dolutegravir (doe-loo-teg-ra-vir) Tivicay

 Indications

Treatment of HIV-1 infection, in combination with other

antiretrovirals.

Action

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

Therapeutic Effects: Evidence of decreased

viral replication and reduced viral load with

slowed progression of HIV and its sequelae.

Pharmacokinetics

Absorption: Absorption follows oral administration;

bioavailability is unknown.

Distribution: Enters CSF.

Protein Binding: 98.9%.

Metabolism and Excretion: Metabobolized 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 metabolizers of dolutegravir

haveqlevels andpclearance.

Half-life: 14 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unk 2–3 hr 12–24 hr†

†Depends on concurrent use of metabolic inducers.

Contraindications/Precautions

Contraindicated in: Concurrent use of dofetilide;

Severe hepatic impairment; Lactation: Breast feeding

not recommended in HIV-infected patients.

Use Cautiously in: Underlying hepatic disease, including

hepatitis B or C (qrisk fo hepatotoxicity); Severe

renal impairment; Geri: Consider age-relatedpin

cardiac, renal and hepatic function, chronic disease

states and concurrent medications; OB: Use during

pregnancy only if clearly needed; Pedi: Children 30 kg

or INSTI-experienced with resistance documented to

other INSTIs (raltegravir) (safety and effectiveness not

established).

Adverse Reactions/Side Effects

CNS: headache, insomnia, fatigue. GI: HEPATOTOXICITY

(qWITH HEPATITIS B OR C). GU: renal impairment.

Derm: pruritus.Metab: fat accumulation/redistribution.

MS: myositis. Misc: HYPERSENSITIVITY REACTIONS

(including rash, constitutional symptoms, and liver injury),

immune reconstitution syndrome.

Interactions

Drug-Drug: Mayqblood levels and toxicity from

dofetilide; concurrent use contraindicated. Blood levels

and effectiveness arepby etravirine (should not

be used concurrently without atazanavir/ritonavir, darunavir/

ritonavir or lopinavir/ritonavir). Blood levels

and effectiveness arepby efavirenz, fosamprenavir/

ritonavir, tipranavir/ritonavir, carbamazepine,

and rifampin;qdose of dolutegravir recommended.

Blood levels and effectiveness may bepby nevirapine;

avoid concurrent use. Mayqblood levels and toxicity

from metformin; do not exceed metformin dose of

1000 mg/day. Blood levels and effectiveness may bep

by oxcarbazepine, phenobarbital, phenytoin;

avoid concurrent use. Absorption and effectiveness may

bepby cation-containing antacids, buffered medications,

calcium supplements (oral), iron supplements

(oral), laxatives, or sucralfate; dolutegravir

should be taken 2 hr before or 6 hr after; may also take

dolutegravir and calcium or iron supplements with

food.

Drug-Natural Products: Blood levels and effectiveness

may bepSt. John’s wort; avoid concurrent

use.

Route/Dosage

PO (Adults): Treatment-naı¨ve or treatment-experienced

INSTI-naı¨ve patients—50 mg once daily;

Treatment-naı¨ve or treatment-experienced INSTInaı

¨ve patients currently receiving efavirenz, fosamprenavir/

ritonavir, tipranvir/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 40 kg): Treatment-naı¨ve or treatment-

experienced INSTI-naı¨ve patients—50 mg

once daily; Treatment-naı¨ve or treatment-experienced

INSTI-naı¨ve patients currently receiving efavirenz,

fosamprenavir/ritonavir, tipranvir/ritonavir,

carbamazepine, or rifampin—50 mg twice daily.

PO (Children 30–39 kg): Treatment-naı¨ve or

treatment-experienced INSTI-naı¨ve patients—35

mg once daily; Treatment-naı¨ve or treatment-experienced

INSTI-naı¨ve patients currently receiving efavirenz,

fosamprenavir/ritonavir, tipranvir/ritonavir,

carbamazepine, or rifampin—35 mg twice daily. 

Availability

Tablets: 10 mg, 25 mg, 50 mg. In combination

with: abacavir and lamivudine (Triumeq). See

Appendix B.