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
Catapres Warnings, Precautions, Pregnancy, Nursing, Abuse - Clonidine
Catapres Warnings, Precautions, Pregnancy, Nursing, Abuse - Clonidine
WARNINGS
Epidural Injection
Use in Postoperative or Obstetrical Analgesia: Epidural
clonidine is not recommended for obstetrical, post-partum, or peri-operative
pain management. The risk
of hemodynamic instability, especially hypotension and bradycardia,
from epidural clonidine
may be unacceptable in these patients.
Hypotension: Because severe hypotension may follow
the administration
of clonidine, it should be used with caution in all patients. It
is not recommended in most patients with severe cardiovascular
disease or in those
who are otherwise hemodynamically unstable. The benefit
of its administration
in these patients should be carefully balanced against the potential
risks resulting from hypotension.
Vital signs should be monitored frequently, especially during the
first few days of epidural
clonidine therapy. When clonidine is infused into the upper thoracic
spinal segments, more
pronounced decreases in the blood pressure may be seen.
Clonidine decreases sympathetic
outflow from the central
nervous system resulting
in decreases in peripheral
resistance, renal
vascular resistance,
heart rate, and blood
pressure. However, in the absence
of profound hypotension, renal blood
flow and glomerular
filtration rate
remain essentially unchanged.
In the pivotal double-blind, randomized study of cancer
patients, where 38 subjects were administered epidural
clonidine HCl at 30 mcg/hr in addition to epidural
morphine, hypertension
occurred in 45% of subjects. Most episodes of hypotension
occurred within the first fours days after beginning epidural clonidine.
However, hypotensive
episodes occurred throughout the duration of the trial. There was
a tendency for these episodes to occur more commonly in women, and
in those with higher serum
clonidine levels. Patients experiencing hypotension also tended
to weigh less than those who did not experience hypotension. The
hypotension usually
responded to intravenous
fluids and, if necessary, parenteral
ephedrine.
Published reports on the use of epidural
clonidine for intraoperative or postoperative analgesia
also show a consistent
and marked hypotensive response to clonidine. Severe hypotension
may occur if intravenous
fluid pretreatment is given.
Withdrawal: Sudden cessation of clonidine treatment,
regardless of the route of administration, hours
in some cases, resulted in symptoms such as nervousness, agitation,
headache, and tremor,
accompanied or followed by a rapid rise in blood
pressure. The likelihood of such
reactions appears to be greater after administration
of higher doses or with concomitant beta-blocker treatment. Special
caution is therefore advised in these situations. Rare instances
of hypertensive
encephalopathy,
cerebrovascular
accidents and death have
been reported after abrupt clonidine withdrawl. Patients with a
history of hypertension
and/or other underlying cardiovascular
conditions may be at risk
of the consequences of abrupt discontinuation of clonidine. In the
pivotal double-blind, randomized cancer
pain study, four of 38
subjects receiving 720 mcg
of clonidine per day experienced
rebound hypertension
following abrupt withdrawl. One of these patients with rebound
hypertension subsequently experienced a cerebrovascular
accident.
Careful monitoring of infusion
pump function
and inspection of
catheter tubing for obstruction
or dislodgement can help reduce
the risk of inadvertent
abrupt withdrawl of epidural
clonidine. Patients should notify their physician immediately if
clonidine administration
is inadvertently interrupted for any reason. Patients should also
be instructed not to discontinue therapy without consulting their
physician.
When discontinuing therapy
with epidural clonidine,
the physician should
reduce the dose gradually
over 2 to 4 days to avoid withdrawl symptoms.
An excessive rise in blood
pressure following
discontinuation of epidural clonidine can be treated by administration
of clonidine or by intravenous phentolamine. If therapy
is to be discontinued in patients receiving a beta-blocker and clonidine
concurrently, the beta-blocker should be withdrawn several days
before the gradual discontinuation of epidural
clonidine.
Infections: Infections related to implantable epidural
catheters pose a serious risk. Evaluation of fever in a patient
receiving epidural
clonidine should include the possibility of catheter-related infection
such as meningitis
or epidural abscess.
PRECAUTIONS
Tablet
General
In patients who have developed
localized contact
sensitization to clonidine film, substitution
of oral clonidine hydrochloride
therapy may be associated with the development
of a generalized skin rash.
In patients who develop an allergic
reaction from clonidine
film that extends beyond
the local patch
site (such as generalized
skin rash,
urticaria, or angioedema), oral
clonidine hydrochloride
substitution may
elicit a similar reaction.
As with all antihypertensive
therapy, clonidine hydrochloride
should be used with caution in patients with severe coronary
insufficiency, recent myocardial infarction, cerebrovascular
disease or chronic
renal failure.
Withdrawal: Patients should be instructed not to
discontinue therapy without consulting their physician. Sudden cessation
of clonidine treatment has resulted in subjective
symptoms such as nervousness,
agitation and headache,
accompanied or followed by a rapid rise in blood
pressure and elevated catecholamine
concentrations in the plasma,
but such occurrences have
usually been associated with previous administration
of high oral doses (exceeding 1.2 mg/day) and/or with continuation
of concomitant beta-blocker
therapy. Rare instances of hypertensive
encephalopathy
and death have been reported.
When discontinuing therapy
with clonidine hydrochloride, the physician should reduce
the dose gradually over
2 to 4 days withdrawal symptomatology.
An excessive rise in blood
pressure following
clonidine hydrochloride discontinuance can be reversed by administration
of oral clonidine or by
intravenous phentolamine. If therapy
is to be discontinued in patients receiving beta-blockers and clonidine
concurrently, beta-blockers should be discontinued several days
before the gradual withdrawal
of clonidine hydrochloride.
Perioperative Use: Administration of clonidine hydrochloride
should be continued to within four hours of surgery
and resumed as soon as possible thereafter. The blood
pressure should be
carefully monitored and appropriate
measures instituted to control
it as necessary.
Information for Patients
See PATIENT INFORMATION
- Tablet.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 132-week (fixed concentration)
dietary administration
study in rats, clonidine hydrochloride administered at 32 to 46
times the maximum recommended
daily human dose was unassociated
with evidence of carcinogenic
potential.
Fertility of male or female
rats was unaffected by clonidine hydrochloride doses as high as
150 mcg/kg or about 3 times the maximum
recommended daily human dose
(MRDHD). Fertility of female
rats did, however, appear to be affected (in another experiment)
at dose levels of 500 to
2000 mcg/kg or 10 to 40 times the MRDHD.
Usage in Pregnancy
Teratogenic Effects: Pregnancy Category C: Reproduction
studies performed in rabbits at doses up to approximately 3 times
the maximum recommended
daily human dose
(MRDHD) of clonidine hydrochloride have revealed no
evidence of teratogenic
or embryotoxic potential
in rabbits. In rats, however, doses as low as 1/3 the MRDHD were
associated with increased resorptions in a study in which dams were
treated continuously from 2 months prior to mating. Increased resorptions
were not associated with treatment at the same or at higher dose
levels (up to 3 times the MRDHD) when dams were treated days 6-15
of gestation. Increased resorptions were observed at much higher
levels (40 times the MRDHD) in rats and mice treated days 1-14 of
gestation (lowest
dose employed in that study
was 500 mcg/kg). There are, however, no
adequate and well-controlled studies in pregnant women. Because
animal reproduction
studies are not always predictive of human response, this drug
should be used during pregnancy
only if clearly needed.
Nursing Mothers
As clonidine hydrochloride
is excreted in human milk, caution should be exercised when clonidine
hydrochloride
is administered to a nursing
woman.
Pediatric Use
Safety and effectiveness
in children have not been established.
Epidural Injection
General
Cardiac Effects: Epidural clonidine frequently causes
decreases in heart rate.
Symptomatic bradycardia
can be treated with atropine. Rarely, atrioventricular block
greater than first degree
has been reported. Clonidine does not alter the hemodynamic response
to exercise, but may mask
the increase in heart
rate associated with hypovolemia.
Respiratory Depression and Sedation: Clonidine administration
may result in sedation
through the activation
of alpha-adrenoceptors in the brainstem. High doses of clonidine
cause sedation
and ventilatory abnormalities that are usually mild. Tolerance to
these effects can develop with chronic administration. These effects
have been reported with bolus
doses that are significantly larger than the infusion
rate recommended for treating
cancer pain.
Depression: Depression has been seen in a small percentage
of patients treated with oral
or transdermal clonidine. Depression commonly occurs in cancer
patients and may be exacerbated by treatment
with clonidine. Patients, especially those with a known history
of affective disorders,
should be monitored for the signs and symptoms of depression.
Pain of Visceral or Somatic Origin: In
the clinical investigations,
at doses tested, epidural
clonidine HCl was most effective in well-localized, ``neuropathic''
pain that was characterized
as electrical, burning, or shooting in nature, and which was localized
to a dermatomal or peripheral nerve distribution. Epidural clonidine
HCl may be less effective, or possibly ineffective in the treatment
of pain that is diffuse,
poorly localized, or visceral
in origin.
Information for the Patient
See PATIENT INFORMATION - Epidural
Injection.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
In a 132-week study in rats, clonidine HCl administered as a dietary
admixture at 5-8 times (based on body
surface area) the 50
mcg/kg maximum recommended daily human
dose (MRDHD) for hypertension
did not show any carcinogenic
potential. Clonidine was inactive in the Ames test
of mutagenicity. Fertility of male
and female rats was unaffected
by oral clonidine HCl doses
as high as 150 mcg/kg, or about 0.5 times the MRDHD. Fertility of
female rats did, however, appear to be affected in another experiment
at oral dose levels of
500-2000 mcg/kg, or 2-7 times the MRDHD.
Usage in Pregnancy
Teratogenic Effects: Pregnancy Category C: Reproduction
studies in rabbits at clonidine HCl doses up to approximately the
MRDHD revealed no evidence
of teratogenic or
embryotoxic potential. In rats, however, doses as low as one-third
the MRDHD were associated with increased resorptions in a study
in which dams were treated continuously from 2 months prior to mating.
Increased resorptions were not associated with treatment
with the same or higher doses up to 0.5 times the MRDHD when dams
were treated on days 6-15 of gestation. Increased resorptions were
observed at higher levels (7-times the MRDHD) in rats and mice treated
on days 1-14 of gestation.
Clonidine readily crosses the placenta
and its concentrations are equal in maternal
and umbilical cord
plasma; amniotic fluid
concentrations can be 4-times those found in serum. There are no
adequate and well-controlled studies in pregnant
women during early gestation
when organ formation
takes place. Studies using epidural
clonidine during labor
have demonstrated no apparent
adverse effects on the infant
at the time of delivery.
However, these studies did not monitor
the infants for hemodynamic effects in the days following delivery.
Clonidine HCl injection
should be used during pregnancy only if the potential
benefits justify the potential
risk to the fetus.
Labor and Delivery
There are no adequate controlled
clinical trials evaluating
the safety, efficacy, and dosing of epidural
clonidine HCl in obstetrical settings. Because maternal
perfusion of the placenta
is critically dependent on blood pressure, use of epidural
clonidine HCl as an analgesic
during labor and delivery
is not indicated (see WARNINGS
.)
Nursing Mothers
Concentrations of clonidine in human
breast milk
are approximately twice those found in maternal
plasma. Caution should be exercised when clonidine is administered
to a nursing woman.
Because of the potential
for severe adverse reactions in nursing
infants, a decision should be made to either discontinue nursing
or to discontinue clonidine.
Pediatric Use
The safety and effectiveness
of epidural clonidine
HCl in this limited indication and clinical
population have been
established in patients old enough to tolerate placement and management
of an epidural catheter,
based on evidence from
adequate and well controlled studies in adults and experience with
the use of clonidine in the pediatric
age group
for other indications. The use of epidural
clonidine HCl should be restricted to pediatric
patients with severe intractable
pain from malignancy
that is unresponsive to epidural or spinal
opiates or other more conventional analgesic
techniques. The starting dose
of epidural clonidine
HCl should be selected on per
kilogram basis (0.5 mcg
per kg
per hour) and cautiously
adjusted based on the clinical response.
top
