DELSTRIGO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DELSTRIGO (DELSTRIGO).
Delstrigo is a fixed-dose combination of doravirine (non-nucleoside reverse transcriptase inhibitor, NNRTI) and lamivudine (nucleoside reverse transcriptase inhibitor, NRTI) plus tenofovir disoproxil fumarate (nucleotide reverse transcriptase inhibitor, NtRTI). Doravirine binds to and inhibits HIV-1 reverse transcriptase, preventing RNA-dependent DNA polymerization. Lamivudine and tenofovir are incorporated into viral DNA, causing chain termination.
| Metabolism | Doravirine is primarily metabolized by CYP3A4. Lamivudine is primarily eliminated renally as unchanged drug. Tenofovir disoproxil fumarate is converted to tenofovir, which is eliminated renally by a combination of glomerular filtration and active tubular secretion. |
| Excretion | Following oral administration of DELSTRIGO (doravirine 100mg/lamivudine 300mg/tenofovir disoproxil fumarate 300mg), doravirine is excreted ~6% unchanged in urine and ~74% as metabolites in feces (biliary/fecal). Lamivudine is primarily excreted unchanged in urine (~70%) via active tubular secretion. Tenofovir is eliminated renally ~70-80% unchanged via glomerular filtration and active tubular secretion. |
| Half-life | Doravirine: terminal half-life ~15 hours (range 12-20), supports once-daily dosing. Lamivudine: ~13-19 hours in adults (prolonged in renal impairment). Tenofovir: ~17 hours (prolonged to ~50 hours in severe renal impairment). Clinical context: half-lives allow once-daily dosing; accumulation occurs in renal dysfunction. |
| Protein binding | Doravirine: ~76% bound to albumin. Lamivudine: <36% bound (mostly albumin). Tenofovir: <7% bound (minimal protein binding). |
| Volume of Distribution | Doravirine: Vd ~100 L (approx 1.3 L/kg in 70 kg adult), indicating extensive tissue distribution. Lamivudine: Vd ~1.3 L/kg, distributes into total body water. Tenofovir: Vd ~1.2 L/kg, distributes widely with affinity for renal tissue. |
| Bioavailability | Oral: doravirine bioavailability ~64% (range 47-82) relative to intravenous; lamivudine ~86%; tenofovir disoproxil fumarate ~25% (enhanced with high-fat meal). |
| Onset of Action | Oral: doravirine reaches therapeutic plasma concentrations within 2-4 hours; full virologic suppression occurs by 4-12 weeks. Lamivudine and tenofovir effects begin within hours; clinical antiviral effect measured by HIV RNA decline at 2-6 weeks. |
| Duration of Action | Duration of effective antiviral activity with once-daily dosing: doravirine maintains inhibitory concentrations for 24 hours; lamivudine and tenofovir provide sustained suppression. Clinical note: adherence is critical; missed doses allow viral rebound. |
One tablet (doravirine 100 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg) orally once daily with or without food.
| Dosage form | TABLET |
| Renal impairment | Not recommended in patients with creatinine clearance (CrCl) <50 mL/min. No dose adjustment for CrCl ≥50 mL/min. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended for severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Not recommended for pediatric patients weighing <35 kg. For patients ≥35 kg, same as adult dosing: one tablet orally once daily. |
| Geriatric use | No specific dose adjustment; use with caution due to age-related renal impairment. Monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DELSTRIGO (DELSTRIGO).
| Breastfeeding | Breastfeeding is not recommended in HIV-infected women to avoid postnatal transmission. Doravirine: unknown excretion in human milk; lamivudine: excreted in breast milk (M/P ratio ~0.6-1.1); tenofovir: excreted in breast milk (M/P ratio ~1.0). Potential for adverse effects in nursing infant. |
| Teratogenic Risk | Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) is classified as FDA Pregnancy Category B. Limited human data; animal studies show no evidence of teratogenicity. However, lamivudine and tenofovir have been associated with lactic acidosis and hepatotoxicity in pregnant women. First trimester: insufficient data to assess risk; second and third trimesters: no increased risk of major malformations reported in antiretroviral pregnancy registries. |
■ FDA Black Box Warning
WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing lamivudine and/or tenofovir disoproxil fumarate. Hepatic function should be monitored closely in these patients. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
| Serious Effects |
["Coadministration with drugs that are strong CYP3A4 inducers, as significant decreases in doravirine plasma concentrations may occur, potentially leading to loss of virologic response","Coadministration with drugs that highly depend on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious or life-threatening events"]
| Precautions | ["Risk of post-treatment acute exacerbation of hepatitis B (see boxed warning)","New onset or worsening renal impairment; tenofovir disoproxil fumarate can cause acute renal failure, Fanconi syndrome, and renal tubular disorders","Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of nucleoside analogues, including lamivudine and tenofovir disoproxil fumarate","Immune reconstitution syndrome, including autoimmune disorders","Risk of osteoporosis and osteomalacia with long-term tenofovir disoproxil fumarate use"] |
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| Fetal Monitoring | Monitor HIV viral load and CD4 count as per standard of care. Assess liver function and renal function (serum creatinine, estimated CrCl) due to tenofovir disoproxil fumarate. Monitor for lactic acidosis and hepatotoxicity. Perform fetal ultrasound as clinically indicated. Monitor infant for HIV serostatus and adverse effects. |
| Fertility Effects | No known adverse effects on fertility based on animal studies. In humans, no specific studies; lamivudine and tenofovir disoproxil fumarate are not associated with impaired fertility. |