doravirine

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: non nucleoside reverse transcriptase inhibitors

REMS

HIV-1 infection in patients with no prior antiretroviral treatment history (in combination with other antiretrovirals).
To replace the current antiretroviral regimen in patients with HIV-1 infection who are virologically suppressed (HIV-1 RNA <50 copies/mL), receiving a stable antiretroviral regimen with no history of treatment failure, and have no known substitutions associated with resistance to doravirine (in combination with other antiretrovirals).

Binds to the enzyme reverse transcriptase, which results in disrupted viral DNA synthesis.

Therapeutic Effects:

Reduced viral load with slowed progression of HIV and its sequelae.

Absorption: 64% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver by the CYP3A enzymes. Primarily excreted in feces (as metabolites), 6% unchanged in urine.

Half-life: 15 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	24 hr

Contraindicated in:

Concurrent use of carbamazepine, enzalutamide, mitotane, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, and St. John's wort
Lactation: Breastfeeding not recommended in women with HIV.

Use Cautiously in:

End-stage renal disease
Severe hepatic impairment
OB: Safety not established in pregnancy
Pedi: Children <35 kg (safety and effectiveness not established)
Geri: Consider age-related ↓ in organ function and body mass, concurrent disease states and medications in older adults.

Derm: rash.

Endo: Graves' disease.

GI: diarrhea, abdominal pain, autoimmune hepatitis, hyperbilirubinemia, ↑ lipase, ↑ liver enzymes, nausea.

GU: ↑serum creatinine.

MS: ↑creatine kinase, polymyositis.

Neuro: abnormal dreams, dizziness, fatigue, Guillain-Barré syndrome, headache, insomnia, sedation.

Misc: immune reconstitution syndrome.

Drug-Drug:

Strong CYP3A inducers, including carbamazepine, enzalutamide, mitotane, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine may significantly ↓ levels and effectiveness; concurrent use contraindicated; should discontinue these medications for 4 wk before initiating doravirine therapy.
Rifabutin may ↓ levels and effectiveness; ↑ doravirine dose to 100 mg twice daily.
Efavirenz, etravirine, and nevirapine may ↓ levels and effectiveness; concurrent use not recommended.

Drug-Natural Products:

St. John's wort may significantly ↓ levels and effectiveness; concurrent use contraindicated; should discontinue this medication for 4 wk before initiating doravirine therapy.

PO (Adults and Children 35 kg): 100 mg once daily.

Tablets: 100 mg;
In combination with: lamivudine and tenofovir disoproxil fumarate (Delstrigo). See Appendix [not included in this PDA edition].

Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.

PO: Administer once daily without regard to food.

Emphasize the importance of taking doravirine as directed. It must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered, but not if almost time for next dose; do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Instruct patient that doravirine should not be shared with others.
Inform patient that doravirine does not cure HIV or prevent associated or opportunistic infections. Doravine may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading HIV to others. Advise patient that the long-term effects of doravirine are unknown at this time.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient to notify health care professional if signs and symptoms of immune reconstitution syndrome (signs and symptoms of an infection) occur.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise female patient to avoid breastfeeding during therapy.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Delayed progression of HIV and decreased opportunistic infections.
Decrease in viral load and increase in CD4 cell counts.

NDC Code^*

0006- Merck Sharp and Dohme Corp.
0006-3069- PIFELTRO 0006-3069-01- 30 TABLET, FILM COATED in 1 BOTTLE (0006-3069-01)

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