Doravirine safety: drug-drug interactions (DDIs)

DELSTRIGO® (Doravirine/Lamivudine/tenofovir disoproxil fumarate)
Prescribing Information (United Kingdom) [External link]
PIFELTRO® (doravirine)
Prescribing Information (United Kingdom) [External link]

Doravirine can be used with a variety of non-HIV medications

Doravirine is primarily metabolised by CYP3A^1,2
It can be co-administered with studied acid-reducing agents without dosing restrictions^1,2,3
Doravirine can also be co-administered with drugs used to treat a range of common co-morbidities such as anti-diabetics and Lipid lowering agents^1,2

Please refer to the relevant Summary of Product Characteristics for full details of potential interactions and contraindications before prescribing.

	DELSTRIGO²	PIFELTRO¹
Proton pump inhibitors Pantoprazole, omeprazole
Acid-modifying medications Aluminium hydroxide/magnesium hydroxide/simethicone-containing antacids
Statins Atorvastatin, rosuvastatin, simvastatin
Antihyperglycemics Metformin
Oral contraceptives Ethinyl estradiol, levonorgestrel
Hepatitis C antiviral agents Elbasvir/grazoprevir, daclatasvir Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir	^a
Benzodiazepines Midazolam
Opioid analgesics Methadone, buprenorphine
Azole antifungal agents Ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole	^b	^b
Dose adjustment required:^cAntimycobacterial Rifabutin	^d	^d

^aMonitor for adverse reactions associated with TDF.

^bConcomitant use of DELSTRIGO or PIFELTRO with azole antifungal agents may cause an increase in the plasma concentrations of doravirine (inhibition of CYP3A enzymes). No dose adjustment is required.

^cCo-administration of doravirine with other moderate CYP3A inducers has not been evaluated, but decreased doravirine concentrations are expected. If co-administration with other moderate CYP3A inducers (e.g. dabrafenib, lesinurad, bosentan, thioridazine, nafcillin, modafinil, telotristat ethyl) cannot be avoided, one 100 mg tablet of doravirine should be taken daily, approximately 12 hours after the dose of DELSTRIGO or PIFELTRO.

^dConcomitant use of DELSTRIGO or PIFELTRO with rifabutin may cause a decrease in the plasma concentrations of doravirine (induction of CYP3A enzymes). If DELSTRIGO is co-administered with rifabutin, one tablet of PIFELTRO should be taken approximately 12 hours after the dose of DELSTRIGO. If PIFELTRO is co-administered with rifabutin, one tablet of PIFELTRO should be taken twice daily (approximately 12 hours apart).

Hypersensitivity to doravirine or any of the excipients listed in section 6.1 of the relevant Summary of Product Characteristics^1,2

	DELSTRIGO²	PIFELTRO¹
Anticonvulsants Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
Antimycobacterials Rifampicin, rifapentine
Herbal products St. John’s wort
Mitotane
Enzalutamide
Lumacaftor

^eCo-administration with medicinal products that are strong cytochrome P450 (CYP)3A enzyme inducers is contraindicated as significant decreases in doravirine plasma concentrations are expected to occur, which may decrease the effectiveness of DELSTRIGO/PIFELTRO. These medicinal products include but are not limited to the above.

NOTE: DELSTRIGO is a complete regimen for the treatment of HIV-1 infection; therefore, DELSTRIGO should NOT be administered with other antiretroviral medicinal products

	PIFELTRO¹
Protease inhibitors (PIs)^f Ritonavir- and cobicistat-boosted PIs
Integrase strand inhibitors (INSTIs) Dolutegravir, raltegravir
Nucleoside reverse transcriptase inhibitors (NRTIs) Emtricitabine, tenofovir alafenamide
Fusion and Entry inhibitors Enfuvirtide, maraviroc

^fConcomitant use of PIFELTRO with ritonavir-/cobicistat-boosted PIs and ritonavir-/cobicistat-boosted elvitegravir may cause an increase in the plasma concentrations of doravirine (inhibition of CYP3A enzymes). No dose adjustment is required when PIFELTRO is co-administered with ritonavir-/cobicistat-boosted PIs and ritonavir-/cobicistat-boosted elvitegravir.

CYP3A = Cytochrome P4503A; DDI = Drug-Drug Interaction; DRV/r = Darunavir/Ritonavir; EFV = Efavirenz; FTC = Emtricitabine; NNRTI = Non-nucleoside Reverse Transcriptase Inhibitor; PPI = Proton Pump Inhibitor; TDF = Tenofovir Disoproxil Fumarate.

References

PIFELTRO Summary of Product Characteristics.
DELSTRIGO Summary of Product Characteristics.
Khalilieh S et al. Co-administration of doravirine with an aluminium/magnesium containing antacid or pantoprazole, a proton pump inhibitor, does not have a clinically meaningful effect on doravirine pharmacokinetics. Presented at 9th IAS Conference on HIV Science, 23-26 July 2017, Paris. Available at: http://programme.ias2017.org/PAGMaterial/eposters/3996.pdf.

Supporting documentation

DELSTRIGO® Prescribing Information (United Kingdom) [External link]
PIFELTRO® Prescribing Information (United Kingdom) [External link]
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Doravirine safety: drug-drug interactions (DDIs)