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. |
| Molecular Weight | 1009.2 |
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 | Use only if potential benefit justifies risk; limited human data, animal studies show teratogenicity at high doses. |
| 2nd trimester | May cause fetal harm based on animal data; use if no safer alternative. |
| 3rd trimester | May cause fetal harm; avoid in third trimester unless essential. |
Clinical note
Comprehensive clinical and safety monograph for TARPEYO (TARPEYO).
| Placental transfer | Predicted to cross placenta based on molecular weight and animal studies; human data lacking. |
| Breastfeeding | Not recommended during breastfeeding due to potential for serious adverse reactions in the infant. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to budesonide or any componentSevere 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase budesonide systemic exposure. Take on an empty stomach (at least 1 hour before or 2 hours after a meal). No other specific dietary restrictions. |
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| 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. |
| 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. |
| Clinical Pearls | TARPEYO (budesonide) is a targeted-release formulation designed to deliver budesonide to the ileum. It is indicated for IgA nephropathy with proteinuria ≥1 g/day. Monitor renal function and blood pressure regularly. Glucocorticoid-related adverse effects (e.g., hyperglycemia, adrenal insufficiency) may occur despite local action. Taper dose gradually after prolonged use (≥3 weeks) to avoid adrenal crisis. Contraindicated in patients with severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take TARPEYO at least 1 hour before or 2 hours after a meal with a full glass of water. · Swallow capsules whole; do not crush, chew, or open them. · Do not take TARPEYO with grapefruit juice. · Report signs of infection, hyperglycemia (increased thirst, urination), or adrenal insufficiency (fatigue, weakness, nausea). · Do not stop TARPEYO abruptly; follow your doctor's tapering schedule. · Inform your doctor if you have liver problems or if you become pregnant. |