Applies to clonidine: compounding powder, injectable solution, oral suspension extended release, oral tablet, oral tablet extended release, transdermal film extended release
The most common adverse side effects are related to the alpha-adrenergic blocking effects of clonidine (the active ingredient contained in Catapres) These side effects are dose-related, typically decrease over time, and mostly affect the nervous system, cardiovascular system, and the gastrointestinal system.
Nervous system side effects have included drowsiness (28%), dizziness (9%), somnolence (19%), fatigue (13%), headache (19%), irritability (6%), insomnia (6%), nightmares (3%), body temperature increased (1%), abnormal sleep-related event (1%), and tremor (3%). Patients with decreased autoregulation of cerebral blood flow appear to be at increased risk for clonidine-induced cerebral hypoperfusion if blood pressure is lowered too much or too quickly. This may be important in some elderly patients. Confusion (13.2%) and hallucinations (5.3%) have been reported with epidural usage. Dose-dependent sedative effects, memory impairment, and reduced cognitive performance have been reported in subjects receiving intravenous clonidine (the active ingredient contained in Catapres)
A study of 13 patients who had pre- and post-clonidine cerebral blood flow (CBF) measured by nuclear scanning revealed that patients with an initially high pretreatment CBF tended to demonstrate decreased CBF after clonidine therapy.
Patients with traumatic spinal cord injury receiving clonidine may experience a delayed-onset of sedation regardless of the route of administration (i.e., intrathecal, intramuscular).
Cardiovascular side effects have included hypotension and sinus and atrioventricular arrhythmias. Postural hypotension occurs in 2% of patients. Rebound hypertension (which may be worse than pretreatment values) can present as irritability, tremors, headache, increased salivation, and palpitations. Rebound hypertension may be minimized by gradual reduction of dosage over two to four days.
Hypotension with epidural clonidine (the active ingredient contained in Catapres) has been reported in 45% of 38 patients in one study. Hypotension occurred more commonly in the first four days, in women, in lower weight patients, and those receiving higher dosages.
Other cardiovascular side effects have included sinus bradycardia in approximately 0.3% of patients. A rare case of sinus arrest associated with clonidine has been reported. Patients with preexisting sinus node dysfunction, patients who have developed bradycardia while taking other sympatholytic agents, patients who are on another sympatholytic agent, and patients with renal dysfunction are at increased risk of clonidine-associated sinus bradycardia. Clonidine may cause hypertension in some patients with idiopathic orthostatic hypotension, particularly those with autonomic nervous system dysfunction. There have also been reports of congestive heart failure, electrocardiographic abnormalities (i.e., sinus node arrest, junctional bradycardia, high degree AV block, and arrhythmias), palpitations, Raynaud's phenomenon, syncope, and tachycardia. Cases of sinus bradycardia and atrioventricular block have been reported, both with and without the use of concomitant digitalis.
A case of sinus arrest associated with clonidine has been reported. A 65-year-old man with diabetes, hypertension and unexplained syncope developed more frequent syncope and dizziness associated with documented episodes of sinus arrest during the first week of clonidine therapy. The patient had no hypoglycemia or orthostatic changes. The syncope and dizziness resolved upon discontinuation of clonidine; continuous electrocardiographic monitoring revealed a gradual and complete disappearance of sinus pauses. Junctional bradycardia and AV heart block have also been reported.
Ventricular tachycardia (VT) relatively refractory to lidocaine, but responsive to intravenous phentolamine, has been associated with clonidine withdrawal (case report). The authors believe that the VT was probably produced by humoral or neural stimulation of unregulated myocardial alpha-adrenergic receptors.
Transdermal clonidine has been implicated with hypertension in a quadriplegic patient with a C4 spinal lesion. The proposed mechanism is predominance of clonidine's peripheral alpha-1 adrenergic effects due to the patient's autonomic dysfunction, resulting in vasoconstriction and hypertension.
Sinus bradycardia or other supraventricular bradyarrhythmias are more likely in patients with underlying renal dysfunction.
In one case report, severe hypotension occurred during separation from cardiopulmonary bypass in a patient given intrathecal clonidine. The patient responded to volume expansion and use of vasoconstrictors.
Gastrointestinal side effects have most commonly included dry mouth (30%) and constipation (15%), abdominal pain, anorexia, nausea, vomiting, diarrhea (1%), parotitis, pseudo-obstruction (including colonic pseudo-obstruction), and salivary gland pain. Nausea (13.2%) and vomiting (10.5%) have been reported with epidural clonidine (the active ingredient contained in Catapres)
Genitourinary side effects have included impotence in male patients (24%), retrograde and delayed ejaculation, and an inability to achieve orgasm in female patients.
A 66-year-old woman with a history of psoriasis in remission developed erythematous, scaly plaques on the extensor surfaces of her forearms within three days after beginning clonidine (the active ingredient contained in Catapres) therapy for control of flushing. The author of this case report suspected that clonidine may cause a fall in intracellular cAMP, leading to epidermal cell proliferation, and, in some cases, a psoriasiform eruption.
Dermatologic reactions have been reported in 10% to 38% of patients who use transdermal clonidine. These reactions include psoriasis exacerbations, local dermatitis and/or pigmentation, alopecia, angioneurotic edema, hives, pruritus, rash, and urticaria.
Psychiatric side effects have included emotional disorder (5%), aggression (1%), tearfulness (3%) and rare reports of depression, which has been the most common psychiatric reaction to clonidine (the active ingredient contained in Catapres) Rare cases of frank psychoses and delirium have been associated with clonidine withdrawal. Hallucinations have been reported postmarketing.
Endocrinologic side effects have been limited to rare cases of gynecomastia, hyperprolactinemia, or hyperglycemia.
A 68-year-old black man with hypertension, status post unilateral nephrectomy, was incidentally found to have 4+ proteinuria, 1+ glycosuria, new elevated blood glucose levels, and between 1.8 and 5.4 grams of protein per 24-hour urine collection within 6 weeks after starting clonidine. The signs and symptoms of diabetes and the nephrotic syndrome disappeared within five months after discontinuation of clonidine. Because of his solitary kidney, a renal biopsy was not performed.
Musculoskeletal side effects have included leg cramps and muscle or joint pain. Moderately severe myalgia has been associated with the use of clonidine (the active ingredient contained in Catapres) in patients treated for opioid withdrawal symptoms.
Immunologic side effects have rarely been reported and include one case of immune-complex disease.
A 46-year-old woman developed forearm edema, mild thenar atrophy, and skin hypopigmentation within three months after beginning clonidine for perimenopausal flushing. Electromyelography was consistent with carpal tunnel syndrome. At surgical decompression, a skin biopsy revealed changes consistent with immune-complex disease. The patient's signs and symptoms abated after physical therapy and discontinuation of clonidine.
A 9-year-old boy with asthma developed a severe asthma attack after an oral clonidine (the active ingredient contained in Catapres) stimulation test. He required hospitalization. The authors of this case report suspect that clonidine may have caused acute pulmonary artery vasoconstriction (directly), which could have decreased pulmonary blood flow, producing relative pulmonary hypoxemia, setting off an asthma attack.
Respiratory system reactions have included nasal congestion (5%), asthma (1%), and nasopharyngitis (3%). A case of severe bronchospasm associated with clonidine has been reported in the pediatric literature.
Ocular side effects have included accommodation disorder, blurred vision, burning of the eyes, decreased lacrimation, and dryness of the eyes.
Metabolic side effects have included thirst (3%) and throat pain (6%).