doe-loo-TEG-ra-vir

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: integrase strand transfer inhibitors (INSTI)

• HIV-1 infection (in combination with other antiretrovirals).
• HIV-1 infection in patients to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for 6 mo with no history of treatment failure or known substitutions associated with resistance to either dolutegravir or rilpivirine (in combination with rilpivirine).

• Inhibits HIV-1 integrase, which is required for viral replication.

• Evidence of decreased viral replication and reduced viral load with slowed progression of HIV and its sequelae.

Absorption: Bioavailability is unknown.

Distribution: Enters CSF.

Protein Binding: >98.9%.

Metabolism/Excretion: Metabolized primarily by the UGT1A1 enzyme system with some metabolism by the CYP3A4 isoenzyme. 53% excreted unchanged in feces. Metabolites are renally excreted; minimal renal elimination of unchanged drug. Poor UGT1A1 metabolizers have ↑ dolutegravir concentrations and an ↑ risk of adverse effects.

Half-life: 14 hr.

(plasma concentrations)

†Depends on concurrent use of metabolic inducers.

Contraindicated in:

• Concurrent use of dofetilide
• Severe hepatic impairment.

Use Cautiously in:

• Underlying hepatic disease, including hepatitis B or C (↑ risk of hepatotoxicity)
• End-stage renal disease requiring dialysis
• Lactation: Safety not established in breastfeeding; breastfeeding should be supported in people with HIV who are taking antiretroviral therapy, as prescribed, and are maintaining an undetectable amount of virus in the body
• Pedi: Children <4 wk, <3 kg, or INSTI-experienced with resistance documented to other INSTIs (safety and effectiveness not established)
• Geri: Consider age-related ↓ in cardiac, renal, and hepatic function; chronic disease states; and concurrent medications in older adults.

Derm: pruritus.

GI: HEPATOTOXICITY (↑ WITH HEPATITIS B OR C).

GU: renal impairment.

MS: myositis.

Neuro: headache, insomnia, fatigue.

Misc: hypersensitivity reactions (including rash, constitutional symptoms, and liver injury), immune reconstitution syndrome.

Drug-Drug:

• May ↑ levels and risk of toxicity of dofetilide; concurrent use contraindicated.
• Etravirine may ↓ levels and effectiveness; should not be used concurrently without atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir).
• Efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, and rifampin may ↓ levels and effectiveness; ↑ dose of dolutegravir.
• Nevirapine may ↓ levels and effectiveness; avoid concurrent use.
• May ↑ levels and risk of toxicity of metformin.
• Oxcarbazepine, phenobarbital, and phenytoin may ↓ levels and effectiveness; avoid concurrent use.
• Cation-containing antacids or laxatives, as well as buffered medications or sucralfate, may ↓ absorption and effectiveness; dolutegravir should be taken 2 hr before or 6 hr after these medications.
• Calcium supplements (oral) or iron supplements (oral) may ↓ absorption and effectiveness; under fasting conditions, dolutegravir should be taken 2 hr before or 6 hr after these medications; when taken with food, dolutegravir and calcium or iron supplements may be taken at the same time.
• May ↑ dalfampridine levels and risk of seizures.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Tablets (Tivicay) and tablets for oral suspension (Tivicay PD) are not interchangeable.

• PO (Adults): Treatment-naive or treatment-experienced INSTI-naive patients or virologically suppressed (HIV RNA <50 copies/mL) patients switching to dolutegravir plus rilpivirine: 50 mg once daily; Treatment-naive or treatment-experienced INSTI-naive patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: 50 mg twice daily; INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance (consider other combinations that do not include metabolic inducers): 50 mg twice daily.
• PO (Children 20 kg): Treatment-naive or treatment-experienced INSTI-naive patients: Tivicay PD: 30 mg once daily; Tivicay tablets: 50 mg once daily Treatment-naive or treatment-experienced INSTI-naive patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 25 mg twice daily; Tivicay tablets: 50 mg twice daily.
• PO (Children 14–<20 kg): Treatment-naive or treatment-experienced INSTI-naive patients: Tivicay PD (preferred): 25 mg once daily; Tivicay tablets: 40 mg once daily; Treatment-naive or treatment-experienced INSTI-naive patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin: Tivicay PD (preferred): 25 mg twice daily; Tivicay tablets: 40 mg twice daily.
• PO (Children 10–<14 kg): Treatment-naive or treatment-experienced INSTI-naive patients: Tivicay PD: 20 mg once daily; Treatment-naive or treatment-experienced INSTI-naive patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 20 mg twice daily.
• PO (Children 4 wk and 6–<10 kg): Treatment-naive or treatment-experienced INSTI-naive patients: Tivicay PD: 15 mg once daily; Treatment-naive or treatment-experienced INSTI-naive patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 15 mg twice daily.
• PO (Children 4 wk and 3–<6 kg): Treatment-naive or treatment-experienced INSTI-naive patients: Tivicay PD: 5 mg once daily; Treatment-naive or treatment-experienced INSTI-naive patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 5 mg twice daily.

(Generic available)

• Tablets (Tivicay): 10 mg; 25 mg; 50 mg;
• Tablets for oral suspension (Tivicay PD): 5 mg;
• In combination with: abacavir and lamivudine (Triumeq, Triumeq PD); lamivudine (Dovato); rilpivirine (Juluca). See Appendix [not included in this PDA edition]