Intravenous Osteolytic lesions associated with multiple myeloma
Adult: 4 mg as a single dose every 3-4 weeks, given via infusion over at least 15 minutes. Co-administer with 500 mg oral Ca supplement and 400 international units vitamin D daily.
Intravenous Hypercalcaemia of malignancy
Adult: 4 mg as a single dose via IV infusion over at least 15 minutes. Re-treatment: 4 mg after at least 7 days, if necessary.
Intravenous Prophylaxis of skeletal events in patients with bone metastases
Adult: In patients with advanced bone malignancies: 4 mg as a single dose every 3-4 weeks, given via infusion over at least 15 minutes. Co-administer with 500 mg oral Ca supplement and 400 international units vitamin D daily.
Intravenous Paget's disease of bone
Adult: 5 mg as a single dose via infusion over at least 15 minutes. Re-treatment in patients who have relapsed: 5 mg after at least 1 year from initial dose. Ensure intake of at least 500 mg Ca with vitamin D supplements bid for at least 10 days after infusion.
Intravenous Corticosteroid-induced osteoporosis, Osteoporosis in men, Postmenopausal osteoporosis
Adult: 5 mg as a single dose once yearly, given via infusion over at least 15 minutes. In patients with a recent low-trauma hip fracture: Initiate infusion at least 2 weeks after hip fracture repair; administer 50,000-125,000 international units loading dose of vitamin D given orally or via IM inj prior to 1st infusion.
Intravenous Prophylaxis of osteoporosis in postmenopausal women
Adult: 5 mg once every 2 years, given via infusion over at least 15 minutes. Treatment recommendations may vary among countries (refer to local or country-specific product guidelines).
What are the brands available for Zoledronic acid in Hong Kong?
Osteolytic lesions associated with multiple myeloma; Prophylaxis of skeletal events in patients with bone metastases:
CrCl (mL/min)
Dosage
<30
Not recommended.
30-39
3 mg every 3-4 weeks.
40-49
3.3 mg every 3-4 weeks.
50-60
3.5 mg every 3-4 weeks.
>60
4 mg every 3-4 weeks.
Measure serum creatinine prior to each dose and withhold treatment if renal function has deteriorated.
Paget's disease of bone; Postmenopausal osteoporosis; Osteoporosis in men; Corticosteroid-induced osteoporosis; Prophylaxis of osteoporosis in postmenopausal women:
CrCl (mL/min)
Dosage
<35
Contraindicated.
Reconstitution
As 4 mg/5 mL concentrate for solution for infusion: Dilute the required volume using 100 mL NaCl 0.9% or dextrose 5% in water. As 4 mg/100 mL or 5 mg/100 mL solution for infusion: If reduced doses are needed, withdraw the excess volume and replace with equal amount of NaCl 0.9% or dextrose 5% in water. Recommendations may vary between individual products (refer to specific product guidelines).
Incompatibility
Ca or other divalent cation-containing infusion solutions (e.g. lactated Ringer's).
Contraindications
Hypocalcaemia. Severe renal impairment with CrCl <35 mL/min (if indicated for prophylaxis or treatment of osteoporosis, or for treatment of Paget's disease). Pregnancy and lactation.
Special Precautions
Patient with aspirin-sensitive asthma; risk factors for developing osteonecrosis of the jaw (e.g. cancer, co-morbid conditions including anaemia, coagulopathy, infection; poor oral hygiene, history of dental disease, poorly fitting dentures, invasive dental procedures [e.g. tooth extractions]; smoking; concomitant treatment with chemotherapy, corticosteroids, angiogenesis inhibitors, radiotherapy to the head and neck); other factors affecting bone and mineral metabolism (e.g. hypoparathyroidism, parathyroid surgery, thyroid surgery, malabsorption syndromes, small intestine excision); risk factors for renal function deterioration (e.g. dehydrated patients, history of repeated infusion or treatment with bisphosphonates, concomitant treatment with nephrotoxic agents or diuretics). Avoid use in patient with history of musculoskeletal pain associated with bisphosphonate therapy. Renal impairment. Elderly.
Adverse Reactions
Significant: Acute kidney injury or renal function deterioration; severe (occasionally debilitating) bone, joint or muscle pain; osteonecrosis of the jaw, external auditory canal, and other bones (including femur, hip, knee, humerus); atypical subtrochanteric and diaphyseal femoral fractures, acute phase reaction-like symptoms or influenza-like illness; bronchoconstriction. Rarely, atrial fibrillation. Blood and lymphatic system disorders: Anaemia, neutropenia. Eye disorders: Conjunctivitis. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, diarrhoea, constipation. General disorders and administration site conditions: Fever, chills, asthenia, pain, lower extremity oedema. Immune system disorders: Hypersensitivity reactions. Investigations: Increased blood creatinine, blood urea; weight loss. Metabolism and nutrition disorders: Decreased appetite, dehydration, hypophosphataemia, hypokalaemia, hypomagnesaemia. Musculoskeletal and connective tissue disorders: Back pain, pain in extremity. Neoplasms benign, malignant and unspecified: Progression of cancer. Nervous system disorders: Headache, dizziness, paraesthesia, hypoaesthesia. Psychiatric disorders: Insomnia, depression, agitation, anxiety, confusion. Respiratory, thoracic and mediastinal disorders: URTI, cough, dyspnoea. Skin and subcutaneous tissue disorders: Alopecia, dermatitis, hyperhidrosis, pruritus, rash, erythema. Vascular disorders: Hypotension, hypertension, flushing. Potentially Fatal: Hypocalcaemia leading to cardiac arrhythmias and neurologic adverse events, including hypoaesthesia, tetany, convulsions. Rarely, acute renal failure.
Women of childbearing potential must use proven birth control methods during and after treatment.
Monitoring Parameters
Correct hypocalcaemia or other disturbances of bone and mineral metabolism (e.g. vitamin D deficiency) before treatment initiation. Evaluate pregnancy status in women of childbearing potential and perform routine oral and dental exam in patients at risk for osteonecrosis. Evaluate fluid status then adequately hydrate patients before and after administration. Monitor serum creatinine (prior to each dose), 25-hydroxyvitamin D, serum electrolytes including Ca, phosphorus, and Mg. Assess for signs and symptoms of atypical femur fractures, musculoskeletal pain, oral symptoms, and ocular inflammation. Osteoporosis: Evaluate serial BMD at baseline, every 1-3 years during treatment (usually at approx 2 years after treatment initiation then more or less frequent according to patient-specific factors and stability of BMD), every 2-4 years during a drug holiday. Monitor height and weight (annually), biochemical markers of bone turnover (e.g. fasting serum C-terminal cross-linked telopeptide [CTX] or urinary N-terminal telopeptide [NTX]) at baseline, 3 months, and 6 months. Paget's disease: Monitor serum total alkaline phosphatase at 6-12 weeks and potentially at 6 months; then at approx 1-2-year intervals following treatment completion. Oncology use: Evaluate Hb or haematocrit regularly. Multiple myeloma: Monitor urine for albuminuria every 3-6 months.
Overdosage
Symptoms: Renal impairment; abnormalities in serum electrolytes levels, including hypocalcaemia, hypophosphataemia, and hypomagnesaemia. Management: Significant reductions in serum electrolytes may be corrected by administering supplemental oral Ca or IV Ca gluconate K or Na phosphate, and Mg sulfate, respectively.
Drug Interactions
Increased risk of hypocalcaemia with aminoglycosides, calcitonin, loop diuretics. Increased risk of nephrotoxicity with other agents that can potentially or significantly impair renal function (e.g. NSAIDs, aminoglycosides, diuretics). Increased incidence of osteonecrosis of the jaw with angiogenesis inhibitors.
Lab Interference
May interfere with diagnostic imaging agents (e.g. technetium-99m-diphosphonate) in bone scans.
Action
Description: Mechanism of Action: Zoledronic acid is an aminobisphosphonate which blocks osteoclast-mediated bone resorption, leading to reduced bone turnover. It inhibits tumour-induced increased osteoclastic activity and skeletal Ca release. Additionally, it decreases serum Ca and phosphorus levels and increases their urinary excretion. Synonym(s): Zoledronate. Pharmacokinetics: Absorption: Plasma protein binding: 23-53%. Metabolism: Not metabolised. Excretion: Via urine (approx 23-55% as unchanged drug); faeces (<3%). Terminal elimination half-life: Approx 146 hours.
Chemical Structure
Zoledronic acid Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 68740, Zoledronic acid. https://pubchem.ncbi.nlm.nih.gov/compound/Zoledronic-acid. Accessed Sept. 24, 2024.
Storage
Intact vial/infusion solution: Store between 15-30°C. Opened vial/infusion solution: Store between 2-8°C; stable for 24 hours. Allow refrigerated solution to reach room temperature before administration. Storage recommendations may vary among countries and between individual products (refer to specific product guidelines).
M05BA08 - zoledronic acid ; Belongs to the class of bisphosphonates. Used in the treatment of bone diseases.
References
Aclasta Solution for Infusion (Sandoz Products Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 23/05/2024.Anon. Zoledronic Acid. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 23/05/2024.Buckingham R (ed). Zoledronate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 23/05/2024.Joint Formulary Committee. Zoledronic Acid. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 23/05/2024.Seacross Zoledronic Acid 4 mg/5 mL Concentrate for Solution for Infusion (Medispec [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 23/05/2024.Viatris Ltd. Zoledronic Acid Viatris, 4 mg/5 mL, Concentrate for Infusion data sheet 10 November 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 23/05/2024.Viatris Ltd. Zoledronic Acid Viatris, 5 mg/100 mL, Solution for Infusion data sheet 03 May 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 23/05/2024.Zoledronic Acid Dr. Reddy's 5 mg/100 mL Solution for Infusion (Dr. Reddy's Laboratories [UK] Ltd). MHRA. https://products.mhra.gov.uk. Accessed 23/05/2024.Zoledronic Acid Injection (Fosun Pharma USA Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 23/05/2024.Zoledronic Acid Injection, Solution, Concentrate (BluePoint Laboratories). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 23/05/2024.Zoledronic Acid Sandoz 4 mg/100 mL Solution for Infusion (Sandoz Limited). MHRA. https://products.mhra.gov.uk. Accessed 21/06/2024.Zoledronic Acid Sandoz 4 mg/5 mL Concentrate for Solution for Infusion (Sandoz Limited). MHRA. https://products.mhra.gov.uk. Accessed 23/05/2024.Zoledronic Acid. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 23/05/2024.Zometa 4 mg/100 mL Solution for Infusion (X3 Lifescience Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 23/05/2024.
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