Medicines
Update of 27/07/2026
CLASTOBAN® 800 mg film-coated tablet
clodronic acid
Forms and presentations
Film-coated tablet (white, oval, convex, with a break bar* on one side): Box of 60, blister packs (PVC/PVDC/aluminium).* The break bar is only intended to make it easier to take the tablet; it does not divide it into equal doses.
Composition
| per tablet | |
| Clodronic acid disodium salt
|
800 mg |
| (as clodronate disodium tetrahydrate: 1000 mg) | |
Indications
- Treatment of malignant hypercalcaemia as a follow-on from the injectable form.
- Palliative treatment of osteolysis of malignant origin, with or without hypercalcaemia, as an adjunct to specific treatment of the tumour (see Warnings and Precautions for Use).
Dosage and administration
DosageThe tablets must be taken away from meals (see Interactions).
Depending on the indication and the dose used, the treatment will be taken in one or two doses. Preferably, the single daily dose or the first of the two daily doses should be taken in the morning on an empty stomach, with a glass of water. During the hour following intake, the patient must not eat, nor drink (except plain water), nor take any other medication by the oral route.
In the case of a twice-daily dosage, the second dose must be taken between meals (at least two hours after) and one hour before the next meal, of a drink (other than plain water), or of another medication.
As Clastoban is eliminated mainly by the renal route, optimal hydration must be maintained during treatment.
- Palliative treatment of osteolysis without hypercalcaemia:
- The recommended daily dose is 1600 mg in a single dose. If the prescribed dose is higher, it is recommended to divide the dose into two doses.
- Treatment of malignant hypercalcaemia as a follow-on from the injectable form and palliative treatment of osteolysis of malignant origin with hypercalcaemia:
- Higher starting doses should be initiated: from 2400 to 3200 mg/day, divided into several doses. Depending on the therapeutic response, these doses will be progressively reduced to 1600 mg.
- Children:
- The efficacy and tolerability of this medicine have not yet been established in children.
- Elderly:
- No specific dose adjustment is necessary in elderly subjects. In patients over 65 years of age included in clinical trials, there were no adverse effects specific to this age group.
- Renal insufficiency:
- Clodronate is essentially eliminated by the renal route. It should therefore be used with caution in cases of renal insufficiency. Doses greater than 1600 mg must not be taken continuously.
- It is recommended to reduce doses according to the scheme below, depending on the degree of renal insufficiency:
-
Degree of renal insufficiency Creatinine clearance (ml/min) Dose Mild 50-80 1600 mg/day (no dose reduction) Moderate 30-50 1200 mg/day Severe* < 30 800 mg/day -
* There are no pharmacokinetic data available in renal insufficiency patients with creatinine clearance below 10 ml/min for oral treatment with clodronate. Use in this type of patient should be avoided, except for short-term use in the case of purely functional renal insufficiency due to an increase in serum calcium level.
Contraindications
- Hypersensitivity to the active substance or to any of the excipients listed in section Composition.
- Association with another bisphosphonate.
Warnings and precautions
Warnings:
- Atypical femoral fractures:
- Atypical subtrochanteric and diaphyseal femoral fractures have been reported under bisphosphonates, mainly in patients treated long-term for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar area. These fractures occur after minimal trauma or no trauma, and some patients experience thigh or groin pain, often associated with radiological signs of stress fractures, weeks or months before the femoral fracture. The fractures are often bilateral; therefore, the contralateral femur should be examined in bisphosphonate-treated patients who have had a diaphyseal femoral fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate treatment in patients in whom an atypical femoral fracture is suspected should be considered, based on an assessment of the benefit/risk for the patient.
- During bisphosphonate treatment, patients should be advised to report any thigh, hip or groin pain, and all patients presenting with such symptoms should be evaluated for an atypical femoral fracture.
- Osteonecrosis of the jaw:
Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis), has been reported in cancer patients receiving intravenous and oral bisphosphonate treatment. Many of these patients were also receiving chemotherapy and corticosteroids.
A dental examination with appropriate preventive dental care should be considered before bisphosphonate treatment in patients with concomitant risk factors (for example: cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).
During treatment, these patients should, if possible, avoid invasive dental procedures. Dental surgery may worsen the condition of patients developing osteonecrosis of the jaw during bisphosphonate treatment. For patients requiring dental procedures, there are no available data suggesting that interrupting bisphosphonate treatment reduces the risk of osteonecrosis of the jaw.
The treating physician's clinical judgement should guide the management of each patient based on the assessment of the individual benefit/risk ratio.
Patients must be adequately hydrated before and during treatment. This is particularly important when Clastoban is used as an intravenous infusion in patients with hypercalcaemia or renal insufficiency, as severe renal damage has been reported with rapid intravenous administration of doses higher than those recommended.
Renal function, serum creatinine level, and calcium-phosphate balance (serum calcium and phosphorus) should be monitored regularly before and during treatment.
In patients with renal insufficiency, Clastoban should be administered with caution, and a dose reduction may be necessary since the elimination of clodronate is essentially renal (see Posology and Method of administration).
Precautions for use- Malignant hyperosteolysis: treatment with Clastoban must not call into question the initiation of specific treatment.
- Asymptomatic and reversible elevations of transaminases occurred during clinical trials, without other changes in liver function tests. Monitoring of serum transaminases is recommended (see Undesirable effects).
Interactions
Drug interactions- Nephrotoxic medicinal products:
- Concomitant use of medicinal products with intrinsic renal toxicity increases the risk of nephrotoxicity. If such a combination is necessary, renal biological monitoring should be strengthened.
- The medicinal products concerned include, in particular, iodinated contrast agents, aminoglycosides, organoplatinum compounds, high-dose methotrexate, certain antivirals such as pentamidine, foscarnet, the "ciclovirs", ciclosporin or tacrolimus.
Contraindicated:
Combination with other bisphosphonates is contraindicated.
Requiring precautions for use:
- NSAIDs (systemic route, including cox-2 inhibitors) and acetylsalicylic acid (> 1 g per dose and/or 3 g per day): risk of additive nephrotoxic effects, particularly in elderly subjects. Monitor renal function at the start of treatment with the NSAID.
- Estramustine: risk of increased plasma concentrations of estramustine caused by clodronate. Clinical monitoring during the combination.
- Calcium (for oral calcium salts): decreased digestive absorption of bisphosphonates. Take calcium salts at a distance from bisphosphonates (at least 1 hour and more than 2 hours if possible, depending on the bisphosphonate).
- Iron (for oral iron salts): decreased digestive absorption of bisphosphonates. Take iron salts at a distance from bisphosphonates (at least 1 hour and more than 2 hours if possible, depending on the bisphosphonate).
- Gastrointestinal topicals, antacids and charcoal: decreased digestive absorption of bisphosphonates. Take gastrointestinal topicals and antacids at a distance from bisphosphonates (at least 1 hour and more than 2 hours if possible, depending on the bisphosphonate).
To be taken into account:
- Aminoglycosides: risk of additive hypocalcaemic effects.
Fertility, pregnancy and breastfeeding
Pregnancy:Studies performed in animals have demonstrated a teratogenic effect at high doses, with bone alterations affecting the skeleton and teeth.
When administered during pregnancy, this medicinal product causes disturbances of bone mineralisation, mainly affecting long bones and resulting in angular deformities. These abnormalities are most often observed at high doses and are reversible after delivery. This effect is probably attributable to the mechanism of action of the molecule, through chelation of calcium.
Although clodronate crosses the placental barrier in animals, this characteristic is not known in humans. In clinical practice, there are currently no sufficiently relevant data to assess a possible malformative or foetotoxic effect of clodronate when administered during pregnancy.
Consequently, the use of clodronate is not recommended during pregnancy and in women of childbearing potential not using effective contraception. This element does not constitute grounds for advising termination of pregnancy but leads to a cautious approach and targeted prenatal monitoring.
Breastfeeding:
The excretion of clodronate into breast milk is not known. The risk to the breastfed infant cannot be excluded. It is recommended to stop breastfeeding during treatment.
Fertility:Studies carried out in animals with clodronate did not demonstrate foetotoxicity, but high doses reduced fertility in males.
There are no clinical data on the effect of clodronate on fertility in humans.
Adverse effects
The most frequently reported adverse reactions are nausea, vomiting and diarrhoea. These reactions are generally mild and are more frequent during treatment with high doses of Clastoban.
Common (from ≥ 1/100 to < 1/10); rare (from ≥ 1/10 000 to < 1/1000).
| System organ class | |
| Frequency | Adverse effects |
| Metabolism and nutrition disorders | |
| Common | Asymptomatic hypocalcaemia |
| Rare | Symptomatic hypocalcaemia
Increased serum parathormone levels, associated with decreased serum calcium Increased serum alkaline phosphatase levels* |
| Gastrointestinal disorders | |
| Common | Diarrhoea**
Nausea** Vomiting** |
| Hepatobiliary disorders | |
| Common | Increased transaminase levels (usually within the normal range) |
| Rare | Increased transaminase levels more than twice the normal values, not associated with an abnormality of liver function |
| Skin and subcutaneous tissue disorders | |
| Rare | Cutaneous hypersensitivity reactions |
** Generally of mild intensity.
The most appropriate MedDRA terms have been used to describe adverse reactions.
- Post-marketing experience:
-
- Isolated cases of osteonecrosis of the jaw have been reported, mainly in patients previously treated with amino-bisphosphonates such as zoledronate and pamidronate (see also Warnings and precautions).
- Following marketing, the following adverse reactions have been reported (rare frequency): subtrochanteric and diaphyseal atypical femoral fractures (class adverse reactions of bisphosphonates).
- Eye disorders:
Cases of uveitis have been reported with Clastoban after marketing. The following effects have been reported with other bisphosphonates: conjunctivitis, episcleritis and scleritis. One isolated case of conjunctivitis has been reported with Clastoban, in a patient treated in combination with another bisphosphonate. - Respiratory, thoracic and mediastinal disorders:
Very rare: impairment of respiratory function in patients with asthma due to aspirin allergy. Hypersensitivity reactions manifesting as respiratory disorders. - Renal and urinary disorders:
Rare: impairment of renal function (increased serum creatinine and increased proteinuria) and severe renal damage, especially after rapid intravenous infusion of high doses of clodronate (see Posology and Method of administration). Isolated cases of renal failure and, in rare cases, fatal outcome have been reported, particularly with concomitant use of NSAIDs (see Interactions). - Musculoskeletal, systemic and bone disorders:
Severe bone, joint and/or muscle pain has very rarely been reported in patients taking Clastoban. Onset varies from a few days to several months after starting treatment with Clastoban.
- Isolated cases of osteonecrosis of the jaw have been reported, mainly in patients previously treated with amino-bisphosphonates such as zoledronate and pamidronate (see also Warnings and precautions).
Reporting of suspected adverse reactions after marketing authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/.
Overdose
- Symptoms:
- An increase in serum creatinine and renal disorders have been observed with high doses of intravenous clodronate.
- Treatment:
- Treatment of overdose must be symptomatic. Satisfactory hydration must be ensured and renal function and serum calcium levels must be monitored.
Pharmacodynamics
Pharmacotherapeutic class: Bisphosphonates, ATC code: M05BA02.
Clodronate disodium belongs to the bisphosphonate family, whose action is specifically exerted on bone. This selective action is based on their strong affinity for the mineral components of bone tissue and results in inhibition of osteoclastic activity.
At concentrations causing inhibition of osteolysis, clodronate disodium has no effect on normal bone mineralisation.
In hypercalcaemic states, clodronate reduces elevated serum levels, and in normocalcaemic patients, the anti-osteolytic action of clodronate disodium is demonstrated by a decrease in urinary excretion of calcium and hydroxyproline.
Daily administration of this product reduces the formation of new osteolytic lesions and slows the extension of existing bone lesions.
In patients with bone metastases or myeloma-related bone lesions, clodronate slows the development of existing skeletal lesions. Clodronate also induces a reduction in pain associated with hyperosteolysis.
Pharmacokinetics
- Absorption:
- Like other bisphosphonates, gastrointestinal absorption of clodronate is low, at approximately 2%. Its absorption is rapid. After oral administration of a single dose of 800 mg, the maximum observed concentration is on average 575 ng/mL. It is reached within approximately 30 minutes.
- As clodronate has a strong affinity for calcium and other divalent cations, its absorption is markedly reduced if it is taken with food or medicines containing divalent cations. Pharmacokinetic studies have shown a clear decrease in the bioavailability of clodronate when it is administered during or near a meal. It is recommended to take clodronate at least one hour before meals. In addition, gastrointestinal absorption of clodronate is subject to considerable intra-individual variability. There is no notable accumulation of clodronate after repeated administration.
- Distribution and elimination:
- The plasma protein binding rate of clodronate is low and its volume of distribution is 20-50 litres. Elimination of clodronate from serum occurs in two distinct phases: a distribution phase, with a half-life of approximately 2 hours, and a terminal elimination phase, which corresponds to the release of clodronate from bone tissue. Clodronate is essentially eliminated via the kidneys. Approximately 80% of the absorbed dose is found in the urine within a few days. Clodronate bound to bone (approximately 20% of the absorbed amount) is excreted more slowly, and renal clearance represents approximately 75% of plasma clearance.
- Risk groups:
-
- Renal impairment: data observed in patients with bone metastases suggest a correlation between creatinine clearance and clodronate clearance. Consequently, accumulation of clodronate is likely to occur in patients with renal insufficiency.
- There are no data in patients with hepatic impairment.
- Renal impairment: data observed in patients with bone metastases suggest a correlation between creatinine clearance and clodronate clearance. Consequently, accumulation of clodronate is likely to occur in patients with renal insufficiency.
Preclinical safety
After single administration in rats, the LD50 was 2200 mg/kg after oral administration and 120 mg/kg after intravenous administration.
Toxicity studies with repeated oral doses over a period of up to 12 months were carried out in rats and minipigs. The identified target organs were bone (sclerosis related to the pharmacological effect of clodronate), the gastrointestinal tract (irritation), blood (lymphopenia, effects on haemostasis), kidney (tubular dilatation, proteinuria) and liver (increased serum transaminases).
In animal reproductive toxicity studies, clodronate did not induce foetal abnormalities, but high doses caused a decrease in fertility in males. After one month of subcutaneous administration of clodronate to newborn rats, skeletal changes resembling osteoporosis were observed, which is explained by the pharmacological effects of clodronate.
Genotoxicity studies do not show any genotoxic potential of clodronate. Carcinogenesis studies conducted in rats and mice revealed no carcinogenic potential.
Storage conditions
- Shelf life
- 3 years.
To be stored at a temperature not exceeding + 30 °C.
HANDLING/DISPOSAL INSTRUCTIONS
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Prescription, supply and reimbursement
LIST I| Marketing authorisation (AMM) | 3400936206601 (2003, RCP rev 19.02.2025). |
| Price: | 214,88 euros (60 tablets). |
| Reimbursed by Social Security at 65 %. Collective. | |
Marketing authorisation holder: Bioprojet Europe Ltd, 101 Furry Park Road, Killester, Dublin 5, D05KD52, Ireland.
Operator:
BIOPROJET Pharma
115, rue d'Aboukir. 75002 Paris
Tel: 01 47 03 66 33
Pharmacovigilance:
E-mail: pharmacovigilance@bioprojet.com
https://www.bioprojet.com/
Source: VIDAL · Updated on 10/11/2026. This information does not replace advice from a healthcare professional.