Clinical trial experience with CATAPRES-TTS (clonidine)
Most systemic adverse effects during Catapres-TTS (clonidine) transdermal therapeutic
system therapy have been mild and have tended to diminish with continued therapy.
In a 3-month multi-clinic trial of Catapres-TTS (clonidine) transdermal therapeutic system
in 101 hypertensive patients, the systemic adverse reactions were, dry mouth
(25 patients) and drowsiness (12), fatigue (6), headache (5), lethargy and sedation
(3 each), insomnia, dizziness, impotence/sexual dysfunction, dry throat (2 each)
and constipation, nausea, change in taste and nervousness (1 each).
In the above mentioned 3-month controlled clinical trial, as well as other
uncontrolled clinical trials, the most frequent adverse reactions were dermatological
and are described below.
In the 3-month trial, 51 of the 101 patients had localized skin reactions such
as erythema (26 patients) and/or pruritus, particularly after using an adhesive
cover throughout the 7-day dosage interval. Allergic contact sensitization to
Catapres-TTS (clonidine) transdermal therapeutic system was observed in 5 patients. Other
skin reactions were localized vesiculation (7 patients), hyperpigmentation (5),
edema (3), excoriation (3), burning (3), papules (1), throbbing (1), blanching
(1), and a generalized macular rash (1).
In additional clinical experience, contact dermatitis resulting in treatment
discontinuation was observed in 128 of 673 patients (about 19 in 100) after
a mean duration of treatment of 37 weeks. The incidence of contact dermatitis
was about 34 in 100 among white women, about 18 in 100 in white men, about 14
in 100 in black women, and approximately 8 in 100 in black men. Analysis of
skin reaction data showed that the risk of having to discontinue Catapres-TTS (clonidine)
transdermal therapeutic system treatment because of contact dermatitis was greatest
between treatment weeks 6 and 26, although sensitivity may develop either earlier
or later in treatment.
In a large-scale clinical acceptability and safety study by 451 physicians
in a total of 3539 patients, other allergic reactions were recorded for which
a causal relationship to Catapres-TTS (clonidine) transdermal therapeutic system was not
established: maculopapular rash (10 cases); urticaria (2 cases); and angioedema
of the face (2 cases), which also affected the tongue in one of the patients.
Marketing Experience with Catapres-TTS (clonidine)
The following adverse reactions have been identified during post-approval use
of Catapres-TTS (clonidine) transdermal therapeutic system. Because these reactions are
reported voluntarily from a population of uncertain size, it is not always possible
to estimate reliably their frequency or establish a causal relationship to drug
exposure. Decisions to include these reactions in labeling are typically based
on one or more of the following factors: (1) seriousness of the reaction, (2)
frequency of reporting, or (3) strength of causal connection to Catapres-TTS (clonidine)
transdermal therapeutic system.
Body as a Whole: Fever; malaise; weakness; pallor; and withdrawal
Cardiovascular: Congestive heart failure; cerebrovascular accident;
electrocardiographic abnormalities (i.e., bradycardia, sick sinus syndrome disturbances
and arrhythmias); chest pain; orthostatic symptoms; syncope; increases in blood
pressure; sinus bradycardia and atrioventricular (AV) block with and without
the use of concomitant digitalis; Raynaud's phenomenon; tachycardia; bradycardia;
Central and Peripheral Nervous System/Psychiatric: Delirium;
mental depression; hallucinations (including visual and auditory); localized
numbness; vivid dreams or nightmares; restlessness; anxiety; agitation; irritability;
other behavioral changes; and drowsiness.
Dermatological: Angioneurotic edema; localized or generalized
rash; hives; urticaria; contact dermatitis; pruritus; alopecia; and localized
hypo or hyper pigmentation.
Gastrointestinal: Anorexia and vomiting.
Genitourinary: Difficult micturition; loss of libido; and decreased
Metabolic: Gynecomastia or breast enlargement and weight gain.
Musculoskeletal: Muscle or joint pain; and leg cramps.
Ophthalmological: Blurred vision; burning of the eyes and dryness
of the eyes.
Adverse Events Associated with Oral Catapres Therapy
Most adverse effects are mild and tend to diminish with continued therapy.
The most frequent (which appear to be dose-related) are dry mouth, occurring
in about 40 of 100 patients; drowsiness, about 33 in 100; dizziness, about 16
in 100; constipation and sedation, each about 10 in 100. The following less
frequent adverse experiences have also been reported in patients receiving Catapres
(clonidine hydrochloride, USP) tablets, but in many cases patients were receiving
concomitant medication and a causal relationship has not been established.
Body as a Whole: Fatigue, fever, headache, pallor, weakness,
and withdrawal syndrome. Also reported were a weakly positive Coombs' test and
increased sensitivity to alcohol.
Cardiovascular: Bradycardia, congestive heart failure, electrocardiographic
abnormalities (i.e., sinus node arrest, junctional bradycardia, high degree
AV block and arrhythmias), orthostatic symptoms, palpitations, Raynaud's phenomenon,
syncope, and tachycardia. Cases of sinus bradycardia and AV block have been
reported, both with and without the use of concomitant digitalis.
Central Nervous System: Agitation, anxiety, delirium, delusional
perception, hallucinations (including visual and auditory), insomnia, mental
depression, nervousness, other behavioral changes, paresthesia, restlessness,
sleep disorder, and vivid dreams or nightmares.
Dermatological: Alopecia, angioneurotic edema, hives, pruritus,
rash, and urticaria.
Gastrointestinal: Abdominal pain, anorexia, constipation, hepatitis,
malaise, mild transient abnormalities in liver function tests, nausea, parotitis,
pseudo-obstruction (including colonic pseudo-obstruction), salivary gland pain,
Genitourinary: Decreased sexual activity, difficulty in micturition,
erectile dysfunction, loss of libido, nocturia, and urinary retention.
Metabolic: Gynecomastia, transient elevation of blood glucose
or serum creatine phosphokinase, and weight gain.
Musculoskeletal: Leg cramps and muscle or joint pain.
Oro-otolaryngeal: Dryness of the nasal mucosa.
Ophthalmological: Accommodation disorder, blurred vision, burning
of the eyes, decreased lacrimation, and dryness of the eyes.