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  • Mimpara
    / Amgen


    Active Ingredient
    Cinacalcet 30, 60, 90 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    28 X 30 mg

    partial basket chart 16828 13658

    Film Coated Tablets

    28 X 60 mg

    partial basket chart 16831 13659

    Film Coated Tablets

    28 X 90 mg

    partial basket chart 16833 13660

    Related information


    Dosage

    Secondary hyperparathyroidism
    Adults and elderly (>65 years): The recommended starting dose for adults is 30 mg once per day. Mimpara should be titrated every 2 to 4 weeks to a maximum dose of 180 mg once daily to achieve a target parathyroid hormone (PTH) in dialysis patients of between 150-300 pg/ml (15.9-31.8 pmol/l) in the intact PTH (iPTH) assay. PTH 2 levels should be assessed at least 12 hours after dosing with Mimpara. Reference should be made to current treatment guidelines.
    PTH should be measured 1 to 4 weeks after initiation or dose adjustment of Mimpara. PTH should be monitored approximately every 1-3 months during maintenance. Either the intact PTH (iPTH) or biointact PTH (biPTH) may be used to measure PTH levels; treatment with Mimpara does not alter the relationship between iPTH and biPTH.
    During dose titration, serum calcium levels should be monitored frequently, and within 1 week of initiation or dose adjustment of Mimpara. Once the maintenance dose has been established, serum calcium should be measured approximately monthly. If serum calcium levels decrease below the normal range, appropriate steps should be taken, including adjustment of concomitant therapy.
    Children and adolescents:
    Mimpara is not indicated for use in children and adolescents due to a lack of data on safety and efficacy.
    Parathyroid carcinoma and primary hyperparathyroidism
    Adults and elderly (> 65 years): The recommended starting dose of Mimpara for adults is 30 mg twice per day. The dose of Mimpara should be titrated every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg three or four times daily as necessary to reduce serum calcium concentration to or below the upper limit of normal. The maximum dose used in clinical trials was 90 mg four times daily.
    Serum calcium should be measured within 1 week after initiation or dose adjustment of Mimpara.
    Once maintenance dose levels have been established, serum calcium should be measured every 2 to 3 months. After titration to the maximum dose of Mimpara, serum calcium should be periodically monitored; if clinically relevant reductions in serum calcium are not maintained, discontinuation of Mimpara therapy should be considered.
    Children and adolescents: Mimpara is not indicated for use in children and adolescents due to a lack of data on safety and efficacy.
    Hepatic impairment: No change in starting dose is necessary. Mimpara should be used with caution in patients with moderate to severe hepatic impairment and treatment should be closely monitored during dose titration and continued treatment.
    Method of administration: For oral use. It is recommended that Mimpara be taken with food or shortly after a meal, as studies have shown that bioavailability of cinacalcet is increased when taken with food.
    Tablets should be taken whole and not divided.


    Indications

    Treatment of secondary hyperparathyrodism (HPT) in patients with end-stage renal disease (ESRD) on maintenance dialysis therapy.
    May be used as part of a therapeutic regimen including phosphate binders and/or vitamin D steroids, as appropriate.
    Reduction of hypercalcemia in patients with:
    – parathyroid carcinoma
    – primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels (as defined by relevant treatment guidelines), but in whom parathyroidectomy is not clinically appropriate or is contraindicated.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    Serum calcium: Mimpara treatment should not be initiated in patients with a serum calcium (corrected for albumin) below the lower limit of the normal range.
    Life threatening events and fatal outcomes associated with hypocalcaemia have been reported in adult and paediatric patients treated with Mimpara. Manifestations of hypocalcaemia may include paraesthesias, myalgias, cramping, tetany and convulsions. Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia secondary to hypocalcaemia.
    Cases of QT prolongation and ventricular arrhythmia have been reported in patients treated with cinacalcet. Caution is advised in patients with other risk factors for QT prolongation such as patients with known congenital long QT syndrome or patients receiving medicinal products known to cause QT prolongation.
    Since cinacalcet lowers serum calcium, patients should be monitored carefully for the occurrence of hypocalcaemia. Serum calcium should be measured within 1 week after initiation or dose adjustment of Mimpara. Once the maintenance dose has been established, serum calcium should be measured approximately monthly.
    General: Adynamic bone disease may develop if PTH levels are chronically suppressed below approximately 1.5 times the upper limit of normal with the iPTH assay. If PTH levels decrease below the recommended target range in patients treated with Mimpara, the dose of Mimpara and/or vitamin D sterols should be reduced or therapy discontinued.
    Hepatic impairment: Due to the potential for 2 to 4 fold higher plasma levels of cinacalcet in patients with moderate to severe hepatic impairment (Child-Pugh classification), Mimpara should be used with caution in these patients and treatment should be closely monitored.
    See prescribing information for full details.


    Side Effects

    The most commonly reported undesirable effects were transient mild to moderate nausea and vomiting. Other common undesirable effects were: dizziness, paraesthesia, rash, myalgia, asthenia, hypocalcemia and reduced testosterone levels.
    See prescribing information for full details.


    Drug interactions

    Effect of other medications on cinacalcet: Cinacalcet is metabolised in part by the enzyme CYP3A4. Co-administration of 200 mg bid ketoconazole, a strong inhibitor of CYP3A4, caused an approximate 2-fold increase in cinacalcet levels. Dose adjustment of Mimpara may be required if a patient receiving Mimpara initiates or discontinues therapy with a strong inhibitor (e.g. ketoconazole, itraconazole, telithromycin, voriconazole, ritonavir) or inducer (eg rifampicin) of this enzyme. In vitro data indicate that cinacalcet is in part metabolised by CYP1A2. Smoking induces CYP1A2; the clearance of cinacalcet was observed to be 36-38% higher in smokers than non-smokers. The effect of CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) on cinacalcet plasma levels has not been studied. Dose adjustment may be necessary if a patient starts or stops smoking or when concomitant treatment with strong CYP1A2 inhibitors is initiated or discontinued.
    Calcium carbonate: Co-administration of calcium carbonate (single 1500 mg dose) did not alter the pharmacokinetics of cinacalcet.
    Sevelamer:
    Co-administration of sevelamer (2400 mg tid) did not affect the pharmacokinetics of cinacalcet.
    Pantoprazole: Co-administration of pantoprazole (80 mg od) did not alter the pharmacokinetics of cinacalcet.
    Effect of cinacalcet on other medications:
    Medicinal products metabolised by the enzyme P450 2D6 (CYP2D6): Cinacalcet is a strong inhibitor of CYP2D6. Dose adjustments of concomitant medicinal products may be required when Mimpara is administered with individually titrated, narrow therapeutic index substances that are predominantly metabolised by CYP2D6 (e.g. flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine).
    Desipramine: Concurrent administration of 90 mg cinacalcet once daily with 50 mg desipramine, a tricyclic antidepressant metabolised primarily by CYP2D6, significantly increased desipramine exposure 3.6-fold (90% CI 3.0, 4.4) in CYP2D6 extensive metabolisers.
    Dextromethorphan: Multiple doses of 50 mg cinacalcet increased the AUC of 30 mg dextromethorphan (metabolised primarily by CYP2D6) by 11-fold in CYP2D6 extensive metabolisers.
    Warfarin: Multiple oral doses of cinacalcet did not affect the pharmacokinetics or pharmacodynamics (as measured by prothrombin time and clotting factor VII) of warfarin. The lack of effect of cinacalcet on the pharmacokinetics of R- and S-warfarin and the absence of auto-induction upon multiple dosing in patients indicates that cinacalcet is not an inducer of CYP3A4, CYP1A2 or CYP2C9 in humans.
    Midazolam: Co-administration of cinacalcet (90 mg) with orally administered midazolam (2 mg), a CYP3A4 and CYP3A5 substrate, did not alter the pharmacokinetics of midazolam. These data suggest that cinacalcet would not affect the pharmacokinetics of those classes of medicines that are metabolized by CYP3A4 and CYP3A5, such as certain immunosuppressants, including cyclosporine and tacrolimus.


    Pregnancy and Lactation

    Pregnancy: There are no clinical data from the use of cinacalcet in pregnant women. Animal studies do not indicate direct harmful effects with respect to pregnancy, parturition or postnatal development. No embryonal/foetal toxicities were seen in studies in pregnant rats and rabbits with the exception of decreased foetal body weights in rats at doses associated with maternal toxicities. Mimpara should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
    Breast-feeding: It is not known whether cinacalcet is excreted in human milk. Cinacalcet is excreted in the milk of lactating rats with a high milk to plasma ratio. Following careful benefit/risk assessment, a decision should be made to discontinue either breast-feeding or treatment with Mimpara.


    Overdose

    Doses titrated up to 300 mg once daily have been safely administered to patients receiving dialysis. Overdose of Mimpara may lead to hypocalcaemia. In the event of overdose, patients should be monitored for signs and symptoms of hypocalcaemia, and treatment should be symptomatic and supportive. Since cinacalcet is highly protein-bound, haemodialysis is not an effective treatment for overdose.


    Important notes

    Shelf life: Blister: 5 years.


    Manufacturer
    Amgen Europe B.V., Breda, Netherlands.
    Licence holder
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