Copalia · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-094688 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile The safety of Copalia has been evaluated in five controlled clinical studies with 5,175 patients, 2,613 of whom received valsartan in combination with amlodipine. The following adverse reactions were found to be the most frequently occurring or the most significant or severe: nasopharyngitis, influenza, hypersensitivity, headache, syncope, orthostatic hypotension, oedema, pitting oedema, facial oedema, oedema peripheral, fatigue, flushing, asthenia and hot flush. Tabulated list of adverse reactions Adverse reactions have been ranked under headings of frequency 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). MedDRA Adverse reactions Frequency System organ Copalia Amlodipine Valsartan class Infections and Nasopharyngitis Common -- -- infestations Influenza Common -- -- Blood and Haemoglobin and -- -- Not known lymphatic system haematocrit decreased disorders Leukopenia -- Very rare -- Neutropenia -- -- Not known Thrombocytopenia, -- Very rare Not known sometimes with purpura Immune system Hypersensitivity Rare Very rare Not known disorders Metabolism and Hyperglycaemia -- Very rare -- nutrition Hyponatraemia Uncommon -- -- disorders Psychiatric Depression -- Uncommon -- disorders Anxiety Rare -- -- Insomnia/sleep disorders -- Uncommon -- Mood swings -- Uncommon -- Confusion -- Rare --

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094684 · has-contraindication-information · PDF-Seite 4

• Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the excipients listed in section 6.1. • Severe hepatic impairment, biliary cirrhosis or cholestasis. • Concomitant use of Copalia with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m2) (see sections 4.5 and 5.1). • Second and third trimesters of pregnancy (see sections 4.4 and 4.6). • Severe hypotension. • Shock (including cardiogenic shock). • Obstruction of the outflow tract of the left ventricle (e.g. hypertrophic obstructive cardiomyopathy and high grade aortic stenosis). • Haemodynamically unstable heart failure after acute myocardial infarction.

HOS-094683 · has-indication-information · PDF-Seite 2

Treatment of essential hypertension. Copalia is indicated in adults whose blood pressure is not adequately controlled on amlodipine or valsartan monotherapy. 2

HOS-094686 · has-interaction-information · PDF-Seite 6

Interactions common to the combination No drug-drug interaction studies have been performed with Copalia and other medicinal products. To be taken into account with concomitant use Other antihypertensive agents Commonly used antihypertensive agents (e.g. alpha blockers, diuretics) and other medicinal products which may cause hypotensive adverse effects (e.g. tricyclic antidepressants, alpha blockers for treatment of benign prostate hyperplasia) may increase the antihypertensive effect of the combination. Interactions linked to amlodipine Concomitant use not recommended Grapefruit or grapefruit juice Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients, resulting in increased blood pressure lowering effects. Caution required with concomitant use CYP3A4 inhibitors Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine exposure. The clinical translation of these pharmacokinetic variations may be more pronounced in the elderly. Clinical monitoring and dose adjustment may thus be required. CYP3A4 inducers (anticonvulsant agents [e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone], rifampicin, Hypericum perforatum) Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary. Therefore, blood pressure should be monitored and dose regulation considered both during and after concomitant medication particularly with strong CYP3A4 inducers (e.g. rifampicin, hypericum perforatum). Simvastatin Co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. It is recommended to limit the dose of simvastatin to 20 mg daily in patients on amlodipine. 6 Dantrolene (infusion) In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalaemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia. Tacrolimus

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094687 · has-pregnancy-information · PDF-Seite 8

Pregnancy Amlodipine The safety of amlodipine in human pregnancy has not been established. In animal studies, reproductive toxicity was observed at high doses (see section 5.3). Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus. Valsartan The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 and 4.4). Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started. Exposure to AIIRA therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 4.3 and 4.4). Breast-feeding Amlodipine is excreted in human milk . The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3–7%, with a maximum of 15%. The effect of amlodipine on infants is unknown. No information is available regarding the use of Copalia during breast-feeding, therefore Copalia is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant. Fertility There are no clinical studies on fertility with Copalia. Valsartan Valsartan had no adverse effects on the reproductive performan

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094685 · has-warning-information · PDF-Seite 4

The safety and efficacy of amlodipine in hypertensive crisis have not been established. Pregnancy Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6). Sodium- and/or volume-depleted patients Excessive hypotension was seen in 0.4% of patients with uncomplicated hypertension treated with Copalia in placebo-controlled studies. In patients with an activated renin-angiotensin system (such as volume- and/or salt-depleted patients receiving high doses of diuretics) who are receiving angiotensin receptor blockers, symptomatic hypotension may occur. Correction of this condition prior to administration of Copalia or close medical supervision at the start of treatment is recommended. If hypotension occurs with Copalia, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once blood pressure has been stabilised. Hyperkalaemia Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (heparin, etc.) should be undertaken with caution and with frequent monitoring of potassium levels. Renal artery stenosis Copalia should be used with caution to treat hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis to a solitary kidney since blood urea and serum creatinine may increase in such patients. Kidney transplantation To date there is no experience of the safe use of Copalia in patients who have had a recent kidney transplantation. 4 Hepatic impairment Valsartan is mostly eliminated unchanged via the bile. The half life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function; dosage recommendations have not been established. Particular caution should be exercised when administering Copalia to patients with mild to moderate hepatic impairment or biliary obstructive disorders. In patients with mild to moderate hepatic impairment

Auszug; vollständigen Abschnitt im Original lesen.