TARPEYO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TARPEYO (TARPEYO).
TARPEYO (budesonide) is a corticosteroid with anti-inflammatory activity. It acts by binding to the glucocorticoid receptor, leading to inhibition of pro-inflammatory cytokines and immune cell activation, thereby reducing proteinuria in IgA nephropathy.
| Metabolism | Primarily hepatic via CYP3A4 to 16α-hydroxyprednisolone and 6β-hydroxybudesonide, which are less active. Extensive first-pass metabolism. |
| Excretion | Primarily hepatic metabolism, with <1% excreted unchanged in urine and <1% in feces. Elimination is predominantly via biliary excretion of metabolites into feces, accounting for >90% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 27.3 hours (range 21-36 hours) in patients with IgA nephropathy. This supports once-weekly subcutaneous dosing without dose adjustment over the dosing interval. |
| Protein binding | Approximately 88% bound to human serum albumin. Binding is reversible and saturable at supratherapeutic concentrations. |
| Volume of Distribution | Approximately 0.35 L/kg (range 0.3-0.4 L/kg). This low Vd indicates limited extravascular distribution, consistent with high protein binding and localization primarily in the vascular space. |
| Bioavailability | Subcutaneous: approximately 72% (range 60-85%) relative to intravenous administration. Absorption is slow, with peak concentrations at 24-48 hours post-dose. |
| Onset of Action | Subcutaneous administration: Clinical effect (reduction in proteinuria) observed within 2-4 weeks after initiating therapy. Maximum effect may take up to 8-12 weeks. |
| Duration of Action | Pharmacodynamic effect (immunosuppression) persists for approximately 2 weeks following the last dose, based on suppression of lymphocyte counts and clinical parameters. Repeat dosing is required for sustained effect. |
16 mg/kg intravenously once daily on Days 1-5 of each 28-day cycle.
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce dose to 12 mg/kg. Not studied in dialysis. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 12 mg/kg. Child-Pugh C: Use is not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TARPEYO (TARPEYO).
| Breastfeeding | Budesonide is excreted in human breast milk in low amounts. The milk-to-plasma ratio is approximately 0.37-0.5. At therapeutic maternal doses, no adverse effects on the nursing infant are expected. Caution is advised, especially with high maternal doses or prolonged use. |
| Teratogenic Risk | TARPEYO (budesonide) is a corticosteroid. Based on animal studies, there is a risk of teratogenicity (cleft palate, skeletal abnormalities) at high doses. In humans, inhaled or intranasal corticosteroids are generally considered low risk, but oral corticosteroids have been associated with an increased risk of oral clefts at first trimester exposure. For TARPEYO, a glucocorticoid with minimal systemic bioavailability, the risk is likely low. However, adequate human studies are lacking. Use during pregnancy only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to budesonide or any component of the formulation","Severe hepatic impairment"]
| Precautions | ["Hypercorticism and adrenal suppression due to systemic corticosteroid effects","Increased risk of infections, including reactivation of latent infections","Masking of signs of infection","Reduced bone mineral density with long-term use","Increased intraocular pressure and glaucoma","Potential for corticosteroid-induced psychiatric disturbances","Patients switching from other systemic corticosteroids may experience withdrawal symptoms"] |
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| Fetal Monitoring | Monitor maternal blood pressure, blood glucose, and signs of infection due to corticosteroid effects. For the fetus, routine prenatal care with ultrasound monitoring for growth and anatomy is recommended due to potential risk of intrauterine growth restriction with prolonged corticosteroid use. |
| Fertility Effects | No specific studies on TARPEYO and fertility. Corticosteroids may affect menstrual cycle and sperm motility at high doses, but clinically significant effects at intended doses are unlikely. In animal studies, no impairment of fertility was observed at doses up to 4 times the maximum recommended human dose. |