Klobir (Clobir)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceClodronic acidClodronic acid
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    • Dosage form: & nbspcapsules
    Composition:

    1 capsule contains:

    active substance: clodronate disodium tetrahydrate 500.0 mg, corresponding to disodium clodronate 400.0 mg;

    Excipients: lactose monohydrate 28.2 mg, glyceryl dipalmitostearate crushed type I (Precirol ATO 5) 10.8 mg, silicon dioxide 1.0 mg;

    shell capsule body capsule: titanium dioxide (E 171) 2.0%, gelatin up to 100%;

    cap capsule: titanium dioxide (E 171) 0.6666%, indigo carmine FD & C Blue 2 (E 132) 0.08%, iron oxide pigment oxide yellow (E 172) 0.55%, gelatin up to 100%.

    Description:

    Hard gelatin capsules No. 1 with an opaque green lid and an opaque white body with an inscription in black ink "SINDRONATE® "and" 400 mgThe contents of capsules are 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. The action of bisphosphonates is based on 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 in the urine.

    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 bone resorption, 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.

    Pharmacokinetics:

    The absorption of clodronic acid in the gastrointestinal tract (GIT) 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.The volume of distribution is 20 liters. Communication with blood plasma proteins is low - about 30%.

    The excretion of 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 is excreted from the body more slowly. Kidney clearance is approximately 75% of the plasma clearance.

    As clodronic acid strongly binds to bone tissue, there is no clear association between clodronic acid concentrations in blood plasma and the therapeutic effect or adverse reactions of the drug.

    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 bone and myeloma(multiple myeloma);

    - prevention of development of bone metastases of primary breast cancer;

    - hypercalcemia due to malignant tumors.

    Contraindications:

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

    - pregnancy and the period of breastfeeding;

    - concomitant therapy with other bisphosphonates;

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

    - Chronic renal failure;

    - lactase insufficiency, lactose intolerance, glucose-galactose malabsorption (lactose is included in the formulation).

    Dosing and Administration:

    Inside.

    Capsules of 400 mg should be swallowed without chewing.

    A daily dose of 1600 mg 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, two hours after or one hour before meals, drinking (other than ordinary water), or ingesting other medicines.

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

    Hypercalcemia, caused by evilquality neoplasms

    If intravenous administration of the drug is impossible, clodronic acid is administered orally at an initial dose of 2400-3200 mg daily. When the calcium content in the blood decreases to a normal level, the dose is gradually reduced to 1600 mg.

    Prophylaxis of development of bone metastases of primary breast cancer

    For 1600 mg daily inside.

    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 up to a maximum of 3200 mg per day.

    Patients with renal insufficiency

    Inside clodronic acid in doses exceeding 1600 mg per day should not be taken for a long period of time.

    Side effects:

    Most often, approximately 10% of patients experience adverse reactions such as nausea, vomiting, diarrhea; these reactions usually appear in mild form and occur most often when the drug is used in high doses.

    From the endocrine system: increase in the concentration of parathyroid hormone in the serum (usually in combination with hypocalcemia).

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

    From the side of the digestive system: often - nausea, vomiting and diarrhea usually in mild form.

    From the skin and skin appendages: rarely - skin reactions, according to the clinical picture, corresponding to allergic reactions (itching, urticaria, exfoliative dermatitis).

    From the urinary system: rarely - renal dysfunction (increased serum creatinine and proteinuria), severe renal failure.

    From the laboratory indicators: often asymptomatic hypocalcemia; rarely - hypocalcemia, accompanied by clinical manifestations. Increase in the level of alkaline phosphatase, aminotransferase and lactate dehydrogenase in blood serum. In patients with metastases, the level of alkaline phosphatase may also increase due to the presence of metastases in the liver and bones.

    Overdose:

    Symptoms: hypercreatininaemia, impaired renal function.

    In case of an overdose, symptomatic treatment should be given. It is necessary to provide the patient with a sufficient supply of fluid, as well as monitor the kidney function and the calcium content in the blood serum.

    Interaction:

    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 probability of hypocalcemia, 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 poorly soluble complexes with divalent cations (calcium, iron, etc.); therefore, simultaneous intake of food products or drugs containing these cations (for example, antacids or iron preparations) leads to a significant decrease in the bioavailability of clodronic acid.

    Special instructions:

    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.

    Form release / dosage:

    Capsules, 400 mg.

    Packaging:

    For 10 capsules in a PVC blister / aluminum foil or 100 capsules in a dark glass bottle with a plastic lid.

    For 1, 3, 6 or 10 blisters or 1 bottle together with instructions for use in a cardboard pack.

    For 50, 100, 200, 400, 600 blisters or 10, 20, 40, 60, 80 or 100 bottles in a cardboard box with instructions for use (for hospitals).

    Storage conditions:

    In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

    Shelf life:

    3 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-005786/10
    Date of registration:23.06.2010
    Expiration Date:Unlimited
    The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland
    Manufacturer: & nbsp
    Representation: & nbspAktavis, Open Company Aktavis, Open Company
    Information update date: & nbsp29.01.2018
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