openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Adverse reactions sections page 1 of 1 · 2 matching rows.
adverse reactions
6 ADVERSE REACTIONS The most common adverse events (incidence greater than or equal to 2%) are: peripheral edema, dizziness, headache and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience The following serious adverse reactions are discussed in greater detail in other sections of the label: Fetal Toxicity [see Warnings and Precautions (5.1)] Anaphylactic Reactions and Head and Neck Angioedema [see Warnings and Precautions (5.3)] Hypotension [see Warnings and Precautions (5.4)] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. Amturnide Amturnide has been evaluated for safety in 1155 patients treated with Amturnide, including 182 patients for over 1 year. In a short-term controlled trial, there were 60.5% males, 84.1% Caucasians, 10% blacks, 6.4% Hispanics, and 19.1% who were 65 years of age and older. In this study, the overall incidence of adverse events on therapy with Amturnide was similar to that observed with the individual components. The overall frequency of adverse events was similar between men and women and black and Caucasian patients. Discontinuation of therapy because of a clinical adverse event in this study occurred in 3.6% of patients treated with Amturnide versus 2.4% in aliskiren/amlodipine, 0.7% in aliskiren/HCTZ, and 2.7% in amlodipine/HCTZ. Table 1. Adverse Events in a Short-term Controlled Trial that Occurred in at Least 2% of Patients Treated with Amturnide Amturnide Ali/amlo Ali/HCTZ Amlo/HCTZ Edema peripheral 7.1% 8.0% 2.0% 4.1% Dizziness 3.6% 2.4% 3.4% 1.7% Headache 3.6% 3.1% 4.0% 5.1% Nasopharyngitis 2.6% 0.7% 2.0% 3.4% In a long-term safety trial, the safety profile was similar to that seen in the short-term controlled trial. Aliskiren Aliskiren has been evaluated for safety in 6460 patients, including 1740 treated for longer than 6 months, and 1250 for longer than 1 year. In placebo-controlled clinical trials, discontinuation of therapy because of a clinical adverse event, including uncontrolled hypertension, occurred in 2.2% of patients treated with aliskiren, versus 3.5% of patients given placebo. These data do not include information from the ALTITUDE study which evaluated the use of aliskiren in combination with ARBs or ACEIs [see Contraindications (4), Warnings and Precautions (5.2), Clinical Studies (14.2)] . Two cases of angioedema with respiratory symptoms were reported with aliskiren use in the clinical studies. Two other cases of periorbital edema without respiratory symptoms were reported as possible angioedema and resulted in discontinuation. The rate of these angioedema cases in the completed studies was 0.06%. In addition, 26 other cases of edema involving the face, hands, or whole body were reported with aliskiren use, including 4 leading to discontinuation. In the placebo-controlled studies, however, the incidence of edema involving the face, hands, or whole body was 0.4% with aliskiren compared with 0.5% with placebo. In a long-term active-controlled study with aliskiren and HCTZ arms, the incidence of edema involving the face, hands, or whole body was 0.4% in both treatment arms. Aliskiren produces dose-related gastrointestinal (GI) adverse reactions. Diarrhea was reported by 2.3% of patients at 300 mg, compared to 1.2% in placebo patients. In women and the elderly (age 65 years and older) increases in diarrhea rates were evident starting at a dose of 150 mg daily, with rates for these subgroups at 150 mg similar to those seen at 300 mg for men or younger patients (all rates about 2%). Other GI symptoms included abdominal pain, dyspepsia, and gastroesophageal reflux, although increased rates for abdominal pain and dyspepsia were distinguished from placebo only at 600 mg daily. Diarrhea and other GI symptoms were typically mild and rarely led to discontinuation. Aliskiren was associated with a slight increase in cough in the placebo-controlled studies (1.1% for any aliskiren use versus 0.6% for placebo). In active-controlled trials with ACE inhibitor (ramipril, lisinopril) arms, the rates of cough for the aliskiren arms were about one-third to one-half the rates in the ACE inhibitor arms. Other adverse reactions with increased rates for aliskiren compared to placebo included rash (1% versus 0.3%), and renal stones (0.2% versus 0%). Single episodes of tonic-clonic seizures with loss of consciousness were reported in 2 patients treated with aliskiren in the clinical trials. One patient had predisposing causes for seizures and had a negative electroencephalogram (EEG) and cerebral imaging following the seizures; for the other patient, EEG and imaging results were not reported. Aliskiren was discontinued and there was no re-challenge in either case. No clinically meaningful changes in vital signs or in ECG (including QTc interval) were observed in patients treated with aliskiren. Amlodipine Amlodipine (Norvasc ® ) has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. Other adverse events that have been reported at less than 1% but greater than 0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain were: Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis Central and Peripheral Nervous System: neuropathy peripheral, paresthesia, tremor, vertigo Gastrointestinal: anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia General: allergic reaction, asthenia,** back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease Musculoskeletal System: arthralgia, arthrosis, muscle cramps,** myalgia Psychiatric: sexual dysfunction (male** and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization Respiratory System: dyspnea, epistaxis Skin and Appendages: angioedema, erythema multiforme, pruritus,** rash,** rash erythematous, rash maculopapular **These events occurred in less than 1% in placebo-controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies. Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus Urinary System: micturition frequency, micturition disorder, nocturia Autonomic Nervous System: dry mouth, sweating increased Metabolic and Nutritional: hyperglycemia, thirst Hemopoietic : leukopenia, purpura, thrombocytopenia Other events reported with amlodipine at a frequency of less than or equal to 0.1% of patients include: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia. Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina. HCTZ Other adverse reactions not listed above that have been reported with HCTZ, without regard to causality, are listed below: Body as a Whole: weakness Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation Hematologic : aplastic anemia, agranulocytosis, hemolytic anemia Hypersensitivity: photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions Musculoskeletal: muscle spasm Nervous System/Psychiatric: restlessness Renal: renal failure, renal dysfunction, interstitial nephritis Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis Special Senses: transient blurred vision, xanthopsia Clinical Laboratory Test Abnormalities Clinical laboratory findings for Amturnide in patients with hypertension not concomitantly treated with an ARB or ACEI were obtained in a controlled trial of Amturnide administered at the maximal dose of 300/10/25 mg compared to maximal doses of dual therapies, i.e., aliskiren/amlodipine 300/10 mg, aliskiren/HCTZ 300/25 mg and amlodipine/HCTZ 10/25 mg. RBC Count, Hemoglobin, and Hematocrit: Small mean changes from baseline were seen in RBC count, hemoglobin and hematocrit in patients treated with Amturnide. This effect is also seen with other agents acting on the renin angiotensin system. In aliskiren monotherapy trials, these decreases led to slight increases in rates of anemia compared to placebo (0.1% for any aliskiren use, 0.3% for aliskiren 600 mg daily, versus 0% for placebo). No patients discontinued Amturnide because of anemia. Blood Urea Nitrogen (BUN)/Creatinine: No patients with hypertension not concomitantly treated with an ARB or ACEI treated with Amturnide had elevations in BUN greater 40 mg/dL or creatinine greater 2.0 mg/dL. Liver Function Tests: Occasional elevations (greater than 150% from baseline) in ALT (SGPT) were observed in 2.7% of patients treated with Amturnide, compared with 1.7% to 2.7% in patients treated with the dual combinations. No patients were discontinued due to abnormal liver function tests. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of either aliskiren, amlodipine or HCTZ. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure: Aliskiren: Hypersensitivity: anaphylactic reactions and angioedema requiring airway management and hospitalization. peripheral edema, severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, urticaria, hepatic enzyme increase with clinical symptoms of hepatic dysfunction, pruritus, erythema, hyponatremia, nausea, vomiting. Amlodipine : The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia. In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine. Hydrochlorothiazide (HCTZ): Acute renal failure, renal disorder, aplastic anemia, erythema multiforme, pyrexia, muscle spasm, asthenia, acute angle-closure glaucoma, bone marrow failure, worsening of diabetes control, hypokalemia, blood lipids increased, hyponatremia, hypomagnesemia, hypercalcemia, hyperchloremic alkalosis, impotence, visual impairment. Pathological changes in the parathyroid gland of patients with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. If hypercalcemia occurs, further diagnostic evaluation is necessary.