Zoledronic Acid

Registered South African indications:

• Osteoporosis
• Paget's disease
• Hypercalcaemia
• Bone lesions in multiple myeloma, breast cancer and prostate cancer
• Slowing progression of skeletal conditions in advanced lung carcinoma

Contraindications

5mg/100ml infusion

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to bisphosphonates
• Pregnancy
• Breastfeeding
• Severe renal impairment (creatinine clearance of <35ml/min): Safety and efficacy in patients with severe renal impairment have not been established
• Hypocalcaemia

4mg/5ml infusion

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to bisphosphonates
• Pregnancy
• Breastfeeding
• Severe renal function impairment (creatinine clearance <30ml/min)
• Children aged 1 year to 17 years, as safety and efficacy have not been established

Cautions

• Mild to moderate renal impairment
• Risk factors for renal impairment
• Disturbances of mineral metabolism
• Unhealed open soft tissue lesions in the mouth
• Cancer
• Smoking
• Poor oral hygiene
• Periodontal disease
• Poorly fitting dentures
• History of dental disease
• Invasive dental procedures
• Prolonged therapy
• Risk factors for cardiac failure

Forms avail. in SA and covered in this monograph: inj

Treatment of postmenopausal osteoporosis
Osteoporosis in men
Glucocorticoid induced osteoporosis

• IV infusion: 5mg, annually

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Adequate supplementation with Vitamin D and calcium is important if dietary intake inadequate

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Treatment of Paget's disease

• IV infusion: 5mg; Repeat dose after 12 months if patients have relapsed, failed to achieve normalisation in serum alkaline phosphatase or in patients with symptoms

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Dilution: 5mg in 100ml aquesous solution via vented infusion line, at a constant infusion rate

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Patients must be appropriately hydrated prior to initiation of treatment

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Adequate supplementation with Vitamin D and at least 500mg elemental calcium, 12hrly for 10 days following treatment

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Tumour induced hypercalaemia

• IV infusion: 4mg, as a single dose infusion over 15min; Wait at least 7 days before considering retreatment

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Reconstitute vial with 5ml water for injection; Dilute further with 100ml 0.9% sodium chloride or 5% glucose solution

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Prevention of skeletal related events in patients with advanced malignancies involving bone
-Multiple myeloma
-Breast cancer
-Prostate cancer
-Lung cancer

• IV: 4mg, infused over 15min every 3-4 weeks

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Reconstitute vial with 5ml water for injection; Dilute further with 100ml 0.9% sodium chloride or 5% glucose solution

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Suppliment with an oral calcium, 500mg, dly and vit D, 400 IU, dly

Not established for use in children below 18 years (see Contraindications)

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Renal Impairment

5mg/100ml infusion

• Severe (CrCl<35ml/min): Contraindicated

4mg/5ml infusion

• Mild to moderate: Caution; dose adjustment recommended

Baseline CrCl (ml/min)	4mg/5ml recommended dose
>60	4.0mg
50-60	3.5mg*
40-49	3.3mg*
30-39	3.0mg*

* Doses have been calculated assuming target AUC of 0.66 (mg•hr/l) (CLcr = 75ml/min). The reduced doses for patients with renal impairment are expected to achieve the same AUC as that seen in patients with creatinine clearance of 75ml/min

• Severe (CrCl<30ml/min): Contraindicated

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Lethargy
• Paraesthesia
• Somnolence
• Tremor
• Syncope
• Dysgeusia
• Insomnia
• Asthenia

Cardiovascular Disorders

• Atrial fibrillation
• Palpitations
• Hypertension
• Flushing
• Hypotension

Respiratory Disorders

• Influenza
• Nasopharyngitis
• Cough
• Dyspnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Dyspepsia
• Abdominal pain
• Gastroesophageal reflux disease
• Constipation
• Dry mouth
• Oesophagitis
• Toothache
• Gastritis

Genitourinary Disorders

• Increased creatinine 
• Pollakiuria
• Proteinuria
• Renal impairment

Endocrine and Metabolic Disorders

• Hypocalcaemia
• Decreased appetite
• Increased C-reactive protein 
• Decreased blood calcium
• Thirst

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Bone pain
• Back pain
• Pain in extremity
• Neck pain
• Musculoskeletal stiffness
• Joint swelling
• Muscle spasms
• Shoulder pain
• Musculoskeletal chest pain
• Musculoskeletal pain
• Joint stiffness
• Arthritis
• Muscular weakness
• Atypical subtrochanteric and diaphyseal femoral fractures
• Osteonecrosis of the external auditory canal
• Osteonecrosis of the jaw 

Skin and Subcutaneous Tissue Disorders

• Rash
• Hyperhidrosis
• Pruritus
• Erythema
• Infusion site reaction

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Hypersensitivity reactions
• Anaphylactic reaction
• Shock
• Acute phase reaction
• Pyrexia
• Influenza-like illness

Sensory Disorders

• Ocular hyperaemia
• Conjunctivitis
• Eye pain
• Uveitis
• Episcleritis
• Iritis
• Scleritis
• Parophthalmia
• Vertigo

Others

• Chills
• Peripheral oedema
• Non-cardiac chest pain
• Dehydration

• Other bisphosphonates
• Nephrotoxic agents
• Aminoglycosides
• Calcitonin
• Loop diuretics
• Thalidomide
• Anti-angiogenic medicinal products

• Renal function
• Serum calcium
• Serum phosphate 
• Serum magnesium
• Dental examination

Specific cases may require

• Alkaline phosphatase
• Bone mineral density
• Albuminuria

Injection 4mg/5ml - EML (Tertiary)

Zoledronate is a bisphosphonic acid which inhibits osteoclastic bone resorption. The action of zoledronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone and partly on its action on farnesyl pyrophosphate (FPP) synthase. Inhibition of FPP synthase in osteoclasts prevents the biosynthesis of isoprenoid lipids, which inhibits osteoclast activity and thus reduces bone resorption and turnover.

Injection (per 5ml) 4mg

• Austell Zoledronic Acid IV (Camox)
• Eurodron (Eurolab)
• Zobone (Ranbaxy)
• Zolapor (Activo)
• Zomabon (Actor)
• Zomedron (Cipla)
• Zometa (Novartis) originator
• Zosteopor (Adcock Ingram)

Injection (per 100ml) 5mg

• Aclasta (Novartis) originator
• Zoclasta (Camox)