zoledronic acid (Rx)

>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

Acqured Fanconi syndrome

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

Cases of osteonecrosis (primarily involving the jaw but also of other anatomical sites including hip, femur and external auditory canal) reported predominantly in cancer patients

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

There are no available data in pregnant women to inform the drug-associated risk

Bisphosphonates are incorporated into bone matrix and are gradually released over periods of weeks to years; there may be a risk of fetal harm (e.g., skeletal and other abnormalities) if a woman becomes pregnant after completing a course of bisphosphonate therapy; advise pregnant women and females of reproductive potential of the potential risk to a fetus

Verify pregnancy status of females of reproductive potential prior to initiation of therapy

Therapy can cause fetal harm when administered to a pregnant woman; drug binds to bone long term and may be released over weeks to years; advise females of reproductive potential to use effective contraception during and after therapy

Based on animal studies, therapy may impair fertility in females of reproductive potential

Animal data

• Based on findings from animal studies and its mechanism of action, drug can cause fetal harm when administered to a pregnant woman; in animal reproduction studies, administration of drug to pregnant rats during organogenesis resulted in fetal malformations and embryo-fetal lethality at maternal exposures that were greater than or equal to 2.4 times the human clinical exposure based on AUC

Lactation

Not known whether drug is present in human milk, or whether it affects milk production, or breastfed child; drug binds to bone long term and may be released over weeks to years

Consider developmental and health benefits of breast-feeding along with the mother’s clinical need for therapy and any potential adverse effects on breast-fed child from drug or from underlying maternal condition

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.

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%)

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)