doe-loo-TEG-ra-vir

• Treatment of HIV-1 infection (in combination with other antiretrovirals).
• Treatment of 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: Absorption follows oral administration; bioavailability is unknown.

Distribution: Enters CSF.

Protein Binding: >98.9%.

Metabolism/Excretion: Metabolized primarily by the UGT1A1 enzyme system with some metabolism by CYP3A4. 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.

Contraindicated in:

• Concurrent use of dofetilide
• Severe hepatic impairment
• OB: Avoid use through first trimester of pregnancy (may ↑ risk of neural tube defects)
• Lactation: Breast feeding not recommended in patients with HIV.

Use Cautiously in:

• Underlying hepatic disease, including hepatitis B or C (↑ risk of hepatotoxicity)
• End-stage renal disease requiring dialysis
• OB: Can consider use during second or third trimester if potential maternal benefit justifies potential fetal risk
• Rep: Women of reproductive potential
• 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

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 ↑ blood levels and toxicity from dofetilide; concurrent use contraindicated.
• Blood levels and effectiveness are ↓ by etravirine (should not be used concurrently without atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir).
• Blood levels and effectiveness are ↓ by efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, and rifampin; ↑ dose of dolutegravir recommended.
• Blood levels and effectiveness may be ↓ by nevirapine; avoid concurrent use.
• May ↑ blood levels and toxicity from metformin.
• Blood levels and effectiveness may be ↓ by oxcarbazepine, phenobarbital, phenytoin; avoid concurrent use.
• Absorption and effectiveness may be ↓ by cation-containing antacids or laxatives, as well as buffered medications, or sucralfate; dolutegravir should be taken 2 hr before or 6 hr after these medications.
• Absorption and effectiveness may be ↓ by calcium supplements (oral) or iron supplements (oral); 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.
• May ↑ dalfampridine levels and risk of seizures.

Drug-Natural Products:

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

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

• PO (Adults): Treatment-nave or treatment-experienced INSTI-nave patients or virologically suppressed (HIV RNA <50 copies/mL) patients switching to dolutegravir plus rilpivirine — 50 mg once daily; Treatment-nave or treatment-experienced INSTI-nave 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-nave or treatment-experienced INSTI-nave patients — Tivicay PD: 30 mg once daily; Tivicay tablets: 50 mg once daily Treatment-nave or treatment-experienced INSTI-nave 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-nave or treatment-experienced INSTI-nave patients — Tivicay PD (preferred): 25 mg once daily; Tivicay tablets: 40 mg once daily; Treatment-nave or treatment-experienced INSTI-nave 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-nave or treatment-experienced INSTI-nave patients — Tivicay PD: 20 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin — Tivicay PD: 20 mg twice daily.
• PO (Children 4 wk and 6–<10 kg): Treatment-nave or treatment-experienced INSTI-nave patients — Tivicay PD: 15 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin — Tivicay PD: 15 mg twice daily.
• PO (Children 4 wk and 3–<6 kg): Treatment-nave or treatment-experienced INSTI-nave patients — Tivicay PD: 5 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin — Tivicay PD: 5 mg twice daily.

• PO: May be administered without regard to food.
  • Tablets for oral suspension are preferred for patients weighing <20 kg. Administer by swallowing tablets for oral suspension whole; do not crush, cut, or chew. Tablets for oral suspension may also be dispersed in 5 mL (for 1 or 3 tablets for oral suspension or 10 mL (for 4–6 tablets for oral suspension) of drinking water. Disperse in cup provided, swirl suspension so no lumps remain. After dispersion, administer within 30 min of mixing.
  • Administer 2 hrs before or 6 hrs after calcium and iron supplements.

Tivicay, Tivicay PD

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: integrase strand transfer inhibitors (INSTI)

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