RUKOBIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RUKOBIA (RUKOBIA).
RUKOBIA (fostemsavir) is a prodrug of temsavir, an HIV-1 attachment inhibitor that binds directly to the gp120 subunit of the viral envelope glycoprotein, preventing the initial attachment of the virus to the host CD4+ T-cell receptor.
| Metabolism | Fostemsavir is rapidly hydrolyzed by intestinal alkaline phosphatase to temsavir, which is primarily metabolized by CYP3A4 with minor contributions from CYP3A5 and CYP2D6. |
| Excretion | Fecal: ~87% (unchanged); Renal: ~13% (unchanged). |
| Half-life | Terminal elimination half-life is approximately 11–13 hours, supporting once-daily dosing. |
| Protein binding | Approximately 99–99.5% bound to plasma albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 5.7 L/kg, indicating extensive extravascular distribution into tissues. |
| Bioavailability | Oral bioavailability is approximately 35–40% under fed conditions (high-fat meal). |
| Onset of Action | Oral: Steady-state achieved within 2–4 days; clinical antiviral effect observed within 1 week. |
| Duration of Action | Duration of antiviral effect is 24 hours with once-daily dosing; maintaining trough concentrations above therapeutic threshold is critical. |
600 mg orally twice daily, co-administered with a ritonavir-boosted protease inhibitor and other antiretroviral agents, with or without food.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for use in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease as safety and efficacy have not been established. |
| Liver impairment | Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B or C). Use with caution in mild hepatic impairment (Child-Pugh class A), with no dose adjustment recommended. |
| Pediatric use | Not approved for use in pediatric patients younger than 18 years of age due to lack of safety and efficacy data. |
| Geriatric use | No specific dose adjustments recommended for elderly patients; clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently. Use with caution due to age-related renal and hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RUKOBIA (RUKOBIA).
| Breastfeeding | No data on presence in human milk; drug excreted in animal milk. Breastfeeding not recommended due to potential for HIV-1 transmission and unknown infant effects. |
| Teratogenic Risk | Insufficient human data; animal studies show no teratogenicity at clinically relevant exposures. Risk cannot be excluded; use only if benefit outweighs potential risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Coadministration with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)"]
| Precautions | ["Immune reconstitution syndrome","Risk of QT interval prolongation","Elevations in liver enzymes (especially in HBV/HCV coinfection)","Risk of embryo-fetal toxicity (based on animal studies)"] |
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| Monitor renal function, serum creatinine, and electrolytes during pregnancy. Assess for signs of hepatotoxicity. Perform HIV-1 RNA viral load and CD4 count at each trimester. |
| Fertility Effects | No human studies on fertility; animal studies show no impairment at clinically relevant doses. |