| Research Briefs|
| Fast Takes|
Ritonavir: QT and PR prolongation
The U.S. Food and Drug Administration (FDA) has cautioned that a recent study confirms earlier reports that ritonavir can prolong QT and PR intervals and may increase the risk of cardiac arrhythmias. In the study cited by the FDA (Study M06-80), HIV-uninfected subjects who were given ritonavir 400 mg twice daily had mean QTcF prolongation of 5.5 msec and mean PR prolongation of 22 msec. The effects of lower dosages of ritonavir on cardiac conduction were not addressed. Pending further studies, clinicians should use caution and monitor closely when using ritonavir for patients with conduction system abnormalities or other cardiac disease and when coadministering ritonavir with other medications that prolong QT or PR intervals (eg, atazanavir, beta-blockers, calcium channel blockers, and macrolides).
The FDA-approved changes to the ritonavir product label are available at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/.
FDA approval for treatment-naive patients
The FDA has granted approval for the use of darunavir (with ritonavir boosting) in treatment-naive adults. The recommended dosage for initial therapy in adults is darunavir 800 mg once daily + ritonavir 100 mg once daily. There is no change in the recommended dosage for treatment-experienced patients: darunavir 600 mg BID + ritonavir 100 mg BID.
Changes in formulation: 400 mg tablet introduced; 300 mg tablet discontinued
|The manufacturer of darunavir, Tibotec Therapeutics, is introducing a new 400 mg formulation, intended primarily for use in initial therapy. The 400 mg tablet should be available soon.|
|Tibotec is discontinuing production of the 300 mg formulation, effective October 2008.|
|The 600 mg tablet will remain available.|
Change in FDA pregnancy category
The FDA has changed the pregnancy category of darunavir from B to C. Darunavir should be used during pregnancy only if the potential benefits justify the potential risks.
Atazanavir + ritonavir: FDA approved for treatment of ARV-naive individuals with HIV infection
In October, the FDA approved ritonavir-boosted atazanavir for use in first-line HIV treatment. This combination has been recommended for some time by the U.S. Department of Health and Human Services (DHHS) guidelines and other consensus guidelines, but previously had been FDA approved only for treatment-experienced individuals.
Tenofovir: FDA approved for treatment of hepatitis B
The nucleotide analogue tenofovir has received FDA approval for treatment of hepatitis B virus (HBV) infection. Approval was based on studies of HIV-uninfected patients, but limited data have demonstrated the efficacy of tenofovir for HIV/HBV-coinfected patients, and in recent years tenofovir commonly has been used in ARV regimens to treat both HIV and hepatitis B for coinfected patients.
Current DHHS adult treatment guidelines and NIH/CDC/HIVMA/IDSA opportunistic infection treatment guidelines recommend that HIV/HBV-coinfected patients who are treated for HIV should be treated simultaneously for HBV, with tenofovir as one option for treating both infections. To avoid the development of HIV-associated resistance, tenofovir should be used only as part of an ARV regimen that will fully suppress HIV viremia.
The recommended tenofovir dosage for the treatment of chronic hepatitis B is the same as for the treatment of HIV: 300 mg once daily. Dosage adjustment is recommended for patients with renal impairment.
For further information, see http://www.viread.com/pdf/Viread_FPI.pdf.
Zidovudine: Pediatric dosing changes
The FDA has approved a twice-daily dosing strategy for pediatric patients aged 6 weeks to 18 years, and allows dosing based on their weight. The previous recommended dosing frequency for children was 3 times daily, and dosage calculations were based on body surface area.
The new pediatric dosing recommendations for children 6 weeks of age or older, based on weight, are as follows:
|4 kg to <9 kg||12 mg/kg BID or 8 mg/kg TID|
|≥9 kg to <30 kg||9 mg/kg BID or 6 mg/kg TID|
|≥30 kg||300 mg/kg BID or 200 mg/kg TID (adult dosage)|
If dosing is based on body surface area, the recommended dosage is 240 mg/m2 BID or 160 mg/m2 TID. Syrup formulation of zidovudine should be used with children for whom tablets or capsules are not appropriate.
Didanosine (capsule formulation): Pediatric dosing
The FDA has approved the use of didanosine extended-release capsules (Videx EC) for pediatric patients who weigh at least 20 kg and can swallow capsules. For these patients, the recommended dosage of the capsule formulation is as follows:
|Weight||Didanosine Extended-Release Dosage|
|20 kg to <25 kg||200 mg QD|
|25 kg to <60 kg||250 mg QD|
|≥60 kg||400 mg QD (adult dosage)|
For smaller children and children who cannot swallow capsules, the previous recommendations for the use of pediatric powder stand; see the product label at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/.