Bonefos
Bonefos: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological action
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in the elderly
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Bonefos
ATX code: M05BA02
Active ingredient: Clodronic acid (Clodronic acid)
Manufacturer: BAYER OY (Finland)
Description and photo update: 2019-06-08
Bonefos is an inhibitor of bone resorption in bone metastases.
Release form and composition
- Capsules 400 mg (in blisters of 10 pieces and bottles of 100 pieces);
- Film-coated tablets, 800 mg (in blisters of 10 pieces);
- Concentrate for the preparation of a solution for intravenous administration 60 mg / ml (in glass ampoules, 5 per pack).
The active ingredient is clodronate disodium tetrahydrate.
Capsules contain as auxiliary components:
- Colloidal anhydrous silicon dioxide - 2.85 mg;
- Lactose monohydrate - 41.5 mg;
- Calcium stearate - 2.85 mg;
- Talc - 22.8 mg.
As part of the capsule shell:
- Titanium dioxide;
- Gelatin;
- Iron oxide yellow;
- Iron oxide red.
The auxiliary components of film-coated tablets are:
- Croscarmellose sodium - 22 mg;
- Magnesium stearate - 8 mg;
- Siliconized microcrystalline cellulose - 165 mg;
- Stearic acid 15 mg
The shell of tablets contains Opadry II white (titanium dioxide 25%, talc 14.8%, polyvinyl alcohol, partially hydrolyzed 40%, macrogol 3350 20.2%).
The concentrate for solution preparation contains as auxiliary components:
- Sodium hydroxide - up to pH 5;
- Water for injection - up to 1 ml.
pharmachologic effect
Pharmacodynamics
The active component of Bonefos - disodium clodronate tetrahydrate - after entering the body is converted into clodronic acid, which belongs to the group of bisphosphonates and is an analogue of natural pyrophosphate. The mechanism of action of clodronic acid is to inhibit the activity of osteoclasts and reduce the resorption of bone tissue caused by them. Confirmation of these properties has been obtained as a result of biochemical, kinetic and histological studies, but the exact mechanism of this process has not yet been studied.
Clodronic acid inhibits osteoclast activity by decreasing serum calcium and decreasing renal excretion of hydroxyproline and calcium. In vitro, the compound slows down the precipitation of calcium phosphate, prevents its transformation into hydroxyapatite, inhibits the aggregation of apatite crystals into larger crystals, and reduces the rate of dissolution of these crystals. When Bonefos was used as a monotherapy in doses sufficient to reduce bone resorption, there was no effect on normal bone mineralization in patients.
In patients with multiple myeloma and breast cancer, taking the drug reduces the likelihood of bone fractures. Clodronic acid reduces the risk of bone metastases in primary breast cancer. The use of the drug for the prevention of bone metastases in patients with operable breast cancer reduces the mortality rate in this category of patients.
Pharmacokinetics
Clodronic acid is rapidly absorbed in the gastrointestinal tract in an amount of about 2%. After oral administration of one dose of Bonefos, the maximum level of the active substance in the blood serum is noted after 30 minutes. Since clodronic acid has a pronounced affinity for calcium and other divalent cations, its absorption is significantly reduced when the drug is taken with food or other drugs that contain divalent cations.
When Bonefos is taken orally 1 hour before meals, the relative bioavailability is 91%, 30 minutes before meals - 69%. A significant variation in the indices of absorption of clodronic acid in the organs of the gastrointestinal tract is also observed both in different patients and in the same patient. Despite significant fluctuations in absorption rates in the same patient, the amount of clodronic acid entering the body during long-term therapy remains constant.
The level of binding of disodium clodronate tetrahydrate with plasma proteins is low. The volume of distribution is 20-50 liters.
The elimination of clodronic acid from the blood serum is characterized by two phases: the distribution phase, in which the half-life is approximately 2 hours, and the elimination phase, which proceeds very slowly due to the strong binding of clodronic acid to bone tissue. The compound is excreted from the body mainly through the kidneys, and approximately 80% of it is found in the urine for several days after taking Bonefos. Clodronic acid associated with bone tissue (which is about 20% of the absorbed amount) is excreted from the body at a slower rate. Renal clearance is approximately 75% of plasma clearance.
There is no clear relationship between the concentration of clodronic acid in blood plasma and the therapeutic effect or adverse reactions. The pharmacokinetic profile of Bonefos does not depend on functional disorders (excluding renal failure, which is the cause of a decrease in renal clearance of clodronic acid), drug metabolism or age.
Indications for use
- Hypercalcemia caused by malignant tumors;
- Multiple myeloma (multiple myeloma);
- Osteolytic metastases of malignant tumors in the bone.
Contraindications
- Severe (terminal) renal failure (CC less than 10 ml / min);
- Concomitant therapy with other bisphosphonates;
- Hypersensitivity of the patient to the components of the drug, as well as to other bisphosphonates;
- Pregnancy and lactation period;
- Childhood.
The drug is prescribed with caution to patients suffering from impaired renal function.
Instructions for the use of Bonefos: method and dosage
Capsules and tablets
Capsules and tablets are intended for oral administration.
- The capsules must be swallowed without violating the integrity of the gelatinous membrane, the tablets can be divided into 2 parts, but they should be taken simultaneously (it is not recommended to dissolve or grind the tablets before use);
- The daily dose of the drug is 1600 mg, it must be taken at one time, in the morning on an empty stomach, with a glass of water;
- When prescribing a drug in a daily dose exceeding 1600 mg, it is recommended to divide it into 2 doses. The first intake is carried out in the same way as described above, the second - 1 hour before or 2 hours after eating, medications, drinking (except water);
- Within an hour after taking the drug, you must refrain from eating and other medications, you can only drink water;
- It is forbidden to take the medicine with food, milk and preparations that contain calcium or other divalent cations, as this interferes with the absorption of clodronic acid.
Solution for infusion
To prepare the solution, the required dose is dissolved in 500 ml of 5% dextrose solution or in 0.9% sodium chloride solution.
During therapy, it is necessary to monitor renal function and serum calcium, as well as to ensure that a sufficient volume of fluid is supplied to the patient's body.
When treating hypercalcemia due to malignant tumors:
- A daily (no more than 7 consecutive days) intravenous drip of 300 mg of the drug is prescribed for 2 hours (at least), until a normal level of calcium in the blood serum is reached (as a rule, the result is achieved within 5 days);
- A single intravenous drip of the drug is also allowed within 4 hours at a dose of 1500 mg. If necessary, it is possible to re-infuse or prescribe Bonefos inside;
- With the development of hypocalcemia, it is recommended to interrupt therapy for a short period of time;
- If intravenous administration of the drug is impossible, the drug is taken orally. The initial dose in this case is 2400-3200 mg daily. Based on the patient's individual response to therapy, with the normalization of the level of calcium in the blood, the daily dose of the drug is reduced to 1600 mg.
In the treatment of osteolytic bone changes caused by malignant tumors without hypercalcemia:
- The exact dosage is determined individually;
- The recommended starting daily dose is 1600 mg;
- If necessary (in accordance with clinical indications) the dose can be increased to 3200 mg per day.
Treatment of patients with renal impairment
Care should be taken when treating patients with renal impairment. It is not recommended to take the drug orally for a long time in doses exceeding 1600 mg per day. The daily dose of Bonefos when taken orally is reduced in accordance with the following recommendations:
- Severe renal failure (CC - 10-30 ml / min) - 800 mg;
- Moderate degree (CC - 30-50 ml / min) - 1200 mg;
- Mild degree (CC - 50-80 ml / min) - 1600 mg.
According to the instructions, Bonefos is contraindicated in patients with CC <10.
Side effects
The most common adverse reaction of the drug is diarrhea, it is most often observed with high doses of the drug and manifests itself in a mild form.
Possible unwanted effects:
- From the gastrointestinal tract: often - nausea and vomiting, diarrhea;
- On the part of the skin and its appendages: rarely - hypersensitivity skin reactions;
- From the side of metabolism: often - asymptomatic hypocalcemia, rarely - increased levels of parathyroid hormone and alkaline phosphatase in the serum, hypocalcemia, accompanied by clinical manifestations;
- On the part of the liver and biliary tract: often - an increase in transaminases (usually within the normal range), rarely - an increase in transaminases by 2 times (compared to the norm) without impaired liver function;
As part of the post-marketing use of the drug, the following adverse reactions were reported:
- From the kidneys and urinary tract: severe renal failure (especially after rapid intravenous administration of the drug in high doses), renal dysfunction (proteinuria, increased serum creatine levels);
- From the musculoskeletal and connective tissue: isolated reports of the development of osteonecrosis of the jaw (mainly among patients who received prior therapy with aminobisphosphonates). Cases of severe pain in joints and muscles, bones were recorded, however, such reports were infrequent and subsequent clinical studies did not establish differences in the incidence of such events among patients from the placebo group and patients undergoing Bonefos therapy;
- From the respiratory system: bronchospasm, respiratory dysfunction (in patients with bronchial asthma, as well as with a history of hypersensitivity to acetylsalicylic acid);
- From the side of the organs of vision: uveitis, conjunctivitis (was noted in only 1 patient).
Overdose
With intravenous administration of Bonefos in high doses, an increase in serum creatinine and renal dysfunction were noted. Similar symptoms were not observed when taking large doses of the drug inside.
In case of overdose, the appointment of symptomatic therapy is recommended. The patient should be provided with a strict drinking regime with the intake of large amounts of fluid into the body, as well as monitoring the concentration of calcium in the blood serum and kidney function.
special instructions
When the drug is administered intravenously in large doses, significantly exceeding the recommended ones, severe kidney damage can develop, especially at a high rate of administration.
Before starting therapy and during treatment, it is recommended to monitor serum calcium concentration and kidney function, as well as to ensure that a sufficient volume of fluid is supplied to the patient's body. Such measures are especially important in cases of prescribing the drug in the form of intravenous infusion, as well as in the presence of renal failure and hypercalcemia in the patient.
Dilute and dilute the Bonefos solution only in accordance with the recommendations described in the instructions.
In the process of bisphosphonate therapy, invasive dental procedures should be avoided. If the patient has risk factors (such as radiation therapy, chemotherapy, corticosteroids, cancer, poor oral hygiene, etc.), it is recommended to discuss the need for preventive dental debridement before starting bisphosphonate therapy.
Influence on the ability to drive vehicles and complex mechanisms
The studies did not reveal the effect of Bonefos on the ability to drive a car and work with complex mechanisms.
Application during pregnancy and lactation
It is not known whether disodium clodronate tetrahydrate penetrates the placental barrier in humans, and whether it can provoke the development of fetal abnormalities or impaired reproductive function. It was found that clodronic acid crosses the placental barrier in animals. It has not been clarified whether this compound passes into breast milk. In connection with the above information, the use of Bonefos during pregnancy and lactation is contraindicated.
Use in the elderly
When using Bonefos, there is no need for dose adjustment in elderly patients. Clinical trials, in which patients over 65 years of age participated, confirmed that the drug is not characterized by side effects specific to this category of patients.
Drug interactions
Concomitant use of other bisphosphonates is contraindicated.
According to the results of some studies, there is a direct relationship between taking the drug and impaired renal function while prescribing non-steroidal anti-inflammatory drugs, mainly diclofenac.
When taking clodronic acid with aminoglycosides, care must be taken to avoid the development of hypokalemia.
The simultaneous use of Bonefos with estramustine causes an increase in the concentration of the latter in the blood serum up to 80%. When clodronic acid is combined with divalent cations (for example, calcium and iron), poorly soluble complexes are formed, therefore, it is undesirable to take tablets of this drug simultaneously with drugs or food products containing divalent cations (in particular, iron-containing agents or antacids). This can cause a decrease in the bioavailability of clodronic acid.
Analogs
The analogue of Bonefos is Klobir.
Terms and conditions of storage
Shelf life of tablets and capsules - 5 years, solution - 3 years. Keep out of the reach of children at a temperature not exceeding 25 ° C.
The prepared solution for infusion is stored for no more than a day at a temperature of 2-8 ° C.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Bonefos
According to reviews, Bonefos is vital for patients suffering from cancer. For this reason, it is issued to such patients free of charge. During treatment, it is important to constantly monitor the biochemical parameters of the blood.
Doctors note that when the concentration of calcium in the blood is 2.2 mmol / l or less, drug therapy must be combined with the intake of additional drugs containing calcium and vitamin D. According to experts, the tablets can be alternated with the use of an infusion solution. It is not recommended to take the medicine together with milk and dairy products due to their slow digestion. Some patients complain of nausea, abdominal pain, diarrhea, and heartburn during drug treatment.
Price for Bonefos in pharmacies
The price for a package of Bonefos in the form of a concentrate for a solution of 60 mg / ml is 5000–5600 rubles (it includes 5 ampoules). You can buy Bonefos in tablets at a dose of 800 mg for 9,300-11,000 rubles (60 pcs per pack). The cost of 400 mg capsules varies in the range of 9000–9600 rubles (per pack 100 pcs.).
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
