Clonidine hydrochloride and transdermal clonidine are used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Although other antihypertensive drug classes (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics) are preferred for the initial management of hypertension in adults, centrally acting agents such as clonidine may be considered as add-on therapy if goal blood pressure cannot be achieved with the recommended drugs.
Although many hypertensive patients may be controlled by clonidine alone, the drug may be more effective when used with a diuretic. Clonidine hydrochloride has been used in conjunction with thiazide diuretics, chlorthalidone, or furosemide, producing a greater reduction in blood pressure than is obtained with either drug alone. Use of a diuretic may aid in overcoming tolerance to clonidine and permit reduction of clonidine dosage.
Clonidine may be useful in some patients who are unable to tolerate other adrenergic blocking agents because of severe postural hypotension. However, the possibility that geriatric patients may not tolerate the adverse cognitive effects of central α2-adrenergic agonists such as clonidine should be considered. Clonidine hydrochloride has been used with other hypotensive agents such as hydralazine, reserpine, or methyldopa, permitting a reduction in the dosage of each drug and, in some patients, minimizing adverse effects while maintaining blood pressure control. As when clonidine is used alone, satisfactory results are obtained in both supine and standing patients during combined drug therapy; marked fluctuations in blood pressure because of postural changes usually do not occur during combined therapy. As with other hypotensive agents, treatment with clonidine is not curative; upon withdrawal of the drug, blood pressure returns to pretreatment levels or greater.
(See Cautions: Withdrawal Effects.)
Transdermal clonidine has been effective in many patients for the management of mild to moderate hypertension when used alone or in combination with an oral thiazide diuretic and has also been successfully substituted for oral clonidine hydrochloride in some patients with mild to moderate hypertension whose therapy included the oral form of the drug. The role of transdermal clonidine relative to oral clonidine hydrochloride remains to be more fully evaluated; transdermal clonidine therapy may prove to be convenient in some patients (e.g., those in whom compliance with a daily dosing regimen may be a problem), but adverse dermatologic reactions may occur frequently.
For additional information on overall principles and expert recommendations for treatment of hypertension,
Oral loading-dose regimens of clonidine hydrochloride have been effective in rapidly reducing blood pressure in patients with severe hypertension in whom reduction of blood pressure was considered urgent, but not requiring emergency treatment. Hypertensive urgencies are those situations in which there is a severe elevation in blood pressure without progressive target organ damage. Hypertensive urgencies can be managed by intensification or reinstitution (e.g., following noncompliance) of the current antihypertensive regimen or with oral doses of short-acting antihypertensive agents such as clonidine hydrochloride followed by several hours of observation; however, there is no evidence suggesting that failure to aggressively reduce blood pressure in these patients is associated with any short-term risk. In fact, overly aggressive management of severe elevations in blood pressure not associated with impending or progressing organ damage can sometimes lead to cumulative hypotensive effects. Excessive falls in blood pressure should be avoided since they may precipitate renal, cerebral, or coronary ischemia.
Clonidine hydrochloride also has been used IV in the management of acute hypertensive crisis and in hypertensive episodes during labor, as well as IM or subcutaneously in the management of late-onset toxemia of pregnancy, with satisfactory results; however, an injectable dosage form is not currently available in the US. When the drug is administered IV, it must be injected very slowly in order to minimize the possible hypertension that may precede its hypotensive effect.
Clonidine hydrochloride administered by epidural infusion is used as adjunctive therapy in combination with opiates in the management of severe cancer pain that is not relieved by opiate analgesics alone. Epidural administration of analgesics should be considered only when maximum tolerated doses of opiate and adjunct analgesics administered by other routes (e.g., oral, transdermal, subcutaneous, IV) fail to relieve pain.
(See Cautions: Precautions and Contraindications.)Consistent with the drug's mechanism of action, epidural clonidine is more likely to be effective in patients with neuropathic pain rather than somatic or visceral pain.
In a double-blind, placebo-controlled, randomized study, cancer patients with severe intractable pain below the cervical dermatomes not controlled by oral, epidural, or IV opiate analgesics received epidural morphine with either clonidine hydrochloride 30 mcg/hour by continuous epidural infusion or placebo for 14 days. Pain relief, measured by a decrease in use of epidural morphine or a decrease in visual analog pain score, was reported in 45 or 21% of patients receiving epidural clonidine or placebo, respectively. In this study, substantial analgesic effects of clonidine appeared to be restricted to patients with neuropathic pain, characterized as localized, burning, shooting, or electric-like pain in a dermatomal or peripheral nerve distribution.
Clonidine is not indicated in patients with pheochromocytoma; however, unlike reserpine and guanethidine, it does not cause acute cardiovascular collapse in patients with this condition. Because of clonidine's ability to suppress plasma norepinephrine concentration in healthy individuals via stimulation of central α-adrenergic receptors, the drug has been used as an aid in the diagnosis of pheochromocytoma in hypertensive patients with suggestive symptoms and borderline catecholamine values; in patients with pheochromocytoma, plasma norepinephrine concentration is generally unchanged following administration of a single oral dose of clonidine, while patients with sympathetic hyperactivity exhibit a decrease in plasma norepinephrine concentration.
Although clonidine has been used in the prophylaxis of migraine headaches, the efficacy of the drug for this condition is questionable. Results of most studies using α-adrenergic agents (e.g., clonidine) for prevention of migraine headaches indicate that these drugs have limited or no efficacy in most patients, and therefore, some experts state that such use is not recommended. For further information on management and classification of migraine headache,
Because clonidine reduces the responsiveness of blood vessels to vasodilators or vasoconstrictors, the drug has been used for the treatment of severe dysmenorrhea.
Vasomotor Symptoms Associated with Menopause
Clonidine has been used orally and transdermally for the management of vasomotor symptoms (e.g., hot flashes) associated with menopause. Although limited data indicate that the drug may improve the severity and frequency of vasomotor symptoms in some patients, albeit modestly, the required dosages (exceeding the equivalent of 0.1 mg daily administered orally) may result in increased and, sometimes, intolerable adverse effects. Therefore, some clinicians recommend the use of clonidine for management of vasomotor symptoms mainly in postmenopausal women in whom estrogen replacement therapy is contraindicated or in those with preexisting hypertension.
Clonidine hydrochloride has been used safely and effectively for rapid detoxification in the management of opiate withdrawal in opiate-dependent individuals, in both inpatient and outpatient settings. The exact role of clonidine and its efficacy compared with other methods of detoxification (e.g., methadone) remain to be clearly determined. Clonidine appears to be most useful as a transitional treatment between opiate dependence and administration of the opiate antagonist naltrexone. Clonidine also may be especially useful when detoxification using methadone is inappropriate, unsuccessful, or unavailable.
Clonidine also has been used in conjunction with benzodiazepines for the management of alcohol withdrawal. Clonidine appears to be effective in reducing symptoms of the hyperadrenergic state associated with alcohol withdrawal, including elevated blood pressure, increased heart rate, tremor, sweating, and anxiety. However, clonidine has not been shown to prevent delirium or seizures, and the drug should be used only as an adjunct to benzodiazepines (not as monotherapy) for the treatment of alcohol withdrawal . Some clinicians state that the use of clonidine may be particularly helpful in patients with certain coexisting conditions (e.g., opiate withdrawal).
Clonidine is used for the management of nicotine (tobacco) dependence. Nicotine dependence is a chronic relapsing disorder that requires ongoing assessment and often repeated intervention. Because effective nicotine dependence therapies are available, every patient should be offered effective treatment, and those who are unwilling to attempt cessation should be provided at least brief interventions designed to increase their motivation to stop tobacco use. The US Public Health Service (USPHS) guideline for the treatment of tobacco use and dependence currently recommends clonidine as a second-line drug for use under the supervision of a clinician. Second-line pharmacotherapy (e.g., clonidine, nortriptyline) is of a more limited role than first-line pharmacotherapy (i.e., bupropion [as extended-release tablets], nicotine polacrilex gum or lozenge, transdermal nicotine, nicotine nasal spray, nicotine oral inhaler, varenicline) in part because of more concerns about potential adverse effects. The use of second-line pharmacotherapy should be considered after first-line therapies have been used without success or are contraindicated. For additional information on smoking cessation, , and also consult the most current USPHS Clinical Practice Guideline on Treating Tobacco Use and Dependence available at http://www.ahrq.gov/professionals/clinicians-providers/guidelines-recommendations/index.html.
Clonidine hydrochloride has been used topically to reduce intraocular pressure in the treatment of open-angle (chronic simple) and secondary glaucoma and hemorrhagic glaucoma associated with hypertension.
Attention Deficit Hyperactivity Disorder
Clonidine has been used for the treatment of attention deficit hyperactivity disorder (ADHD). Although pooled data from a retrospective analysis of studies in children with ADHD (with and without comorbid conditions [e.g., developmental delay, conduct or tic disorders]) indicate that the drug has produced a moderate reduction in symptoms of ADHD, stimulants (e.g., methylphenidate, amphetamines) remain the drugs of choice for the management of ADHD because of their greater efficacy compared with that of other drugs (e.g., clonidine). Clonidine generally has been shown to be more effective than placebo in the treatment of core symptoms of ADHD, but the magnitude of its effects is lower than with stimulants and efficacy has been established mainly in children with ADHD and comorbid conditions, especially sleep disturbances. However, because clonidine may improve motor tics in patients with Tourette's syndrome, some experts recommend its use as an adjunct to stimulant therapy in pediatric patients with ADHD whose comorbid tic disorder is not controlled by therapy with a stimulant alone. In pediatric patients without such comorbid psychiatric disorders, use of clonidine for the treatment of ADHD usually is not recommended, because of the current lack of evidence establishing safety and efficacy. For a more detailed discussion on the management of ADHD,
Because of its GI effects
(see Pharmacology: Other Effects), clonidine hydrochloride has been used with some success in a limited number of patients for the management of diarrhea of various etiologies (e.g., narcotic bowel syndrome, idiopathic diarrhea associated with diabetes).