Summary of the safety profile Serious adverse reactions include anaphylactic reaction and angioedema which have been reported in post-marketing experience and may occur rarely (less than 1 case per 1,000 patients). The most common adverse reaction is diarrhoea.
Tabulated list of adverse reactions Aliskiren has been evaluated for safety in more than 7,800 patients, including over 2,300 treated for over 6 months, and more than 1,200 for over 1 year. The adverse reactions are ranked under heading of frequency, the most frequent first, 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) and not known (cannot be estimated from the available data).
9 Table 1 Immune system disorders Rare: Anaphylactic reactions, hypersensitivity reactions Nervous system disorders Common: Dizziness Ear and labyrinth disorders Not known: Vertigo Cardiac disorders Uncommon: Palpitations, oedema peripheral Vascular disorders Uncommon: Hypotension Respiratory, thoracic and mediastinal disorders Uncommon: Cough Not known: Dyspnoea Gastrointestinal disorders Common: Diarrhoea Not known: Nausea, vomiting Hepatobiliary disorders Not known: Liver disorder*, jaundice, hepatitis, liver failure** Skin and subcutaneous tissue disorders Uncommon: Severe cutaneous adverse reactions (SCARs) including Stevens Johnson syndrome, toxic epidermal necrolysis (TEN) and oral mucosal reactions, rash, pruritus, urticaria Rare: Angioedema, erythema Musculoskeletal and connective tissue disorders Common: Arthralgia Renal and urinary disorders Uncommon: Acute renal failure, renal impairment Investigations Common: Hyperkalaemia Uncommon: Liver enzyme increased Rare: Haemoglobin decreased, haematocrit decreased, blood creatinine increased Not known: Hyponatraemia *Isolated cases of liver disorder with clinical symptoms and laboratory evidence of more marked hepatic dysfunction.
**Including one case of ‘liver failure fulminant’ reported in the post-marketing experience, for which a causal relationship with aliskiren cannot be excluded. Description of selected adverse reactions Hypersensitivity reactions including anaphylactic reactions and angioedema In controlled clinical studies, angioedema and hypersensitivity reactions occurred rarely during treatment with aliskiren with rates comparable to treatment with placebo or comparators.
Cases of angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or tongue) have also been reported in post-marketing experience. A number of these patients had a history of angioedema or symptoms suggestive of angioedema which in some cases was associated with the administration of other medicines known to cause angioedema, including RAAS blockers (ACEIs or ARBs).
In post-marketing experience, cases of angioedema or angioedema-like reactions have been reported when aliskiren was co-administered with ACEIs and/or ARBs. 4). 4). Arthralgia has been reported in post-marketing experience. In some cases this occurred as part of a hypersensitivity reaction.
4). Laboratory findings In controlled clinical trials, clinically relevant changes in standard laboratory parameters were uncommonly associated with the administration of aliskiren. In clinical studies in hypertensive patients, Rasilez had no clinically important effects on total cholesterol, high density lipoprotein cholesterol (HDL-C), fasting triglycerides, fasting glucose or uric acid.
16 volume percent, respectively) were observed. No patients discontinued therapy due to anaemia. This effect is also seen with other agents acting on the renin-angiotensin system, such as ACEIs and ARBs. Serum potassium Increases in serum potassium have been observed with aliskiren and these may be exacerbated by concomitant use of other agents acting on the RAAS or by NSAIDs.
Consistent with standard medical practice, periodic determination of renal function including serum electrolytes is advised if co-administration is considered necessary. Paediatric population Aliskiren has been evaluated for safety in a randomised, double-blind, 8-week study in 267 hypertensive patients aged 6 to 17 years, mostly overweight/obese, followed by an extension study including 208 patients treated for 52 weeks.
An additional 52 to 104 week non-interventional observational extension study in 106 patients (no study treatment administered) was conducted with the objective to evaluate the long-term safety in terms of growth and development of children 6-17 years of age with hypertension (primary or secondary) at baseline in the core study, previously treated with aliskiren.
The frequency, type and severity of adverse reactions in children were generally similar to those seen in hypertensive adults. 2). Reporting of […]