DOVATO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOVATO (DOVATO).
Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration. Lamivudine is a nucleoside reverse transcriptase inhibitor that inhibits HIV reverse transcriptase via DNA chain termination.
| Metabolism | Dolutegravir is metabolized by UGT1A1 and CYP3A4; lamivudine is minimally metabolized via hepatic and renal pathways. |
| Excretion | Dolutegravir: ~53% renal (unchanged), ~31% fecal (unchanged), ~5% biliary; Lamivudine: ~70% renal (unchanged) via OCT2/MATE transporters. |
| Half-life | Dolutegravir: ~14 hours (single dose), ~11-12 hours at steady state; Lamivudine: ~18-19 hours. Clinical context: supports once-daily dosing for both. |
| Protein binding | Dolutegravir: ~98-99% bound to plasma albumin; Lamivudine: <36% bound (primarily to albumin). |
| Volume of Distribution | Dolutegravir: ~17.4 L (0.25 L/kg); Lamivudine: ~1.3 L/kg. Indicates extensive tissue penetration for both. |
| Bioavailability | Dolutegravir: oral bioavailability not established, but rapid absorption with Tmax 2-3 hours; Lamivudine: oral bioavailability ~86%. |
| Onset of Action | Oral: Dolutegravir reaches steady-state viral suppression within 2-4 weeks; Lamivudine inhibits reverse transcriptase within hours of first dose. |
| Duration of Action | Dolutegravir: >24 hours (once-daily dosing); Lamivudine: ~24 hours. Missed dose should be taken as soon as remembered unless next dose is due within 12 hours. |
One tablet (50 mg dolutegravir/300 mg lamivudine) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if CrCl <30 mL/min; no adjustment needed for CrCl ≥30 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: not recommended due to lack of data. |
| Pediatric use | Not recommended for pediatric patients weighing <40 kg due to fixed-dose combination tablet strength; for those ≥40 kg, same as adult dose. |
| Geriatric use | No specific dose adjustment; monitor renal function closely; increased risk of adverse effects due to age-related decline in organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DOVATO (DOVATO).
| Breastfeeding | Both dolutegravir and lamivudine are excreted into human breast milk. The milk-to-plasma (M/P) ratio for dolutegravir is approximately 0.41, and for lamivudine, it is approximately 3.3. Due to the potential for HIV transmission and adverse effects in the nursing infant, the manufacturer recommends that HIV-infected mothers should not breastfeed, regardless of antiretroviral therapy. |
| Teratogenic Risk | Dolutegravir and lamivudine: Dolutegravir has been associated with an increased risk of neural tube defects when administered at the time of conception and during early pregnancy (first trimester). Data suggest a prevalence of approximately 0.3% compared to 0.1% in the general population. For later trimesters, no specific fetal risks have been identified. Lamivudine: Not associated with an increased risk of major birth defects. Overall, DOVATO is contraindicated in women of childbearing potential unless effective contraception is used, and should not be used during pregnancy, especially the first trimester, unless no suitable alternative exists. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concurrent use with dofetilide","Hypersensitivity to dolutegravir or lamivudine"]
| Precautions | ["Hepatic adverse events including hepatotoxicity and exacerbation of hepatitis B infection if lamivudine is discontinued","Hypersensitivity reactions","Lactic acidosis and severe hepatomegaly with steatosis","Immune reconstitution syndrome","Effects on bone mineral density and fat redistribution"] |
| Food/Dietary | No significant food interactions. DOVATO can be taken with or without food. However, avoid high-fat meals if also taking calcium or iron supplements (separate by 6 hours). |
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| Fetal Monitoring | Monitor maternal HIV viral load, CD4 count, and liver function tests throughout pregnancy. Perform fetal ultrasound for neural tube defects if exposure occurs during the periconceptional period. Monitor for maternal adverse effects such as hepatotoxicity, hypersensitivity reactions, and depressive symptoms. Additionally, monitor infant for HIV serostatus and for potential drug-related adverse effects (e.g., lactic acidosis, hepatic steatosis). |
| Fertility Effects | Dolutegravir has been associated with reversible decreases in sperm count and motility in animal studies, but clinical data in humans are limited. No significant effects on female fertility have been reported. Lamivudine is not known to affect fertility. Overall, DOVATO is not expected to impair fertility in humans, but caution is advised in men attempting conception. |
| Clinical Pearls |
| DOVATO is a 2-drug regimen (dolutegravir + lamivudine) for HIV-1; contraindicated in patients with known or suspected resistance to any component or with severe hepatic impairment (Child-Pugh C). Avoid coadministration with dofetilide or antiarrhythmics due to dolutegravir’s inhibition of OCT2. For women of childbearing potential, assess pregnancy risk; dolutegravir associated with neural tube defects when used at conception. Monitor renal function before initiation and periodically; dose adjustment of lamivudine needed if CrCl <30 mL/min (contraindicated). |
| Patient Advice | Take one tablet once daily with or without food. · Do not miss doses; if missed within 8 hours, take as soon as remembered; if >8 hours, skip and take next dose at regular time. · Avoid taking with antacids, laxatives, or supplements containing calcium, iron, or magnesium within 6 hours of DOVATO. · Inform your doctor immediately if you become pregnant or plan to become pregnant. · Report any signs of hypersensitivity (rash, fever, joint pain) or liver problems (yellowing of skin/eyes, dark urine). · DO not breastfeed while taking DOVATO; HIV can pass to baby through breast milk. |