DOLUTEGRAVIR SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOLUTEGRAVIR SODIUM (DOLUTEGRAVIR SODIUM).
Integrase strand transfer inhibitor (INSTI); inhibits HIV-1 integrase, blocking viral DNA integration into host genome.
| Metabolism | Primarily metabolized by UGT1A1 with minor contribution by CYP3A4. |
| Excretion | Primarily (64%) excreted unchanged in feces via biliary secretion; 31% in urine, of which 18.9% is unchanged drug and the rest as glucuronide conjugate (5.1%) and other minor metabolites. Total clearance: 0.56 L/h. |
| Half-life | Terminal elimination half-life is approximately 14 hours (range 11-17 hours) in healthy subjects; supports once-daily dosing. Half-life may be prolonged in severe renal impairment but no dose adjustment required. |
| Protein binding | Approximately 99% bound to human plasma proteins, primarily to albumin. |
| Volume of Distribution | Apparent volume of distribution is 17.4 L (approximately 0.25 L/kg for a 70 kg adult), indicating distribution into tissues beyond plasma water. |
| Bioavailability | Oral bioavailability is not determined due to lack of intravenous formulation; however, absorption is rapid with Tmax of 2-3 hours. Food reduces Cmax by 28% and AUC by 9%, but does not affect clinical efficacy; therefore, can be taken with or without food. |
| Onset of Action | Oral: Onset of virologic suppression begins within 1-2 weeks of therapy; maximal antiviral effect achieved by 4-6 weeks. |
| Duration of Action | Duration of antiviral effect is 24 hours with once-daily dosing, based on trough concentrations exceeding protein-adjusted 90% inhibitory concentration (IC90) for wild-type HIV-1. Clinical duration of suppression sustained with continuous therapy. |
| Molecular Weight | 419.38 |
50 mg orally once daily, with or without food. For INSTI-naive patients, 50 mg twice daily when co-administered with potent UDP-glucuronosyltransferase (UGT)1A1 or CYP3A inducers (e.g., efavirenz, nevirapine, tipranavir/ritonavir, rifampin).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to severe renal impairment (CrCl <30 mL/min). Not studied in dialysis; use with caution. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution; no specific dose recommendation. Child-Pugh Class C: Not recommended (no data). |
| Pediatric use | Weight-based dosing: <20 kg: 5 mg/kg once daily; 20 to <40 kg: 35 mg once daily; ≥40 kg: 50 mg once daily. Maximum dose 50 mg. For INSTI-naive adolescents (≥12 years and ≥40 kg): 50 mg once daily. |
| Geriatric use | No specific dose adjustment; limited data in patients >65 years. Monitor renal function due to age-related decline, though no renal dose adjustment required. Consider potential for increased adverse effects due to comorbidities and polypharmacy. |
| 1st trimester | Dolutegravir is associated with a small increased risk of neural tube defects when used at the time of conception and in early pregnancy. Based on data from the Tsepamo study, the prevalence of neural tube defects was 0.3% among women exposed at conception. Therefore, it is generally avoided during the first trimester unless no other options are available. |
| 2nd trimester | No increased risk of fetal adverse outcomes has been reported with use during the second trimester. The drug is considered safe and is often continued for maternal HIV treatment. |
| 3rd trimester | Similar to second trimester, no substantial risk to the fetus. Dolutegravir can be used during the third trimester without concerns for major fetal harm. It is a preferred agent in many HIV guidelines. |
Clinical note
Comprehensive clinical and safety monograph for DOLUTEGRAVIR SODIUM (DOLUTEGRAVIR SODIUM).
| Placental transfer | Dolutegravir crosses the placenta with a cord blood-to-maternal ratio of approximately 0.5–1.0, indicating significant placental transfer. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to dolutegravir or any component of the formulationCo-administration with dofetilide
| Precautions | Hypersensitivity reactions (e.g., rash, hepatic toxicity), Hepatotoxicity in patients with pre-existing liver disease or co-infection with HBV/HCV, Immune reconstitution syndrome, Decreased renal function when co-administered with nephrotoxic agents, Risk of neural tube defects if administered at time of conception or early pregnancy |
| Food/Dietary | Dolutegravir can be taken with or without food. However, taking with a high-fat meal may increase absorption and is not clinically required. No specific dietary restrictions. |
Loading safety data…
| Dolutegravir is excreted into human breast milk in low concentrations. The estimated infant daily dose is approximately 1% of the maternal dose. While this is generally considered safe, caution is advised due to potential long-term neurodevelopmental effects, which are still under investigation. In HIV-infected mothers, breastfeeding is not recommended in settings where safe alternatives are available to avoid transmission. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Dolutegravir is associated with an increased risk of neural tube defects (NTDs) when used at the time of conception and during the first trimester. The absolute risk of NTDs is approximately 0.3% (3 per 1000 pregnancies) based on observed data from the Tsepamo study. For second and third trimester exposure, no increased risk of major malformations has been identified. Overall, the risk is highest with periconceptional use. |
| Fetal Monitoring | Monitor maternal complete blood count, renal and hepatic function, and HIV RNA viral load regularly. Fetal ultrasound should be performed at 18-20 weeks of gestation to assess for neural tube defects if dolutegravir was used at conception or during the first trimester. Additionally, monitor for signs of lactic acidosis or hepatotoxicity in the mother. |
| Fertility Effects | Dolutegravir has not been associated with clinically significant effects on male or female fertility in human studies. Preclinical studies showed no adverse effects on fertility or reproductive performance. |
| Clinical Pearls |
| Dolutegravir is a first-line integrase strand transfer inhibitor (INSTI) for HIV-1 treatment. It has a high barrier to resistance and can be used in patients with prior virologic failure. Avoid coadministration with dofetilide due to increased risk of arrhythmia. Monitor for neuropsychiatric adverse effects (insomnia, headache) especially in patients with pre-existing depression. Dose adjustment to 50 mg twice daily is recommended when coadministered with potent UGT1A1 or CYP3A4 inducers like rifampin, carbamazepine, or phenytoin. Dolutegravir can be taken without regard to food, but taking with a fatty meal increases absorption. For women of childbearing potential, assess pregnancy risk and consider alternative therapy during the first trimester due to small increased risk of neural tube defects. |
| Patient Advice | Take dolutegravir exactly as prescribed, usually once or twice daily with or without food. · Do not stop taking this medication without consulting your doctor, as missing doses can lead to drug resistance. · Inform your doctor immediately if you become pregnant or plan to become pregnant, as there is a small risk of birth defects. · Report any symptoms of allergic reaction (rash, fever, muscle/joint pain) or depression (sadness, anxiety, sleep problems). · Keep a list of all medications you take, including supplements, as some may interact with dolutegravir. · This medication does not cure HIV or prevent transmission; continue to practice safe sex and use condoms. |