Active substancePamidronic acidPamidronic acid
Similar drugsTo uncover
  • Pamidronate medak
    concentrate d / infusion 
    medac GmbH     Germany
  • Pomegara
    concentrate d / infusion 
    Genfa Medica S.A.     Switzerland
  • Dosage form: & nbspconcentrate for solution for infusion
    Composition:

    1 ml of the preparation contains:

    active substance: disodium pamidronate (derived from: pamidronic acid 5.05 mg / 7.58 mg, sodium hydroxide 1.72 mg / 2.58 mg) 6 mg / 9 mg;

    Excipients: mannitol 40.0 mg / 37.5 mg, water for injection up to 1 ml
    Description:

    Transparent colorless liquid.

    Pharmacotherapeutic group:bone resorption inhibitor, bisphosphonate
    ATX: & nbsp

    M.05.B.A   Bisphosphonates

    M.05.B.A.03   Pamidronic acid

    Pharmacodynamics:Pamidronic acid is an inhibitor of bone resorption mediated by osteoclasts. Pamidronic acid forms a stable compound with crystals of hydroxyapatite of bone tissue and inhibits the dissolution of these crystals in vitro.

    It is believed that in vivo inhibition of resorption of bone tissue can, at least in part, be explained by the binding of pamidronic acid with mineral substances. Pamidronic acid inhibits the entry of osteoclast precursors into bone tissue and their subsequent transformation into mature osteoclasts responsible for the resorption of this tissue.

    In patients with malignant neoplasms pamidronic acid suppresses osteolysis and in the presence of hypercalcaemia caused by the tumor, reduces the levels of calcium and phosphorus in the blood serum and reduces their excretion 'and the excretion of hydroxyproline in the urine.

    Reducing the severity of hypercalcemia, increases the rate of glomerular filtration, which in most patients is accompanied by a decrease in the initially elevated serum creatinine concentration.

    Pharmacokinetics:

    Pamidronic acid has a high affinity for calcified tissues, which are considered the "place of apparent elimination" of pamidronic acid.

    After the start of infusion, the concentration of pamidronic acid in the blood plasma increases rapidly, and at the end of the infusion, it also decreases rapidly. The apparent half-life of pamidronic acid in plasma is about 0.8 hours. Therefore, the equilibrium concentration of pamidronic acid is reached with an infusion time of more than 2-3 hours.

    Cumulation of pamidronic acid in bone tissue is not limited by the volume of this tissue, but depends solely on the total dose of the drug administered.

    The association of circulating pamidronic acid with plasma proteins is about 54% and increases when the upperlimit of the normal value of the concentration of calcium in the blood.

    It is believed that pamidronic acid It does not undergo biotransformation and is excreted almost exclusively by the kidneys. After intravenous infusion, approximately 20-55 % The administered dose of pamidronic acid is detected in urine for 72 hours in unchanged form. Remained. the amount is delayed in the body for an indefinitely long time. The excretion of pamidronic acid with urine is biphasic, the apparent half-lives are, respectively, 1.6 and 27 hours.

    When a violation of liver function higher average values ​​of the area under the concentration-time curve (AUC) (39.7%) and Cmax (28.6%) were noted. Nevertheless, pamidronic acid all as quickly removed from the plasma. After 12-36 hours after the infusion, the drug was not detected in the plasma. Since the drug is used only once a month, cumulation of pamidronic acid does not occur.

    With significant violations of kidney function (creatinine clearance <30 ml / min) mean AUC increases about 3 times. Although the rate of excretion of pamidronic acid decreases depending on the creatinine clearance, the total amount of pamidronic acid excreted by the kidneys remains essentially unchanged.

    Indications:

    - Hypercalcemia caused by malignant tumors.

    - Diseases accompanied by increased activity of osteoclasts: bone metastases of malignant tumors (mainly osteolytic) and multiple myeloma.

    - Bone disease of Paget.

    Contraindications:

    - Hypersensitivity to pamidronic acid or other bisphosphonates, as well as to other ingredients that make up the drug.

    - Pregnancy (except for cases of hypercalcemia, life threatening) and the period of breastfeeding.

    - Child age (no experience with children)

    Carefully:Impaired renal function.
    Pregnancy and lactation:There were no reliable clinical studies of the drug on pregnant women. Pamidronic acid can have harmful effects on the embryo. Do not use the drug during pregnancy, except for life-threatening hypercalcemia (in animals there is no teratogenic effect of pamidronic acid, as well as negative effects on reproductive function and fertility).

    When taking pamidronic acid during lactation, breastfeeding should be discontinued.

    Dosing and Administration:

    Intravenously in the form of infusion with a rate of administration of not more than 1 mg / min.

    Use in adults and elderly patients

    Hyperkalciemia caused by malignant tumors. Before starting the use of Pomegra or during therapy it is recommended to rehydrate the patient with a 0.9% solution of sodium chloride. The total dose of Pomgana used during the course of treatment depends on the initial level of calcium in the patient's serum. Below in the table are recommendations on the choice of the required dose of pamidronic acid depending on the values ​​of calcium concentration in the blood serum.

    The baseline level of calcium in the blood

    Recommended total dose of pamidronic acid

    (mmol / L)

    (mg%)

    (mg)

    not more than 3,0

    Not more than 12,0

    15-30

    3,0-3,5

    12,0-14,0

    30-60

    3,5-4,0

    14,0 -16,0

    60 -90

    more than 4,0

    90

    The total dose of Pomegra can be administered both at a time and in the form of several infusions performed within 2-4 consecutive days. The maximum course dose of the drug (for both the first and subsequent courses of treatment) is 90 mg. A significant decrease in serum calcium concentration is usually observed 24-48 hours after the administration of pamidronic acid, the normalization of this indicator is within 3-7 days.If normalization of the level of calcium in the blood within the specified time is not achieved, additional administration of the drug is possible. The duration of the preservation of the effect in individual patients is different. With the resumption of hypercalcemia, repeated courses of therapy of pamidronic acid are carried out. With increasing number of courses of administration, the efficacy of pamidronic acid may decrease.

    Bone metastases of malignant tumors (mainly osteolithinic nature) and myeloma. The recommended dose is 90 mg, once every 4 weeks. In patients with bone metastases of malignant tumors receiving chemotherapy at 3-week intervals, Pmegara at a dose of 90 mg can also be administered at 3-week intervals.

    Bone disease of Paget. The recommended total dose of Pomegary during the course of treatment is 180 - 210 mg. The total dose of the drug, 180 mg, can be administered either as 6 infusions (30 mg once a week) or as 3 infusions (60 mg once every 2 weeks). If the total dose is supposed to be 210 mg, then a dose of 30 mg is recommended for the first dose.This dosage regimen (but with an initial dose of 30 mg) can be repeated 6 months before remission of the disease or in case of an exacerbation.

    Use in patients with impaired renal function

    Pamidronic acid is not recommended for patients with severe renal dysfunction (creatinine clearance less than 30 ml / min), except in cases of life-threatening hypercalcemia, if the potential benefit of the application exceeds the risk of possible complications.

    In patients with mild (creatinine clearance 61-90 ml / min) or moderately (creatinine clearance of 30-60 ml / min) marked renal dysfunction, correction of the dosing regimen is not required. The rate of infusion of pamidronic acid in such patients should not exceed 90 mg / 4 hours (approximately 20-22 mg / h).

    When there are signs of impaired renal function, therapy with pamidronic acid should be canceled until the kidney function is restored (exceeding the creatinine concentration by no more than 10% of the baseline level).

    Use in patients with impaired liver function

    For patients with mild or moderate impairment of liver function, dosage adjustment of the drug is not required.

    Rules of preparation of infusion solution.

    The contents of the vial before administration should be further diluted with a solution for infusions that do not contain calcium (for example, 0.9 % solution of sodium chloride or 5 % solution of dextrose) to a concentration not exceeding 90 mg / 250 ml.

    Side effects:

    Adverse reactions with pamidronic acid are usually mild and temporary. The most frequent adverse reactions are asymptomatic hypocalcemia and fever (1-2 ° C body temperature increase), usually developing in the first 48 hours after the infusion of the drug. The fever usually passes independently and does not require treatment.

    Criteria for assessing the incidence of adverse events: "very often" - 10%, "often" from 1% to <10%, "sometimes" from 0.1% to <1%, "rarely" - from 0.01% to <0.1%, "very rarely" - <0.001%, including individual messages.

    From the side of the blood and lymphatic system: often - anemia, thrombocytopenia, lymphocytopenia; very rarely - leukopenia.

    From the immune system: sometimes allergic reactions, including anaphylactoid reactions, bronchospasm / dyspnea, Quincke's edema; very rarely - anaphylactic shock.

    From the nervous system: often - paresthesia, tetany (as manifestations of hypocalcemia), headache, insomnia or increased drowsiness; sometimes - cramps, agitation, dizziness; very rarely - confusion, visual hallucinations.

    From the sense organs: often - conjunctivitis; sometimes - uveitis (iritis, iridocyclitis); very rarely - scleritis, episcleritis, xanthopsia (vision of objects in yellow color).

    From the cardiovascular system: often marked increase in blood pressure (BP); sometimes - a marked decrease in blood pressure; very rarely - dyspnea, pulmonary edema (as signs of left ventricular failure), edema (as a sign of congestive heart failure) due to overload of the injected fluid.

    From the gastrointestinal tract: often - nausea, vomiting, anorexia, abdominal pain, diarrhea, constipation, gastritis; sometimes - dyspepsia.

    From the skin: often - a rash; sometimes itching.
    From the musculoskeletal system: often - transient pain in the bones, pain in the joints, myalgia; sometimes - muscle spasms.

    From the urinary system: sometimes - acute renal failure; rarely - focal segmental glomerulosclerosis,including collapoid variant, nephrotic syndrome; very rarely - exacerbation of concomitant kidney disease, hematuria.

    Exacerbation of infectious diseases: very rarely - reactivation of latent viral infections (Herpes simplex, Herpes Zoster).

    Local reactions: often - pain, redness, swelling, denseness, phlebitis, thrombophlebitis at the injection site.

    Laboratory indicators: very often - hypocalcemia, hypophosphatemia; often hypokalemia, hypomagnesemia, increased serum creatinine concentration; sometimes - changes in functional liver samples, increased urea concentration in blood serum; Very rarely - hyperkalemia, hypernatremia

    Other: very often - fever and flu-like symptoms, sometimes accompanied by malaise, chills, a sense of fatigue and tidal flare.

    Very rarely - the development of osteonecrosis (mainly the jaw, usually after extraction of the tooth or other dental intervention). A clear causal relationship between the development of osteonecrosis is not established.

    Overdose:

    When exceeding the recommended doses of the drug, careful monitoring of the patient's condition is necessary. The antidote is not known.With the development of clinical signs of hypocalcemia (paresthesia, tetany, pronounced decrease in blood pressure) should be an infusion of calcium gluconate.

    Interaction:

    The combined use of pamidronic acid with frequently used antineoplastic agents was not accompanied by any significant interactions.

    When combined with calcitonin in patients with severe hypercalcemia synergism of action was noted, which led to a more rapid decrease in serum calcium concentration.

    Caution is necessary when concomitant administration with other drugs that have a nephrotoxic effect.

    In patients with myeloma disease, when combined with tolbutamide, the risk of renal impairment increases.

    Pharmaceutical incompatibility. Pamidronic acid can form complexes with divalent cations and therefore should not be added to intravenous solutions containing calcium (for example, with Ringer's solution).

    Special instructions:

    The use of bisphosphonates, including pamidronic acid, can lead to impaired renal function.Because of the risk of developing clinically significant renal dysfunction, a single dose should not exceed 90 mg, and the recommended rates of dilution and the rate of administration of the drug should also be observed. Usually pamidronic acid in a dose of 90 mg in 250 ml of the infusion solution is introduced within 2 hours. In patients with myeloma and with hypercalcemia due to malignant tumors, a dose of pamidronic acid of 90 mg is diluted in 500 ml of an infusion solution and injected for more than 4 hours.

    During the treatment, monitoring of renal function (determination of serum creatinine concentrations before each infusion of pamidronic acid), concentration of electrolytes, calcium and phosphorus in the blood serum is necessary.

    The risk of hypocalcemia is elevated in patients who underwent surgical intervention on the thyroid gland, due to latent hypoparathyroidism.

    In patients suffering from heart disease, especially in elderly patients, the introduction of additional amounts of saline can lead to the appearance or strengthening of signs of heart failure (acute left ventricular or chronic).Fever (or flu-like syndrome) can also contribute to the development of this complication.

    In order to reduce the risk of developing hypocalcemia in patients with Paget's bone disease, who are at increased risk of developing calcium and vitamin deficiency D, should additionally prescribe these drugs inside.

    Pamidronic acid should not be used in conjunction with other bisphosphonates, since the effects of this combination treatment have not been studied.

    There were cases of osteonecrosis of the jaw in patients with oncological diseases receiving bisphosphonates (including pamidronic acid).

    In this regard, before appointment to oncological patients of pamidronic acid, as well as other bisphosphonates, patients should undergo dental examination and conduct all necessary preventive procedures. During the treatment period, strictly observe oral hygiene and, if possible, avoid dental operations.

    Effect on the ability to drive transp. cf. and fur:Some side effects of the drug, such as drowsiness and / or dizziness, can adversely affect the ability to drive and perform potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.
    Form release / dosage:

    Concentrate for the preparation of a solution for infusions of 6 mg / ml or 9 mg / ml.

    Packaging:

    For 10 ml of the preparation in a colorless glass USP type I bottle capped with a rubber lid, rolled with an aluminum cap and closed with a plastic lid for - first opening control.

    1 bottle with instructions for use in a pack of cardboard.

    Storage conditions:

    At a temperature of 15 to 25 ° C. Do not freeze.

    Keep out of the reach of children.

    Shelf life:

    3 years

    The drug should not be used after the expiry date indicated on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-002437
    Date of registration:11.01.2012
    The owner of the registration certificate: Genfa Medica S.A. Genfa Medica S.A. Switzerland
    Manufacturer: & nbsp
    Representation: & nbspHEAD OF MEDICA SAHEAD OF MEDICA SASwitzerland
    Information update date: & nbsp10.08.2015
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