Cinacalcet Viatris (previously Cinacalcet Mylan) · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-217069 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile Secondary hyperparathyroidism, parathyroid carcinoma and primary hyperparathyroidism Based on available data from patients receiving cinacalcet in placebo controlled studies and single-arm studies the most commonly reported adverse reactions were nausea and vomiting. Nausea and vomiting were mild to moderate in severity and transient in nature in the majority of patients. Discontinuation of therapy as a result of undesirable effects was mainly due to nausea and vomiting. 9 Tabulated list of adverse reactions Adverse reactions, considered at least possibly attributable to cinacalcet treatment in the placebo controlled studies and single-arm studies based on best-evidence assessment of causality are listed below using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Incidence of adverse reactions from controlled clinical studies and post-marketing experience System organ class Very Common Common Not known Immune system disorders Hypersensitivity reactions* Metabolism and nutrition Anorexia disorders Decreased appetite Nervous system disorders Seizures† Dizziness Paraesthesia Headache Cardiac disorders Worsening heart failure* † QT prolongation and ventricular arrhythmia secondary to hypocalcaemia* † Vascular disorders Hypotension Respiratory, thoracic and Upper respiratory infection mediastinal disorders Dyspnoea Cough Gastrointestinal disorders Nausea

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217065 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Hypocalcaemia (see sections 4.2 and 4.4).

HOS-217064 · has-indication-information · PDF-Seite 2

Secondary hyperparathyroidism Adults Treatment of secondary hyperparathyroidism (HPT) in adult patients with end-stage renal disease (ESRD) on maintenance dialysis therapy. 2 Paediatric population Treatment of secondary hyperparathyroidism (HPT) in children aged 3 years and older with end-stage renal disease (ESRD) on maintenance dialysis therapy in whom secondary HPT is not adequately controlled with standard of care therapy (see section 4.4). Cinacalcet Viatris may be used as part of a therapeutic regimen including phosphate binders and/or vitamin D sterols, as appropriate (see section 5.1). Parathyroid carcinoma and primary hyperparathyroidism in adults Reduction of hypercalcaemia in adult 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.

HOS-217067 · has-interaction-information · PDF-Seite 8

Medicinal products known to reduce serum calcium Concurrent administration of other medicinal products known to reduce serum calcium and cinacalcet may result in an increased risk of hypocalcaemia (see section 4.4). Patients receiving cinacalcet should not be given etelcalcetide (see section 4.4). Effect of other medicinal products on cinacalcet Cinacalcet is metabolised in part by the enzyme CYP3A4. Co-administration of 200 mg, twice daily ketoconazole, a strong inhibitor of CYP3A4, caused an approximate 2-fold increase in cinacalcet levels. Dose adjustment of cinacalcet may be required if a patient receiving cinacalcet initiates or discontinues therapy with a strong inhibitor (e.g. ketoconazole, itraconazole, telithromycin, voriconazole, ritonavir) or inducer (e.g. 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 1,500 mg dose) did not alter the pharmacokinetics of cinacalcet. Sevelamer Co-administration of sevelamer (2,400 mg, three times a day) did not affect the pharmacokinetics of cinacalcet. Pantoprazole Co-administration of pantoprazole (80 mg, once daily) did not alter the pharmacokinetics of cinacalcet. Effect of cinacalcet on other medicinal products 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 cinacalcet 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

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217068 · has-pregnancy-information · PDF-Seite 9

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 (see section 5.3). Cinacalcet Viatris 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 Cinacalcet Viatris. Fertility There are no clinical data relating to the effect of cinacalcet on fertility. There were no effects on fertility in animal studies.

HOS-217066 · has-warning-information · PDF-Seite 6

Serum calcium Life threatening events and fatal outcomes associated with hypocalcaemia have been reported in adult and paediatric patients treated with cinacalcet. 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 (see section 4.8). 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 (see section 4.2). Serum calcium should be measured within 1 week after initiation or dose adjustment of cinacalcet. Adults Cinacalcet treatment should not be initiated in patients with a serum calcium (corrected for albumin) below the lower limit of the normal range. In Chronic Kidney Disease (CKD) patients receiving dialysis who were administered cinacalcet, approximately 30% of patients had at least one serum calcium value less than 7.5 mg/dl (1.9 mmol/l). Paediatric population Cinacalcet Viatris should only be initiated for the treatment of secondary HPT in children ≥ 3 years old with ESRD on maintenance dialysis therapy, in whom secondary HPT is not adequately controlled with standard of care therapy, where serum calcium is in the upper range of, or above, the age- specified reference interval. Closely monitor serum calcium levels (see section 4.2) and patient compliance during treatment with cinacalcet. Do not initiate cinacalcet or increase the dose if non-compliance is suspected. Prior to initiating cinacalcet and during treatment, consider the risks and benefits of treatment and the ability of the patient to comply with the recommendations to monitor and manage the risk of hypocalcaemia. 6 Inform paediatric patients and/or their caregivers about the symptoms of hypocalcaemia and about the importance of adherence to instructions about serum calcium monitoring, and posology and method of administration. CKD patients not on dialysis Cinacalcet is not indicated for CKD patients not on dialysis. Investigational studies have shown that CKD patients not on dia

Auszug; vollständigen Abschnitt im Original lesen.