Non-refrigerated ritonavir tablet approved in Europe and the US

2 April 2010. Related: Antiretrovirals.

On 25 January in Europe and on 10 February 2010 in the US, the EMA and FDA respectively, approved the new tablet formulation of ritonavir (Norvir) that does not require refrigeration.

The previous capsule formulation was less heat-stable and required refrigerated storage.

This will affect patients using ritonavir as a booster for other protease inhibitors.

Differences in the labels for the new formulation includes new information on food. Unlike the capsule formulation, ritonavir tablets must be taken with meals. This is the current recommendation for all currently boosted protease inhibitors.

The US product label includes the following information about pharmacokinetics:

• Ritonavir tablets are not bioequivalent to ritonavir capsules. Under moderate fat conditions (857 kcal; 31% fat, 13% protein, 56% carbohydrates), when a single 100 mg ritonavir dose was administered as a tablet compared with a capsule, AUC (0-inf) met equivalence criteria but mean Cmaxwas increased by 26% (92.8% confidence intervals: ?15 -?39%).
• No information is available comparing ritonavir tablets to ritonavir capsules under fasting conditions
• A food effect is observed for ritonavir tablets. Food decreased the bioavailability of the ritonavir tablets when a single 100 mg dose of ritonavir was administered.  Under high fat conditions (907 kcal; 52% fat, 15% protein, 33% carbohydrates), a 23% decrease in mean AUC (0-inf) [90% confidence intervals: ?30%-?15%], and a 23%
  decrease in mean Cmax [90% confidence intervals: ?34%-?11%]) was observed relative to fasting conditions. Under moderate fat conditions, a 21% decrease
  in mean AUC(0-inf) [90% confidence intervals: ?28%-?13%], and a 22% decrease in mean Cmax [90% confidence intervals: ?33%-?9%]) was observed relative to
  fasting conditions.
• However, the type of meal administered did not change ritonavir tablet bioavailability when high fat was compared to moderate fat meals.”

comment

Final sign off by the European Medicines Agency (EMA) is expected in April, and
this new formulation is expected to be available for patients in the UK from June/July 2010.

Sources:

1. Abbott press statement. (25 January 2010).
   http://www.abbott.com/global/url/content/en_US/40.45:45/general_content/General_Content_00517.htm
2. FDA list serve. (10 February 2010).