Rosiglitazone with metformin combination tablets (Avandamet) listed on the PBS

Rosiglitazone with metformin in a fixed-dose combination tablet (Avandamet) was listed on the PBS on 1 December 2006. The tablets are available in strengths of rosiglitazone 2 mg or 4 mg with metformin 500 mg or 1000 mg.

The authority listing allows people already eligible to receive the individual components on the PBS to be prescribed the combination tablets. These are people with glycated haemoglobin levels (HbA_1c) > 7% despite treatment with:

• metformin monotherapy, and being unable to take a sulfonylurea because of a contraindication or intolerance (dual oral therapy).
• maximally tolerated doses of metformin and a sulfonylurea (triple oral therapy).

People already stabilised on either of the PBS-subsidised thiazolidinediones ('glitazones') plus metformin, with or without a sulfonylurea, are eligible to switch to the combination tablets. People using insulin are not eligible for PBS-subsidised rosiglitazone with metformin combination tablets, but can be prescribed PBS-subsidised rosiglitazone tablets.

Combination tablets may be convenient for some people

Rosiglitazone is a third-line choice, after metformin and/or a sulfonylurea.

The combination tablets could be considered for people already stabilised on equivalent doses of metformin and rosiglitazone and who can switch to an equivalent strength of the combination tablet. The combination tablets could also be used to initiate rosiglitazone treatment.

Compared with taking rosiglitazone and metformin as separate tablets, the combination tablets allow patients to take fewer tablets each day and are cheaper because only one co-payment is required for both medicines. However, switching to the combination tablets may cause confusion: ensure that people switching to the combination tablets understand that they need to stop taking their separate metformin and rosiglitazone tablets.

Combination tablet doses are not suitable for everyone

Titrate metformin to the highest tolerated dose before starting rosiglitazone or the combination tablets. Consider whether the available strengths of the combination tablets allow the same dose of metformin to be given. The combination tablets may not be suitable for people taking metformin 3 times daily or taking a daily metformin dose other than 1000 mg or 2000 mg, because of the difficulty of maintaining the metformin dose at the same level with the available strengths of the combination tablets.

Using the combination tablets for people taking metformin doses above 2 g/day is outside the approved dosing recommendations, which state that the maximum recommended daily dose is rosiglitazone 8 mg/metformin 2000 mg.¹ Standard metformin tablets can be used up to 3 g/day.

Starting the combination tablets

If switching to the combination tablets from stable doses of rosiglitazone and metformin, choose the equivalent tablet strength, if available. The combination tablets are bioequivalent with the same strengths of standard rosiglitazone and metformin tablets.¹

If using the combination tablets to introduce rosiglitazone treatment, start at rosiglitazone 4 mg/day and maintain the metformin dose at the same level. Wait at least 8 weeks to see the full glycaemic response to rosiglitazone before increasing the dose.

The PBS listing allows people already taking subsidised pioglitazone to switch to rosiglitazone with metformin combination tablets. Equivalent doses of rosiglitazone and pioglitazone have not been established. Several studies not designed to assess dose equivalence have estimated comparable glycaemic effects of rosiglitazone 2 mg, 4 mg and 8 mg with pioglitazone 15 mg, 30 mg and 45 mg, respectively. ^2-4