BUVIDAL

What it is

Buvidal is a buprenorphine modified release solution for injection available in weekly and monthly formulations. It is given by subcutaneous injection. Buvidal Weekly is available in strengths of 8 mg/0.16 mL, 16 mg/0.32 mL, 24 mg/0.48 mL or 32 mg/0.64 mL, whilst Buvidal Monthly is available in strengths of 64 mg/0.18 mL, 96 mg/0.27 mL, 128 mg/0.36 mL or 160 mg/0.45 mL. Buprenorphine is a high-affinity partial agonist at the human μ (mu) opioid receptor and is a high-affinity antagonist at the δ (delta) and κ (kappa) opioid receptors.

Approved indications

— Buvidal Weekly is indicated for initiation and maintenance treatment of opioid dependence, with or without prior stabilisation on sublingual buprenorphine or buprenorphine/naloxone, within a framework of medical, social and psychological support. — Buvidal Monthly is indicated for maintenance treatment of opioid dependence with prior stabilisation on Buvidal Weekly or sublingual buprenorphine or buprenorphine/naloxone within a framework of medical, social and psychological support.

Dosing overview

The recommended starting dose is 16 mg of Buvidal Weekly, with one or two additional 8 mg doses at least 1 day apart, to a target dose of 24 mg or 32 mg during the first treatment week. Treatment with Buvidal Monthly can be started after treatment initiation with Buvidal Weekly, in accordance with dose conversion, once patients have been stabilised on weekly treatment. Patients stabilised on sublingual buprenorphine or buprenorphine/naloxone may be transitioned directly to Buvidal Weekly or Buvidal Monthly, starting on the day after the last daily sublingual treatment dose, with specific transition recommendations available. The maximum dose per week for Buvidal Weekly treatment is 32 mg with an additional 8 mg dose, and the maximum dose per month for Buvidal Monthly treatment is 160 mg. The weekly dose may be administered up to 2 days before or after the weekly timepoint and the monthly dose may be administered up to 1 week before or after the monthly timepoint.

Key safety warnings

Serious harm or death could result if Buvidal is administered intravenously, as it forms a gel depot upon contact with body fluids and may cause occlusion, local tissue damage and thrombo-embolic events, including life threatening pulmonary emboli. Serious, life-threatening or fatal respiratory depression may occur with the use of Buvidal, and patients should be monitored closely, especially on initiation or following a dose increase. Concomitant use of opioids with benzodiazepines, gabapentinoids, antihistamines, tricyclic antidepressants, antipsychotics, cannabis or other central nervous system depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Although Buvidal is indicated for the treatment of opioid dependence, it still poses risks of hazardous and harmful use which can lead to overdose and death, and the patient's ongoing risk should be monitored regularly. Cases of acute hepatic injury have been reported in opioid-dependent patients, with the spectrum of abnormalities ranging from transient asymptomatic elevations in hepatic transaminases to cytolytic hepatitis, hepatic failure, hepatic necrosis, hepatorenal syndrome, hepatic encephalopathy and death.

Contraindications

Buvidal is contraindicated in patients with hypersensitivity to buprenorphine or to any of the excipients, children less than 16 years of age, severe respiratory insufficiency, severe hepatic insufficiency (Child-Pugh C), and acute alcoholism or delirium tremens.

PBS listing

Buvidal is listed on the PBS for all strengths with streamlined restriction. The 8 mg, 16 mg, 24 mg and 32 mg weekly strengths each have an ex-manufacturer price of A$87.78, whilst the 64 mg, 96 mg, 128 mg and 160 mg monthly strengths each have an ex-manufacturer price of A$351.12.

Regulatory history

Buvidal Weekly and Monthly formulations were first registered on the ARTG on 28 November 2018, with the 160 mg monthly strength added on 30 April 2021. In March 2019, the PBAC recommended Buvidal for listing on a cost-minimisation basis with sublingual buprenorphine with naloxone under Section 100 (Opiate Dependence Treatment Program). In November 2021, the PBAC recommended a change to include the 160 mg strength and restriction change, but did not recommend a price increase or dual Section 85/100 listing.