Over 1000 patients from both controlled and open trials
with PROCARDIA XL Extended Release Tablets in hypertension and angina were
included in the evaluation of adverse experiences. All side effects reported
during PROCARDIA XL Extended Release Tablet therapy were tabulated independent
of their causal relation to medication. The most common side effect reported
with PROCARDIA XL was edema which was dose related and ranged in frequency from
approximately 10% to about 30% at the highest dose studied (180 mg). Other
common adverse experiences reported in placebo-controlled trials include:
||PROCARDIA XL (%)
Of these, only edema and
headache were more common in PROCARDIA XL patients than placebo patients.
The following adverse reactions
occurred with an incidence of less than 3.0%. With the exception of leg cramps,
the incidence of these side effects was similar to that of placebo alone.
Body as a Whole/Systemic: asthenia, flushing, pain Cardiovascular:
Central Nervous System: insomnia, nervousness,
Dermatologic: pruritus, rash
Gastrointestinal: abdominal pain, diarrhea, dry
mouth, dyspepsia, flatulence
Musculoskeletal: arthralgia, leg cramps
Respiratory: chest pain (nonspecific), dyspnea
Other adverse reactions were reported sporadically with
an incidence of 1.0% or less. These include:
Body as a Whole/Systemic: face edema, fever, hot
flashes, malaise, periorbital edema, rigors
Cardiovascular: arrhythmia, hypotension, increased
angina, tachycardia, syncope
Central Nervous System: anxiety, ataxia, decreased
libido, depression, hypertonia, hypoesthesia, migraine, paroniria, tremor,
Dermatologic: alopecia, increased sweating,
Gastrointestinal: eructation, gastroesophageal
reflux, gum hyperplasia, melena, vomiting, weight increase
Musculoskeletal: back pain, gout, myalgias
Respiratory: coughing, epistaxis, upper
respiratory tract infection, respiratory disorder, sinusitis
Special Senses: abnormal lacrimation, abnormal
vision, taste perversion, tinnitus
Urogenital/Reproductive: breast pain, dysuria,
Adverse experiences which occurred in less than 1 in 1000
patients cannot be distinguished from concurrent disease states or medications.
The following adverse experiences, reported in less than
1% of patients, occurred under conditions (e.g., open trials, marketing
experience) where a causal relationship is uncertain: gastrointestinal
irritation, gastrointestinal bleeding, gynecomastia.
Gastrointestinal obstruction resulting in hospitalization
and surgery, including the need for bezoar removal, has occurred in association
with PROCARDIA XL, even in patients with no prior history of gastrointestinal
disease (see WARNINGS).
Cases of tablet adherence to the gastrointestinal wall
with ulceration have been reported, some requiring hospitalization and
In multiple-dose U.S. and foreign controlled studies with
nifedipine capsules in which adverse reactions were reported spontaneously,
adverse effects were frequent but generally not serious and rarely required
discontinuation of therapy or dosage adjustment. Most were expected
consequences of the vasodilator effects of nifedipine.
|Dizziness, lightheadedness, giddiness
|Flushing, heat sensation
|Muscle cramps, tremor
|Nervousness, mood changes
|Dyspnea, cough, wheezing
|Nasal congestion, sore throat
There is also a large
uncontrolled experience in over 2100 patients in the United States. Most of the
patients had vasospastic or resistant angina pectoris, and about half had
concomitant treatment with beta-adrenergic blocking agents. The relatively
common adverse events were similar in nature to those seen with PROCARDIA XL.
In addition, more serious
adverse events were observed, not readily distinguishable from the natural
history of the disease in these patients. It remains possible, however, that
some or many of these events were drug related. Myocardial infarction occurred
in about 4% of patients and congestive heart failure or pulmonary edema in
about 2%. Ventricular arrhythmias or conduction disturbances each occurred in
fewer than 0.5% of patients.
In a subgroup of over 1000
patients receiving PROCARDIA with concomitant beta blocker therapy, the pattern
and incidence of adverse experiences was not different from that of the entire
group of PROCARDIA-treated patients (see PRECAUTIONS).
In a subgroup of approximately
250 patients with a diagnosis of congestive heart failure as well as angina,
dizziness or lightheadedness, peripheral edema, headache, or flushing each
occurred in one in eight patients. Hypotension occurred in about one in 20
patients. Syncope occurred in approximately one patient in 250. Myocardial infarction or symptoms of congestive heart failure each occurred in about one
patient in 15. Atrial or ventricular dysrhythmias each occurred in about one
patient in 150.
In post-marketing experience,
there have been rare reports of exfoliative dermatitis caused by nifedipine.
There have been rare reports of exfoliative or bullous skin adverse events
(such as erythema multiforme, Stevens-Johnson Syndrome, and toxic epidermal necrolysis)
and photosensitivity reactions. Acute generalized exanthematous pustulosis also
has been reported.