Both lopinavir and ritonavir interact with many other drugs, including some anti-HIV drugs. Consequently, patients taking Kaletra should avoid, or alter the dose of other drugs they are taking.
Since both lopinavir and ritonavir are inhibitors of the enzyme CYP3A4, the following drugs should not be taken alongside Kaletra:
- Alfuzosin
- Amiodarone (Cordarone X)
- Astemizole
- Cisapride
- Colchicine in patients with renal or hepatic impairment
- Ergotamine tartrate (Cafergot / Migril)
- Flecainide (Tambocor)
- Halofantrine
- Hypericin (St John’s wort)
- Lovastatin
- Lumefantrine
- Midazolam (Hypnovel)
- Pimozide (Orap)
- Propafenone (Arythmol)
- Rifampicin (Rifadin / Rimactane)
- Rifapentin
- Simvastatin (Zocor)
- Terfenadine
- Triazolam
- Voriconazole (Vfend).
Kaletra interacts with many other anti-HIV drugs, and requires non-standard doses to be used. Kaletra boosts the levels of other protease inhibitors:
- Fosamprenavir (Telzir) interacts with Kaletra, with exposure to both drugs being reduced by more than half.1 Treatment-experienced patients should take an increased dose of three Kaletra tablets twice a day. There is no recommended dose adjustment for treatment-naive patients or for patients taking Kaletra capsules. This interaction is not overcome by separating the doses of the drugs.2
- Indinavir (Crixivan) should be taken at a dose of 600mg twice a day.
- Nelfinavir (Viracept): treatment-experienced patients need to take an increased dose of four capsules or three tablets of Kaletra twice a day.
- Saquinavir (Invirase) should be taken at a dose of 1000mg twice a day.
- Tipranavir (Aptivus) reduces the levels of lopinavir when both drugs are boosted with ritonavir.3 Further studies need to be done to ascertain how drug doses should be adjusted to counteract this effect.
Increasing the dose of Kaletra to four capsules or three tablets twice daily when co-administered with efavirenz (Sustiva) or nevirapine (Viramune) is necessary for treatment-experienced patients.4
Kaletra must not be administered once daily in combination with efavirenz, nevirapine, nelfinavir, amprenavir, carbamazepine, phenobarbital or phenytoin.
Concentrations of the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir (Viread) are slightly elevated when taken in combination with Kaletra. Although this does not produce an increased risk of kidney toxicity, patients taking both drugs should be monitored closely for the development of side-effects.5 Tenofovir has also been shown to reduce lopinavir levels. A dose increase to four capsules or three tablets twice a day may be necessary.6
ddI (didanosine, Videx) should be taken one hour before or two hours after Kaletra capsules, but can be taken at the same time as Kaletra tablets.
Patients taking the following drugs and Kaletra need to adjust the doses of one or both drugs, or to take the drugs with caution:
- Bepedril levels are increased by Kaletra, so it should be used with caution.
- Carbamazepine (Tegretol) should be used with caution, as combining it with Kaletra can cause including drowsiness and unsteadiness.7
- Chlorphenamine maleate (Piriton) can affect the heart in patients taking Kaletra, so it should be used with caution.
- Ciclosporin (Neoral / Sandimmun) levels are increased by Kaletra. In one study, dose reductions of 5 to 20% were required to maintain target drug concentrations.8
- Clarithromycin (Klaricid / Klaricid XL) levels are significantly increased by Kaletra and dose adjustment may be required if kidney problems occur. This drug also can affect the heart in patients taking Kaletra.
- Erythromycin (Erymax / Erythrocin / Erythroped / Erythoped A) can affect the heart in patients taking Kaletra, so it should be used with caution.
- Felodipine (Plendil) levels are increased by Kaletra, so it should be used with caution.
- Fluticasone propionate (Flixotide) levels are increased by Kaletra, raising the risk of side-effects such as weight gain, excess sweating and thinning of the skin.
- Lidocaine (Minijet Lignocaine) levels are increased by Kaletra, so it should be used with caution.
- Ketoconazole (Nizoral) and Kaletra should be co-administered with caution. The dose of ketoconazole should not exceed 200mg daily.
- Methadone hydrochloride (Methadose) increases concentrations of ritonavir but this effect is blunted when it is dosed with Kaletra.9 However, Kaletra may decrease concentrations of methadone, so monitoring of methadone blood concentrations and withdrawal symptoms is advised.10
- Nicardipine (Cardene) levels are increased by Kaletra, so it should be used with caution.
- Nifedipine (Adalat) levels are increased by Kaletra, so it should be used with caution.
- Phenobarbital should be used with caution by patients also taking Kaletra.
- Phenytoin (Epanutin) should be taken with a higher dose of Kalet ra of 533mg lopinavir with 133mg ritonavir, or with an extra 100mg ritonavir (Norvir). Levels of phenytoin in the blood should be monitored, if possible.11
- Quinidine (Kinidin Dureles) levels are increased by Kaletra, and quinidine can affect the heart in patients taking Kaletra. It should be used with caution.
- Rifabutin (Mycobutin) levels are increased by Kaletra. Doses should be reduced to 150mg.12
- Sildenafil (Viagra) concentrations are significantly increased by ritonavir. Concurrent use of Kaletra and sildenafil should be used with caution, to avoid the risk of sildenafil-associated side-effects. Sildenafil should be started at a dose of 25mg and increased every two days, while close monitoring occurs. Sildenafil is contraindicated if used for treatment of pulmonary arterial hypertension, due to dose required.
- Tacrolimus (Prograf) levels are increased by Kaletra, so should be used with caution.
- Tadalafil (Cialis) should be taken at reduced doses of 10mg every 72 hours
- Vardenafil (Levitra) should be taken at no more than 2.5mg every 72 hours.
- Warfarin levels are increased by Kaletra, so should be used with caution.