Bonefos

To treat hypercalcemia (high blood calcium) for people who have cancer, clodronate is started with an intravenous infusion (injection into the vein), and then switched to oral (by mouth) maintenance treatment.

The recommended adult dose of the intravenous (IV) infusion is 300 mg daily, infused over 2 to 6 hours. Daily IV doses are continued until the level of calcium in the blood returns to normal. In certain situations, the dose may be given as a single infusion of 1500 mg. Following intravenous treatment, oral treatment is started at a recommended dose of 1600 mg to 2400 mg daily given as a single daily dose or as 2 divided doses. The maximum recommended daily dose is 3200 mg.

To treat cancer that has spread to bones (bone metastases) due to different types of tumours, the recommended initial dose is 1600 mg daily given orally (by mouth). If needed, your doctor may increase this dose. The maximum daily dose is 3200 mg.

Clodronate capsules should be swallowed whole (not chewed) on an empty stomach while sitting in an upright position. Take Bonefos (Clodronate-disodium) with a glass of plain water, at least 2 hours before or after food. Do not lie down for at least 30 minutes after taking the medication to prevent any irritation to your esophagus (the tube connecting the mouth and stomach).

If you are taking calcium supplements or aluminum-, iron-, or magnesium-containing medications (e.g., antacids and mineral supplements), you should take them at a different time of day. When taken together with clodronate, they will decrease the amount of clodronate that is delivered from your stomach into your body and reduce the effectiveness of the clodronate.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important to take Bonefos (Clodronate-disodium) exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store Bonefos (Clodronate-disodium) at room temperature and keep it out of reach of children and pets.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Injection

Each mL of the intravenous solution for infusion contains clodronate tetrahydrate, corresponding to 60 mg of anhydrous clodronate. Nonmedicinal ingredients: sodium hydroxide (to adjust the pH) and water for injection.

Capsules

Each yellow, hard gelatin capsule contains 400 mg of anhydrous clodronate (as the tetrahydrate). Nonmedicinal ingredients: calcium stearate, colloidal anhydrous silica, gelatin, iron oxide (red and yellow), lactose, talc, and titanium dioxide.

Do not use Bonefos (Clodronate-disodium) if you:

• are allergic to clodronate or any ingredients of Bonefos (Clodronate-disodium)
• are allergic to other bisphosphonates (e.g., Alendronate, etidronate, Risedronate)
• are pregnant or breast-feeding
• are taking other bisphosphonate medications (e.g., alendronate, etidronate, risedronate)
• have reduced kidney function
• have severe inflammation of the gastrointestinal tract

There may be an interaction between clodronate and any of the following:

• aminoglycosides (e.g., gentamicin, tobramycin)
• angiogenesis inhibitors (medications that prevent blood vessel growth in tumours; e.g., Axitinib, Bevacizumab, Lenalidomide, Pazopanib, Regorafenib, Sorafenib, Sunitinib, thalidomide)
• antacids or any medications or supplements containing calcium, iron, magnesium, or aluminum
• bisphosphonates (e.g., alendronate, etidronate)
• Calcitonin
• calcium-containing intravenous solutions (e.g., Ringer's solution)
• corticosteroids (e.g., Prednisone)
• Deferasirox
• dietary supplements containing calcium, iron, magnesium, or aluminum
• Estramustine phosphate
• loop diuretics (e.g., Furosemide)
• multivitamins
• nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., Diclofenac, Ibuprofen, Naproxen, Ketoprofen)
• phosphate supplements
• proton pump inhibitors (e.g., Lansoprazole, Omeprazole)

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications that you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the Nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or Allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Atypical femur fracture: There is evidence that long-term use of this class of medication may contribute to a type of rare fracture of the long bone in the thigh (femur), without any form of trauma.

If you experience new or unusual pain in the groin, hip, or thigh area, contact your doctor as soon as possible.

Deterioration of the jaw bone: People with cancer treated with clodronate (or other bisphosphonates) may, though rarely, develop osteonecrosis of the jaw (deterioration of the jaw bone). If you experience any pain, swelling, or infection of the jaw report this to your doctor. Before starting treatment with clodronate, your doctor may recommend that you see a dentist for an examination and any necessary dental treatment. While receiving clodronate, try to avoid invasive dental procedures such as tooth extractions.

Effects on the esophagus: Clodronate can cause irritation or ulcers of the esophagus (the passage from the throat to the stomach). In some cases, these effects have been severe and have required hospitalization. Stop taking the medication and contact your doctor immediately if you suddenly experience problems swallowing, find it painful to swallow, develop pain behind the sternum (breastbone), or have new or worsening heartburn.

To reduce the risk of irritation of the esophagus, swallow Bonefos (Clodronate-disodium) with a full glass of plain water. Do not lie down until 30 minutes have passed and you have eaten your first food of the day. Do not chew, suck, or crush the capsule, as this may lead to ulcers in the mouth or throat. Do not take Bonefos (Clodronate-disodium) at bedtime or before getting up for the day.

Inflammation of the eye: Conditions of eye inflammation have been reported by people using clodronate. If you experience changes to your vision, red eyes, or eye pain, contact your doctor as soon as possible.

Kidney problems: Clodronate may cause kidney problems. If you have reduced kidney function, discuss with your doctor how Bonefos (Clodronate-disodium) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Bonefos (Clodronate-disodium), and whether any special monitoring is needed. Your doctor will monitor your kidney function during and after intravenous infusions of clodronate.

Low calcium levels: Clodronate may cause low calcium levels. You will need to have regular blood tests to monitor your calcium levels while taking clodronate. If you experience symptoms of low levels of calcium in the blood, such as muscle spasms, tingling or numbness of the fingers and mouth, twitching, or memory loss, contact your doctor as soon as possible.

Pregnancy: Bonefos (Clodronate-disodium) should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: It is not known if clodronate passes into breast milk. If you are a breast-feeding mother and are taking Bonefos (Clodronate-disodium), it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using Bonefos (Clodronate-disodium) has not been established for children.