TEZRULY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TEZRULY (TEZRULY).
Tezrul is a small molecule inhibitor of the human immunodeficiency virus (HIV) integrase enzyme, blocking the integration of viral DNA into the host genome. It also inhibits the HIV protease enzyme at higher concentrations, disrupting viral maturation.
| Metabolism | Hepatic via CYP3A4 and CYP2D6; also undergoes UGT1A1-mediated glucuronidation. Tezrul is a moderate inducer of CYP3A4 and a weak inhibitor of CYP2D6. |
| Excretion | Primarily excreted unchanged in urine via glomerular filtration and active tubular secretion; renal clearance accounts for approximately 80% of total clearance, with fecal elimination as a minor route (~15%). |
| Half-life | Terminal elimination half-life is approximately 12 hours, supporting once-daily dosing; steady-state is achieved within 2-3 days. |
| Protein binding | Approximately 92% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.35 L/kg, indicating distribution primarily into extracellular fluid and minimal tissue binding. |
| Bioavailability | Subcutaneous: Absolute bioavailability is 75-90% after SC administration, with no significant food effect. |
| Onset of Action | Subcutaneous: Onset of action occurs within 1-2 hours post-dose; peak effect on blood glucose reduction is observed at 4-6 hours. |
| Duration of Action | Duration of action is approximately 24 hours, consistent with once-daily dosing; effects on glycemic control persist for the full dosing interval. |
150 mg subcutaneously once every 4 weeks. Initiate with a single loading dose of 150 mg.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²) or ESRD; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe (Child-Pugh B or C); use with caution. |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment recommended. Limited data in patients ≥65 years; monitor for adverse effects due to potential age-related renal or hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TEZRULY (TEZRULY).
| Breastfeeding | Not known if excreted in human milk; M/P ratio not available. Caution recommended; consider developmental and health benefits of breastfeeding along with maternal need for drug. |
| Teratogenic Risk | First trimester: No adequate human data; animal studies show no teratogenicity at clinically relevant doses. Second/third trimester: No known risks; however, limited human data available. Overall risk cannot be excluded. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Absolute: Coadministration with rifampin, St. John's wort, or certain anticonvulsants (e.g., carbamazepine, phenytoin) due to significant reduction in tezrul exposure.","Relative: Severe hepatic impairment (Child-Pugh class C); use only if benefits outweigh risks."]
| Precautions | ["Hepatotoxicity: Elevations in liver enzymes have been observed; monitor hepatic function at baseline and periodically.","Lipodystrophy: May cause redistribution/accumulation of body fat.","Immune reconstitution syndrome: Inflammatory response to indolent or residual opportunistic infections.","Drug interactions: Contraindicated with drugs highly dependent on CYP3A4 for clearance, as reduced efficacy may occur."] |
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| Monitor for maternal adverse effects; fetal monitoring not specifically required but standard prenatal care applies. |
| Fertility Effects | No human data on fertility; animal studies show no impairment at clinically relevant doses. |