TIVICAY PD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIVICAY PD (TIVICAY PD).
Tivicay PD (dolutegravir) is an HIV-1 integrase strand transfer inhibitor (INSTI) that inhibits the catalytic activity of HIV-1 integrase, preventing the integration of viral DNA into host chromosomal DNA, which is essential for viral replication.
| Metabolism | Dolutegravir is primarily metabolized by UGT1A1, with minor contribution from CYP3A4. |
| Excretion | Primarily metabolized by UGT1A1 with minor CYP3A4; 53% of dose recovered in feces (30% as unchanged drug) and 31% in urine (18% as unchanged drug). |
| Half-life | Terminal elimination half-life is approximately 12-15 hours in adults, supporting once-daily dosing. |
| Protein binding | Approximately 90% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 0.6 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is not determined due to lack of IV formulation; relative bioavailability from tablets vs. suspension is comparable. |
| Onset of Action | Not applicable as clinical effect correlates with viral suppression; maximal suppression observed within 2-4 weeks of initiating therapy. |
| Duration of Action | Sustained viral suppression with once-daily dosing; trough concentrations remain above protein-adjusted IC90 for HIV-1. |
50 mg orally once daily, with or without food.
| Dosage form | TABLET, FOR SUSPENSION |
| Renal impairment | No dose adjustment required for mild to severe renal impairment (CrCl ≥15 mL/min). For patients on dialysis, no dose adjustment; administer without regard to dialysis timing. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate to severe impairment (Child-Pugh B or C): not recommended due to lack of data. |
| Pediatric use | Weight-based dosing: for patients ≥40 kg: 50 mg once daily; for 25 to <40 kg: 35 mg once daily; for 14 to <25 kg: 25 mg once daily; for 6 to <14 kg: 10 mg once daily; for 3 to <6 kg: 5 mg once daily. Administer as tablets for suspension or oral suspension. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and consider potential comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIVICAY PD (TIVICAY PD).
| Breastfeeding | Dolutegravir is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 0.41. Estimated infant daily dose is about 2.1% of the maternal weight-adjusted dose, which is below the therapeutic dose for infants. However, due to the risk of HIV transmission through breast milk, breastfeeding is contraindicated in HIV-positive women in settings where formula feeding is safe and feasible. |
| Teratogenic Risk | Dolutegravir (TIVICAY PD) is associated with an increased risk of neural tube defects (NTDs) when administered during the periconceptional period (first 5-6 weeks of gestation). Data from the Tsepamo study in Botswana showed a prevalence of NTDs of 0.3% (3/1,009) with dolutegravir exposure at conception, compared to 0.1% with other antiretrovirals. No increased risk of other congenital anomalies has been consistently demonstrated. For second and third trimester exposure, no specific fetal risks have been identified beyond those related to maternal HIV infection. Use during pregnancy should be guided by the necessity of maintaining viral suppression. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with dofetilide is contraindicated due to potential for severe or life-threatening cardiac events (e.g., torsades de pointes).","History of hypersensitivity reaction to dolutegravir."]
| Precautions | ["Hypersensitivity reactions including rash and constitutional findings have been reported; discontinue if signs or symptoms develop.","Hepatotoxicity, including elevations in liver enzymes and bilirubin, has been observed; monitor liver function.","Risk of neural tube defects when administered at the time of conception; pregnancy testing should be performed before initiation in females of childbearing potential.","Immune reconstitution syndrome may occur during initial therapy.","Potential for drug interactions, particularly with inducers of UGT1A1 or CYP3A4 (e.g., rifampin), which may reduce dolutegravir concentrations.","In patients co-infected with hepatitis B or C, monitor for transaminase elevations."] |
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| Fetal Monitoring | Monitor maternal HIV viral load, CD4 count, and liver function tests (especially in patients with hepatitis B/C coinfection). Assess for signs of hypersensitivity reaction. For fetal monitoring, perform detailed ultrasound at 18-20 weeks of gestation to screen for neural tube defects if exposed during the first trimester. Standard obstetric monitoring for high-risk pregnancies should be considered. |
| Fertility Effects | Dolutegravir has not been associated with significant effects on fertility in animal studies. In humans, no adverse effects on male or female fertility have been reported. However, untreated HIV infection can impact fertility, so viral suppression with ART may improve fertility outcomes. |