TIVICAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIVICAY (TIVICAY).
Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration, which is essential for HIV replication.
| Metabolism | Primarily metabolized by UGT1A1 with some contribution from CYP3A4. |
| Excretion | Primarily metabolized by UGT1A1 with minor CYP3A4 contribution; 53% of dose excreted in feces (31% as unchanged drug) and 33% in urine (1% unchanged). |
| Half-life | Terminal elimination half-life approximately 14 hours (range 11-20 hours) in healthy subjects; supports once-daily dosing with a low pharmacokinetic boost. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 28 L (0.4 L/kg in 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability not determined; relative bioavailability from oral tablet is approximately 100% compared to solution; no food effect on AUC. |
| Onset of Action | Not applicable for oral route; antiretroviral effect begins within hours of first dose, with viral load reduction evident by day 3-7. |
| Duration of Action | Maintained over 24-hour dosing interval due to half-life; trough concentrations remain above protein-adjusted IC50 for wild-type HIV-1. |
50 mg orally once daily, or 50 mg twice daily when coadministered with potent UGT1A1 inducers (e.g., rifampin). For INSTI-naive patients: 50 mg once daily. For INSTI-experienced patients with suspected resistance: 50 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min) or ESRD not on dialysis: insufficient data; use with caution. For patients on dialysis: no dose adjustment recommended as drug is not significantly removed by dialysis. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate to severe hepatic impairment (Child-Pugh B or C): not recommended due to lack of data. |
| Pediatric use | Weight-based dosing: For body weight ≥40 kg: 50 mg once daily. For 20 to <40 kg: 35 mg (using 10 mg and 25 mg tablets) once daily. For 14 to <20 kg: 25 mg once daily. For 6 to <14 kg: 10 mg once daily. For patients unable to swallow tablets, use dispersible tablets (5 mg or 10 mg) as oral suspension. Twice daily dosing in pediatric patients not established. |
| Geriatric use | No specific dose adjustments recommended for elderly patients based on age alone. Due to age-related decline in renal function, monitor renal function and consider potential for increased adverse effects. Limited data in patients >65 years; use with caution. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIVICAY (TIVICAY).
| Breastfeeding | Dolutegravir is present in human breast milk at low concentrations. The milk-to-plasma (M/P) ratio is approximately 0.003-0.006. Based on limited data, an exclusively breastfed infant would receive a subtherapeutic dose (<0.5% of maternal weight-adjusted dose). However, guidelines recommend avoiding breastfeeding in high-resource settings due to risk of HIV transmission. In low-resource settings with access to antiretroviral therapy, breastfeeding may be considered under expert guidance. |
| Teratogenic Risk | Dolutegravir (Tivicay) is associated with increased risk of neural tube defects (NTDs) when used at the time of conception and during first trimester. Data from the Tsepamo study showed a prevalence of NTDs of 0.3% (95% CI 0.13-0.69) with periconceptional dolutegravir exposure, compared to 0.1% with other antiretrovirals. No increased risk of other major congenital anomalies has been consistently demonstrated. During second and third trimesters, no specific fetal risks have been identified, but limited data exist. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Coadministration with dofetilide due to potential for serious or life-threatening reactions.","Coadministration with adagrasib (a UGT1A1 inhibitor) due to potential for increased dolutegravir exposure."]
| Precautions | ["Hypersensitivity reactions including rash, constitutional findings, and organ dysfunction; discontinue immediately if signs/symptoms develop.","Hepatotoxicity reported in patients with underlying hepatitis B or C; monitor liver enzymes.","Risk of immune reconstitution syndrome.","Decreased dolutegravir exposure with polyvalent cation-containing antacids or supplements; separate dosing by at least 2 hours (or 6 hours if cation-containing).","Increased risk of neural tube defects when used at time of conception; avoid in pregnant women attempting to conceive unless no alternative."] |
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| Fetal Monitoring | Monitor maternal HIV viral load and CD4 count at least once per trimester. Perform fetal anatomy ultrasound at 18-20 weeks gestation, with attention to the neural tube, in women exposed to dolutegravir around conception. Monitor for maternal liver function tests and signs of hypersensitivity. In infants, HIV testing should be performed per standard protocols (e.g., at birth, 4-6 weeks, 4-6 months). |
| Fertility Effects | Preclinical animal studies showed no adverse effects on fertility or reproductive performance. In humans, dolutegravir has not been associated with impaired fertility. However, HIV itself may affect fertility; antiretroviral therapy including dolutegravir may improve fertility by improving overall health. |