Treatment News

Compiled by Gus Cairns

Generic lopinavir and ritonavir tablets often deficient in drug

Drug company Abbott has found that generic tablet versions of their drugs ritonavir and lopinavir/ritonavir sometimes provide sub-optimal levels of drugs in the body and in one case virtually no drug.

Abbott tested generic formulations, all made by Indian manufacturers: two ritonavir tablets (Empetus®, made by the firm Emcure, and Ritomune, by Cipla) and three lopinavir/r formulations (Emletra® by Emcure, Lopimune by Cipla and Ritocom by Hetero Drugs) by measuring drug levels in dogs given appropriate doses.
Levels of drug measured directly in the tablets were near to Abbott’s own levels, with all levels within 90% of Abbott’s own pills, except for Ritocom, which had 79% as much lopinavir in it as Aluvia.

However when the drugs were given to dogs Abbot found that virtually no drug was absorbed in the case of the two Emcure products, with only 1% as much of either drug in the dogs’ blood as in the case of Aluvia and Norvir – clearly an ineffective dose. Ritocom provided about 20% less lopinavir and 30% less ritonavir, though the amount absorbed would probably still be therapeutic. But in the case of Ritomune only half as much ritonavir was absorbed compared to Norvir and there was only one-third as much total exposure to the drug. Abbott explains the deficiencies by differences in formulation, which lead to the drugs being more poorly absorbed and thus less bioavailable.

One criticism is that the same results might not apply in humans, but Abbott studies show no cases in which either of their drugs reach higher blood levels in humans than they do in dogs, and a few cases in which they are higher in dogs than humans. Thus dog studies should if anything over-estimate drug availability.

Lopinavir/ritonavir, sold as Aluvia®, is the most widely-licensed HIV drug in the developing world, and ritonavir (Norvir®) is essential as a ‘booster’ drug for other protease inhibitors. Aluvia (sold in the west as Kaletra®) has had a tablet formulation for two years but Abbott still only make the capsule form of ritonavir, which has to be refrigerated: Abbott say a tablet formulation will hopefully available by next year.
Abbott has been criticised for not agreeing with low-income countries that they can supply generic versions of the drugs. Abbott’s answer is that it will agree to supply their own drugs as prices comparable with generics.

In one case, Thailand, the government’s insistence on going ahead an agreement to supply generics has resulted in Abbott suspending negotiations with them. Abbott has offered to supply the drug for $1000 a year per person to low and lower-middle income countries including Thailand, but Thailand went ahead with a Clinton Foundation-backed agreement with another Indian firm, Matrix, to supply lopinavir/ritonavir at $700 a year. Other countries have largely made agreements with Abbott, with South Africa announcing on 3 June that Aluvia would be available to its citizens henceforth.
Dr Joseph Hamied, CEO of Cipla, disputed Abbott’s claims, saying that Cipla’s own studies had shown that their drug Lopimune achieved levels of 85% to 125% of the Abbott product and were essentially bioequivalent.

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