Edarbi · 4.1 Therapeutic indications · 1

HOS-095992 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile Edarbi at doses of 20, 40 or 80 mg has been evaluated for safety in clinical studies in adult patients treated for up to 56 weeks. In these clinical studies, adverse reactions associated with treatment with Edarbi were mostly mild or moderate, with an overall incidence similar to placebo. The most common adverse reaction was dizziness. The incidence of adverse reactions with this treatment was not affected by gender, age, or race. Adverse reactions were reported at a similar frequency for the Edarbi 20 mg dose as with the 40 and 80 mg doses in one placebo controlled study. Tabulated list of adverse reactions Adverse reactions based on pooled data (40 and 80 mg doses) are listed below according to system organ class and preferred terms. These are ranked by 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Adverse drug reactions from clinical trials and post marketing experience System organ class Frequency Adverse reaction Nervous system disorders Common Dizziness Vascular disorders Uncommon Hypotension Gastrointestinal disorders Common Diarrhoea Uncommon Nausea Skin and subcutaneous tissue Uncommon Rash, pruritus disorders Rare Angioedema Musculoskeletal and Not known Arthralgia connective tissue disorders Uncommon Muscle spasms General disorders and Uncommon Fatigue administration site conditions Peripheral oedema Investigations Common Blood creatine phosphokinase increased Uncommon Blood creatinine increased Blood uric acid increased / Hyperuricemia Description of selected adverse reactions When Edarbi was coadministered with chlortalidone, the frequencies of blood creatinine increased and hypotension were increased from uncommon to common. When Edarbi was coa

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095988 · has-contraindication-information · PDF-Seite 3

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - Second and third trimester of pregnancy (see sections 4.4 and 4.6). - The concomitant use of Edarbi with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m2) (see sections 4.5 and 5.1). 3

HOS-095987 · has-indication-information · PDF-Seite 2

Edarbi is indicated for the treatment of essential hypertension in adults.

HOS-095990 · has-interaction-information · PDF-Seite 5

Concomitant use not recommended Lithium Reversible increases in serum lithium concentrations and toxicity have been reported during concurrent use of lithium and angiotensin-converting enzyme inhibitors. A similar effect may occur with angiotensin II receptor antagonists. Due to the lack of experience with concomitant use of azilsartan medoxomil and lithium, this combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended. Caution required with concomitant use Non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day), and non-selective NSAIDs When angiotensin II receptor antagonists are administered simultaneously with NSAIDs (i.e. selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II receptor antagonists and NSAIDs may lead to an increased risk of worsening of renal function and an increase in serum potassium. Therefore, adequate hydration and monitoring of renal function at the beginning of the treatment are recommended. Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products (e.g. heparin) may increase potassium levels. Monitoring of serum potassium should be undertaken as appropriate (see section 4.4). Additional information 5 Clinical trial data has shown that dual blockade of the RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1). No clinically significant interactions have been reported in studies of azilsartan medoxomil or azilsartan given with amlodipine, antacids, chlortalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin, and warfarin. Following administration with a mixture of cytochrome P450 (CYP) probe substrates, no clinically significant drug interactions were observed with caffeine (CYP1A2), tolbutamide (CYP2C9),

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095991 · has-pregnancy-information · PDF-Seite 6

Pregnancy The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy (see section 4.4). The use of angiotensin II receptor antagonists is contraindicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4). There are no data from the use of azilsartan medoxomil in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Epidemiological evidence regarding the risk of teratogenicity following exposure to angiotensin converting enzyme inhibitors during the first trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Whilst there are no controlled epidemiological data on the risk with angiotensin II receptor antagonists, similar risks may exist for this class of medicinal products. Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately and, if appropriate, alternative therapy should be started. Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken Angiotensin II receptor antagonists should be closely observed for hypotension (see sections 4.3 and 4.4). Breast-feeding Because no information is available regarding the use of azilsartan medoxomil during breastfeeding, Edarbi is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while breast-feeding a newborn or preterm infant. Fertility No data are available on the effect of azilsartan medoxomil on human fertility. Nonclinical studies demonstrated that azilsartan did not appear to affect male or female fertility in the rat (see section 5.3). 6

HOS-095989 · has-warning-information · PDF-Seite 4

Activated renin-angiotensin-aldosterone system (RAAS) In patients whose vascular tone and renal function depend predominantly on the activity of the RAAS (e.g. patients with congestive heart failure, severe renal impairment or renal artery stenosis), treatment with medicinal products that affect this system, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. The possibility of similar effects cannot be excluded with Edarbi. Caution should be exercised in hypertensive patients with severe renal impairment, congestive heart failure or renal artery stenosis, as there is no experience of use of Edarbi in these patients (see sections 4.2 and 5.2). Excessive blood pressure decreases in patients with ischaemic cardiomyopathy or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke. Dual blockade of the RAAS There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1). If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Kidney transplantation There is currently no experience on the use of Edarbi in patients who have recently undergone kidney transplantation. Hepatic impairment Edarbi has not been studied in patients with severe hepatic impairment and therefore its use is not recommended in this patient group (see sections 4.2 and 5.2). Hypotension in volume- and /or salt-depleted patients In patients with marked volume- and/or salt-depletion (e.g. patients with vomiting, diarrhoea or taking high doses of diuretics) symptomatic hypotension could occur after initiation of treatment with Edarbi. Hypovolemia should be corrected prior to administration of Edarbi, or the treatment should start under close medical supervision, and consideration can be given to a starting dose of 20 mg. Primary hyperal

Auszug; vollständigen Abschnitt im Original lesen.