DOLUTEGRAVIR SODIUM AND ABACAVIR SULFATE AND LAMIVUDINE
Clinical safety rating: safe
Trimethoprim/sulfamethoxazole increases lamivudine exposure Severe acute exacerbations of hepatitis B have been reported upon discontinuation.
Dolutegravir is an HIV integrase strand transfer inhibitor that blocks integration of HIV-1 DNA into host cell DNA. Abacavir and lamivudine are nucleoside reverse transcriptase inhibitors that inhibit HIV-1 reverse transcriptase via incorporation into viral DNA, causing chain termination.
| Metabolism | Dolutegravir is metabolized primarily by UGT1A1 with minor contribution from CYP3A. Abacavir is metabolized by alcohol dehydrogenase and glucuronyl transferase. Lamivudine is minimally metabolized (5-10%) via endogenous metabolism. |
| Excretion | abacavir: 83% renal (metabolites), 16% fecal; lamivudine: 70% renal (unchanged); dolutegravir: 64% fecal, 32% renal |
| Half-life | abacavir: 1.5 hr; lamivudine: 5-7 hr; dolutegravir: 14 hr. Twice-daily dosing for abacavir/lamivudine, once-daily for dolutegravir |
| Protein binding | abacavir: ~50% (mainly albumin); lamivudine: <36%; dolutegravir: ~99% (albumin and alpha-1-acid glycoprotein) |
| Volume of Distribution | abacavir: 0.86 L/kg; lamivudine: 1.3 L/kg; dolutegravir: 17.4 L (approx 0.25 L/kg in 70 kg adult). Indicates extensive tissue penetration for abacavir and lamivudine, moderate for dolutegravir |
| Bioavailability | abacavir: 83%; lamivudine: 86%; dolutegravir: no data, but high oral absorption (postprandial reduces rate, not extent). Fixed-dose combination tablets are bioequivalent to separate formulations |
| Onset of Action | oral: antiviral effect detectable within 24-48 hours; clinical improvement often within 1-2 weeks |
| Duration of Action | dosing interval: once daily for dolutegravir, twice daily for abacavir/lamivudine; antiviral effect persists for 24-48 hours after last dose |
One tablet (dolutegravir 50 mg / abacavir 600 mg / lamivudine 300 mg) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Not recommended for creatinine clearance <50 mL/min. For CrCl ≥50 mL/min, no dose adjustment required. |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class A or B, no dose adjustment required. |
| Pediatric use | For body weight ≥40 kg: one tablet (50/600/300 mg) orally once daily. For weight <40 kg: use individual components. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function (CrCl) and hemoglobin (risk of anemia) more frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Trimethoprim/sulfamethoxazole increases lamivudine exposure Severe acute exacerbations of hepatitis B have been reported upon discontinuation.
| FDA category | Human |
| Breastfeeding | Breastfeeding not recommended for HIV+ mothers in high-resource settings. Dolutegravir: M/P ratio 0.4-0.6, infant dose ~2% maternal weight-adjusted dose. Abacavir: M/P ratio 0.85, infant exposure ~1% maternal dose. Lamivudine: M/P ratio 0.4-1.0, infant exposure ~2-4% maternal dose. All three drugs present in breast milk but risk of HIV transmission outweighs benefits. |
| Teratogenic Risk |
■ FDA Black Box Warning
WARNING: HYPERSENSITIVITY REACTIONS and LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS. Abacavir: Serious and sometimes fatal hypersensitivity reactions, with multi-organ involvement, have occurred. Patients who carry the HLA-B*5701 allele are at higher risk. Discontinue immediately if hypersensitivity suspected. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogues.
| Common Effects | Hepatitis B |
| Serious Effects |
HLA-B*5701 positive patients (abacavir hypersensitivity), patients with moderate or severe hepatic impairment, coadministration with dofetilide (organic cation transporter 2 inhibition by dolutegravir may increase dofetilide levels and risk of arrhythmias).
| Precautions | Hypersensitivity reactions (abacavir), lactic acidosis and severe hepatomegaly with steatosis, immune reconstitution syndrome, hepatotoxicity, risk of myocardial infarction (abacavir), fat redistribution, and drug interactions (e.g., with dofetilide, dofetilide contraindicated). |
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| Dolutegravir: First trimester exposure associated with neural tube defects (NTDs) (OR 1.48, 95% CI 1.12-1.95); risk is low (~0.2%). Second/third trimester: no increased risk of fetal anomalies. Abacavir and lamivudine: Human data do not show increased risk of major birth defects. For all three, maternal HIV infection must be treated to prevent vertical transmission. |
| Fetal Monitoring | Maternal: HIV viral load, CD4 count, liver function tests, renal function, hemoglobin, and lactic acid levels; assess for hypersensitivity reactions (esp. abacavir, HLA-B*5701 screening required). Fetal: First trimester ultrasound for NTD screening (if dolutegravir exposure); standard fetal growth monitoring. |
| Fertility Effects | No significant adverse effects on fertility reported for dolutegravir, abacavir, or lamivudine. In men, abacavir may cause mild sperm abnormalities but clinical significance unclear. Dolutegravir may slightly reduce testosterone levels, but fertility impact not documented. |