European marketing approval granted for lopinavir/r (Kaletra)

Abbott Laboratories have announced that it has received approval from the European Agency for the Evaluation of Medicinal Products (EMEA) to market its second-generation protease inhibitor (PI), lopinavir/ritonavir (lopinavir/r), previously known as ABT-378/r, for the treatment of HIV-infection. Lopinavir/r is to be marketed under the tradename Kaletra™.

The approval of lopinavir/r was based on extensive clinical data from studies conducted around the world. Phase II and Phase III clinical trials included more than 800 patients from a broad range of patient groups, including those not previously treated with HIV therapy and those who have failed other HIV treatment regimens.

Lopinavir/r is a co-formulation of lopinavir (133.3mg) plus ritonavir (33.3mg). At the recommended dosage (400/100mg twice daily in adults) ritonavir has no antiviral activity, but acts as a pharmacokinetic enhancer – slowing the clearance of lopinavir from the blood. This novel formulation ensures high and sustained levels of lopinavir, which result in effective viral suppression.

The safety of lopinavir/r has been investigated in 612 patients in phase II/III clinical trials.

The following adverse reactions of moderate to severe intensity with possible or probable relationship to lopinavir/r have been reported in >2 % of patients: diarrhoea 14 %, nausea 6 %, vomiting 2 %, abdominal pain 2.5 %, asthenia 4 % and headache 3 %.

Marked clinical laboratory abnormalities (Grade 3 or 4) reported in > 2 % of patients included: increased glucose (2.5 %), increased SGOT/AST (2 %), increased SGPT/ALT (2 %) increased GGT (9 %), increased total cholesterol (8.5 %) and increased triglycerides (8 %). Importantly, discontinuations due to study drug were low in both na•ve (2-3%)2, 3 and experienced patients (approximately 3-8%).

Lopinavir/r will be available as soft capsules or as an oral solution (400mg lopinavir/100mg ritonavir per 5 ml).

The recommended dosage of lopinavir/r, in adults is 3 capsules twice daily or 5ml oral solution twice daily taken with food. The dosage for children is based on body weight. Lopinavir/r soft capsules and oral solution should be stored under refrigeration between +2¼C to + 8¼C until they are dispensed to the patient. Refrigeration by the patient is not required if the product is used within 42 days (6 weeks) and stored below 25¼C.