Dosing & Uses
Dosage Forms & 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
Dosage 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
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
Glioma (Orphan)
Orphan designation for treatment of glioma
Sponsor
- Laboratorio Italiano Biochimico Farmaceutico Lisapharma SpA; Via Licinio 11; Erba (CO), Italy
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (1)
- human parathyroid hormone, recombinant
zoledronic acid decreases effects of human parathyroid hormone, recombinant by Other (see comment). Contraindicated. Comment: Coadministration of bisphosphonates with rhPTH leads to reduction in rhPTH's calcium sparing effect, which can interfere with the normalization of serum calcium.
Serious - Use Alternative (0)
Monitor Closely (13)
- aluminum hydroxide
aluminum hydroxide decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.
- calcium acetate
calcium acetate decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 30 minutes.
- calcium carbonate
calcium carbonate decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 30 minutes.
- calcium chloride
calcium chloride decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 30 minutes.
- calcium citrate
calcium citrate decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 30 minutes.
- calcium gluconate
calcium gluconate decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 30 minutes.
- dichlorphenamide
dichlorphenamide and zoledronic acid both decrease serum potassium. Use Caution/Monitor.
- peramivir
zoledronic acid increases levels of peramivir by decreasing renal clearance. Use Caution/Monitor. Caution when peramivir coadministered with nephrotoxic drugs.
- sodium bicarbonate
sodium bicarbonate decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.
- sodium citrate/citric acid
sodium citrate/citric acid decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of zoledronic acid by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of zoledronic acid by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- voclosporin
voclosporin, zoledronic acid. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.
Minor (17)
- amikacin
amikacin, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- aspirin
aspirin decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- aspirin rectal
aspirin rectal decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- bumetanide
bumetanide, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- entecavir
zoledronic acid, entecavir. Either increases effects of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.
- ethacrynic acid
ethacrynic acid, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- foscarnet
foscarnet increases effects of zoledronic acid by pharmacodynamic synergism. Minor/Significance Unknown. Risk of severe hypocalcemia.
- furosemide
furosemide, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- gentamicin
gentamicin, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- indomethacin
indomethacin increases levels of zoledronic acid by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- neomycin PO
neomycin PO, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- paromomycin
paromomycin, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- streptomycin
streptomycin, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- teriparatide
teriparatide, zoledronic acid. Other (see comment). Minor/Significance Unknown. Comment: No advantage to bone density with combined treatment.
- tobramycin
tobramycin, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
- torsemide
torsemide, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
Adverse 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
Acqured Fanconi syndrome
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
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 & Lactation
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.Pharmacology
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)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| zoledronic acid intravenous - | 4 mg/5 mL vial |  | |
| zoledronic acid intravenous - | 4 mg/5 mL vial |  | |
| zoledronic acid intravenous - | 4 mg/5 mL vial |  | |
| zoledronic acid intravenous - | 4 mg/5 mL vial |  | |
| zoledronic acid intravenous - | 4 mg/5 mL vial |  | |
| zoledronic acid intravenous - | 4 mg vial |  | |
| zoledronic acid intravenous - | 4 mg/5 mL vial |  | |
| zoledronic acid intravenous - | 4 mg/5 mL vial |  | |
| zoledronic acid intravenous - | 4 mg/5 mL vial |  |
Copyright © 2010 First DataBank, Inc.
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