Drug interactions

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.

References

  1. Kashuba ADM et al. Combining fosamprenavir with lopinavir / ritonavir substantially reduces amprenavir and lopinavir exposure: ACTG protocol A5143 results. AIDS 19: 145-152, 2005
  2. Corbett AH et al. Dose separation does not overcome the pharmacokinetic interaction between fosamprenavir and lopinavir / ritonavir. Antimicrob Agents Chemother 50: 2756-2761, 2006
  3. Curry K et al. Pharmacokinetics and safety of tipranavir / ritonavir (TPV / r) alone or in combination with saquinavir (SQV), amprenavir (APV), or lopinavir (LPV): interim analysis of BI1181.51. Fifth International Workshop on Clinical Pharmacology of HIV Therapy, Rome, abstract 5.1, 2004
  4. Hsu A et al. Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 47: 350-359, 2003
  5. Kearney BP et al. Pharmacokinetic drug interaction and long term safety profile of tenofovir DF and lopinavir / ritonavir. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, abstract A-1617, 2003
  6. Breilh D et al. Pharmacokinetic drug interaction of lopinavir / ritonavir in combination with tenofovir in experienced HIV+ patients. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract A-445, 2004
  7. Bates DE et al. Carbamazepine toxicity induced by lopinavir / ritonavir and nelfinavir. Ann Pharmacother 40: 1190-1195, 2006
  8. Vogel M et al. Management of drug-to-drug interactions between cyclosporine A and the protease-inhibitor lopinavir / ritonavir in liver-transplanted HIV-infected patients. Liver Transpl 10: 939-944, 2004
  9. Smith P et al. Methadone increases ritonavir exposure when administered alone but not lopinavir / ritonavir in combination. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, abstract H-2000, 2003
  10. Rapaport S et al. Lack of methadone dose alterations or withdrawal symptoms with lopinavir/ritonavir (Kaletra). 14th International AIDS Conference, Barcelona, abstract TuPeB4539, 2002
  11. Lim ML et al. Coadministration of lopinavir / ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. J Acquir Immune Defic Syndr 36: 1034-1040, 2004
  12. Bonora S et al. Pharmacokinetics (PKs) of rifabutin (RIF) coadministered with lopinavir / ritonavir (LPV / r) in HIV patients affected by tuberculosis (TB). Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 863, 2003
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.