Lopinavir/ritonavir is an inhibitor of CYP3A (cytochrome P450 3A both in vitro and in vivo. Co-administration with drugs primarily metabolised by CYP3A (eg. dihydropyridine calcium channel blockers.

HMG CoA reductase inhibitors, immuno suppresants and sidenafil ) may result ion increased plasma concentration of the other drugs that could increase or prolong their therapeutic and adverse effects. Drugs that could NOT be administered concomiitantly with liponavir/ritonavir are - rifampicin, ergot derivatives, cisapride St.Johns wart, HMG CoG inhibitors, pimozide, and sedatives ( midozolam, triamzolam). Many other drugs have an established or potentially significant drug interactions with Lopinavir/ritonavir.

Liponavir/ ritonavir is well tolerated by most patients.

The most common side efects include diarrhoea, vomitting, headache, asthenia, abdominal pain, and nausea. Elevation in liver enzymes, total cholesterol and triglycerides have also been reported.

Liponavir/ritonavir is contraindicated in patients with known hypersensitivity to any of its ingredients including ritonavir.

Should not be concomitantly administred with ergot derivatives, (dihydroergotamine, ergonovine, ergotamine, methylergonavine), cisapride, pimozide and sedatives (medazolam, triamzolam)

For the treatment of HIV infection, in combination with other anti-retroviral agents

Dosage-

Each capsule contains lopinavir 133.33 mg and ritonavir 33.3mg.

Capsules should be swallowed whole Usually 2 caps twice daily with food

Children who can not swallow - 230/57.5mg/m2 twice daily with food

Maximum 400/100mgbtwicedaily

Capsules should be swallowed whole

Pharmacology-

Lopinavir is HIV -1 protease inhibitor which prevents the clevage of the gag-pol polyprotein resulting in the production of immature , non-infectious viral particles. Lopinavir was specifically engineerred to overcome issues with resistence to earlier prrotease inhibitors, aroblem taht has limited the use of other agents in this class. Failure to maintain effective plasma protease inhibitors due to the drug limits the use of many available protease inhibitors due to the risk of developing resistence. Lopinavir/ritonavir has ben coformulated in order to take advantage of the drug-drug interaction between lopinavir and ritonavir which significantly increases and maintains the plasma concentration of lopinavir. Ritonavir is a potent inhibitor of the CYP3A liver enzyme and as such it inhibits CYP3A liver enzyme and as such it inhibits CYP3A medated biotransformations. Coadmin of low dose ritonovir with several other protease inhibitors results in elevated and sustained plasma drug levels.

Pharmaokinetics-

After oral admin peak intracellularplasma concentrations of liponavir/ritonavir occur around 3 hours after dosing.Liponavir/ritonavir should be dosed with food to maximise bioavailability and decreased variability. Liponavir is primarily metabolised through oxidation by hepatic microsome via NADPH-dependent pathways with the formation of 12 metabolites. Liponavir/ritonavir is primarily excreted in feces the rest being through urine. The apparent clearance of an orally administred dose of liponavir is 5.98 +/- 5.7l /h