Taking it

The standard adult dose of Kaletra is two tablets (each containing 200mg lopinavir/50mg ritonavir) twice daily. An oral solution containing 80mg/ml LPV and 20mg/ml RTV is available and generally dosed twice daily. Each dose of 5ml contains 400mg LPV/100mg RTV. The oral solution contains 42% alcohol, needs to be refrigerated, and should be taken with food.

In 2009, The European Medicines Agency approved once-daily dosing of Kaletra in a co-formulation (800mg/200mg) for patients new to HIV treatment. According to a press release from its manufacturer Abbott, Kaletra dosed once daily may be associated with a lesser sustainability of virologic suppression and a higher risk of diarrhoea compared to the recommended standard twice-daily dosage.¹

Once-daily dosing of Kaletra was approved in the US for treatment-naive adults in April 2010 for patients with less than three lopinavir-associated resistance mutations.²

The 48-week results from the MO6-802 study showed that in treatment-experienced patients, there was no significant difference in viral load suppression or side-effects between patients who took the drug once or twice daily.³ 

A particular concern in once-daily dosing is the risk of lopinavir levels falling to low levels between once-daily doses. This occurred in six of 20 patients in one study and only dose escalation was able to resolve the problem in one patient.⁴

A later 48-week long ACTG 5073 study (AIDS Clinical Trials Group) found no difference in the probability of achieving sustained virological response between the once-daily and twice-daily arms of the study. However, in those who entered the study with a higher viral load, a significantly higher proportion of patients receiving twice-daily therapy achieved a sustained response than did patients taking Kaletra once daily.⁵

In the ARTEMIS study, another 48-week study reported on in 2007, more patients in the twice-daily lopinavir/r arm achieved a viral load less than 50 copies/ml than did those on once-daily dosing. Additionally, participants in the once-daily dosing arm experienced more gastrointestinal adverse events and diarrhoea.⁶

However, the MO5-739 study looking at dosing frequency found that at 48-weeks, Kaletra tablets dosed once daily were no less safe and effective than twice-daily dosing. Each study arm received Kaletra in combination with Truvada and after a year, an equal number of patients in both study arms had undetectable viral load and comparable CD4 cell count increases. In this study, once-daily Kaletra did not increase the risk of side-effects (including diarrhoea).⁷ 

Kaletra was originally available in capsules containing 133mg LPV/33.3mg RTV, with a standard dose being three capsules twice a day. Lopinavir/ritonavir in capsule and oral solution form was approved by the US FDA in 2000 for use with other antiretrovirals in the treatment of adults and children 6 months of age or older. Marketing approval in the EU followed soon after. The film-coated tablet was approved in the US in 2005 and in the European Union in 2006. In developing and middle-income countries, the tablets are marketed under the trade name Aluvia. Tablets cannot be crushed or split; they must be taken whole.

The tablet formulation produces equivalent exposure and maximal blood concentrations of both drugs to the capsules. It also carries a lower risk of causing extreme peaks and troughs in blood drug levels.⁸

The approval of a low-dose tablet (100mg lopinavir/25mg ritonavir) in both the EU and the US should make it easier for patients on non-standard dosing schedules to achieve the correct blood levels of both drugs.

Caution should be exercised in patients with hepatitis C co-infection, as mild to moderate hepatic impairment can increase blood levels of lopinavir by 30%.