Kaletra (Abbott Australia)
capsules containing 133.3 mg lopinavir/33.3 mg ritonavir
oral solution containing 400 mg lopinavir/100 mg ritonavir in 5 mL
Approved indication: HIV
Australian Medicines Handbook Section 5.3
Combinations of antiviral drugs which include a protease inhibitor effectively suppress HIV. By inhibiting viral proteases drugs, such as ritonavir, reduce replication of the virus.
Lopinavir is also a protease inhibitor. After absorption it undergoes high first-pass metabolism and is rapidly cleared from the circulation. Lopinavir is extensively metabolised by cytochrome P450 3A. This is one of the enzymes inhibited by ritonavir, so giving ritonavir in combination with lopinavir increases the plasma concentrations of lopinavir.
The combination should not be prescribed with drugs such as triazolam, midazolam, simvastatin, lovastatin, ergot derivatives, cisapride or rifampicin. Other drugs with potentially significant interactions include atorvastatin, cerivastatin, dihydropyridines, oral contraceptives, sildenafil and warfarin. Patients should not take St John's wort as this reduces the plasma concentrations of lopinavir/ritonavir.
A randomised double-blind trial has studied lopinavir/ritonavir in combination with stavudine and lamivudine in patients who have not been previously treated with antiretroviral drugs. After 48 weeks of treatment the concentration of HIV RNA had fallen below 400 copies/mL in most patients.1
In a comparison with nelfinavir, another protease inhibitor, lopinavir/ritonavir was given to patients who also took stavudine and lamivudine. After 24 weeks the HIV RNA was below 400 copies/mL in 71% of the patients taking nelfinavir and in 79% of those taking lopinavir/ritonavir. This difference is statistically significant.
Lopinavir/ritonavir has also been studied in patients previously treated with a protease inhibitor. It has been given in a regimen with two nucleoside reverse transcriptase inhibitors and nevirapine (a non-nucleoside reverse transcriptase inhibitor). After 72 weeks, 75% of the patients had less than 400 copies/mL.
Approximately 3% of the patients withdrew from clinical trials of lopinavir/ritonavir because of adverse reactions. Diarrhoea affects 14-22% of patients. Other adverse effects include nausea, abdominal pain and asthenia. The combination alters liver function and can also increase concentrations of total cholesterol and triglycerides. Possibly related to the changes in triglycerides, are reports of pancreatitis in patients taking lopinavir/ritonavir.
Although lopinavir/ritonavir can be used to treat patients who have previously been treated with a protease inhibitor the extent of cross-resistance is uncertain. Some viruses will develop a reduced sensitivity to lopinavir/ritonavir during treatment.
Lopinavir/ritonavir may have a role in treating patients who are infected with HIV that is resistant to other drugs. Its precise role and the most suitable regimen will need further study as there are no data about the clinical outcomes of treatment.
