zoledronic acid

zoe-led-DRON-ic AS-id

Therapeutic Classification: bone resorption inhibitors, electrolyte modifiers, hypocalcemics

Pharmacologic Classification: biphosphonates

REMS

Hypercalcemia of malignancy.
Multiple myeloma and metastatic bone lesions from solid tumors.
Paget's disease.
Treatment of osteoporosis in men.
Treatment and prevention of osteoporosis in postmenopausal women.
Treatment and prevention of glucocorticoid-induced osteoporosis in patients expected to be on glucocorticoids for ≥12 mo.

Inhibits bone resorption.
Inhibits increased osteoclast activity and skeletal calcium release induced by tumors.

Therapeutic effects:

Decreased serum calcium.
Decreased serum alkaline phosphatase.
Decreased fractures, radiation/surgery to bone, or spinal cord compression in patients with multiple myeloma or metastatic bone lesions.
Decreased hip, vertebral, or non-vertebral osteoporosis-related fractures in postmenopausal women.
Increased bone mass in men, postmenopausal women, and patients on prolonged corticosteroid therapy.

Absorption: IV administration results in complete bioavailability.

Distribution: Concentrated in and binds to bone.

Metabolism/Excretion: Mostly excreted unchanged by the kidneys.

Half-Life: 167 hr.

(effect on serum calcium)

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

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.

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 osteonecrosis of the jaw [ONJ]);
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 in children only if potential benefit outweighs potential risk;
Geri: risk of renal impairment in older adults.

CV: hypotension, chest pain, leg edema

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

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 ONJ)

Neuro: agitation, anxiety, confusion, insomnia

Resp: asthma exacerbation

Misc: fever, flu-like syndrome

Drug-drug:

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

Paget's Disease

IV (Adults ): 5 mg as a single dose (information regarding retreatment unknown).

Treatment of Osteoporosis in Men or Postmenopausal Women or Treatment/Prevention of Glucocorticoid-Induced Osteoporosis

IV (Adults ): 5 mg once yearly.

Prevention of Osteoporosis in Postmenopausal Women

IV (Adults ): 5 mg every 2 yr.

Hypercalcemia of Malignancy

IV (Adults ): 4 mg; may be repeated after 7 days.

Multiple Myeloma or Bone Metastases from Solid Tumors

IV (Adults ): 4 mg every 3–4 wk (has been used for up to 15 mo).

(Generic available)

Premixed infusion: 4 mg/100 mL; 5 mg/100 mL
Solution for injection: 0.8 mg/mL

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 ONJ.
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 CCr, 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.

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 units 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: Diluent: Dilute 4-mg dose further with 100 mL of 0.9% NaCl or D5W. If not used immediately, may be refrigerated for up to 24 hr. Reclast comes ready to use 5 mg in 100-mL solution. If refrigerated, allow solution to reach room temperature prior to administration. Do not administer solution that is discolored or contains particulate matter.
Rate: Administer as a single infusion over at least 15 min. Rapid infusions increase risk of renal deterioration and renal failure.
Do not mix with solutions containing calcium, such as Lactated Ringer’s solution.

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 of ONJ (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 to use effective contraception and avoid breastfeeding during and after therapy. May impair fertility in females.
Emphasize the importance of lab tests to monitor progress.

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.

Reclast

Aclasta, Zometa

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

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