Label Changes for:
Norvasc (amlodipine besylate) Tablets
Changes have been made to the PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
- added...Postmarketing reporting has also revealed a possible association between extrapyramidal disorder and amlodipine.
Impact of Other Drugs on Amlodipine
- Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment [see Clinical Pharmacology (12.3)].
- No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.
- Monitor for hypotension when sildenafil is co-administered with amlodipine [see Clinical Pharmacology (12.2)].
Impact of Amlodipine on Other Drugs
- Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate [ [see Clinical Pharmacology (12.3)].
7 DRUG INTERACTIONS
- A prospective study in renal transplant patients (N=11) showed on an average of 40% increase in trough cyclosporine levels when concomitantly treated with amlodipine
8 USE IN SPECIFIC POPULATIONS
8.4 Pediatric Use
- NORVASC (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years [see Clinical Studies (14.1)]. Effect of NORVASC on blood pressure in patients less than 6 years of age is not known.
NOTE: multiple deletions of text in ADVERSE REACTIONS/Clinical Trial Experience
- added...... Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
WARNINGS AND PRECAUTIONS
- Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension in unlikely.
Increased Angina or Myocardial Infarction
- Worsening of angina and acute myocardial infarction can develop after starting or increasing the dose of Norvasc, particularly in patients with severe obstructive coronary artery disease.
Patients With Hepatic Failure
- Because Norvasc is extensively metabolized by the liver and the plasma elimination half-life (t 1/2) is 56 hours in patients with impaired hepatic function, titrate slowly when administering NORVASC to patients with severe hepatic impairment.
Clinical Trial Experience
- 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 the clinical trials of another drug and may not reflect the rates observed in practice.
- Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.