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
Adalat Warnings, Precautions, Pregnancy, Nursing, Abuse - Nifedipine
Adalat Warnings, Precautions, Pregnancy, Nursing, Abuse - Nifedipine
WARNINGS
Excessive Hypotension
Although in most patients the hypotensive
effect of nifedipine is modest and well tolerated, occasional patients
have had excessive and poorly tolerated hypotension. These responses
have usually occurred during initial
titration or at the
time of subsequent upward
dosage adjustment, and may be more likely in patients using concomitant
beta-blockers. Severe hypotension
and/or increased fluid
volume requirements have
been reported in patients who received immediate
release capsules together
with a beta-blocking agent
and who underwent coronary
artery bypass surgery
using high dose fentanyl
anesthesia. The interaction with high dose
fentanyl appears to be due to the combination of nifedipine and
a beta-blocker, but the possibility that it may occur with nifedipine
alone, with low doses of fentanyl, in other surgical
procedures, or with other narcotic
analgesics cannot be ruled out. In
nifedipine treated patients where surgery
using high dose fentanyl
anesthesia is contemplated,
the physician should be aware of these potential
problems and if the patient’s
condition permits, sufficient time
(at least 36 hours) should be allowed for nifedipine to be washed
out of the body prior to
surgery.
Increased Angina and/or Myocardial Infarction
Rarely, patients,
particularly those who have severe obstructive coronary
artery disease,
have developed well documented increased frequency, duration
and/or severity of angina or acute
myocardial infarction
upon starting nifedipine or at the time of dosage
increase. The mechanism
of this effect is not
established.
Beta-Blocker Withdrawal
When discontinuing a beta-blocker it is important to taper its
dose, if possible, rather than stopping abruptly before beginning
nifedipine. Patients recently withdrawn from beta
blockers may develop a withdrawal
syndrome with increased
angina, probably related
to increased sensitivity to catecholamines. Initiation of nifedipine
treatment will not
prevent this occurrence and on occasion has been reported to increase
it.
Congestive Heart Failure
Rarely, patients (usually while receiving a beta-blocker) have
developed heart failure
after beginning nifedipine. Patients with tight aortic
stenosis may be at
greater risk for such
an event, as the unloading effect
of nifedipine would be expected to be of less benefit
to these patients, owing to their fixed impedance
to flow across the aortic
valve.
PRECAUTIONS
General
Hypotension: Because nifedipine decreases peripheral
vascular resistance, careful monitoring of blood
pressure during the
initial administration
and titration of A.A.A.
CC is suggested. Close observation is especially recommended for
patients already taking medications that are known to lower blood
pressure (See WARNINGS).
Peripheral Edema: Mild to moderate peripheral
edema occurs in a dose-dependent
manner with A.A.A. CC.
The placebo subtracted
rate is approximately 8%
at 30 mg, 12% at 60 mg, and 19% at 90 mg.
Information for Patients
ADALAT CC is an extended release
tablet and should be
swallowed whole and taken on an empty stomach. It should not be
administered with food. Do not chew, divide or crush tablets.
Laboratory Tests
Rare, usually transient, but occasionally significant elevations
of enzymes such as alkaline
phosphatase, CPK, LDH, SGOT, and SGPT have been noted. The relationship
to nifedipine therapy
is uncertain in most cases, but probable in some. These laboratory
abnormalities have rarely been associated with clinical
symptoms; however, cholestasis
with or without jaundice
has been reported. A small increase (4%) in mean
alkaline phosphatase
was noted in patients treated with ADALAT CC. This was an isolated
finding and it rarely resulted in values which fell outside the
normal range. Rare instances
of allergic hepatitis
have been reported with nifedipine treatment. In
controlled studies, ADALAT CC did not adversely affect
serum uric
acid, glucose,
cholesterol or potassium.
Nifedipine, like other calcium
channel blockers, decreases
platelet aggregation
in vitro. Limited clinical
studies have demonstrated a moderate but statistically significant
decrease in platelet
aggregation and
increase in bleeding
time in some nifedipine patients. This is thought to be a function
of inhibition of calcium
transport across the
platelet membrane.
No clinical
significance for these findings has been demonstrated. Positive
direct Coombs’ test with or without hemolytic
anemia has been reported
but a causal relationship between nifedipine administration
and positivity of this laboratory
test, including hemolysis,
could not be determined. Although nifedipine has been used safely
in patients with renal
dysfunction and
has been reported to exert a beneficial effect
in certain cases, rare reversible
elevations in BUN and serum
creatinine have been
reported in patients with pre-existing chronic renal
insufficiency. The relationship to nifedipine therapy
IS uncertain in most cases but probable in some.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Nifedipine was administered orally to rats for two years and was
not shown to be carcinogenic. When given to rats prior to mating,
nifedipine caused reduced fertility at a dose
approximately 30 times the maximum
recommended human dose.
In vivo mutagenicity studies were negative.
Pregnancy
Pregnancy Category C. In
rodents, rabbits and monkeys, nifedipine has been shown to have
a variety of embryotoxic,
placentotoxic and fetotoxic effects, including stunted fetuses (rats,
mice and rabbits), digital anomalies (rats and rabbits), rib
deformities (mice), cleft
palate (mice), small
placentas and underdeveloped chorionic villi
(monkeys), embryonic
and fetal deaths (rats, mice and rabbits), prolonged pregnancy
(rats; not evaluated in other species), and decreased neonatal
survival (rats; not
evaluated in other species). On a mg/kg or mg/m2 basis,
some of the doses associated with these various effects are higher
than the maximum recommended
human dose and some are lower, but all are within an order
of magnitude of it.
The digital anomalies seen in nifedipine-exposed rabbit pigs
are strikingly similar to those seen in pigs
exposed to phenytoin, and these are in turn similar to the phalangeal
deformities that are the most common malformation seen in human
children with in utero exposure
to phenytoin. There are no adequate and well-controlled studies
in pregnant women.
A.A.A. CC should be used
during pregnancy only
if the potential benefit
justifies the potential risk to the fetus.
Nursing Mothers
Nifedipine is excreted in human
milk. Therefore, a decision should be made to discontinue nursing
or to discontinue the drug, taking into account the importance of
the drug to the mother.
Geriatric Use: Although small
pharmacokinetic studies have identified an increased half-life and
increased C max and AUC (See CLINICAL PHARMACOLOGY : Pharmacokinetics and
Metabolism ), clinical studies of nifedipine did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond
differently from younger subjects. Other reported clinical experience has
not identified differences in responses between the elderly and younger
patients. In general, dose selection for an elderly patient should be
cautious, usually starting at the low end of the dosing range, reflecting
the greater frequency of decreased hepatic, renal, or cardiac function,
and of concomitant disease or other drug
top
