integrase strand transfer inhibitors
- 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 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 have ↑ levels and ↓ clearance.
Half-life: 14 hr
TIME/ACTION PROFILE (blood levels)
|PO||unknown||2–3 hr||12–24 hr†|
- Concurrent use of dofetilide;
- Severe hepatic impairment;
- Lactation: Breastfeeding not recommended in HIV-infected patients.
Use Cautiously in:
- Underlying hepatic disease, including hepatitis B or C (↑ risk fo hepatotoxicity);
- Severe renal impairment;
- Geri: Consider age-related ↓ in 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 (↑ WITH HEPATITIS B OR C)
GU: renal impairment
Misc: hypersensitivity reactions (including rash, constitutional symptoms, and liver injury), immune reconstitution syndrome
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- 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; do not exceed metformin dose of 1000 mg/day.
- Blood levels and effectiveness may be ↓ by oxcarbazepine, phenobarbital, phenytoin; avoid concurrent use.
- Absorption and effectiveness may be ↓ by 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.
Blood levels and effectiveness may be ↓ St. John's wort; avoid concurrent use.
PO: (Adults) Treatment-naïve or treatment-experienced INSTI-naïve patients or virologically suppressed (HIV RNA <50 copies/mL) patients switching to dolutegravir plus rilpivirine– 50 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve 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 ≥40 kg): Treatment-naïve or treatment-experienced INSTI-naïve patients– 50 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin– 50 mg twice daily.
PO: (Children 30–39 kg): Treatment-naïve or treatment-experienced INSTI-naïve patients– 35 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin– 35 mg twice daily.
Tablets: 10 mg, 25 mg, 50 mg
In Combination with: abacavir and lamivudine (Triumeq). See combination drugs
- Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
- Monitor for signs and symptoms of hypersensitivity reactions (rash, fever, malaise, fatigue, muscle or joint aches, blisters or peeling of skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Discontinue therapy and do not restart.
Lab Test Considerations: Monitor viral load and CD4 counts regularly during therapy.
- Obtain a negative pregnancy before starting therapy.
- May cause ↓ ANC, hemoglobin, total neutrophils, and platelet counts.
- Monitor liver function periodically during therapy. May cause ↑ serum glucose, lipase, AST, ALT, total bilirubin, creatine kinase concentrations.
- PO: May be administered without regard to food.
- Administer 2 hrs before or 6 hrs after calcium and iron supplements.
- Emphasize the importance of taking dolutegravir as directed. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered unless within 4 hr of next dose; then skip dose. Do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx renewal in case of changes.
- Instruct patient that dolutegravir should not be shared with others.
- 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, especially St. John's wort.
- Inform patient that dolutegravir does not cure AIDS or prevent associated or opportunistic infections. Dolutegravir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of dolutegravir are unknown at this time.
- Advise patient to notify health care professional if signs and symptoms of hypersensitivity or infection occur.
- Rep: Advise patients to notify health care professional if pregnancy is planned or suspected. Breast feeding should be avoided during therapy. Pregnant patients should be encouraged to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
- Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
- Decrease in viral load and improvement in CD4 cell counts.
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