zoledronic acid

Contraindicated in:

Hypersensitivity to zoledronic acid or other bisphosphonates
Severe renal impairment (CCr <35 mL/min) or acute renal failure
Hypocalcemia (correct before administering); adequate supplemental calcium and vitamin D required
OB: Pregnancy (may cause fetal harm)

Use Cautiously in:

History of aspirin-induced asthma
Chronic renal impairment
Chronic renal impairment, concurrent use of diuretics or nephrotoxic drugs, or dehydration (↑ risk of renal impairment; correct deficits prior to use)
Concurrent use of nephrotoxic drugs
Invasive dental procedures, cancer, receiving chemotherapy, corticosteroids, or angiogenesis inhibitors, undergoing radiation, poor oral hygiene, periodontal disease, dental disease, anemia, coagulopathy, infection, or poorly-fitting dentures (may ↑ risk of jaw osteonecrosis)
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.
Pedi: Potential for long-term retention in bone in children; use only if potential benefit outweighs potential risk
Geri: ↑risk of renal impairment in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, chest pain, leg edema.

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, pruritus, rash.

EENT: conjunctivitis.

F and E: hypophosphatemia, hypocalcemia, hypokalemia, hypomagnesemia.

GI: abdominal pain, constipation, diarrhea, nausea, vomiting, dysphagia.

GU: ↓fertility (females), renal impairment/failure.

Hemat: anemia.

MS: musculoskeletal pain, femur fractures, osteonecrosis (primarily of jaw).

Neuro: agitation, anxiety, confusion, insomnia.

Resp: asthma exacerbation.

Misc: fever, flu-like syndrome.

Interactions ⬆ ⬇

Drug-Drug:

Concurrent use of loop diuretics, calcitonin, or aminoglycosides↑ risk of hypocalcemia.
Concurrent use of NSAIDs may ↑ risk of nephrotoxicity.

Route/Dosage ⬆ ⬇

Reclast

IV (Adults): Paget's disease — 5 mg as a single dose (information regarding retreatment unknown); Treatment of osteoporosis in men or postmenopausal women, treatment/prevention of glucocorticoid-induced osteoporosis — 5 mg once yearly; Prevention of osteoporosis in postmenopausal women — 5 mg every 2 yr.

Zometa

IV (Adults): Hypercalcemia of malignancy — 4 mg; may be repeated after 7 days; Multiple myeloma and bone metastases from solid tumors — 4 mg every 3–4 wk (has been used for up to 15 mo).

Implementation ⬆ ⬇

Vigorous saline hydration alone may be sufficient to treat mild, asymptomatic hypercalcemia. Adequate rehydration is required prior to administration.
- Patients on long-term therapy should have 1200 mg of oral calcium and 800–1000 units of Vitamin D each day.
- Patients treated for Paget's disease should receive 1500 mg elemental calcium and 800 IU of vitamin D daily, particularly during the 2 wk after dosing. Patients with osteoporosis should take 1200 mg of calcium and 800–1000 units of vitamin D daily. Patients with multiple myeloma and bone metastasis of solid tumors take an oral calcium supplement of 500 mg and a multiple vitamin containing 400 international units of vitamin D daily.
- Administration of acetaminophen or ibuprofen following administration may reduce the incidence of acute-phase reaction symptoms.

IV Administration:

Intermittent Infusion:
Rate: Administer as a single infusion over at least 15 min. Rapid infusions increase risk of renal deterioration and renal failure.
Y-Site Compatibility:
- acyclovir
- alfentanil
- allopurinol
- amifostine
- amikacin
- aminocaproic acid
- aminophylline
- amiodarone
- amphotericin B lipid complex
- amphotericin B liposome
- ampicillin
- ampicillin/sulbactam
- anidulafungin
- argatroban
- arsenic trioxide
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- busulfan
- butorphanol
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- chlorpromazine
- ciprofloxacin
- cisatracurium
- cisplatin
- clindamycin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin hydrochloride
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxorubicin liposomal
- doxycycline
- droperidol
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- eptifibatide
- ertapenem
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fenoldopam
- fentanyl
- fluconazole
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemcitabine
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hydralazine
- hydrocortisone
- hydromorphone
- idarubicin
- ifosfamide
- imipenem/cilastatin
- insulin, regular
- irinotecan
- isoproterenol
- ketorolac
- labetalol
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- melphalan
- meperidine
- meropenem
- mesna
- methadone
- methotrexate
- methylprednisolone
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- mitomycin
- mitoxantrone
- morphine
- moxifloxacin
- mycophenolate
- nafcillin
- nalbuphine
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- oxytocin
- paclitaxel
- pancuronium
- pantoprazole
- pemetrexed
- pentamidine
- pentobarbital
- phenobarbital
- phenylephrine
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- prochlorperazine
- promethazine
- propranolol
- quinupristin/dalfopristin
- remifentanil
- rocuronium
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- streptozocin
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiopental
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- topotecan
- trimethoprim/sulfamethoxazole
- vancomycin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
Y-Site Incompatibility:
- alemtuzumab
- calcium-containing solutions
- dantrolene
- diazepam
- gemtuzumab ozogamicin
- phenytoin.
Additive Incompatibility: Do not mix with solutions containing calcium, such as Lactated Ringer’s solution.

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Classifications ⬆ ⬇

Therapeutic Classification: bone resorption inhibitors, electrolyte modifiers, hypocalcemics

Pharmacologic Classification: biphosphonates

Availability ⬆ ⬇

(Generic available)

Premixed infusion (Reclast): 5 mg/100 mL;
Premixed infusion (Zometa): 4 mg/100 mL;
Solution for injection (Zometa): 0.8 mg/mL;

Time/Action Profile ⬆ ⬇

(effect on serum calcium)

ROUTE	ONSET	PEAK	DURATION
IV	within 4 days	4–7 days	30 days

Assessment ⬆ ⬇

Monitor intake and output ratios. Initiate a vigorous saline hydration promptly and maintain a urine output of 2 L/day during therapy. Patients should be adequately hydrated, but avoid overhydration. Do not use diuretics prior to treatment of hypovolemia.
Assess for acute-phase reaction (fever, myalgia, flu-like symptoms, headache, arthralgia). Usually occur within 3 days of dose and resolve within 3 days of onset, but may take 7–14 days to resolve; incidence decreases with repeat dosing.
Perform a routine oral exam prior to initiation of therapy. Dental exam with appropriate preventative dentistry should be considered prior to therapy. Patients with history of tooth extraction, poor oral hygiene, gingival infections, diabetes, cancer, receiving radiation, anemia, coagulopathy, or use of a dental appliance or those taking immunosuppressive therapy, angiogenesis inhibitors, or systemic corticosteroids are at greater risk for osteonecrosis of the jaw.
Hypercalcemia: Monitor symptoms of hypercalcemia (nausea, vomiting, anorexia, weakness, constipation, thirst, cardiac arrhythmias).
Observe for evidence of hypocalcemia (paresthesia, muscle twitching, laryngospasm, Chvostek’s or Trousseau’s sign).
Paget's Disease: Assess for symptoms of Paget's disease (bone pain, headache, decreased visual and auditory acuity, increased skull size) periodically during therapy.
Osteoporosis: Assess patients via bone density study for low bone mass before and periodically during therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor serum creatinine, calculated based on actual body weight using the Cockcroft-Gault formula, prior to each treatment. Patients with a normal serum creatinine prior to treatment, who develop an increase of 0.5 mg/dL within 2 wk of next dose should have next dose withheld until serum creatinine is within 10% of baseline value. Patients with an abnormal serum creatinine prior to treatment who have an increase of 1.0 mg/dL within 2 wk of next dose should have next dose withheld until serum creatinine is within 10% of baseline value.
- Assess serum calcium, phosphate, and magnesium before and periodically during therapy. If hypocalcemia, hypophosphatemia, or hypomagnesemia occur, temporary supplementation may be required. Hypocalcemia and vitamin D deficiency should be treated before initiating zoledronic acid therapy.
- Monitor CBC with differential and hemoglobin and hematocrit closely during therapy.
- Paget's Disease: Monitor serum alkaline phosphatase prior to and periodically during therapy to monitor effectiveness.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of zoledronic acid to patient. Advise patient to read Medication Guide prior to each administration in case of changes.
Advise patients of the importance of adequate hydration. Patient should be instructed to drink at least two glasses of water prior to receiving dose.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Advise patient to eat a balanced diet and consult health care professional about the need for supplemental calcium and vitamin D.
Inform patient that severe musculoskeletal pain may occur within days, mo, or yr after starting zoledronic acid. Symptoms may resolve completely after discontinuation or slow or incomplete resolution may occur. Notify health care professional if severe pain occurs.
Encourage patient to participate in regular exercise and to modify behaviors that increase the risk of osteoporosis (stop smoking, reduce alcohol consumption).
Advise patient to notify health care professional if signs and symptoms if osteonecrosis of the jaw (pain, numbness, swelling of or drainage from the jaw, mouth, or teeth) or hypocalcemia (spasms, twitches, or cramps in muscles; numbness or tingling in fingers, toes, or around mouth) or thigh, hip, or groin pain occur.
Advise patient to inform health care professional of zoledronic acid therapy prior to dental surgery.
Rep: May cause fetal harm. Advise females of reproductive potential use effective contraception and avoid breastfeeding during and after therapy. May impair fertility in females.
Emphasize the importance of lab tests to monitor progress.

Evaluation/Desired Outcomes ⬆ ⬇

Decrease in serum calcium.
Decrease in serum alkaline phosphatase and the progression of Paget's disease.
Reversal of the progression of osteoporosis with decreased fractures and other sequelae. Discontinuation after 3–5 yr should be considered for postmenopausal women with low risk for fractures.

Code ⬆

NDC Code^*

0078- Novartis Pharmaceuticals Corporation
0078-0387- Zometa 0078-0387-25- 1 VIAL in 1 CARTON (0078-0387-25) > 5 mL in 1 VIAL

0078- Novartis Pharmaceuticals Corporation
0078-0435- Reclast 0078-0435-61- 100 mL in 1 BOTTLE (0078-0435-61)

0078- Novartis Pharmaceuticals Corporation
0078-0590- Zometa 0078-0590-61- 1 BOTTLE in 1 CARTON (0078-0590-61) > 100 mL in 1 BOTTLE

0143- West-Ward Pharmaceuticals Corp
0143-9642- Zoledronic Acid 0143-9642-01- 5 mL in 1 VIAL (0143-9642-01)

0409- Hospira, Inc.
0409-4215- ZOLEDRONIC ACID 0409-4215-01- 1 VIAL, PLASTIC in 1 CARTON (0409-4215-01) > 5 mL in 1 VIAL, PLASTIC

0409- Hospira, Inc.
0409-4215- ZOLEDRONIC ACID 0409-4215-05- 1 VIAL, PLASTIC in 1 CARTON (0409-4215-05) > 5 mL in 1 VIAL, PLASTIC

0409- Hospira, Inc.
0409-4228- ZOLEDRONIC ACID 0409-4228-01- 1 BAG in 1 CARTON (0409-4228-01) > 100 mL in 1 BAG

0409- Hospira, Inc.
0409-4229- Zoledronic Acid 0409-4229-01- 1 BAG in 1 CARTON (0409-4229-01) > 100 mL in 1 BAG

16714- Northstar RxLLC
16714-815- Zoledronic acid 16714-815-01- 1 VIAL in 1 CARTON (16714-815-01) > 5 mL in 1 VIAL

16729- Accord Healthcare Inc.
16729-242- Zoledronic acid 16729-242-31- 1 VIAL in 1 CARTON (16729-242-31) > 5 mL in 1 VIAL

17478- Akorn, Inc.
17478-324- Zoledronic Acid 17478-324-91- 1 BAG in 1 CARTON (17478-324-91) > 100 mL in 1 BAG

17478- Akorn
17478-327- Zoledronic Acid 17478-327-05- 1 VIAL, SINGLE-USE in 1 CARTON (17478-327-05) > 5 mL in 1 VIAL, SINGLE-USE

17478- Akorn
17478-327- Zoledronic Acid 17478-327-45- 4 VIAL, SINGLE-USE in 1 CARTON (17478-327-45) > 5 mL in 1 VIAL, SINGLE-USE

23155- Heritage Pharmaceuticals Inc.
23155-170- Zoledronic acid 23155-170-31- 1 VIAL, GLASS in 1 CARTON (23155-170-31) > 5 mL in 1 VIAL, GLASS

23155- Heritage Pharmaceuticals Inc.
23155-186- Zoledronic acid 23155-186-31- 1 VIAL, GLASS in 1 CARTON (23155-186-31) > 100 mL in 1 VIAL, GLASS

25021- Sagent Pharmaceuticals
25021-801- zoledronic acid 25021-801-66- 1 VIAL in 1 CARTON (25021-801-66) > 5 mL in 1 VIAL

25021- Sagent Pharmaceuticals
25021-826- zoledronic acid 25021-826-67- 1 BAG in 1 CARTON (25021-826-67) > 100 mL in 1 BAG

25021- Sagent Pharmaceuticals
25021-826- zoledronic acid 25021-826-82- 1 BAG in 1 CARTON (25021-826-82) > 100 mL in 1 BAG

25021- Sagent Pharmaceuticals
25021-830- zoledronic acid 25021-830-82- 1 BAG in 1 CARTON (25021-830-82) > 100 mL in 1 BAG

43598- Dr. Reddy's Laboratories Inc
43598-255- Zoledronic acid 43598-255-52- 1 BOTTLE in 1 CARTON (43598-255-52) > 100 mL in 1 BOTTLE

43598- Dr. Reddy's Laboratories Inc.
43598-330- Zoledronic Acid 43598-330-11- 1 VIAL, GLASS in 1 CARTON (43598-330-11) > 5 mL in 1 VIAL, GLASS

43598- Dr.Reddy's Laboratories Inc
43598-331- Zoledronic Acid 43598-331-11- 100 mL in 1 BOTTLE, GLASS (43598-331-11)

51991- Breckenridge Pharmaceutical, Inc
51991-064- Zoledronic Acid 51991-064-98- 1 CONTAINER in 1 CARTON (51991-064-98) > 100 mL in 1 CONTAINER

51991- Breckenridge Pharmaceutical, Inc
51991-065- Zoledronic Acid 51991-065-98- 1 VIAL in 1 CARTON (51991-065-98) > 5 mL in 1 VIAL

54288- BPI Labs, LLC
54288-100- ZOLEDRONIC ACID 54288-100-01- 1 VIAL in 1 CARTON (54288-100-01) > 5 mL in 1 VIAL

55111- Dr. Reddy's Laboratories Limited
55111-685- Zoledronic Acid 55111-685-07- 1 VIAL, GLASS in 1 CARTON (55111-685-07) > 5 mL in 1 VIAL, GLASS

55111- Dr.Reddy's Laboratories Ltd
55111-688- Zoledronic Acid 55111-688-52- 100 mL in 1 BOTTLE, GLASS (55111-688-52)

55150- AuroMedics Pharma LLC
55150-266- Zoledronic Acid 55150-266-05- 1 VIAL, SINGLE-DOSE in 1 CARTON (55150-266-05) > 5 mL in 1 VIAL, SINGLE-DOSE

55150- AuroMedics Pharma LLC
55150-283- Zoledronic Acid 55150-283-99- 1 BOTTLE, GLASS in 1 CARTON (55150-283-99) > 100 mL in 1 BOTTLE, GLASS

60505- Apotex Corp
60505-6110- Zoledronic Acid 60505-6110-0- 1 VIAL in 1 CARTON (60505-6110-0) > 5 mL in 1 VIAL

63323- Fresenius Kabi USA, LLC
63323-961- Zoledronic Acid 63323-961-98- 1 VIAL in 1 CARTON (63323-961-98) > 5 mL in 1 VIAL

63323- Fresenius Kabi USA, LLC
63323-966- Zoledronic Acid 63323-966-00- 1 VIAL, GLASS in 1 CARTON (63323-966-00) > 100 mL in 1 VIAL, GLASS

67457- Mylan Institutional LLC
67457-390- Zoledronic acid 67457-390-54- 1 VIAL in 1 CARTON (67457-390-54) > 5 mL in 1 VIAL

67457- Mylan Institutional LLC
67457-619- Zoledronic Acid 67457-619-10- 1 VIAL in 1 CARTON (67457-619-10) > 100 mL in 1 VIAL

67457- Mylan Institutional LLC
67457-794- Zoledronic Acid 67457-794-10- 1 BAG in 1 POUCH (67457-794-10) > 100 mL in 1 BAG

68001- BluePoint Laboratories
68001-366- Zoledronic Acid 68001-366-25- 1 VIAL in 1 CARTON (68001-366-25) > 5 mL in 1 VIAL (68001-366-22)

68083- Gland Pharma Limited
68083-116- Zoledronic Acid 68083-116-01- 1 VIAL in 1 CARTON (68083-116-01) > 5 mL in 1 VIAL

68083- Gland Pharma Limited
68083-135- Zoledronic Acid 68083-135-01- 1 VIAL, GLASS in 1 CARTON (68083-135-01) > 100 mL in 1 VIAL, GLASS

68083- Gland Pharma Limited
68083-142- Zoledronic Acid 68083-142-01- 1 VIAL in 1 CARTON (68083-142-01) > 100 mL in 1 VIAL

68083- Gland Pharma Limited
68083-256- Zoledronic acid 68083-256-01- 1 BAG in 1 CARTON (68083-256-01) > 100 mL in 1 BAG

69097- Cipla USA Inc.
69097-399- ZOLEDRONIC ACID 69097-399-44- 1 BOTTLE in 1 CARTON (69097-399-44) > 100 mL in 1 BOTTLE

70860- Athenex Pharmaceutical Division, LLC.
70860-210- Zoledronic Acid 70860-210-51- 1 VIAL, SINGLE-USE in 1 CARTON (70860-210-51) > 100 mL in 1 VIAL, SINGLE-USE

70860- Athenex Pharmaceutical Division, LLC.
70860-802- Zoledronic Acid 70860-802-82- 1 BAG in 1 CARTON (70860-802-82) > 100 mL in 1 BAG

section name header

Pronunciation ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Contraind./Precautions ⬆ ⬇