Dolutegravir Sodium

Antiretroviral; HIV integrase strand transfer inhibitor (INSTI).1 200

Absorption

Bioavailability

Absolute bioavailability of dolutegravir not established.1

Dolutegravir (Tivicay): Following 50 mg orally once or twice daily, peak plasma concentrations occur 2–3 hours after a dose.1 Steady state achieved within approximately 5 days with once-daily dosing.1

Food

Dolutegravir: Administration with high-fat meal increases AUC by 66%, increases peak concentrations by 67%, and prolongs time to peak concentrations from 2 hours to 5 hours compared with administration in fasting state.1

Abacavir/dolutegravir/lamivudine (Triumeq): Administration with high-fat meal increases dolutegravir peak plasma concentrations and AUC by 37 and 48%, respectively, compared with administration in fasting state;240 abacavir peak plasma concentrations decreased by 23%;240 lamivudine exposures not affected.240

Distribution

Extent

Dolutegravir distributed into CSF;1 32 clinical importance unknown.1

Crosses placenta in animals.1 202

Distributed into milk in rats;1 202 not known whether distributed into human milk.1 202

Plasma Protein Binding

≥98.9%.1

Elimination

Metabolism

Dolutegravir metabolized primarily by UGT1A1;1 CYP3A plays minor role.1

Elimination Route

Dolutegravir excreted in feces (53%) and urine (31%).1

Half-life

Approximately 14 hours.1

Special Populations

Moderate hepatic impairment: No clinically important effect on dolutegravir pharmacokinetics.1

Severe hepatic impairment: Dolutegravir pharmacokinetics not studied.1

HCV coinfection: No clinically important effect on dolutegravir pharmacokinetics.1

Mild to moderate renal impairment: No clinically important effect on dolutegravir pharmacokinetics.1

Severe renal impairment (Clcr <30 mL/minute): Dolutegravir AUC decreased by 40%;1 peak plasma concentration decreased by 23%.1 (See Renal Impairment under Cautions.)

Polymorphism in UGT1A1: Genotypes of UGT1A1 conferring poor dolutegravir metabolism result in 32% lower clearance and 46% higher AUC compared with genotypes associated with normal UGTIA1 metabolism.1

HIV-1-infected pediatric patients weighing >30 kg: Pharmacokinetic profile of dolutegravir similar to HIV-1-infected adults receiving dolutegravir 50 mg once daily.1

Storage

Oral

Dolutegravir (Tivicay): 25°C (may be exposed to 15–30°C).1

Abacavir/dolutegravir/lamivudine (Triumeq): 25°C (may be exposed to 15–30°C).240 Store and dispense in original package;240 do not remove desiccant;240 protect from moisture.240

• Dolutegravir is an HIV INSTI antiretroviral.1 200 Inhibits activity of HIV integrase, an enzyme that integrates HIV DNA into the host cell genome.4 1 Inhibition of integrase prevents propagation of viral infection.1 4

• Dolutegravir binds to active site of HIV integrase and blocks strand transfer step of retroviral DNA integration, which is essential for HIV replication.1

• Active against HIV type 1 (HIV-1);1 also has in vitro activity against HIV type 2 (HIV-2).1 20 25 Not active against HCV.20

• Has been active against HIV-1 resistant to HIV NRTIs, HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs), or HIV protease inhibitors (PIs).1

• HIV-1 resistant to dolutegravir have been produced in vitro and have emerged during dolutegravir therapy.1 12 13

• Appears to have a different resistance profile than other INSTIs and has been active in vitro against some HIV-1 resistant to other INSTIs (e.g., elvitegravir, raltegravir).1 12 13 14 15 16 However, cross-resistance between dolutegravir and other INSTIs (e.g., elvitegravir and/or raltegravir) reported.1 12 15 16

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.