doravirine

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), are 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).

Contraind./Precautions ⬆ ⬇

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.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

Endo: Graves' disease

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

GU: ↑serum creatinine

MS: ↑CK, polymyositis

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

Misc: immune reconstitution syndrome

Interactions ⬆ ⬇

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.

Availability ⬆ ⬇

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

Route/Dosage ⬆ ⬇

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

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: non nucleoside reverse transcriptase inhibitors

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of doravirine. 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.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
Instruct patient that doravirine should not be shared with others.
Inform patient that doravirine does not cure HIV or prevent associated or opportunistic infections. Doravirine may ↓ 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; St. John's wort should be avoided while taking doravirine.
Advise patient to notify health care professional if signs and symptoms of immune reconstitution syndrome (signs and symptoms of an infection) occur.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263 and visit https://www.apregistry.com for more information.

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Indications ⬇