What are the side effects of clonidine (antihypertensive medication)?

From the Guidelines

Clonidine can cause significant CNS adverse effects, especially in older adults, and should be used with caution due to the risk of rebound hypertension if discontinued abruptly. The side effects of clonidine, an antihypertensive medication, include drowsiness, fatigue, dry mouth, constipation, dizziness, and sedation, which occur due to its mechanism of stimulating alpha-2 adrenergic receptors in the brain, reducing sympathetic outflow, and lowering blood pressure 1. Some patients may experience more serious side effects such as hypotension, bradycardia, and rebound hypertension if the medication is stopped suddenly. Other potential side effects include depression, sleep disturbances, headache, and sexual dysfunction. Elderly patients may be more sensitive to these effects.

Key Considerations

• The medication should not be discontinued abruptly to avoid rebound hypertension; instead, the dose should be gradually reduced over 2-4 days under medical supervision 1.
• Patients should report severe dizziness, fainting, unusual mood changes, or irregular heartbeat to their healthcare provider immediately.
• Side effects often improve after the first few weeks of treatment as the body adjusts to the medication.

Management of Side Effects

• Monitoring of blood pressure and heart rate is essential when initiating or adjusting clonidine therapy.
• Patients should be educated on the potential side effects and the importance of gradual dose reduction if discontinuation is necessary.
• Alternative antihypertensive medications may be considered if side effects are severe or intolerable. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, clonidine is generally reserved as a last-line treatment due to its significant CNS adverse effects, especially in older adults 1.

From the FDA Drug Label

In patients who develop an allergic reaction to clonidine transdermal system, substitution of oral clonidine hydrochloride may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema). The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs Patients should be cautioned against interruption of clonidine hydrochloride tablets therapy without their physician's advice. Since patients may experience a possible sedative effect, dizziness, or accommodation disorder with use of clonidine, caution patients about engaging in activities such as driving a vehicle or operating appliances or machinery Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction, e.g., digitalis, calcium channel blockers, and beta-blockers. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil. OVERDOSAGE Hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, weakness, irritability and miosis.

The side effects of clonidine include:

• Allergic reactions: generalized rash, urticaria, or angioedema
• Cardiovascular effects: worsening of sinus node dysfunction and atrioventricular (AV) block, bradycardia, hypotension, hypertension
• CNS effects: sedative effect, dizziness, accommodation disorder, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, weakness, irritability, and miosis
• Other effects: dryness of eyes, corneal lesions (in combination with amitriptyline) 2, 2

From the Research

Common Side Effects

• Sedation: Clonidine has been shown to cause sedation in patients, with all subjects in one study complaining of severe sedation 3.
• Dryness of the mouth: Dry mouth is a common side effect of clonidine, with a significant correlation between the plasma concentrations of the drug and the occurrence of this side effect 3.
• Rebound increase in blood pressure: Rapid withdrawal of clonidine can lead to a rebound increase in blood pressure, which can be potentially serious 4.

Less Common Side Effects

• Altered mentation: Clonidine has been reported to cause altered mentation in some patients, particularly those with idiopathic orthostatic hypotension 5.
• Excessive hypertension: Clonidine can cause excessive hypertension in some patients, particularly those with idiopathic orthostatic hypotension 5.
• Coronary vasospasm: A case study reported a rare instance of coronary vasospasm secondary to clonidine overdose 6.
• Heart failure: Clonidine overdose has been reported to cause heart failure in rare cases 6.

Special Considerations

• Idiopathic orthostatic hypotension: Clonidine can raise blood pressure in patients with severe idiopathic orthostatic hypotension, but can also cause adverse effects such as sedation, dry mouth, and excessive hypertension 5.
• Baroreceptor dysfunction: Clonidine can cause severe hypotension in patients with baroreceptor dysfunction, and should be used with caution in these patients 5.