Clodronic Acid

Registered South African indications:

• Hypercalcaemia due to malignancy
• Treatment of sequelae of osteolysis due to malignancy

Contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• Breastfeeding 
• Severe renal impairment
• Coadministration with other bisphosphonates

Cautions

• Pregnancy
• Moderate renal impairment
• Prolonged use
• Local infection or trauma of the external auditory canal
• Cancer
• Chemotherapy
• Radiotherapy
• Poor oral hygiene
• Low sodium diet
• Dental conditions and osteonecrosis of the jaw
• Osteonecrosis of the external auditory canal
• Atypical fractures of the femur

Forms avail. in SA covered in this monograph: tab

Hypercalcaemia of malignancy

• Oral (tab): Initial: 2400-3200mg, dly; May be titrated down gradually to 1600mg, dly to maintain normocalcaemia; Max: 3200mg/24hrs

When doses higher than 1600mg are used daily, the portion of the dose greater than 1600mg must be taken as a separate dose between meals (more than 2 hours after and 1 hour before eating)

Treatment of sequelae of osteolysis of malignancy including fractures

• Oral (tab): 1600mg, dly; Max: 3200mg/24hrs

To be swallowed whole or cut in half

Do not crush/chew/dissolve

To be taken on an empty stomach with a full glass of water

To refrain from eating or drinking or taking any other oral medication for an hour after administration

Not to be taken with milk or other food or medications containing calcium

Not established for use in children

Pregnancy 

• Caution; not recommended
• There is a limited amount of data from the use of clodronate in pregnant women
• Clodronate is not recommended during pregnancy and in women of childbearing potential not using effective contraception
• Although in animals, clodronate passes through the placental barrier it is not known if it passes into the foetus in humans. Furthermore, it is not known if clodronic acid can cause foetal damage or affect reproduction in humans. Studies in animals have shown reproductive toxicity

Breastfeeding 

• Contraindicated 
• It is unknown whether clodronate is excreted in human milk. A risk to the suckling child cannot be excluded
• Breastfeeding should be discontinued during treatment with clodronate

Fertility

• In animal studies, clodronate did not cause foetal damage, but large doses decreased male fertility
• No clinical data on the effect of clodronate on fertility in humans is available

Renal Impairment

• Moderate: Caution; dose adjustment recommended 
• Severe: Contraindicated 

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Respiratory Disorders

• Bronchospasm
• Impairment of respiratory function in patients with aspirin-sensitive asthma

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting

Hepatobiliary Disorders

• Increased transaminases

Genitourinary Disorders

• Elevated serum creatinine
• Proteinuria
• Renal failure

Endocrine and Metabolic Disorders

• Asymptomatic hypocalcaemia
• Symptomatic hypocalcaemia
• Increased serum parathyroid hormone
• Increased serum alkaline phosphatase

Musculoskeletal disorders

• Atypical subtrochanteric and diaphyseal femoral fractures 
• Osteonecrosis of the external auditory canal 
• Osteonecrosis of the jaw
• Severe bone, joint and/or muscle pain

Skin and Subcutaneous Tissue Disorders

• Hypersensitivity reaction

Sensory Disorders

• Uveitis
• Conjunctivitis

• Bisphosphonates
• Aminoglycosides
• Non-steroidal anti-inflammatory drugs
• Estramustine phosphate
• Food
• Antacids
• Mineral supplements
• Corticosteroids

• Electrolytes
• Full blood count
• Renal function
• Hepatic function

Clodronate is a bisphosphonate which inhibits the formation and dissolution of calcium phosphate. In vivo, they have been shown to inhibit bone resorption to a greater or lesser extent. The most important mechanism of action of clodronate is its inhibitory effect on osteoclastic bone resorption, which reduce the serum calcium concentration and urinary excretion of calcium and hydroxyproline.

Tablet 800mg

• Bonephos (Bayer) originator