TEZRULY
Clinical safety rating
cautionComprehensive clinical and safety monograph for TEZRULY (TEZRULY).
Comprehensive clinical and safety monograph for TEZRULY (TEZRULY).
FDA-approved: Treatment of HIV-1 infection in combination with other antiretroviral agents in treatment-experienced adults with multidrug-resistant HIV-1 infection.Off-label: HIV-1 pre-exposure prophylaxis (PrEP) in high-risk populations (limited data).
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. |
| Molecular Weight | 150000 |
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 | No adequate human data; animal studies show fetal harm. Contraindicated in pregnancy. |
| 2nd trimester | No adequate human data; animal studies show fetal harm. Contraindicated in pregnancy. |
| 3rd trimester | No adequate human data; animal studies show fetal harm. Contraindicated in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for TEZRULY (TEZRULY).
| Placental transfer | Based on molecular weight (approximately 1500 Da) and animal studies, tezepelumab is expected to cross the placenta, especially during the second and third trimesters. |
| Breastfeeding | Not recommended during breastfeeding. No data on presence in human milk. Because of the potential for serious adverse reactions in the breastfed infant, women should not breastfeed during treatment and for at least 5 months after the last dose. |
| Lactation Rating | L5 |
| 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 | 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. |
■ FDA Black Box Warning
None
| Serious Effects |
History of anaphylaxis to tezepelumab or any excipient
| 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. |
| Food/Dietary | No specific food interactions reported. Take without regard to meals. |
| Clinical Pearls | Tezrully (tezepelumab-ekko) is a first-in-class thymic stromal lymphopoietin (TSLP) antagonist for severe asthma. Monitor for hypersensitivity reactions, including anaphylaxis. Do not use for acute asthma exacerbations. Administer subcutaneously every 4 weeks; no dose adjustment for renal/hepatic impairment. May reduce exacerbations independent of eosinophil count. |
| Patient Advice | This medication is given as an injection under the skin every 4 weeks. · Do not use to treat sudden asthma attacks; use your rescue inhaler as needed. · Seek immediate medical help if you have signs of allergic reaction like rash, hives, swelling, or trouble breathing. · Store in refrigerator (36-46°F) in original carton; protect from light. Do not freeze or shake. · Tell your healthcare provider about all medicines, including over-the-counter and herbal supplements. · You may not notice immediate improvement; continue regular asthma medications as prescribed. |
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