Dosing and uses of Reclast, Zometa (zoledronate)
Adult dosage forms and strengths
IV injectable solution
- 4mg/5mL (5mL)
- 5mg/100mL
Hypercalcemia of Malignancy
Zometa: No more than 4 mg IV (infused over >15 minutes) once; may be repeated in 7 days
Monitor serum calcium, and wait at least 7 days before considering retreatment
Multiple Myeloma; Bone Metastases From Solid Tumors
Zometa: 4 mg IV (infused over >15 minutes) every 3-4 weeks
Osteoporosis
Reduction in incidence of fractures (hip, vertebral, and nonvertebral osteoporosis-related fractures)
Prevention in postmenopausal women
- Reclast: 5 mg IV over >5 minutes every 2 years
Treatment in men and postmenopausal women
- Reclast: 5 mg IV over >15 minutes every year
Glucocorticoid-Induced Osteoporosis
Treatment and prevention
Reclast: 5 mg IV over >15 minutes every year; supplemented with elemental calcium and vitamin d
Paget Disease
Reclast: 5 mg IV over >15 minutes once; supplemented with elemental calcium and vitamin d
Complex Regional Pain Syndrome (Orphan)
Orphan designation for treatment of complex regional pain syndrome (CRPS)
Sponsors
- Axsome Therapeutics, Inc.; 45 Rockefeller Plaza, Suite 2000; New York, NY 10111
- Thar Pharmaceuticals; 150 Gamma Drive; Pittsburgh, PA 15238
Dosing Modifications
Renal impairment (Zometa)
- CrCl >60 mL/min: 4 mg
- CrCl 50-60 mL/min: 3.5 mg
- CrCl 40-49 mL/min: 3.3 mg
- CrCl 30-39 mL/min: 3 mg
- CrCl <30 mL/min: Not recommended
Renal impairment (Reclast)
- CrCl >35 mL/min: No adjustment needed
- CrCl <35 mL/min: Contraindicated
Hepatic impairment
- Safety and efficacy not established
Pediatric dosage forms and strengths
Safety and efficacy not established
Reclast, Zometa (zoledronate) adverse (side) effects
>10%
Bone pain (55%)
Nausea (29-46%)
Fever (32-44%)
Fatigue (39%)
Anemia (22-33%)
Vomiting (14-32%)
Constipation (27-31%)
Dyspnea (22-27%)
Diarrhea (17-24%)
Anorexia (9-22%)
Arthralgia (5-21%)
Headache (5-19%)
Dizziness (18%)
Insomnia (15-16%)
Urinary tract infection (UTI; 12-14%)
Anxiety (11-14%)
Hypophosphatemia (5-14%)
Hypokalemia (12%)
Hypotension (11%)
Hypomagnesemia (11%)
Rash (11%)
Frequency not defined
Ocular inflammation (eg, uveitis, scleritis, episcleritis, conjunctivitis, iritis, orbital inflammation)
Postmarketing Reports
Ocular: Uveitis, scleritis, episcleritis, conjunctivitis, iritis, blurred vision, orbital inflammation (including orbital edema)
CNS: Taste disturbance, hyperesthesia, tremor
GI: Dry mouth
Skin: Increased sweating
Musculoskeletal: Muscle cramps, osteonecrosis of jaw, pain, atypical subtrochanteric and diaphyseal femoral fractures
Osteonecrosis of other bones including femur, hip, knee, ankle, wrist and humerus
Cardiovascular: Hypertension, bradycardia, hypotension (associated with syncope or circulatory collapse, primarily in patients with underlying risk factors)
Acute-phase reaction (≤3 days after administration) with symptoms including pyrexia, fatigue, bone pain or arthralgias, myalgias, chills, flulike illness, arthritis with subsequent joint swelling
Hypersensitivity: Bronchoconstriction or bronchospasm, interstitial lung disease, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis
Renal: Hematuria, proteinuria
General disorders and administration site: Weight increase, flulike illness (pyrexia, asthenia, fatigue or malaise) persisting for >30 days
Laboratory abnormalities: Hyperkalemia, hypernatremia
Warnings
Contraindications
Pregnancy
All indications: Hypersensitivity, including rare cases of urticaria, angioedema, and anaphylactic reaction or shock
Nononcologic uses: Hypocalcemia, severe renal impairment (CrCl <35 mL/min or evidence of acute renal impairment)
Cautions
Assess renal function before and after treatment; if renal function is decreased after treatment, withhold additional treatment until it returns to within 10% of baseline
Before each Reclast dose, calculate CrCl on basis of actual body weight, using Cockcroft-Gault formula
Other risks for renal impairment include coadministration of zoledronic acid with nephrotoxic or diuretic medications, severe dehydration before or after zoledronic acid administration, and advanced age
Previous renal insufficiency (serum creatinine >3 mg/dL [265 mmol/L]), hepatic insufficiency, musculoskeletal pain
Infuse over ≥15 minutes; faster infusion increases renal toxicity
May cause significant risk of hypocalcemia (seizures, tetany, and numbness); hypocalcemia must be corrected before initiation of therapy; adequately supplement patients with calcium and vitamin D; monitor serum calcium closely with concomitant administration of other drugs known to cause hypocalcemia to avoid severe or life-threatening hypocalcemia
Use with caution in aspirin-sensitive asthma; may cause bronchoconstriction
Increased risk of osteonecrosis of jaw (advise patients against dental work); reported predominantly in cancer patients treated with IV bisphosphonates, including zoledronic acid; many patients were also receiving chemotherapy and corticosteroids which may be risk factors; risk may increase with duration of exposure to bisphosphonates; perform preventive dental exams before initiating therapy; avoid invasive dental procedures; monitor diabetic patients carefully
Risk of osteonecrosis of the jaw may increase with duration of exposure to bisphosphonates
Possible increased risk for atypical subtrochanteric and diaphyseal femur fractures; consider periodic reevaluation of need for continued bisphosphonate therapy, particularly if treatment lasts >5 years
If patients are receiving Zometa, they should not receive Reclast
Severe bone, joint, and muscle pain may occur; withhold future doses of zoledronic acid if severe symptoms occur
Rehydrate patients with hypercalcemia of malignancy prior to administration of zoledronic acid injection and monitor electrolytes during treatment
Women of childbearing age should be advised of potential hazard to fetus and avoid becoming pregnant
Femur Fractures reported; patients with thigh or groin pain should be evaluated to rule out a femoral fracture
Severe bone, joint, and muscle pain may occur; withhold future doses of reclast if severe symptoms occur
Pregnancy and lactation
Pregnancy category: d
Lactation: Unknown whether drug crosses into breast milk; avoid using
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Reclast, Zometa (zoledronate)
Mechanism of action
Bisphosphonate; inhibits bone resorption via actions on osteoclast activity, leading to indirect increase in bone density
Absorption
Onset: Hypercalcemia of malignancy, 4-7 days; osteolytic bone metastases, 1 week
Duration: 32 days
Distribution
Protein bound: 28-53%
Metabolism
Not metabolized
Elimination
Half-life: 146 hr (terminal)
Renal clearance: 66 mL/min
Total body clearance: 5.6 L/hr
Excretion: Urine (39% as unchanged drug) within 24 hr, feces (<3%)
Administration
IV Incompatibilities
Calcium-containing solutions
IV Preparation
Zometa: Reconstitute powder with 5 mL SWI; once powder is fully dissolved, dilute further in 100 mL NS or D5W before administering
Infusion of solution must be completed within 24 hours of initial reconstitution
IV Administration
Zometa: Infuse over ≥15 minutes, in line separate from other medications
Reclast: Infuse over ≥15 minutes, using ready-to-use infusion solution
Ensure appropriate hydration, especially in patients on diuretics
Storage
Zometa: Before dilution, store vials at 25°C (77°F); after final dilution, use solution immediately or store at 2-8°C (36-46°F)
Reclast: Store at 25°C (77°F)
