A comprehensive medication history (including over-the-counter medications, vitamin and mineral supplements and recreational drugs) is essential before initiating PEP.

Potential drug-drug interactions can be checked using the Liverpool HIV Drug Interactions checker website.

Tenofovir disoproxil and emtricitabine

• no significant drug-drug interactions
• caution and consideration of more frequent renal monitoring if co-administered with other potentially nephrotoxic agents, although a short PEP course is unlikely to cause significant issues.

Lamivudine

• no significant drug-drug interactions.

Raltegravir

• few significant drug-drug interactions
• binds to polyvalent cations such as iron, aluminium, magnesium and calcium which results in lower absorption; more pronounced when administered once versus twice daily
• avoid use of metal cation-containing antacids, iron supplements and multivitamins with ONCE DAILY dosing; separate by at least four hours with TWICE DAILY dosing
• metabolised primarily via the gene UGT1A1
• caution with strong inducers of UGT1A1 (e.g. rifampicin, carbamazepine, phenytoin)
• if co-administration is unavoidable, do not use once-daily raltegravir 1200 mg; may use twice-daily raltegravir 400 mg 
• dose modification is unnecessary with less potent UGT1A1 inducers (e.g. rifabutin, glucocorticoids, St John’s wort, pioglitazone). 

Dolutegravir

• few significant drug-drug interactions
• binds to polyvalent cations such as iron, aluminium, magnesium and calcium which results in lower absorption 
• avoid use of metal cation containing antacids, iron supplements and multivitamins; if co-administration necessary, dolutegravir should be administered two hours before or six hours after 
• metabolised primarily via the gene UGT1A1
• caution with strong inducers of UGT1A1 (e.g. rifampicin, carbamazepine, phenytoin)
• if co-administration is unavoidable, double the dose of dolutegravir (to 50 mg twice daily)
• dolutegravir increases plasma levels of metformin; a dose reduction of metformin and close monitoring of blood glucose are likely to be required;⁷² consider using raltegravir instead.

Discuss any concerns about drug interactions or co-morbidities with a specialist pharmacist.

For more information on drug dosing and adverse events, please refer to the Australian Commentary on the US DHHS Guidelines for the use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents.