Zoledronic Acid

• Osteoporosis
• Paget's Disease
• Bone Metastases
• Hypercalcemia of Malignancy

Zoledronic acid is a potent nitrogen-containing bisphosphonate used for various bone-related conditions including osteoporosis, Paget's disease, hypercalcemia of malignancy, and bone metastases. It is administered intravenously and provides long-lasting effects.

Mechanism of Action

Zoledronic acid inhibits osteoclast-mediated bone resorption:

• Binds to hydroxyapatite: Concentrates at sites of active bone turnover
• Inhibits farnesyl pyrophosphate synthase: Key enzyme in mevalonate pathway
• Disrupts osteoclast function: Prevents prenylation of small GTPases essential for osteoclast activity
• Induces osteoclast apoptosis: Results in reduced bone resorption
• Most potent bisphosphonate: Higher binding affinity and longer duration than other bisphosphonates

Available Formulations

• Reclast: 5 mg/100 mL (for osteoporosis, Paget's disease)
• Zometa: 4 mg/5 mL concentrate, 4 mg/100 mL premixed (for oncology indications)

Different formulations are NOT interchangeable.

Medical Uses

FDA-Approved Indications:

Reclast (5 mg annually):

• Treatment and prevention of postmenopausal osteoporosis
• Treatment of osteoporosis in men
• Treatment and prevention of glucocorticoid-induced osteoporosis
• Paget's disease of bone

Zometa (4 mg):

• Hypercalcemia of malignancy
• Bone metastases from solid tumors (with standard antineoplastic therapy)
• Multiple myeloma bone disease

Dosing Guidelines

Osteoporosis (Reclast):

• 5 mg IV once yearly (treatment)
• 5 mg IV every 2 years (prevention)
• Infuse over at least 15 minutes

Paget's Disease (Reclast):

• 5 mg IV as a single dose
• Retreatment may be considered after 12 months

Hypercalcemia of Malignancy (Zometa):

• 4 mg IV over at least 15 minutes
• Consider retreatment after 7 days if needed

Bone Metastases/Multiple Myeloma (Zometa):

• 4 mg IV every 3-4 weeks
• Infuse over at least 15 minutes

Important Safety Information

Contraindications:

• Hypocalcemia (correct before administration)
• CrCl <35 mL/min (osteoporosis) or as specified for oncology
• Known hypersensitivity to zoledronic acid or bisphosphonates

Warnings and Precautions:

• Acute phase reactions: Flu-like symptoms common after first dose; usually self-limited
• Hypocalcemia: May occur; supplement with calcium and vitamin D
• Renal impairment: Assess before each dose; hydrate adequately
• Osteonecrosis of the jaw: Risk with dental procedures; consider dental exam before starting
• Atypical femur fractures: Risk with prolonged bisphosphonate use
• Severe bone, joint, and muscle pain: May occur at any time

Drug Interactions

• Aminoglycosides: Additive hypocalcemia effect
• Loop diuretics: May increase hypocalcemia risk
• Nephrotoxic drugs: Increased risk of renal impairment
• NSAIDs: May increase GI adverse effects

Special Populations

• Hepatic Impairment: No adjustment needed
• Renal Impairment: Reclast contraindicated if CrCl <35 mL/min; Zometa requires dose adjustments
• Pregnancy: May cause fetal harm; contraindicated
• Lactation: Not recommended
• Pediatric: Not approved for children
• Elderly: Ensure adequate renal function; hydrate well