of withdrawal problems. An abrupt withdrawal after a longer time of treatment with soporifics sometimes may lead to withdrawal symptoms. The patient should be informed about this and to reduce the dose gradually (see section 4.8).
Clinical experience from treating children is not available. Risk of dependence is at hand, which should be noted while prescribing this drug.
Paediatric population:
Zopicloneshouldnotbeused inchildrenand adolescentslessthan18 years. The safety and efficacy of zopiclone in children and adolescents aged less than 18 years have not been established.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Alcohol should be avoided as well as combination with CNS depressive drugs.
Since zopiclone is metabolised by CYP3A4 the activity of zopiclone may be increased when used in combination with drugs which inhibit CYP3A4, such as macrolide antibiotics, azole anti-mycotics and HIV-protease inhibitors, as well as with grape fruit juice. In healthy volunteers that have been pre-treated with erythromycin, a higher plasma concentration and a more pronounced hypnotic effect of zopiclone have been observed compared to controls. Concomitant administration of itraconazole (that inhibits CYP 3A4-mediated metabolism) increases the biological availability of zopiclone by 70%. Dose reduction should be considered if zopiclone is administered concomitantly with CYP3A4 inhibitors.
The activity of zopiclone could be decreased when used in combination with drugs which induce CYP3A4, such as phenobarbital, phenytoin, carbamazepine and products containing St John´s wort (Hypericum perforatum). Rifampicine induces strongly the metabolism of zopiclone most likely via CYP3A4. The plasma concentration of zopiclone decreases with about 80% and its effects in psychomotoric tests are reduced significantly. An increased dose of zopiclone may be needed under these conditions.
Pregnancy and lactation
Pregnancy:
Clinical experience relating to pregnant women is limited. Experimental animal data do not show an increased risk of damaging the foetus. During the last trimester, there is a risk of negative pharmacological effects on the foetus and/or the newborn baby such as hypotension, effects on respiratory function and hypothermia. Therefore, during pregnancy, Zopiclone should not be administered.
Breast feeding:
Zopiclone passes into breast milk. Zopiclone is not recommended to breast feeding mothers in spite of the fact that the concentration in breast milk is low.
4.7 Effects on ability to drive and use machines
During treatment with Zopiclone, an impaired ability to react may be observed. This should be taken into consideration when enhanced attentiveness is required, e.g. when driving. There is a risk of residual effects the day after intake. Therefore, the patients are advised not to operate machinery or drive the day after treatment until it is established that their performance is unimpaired.
4.8 Undesirable effects
About 10% of the treated patients do experience some kind of side effect. The most common side effect is a taste of bitter, mostly transient, appearing in about 4% of the patients. Thereafter comes drowsiness, which is dose dependent.
Withdrawal symptoms have been reported after cessation of treatment. The symptoms of withdrawal vary and include disturbed sleep, anxiety, hyperhidrosis, agitation, confusion, headache, palpitations, tachycardia, delirium, nightmares, hallucinations and irritability. Very rare cases of seizures have been reported.
Undesirable effects frequencies are defined as: very common (≥1/10),
common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100),
rare (≥1/10,000, <1/1,000), or very rare (<1/10000), not known (cannot be estimated from available data).
SOC |
Frequency |
Reactions |
|
Immune system disorders |
Rare |
Anaphylactic reactions |
|
Nervous System Disorders |
Common |
Drowsiness |
|
Uncommon |
Anxiety, disturbed dream pattern. |
|
|
Rare |
Irritability, aggressiveness, hallucinations, confusion, concentration difficulties, memory impairment (anterograde amnesia). |
|
|
Gastrointestinal Disorders |
Uncommon |
Nausea. |
|
Hepatobiliary disorders |
Rare |
Mild to moderate increases in serum transaminases and/or alkaline phosphatase |
|
Skin and Subcutaneous tissue disorders |
Rare |
Exanthema, angioedema |
|
General Disorders |
Common |
Disturbance of the sense of taste (taste of bitter), dry mouth. |
|
Uncommon |
Headache, dizziness. |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Overdose
Toxicity: Great individual variations. 5 mg to a 11-year-old gave mild intoxication.
About 30 mg to a 6-year-old gave moderate intoxication. 22.5-50 mg to adults and 40 mg to an elderly gave mild to moderate intoxication. >50- <100 mg to adults gave mild to moderate intoxication. 100 mg to adults gave deep unconsciousness. 187 mg and alcohol to adults gave severe intoxication.
Symptoms: Tiredness, somnolence, coma that sometimes is preceded or followed by agitation and hallucinations. Breathing depression (mostly in combination with alcohol or CNS depressing drugs). Hypotension, sinus tachycardia or bradycardia. Possibly intraventricular block, AV-block. Hypokalaemia, hyperglycaemia. Possibly transient prolongation of APTT, slight bilirubin increase. Gastrointestinal symptoms.
Treatment: If necessary, ventricular emptying, charcoal. Flumazenil works like an antidote and may be tested at pronounced intoxication. To adults, 0.3 mg is administered intravenously and thereafter, if needed, in repeated doses by one minute's intervals until effect has been achieved. (2-3 doses are often enough and in total not more than 2 mg is given). Observe that the effect duration for flumazenil is shorter than for zopiclone. Symptomatic treatment.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Hypnotics and sedatives
ATC-code: N05CF01
The active substance in Zopiklon NM Pharma Mylan is zopiclone belonging to the group of cyclopyrrolones which are structurally different from other hypnotic drugs. Zopiclone has a high affinity to the binding sites within the macro molecular GABA-receptor complex, where it induces specific conformation changes and strengthens the normal transmission of the signal substance GABA in the central nervous system. Zopiclone has a quick onset of action (within 30 minutes), shortens the time to fall asleep, prolongs the sleep duration and reduces the number of awakenings during the night. The amount of REM-sleep and deep sleep (stadium III and IV) is maintained at recommended dosage.
Tolerance development when it comes to hypnotic effect has not been shown.
Pharmacokinetic properties
The biological availability of zopiclone is 80%. Maximum plasma concentration is achieved within 1-2 hours and is about 60 mg/ml after a dose of 7.5 mg. The absorption might be delayed if zopiclone is administered in a lying position. The distribution volume is 1.3 l/kg and the protein binding level is about 45%.
Zopiclone is to a great extent metabolised in the liver by decarboxylation.
The metabolism is not fully described, about 15% are transformed into inactive N-desmethyl-zopiclone and about 11% to N-oxide-zopiclone that is less active than the mother substance and of no clinical significance. The half-life is 4-6 hours, increased to 7 hours in elderly persons.
The half-life is significantly prolonged at impaired liver function. Total plasma clearance is about 19 l/hour. About 5% of administered dose is excreted unchanged in the urine.
5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
lactose, anhydrous 20.5 mg
calcium hydrogen phosphate, anhydrous
maize starch
povidone
magnesium stearate
hypromellose
titanium dioxide (E 171)
macrogol
6.2 Incompatibilities
Not relevant.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Do not store above 25ºC
6.5 Nature and contents of container
Cartons containing PVC/PVdC/Aluminium blister strips, available in packs of
10, 30 and 100 tablets in blister and (100x1) tablets in unit dose blister.
Also available in packs of 100, 250 and 500 tablets in polypropylene containers.
6.6 Special precautions for disposal <and other handling>
No special requirements
7. MARKETING AUTHORISATION HOLDER
Mylan AB
Box 23033
10435 Stockholm
Phone: 08 555 227 50
Fax: 08 555 227 51
8. MARKETING AUTHORISATION NUMBER(S)
To be completed nationally
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
2000-01-28/2005-01-28
10. DATE OF REVISION OF THE TEXT
6 November 2015
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