Bonefos - instructions for use, doses, side effects, contraindications

Active substanceClodronic acidClodronic acid

Similar drugsTo uncover

Bonefos®

pills inwards

Bayer Oy Finland

Bonefos®

capsules inwards

Bayer Oy Finland

Bonefos®

concentrate in / in

Bayer Oy Finland

Klobir

concentrate in / in

AKTAVIS, LTD. Russia

Klobir

capsules inwards

AKTAVIS GROUP, AO Iceland

Dosage form: & nbspcapsules

Composition:

1 capsule contains:

active substance: disodium clodronate tetrahydrate 500 mg (equivalent to disodium clodronate anhydrous 400 mg);

Excipients: talc 22,80 mg, calcium stearate 2,85 mg, silicon dioxide colloidal anhydrous 2,85 mg, lactose monohydrate 41,50 mg.

The hard gelatin capsule contains: iron oxide dye red 0.0080%, iron oxide dye yellow 0.0080%, titanium dioxide 2,0000%, gelatin to 100%.

Description:

Hard gelatin capsules of light yellow color; on the cap of the capsule with black ink marked "BONEFOS". The contents of the capsules are almost white partially granulated powder.

Pharmacotherapeutic group:Bone resorption inhibitor-bisphosphonate

ATX: & nbsp

M.05.B.A.02 Clodronic acid

Pharmacodynamics:

Clodronic acid 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. Clodronic acid suppresses the activity of osteoclasts, reducing the concentration of calcium in the blood serum, as well as the release of calcium and hydroxyproline with the kidneys. In vitro 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 frequency of development of metastases in the bone in primary breast cancer.In patients with operable breast cancer, the use of clodronic acid for the prevention of metastases in the bone also showed a decrease in mortality.

Pharmacokinetics:

Suction Clodronic acid in the gastrointestinal tract occurs rapidly and is approximately 2%. The maximum concentration in the blood serum after oral administration of a single dose of the drug is achieved after 30 minutes. Due to the expressed affinity of clodronic acid for calcium and other divalent cations, the absorption of clodronic acid is significantly reduced when taking the drug with food or drugs containing divalent cations. When taking clodronic acid inside for 1 hour before a meal, relative bioavailability is 91%, in 30 minutes - 69%, respectively (the decrease in bioavailability is statistically insignificant in this case). Significant fluctuations in the rates of absorption of clodronic acid in 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.

Binding clodronic acid with blood plasma proteins is low.

The volume of distribution is 20-50 liters.

Excretion clodronic acid from blood serum is characterized by two phases: a distribution phase with a half-life period of about 2 hours and a phase of elimination proceeding very slowly, since clodronic acid firmly binds to bone tissue. Clodronic acid is excreted from the body, 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.

Features in patients

There is no clear relationship 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 and myeloma (multiple myeloma);

- hypercalcemia caused by malignant tumors.

Contraindications:

- Hypersensitivity to clodronic acid, other bisphosphonates or any other components that make up the drug;

- concomitant therapy with other bisphosphonates;

- severe (terminal) renal failure (creatinine clearance <10 ml / min);

- pregnancy and the period of breastfeeding;

- Children's age (due to lack of clinical experience).

Carefully:

In patients with impaired renal function.

The preparation Bonefos®, capsules, contains 46.36 mg of lactose. Patients with rare hereditary diseases, such as lactase deficiency, galactose intolerance, or glucose-galactose malabsorption, should not use this drug.

Pregnancy and lactation:

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

It is not known whether the clodronic acid in breast milk.

Dosing and Administration:

Inside. Capsules should be swallowed without chewing.

Tablets 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.

When appointing a daily dose of more than 1600 mg, it should be taken in two divided doses. The first part of the dose should be taken as recommended above. The rest of the dose should be taken between meals, 2 hours after or 1 hour before meals, drinking (except ordinary water) and taking other medications.

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.

Hypercalcemia due to malignant tumors

Intravenous injection is recommended. The preparation Bonefos® is administered orally at the initial high 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

Dosage 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, the treatment of patients with renal insufficiency requires caution; Inside should not take the drug at doses exceeding 1600 mg per day for a long period of time.

The dose of Bonefos ® should be reduced in accordance with the following recommendations:

Creatinine clearance (ml / min)	Dose
50-80 ml / min	1600 mg / day (dose reduction not recommended)
30-50 ml / min	1200 mg / day
10-30 ml / min	800 mg / day
<10 ml / min	Bonefos® is contraindicated

Elderly age

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 effects:

The most common side effect is diarrhea, which usually manifests itself in a mild form and is observed most often when the drug is used in high doses. Similar reactions can be observed both when taking the drug inside, and with its intravenous administration, although the frequency of their occurrence may differ.

The data are presented on the basis of the classification of organ systems by MedDRA (medical dictionary for regulatory activities). Consideration should be given to previously known side effects and other conditions associated with the use of Bonefos ®. The incidence of side effects is defined as: often> 1% and <10% (1/100 of prescriptions), rarely> 0.01% and <0.1% (1/10000 prescriptions).

Metabolic disorders: often asymptomatic hypocalcemia; rarely - hypocalcemia,accompanied by clinical manifestations; an increase in the concentration of parathyroid hormone in the serum (associated with a decrease in serum calcium concentration), an increase in the concentration of alkaline phosphatase in the serum (in patients with metastases, the activity of alkaline phosphatase may also increase due to the presence of metastases in the liver and bones).

Disorders from the gastrointestinal tract: often - diarrhea *, nausea *, vomiting *.

Disorders from the liver and bile ducts: often - increased transaminases are usually within normal limits; rarely - an increase in transaminases in 2 times, in comparison with the norm, without disturbing the liver function.

Disturbances from the skin and its appendages: rarely - reactions of increased sensitivity, manifested as skin reactions.

* usually in a light form.

Adverse reactions reported in the post-marketing application of the drug:

Disorders from the organs of vision: the occurrence of uveitis in patients receiving the preparation Bonefoe®. Conjunctivitis, episcleritis, scleritis against the background of therapy with other bisphosphonates. The emergence of conjunctivitis was observed only in one patient who took the preparation Bonefos ® simultaneously with another bisphosphonate.The incidence of episcleritis and scleritis against the background of therapy with Bonefos ® was not detected.

From the respiratory system: in patients with bronchial asthma, increased sensitivity to acetylsalicylic acid in history, there were violations of respiratory function, bronchospasm.

From the side of the kidneys and urinary tract: impaired renal function (increased serum creatinine and proteinuria), severe renal failure, especially after rapid IV administration of clodronic acid in high doses.

Single cases of renal failure, incl. with a fatal outcome, especially with simultaneous application with NSAIDs, most often - with diclofenac.

From the musculoskeletal and connective tissue: isolated reports of osteonecrosis of the jaw, mainly in patients who received previous therapy with aminobisphosphonates, such as zoledronic acid and pamidronic acid. There have been reports of cases of severe pain in the bones, joints and / or muscles in patients taking Bonnefos®. However, such reports were infrequent,and, according to randomized clinical trials, there was no difference in the frequency of occurrence of these events in patients taking Bonefos ® and in patients in the placebo group. Similar symptoms developed several days or several months after the start of Bonefos®.

During the postmarketing use of other bisphosphonates, the following adverse reactions were reported: an atypical fracture-prone femur and a fracture of the femoral diaphysis. On the background of therapy with Bonefos ®, no adverse reactions were noted.

Overdose:When intravenous high doses of clodronic acid were reported, an increase in serum creatinine and impaired renal function was reported. Similar symptoms were not reported when high doses of clodronic acid were administered orally.

Interaction:

Simultaneous use with other bisphosphonates is contraindicated.

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

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

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 with divalent cations (for example, Ca²⁺ and Fe²⁺) poorly soluble complexes, therefore, Bonefos ® 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 clodronic acid.

Special instructions:

During the treatment with Bonefos®, 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.

There are reports of the development of 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 administration of bisphosphonates. Many of these patients also received chemotherapy or glucocorticosteroids.

The need for preventive sanitation before bisphosphonate therapy in patients with risk factors should be discussed (eg, cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene); should avoid invasive dental interventions in patients receiving bisphosphonates.

Against the background of long-term treatment with bisphosphonates for osteoporosis, cases of atypical susceptible fractures of the femur and fractures of the femoral diaphysis were reported. These fractures include transverse or transverse oblique fractures, which can occur on any part of the femur below the small trochanter and above the epicondyles. These fractures can occur as a result of a minor injury or not be associated with injury in general. In some patients with pain in the thigh or groin, diagnostic signs of fractures inbackground of the load for several weeks or months before the onset of a complete fracture of the femur. Fractures were usually bilateral, therefore, it is necessary to examine the opposite thigh in patients receiving bisphosphonate treatment who have already suffered a fracture of the femoral diaphysis. These fractures are characterized by a slow fusion of the bone.

Bisphosphonates should be discontinued before the examination in patients with suspected atypical fracture of the femur, based on an individual assessment of benefit and risk.

Patients receiving bisphosphonate treatment should be advised to report pain in the hip, groin or hip joint. Also, patients with these symptoms should be examined for incomplete fracture of the femur.

With the use of Bonefos ®, there were no cases of atypical susceptible fractures of the femur and fractures of the femoral diaphysis.

Effect on the ability to drive transp. cf. and fur:

Not studied.

Form release / dosage:

Capsules, 400 mg.

Packaging:

For 100 capsules in a plastic bottle.

1 bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014659 / 02

Date of registration:14.05.2009 / 25.03.2013

Expiration Date:Unlimited

The owner of the registration certificate:Bayer OyBayer Oy Finland

Manufacturer: & nbsp

BAYER, OY Finland

Representation: & nbspBAYER, AOBAYER, AO

Information update date: & nbsp19.02.2017

Illustrated instructions

Instructions

Bonefos® (Bonefos®)