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Bisphosphonate Pregnancy: CONTRAINDICATED in pregnancy and lactation (§4.3). §4.6: 'Clodronate is not recommended during pregnancy and in women of childbearing potential not using effective contraception.' 'It is unknown whether clodronate is excreted in human milk. A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with clodronate.' Fertility: no human data; in animal studies large doses decreased male fertility.

Clodronate disodium

Brand names: Bonefos, Loron

Clodronate disodium is a first-generation (non-nitrogen-containing) bisphosphonate used to manage osteolytic disease and hypercalcaemia of malignancy, including in multiple myeloma.

Adult dose

Dose: ORAL clodronate for bone disease of malignancy — 1040 mg clodronate disodium daily (2 x 520 mg film-coated tablets). §4.1 licenses this product for 'the management of osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastases in patients with carcinoma of the breast or multiple myeloma' and for 'the maintenance of clinically acceptable serum calcium levels in patients with hypercalcaemia of malignancy initially treated with an intravenous infusion of clodronate disodium'. §4.2 gives ONE adult dose covering all of those uses, verbatim: 'The recommended dose is 2 film-coated tablets (1040 mg clodronate disodium) daily.' SCOPE — ORAL TABLET ONLY: this bundle contains no intravenous product, so the IV clodronate infusion that §4.1 names as the initial treatment of hypercalcaemia of malignancy is NOT sourced here; use a clodronate infusion SPC for the IV loading regimen.
Route: Oral. §4.2: 'The film-coated tablets may be taken as a single dose or in two equally divided doses if necessary to improve gastrointestinal tolerance.' The single daily dose, and the first of two doses, 'should preferably be taken in the morning on an empty stomach together with a glass of water. The patient should then refrain from eating, drinking (other than plain water), and taking any other oral drugs for one hour.' A second dose is taken between meals, 'more than two hours after and one hour before eating, drinking (other than plain water), or taking any other oral drugs.' 'Clodronate should in no case be taken with milk, food or drugs containing calcium or other divalent cations because they impair the absorption of clodronate.' 'After taking Loron the patient should not lay down, but remain in an upright position to prevent upper abdominal pain.'
Frequency: Once daily, or as two equally divided doses daily
Max: 2080 mg clodronate disodium (4 film-coated tablets) daily — §4.2 verbatim: 'If necessary, the dosage may be increased but should not exceed a maximum of 4 film-coated tablets (2080 mg clodronate disodium) daily.' This is the ceiling for the same licensed indication as the dose above; no separate ceiling is given per indication.
Bioavailability caveat, §4.2 verbatim: 'The oral bioavailability of bisphosphonates is poor. Bioequivalence studies have shown appreciable differences in bioavailability between different oral formulations of clodronate disodium, as well as marked inter and intra patient variability. Dose adjustment may be required if the formulation is changed.' Duration, §4.4: 'No information is available on the potential carcinogenicity of clodronate disodium, but patients have been treated in clinical trials for up to 2 years. The duration of the treatment is therefore at the discretion of the physician, according to the status of the underlying malignancy.' Paediatrics, §4.2 verbatim: 'Children Safety and efficacy in children has not been established.' — no paediatric dose is published. Elderly, §4.2: 'No special dosage recommendations.'

Dose adjustments

Renal

VERBATIM §4.2: 'In patients with renal insufficiency with creatinine clearance between 10 and 30 ml/min, the daily dose should be reduced to one half of the recommended adult dose. Serum creatinine should be monitored during therapy. Clodronate disodium is contra-indicated in patients with creatinine clearance below 10 ml/min.' §4.4 adds that Loron tablets should be administered with care to patients with renal insufficiency, and that adequate fluid intake is particularly important in patients with hypercalcaemia or renal insufficiency.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
  • Acute, severe inflammatory conditions of the gastrointestinal tract
  • Pregnancy and lactation
  • Renal failure with creatinine clearance below 10 ml/min — 'except for short term use in the presence of purely functional renal insufficiency caused by elevated serum calcium levels'
  • Concomitant use of other bisphosphonates
  • Excipient caution (§4.4): 'Owing to the presence of lactose monohydrate, patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.'

Side effects

  • Diarrhoea — §4.8: 'The most common reported drug reaction is diarrhoea which is usually mild and occurs more commonly with higher doses'
  • Common: nausea and vomiting (usually mild)
  • Common: asymptomatic hypocalcaemia; increased serum parathyroid hormone associated with decreased serum calcium; increased serum alkaline phosphatase
  • Common: transaminases increased, usually within the normal range
  • Rare: symptomatic hypocalcaemia
  • Rare: transaminases increased exceeding twice the normal range without other hepatic function abnormality
  • Allergic reaction; bronchoconstriction; hypersensitivity reaction manifesting as skin reaction
  • Atypical subtrochanteric and femoral shaft fractures (a bisphosphonate class effect)
  • Osteonecrosis of the jaw
  • Osteonecrosis of the external auditory canal (a bisphosphonate class effect)
  • Renal function impaired; decreased serum phosphate; increased serum lactate dehydrogenase
  • Upper GI mucosal injury (§4.4): oesophagitis, oesophageal ulcers and oesophageal erosions, 'in some cases severe and requiring hospitalisation, rarely with bleeding or followed by oesophageal stricture or perforation', reported with oral bisphosphonates; post-marketing reports of gastric and duodenal ulcers
  • Post-marketing: uveitis has been reported with clodronate
  • Post-marketing: impairment of respiratory function in patients with aspirin-sensitive asthma; hypersensitivity reactions manifesting as respiratory disorder
  • Post-marketing: 'Impairment of renal function (elevation of serum creatinine and proteinuria), severe renal damage especially after rapid intravenous infusion of high doses. Single cases of renal failure, in rare cases with fatal outcome have been reported especially with concomitant use of NSAIDs, most often diclofenac.'
  • Post-marketing: severe bone, joint and/or muscle pain (reports infrequent; onset varied from days to several months after starting)
  • This side-effect list may be incomplete — check the full SPC.

Monitoring

  • Fluid intake — §4.2: 'Clodronate is mainly eliminated via the kidneys. Therefore, adequate fluid intake must be maintained during clodronate treatment.'
  • §4.4: 'Renal function with serum creatinine, serum calcium and phosphate levels should be monitored before and during treatment.'
  • §4.4: 'In clinical trials, asymptomatic, reversible elevations of transaminases have occurred, without changes in other liver function tests. Monitoring of serum transaminases is advised.'
  • Osteonecrosis of the jaw — §4.4: 'A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene). While on treatment, these patients should avoid invasive dental procedures if possible.'
  • Osteonecrosis of the external auditory canal — §4.4: 'The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.'
  • Oesophageal symptoms — §4.4: 'patients should be instructed to discontinue clodronate disodium and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn.'
  • Atypical femoral fracture — §4.4: 'During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.'
  • Elderly: §4.2 states 'No special dosage recommendations.'
  • §4.4 is TRUNCATED in this bundle (it breaks off in the excipients paragraph) — this monitoring list is not the label's complete set of precautions

Clinical monograph

How it works

It is incorporated into bone and taken up by osteoclasts, where it forms a cytotoxic ATP analogue that impairs osteoclast function and induces apoptosis, reducing bone resorption.

Prescribing in practice

  • Ensure adequate hydration and assess renal function before and during treatment, as it can impair renal function.
  • Osteonecrosis of the jaw is a recognised class risk; a dental check before starting and good oral hygiene are advisable.
  • Oral absorption is reduced by food and by calcium-, iron- and other cation-containing products, which should be separated from dosing.

Monitoring

Monitor renal function and serum calcium during therapy, with dental review for jaw symptoms.

Counselling the patient

  • Take oral tablets with plenty of water and avoid food, milk and calcium or iron supplements around the dose.
  • Report any dental pain, swelling or non-healing of the mouth, and maintain good oral hygiene.
  • Maintain a good fluid intake while on treatment.

Evidence & guidelines

Bisphosphonates reduce skeletal-related events in myeloma and metastatic bone disease; consult the SPC and current prescribing references for indication-specific use.

Reference: Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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