Fosrenol (Fosrenol)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceLantana carbonateLantana carbonate
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  • Fosrenol
    pills inwards 
    Johnson & Johnson, LLC     Russia
    • Dosage form: & nbspchewing tablets
    Composition:

    1 tablet contains:

    Active substance:

    Lanthanum (III) carbonate hydrate 954 mg in terms of lanthanum 500 mg

    Lanthanum (III) carbonate hydrate 1431 mg in terms of lanthanum 750 mg

    Lanthanum (III) carbonate hydrate 1908 mg in terms of lanthanum 1000 mg

    Excipients:

    Tablets 500 mg: dextrates (hydrated) 1066.4 mg, silicon dioxide colloid 42.4 mg, magnesium stearate 21.2 mg.

    Tablets 750 mg: dextrates (hydrated) 1599.6 mg, silicon colloid dioxide 63.6 mg, magnesium stearate 31.8 mg.

    Tablets 1000 mg: dextrates (hydrated) 2132.8 mg, silicon dioxide colloid 84.8 mg, magnesium stearate 42.4 mg.

    Description:

    Tablets 500 mg: round flat tablets white or almost white, with bevelled edges and engraved "S405" over "500".

    Tablets 750 mg: round flat tablets white or almost white, with bevelled edges and engraved "S405" over "750".

    Tablets 1000 mg: round flat tablets white or almost white, with beveled edges and engraved "S405" over "1000".

    Pharmacotherapeutic group:Hyperphosphatemia treatment
    ATX: & nbsp

    V.03.A.E.   Drugs for the treatment of hyperkalemia and hyperphosphataemia

    V.03.A.E.03   Lanthanum carbonate

    Pharmacodynamics:

    Fosrenol contains lanthanum carbonate. The activity of lanthanum carbonate as a binding agent phosphate, determined by the high affinity of lanthanum ions, which are released from the connection with the carbonate anion in the acidic environment of the stomach, to the food phosphates. An insoluble lanthanum phosphate forms, which reduces the absorption of phosphate from the gastrointestinal tract.

    Pharmacokinetics:

    Since the binding of lanthanum with dietary phosphate occurs in the lumen of the stomach and upper small intestine, the therapeutic effect of the drug Fosrenol does not depend on the concentration of lanthanum in plasma.

    Lanthanum is present in the environment. In phase III clinical trials background concentration of the substance in patients with chronic renal insufficiency, untreated lanthanum carbonate ranged from <0.05 to 0.90 ng / ml in blood plasma and from <0.006 to 1.0 ug / kg in bone biopsy samples .

    Suction

    Lanthanum carbonate is slightly soluble in water (<0.01 mg / ml at pH 7.5) and is minimally absorbed after oral administration. Absolute bioavailability in humans after oral administration is estimated at <0.002%.

    After oral ingestion by healthy people, the area under the concentration-time curve (AUC) and the maximum concentration (CmOh) of lanthanum in the blood plasma increase more slowly than in direct dose dependence in the range of 250-1000 mg of lanthanum, which corresponds to absorption limited by solubility. Half-life in healthy people is 36 hours.

    In patients who were on hemodialysis and received 1000 mg of lanthanum 3 times a day for 10 days, the average concentration of the substance in the blood plasma was 1.06 (± 1.04) ng / ml, and the mean AUCo-After - 31.1 (± 40.5) ng x hour / ml. Regular monitoring of the concentration of lanthanum in the blood of 1,707 patients on hemodialysis who received lanthanum carbonate for a period of up to 2 years, did not reveal an increase in the concentration of the substance in the blood plasma during this period.

    Distribution

    With repeated oral administration of lanthanum carbonate, lanthanum does not accumulate in the blood plasma of humans and animals. A small fraction of lanthanum, which is absorbed after oral administration, almost completely (> 99.7%) binds to plasma proteins. In studies on animals after absorption, lanthanum was widely distributed throughout the tissues of the body, mainly in bones, the liver, the gastrointestinal tract and mesenteric lymph nodes.In long-term studies in animals, it was found that the concentration of lanthanum in some tissues, including the gastrointestinal tract, bones and liver, eventually increased to a value several orders of magnitude higher than the concentration of the substance in the blood plasma. In some tissues, for example, in liver cells, the equilibrium concentration of lanthanum was gradually achieved, and in the gastrointestinal tract the concentration of the substance increased during the entire period of application of the preparation. After the drug was discontinued, the concentration of lanthanum varied in different tissues in different tissues, with a relatively high proportion of accumulated lanthanum in the tissues retained for more than 6 months after cancellation (median percentage of the remaining lanthanum in bones: <100% (rat), <87% (dogs); liver: <6% (rats), <82% (dogs)). In long-term studies on animals, the accumulation of lanthanum in tissues with oral administration of high doses of lanthanum carbonate was not accompanied by any adverse effects.

    Metabolism

    Lanthanum is not metabolized.

    Clinical studies of the use of the drug on patients with renal insufficiency and impaired liver function were not conducted.In patients who had concomitant liver disease at the time of inclusion in the P1 phase of clinical trials, there was no evidence of an increase in lanthanum concentration in the blood plasma or an increase in liver function impairment with the use of the drug Fosrenol for up to 2 years.

    Excretion

    In healthy people lanthanum is excreted mainly with feces, and only about 0.000031% of the orally taken dose is excreted in the urine (renal clearance of approximately 1 ml / min, which corresponds to <2% of the total clearance from the blood plasma).

    After intravenous administration, lanthanum was excreted mainly with feces (74% of the dose), both with bile and through direct penetration through the intestinal wall. Excretion through the kidneys was insignificant.

    Indications:

    Fosrenol is used as a phosphate binding substance to control hyperphosphataemia in patients with chronic renal failure receiving hemodialysis or permanent ambulatory peritoneal dialysis (CAPD).

    Fosrenol is also indicated in adult patients with chronic kidney disease not on hemodialysis, with a plasma phosphate concentration of> 1.78 mmol / L, for which a low-phosphate diet is not sufficient to control the concentration of phosphate in the plasma.

    Contraindications:

    hypersensitivity to lanthanum carbonate or to any auxiliary component of the drug;

    hypophosphatemia;

    children's age till 18 years.

    Carefully:

    conditions associated with a marked violation of bile outflow;

    gastric ulcer in the exacerbation stage, ulcerative colitis, Crohn's disease, intestinal obstruction.

    Pregnancy and lactation:

    Data on the use of the drug Fosrenol in pregnant women is not enough.

    In one study, rats were found to have fetal toxicity (delay in eye opening and puberty) and decrease in the body weight of the offspring at high doses of the drug. The possible risk to people is unknown. Fosrenol is not recommended for use during pregnancy.

    It is not known whether lanthanum is excreted in breast milk. In animal studies, excretion of lanthanum with breast milk has not been studied. The doctor must decide whether to continue breastfeeding or continue treatment with the drug based on the risk / benefit ratio for the mother and the baby.

    Dosing and Administration:

    Inside. Tablets should be chewed, not swallowed whole.

    The experience of using the drug for more than 2 years is limited.It is necessary to carefully evaluate the risk-benefit relationship with the duration of the drug for more than 2 years.

    Adults, including the elderly (> 65 years)

    Fosrenol should be taken with or immediately after a meal, and the daily dose should be divided between meals. Patients should follow the recommended diet to control the concentration of phosphate and water balance. Fosrenol is available in the form of chewable tablets, which avoids additional fluid intake. The concentration of phosphates in serum should be monitored and the dose of Phosrenol should be increased every 2-3 weeks until an acceptable phosphate concentration is reached, after which the concentration of phosphates should be monitored regularly.

    There is evidence that control of the phosphate concentration in the blood is achieved at an initial dose of 750 mg / day. In clinical trials, the maximum dose of the drug (in a limited number of patients) was 3750 mg. In patients sensitive to the use of lanthanum, an acceptable concentration of phosphates in the blood serum is usually achieved with a lanthanum dose of 1500-3000 mg / day.

    Children and teens

    Safety and effectiveness of the drug Fosrenol in patients under the age of 18 years has not been studied.

    Impaired liver function

    Influence of violations of the liver on the pharmacokinetics of the drug Fosrenol has not been studied. Due to the peculiarities of the mechanism of action and the absence of hepatic metabolism, the dose of the drug does not need to be corrected if the liver functions are disturbed, but the patients should be carefully monitored.

    Side effects:

    Adverse reactions associated with the use of the drug (according to the researcher), were recorded in approximately 24% of participants in studies with the terminal stage of chronic renal failure. For no adverse reaction the frequency did not exceed 10%. The most frequent adverse drug reactions (except for hypocalcemia) were gastrointestinal effects; they were minimized when taking the drug Fosrenol during meals, and decreased with continued treatment.

    Organ / system

    Frequent reactions (1-10%)

    Infrequent reactions (0.1-1%)

    Infections


    gastroenteritis, laryngitis

    Blood and lymphatic system


    eosinophilia

    Endocrine system


    hyperparathyroidism

    Metabolism and nutrition

    hypocalcemia

    hypercalcemia, hyperglycemia, hyperphosphataemia, hypophosphatemia, anorexia, increased appetite

    Nervous system


    dizziness, headache, taste disorder

    Ear and labyrinth


    vertigo

    Gastrointestinal

    tract

    abdominal pain, constipation, diarrhea, indigestion, flatulence, nausea, vomiting

    eructations, digestive disorders, irritable bowel syndrome, dry mouth, esophagitis, stomatitis, loose stools, dental lesions, gastrointestinal disorders, unspecified

    Skin and subcutaneous tissue


    alopecia, itching, erythematous rash, hyperhidrosis

    Musculoskeletal system and connective tissue


    arthralgia, myalgia, osteoporosis

    General state


    asthenia, chest pain, weakness,



    general poor health, peripheral edema, pain, thirst

    Changes in laboratory indicators


    increased concentration of aluminum in the blood, increased activity

    gamma glutamyltranspeptidase, hepatic transaminases, alkaline phosphatase, weight loss

    There was a transient change in the interval QT, but it was not accompanied by an increase in the incidence of cardiac adverse events.

    Overdose:

    Cases of overdose are not described. The largest daily dose of lanthanum for healthy volunteers was 4718 mg for 3 days.Adverse events were mild or moderate and included nausea and headache.

    Interaction:

    Lantana carbonate can increase the pH of gastric juice. It is not recommended to take drugs that interact with antacids (for example, chloroquine, hydroxychloroquine, ketoconazole), within 2 hours before and after taking the drug Fosrenol.

    In healthy people, simultaneous intake of citrate does not affect the absorption and pharmacokinetics of lanthanum.

    In clinical trials, the use of the drug Fosrenol did not affect the content of fat-soluble vitamins A, D, E and K in serum.

    In studies involving healthy volunteers, taking Fosrenol together with digoxin, warfarin, or metoprolol did not lead to a clinically significant change in the pharmacokinetics of these drugs.

    In a solution modeling gastric juice, lanthanum carbonate did not form insoluble complexes with warfarin, digoxin, furosemide, phenytoin, metoprolol or enalapril, suggesting a weak ability to influence the absorption of these substances.

    However, it is theoretically possible to interact with tetracycline, doxycycline, and floxacin derivatives, and,if these drugs should be used simultaneously, it is recommended to take them 2 hours before or 2 hours after taking the drug Fosrenol.

    Lanthanum carbonate is not a substrate of cytochrome P450 and does not significantly inhibit in vitro activity of the main isoenzymes of the human cytochrome P450 system, including CYP1A2, CYP2D6, CYP3A4, CYP2C9 and CYP2C19.

    Special instructions:

    When using the drug Fosrenol in animals shows the accumulation of lanthanum in tissues. When analyzing 105 biopsy specimens of the bones of patients who received Fosrenol (some up to 4.5 years), lanthanum concentrations increased over time. There are no clinical data on the accumulation of lanthanum in other tissues. Currently, data on the safety of the drug for a period of more than 24 months are limited. It is necessary to carefully evaluate the risk-benefit relationship with prolonged use of the drug.

    In clinical trials of the drug, Fosrenol did not include patients with acute gastric ulcer, ulcerative colitis, Crohn's disease or intestinal obstruction. In such patients, Fosrenol should only be used after a thorough assessment of the risk-benefit ratio.

    In patients with renal insufficiency, hypocalcemia may develop. Fosrenol does not contain calcium.Therefore, in this category of patients should regularly monitor the concentration of calcium in the blood serum, and if necessary, should prescribe calcium preparations.

    Lanthanum is not metabolized by liver enzymes, but is most likely excreted with bile. Conditions associated with a marked violation of bile outflow may be accompanied by a delay in lanthanum excretion, which may lead to an increase in its concentration in the blood plasma and to an increase in lanthanum deposition in the tissues. Since the liver is the main organ of excretion of absorbed lanthanum, it is recommended that liver function monitoring be performed.

    With the development of hypophosphatemia, phosrenol should be discontinued.

    In patients taking lanthanum carbonate, radiation absorption typical of contrast agents may be observed with radiography of the abdominal cavity organs.

    Effect on the ability to drive transp. cf. and fur:Phosrenol can cause dizziness and vertigo, which can disrupt the ability to drive and move vehicles. When symptoms occur, patients are advised to refrain from driving and moving machinery.
    Form release / dosage:Tchewing gum flies 500 mg, 750 mg, 1000 mg.
    Packaging:

    500 mg: 45 tablets per bottle of high-density polyethylene with a polypropylene screw cap with first opening control, protected from accidental opening by children. 2 bottles together with instructions for medical use are placed in a cardboard box.

    750 mg, 1000 mg: 15 tablets per bottle of high-density polyethylene with a polypropylene screw cap with a first opening control, protected from accidental opening by children. 6 bottles together with instructions for medical use are placed in a cardboard box.

    Storage conditions:

    Store at a temperature not exceeding 25 ° C. Store the vial in its own carton. Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-000080
    Date of registration:10.12.2010
    The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia
    Manufacturer: & nbsp
    HAMOL, Limited United Kingdom
    Information update date: & nbsp27.09.2015
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