zoledronic acid

zoledronic acid /zo·le·dron·ic ac·id/ (zo´le-dron?ik) a bisphosphonate inhibitor of osteoclastic bone resorption, used for the treatment of hypercalcemia of malignancy.

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zoledronic acid

Reclast, Zometa

Pharmacologic class: Third-generation bisphosphonate

Therapeutic class: Calcium regulator

Pregnancy risk category D

Action

Inhibits osteoclast-mediated bone by blocking resorption of mineralized bone and cartilage, eventually causing cell death and limiting tumor growth. Also limits calcium release produced by tumor.

Availability

Lyophilized powder for injection (Zometa): 4 mg/vial

Solution for infusion (Reclast): 5 mg/100 ml

⊘Indications and dosages

➣ Hypercalcemia caused by cancer

Adults: 4 mg (Zometa) I.V. as a single dose infused over 15 minutes. If albumin-corrected calcium level doesn't return to normal or stay normal, retreatment with 4 mg I.V. begins no sooner than 7 days after initial treatment. For single dose, maximum recommended dosage is 4 mg.

➣ Multiple myeloma; bone metastasis from solid tumors

Adults: 4 mg I.V. (Zometa) as a single dose infused over 15 minutes q 3 to 4 weeks. Treatment may continue for 9 to 15 months, depending on clinical condition.

➣ Paget's disease of bone

Adults: 5 mg (Reclast) I.V. as single dose in 100 ml ready-to-infuse solution infused over 15 minutes with constant infusion rate by vented infusion line

➣ Osteoporosis in postmenopausal women

Adults: 5 mg (Reclast) I.V. as single 5-mg infusion over 15 minutes once yearly

Dosage adjustment

• Renal impairment

Contraindications

• Hypersensitivity to drug, its components, or other bisphosphonates
• Hypocalcemia (Reclast)
• Pregnancy (Zometa)
• Breastfeeding (Reclast)

Precautions

Use cautiously in:
• Bone metastasis with severe renal impairment
• asthma, renal dysfunction, hepatic insufficiency, history of hypoparathyroidism
• pregnant patients (Reclast use not recommended).

Administration

• Before starting therapy, make sure patient is adequately hydrated.
• Don't allow drug to come in contact with calcium-containing solutions; administer as single I.V. solution.
• Reconstitute Zometa by adding 5 ml of sterile water for injection to 4-mg vial. Dilute further by adding reconstituted drug to 100 ml of normal saline solution or dextrose 5% in water.
• Give Reclast I.V. in 100 ml ready-to-infuse solution administered by vented infusion line. Infusion time must not be less than 15 minutes, with constant infusion rate.
• Be aware that a single Reclast dose shouldn't exceed 5 mg.
☞ Give by I.V. infusion over no less than 15 minutes. (Faster infusion may cause renal failure.)
• Be aware that patient receiving Zomata usually receives daily oral calcium supplement of 500 mg and multivitamin containing 400 international units of vitamin D.
• Patients with Paget's disease should receive 1,500 mg elemental calcium and 800 international units vitamin D daily, particularly during the 2 weeks after Reclast dosing.

Route	Onset	Peak	Duration
I.V. (Zometa)	Unknown	Unknown	7-28 days
I.V. (Reclast)	Rapid	End of infusion	Short

Adverse reactions

CNS: dizziness, lethargy, rigors, asthenia, headache, agitation, confusion, insomnia, anxiety, drowsiness, fatigue, paresthesia

CV: hypotension

EENT: conjunctivitis

GI: nausea, vomiting, diarrhea, constipation, dysphagia, anorexia

GU: urinary tract infection, renal toxicity

Hematologic: anemia, neutropenia

Metabolic: dehydration, hypomagnesemia, hypocalcemia, hypophosphatemia

Musculoskeletal: myalgia, joint or bone pain osteonecrosis of jaw

Respiratory: dyspnea, cough, pleural effusion

Skin: rash

Other: flulike syndrome, pyrexia, pain, peripheral edema, infection, fever, chills, infusion site reactions

Interactions

Drug-drug. Aminoglycosides, loop diuretics, other nephrotoxic agents, thalidomide: increased risk of renal toxicity

Drug-diagnostic tests. Calcium, hemoglobin, magnesium, phosphorus, platelets, potassium, red blood cells, white blood cells: decreased levels

Creatinine: increased or decreased level

Patient monitoring

• Monitor electrolyte levels (especially calcium). Watch for signs and symptoms of electrolyte imbalance.
• Assess vital signs. Stay alert for hypotension, dyspnea, and pleural effusion.
☞ Closely monitor fluid intake and output and creatinine level. Check for signs and symptoms of renal toxicity.
• Monitor CBC with platelet count.

Patient teaching

• Explain therapy to patient, including associated risk of renal failure and need for follow-up laboratory tests.
• Tell patient to report shortness of breath, unusual bleeding or bruising, decreased urine output, or other significant problems.
• Instruct patient to take daily oral calcium supplement and multivitamin containing vitamin D as prescribed.
• Tell patient to avoid invasive dental procedures while taking this drug.
• Advise female of childbearing age to avoid pregnancy and breastfeeding.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.