TANDEARIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TANDEARIL (TANDEARIL).
ACE inhibitor; inhibits angiotensin-converting enzyme, reducing angiotensin II production, leading to vasodilation and decreased aldosterone secretion.
| Metabolism | Primarily hepatic via glucuronidation and ester hydrolysis; active metabolite enalaprilat. Minimal CYP450 involvement. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 60% of elimination; biliary/fecal excretion accounts for 35%, with the remainder as metabolites. |
| Half-life | Terminal elimination half-life is 45 hours, allowing once-daily dosing; steady-state achieved in 7-10 days. |
| Protein binding | 99.5% bound, primarily to albumin; also binds to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2 L/kg, indicating distribution primarily in extracellular fluid; higher in inflammatory states. |
| Bioavailability | Oral: 90%; Topical: 15% (systemic absorption negligible); Rectal: 80%. |
| Onset of Action | Oral: 2-4 hours; Intravenous: 15-30 minutes; Topical: 1-2 hours. |
| Duration of Action | Oral: 24 hours; Intravenous: 8-12 hours; Topical: 6-8 hours; clinical effect may outlast plasma levels due to tissue binding. |
200 mg orally twice daily with food.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: no adjustment. GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: contraindicated. |
| Pediatric use | Not recommended for use in children. Safety and efficacy not established. |
| Geriatric use | Start at 100 mg twice daily and titrate cautiously due to increased risk of renal and hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TANDEARIL (TANDEARIL).
| Breastfeeding | Excreted in breast milk; M/P ratio unknown. Contraindicated in breastfeeding due to potential for serious adverse effects in infants, including gastrointestinal bleeding, renal impairment, and bone marrow suppression. |
| Teratogenic Risk | Tandearil (oxyphenbutazone) is contraindicated in all trimesters. First trimester: Associated with congenital heart defects, cleft palate, and neural tube defects due to prostaglandin synthesis inhibition. Second trimester: Risk of oligohydramnios and fetal renal dysfunction. Third trimester: High risk of premature closure of ductus arteriosus, persistent pulmonary hypertension of the newborn, and bleeding complications due to platelet inhibition. |
■ FDA Black Box Warning
Fetal toxicity: Use during pregnancy can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Serious Effects |
Hypersensitivity to any ACE inhibitor, history of ACE inhibitor-induced angioedema, concomitant use with aliskiren in patients with diabetes mellitus, pregnancy.
| Precautions | Angioedema (higher risk in Black patients), hypotension (especially in volume-depleted patients), hyperkalemia, renal impairment (monitor renal function), cough, and rare hepatotoxicity. Avoid concomitant use with aliskiren in patients with diabetes or renal impairment. |
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| Fetal Monitoring | If inadvertently used during pregnancy, monitor fetal ultrasound for structural anomalies, amniotic fluid index, and ductus arteriosus patency (Doppler echocardiography). Maternal monitoring for signs of gastrointestinal bleeding, renal function, and complete blood count. |
| Fertility Effects | May impair female fertility due to inhibition of prostaglandin synthesis, affecting ovulation and implantation. Reversible upon discontinuation. Male fertility may also be affected by altered sperm function. |