Posology : מינונים

4.2 Posology and method of administration

Posology
Treatment with Subutex sublingual tablets is intended for use in adults and children aged 16 years or over who have agreed to be treated for opioid dependence.

Precautions to be taken before dosing
Prior to treatment induction, physicians should be aware of the partial agonist profile of buprenorphine to the opiate receptors, which may precipitate a withdrawal syndrome in opioid- dependent patients and consideration should be given to the types of opioid dependence (i.e.
long- or short- acting opioid), the time since last opioid use and the degree of opioid dependence.
To avoid precipitating withdrawal, induction with Subutex should be undertaken when objective and clear signs of withdrawal are evident e.g. a score higher than 12 on the Clinical Opioid Withdrawal Scale (COWS).

•   For patients dependent on heroin or short-acting opioids: the first dose of buprenorphine should be started when objective signs of withdrawal appear, but not less than 6 hours after the patient last used opioids.

•   For patients receiving methadone: before beginning Subutex therapy, the dose of methadone should be reduced to a maximum of 30 mg/day. Subutex may precipitate symptoms of withdrawal in patients dependent upon methadone. The first dose of buprenorphine should be started only when objective signs of withdrawal appear and 
generally not less than 24 hours after the patient last used methadone because of the long half- life of methadone.

Baseline liver function tests and documentation of viral hepatitis status is recommended prior to commencing therapy.

Induction:
The initial dose is from 0.8 mg to 4 mg, administered as a single daily dose.

Dosage adjustment and maintenance:
The dose of Subutex should be increased progressively according to the clinical effect of the individual patient and should not exceed a maximum single daily dose of 32 mg. The dosage is titrated according to reassessment of the clinical and psychological status of the patient.

Dosage reduction and termination of treatment:
After a satisfactory period of stabilisation has been achieved, the dosage may be reduced gradually to a lower maintenance dose; when deemed appropriate, treatment may be discontinued in some patients. The availability of the sublingual tablet in doses of 2 mg and 8 mg, respectively, allows for a downward titration of dosage. Patients should be monitored following termination of buprenorphine treatment because of the potential for relapse.

Special populations

Elderly
The safety and efficacy of buprenorphine in elderly patients over 65 years of age has not been established.

Hepatic impairment
Patients who are positive for viral hepatitis, on concomitant medicinal products and / or have existing liver dysfunction are at risk of greater liver injury. Patients should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine (see section    4.4). Buprenorphine should be used with caution in patients with hepatic insufficiency (see section 5.2). Buprenorphine is contraindicated in patients with severe hepatic insufficiency (see section 4.3).

Renal impairment
Modification of the buprenorphine dose is not generally required for patients with renal impairment. Caution is recommended when dosing patients with severe renal impairment, which may require dose adjustment (creatinine clearance < 30 ml/min) (see section 5.2).

Paediatric population
Subutex is contraindicated in children under the age of 16 (see section 4.3).

Method of administration
Administration is sublingual. Physicians must advise patients that the sublingual route is the only effective and safe route of administration for this drug. The tablet should be kept under the tongue until dissolved, which usually occurs within 5 to 10 minutes.