A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Norvasc Side Effects, and Drug Interactions - Amlodipine
Norvasc Side Effects, and Drug Interactions - Amlodipine
SIDE EFFECTS
Amlodipine besylate has been evaluated for safety in more than 11,000
patients in U.S. and foreign clinical
trials. In general, treatment
with amlodipine besylate was well-tolerated at doses up to 10 mg
daily. Most adverse reactions reported during therapy with amlodipine
besylate were of mild or moderate severity. In
controlled clinical trials
directly comparing amlodipine
besylate (N=1730) in doses up to 10 mg
to placebo (N=1250), discontinuation
of amlodipine besylate due to adverse reactions was required in only about
1.5% of patients and was not significantly different from placebo
(about 1%). The most common side effects are headache
and edema. The incidence
(%) of side effects which occurred
in a dose related manner are
found in TABLE 1.
| TABLE 1 |
| Adverse Event |
2.5 mg |
5.0 mg |
10.0 mg |
Placebo |
| |
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 experiences which were not clearly dose
related but which were reported with an incidence
greater than 1.0% in placebo-controlled clinical trials can be found in
TABLE 2.
| TABLE 2 Placebo Controlled Studies |
| Adverse Event |
Norvasc (%) |
Placebo (%) |
| |
(N=1730) |
(N=1250) |
| Headache |
7.3 |
7.8 |
| 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
greater incidence in women
than men associated with amlodipine treatment as shown in TABLE 3.
| TABLE 3 |
| |
Amlodipine Besylate |
Placebo |
| ADR |
M=% |
F=% |
M=% |
F=% |
| |
(N=1218) |
(N=512) |
(N=914) |
(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 |
| Somnolence |
1.3 |
1.6 |
0.8 |
0.3 |
The following events occurred in £1%
but >0.1% of patients in controlled clinical trials or under conditions
of open trials or marketing experience
where a casual relationship is uncertain; they are listed to alert the
physician to a possible relationship:
Cardiovascular: Arrhythmia (including ventricular
tachycardia and atrial fibrillation),
bradycardia, chest pain, hypotension,
peripheral ischemia, syncope, tachycardia, postural
dizziness, postural hypotension.
Central and Peripheral Nervous System: Hypoesthesia, paresthesia,
tremor, vertigo.
Gastrointestinal: Anorexia, constipation, dyspepsia,†
dysphagia, diarrhea, flatulence, vomiting, gingival
hyperplasia.
General: Asthenia,† back
pain, hot flushes, malaise, pain,
rigors, weight gain.
Musculo-skeletal 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: Pruritus,† rash,† rash erythematous,
rash maculopapular.
*Based on patient weight
of 50 kg.
†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, increased sweating.
Metabolic and Nutritional: thirst.
Hemopoietic: purpura.
The Following Events Occurred In
£ 0.1% Of Patients: 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, coughing, 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.
Amlodipine besylate therapy has not been associated with clinically significant
changes in routine laboratory tests. No clinically relevant changes were
noted in serum potassium, serum
glucose, total triglycerides, total cholesterol, HDL cholesterol, uric
acid, blood urea
nitrogen, creatinine or
liver function tests.
Amlodipine besylate has been used safely in patients with chronic
obstructive pulmonary disease, well compensated congestive heart
failure, peripheral vascular
disease, diabetes mellitus,
and abnormal lipid profiles.
DRUG INTERACTIONS
In vitro data in human
plasma indicate that amlodipine
besylate has no effect on the
protein binding of drugs tested
(digoxin, phenytoin, warfarin, and indomethacin). Special studies have
indicated that the co-administration of amlodipine
besylate with digoxin did
not change serum digoxin levels
or digoxin renal
clearance in normal
volunteers; that co-administration with cimetidine
did not alter the pharmacokinetics
of amlodipine; and that co-administration with warfarin did not change
the warfarin prothrombin response time.
In clinical trials, amlodipine
besylate has been safely administered with thiazide diuretics, beta-blockers,
angiotensin converting
enzyme inhibitors, long-acting
nitrates, sublingual nitroglycerin,
digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics,
and oral hypoglycemic drugs.
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