Bonefos - instructions for use, reviews, analogs and forms of release (tablets 800 mg, capsules 400 mg, injections in ampoules) for the treatment of hypercalcemia, tumors in bones with metastases in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Bonefos. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors specialists on the use of Bonefos in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Bonefos in the presence of existing structural analogs.Use for the treatment of hypercalcemia, tumors in bones with metastases, myeloma in adults, children, as well as in pregnancy and lactation. Composition of the drug.

Bonefos - inhibitor of bone resorption, bisphosphonate. Clodronic acid (the active substance of the preparation Bonefos) belongs to the group of bisphosphonates and is an analog of natural pyrophosphate. Bisphosphonates have a high affinity for the mineral components of bone tissue. The main mechanism of action of clodronic acid is suppression of osteoclast activity and a decrease in bone resorption mediated by them.

The ability of clodronic acid to inhibit bone resorption in humans has been confirmed in the course of histological, kinetic and biochemical studies. Nevertheless, the exact mechanisms of this process are not fully understood.

Bonefos suppresses the activity of osteoclasts, reducing the concentration of calcium in the blood serum, as well as the release of calcium and hydroxyproline in the urine.

Bisphosphonates inhibit the precipitation of calcium phosphate, block its transformation into hydroxyapatite, delay the aggregation of apatite crystals into larger crystals, and slow the dissolution of these crystals.

When clodronic acid was used in monotherapy in doses sufficient to inhibit the resorption of bone tissue, no effect on normal bone mineralization was observed in humans. In patients with breast cancer and multiple myeloma, there was a decrease in the probability of bone fractures.

Clodronic acid reduces the incidence of bone metastases in primary breast cancer. In patients with operable breast cancer for the prevention of metastases in the bone, there was also a decrease in mortality.

Composition

Disodium clodronate tetrahydrate + auxiliary substances.

Pharmacokinetics

The absorption of clodronic acid from the gastrointestinal tract occurs quickly and is approximately 2%. Due to the expressed affinity of clodronic acid for calcium and other divalent cations, clodronic acid absorption is significantly reduced when taking the drug with food or drugs containing divalent cations. Significant fluctuations in the absorption of clodronic acid from the gastrointestinal tract are also observed, both among different patients and in the same patient.Despite significant fluctuations in the rates of absorption in the same patient, the amount of clodronic acid obtained during long-term treatment remains constant. Clodronic acid binding to blood plasma proteins is low. Clodronic acid is excreted mainly by the kidneys. About 80% is detected in the urine within a few days after taking the drug. Clodronic acid, associated with bone tissue (about 20% of the absorbed dose), is excreted more slowly from the body. Kidney clearance is approximately 75% of the plasma clearance. There is no clear connection between the concentration of clodronic acid in the blood plasma and the therapeutic effect or adverse reactions. Pharmacokinetic profile of the drug does not depend on age, metabolism of the drug or functional disorders, with the exception of renal failure, which causes a decrease in renal clearance of clodronic acid.

Indications

osteolytic metastases of malignant tumors in the bone;
myeloma (multiple myeloma);
hypercalcemia due to malignant tumors.

Forms of release

Tablets coated with 800 mg.

Capsules 400 mg.

Concentrate for the preparation of a solution for intravenous administration (injections in ampoules for injections).

Instructions for use and dosing regimen

The drug is administered orally and intravenously in the form of infusions.

Capsules of 400 mg should be swallowed without chewing.

Tablets of 800 mg can be divided into two parts, but both parts should be taken simultaneously. Do not grind or dissolve tablets before taking.

The daily dose of 1600 mg (2 tablets) is recommended to be taken once a morning on an empty stomach, with a glass of water. After taking the drug, the patient should refrain from eating, drinking (except for ordinary water) and taking other medicines within an hour.

If the daily dose exceeds 1600 mg, it is taken in two divided doses. The first dose should be taken as recommended above. The second dose should be taken between meals, 2 hours after or 1 hour before meals, drinking (except ordinary water) or taking any other medicines inside.

Bonefos should not be taken with milk, food, or with preparations containing calcium or other divalent cations, since they all interfere with the absorption of clodronic acid.

To prepare the solution for infusion, the required dose is dissolved in 500 ml of 0.9% sodium chloride solution or 5% Dextrose solution.

Before and during treatment, you should ensure sufficient fluid intake for the patient, as well as monitor kidney function and calcium concentration in the blood serum.

Hypercalcemia caused by malignant neoplasms

The drug is given by 300 mg intravenously drip for 2 hours (at least) daily (no more than 7 consecutive days) until the normal concentration of calcium in the blood serum (which usually occurs within 5 days) or 1500 mg IV drip within 4 h once. If necessary, the infusion can be repeated or Bonefos administered inside. With the development of hypocalcemia, a brief interruption in treatment is recommended.

If intravenous administration is not possible, then Bonefos is administered orally at an initial dose of 2400-3200 mg daily. Depending on the individual response to treatment, with a decrease in the calcium content in the blood to normal levels, the dose is gradually reduced to 1600 mg.

Osteolytic bone changes due to malignant tumors without hypercalcemia

The dose in each case is determined individually. The recommended initial dose is 1600 mg per day. According to clinical indications, it can be increased, maximum - up to 3200 mg per day.

Patients with renal insufficiency

Clodronic acid is excreted mainly by the kidneys. Therefore, care should be taken when treating patients with renal insufficiency. The drug should not be administered orally at doses exceeding 1600 mg per day for a long time.

Elderly patients

There is no data on the need to change the dose of the drug in elderly patients. In clinical trials involving patients over 65 years of age, there were no side effects specific to this group of patients.

Side effect

asymptomatic hypocalcemia or rarely hypocalcemia accompanied by clinical manifestations;
increase in the concentration of parathyroid hormone in the serum (associated with a decrease in serum calcium levels);
an increase in serum AF in the serum (in patients with metastases, the level of AF may also increase due to the presence of metastases in the liver and bones);
diarrhea;
nausea, vomiting;
increased transaminases;
reactions of hypersensitivity, manifested as skin reactions;
in patients with bronchial asthma, with increased sensitivity to acetylsalicylic acid in the anamnesis, there were abnormalities in the function of respiration, bronchospasm;
impaired renal function (increased serum creatinine and proteinuria concentration);
severe renal failure, especially after rapid intravenous administration of clodronic acid in high doses;
osteonecrosis of the jaw;
pain in the bones, joints and / or muscles.

Contraindications

pregnancy;
lactation period;
concomitant therapy with other bisphosphonates;
severe (terminal) renal failure (CC less than 10 ml / min);
children's age (due to lack of clinical experience);
hypersensitivity to clodronic acid, other bisphosphonates or any other components that make up the drug.

Application in pregnancy and lactation

It is not known whether clodronic acid penetrates the placental barrier in humans, and whether Bonefos can cause fetal damage or affect the reproductive function of a person.It was found that clodronic acid penetrates the placental barrier in animals.

It is not known whether clodronic acid penetrates into breast milk.

Use in children

Contraindicated use of the drug in children and adolescents under the age of 18 (due to lack of clinical experience).

special instructions

Before and during the treatment with Bonephos, it is necessary to provide the patient with a sufficient amount of fluid, and also to monitor the kidney function and the concentration of calcium in the blood serum. This is especially important in the appointment of Bonefos in the form of intravenous infusions, as well as for patients with hypercalcemia and renal insufficiency.

In / in the administration of Bonefos in doses much higher than recommended, can cause severe damage to the kidneys, especially if the infusion rate is too high.

There are reports of the development of an osteonecrosis of the jaw, usually associated with tooth extraction and / or local infection (including osteomyelitis) in patients receiving antitumor therapy, including both intravenous and oral bisphosphonates.

It should be discussed the need for preventive sanation of teeth before therapybisphosphonates in patients with risk factors (eg, cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene); should avoid invasive dental interventions in patients receiving bisphosphonates.

The compatibility of the concentrate for the infusion solution with other drugs or solutions for injection has not been investigated. The drug should be diluted and administered only in accordance with the recommendations in the "Dosage regimen" section.

Impact on the ability to drive vehicles and manage mechanisms

Not studied.

Drug Interactions

Simultaneous use with other bisphosphonates is contraindicated.

There is evidence of a link between the use of clodronic acid and impaired renal function with the simultaneous administration of non-steroidal anti-inflammatory drugs (NSAIDs), most commonly diclofenac.

Due to the high probability of hypocalcemia, caution should be exercised when administering clodronic acid together with aminoglycosides.

It was reported that simultaneous administration of estramustine phosphate together with clodronic acid leads to an increase in the concentration of estramustine phosphate in the blood serum to 80%.

It was reported that simultaneous administration of estramustine together with clodronic acid leads to an increase in the concentration of estramustine in the serum up to 80%. Clodronic acid forms poorly soluble complexes with divalent cations (for example, calcium and iron), therefore Bonefos preparation tablets should not be taken concomitantly with food or drugs containing divalent cations (for example, antacids or iron preparations), which may lead to a decrease in the bioavailability of clopidone acid.

Pharmaceutical interaction

Analogues of the drug Bonefos

Structural analogs for the active substance:

Clobyr.

Analogues for the pharmacological group (inhibitors of bone resorption bisphosphonates):

Aklast;
Alendronate;
Blazter;
Bonviva;
Bondronate;
Veroclast;
Zolendronate Teva;
Zoledrax;
Zolendronik Rus 4;
Zolerix;
Zometa;
Ibandronic acid Sandoz;
Klobir;
Xidifon;
Ostalon;
Ostererepair;
Pamidronate Medak;
Pimegar;
Resoclastine;
Resorb;
Rizarteva;
Risendros;
Stringos;
Tevanath;
Forosa;
Fosamax.

If there are no analogues of the medication for the active substance, you can go to the links below for diseases, from which the corresponding drug helps, and to look at the available analogs for therapeutic effects.

Used for the treatment of diseases: tumor, cancer, myeloma, hypercalcemia, bone cancer, myeloma, multiple myeloma