Coadministration has not been studied and is difficult to predict. Cyclophosphamide is activated to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9, and 3A4. The inactivation pathway (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is mainly by CYP3A4. Efavirenz could either potentially increase the conversion to the active metabolite or increase the amount of drug converted to the inactive neurotoxic metabolite. Careful monitoring of cyclophosphamide efficacy and toxicity is recommended.

Coadministration has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for a pharmacokinetic interaction. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.) However, possible cardiac toxicities (ECG abnormalities and sometimes arrhythmias) have been reported with doxorubicin. Use with caution. ECG monitoring is recommended. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Ondansetron has a known risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of Torsade de Pointes whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.

Pharmacokinetics of prednisolone were determined following administration of prednisone (20 mg single dose) in three groups of ten HIV+ subjects receiving either lopinavir/ritonavir or efavirenz or no antiretrovirals. Prednisolone AUC was 20% lower in the presence of efavirenz than in subjects on no antiretrovirals and was significantly lower (40% decrease) in the presence of efavirenz versus lopinavir/ritonavir. Prednisolone concentrations may fluctuate widely when patients on efavirenz switch to lopinavir/ritonavir or vice versa.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

Coadministration has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. When prednisone (more than 80% of which is converted to prednisolone by first pass hepatic metabolism) was coadministered with dolutegravir there was no clinically significant effect on the pharmacokinetics of dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Dolutegravir does not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rituximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as vincristine is excreted primarily by the biliary route.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase.

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