Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Subutex (Reckitt Benckiser)
0.4 mg, 2 mg and 8 mg sublingual tablets
Approved indication: opiate dependence
Australian Medicines Handbook Section 18.6.3

Buprenorphine is a partial agonist of opioid receptors. The drug has been used, at low doses (0.2 mg), as a sublingual analgesic. Higher doses have now been approved for the treatment of opiate dependence. Buprenorphine can be used in detoxification or as a maintenance treatment. Its action on the receptors reduces the cravings for opioid drugs.

The drug is taken sublingually because of the first-pass metabolism which follows an oral dose. Even when given sublingually, the tablets only have a bioavailability of 30-35%. Buprenorphine is metabolised by the cytochrome P450system. As CYP3A4 is involved, inhibitors of this enzyme, such as macrolide antibiotics, have the potential to increase concentrations of buprenorphine. Most of the metabolites are excreted in the bile. As buprenorphine has a mean half-life of 35 hours it is feasible to give some patients less than daily dosing.

A randomised trial has compared the efficacy of buprenorphine with that of clonidine and naltrexone in162 patients undergoing detoxification. The detoxification was successfully completed by 65% of the patients given clonidine, 81% of those given clonidine and naltrexone, and 81% of those given buprenorphine.1 The Cochrane Collaboration has reviewed the evidence supporting buprenorphine in the management of opioid withdrawal, but has not reached a firm conclusion.2

For maintenance treatment, buprenorphine should be taken at least six hours after the last dose of heroin. This is to reduce the risk of triggering withdrawal symptoms. For patients transferring from methadone there should be a delay of at least 24 hours before starting buprenorphine. Treatment begins with a4 mg dose which is increased according to the patient's response. The maximum dose is 32 mg a day. Once the patient is stable the dose frequency can be reduced. Some patients will manage with three doses a week.

Buprenorphine has been compared with methadone. One trial studied 72 patients for six months. While more patients taking methadone were retained in treatment, both treatments worked well. Urine tests showed reduced opioid use; 60% of the tests were negative for patients taking buprenorphine compared to 66% of the tests from patients taking methadone.3

A major problem with buprenorphine is the risk of abuse. As patients given buprenorphine for pain can become addicted it is clear that it can cause dependence. Some patients grind up the tablets so that they can inject the drug. This is dangerous, particularly if the patient is also using benzodiazepines. Deaths have occurred from cardio respiratory depression when buprenorphine and benzodiazepines have been injected.

Other adverse effects are difficult to identify as the adverse reactions reported in clinical trials may be due to withdrawal or opioid toxicity. Symptoms reported include headache, abdominal pain, chills, insomnia, nausea, vomiting and diarrhoea. Liver function may be altered and some patients will develop hepatitis.

If a decision is made to cease treatment, buprenorphine should not be stopped suddenly. A gradual reduction of the dose over three weeks is recommended.

Buprenorphine has been used to treat drug addiction in France since 1996. Australian Prescriber's sister journal La Revue Prescrire has reviewed its use and found it to be an effective treatment. The French experience confirms that the main risks of buprenorphine are linked to misuse. They recommend that there should be good communication between the prescribing doctor and the pharmacist, particularly about how many tablets to dispense at a time. Using buprenorphine as one part of a co-ordinated medical and psychosocial treatment program is also important.4