Бонефос

Бонефос – inhibitor of a bone resorption at metastasises in a bone.

Form of release and structure

Active ingredient of Bonefos is clodronate dinatrium tetrahydrate.

Drug is produced in shape:

• Capsules of 400 mg (in blisters on 10 pieces and bottles on 100 pieces);
• Tablets, film coated 800 mg (in blisters on 10 pieces);
• Concentrate for preparation of solution for intravenous administration of 60 mg/ml (in glass ampoules on 5 pieces in packaging).

Capsules as auxiliary components contain:

• Silicon dioxide colloid anhydrous – 2,85 mg;
• Lactoses monohydrate – 41,5 mg;
• Calcium stearate – 2,85 mg;
• Talc – 22,8 mg.

As a part of a cover of capsules:

• Titanium dioxide;
• Gelatin;
• Ferrous oxide yellow;
• Ferrous oxide red.

Auxiliary components of tablets, film coated, are:

• Croscarmellose sodium – 22 mg;
• Magnesium stearate – 8 mg;
• Cellulose microcrystallic silitsinizirovanny – 165 mg;
• Stearic acid – 15 mg.

The cover of tablets supports Opadry II white (titanium dioxide of 25%, talc of 14,8%, the polyvinyl alcohol which is partially hydrolyzed 40%, a macrogoal of 3350 20,2%).

The concentrate for preparation of solution as auxiliary components contains:

• Sodium hydroxide – to рН 5;
• Water for injections – to 1 ml.

Indications to use

Indications to Bonefos's use are:

• The hypercalcemia caused by malignant tumors;
• Multiple myeloma (multiple myeloma);
• Osteolytic metastasises of malignant tumors in a bone.

Contraindications

Contraindications to Bonefos's use are:

• Heavy (terminal) renal failure (KK less than 10 ml/min.);
• The accompanying therapy by other bisfosfonata;
• Hypersensitivity of the patient to drug components, and also to other bisfosfonata;
• Period of pregnancy and lactation;
• Children's age.

With care drug is appointed to the patients suffering from a renal failure.

Route of administration and dosage

Use of capsules and tablets:

Capsules and tablets of Bonefos are intended for intake.

• It is necessary to swallow of capsules, without breaking integrity of a gelatinous cover, tablets can be divided into 2 parts, but it is necessary to accept them at the same time (it is not recommended to dissolve or crush tablets before use);
• The daily dose of drug makes 1600 mg, it is necessary to accept it in one step, in the morning on an empty stomach, washing down with a glass of water;
• At prescription of medicine in the daily dose exceeding 1600 mg it is recommended to be divided into 2 receptions. The first reception is carried out the same as is described above, the second – in 1 hour prior to or in 2 hours after meal, medicines, drink (except water);
• Within an hour after Bonefos's reception it is necessary to refrain from meal and other medicines, it is possible to drink only water;
• It is forbidden to take medicine with food, milk and drugs which part calcium or other bivalent cations as it interferes with absorption of klodronovy acid is.

Use of solution for инфузй:

For solution preparation, a necessary dose dissolve in 500 ml 5% of solution of a dextrose or in 0,9% of solution of sodium chloride.

In the course of therapy it is necessary to control function of kidneys and content of calcium in blood serum, and also to provide receipt of sufficient volume of liquid in the patient's organism.

At treatment of the hypercalcemia caused by malignant tumors:

• Intravenous drop administration of 300 mg of drug within 2 hours (not less), before achievement of normal level of calcium in blood serum is appointed daily (no more than 7 days in a row) (as a rule, the result is achieved within 5 days);
• Also single intravenous drop administration of medicine within 4 hours in the dose making 1500 mg is allowed. Repeated infusion or Bonefos's appointment inside is in case of need possible;
• At development of a hypocalcemia it is recommended to interrupt therapy for a short span;
• At impossibility of intravenous administration of drug medicine is taken inside. The initial dose in this case makes 2400-3200 mg daily. Proceeding from individual reaction of the patient to therapy, at normalization of level of calcium in blood the daily dose of drug is reduced to 1600 mg.

At treatment of osteolytic changes of the bones caused by malignant tumors without hypercalcemia:

• The exact dosage is defined individually;
• The recommended initial daily dose – 1600 mg;
• If necessary (according to clinical indications) the dose can be increased to 3200 mg a day.

At treatment of patients with a renal failure:

At treatment of patients it is necessary to be careful with a renal failure. It is not recommended to accept drug inside in the doses exceeding 1600 mg a day for a long time. The daily dose of Bonefos at intake decreases according to the following recommendations:

• Heavy degree of a renal failure (KK – 10-30 ml/min.) – 800 mg;
• Moderate degree (KK – 30-50 ml/min.) – 1200 mg;
• Easy degree (KK – 50-80 ml/min.) – 1600 mg.

Bonefos's use is contraindicated to patients with KK < 10.

Side effects

The most frequent side reaction against the background of Bonefos's use is diarrhea, most often it is noted at reception of high doses of medicine and is shown benign.

Side effects at drug use inside and intravenously:

• From digestive tract: often – nausea and vomiting, diarrhea;
• From skin and its appendages: seldom – skin hypersensitivity reactions;
• From metabolism: often – an asymptomatic hypocalcemia, it is rare – increase in level of parathyroid hormone and an alkaline phosphatase in blood serum, the hypocalcemia which is followed by clinical manifestations;
• From a liver and biliary tract: often – increase in transaminases (as a rule, within norm), is rare – increase in transaminases twice (in comparison with norm) without abnormal liver function;

Within post-marketing use of drug it was reported about the following side reactions:

• From kidneys and urinary tract: a heavy renal failure (especially after bystry intravenous administration drug in high doses), renal failures (a proteinuria, increase in level of creatine of blood serum);
• From skeletal and muscular and connecting fabric: single messages on development of an osteonecrosis of a jaw (it is preferential among the patients who received the previous therapy of an aminobisfosfonatama). Cases of severe pain in joints and muscles, bones are recorded, however such messages were infrequent and the subsequent clinical trials did not establish distinction in the frequency of occurrence of the similar phenomena among patients from group of the placebo and patients undergoing therapy by Bonefos;
• From respiratory system: a bronchospasm, breath dysfunctions (at patients with bronchial asthma, and also with hypersensitivity to acetylsalicylic acid in the anamnesis);
• From organs of sight: a uveitis, conjunctivitis (it was noted only at 1 patient).

Special instructions

At administration of drug intravenously in the high doses considerably exceeding recommended heavy injuries of kidneys can develop, especially at high rate of administering.

Before therapy by Bonefos and in the course of treatment it is recommended to control concentration of calcium in blood serum and function of kidneys, and also to provide receipt of sufficient volume of liquid in the patient's organism. Such measures are especially important in cases of purpose of drug in the form of intravenous infusions, and also in the presence at the patient is a renal failure and a hypercalcemia.

It is necessary to dilute and dissolve solution of Bonefos only according to the recommendations described in the instruction.

In the course of therapy of a bisfosfonatama it is necessary to avoid invasive dental interventions. In the presence at the patient of risk factors (such as radiation therapy, chemotherapy, reception of corticosteroids, cancer, unsatisfactory hygiene of an oral cavity, etc.) it is recommended to discuss a question of need of preventive sanitation of teeth before therapy of a bisfosfonatama.

Analogs

Bonefos's analog is Klobir.

Terms and storage conditions

Period of validity of tablets and capsules – 5 years, solution – 3 years. To store in the place, unavailable to children, at a temperature not above 25 °C.

The prepared solution for infusion is stored no more days at a temperature of 2-8 °C.