Norvasc Protect Special Precautions

Use in Patients with Heart Failure: In a long-term, placebo-controlled study (PRAISE-2) of amlodipine-treated patients with New York Heart Association (NYHA) class III-IV heart failure of nonischemic etiology, amlodipine was associated with increased reports of pulmonary edema despite no significant difference in the incidence of worsening heart failure as compared to placebo (see Pharmacology: Pharmacodynamics under Actions).
Use in Patients with Impaired Hepatic Function (see also Contraindications): Hepatic Effects: As with other lipid-lowering agents of the HMG-CoA reductase inhibitor class, moderate (>3 x ULN) elevations of serum transaminases have been reported following therapy with atorvastatin. Liver function was monitored during pre-marketing as well as post-marketing clinical studies of atorvastatin given at doses of 10 mg, 20 mg, 40 mg and 80 mg.
Persistent increases in serum transaminases (>3 x ULN on two or more occasions) occurred in 0.7% of patients who received atorvastatin in these clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10 mg, 20 mg, 40 mg and 80 mg respectively. Increases were generally not associated with jaundice or other clinical signs or symptoms. When the dosage of atorvastatin was reduced, or drug treatment interrupted or discontinued, transaminase levels returned to pre-treatment levels. Most patients continued treatment on a reduced dose of atorvastatin without sequelae.
Liver function tests should be performed before the initiation of treatment and periodically thereafter. Patients who develop any signs or symptoms suggesting liver injury should have liver function tests performed. Patients who develop increased transaminase levels should be monitored until the abnormality(ies) resolve(s). Should an increase in alanine transaminase (ALT) or aspartate transaminase (AST) >3 x ULN persist, reduction of dose or withdrawal of Amlodipine besilate/Atorvastatin calcium (Norvasc Protect) is recommended. Atorvastatin can cause an elevation in transaminases (see Adverse Reactions).
Amlodipine besilate/Atorvastatin calcium (Norvasc Protect) should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of Amlodipine besilate/Atorvastatin calcium (Norvasc Protect) (see Contraindications).
Skeletal Muscle Effects: Myalgia has been reported in atorvastatin-treated patients (see Adverse Reactions). Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10 x ULN, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Amlodipine besilate/Atorvastatin calcium (Norvasc Protect) therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. The risk of myopathy is increased with concurrent administration of drugs that increase the systemic concentration of atorvastatin (see Interactions and Pharmacology: Pharmacokinetics under Actions). Many of these drugs inhibit cytochrome P450 3A4 metabolism and/or drug-transport. CYP3A4 is the primary hepatic isozyme known to be involved in the biotransformation of atorvastatin. Physicians considering combined therapy with atorvastatin and fibric acid derivatives, erythromycin, immunosuppressive drugs, azole antifungals, HIV/HCV protease inhibitors, HCV NS5A/NS5B inhibitors, letermovir, or lipid-modifying doses of niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Therefore, lower starting and maintenance doses of the atorvastatin component should also be considered when taken concomitantly with the aforementioned drugs (see Dosage & Administration). The concurrent use of atorvastatin and fusidic acid is not recommended, therefore, temporary suspension of atorvastatin is advised during fusidic acid therapy (see Interactions). Periodic CPK determinations may be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy. Amlodipine besilate/Atorvastatin calcium (Norvasc Protect) may cause an elevation of CPK due to the atorvastatin component (see Adverse Reactions).
There have been very rare reports of an immune-mediated necrotizing myopathy (IMNM) during or aftertreatment with some statins (see Adverse Reactions). IMNM is clinically characterized by persistent proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment, positive anti-HMG CoA reductase antibody and improvement with immunosuppressive agents.
As with other drugs in the class of HMG-CoA reductase inhibitors, rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria, have been reported. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects. Amlodipine besilate/Atorvastatin calcium (Norvasc Protect) therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., severe acute infection; hypotension; major surgery; trauma; severe metabolic, endocrine and electrolyte disorders; and uncontrolled seizures). Control of hypertension may be continued with the appropriate dose of amlodipine.
Hemorrhagic Stroke: A post-hoc analysis of a clinical study in 4,731 patients without CHD who had a stroke or transient ischemic attack (TIA) within the preceding 6 months and were initiated on atorvastatin 80 mg revealed a higher incidence of hemorrhagic stroke in the atorvastatin 80 mg group compared to placebo (55 atorvastatin vs. 33 placebo). Patients with hemorrhagic stroke on entry appeared to be at increased risk for recurrent hemorrhagic stroke (7 atorvastatin vs. 2 placebo). However, in patients treated with atorvastatin 80 mg there were fewer strokes of any type (265 atorvastatin vs. 311 placebo) and fewer CHD events (123 atorvastatin vs. 204 placebo) (see Pharmacology: Pharmacodynamics: Recurrent Stroke under Actions).
Endocrine Function: Increases in glycated hemoglobin (HbA1c) and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin. The risk of hyperglycemia, however, is outweighed by the reduction in vascular risk with statins.
Effects on Ability to Drive and Use Machines: Based on the available information on amlodipine and atorvastatin, this medication is unlikely to impair a patient's ability to drive or use machinery.