y with amlodipine were of mild or moderateseverity. In controlled clinical trials directly comparing amlodipine (N=1730) at doses up to10 mg to placebo (N=1250), discontinuation of amlodipine because of adverse reactions wasrequired in about 1.5% of patients and was not different from placebo (about 1%). The mostcommonly reported adverse reactions more frequent than placebo are reflected in the tablebelow. The incidence (%) of adverse reactions that occurred in a dose related manner are asfollows:
Table 1: Most Common Dose-Related Adverse Events Compared to Placebo
Amlodipine Placebo
2.5 mg 5 mg 10 mg
N=275 N=296 N=268 N=520
Edema 1.8 3.0 10.8 0.6
Dizziness 1.1 3.4 3.4 1.5
Flushing 0.7 1.4 2.6 0.0
Palpitation 0.7 1.4 4.5 0.6
Other adverse reactions that were not clearly dose related but were reported with an incidencegreater than 1.0% in placebo-controlled clinical trials included the following:
Table 2: Other Adverse Events with a Reported Incidence Greater Than 1%
Amlodipine (%)
(N=1730)
Placebo (%)
(N=1250)
Fatigue 4.5 2.8
Nausea 2.9 1.9
Abdominal Pain 1.6 0.3
Somnolence 1.4 0.6
For several adverse experiences that appear to be drug and dose related, there was a greaterincidence in women than men associated with amlodipine treatment as shown in the followingtable:
Table 3: Comparison of Drug and Dose-Related Adverse Events Reported by Men and WomenAmlodipine Placebo
Male=%
(N=1218)
Female=%
(N=512)
Male=%
(N=914)
Female=%
(N=336)
Edema 5.6 14.6 1.4 5.1
Flushing 1.5 4.5 0.3 0.9
Palpitations 1.4 3.3 0.9 0.9
6.2 Postmarketing Experience
Because these reactions are reported voluntarily from a population of uncertain size, it is notalways possible to reliably estimate their frequency or establish a causal relationship to drugexposure.
General: gynecomastia.
Hepatic: jaundice and hepatic enzyme elevations, some requiring hospitalization
Neurologic: extrapyramidal disorder
7 DRUG INTERACTIONS
7.1 Impact of Other Drugs on Amlodipine
CYP3A Inhibitors
Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemicexposure 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)].
CYP3A Inducers
No information is available on the quantitative effects of CYP3A inducers on amlodipine. Bloodpressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.
7.2 Impact of Amlodipine on Other Drugs
Simvastatin
Co-administration of simvastatin with amlodipine increases the systemic exposure ofsimvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily [see ClinicalPharmacology (12.3)].
Immunosuppressants
Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus whenco-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus isrecommended and adjust the dose when appropriate [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
The limited available data based on post-marketing reports with amlodipine use in pregnantwomen are not sufficient to inform a drug-associated risk for major birth defects andmiscarriage. There are risks to the mother and fetus associated with poorly controlledhypertension in pre |
