Coadministration has not been studied. Lopinavir/ritonavir is metabolised by CYP3A and inhibits CYP3A. Chloroquine is metabolised by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). No effect on lopinavir/ritonavir is expected, but inhibition of CYP3A by lopinavir/ritonavir may increase chloroquine concentrations (although to a moderate extent due to the multiple elimination pathways), thereby increasing the risk of QT prolongation as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (known risk for chloroquine; possible risk for lopinavir). Due to the very long half-life, the risk of QT prolongation may persist even after discontinuation of chloroquine. No dosage adjustment is recommended for chloroquine but ECG monitoring is advised.

A case report suggests that lopinavir/ritonavir has no clinically significant interaction with dabigatran. A reduced dabigatran dosage of 75 mg twice daily (due to the anticipated interaction with lopinavir/ritonavir) resulted in insufficient dabigatran plasma concentrations. Dabigatran concentrations comparable to historical data were achieved in this patient at a dosage of 110 mg twice daily. However, due to limited data, close clinical monitoring is recommended when ritonavir-boosted protease inhibitors are used with dabigatran particularly in patients with mild or moderate renal impairment as data with verapamil (a P-gp inhibitor) and dabigatran suggest the dabigatran dose might need to be reduced in presence of a P-gp inhibitor such as lopinavir/ritonavir. Note, dabigatran is not recommended in patients with severe renal impairment.

Coadministration of dabigatran (150 mg single dose) simultaneously with or 2 h before ritonavir alone (100 mg once daily administered at steady state) was studied in HIV negative subjects. Simultaneous administration did not significantly change dabigatran PK (possibly due to mixed induction and inhibition of P-gp by ritonavir as dabigatran is a substrate of P-gp). Administration 2 hours before ritonavir decreased dabigatran AUC by 29% and Cmax by 27% (n=16). These results suggest that dabigatran can be administered simultaneously with ritonavir when used once daily as a pharmacokinetic enhancer in patients with no renal impairment, though no data are available when ritonavir is used twice daily as a pharmacokinetic enhancer. Data with verapamil (a P-gp inhibitor) and dabigatran suggest caution is needed in patients with mild or moderate renal impairment as the dabigatran dose might need to be reduced in presence of a P-gp inhibitor such as ritonavir. Note, dabigatran is not recommended in patients with severe renal impairment.

Coadministration has not been studied. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Lopinavir/ritonavir could potentially increase ondansetron exposure although to a limited extent. No a priori dosage adjustment is recommended. Caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for ondansetron). If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration of ritonavir (100 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) increased lopinavir Cmax (28%) and AUC (46%), and Cmin (116%). Appropriate doses of additional ritonavir in combination with lopinavir/ritonavir with respect to safety and efficacy have not been established.

Coadministration has not been studied. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). As ritonavir induces glucuronidation, coadministration could potentially decrease morphine concentration but facilitate the formation of the active metabolite morphine-6-glucuronide. Morphine and morphine-6-glucuronide are substrates of P-gp and coadministration may potentiate the effects of opiate in the CNS (via inhibition of P-gp at the blood-brain barrier). Monitor for sign of opiate toxicity.

Coadministration is contraindicated with lopinavir/ritonavir ORAL SOLUTION. No interaction expected with lopinavir/ritonavir tablets.

Ritonavir oral solution and soft gel capsules contain alcohol which can produce disulfiram-like reactions when coadministered with metronidazole. No interaction is expected with ritonavir film coated tablets or with powder for oral suspension.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolized by CYP450 system (mainly CYP2D6). Ritonavir when used 100 mg as a booster is a weak inhibitor of CYP2D6 and thus lopinavir/ritonavir is unlikely to significantly alter metoclopramide concentrations. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; conditional risk for metoclopramide). The product label for metoclopramide recommends caution when administering with drugs with QT prolongation risk. 

Coadministration has not been studied. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Ritonavir could potentially increase chloroquine exposure by inhibition of CYPs 3A4 and 2D6. No dosage adjustment is recommended for chloroquine but monitor toxicity.

Coadministration has not been studied. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Ritonavir could potentially increase ondansetron exposure although to a limited extent. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Codeine is a substrate of CYP2D6 (major) and CYP3A4. Ritonavir inhibits CYP2D6 at higher doses but at the 100 mg dose, ritonavir does not appear to markedly inhibit CYP2D6. While no a priori dose adjustment is required, the analgesic effect requires conversion of codeine to morphine via CYP2D6 and lopinavir/ritonavir could potentially reduce the analgesic efficacy.

Coadministration has not been studied. Codeine is a substrate of CYP2D6 (major) and CYP3A4. Ritonavir inhibits CYP2D6 at higher doses but at the 100 mg dose, ritonavir does not appear to markedly inhibit CYP2D6. While no a priori dose adjustment is required, the analgesic effect requires conversion of codeine to morphine via CYP2D6 and ritonavir could potentially reduce the analgesic efficacy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly eliminated unchanged via the kidneys.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefazolin is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied. Lopinavir/ritonavir induces glucuronidation and therefore has the potential to reduce zidovudine plasma concentrations. The clinical significance of this potential interaction is considered low.

No change in the pharmacokinetics of lopinavir was observed when lopinavir/ritonavir was given alone or in combination with stavudine and lamivudine in clinical studies.

Lamivudine metabolism does not involve CYP3A, making interactions with protease inhibitors unlikely.

Coadministration of ritonavir (300 mg four times daily) and zidovudine (200 mg three times daily) had no effect on ritonavir AUC, Cmax or Cmin, but decreased zidovudine AUC and Cmax by 25% and 27% respectively. Dose alterations should not be necessary.

Coadministration of zidovudine (200 mg single dose) and lamivudine (300 mg twice daily) to 12 asymptomatic HIV-infected adult patients increased zidovudine Cmax and AUC by 28% and 13%. Zidovudine had no effect on the pharmacokinetics of lamivudine. No dose adjustments are necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.