SELZENTRY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SELZENTRY (SELZENTRY).
Selective CCR5 receptor antagonist; blocks HIV-1 entry by binding to the chemokine receptor CCR5 on CD4+ T cells, preventing viral gp120 from interacting with the receptor.
| Metabolism | Hepatic via CYP3A4, CYP3A5, and CYP2C9; also a substrate of P-glycoprotein. |
| Excretion | Primarily hepatobiliary and fecal: ~76% of dose recovered in feces as parent drug and metabolites; renal elimination minor (~8-10% of dose in urine, mostly as metabolites). |
| Half-life | Terminal elimination half-life is approximately 2-3 hours (single dose), but due to irreversible binding to CCR5, pharmacodynamic half-life is 2-4 days. Clinical context: Twice-daily dosing maintains CCR5 blockade. |
| Protein binding | 76% bound to human plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Approximately 1.2 L/kg (range 0.8-1.5 L/kg), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability: 23% (with high-fat meal) to 33% (fasted). |
| Onset of Action | Not applicable (NA) – Selzentry is not used for acute effects; therapeutic effect requires steady-state concentrations (achieved in ~3-5 days). |
| Duration of Action | Duration of CCR5 blockade: ~2-4 days after single dose; clinical effect persists with continued dosing. |
150 mg orally twice daily, 300 mg orally twice daily, or 600 mg orally twice daily depending on concomitant medications; must be adjusted for CYP3A inducers or inhibitors.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment recommended for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min) or end-stage renal disease (ESRD) on dialysis, the recommended dose is 150 mg twice daily regardless of concomitant medications; use with caution and monitor for increased adverse effects. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). For mild to moderate hepatic impairment (Child-Pugh A or B), no dosage adjustment is required, but use with caution. |
| Pediatric use | Approved for children aged ≥2 years and weighing ≥10 kg. Weight-based dosing (oral solution 20 mg/mL): 10-<20 kg: 150 mg twice daily; 20-<40 kg: 225 mg twice daily; ≥40 kg: 300 mg twice daily. Adjust dose based on concomitant CYP3A inducers/inhibitors. |
| Geriatric use | No specific dose adjustment; however, monitor renal function closely (use CrCl-based dosing for severe renal impairment) and watch for age-related comorbidities and drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SELZENTRY (SELZENTRY).
| Breastfeeding | Present in rat milk; unknown in human milk. Caution advised; M/P ratio unknown. |
| Teratogenic Risk | Animal studies show no teratogenicity; no adequate human studies in pregnant women. Use only if potential benefit justifies risk to fetus. |
| Fetal Monitoring | Monitor for hypersensitivity reactions, liver function tests, and signs of infection. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Patients with CXCR4-tropic or dual/mixed-tropic HIV-1 infection (due to lack of efficacy).","Severe hepatic impairment (Child-Pugh class C) if CCR5 antagonist-naive."]
| Precautions | ["Hepatotoxicity including allergic hepatitis and hepatic failure; monitor liver function tests.","Risk of severe and potentially fatal hypersensitivity reactions (e.g., Stevens-Johnson syndrome).","Increased risk of cardiovascular events (e.g., myocardial infarction) in patients with underlying cardiovascular disease.","Hepatic impairment: dose adjustment required for severe impairment (Child-Pugh class C).","Risk of immune reconstitution syndrome and opportunistic infections."] |
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| Fertility Effects | No adverse effects on fertility observed in animal studies; no human data. |