RECLAST
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RECLAST (RECLAST).
Inhibits osteoclast-mediated bone resorption by binding to hydroxyapatite in bone and inhibiting farnesyl diphosphate synthase (FPPS), a key enzyme in the mevalonate pathway, leading to disruption of osteoclast activity and induction of apoptosis.
| Metabolism | Not metabolized; excreted unchanged primarily by the kidneys via glomerular filtration and tubular secretion. |
| Excretion | Primarily renal; unchanged drug is excreted in urine. Approximately 50% of an absorbed dose is excreted unchanged in urine within 24 hours. The remainder is eliminated via renal excretion over an extended period, with negligible fecal or biliary elimination. |
| Half-life | The terminal elimination half-life of zoledronic acid in plasma is approximately 146 hours (range 76-250 hours) due to slow release from bone. Clinically, this supports a once-yearly dosing interval for osteoporosis. |
| Protein binding | Approximately 22-40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Steady-state volume of distribution is approximately 0.92-1.42 L/kg, indicating extensive distribution into bone and other tissues. |
| Bioavailability | Intravenous: 100% bioavailability. Oral: Not applicable due to negligible oral absorption (<0.1%). |
| Onset of Action | Intravenous: Suppression of bone resorption occurs within 24-48 hours, with significant reductions in bone turnover markers observed by 3 days. |
| Duration of Action | Single IV dose: Pharmacodynamic effect on bone turnover markers persists for at least 12 months, supporting annual dosing. Effects on fracture risk reduction last for at least 3 years with continued annual administration. |
5 mg intravenously over at least 15 minutes once yearly for osteoporosis.
| Dosage form | INJECTABLE |
| Renal impairment | Not recommended if CrCl <35 mL/min; no adjustment needed for CrCl >=35 mL/min. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment; not studied in severe impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No dose adjustment based on age alone; consider renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RECLAST (RECLAST).
| Breastfeeding | Zoledronic acid is excreted in human milk at low concentrations; M/P ratio is not established. Potential for bone growth suppression in the infant due to calcium binding. Consider the need for the drug and the infant's health; avoid breastfeeding due to unknown long-term effects. |
| Teratogenic Risk | RECLAST (zoledronic acid) is a pregnancy category D drug. In animal studies, maternal toxicity led to fetal skeletal and visceral abnormalities. Human data are limited, but bisphosphonates may cause fetal harm due to inhibition of bone resorption and potential hypocalcemia. First trimester exposure carries risk of skeletal developmental anomalies; second and third trimester exposure may cause fetal skeletal abnormalities and neonatal hypocalcemia. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
Zoledronic acid (RECLAST) is not recommended for use in patients with severe renal impairment (CrCl <35 mL/min) due to increased risk of renal failure. Patients should be assessed for hypocalcemia before initiating therapy. Atypical femur fractures have been reported.
| Serious Effects |
["Hypersensitivity to zoledronic acid or any component of the formulation","Hypocalcemia (uncorrected)","Severe renal impairment (CrCl <35 mL/min or evidence of acute renal impairment)","Pregnancy (Category D; potential fetal harm)"]
| Precautions | ["Renal toxicity: Monitor renal function, especially in patients with pre-existing renal disease or those receiving nephrotoxic agents","Hypocalcemia: Correct pre-existing hypocalcemia before initiation; ensure adequate calcium and vitamin D intake","Osteonecrosis of the jaw (ONJ): Risk with dental procedures; perform dental exam before therapy","Atypical femur fractures: May occur with long-term use; evaluate thigh or groin pain","Severe musculoskeletal pain: May occur rarely","Flu-like symptoms: Common after first infusion; may be managed with acetaminophen or ibuprofen"] |
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| Fetal Monitoring | Monitor serum calcium, phosphate, magnesium, and renal function before and during treatment. Assess for signs of hypocalcemia (e.g., tetany, arrhythmias). Fetal growth and skeletal development should be monitored by ultrasound during pregnancy. Neonates should be monitored for hypocalcemia and skeletal abnormalities after delivery. |
| Fertility Effects | In animal studies, zoledronic acid caused impaired fertility at high doses due to ovarian and uterine changes. Human data insufficient; potential for reversible ovarian dysfunction. Advise women of childbearing age about fertility considerations and use effective contraception during treatment. |