Reclast - Drug Monograph

Introduction

Reclast (zoledronic acid) is a bisphosphonate medication administered as a once-yearly intravenous infusion for the treatment of osteoporosis. It belongs to a class of drugs that inhibit bone resorption and is specifically formulated for intravenous use, distinguishing it from oral bisphosphonates.

Mechanism of Action

Zoledronic acid works by inhibiting osteoclast-mediated bone resorption. It binds to hydroxyapatite in bone tissue and is internalized by osteoclasts, where it inhibits farnesyl pyrophosphate synthase in the mevalonate pathway. This disruption prevents the prenylation of GTP-binding proteins essential for osteoclast function, ultimately leading to osteoclast apoptosis and reduced bone turnover.

Indications

• Treatment of osteoporosis in postmenopausal women and men
• Treatment and prevention of glucocorticoid-induced osteoporosis
• Treatment of Paget's disease of bone
• Prevention of new clinical fractures in patients with recent low-trauma hip fracture

Dosage and Administration

• Osteoporosis: 5 mg IV infusion over at least 15 minutes once yearly
• Paget's disease: 5 mg IV infusion over at least 15 minutes as a single dose
• Administration: Must be diluted in 100 mL of 0.9% sodium chloride or 5% dextrose solution
• Renal impairment: Not recommended for patients with CrCl <35 mL/min
• Hydration: Patients should be adequately hydrated before administration

Pharmacokinetics

• Absorption: 100% bioavailable via IV administration
• Distribution: Binds extensively to bone tissue (approximately 43% of dose)
• Metabolism: Not metabolized hepatically
• Elimination: Primarily renal excretion as unchanged drug
• Half-life: Biphasic - initial half-life of 0.24 hours and terminal half-life of 146 hours
• Protein binding: Approximately 22% plasma protein binding

Contraindications

• Hypersensitivity to zoledronic acid or other bisphosphonates
• Hypocalcemia
• Severe renal impairment (CrCl <35 mL/min)
• Pregnancy and breastfeeding

Warnings and Precautions

• Renal impairment: Monitor renal function before each dose
• Hypocalcemia: Correct hypocalcemia before initiation
• Osteonecrosis of the jaw: Risk increases with duration of therapy
• Atypical femoral fractures: Monitor for thigh/groin pain
• Atrial fibrillation: Observe for cardiac arrhythmias
• Ocular inflammation: May cause uveitis, scleritis, or episcleritis
• Acute phase reaction: Common after first infusion (fever, myalgia, arthralgia)

Drug Interactions

• Aminoglycosides: Increased risk of hypocalcemia
• Loop diuretics: Enhanced calcium-lowering effects
• Nephrotoxic drugs: Increased risk of renal impairment
• Calcium supplements: May interfere with absorption if administered concurrently

Adverse Effects

• Fever
• Myalgia
• Arthralgia
• Headache
• Fatigue
• Nausea

• Acute renal failure
• Osteonecrosis of the jaw
• Atypical femoral fractures
• Severe hypocalcemia
• Atrial fibrillation
• Ocular inflammation

Monitoring Parameters

• Baseline: Serum creatinine, calcium, phosphorus, magnesium, 25-hydroxyvitamin D
• During therapy: Renal function before each infusion
• Periodic: Serum calcium and vitamin D levels
• Dental health: Regular dental examinations
• Bone density: DEXA scans every 1-2 years
• Symptoms: Monitor for thigh/groin pain, jaw pain, or ocular symptoms

Patient Education

• Importance of adequate calcium (1200 mg daily) and vitamin D (800-1000 IU daily) intake
• Report any jaw pain, dental problems, or thigh/groin pain immediately
• Maintain good oral hygiene and regular dental care
• Stay upright for at least 30 minutes after infusion to reduce risk of renal complications
• Understand potential acute phase reaction symptoms after first infusion
• Inform all healthcare providers about Reclast therapy before any dental procedures

References

1. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809-1822. 2. Reid IR, Brown JP, Burckhardt P, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002;346(9):653-661. 3. Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357(18):1799-1809. 4. Reclast (zoledronic acid) prescribing information. Novartis Pharmaceuticals Corporation. 5. Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357(20):2028-2039. 6. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015;30(1):3-23.