Norvasc Protect Adverse Reactions

Combination therapy with amlodipine and atorvastatin has been evaluated for safety in 1,092 patients in double blind, placebo-controlled studies treated for concomitant hypertension and dyslipidemia. In clinical trials, no adverse events peculiar to combination therapy with amlodipine and atorvastatin have been observed. Adverse events have been limited to those that were reported previously with amlodipine and/or atorvastatin (please see respective adverse event experiences as follows).
In general, combination therapy with amlodipine and atorvastatin was well tolerated. For the most part, adverse events have been mild or moderate in severity. In controlled clinical trials, discontinuation of therapy due to adverse events or laboratory abnormalities was required in 5.1% of patients treated with both amlodipine and atorvastatin compared to 4.0% of patients given placebo.
The following information is based on clinical trials and postmarketing experience with amlodipine and atorvastatin.
Amlodipine Experience: Amlodipine is well tolerated. In placebo-controlled clinical trials involving patients with hypertension or angina, the most commonly observed side effects were: See Table 13.

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In these clinical trials no pattern of clinically significant laboratory test abnormalities related to amlodipine has been observed.
Less commonly observed side effects in marketing experience with amlodipine include: See Table 14.

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Rarely reported events were allergic reactions including pruritus, rash, angioedema, and erythema multiforme.
Hepatitis, jaundice and hepatic enzyme elevations have also been reported very infrequently (mostly consistent with cholestasis). Some cases severe enough to require hospitalization have been reported in association with use of amlodipine. In many instances, causal association is uncertain.
As with other calcium channel blockers, the following adverse events have been rarely reported and cannot be distinguished from the natural history of the underlying disease: MI, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) and chest pain.
Pediatric Patients (Aged 6-17 years): Amlodipine is well tolerated in children. Adverse events were similar to those seen in adults. In a study of 268 children, the most frequently reported adverse events were: See Table 15.

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The majority of adverse events were mild or moderate. Severe adverse events (predominantly headache) were experienced by 7.2% with amlodipine 2.5 mg, 4.5% with amlodipine 5 mg, and 4.6% with placebo. The most common cause of discontinuation from the study was uncontrolled hypertension. There were no discontinuations due to laboratory abnormalities. There was no significant change in heart rate.
Atorvastatin Experience: Atorvastatin is generally well-tolerated. Adverse reactions have usually been mild and transient. In the atorvastatin placebo-controlled clinical trial database of 16,066 (8,755 atorvastatin vs. 7,311 placebo) patients treated for a median period of 53 weeks, 5.2% of patients on atorvastatin discontinued due to adverse reactions compared to 4.0% of the patients on placebo.
The most frequent (≥1%) adverse effects that may be associated with atorvastatin therapy, reported in patients participating in placebo-controlled clinical studies include: Infections and infestations: Nasopharyngitis.
Metabolism and nutrition disorders: Hyperglycemia.
Respiratory, thoracic and mediastinal disorders: Pharyngolaryngeal pain, epistaxis.
Gastrointestinal disorders: Diarrhea, dyspepsia, nausea, flatulence.
Musculoskeletal and connective tissue disorders: Arthralgia, pain in extremity, musculoskeletal pain, muscle spasms, myalgia, joint swelling.
Investigations: Liver function test abnormal, blood creatine phosphokinase increased.
Additional adverse effects reported in atorvastatin placebo-controlled clinical trials include: Psychiatric disorders: Nightmare.
Eye disorders: Blurred vision.
Ear and labyrinth disorders: Tinnitus.
Gastrointestinal disorders: Abdominal discomfort, eructation.
Hepatobiliary disorders: Hepatitis, cholestasis.
Skin and subcutaneous tissue disorders: Urticaria.
Musculoskeletal and connective tissue disorders: Muscle fatigue, neck pain.
General disorders and administration site conditions: Malaise, pyrexia.
Investigations: White blood cells positive in urine.
Not all effects listed previously have been causally associated with atorvastatin therapy.
Pediatric Patients: Patients treated with atorvastatin had an adverse experience profile generally similar to that of patients treated with placebo. The most common adverse experiences observed in both groups, regardless of causality assessment, were infections.
No clinically significant effect on growth and sexual maturation was observed in a 3-year study in children ages 6 and above based on the assessment of overall maturation and development, assessment of Tanner Stage, and measurement of height and weight. The safety and tolerability profile in pediatric patients was similar to the known safety profile of atorvastatin in adult patients.
Post-marketing Experience: In post-marketing experience, the following additional undesirable effects have been reported with atorvastatin: Blood and lymphatic system disorders: Thrombocytopenia.
Immune system disorders: Allergic reactions (including anaphylaxis).
Injury, poisoning and procedural complications: Tendon rupture.
Metabolism and nutrition disorders: Weight gain.
Nervous system disorders: Hypoesthesia, amnesia, dizziness, dysgeusia.
Gastrointestinal disorders: Pancreatitis.
Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, erythema multiforme, bullous rashes.
Musculoskeletal and connective tissue disorders: Rhabdomyolysis, immune-mediated necrotizing myopathy, myositis, back pain.
General disorders and administration site conditions: Chest pain, peripheral edema, fatigue.