DURACLON adverse reactions

# Adverse Reactions
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 clonidine.
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 morphine.
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 Coombs test, and increased sensitivity to alcohol.

## Cardiovascular
Palpitations and tachycardia, and bradycardia, each 0.5%. Syncope, Raynauds 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 rarely reported.

## Ophthalmological
Dryness of the eyes, burning of the eyes and blurred vision were rarely reported.