Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Umsebe Healthcare, Unit 20, Sunclare Building, 3rd Floor, 21 Dreyer Street, Claremont, Cape Town, 7708, South Africa
Substitution treatment in opiate/opioid dependence in adults in conjunction with appropriate medical, social and psychological therapy.
For oral administration only. MISYO 10 mg/ml concentrate for oral solution should be diluted by a healthcare professional before use. Please refer to section 6.6 for further instructions.
MISYO should always be taken orally with or without food.
MISYO must not be injected.
Dosage should be titrated to individual needs of patients.
Substitution treatment with methadone should be prescribed by a doctor with experience of treating opiate/opioid-dependent patients, preferably at centres that are specialised in the treatment of opiate/opioid dependency.
The dose is based on the occurrence of withdrawal symptoms and must be adjusted for each patient according to his or her individual situation and the way he or she feels. In general, after adjustment of the dose, the aim is to administer the lowest possible maintenance dose.
The standard initial dose is 20 mg methadone once daily.
The dose may be increased at 10 mg increments over a period of three weeks, usually to 70 or 80 mg. After a recommended stabilisation period of four weeks, the dose is adjusted until the patient feels well, does not feel a need for intoxication and is without clinical signs of psychomotor function effects or abstinence symptoms. The normal dose is 60 to 120 mg of methadone per 24 hours, but some individuals may require higher doses.
The dosage must be determined based upon the clinical evaluation, supported by serum level monitoring. The recommended serum level is 600 to 1200 nmol/I (200 to 400 ng/ml). Great importance is attached to the clinical assessment.
MISYO is normally administered once daily. If administered more frequently, there will be a risk of accumulation and overdose.
Certain patients develop auto-induction, which leads to the medication being metabolised more rapidly in the body. In such cases, the dose must be adjusted upwards once or more to maintain the optimum effect.
The highest recommended dose, that rarely should be used, is 150 mg/day. The reason for this limitation is an increased frequency of QT-prolongation, Torsades de Pointes and cases of cardiac arrest within higher dose ranges (see section 4.4).
If the patient has been treated with a combined agonist/antagonist (e.g. buprenorphine), the dose should be reduced gradually when the methadone treatment is initiated. If the methadone treatment is interrupted and a switch to sublingual buprenorphine treatment is planned (especially in combination with naloxone), the methadone dose should be reduced to 30 mg/day initially to avoid withdrawal symptoms caused by buprenorphine/naloxone.
Treatment must be stopped if it is insufficiently effective or if the patient cannot tolerate it. The effect must be evaluated in accordance with national guidelines.
Treatment discontinuation must always be done gradually by dose reduction in weekly steps of 5–10 mg over several weeks to months. The dose may be reduced relatively rapidly to start with, but reduction must be slow in the final phase (from 20 mg daily and downwards).
During this period of gradual dose reduction, it is necessary to pay attention to any recurrence of withdrawal symptoms which would require a return to the previous dosage, and to any resumption of addictive behaviours.
Caution must be exercised when treating elderly patients, as they may require a reduced dose (see section 4.4).
In patients with renal disorders or mild to moderate hepatic disorders it is advisable to reduce the dose (for more information see section 4.4 and also section 4.3).
Patients with hypothyroidism or prostatic hypertrophy must receive a lower initial dose.
There are no data available on the use in patients under 18 years of age. Therefore, the use of MISYO is not recommended for children and adolescents (see section 4.4).
MISYO 10 mg/ml concentrate for oral solution must be diluted before use by a health professional and may only be used orally and under medical supervision.
Serious overdose is characterised by respiratory depression, extreme somnolence progressing to stupor or coma, maximally constricted pupils, skeletal muscle flaccidity, cold and clammy skin and sometimes bradycardia and hypotension. Hypoglycaemia has been reported. In severe overdose, particularly by the intravenous route, apnoea, circulatory collapse, cardiac arrest and death may occur.
A patent airway and assisted or controlled ventilation must be assured. Narcotic antagonists may be required, but it should be remembered that methadone is a long-acting depressant (36 to 48 hours), whereas antagonists act for 30 to 60 minutes, so that treatment with the latter must be repeated as needed. An antagonist should not be administered, however, in the absence of clinically significant respiratory or cardiovascular depression. The administration of naloxone is advised.
Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated. In a person physically dependent on narcotics, administration of the usual dose of a narcotic antagonist will precipitate an acute withdrawal syndrome; use of the antagonist in such a person should be avoided if possible, but if it must be used to treat serious respiratory depression if should be administered with great care.
36 months.
Shelf life after first opening container: 90 days.
Shelf life after dilution: 14 days.
Store at or below 30°C in the original package to protect from light.
After first opening store at or below 25°C in the original package to protect from light, for not more than 90 days.
Once diluted to a concentration of 1 mg/ml or 5 mg/ml it has a shelf life of 14 days when stored in PET bottles at or below 25°C protected from light.
Keep out of the sight and reach of children.
Type III, brown glass bottle containing 100 ml concentrate for oral solution, sealed with a PP 28 screw cap with PE-liner or with a PP 28 screw cap child-resistant, tamper evident ring with embossing and PE-liner. One bottle is packed in to a cardboard carton.
Type III, brown glass bottle containing 1000 ml concentrate for oral solution, sealed with a PP 28 screw cap with PE-liner or with a PP 28 screw cap child-resistant, tamper evident ring with embossing and PE-liner. One bottle is packed in to a cardboard carton.
Not all pack sizes may be marketed.
MISYO 10 mg/ml concentrate for oral solution is supplied in dispensing packs which are only to be used by healthcare professionals.
MISYO 10 mg/ml concentrate for oral solution should be diluted with purified water to produce either a 1 mg/ml or a 5 mg/ml methadone hydrochloride oral solution before being used by the patient.
The 1 mg/ml methadone hydrochloride oral solution is prepared by diluting 1 part of the concentrate for oral solution with 9 parts of purified water (10-fold dilution).
The 5 mg/ml methadone hydrochloride oral solution is prepared by diluting 1 part of the concentrate for oral solution with 1 part of purified water (2-fold dilution).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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