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US approval for paediatric use of raltegravir, new chewable tablet also gets the go-ahead
Michael Carter, 2012-01-05 08:30:00

Drug regulatory authorities in the US have approved raltegravir (Isentress) for the treatment of HIV-positive children. In addition, chewable raltegravir tablets in 100mg scored and 250 mg formulations have been given the go-ahead for paediatric use.

Raltegravir belongs to a class of antiretrovirals known as integrase inhibitors. It has a potent anti-HIV effect and has a generally mild side-effect profile.

The drug is likely to provide an important treatment option for HIV-positive children, many of who have resistance to older antiretroviral drugs.

The new Food and Drug Administration dosing recommendations concern children aged between two and 18 years weighing at least 10kg.

General dosing recommendations state that both film-coated and chewable formulations of raltegravir can be taken with or without food. The maximum dose of the chewable tablets is 300 mg twice daily. The tablets can be swallowed whole or chewed.

The 300 mg twice-daily dose of the chewable tablet is lower than the 400 mg twice-daily dose for the film-coated tablets. This is because the chewable tablets are more readily converted into active drug in the bloodstream than the film-coated tablets, so a smaller dose of the drug in the chewable tablet is needed to achieve the same blood levels .

Because of this, the FDA guidance stresses that the chewable tablets must not be substituted for the 400 mg film-coated formulation.

Specific guidance for paediatric raltegravir dosing varies according to age and body weight.

For children aged twelve and over the recommended dose is one 400 mg film-coated tablet orally, twice daily. Children aged between six and twelve years and weighing over 25 kg can either take a 400 mg film-coated tablet twice-daily, or a weight-based dose of the chewable tablet to a maximum of 300 mg twice daily.

Children aged between two and six years should take the chewable tablet. Once again, the exact dose is weight-based and should not be greater than 300 mg twice daily.

The “Warning and Precautions” section of raltegravir’s product information has also been updated. It cautions that the chewable tablet contains phenylalanine, which can be harmful to patients with phenylketonuria  (inability to break down phenylalanine).

Information about the side-effect profile of raltegravir has also been updated detailing the adverse events observed in children and adolescents enrolled in the IMPAACT P1066 study. Frequency, type and severity of side-effects were similar to those observed in adults treated with the drug.

One child developed drug-related Grade 3 hyperactivity, abnormal behaviour and insomnia. A Grade 2 serious drug-related rash developed in a separate patient, and one child experienced Grade 3-4 elevations in AST and ALT levels.

Studies exploring possible interactions between raltegravir and other drugs have all involved adults. Therefore the product label is unable to provide any information concerning this issue.