BMS and Merck discontinue 100mg capsule formulation of efavirenz used for paediatric treatment

In June 2007, the 100mg capsule formulation of efavirenz (Sustiva), was discontinued by Bristol-Myers Squibb (BMS), the European manufacturer and distributor. This alarmed UK doctors and pharmacists. Pharmacists only learnt of this through a news item in The Pharmaceutical Journal, rather than from any direct communication from BMS. This was without prior notification.

i-Base have since learnt that BMS and Merck (who manufacture and distribute efavirenz outside the US and five European countries), actually discontinued this formulation in 2006 due to their analysis of low patient usage, and that the existing stocks were then used until they eventually ran down.

This has caused significant difficulties for children on this formulation, including increasing pills counts, use of higher doses, and increased use of therapeutic drug monitoring (TDM), for which doctors are hoping that BMS agree to fund.

The lack of 100mg capsules predictably increased for the 50mg formulation. This resulted in problems in the supply chain leading to patients being juggled between capsule sizes and formulations, being unable to receive standard three-month prescriptions, and the emergency importation and use of the US packaged formulation (which is not approved in Europe) at the end of 2007.

Efavirenz is now available for paediatric use in an oral solution and in 50mg and 200mg capsules. For many children, for example those using a 350mg dose, the withdrawal of the 100mg formulation has increased the pill count from 4 to 7 capsules. Some children, who are able to swallow the larger 200mg capsules are now using higher doses than clinically recommended to reduce pill count and improve this aspect of their quality of life.

In France, following complaints by patient organisations including TRT-5, BMS responded by maintaining the 100mg formulation until December 2008. After meeting with TRT-5, who are raising this with the French regulatory agency, BMS France are preparing a letter and leaflet to accompany the switch.

BMS UK say their “decision to discontinue 100mg capsules in June 2007, was based on very low usage of the capsule and the ability to substitute two 50 mg capsules for the 100 mg dose” – and that “50 mg capsules, 200 mg capsules and 600 mg tablets, as well as 30 mg/ml oral solution are still available”.

The company statement, issued on 10 July, continued “the discontinuation was communicated through the medical press ?- and that the MHRA and Department of Health were informed. We recognise that we did not communicate directly with the HIV advocacy community about this decision and in the future we will do this”.

Comment

It is strange that a paediatric formulation of one of the most important antiretroviral drugs could have been discontinued without broader community and provider awareness. It is also disconcerting that many of these details are only now coming to light.

With many public and private organisations now at last recognising the importance of more and better paediatric formulations, even with relatively low patient numbers, it is a worrying signal for BMS to stop an existing one.

If the 100mg formulation is permanently discontinued, some activists in France are calling for children to be able to use the FDA-approved generic version of efavirenz, produced by Aurobindo.