ADVERSE REACTIONS
CLINICAL TRIAL EXPERIENCE WITH CATAPRES-TTS
Most systemic adverse effects during CATAPRES-TTS therapy have been mild and have tended to diminish with continued therapy. In a 3-month multiclinic trial of CATAPRES-TTS 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 overlay throughout the 7-day dosage interval. Allergic contact sensitization to CATAPRES-TTS 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 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 applicability 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 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
Other adverse effects reported since the drug has been marketed are listed below by body system. In this setting, an incidence or causal relationship cannot always be accurately determined. However, none of the events listed below occurred in a frequency greater than 0.5%. Body as a Whole Fever; malaise; weakness; pallor; and withdrawal syndrome.
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 block with and without the use of concomitant digitalis; Raynaud's phenomenon; tachycardia; bradycardia; and palpitations. Central and Peripheral Nervous System/Psychiatric Delirium; mental depression; visual and auditory hallucinations; 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 sexual activity.
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 events 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), but in many cases patients were receiving concomitant medication and a causal relationship has not been established. Body as a Whole Weakness, about 10 in 100 patients; fatigue, about 4 in 100; headache and withdrawal syndrome each about 1 in 100. Also reported were pallor; a weakly positive Coombs' test; increased sensitivity to alcohol; and fever.
Cardiovascular Orthostatic symptoms, about 3 in 100 patients; palpitations and tachycardia, and bradycardia, each about 5 in 1000. Syncope, Raynaud's phenomenon, congestive heart failure, and electrocardiographic abnormalities (i.e., sinus node arrest, functional bradycardia, high degree AV block and arrhythmias) have been reported rarely. Rare cases of sinus bradycardia and AV block have been reported, both with and without the use of concomitant digitalis. Central Nervous System Nervousness and agitation, about 3 in 100 patients, mental depression, about 1 in 100 and insomnia, about 5 in 1000. Other behavioral changes, vivid dreams or nightmares, restlessness, anxiety, visual and auditory hallucinations and delirium have rarely been reported. Dermatological Rash, about 1 in 100 patients; pruritus, about 7 in 1000; hives, angioneurotic edema and urticaria, about 5 in 1000; alopecia, about 2 in 1000. Gastrointestinal Nausea and vomiting, about 5 in 100 patients; anorexia and malaise, each about 1 in 100; mild transient abnormalities in liver function tests, about 1 in 100; hepatitis, parotitis, constipation, pseudo-obstruction, and abdominal pain, rarely. Genitourinary Decreased sexual activity, impotence and loss of libido, about 3 in 100 patients; nocturia, about 1 in 100; difficulty in micturition, about 2 in 1000; urinary retention, about 1 in 1000. Hematologic Thrombocytopenia, rarely. Metabolic Weight gain, about 1 in 100 patients; gynecomastia, about 1 in 1000; transient elevation of blood glucose or serum creatine phosphokinase, rarely. Musculoskeletal Muscle or joint pain, about 6 in 1000 and leg cramps, about 3 in 1000. Oro-otolaryngeal Dryness of the nasal mucosa was rarely reported. Ophthalmological Dryness of the eyes, burning of the eyes and blurred vision were reported.
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