Subutex

/ NSE

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 degrees 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 methadrone should be reduced to a maximum of 30mg/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 0.8mg to 4mg, administered as a single daily dose.
Dosage adjustment and maintenance: The dose of Subutex should be increased progressively according to the clinical effort of the individual patient and should not exceed a maximum single daily dose of 32mg. 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 2mg and 8mg, respectively, allows for a downward titration of dosage. Patients should be monitored following termination of buprenorphine treatment because of the potential for relapse.
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. Buprenorphine should be used with caution in patients with hepatic insufficiency. Buprenorphine is contraindicated in patients with severe hepatic insufficiency.
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).
Paediatric population: Subutex is contraindicated in children under the age of 16.
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.

Substitution treatment for opioid drug dependence, within framework of medical, social and psychological treatment.

– Hypersensitivity to buprenorphine or any other component of the tablet
– Children less than 16 years of age
– Severe respiratory insufficiency
– Severe hepatic insufficiency
– Acute alcoholism or delirium tremens
– Breast feeding

Subutex sublingual tablets are recommended only for the treatment of opioid drug dependence. It is also recommended that treatment is prescribed by a physician who ensures comprehensive management of the opioid-dependent patient(s).
See prescribing information for full details.

The most commonly reported adverse drug reactions were those related to withdrawal symptoms (e.g. insomnia, headache, nausea and hyperhidrosis) and pain.
See prescribing information for full details.

This product should not be taken together with alcoholic drinks or medications containing alcohol. Alcohol increases the sedative effect of buprenorphine. this product should be used cautiously together with:
Benzodiazepines: This combination may potentiate respiratory depression of central origin, with risk of death; therefore, patients must be closely monitored and this combination should be avoided in cases where there is risk of misuse. Patients should be warned that it is extremely dangerous to self administer non-prescribed benzodiazepines whilst taking this product, and should also be cautioned to use benzodiazepines concurrently with this product only as prescribed.
Other central nervous system depressants; other opioid derivatives (analgesics and antitussives); certain antidepressants, sedative H1-receptor antagonists, barbiturates, anxiolytics other than benzodiazepines, neuroleptics, clonidine and related substances. This combination increases central nervous system depression. The reduced level of alertness can make driving and
using machinery hazardous.
Opioid analgesics: Adequate analgesia may be difficult to achieve when administering a full opioid agonist in patients receiving buprenorphine. The potential for overdose also exists with a full agonist, especially when attempting to overcome buprenorphine partial agonist effects, or when buprenorphine plasma levels are declining.
Naltrexone: This is an opioid antagonist that can block the pharmacological
effects of buprenorphine. For opioid dependent patients currently receiving
buprenorphine treatment, naltrexone may precipitate a sudden onset of prolonged and intense opioid withdrawal symptoms. For patients currently receiving naltrexone treatment, the intended therapeutic effects of buprenorphine administration may be blocked by naltrexone.
CYP 3A4 inhibitors: An interaction study of buprenorphine with ketoconazoles
(a potent inhibitor of CYP3A4) resulted in increased Cmax and AUC of buprenorphine (approximately 70% and 50% respectively) and, to a lesser extent, of the metabolite, norbuprenorphine. Patients receiving Subutex should be closely monitored and may require dose reduction if combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir, or azole antifungals such as ketoconazole and itraconazole, or macrolide antibiotics).
CYP3A4 inducers: Concomitant use of CYP3A4 inducers with buprenorphine may decrease buprenorphine plasma concentrations, potentially resulting in suboptimal treatment of opioid dependence with buprenorphine. It is recommended that patients receiving Subutex should be closely monitored if inducers (e.g. phenobarbital, carbamazepine, phenytoin or rifampicin) are co-administered. Use of these medications may increase metabolism of buprenorphine and The dose of either buprenorphine or the CYP3A4 inducer may need to be adjusted accordingly.
Monoamine oxidase inhibitors (MAOI): Possible exaggeration of the effects of opioids, based on experience with morphine.

Pregnancy: There are no adequate data from the use of buprenorphine in pregnant women.
Buprenorphine should be used during pregnancy only if the potential benefit outweighs the potential risk to the foetus.
Towards the end of pregnancy, buprenorphine may induce respiratory depression in newborn infant even after a short period of administration.. Long-term administration during the last three months of pregnancy may cause a withdrawal syndrome in neonates (e.g. hypertonia, neonatal tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed from several hours to several days after birth.
Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered at the end of pregnancy to prevent the risk of respiratory depression or withdrawal syndrome in neonates.
Breast-feeding: Buprenorphine and its metabolites are excreted in human breast milk. In rats, buprenorphine has been found to inhibit lactation.
Therefore, breast feeding should be discontinued during treatment with Subutex.

Symptoms: Respiratory depression, as a result of central nervous system depression, is the primary symptom requiring intervention in the case of overdose because it may lead to respiratory arrest and death. Preliminary symptoms of overdose may also include somnolence, amblyopia, miosis, hypotension, nausea, vomiting and / or speech disorders.
Treatment: Symptomatic treatment of respiratory depression, following standard intensive care measures, should be instituted. A patent airway and assisted or controlled ventilation must be assured. The patient should be transferred to an environment within which full resuscitation facilities are available. Use of an opioid antagonist (i.e., naloxone) is recommended, despite the modest effect it may have in reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid agents. The long duration of action of this product should be taken into consideration when determining length of treatment needed to reverse the effects of an overdose.