Adverse reactions seen during continuous epidural
clonidine infusion are dose-dependent and typical for a compound of this
pharmacologic class. The adverse events most frequently reported in the pivotal
controlled clinical trial of continuous epidural clonidine administration
consisted of hypotension, postural hypotension, decreased heart rate, rebound
hypertension, dry mouth, nausea, confusion, dizziness, somnolence, and fever.
Hypotension is the adverse event that most frequently requires treatment. The hypotension
is usually responsive to intravenous fluids and, if necessary, appropriate parenterally-administered
pressor agents. Hypotension was observed more frequently in women and in lower
weight patients, but no dose-related response was established.
Implantable epidural catheters are associated with a risk
of catheter-related infections, including meningitis and/or epidural abscess.
The risk depends on the clinical situation and the type of catheter used, but
catheter related infections occur in 5%-20% of patients, depending on the kind
of catheter used, catheter placement technique, quality of catheter care, and
length of catheter placement.
The inadvertent intrathecal administration of clonidine
has not been associated with a significantly increased risk of adverse events,
but there are inadequate safety and efficacy data to support the use of intrathecal
Epidural clonidine was compared to placebo in a two week
double-blind study of 85 terminal cancer patients with intractable pain
receiving epidural morphine. The following adverse events were reported in two
or more patients and may be related to administration of either Duraclon or
Incidence of Adverse Events in the Two-Week Trial
N = 38 n (%)
N = 47 n (%)
|Total Number of Patients Who Experienced at Least One Adverse Event
An open label long-term extension of the above trial was
performed. Thirty-two subjects received epidural clonidine and morphine for up
to 94 weeks with a median dosing period of 10 weeks. The following adverse
events (and percent incidence) were reported: hypotension/postural hypotension (47%);
nausea (13%); anxiety/confusion (38%); somnolence (25%); urinary tract
infection (22%); constipation, dyspnea, fever, infection (6% each); asthenia,
hyperaesthesia, pain, skin ulcer, and vomiting (5% each). Eighteen percent of
subjects discontinued this study as a result of catheter-related problems
(infections, accidental dislodging, etc.), and one subject developed
meningitis, possibly as a result of a catheter-related infection. In this
study, rebound hypertension was not assessed, and ECG and laboratory data were
not systematically sought.
The following adverse reactions have also been reported
with the use of any dosage form of clonidine. In many cases patients were
receiving concomitant medication and a causal relationship has not been established:
Body as a Whole: Weakness, 10%; fatigue, 4%;
headache and withdrawal syndrome, each 1%. Also reported were pallor, a weakly
positive Coomb's test, and increased sensitivity to alcohol.
Cardiovascular: Palpitations and tachycardia, and
bradycardia, each 0.5%. Syncope, Raynaud's phenomenon, congestive heart
failure, and electrocardiographic abnormalities (i.e., sinus node arrest, functional
bradycardia, high degree AV block) have been reported rarely. Rare cases of
sinus bradycardia and atrioventricular block have been reported, both with and
without the use of concomitant digitalis.
Central Nervous System: Nervousness and agitation,
3%; mental depression, 1%; insomnia, 0.5%. Cerebrovascular accidents, other
behavioral changes, vivid dreams or nightmares, restlessness, and delirium have
been reported rarely.
Dermatological: Rash, 1%; pruritus, 0.7%; hives,
angioneurotic edema and urticaria, 0.5%; alopecia, 0.2%.
Gastrointestinal: Anorexia and malaise, each 1%;
mild transient abnormalities in liver function tests, 1%; hepatitis, parotitis,
ileus and pseudo obstruction, and abdominal pain, rarely.
Genitourinary: Decreased sexual activity,
impotence, and libido, 3%; nocturia, about 1%; difficulty in micturition, about
0.2%; urinary retention, about 0.1%.
Hematologic: Thrombocytopenia, rarely.
Metabolic: Weight gain, 0.1%; gynecomastia, 1%;
transient elevation of glucose or serum phosphatase, rarely.
Musculoskeletal: Muscle or joint pain, about 0.6%;
leg cramps, 0.3%.
Oro-otolaryngeal: Dryness of the nasal mucosa was
Ophthalmological: Dryness of the eyes, burning of
the eyes and blurred vision were rarely reported.