Major Side Effects of Clonidine
Clonidine therapy is associated with significant central nervous system side effects, which is why it is generally reserved as a last-line treatment for hypertension. 1
Common Side Effects
- Sedation/drowsiness - One of the most frequent adverse effects, usually dose-related 1, 2
- Dry mouth - Very common, typically dose-dependent 2
- Dizziness - May affect ability to operate machinery or drive 2
- Accommodation disorder (vision changes) - May cause dryness of eyes in contact lens wearers 2
Serious Adverse Effects
Cardiovascular Effects
- Bradycardia - Especially concerning in patients with pre-existing conduction abnormalities 2
- Orthostatic hypotension - More pronounced in elderly patients 3
- Rebound hypertension - Can occur with sudden discontinuation 2
- Cardiac conduction defects - May worsen sinus node dysfunction and AV block 2
Neurological Effects
- CNS depression - More frequent in children than adults 2
- Irritability - Can occur with both therapeutic use and overdose 2
Withdrawal Syndrome
- Abrupt discontinuation can lead to:
- Nervousness and agitation
- Headache and tremor
- Rapid rise in blood pressure
- Elevated catecholamine levels
- Rare instances of hypertensive encephalopathy, cerebrovascular accidents, and death 2
Special Populations
Pregnancy and Breastfeeding
- Breastfeeding concerns: Clonidine is found in human milk with a milk-to-plasma ratio of 2 and relative infant dose up to 7.1% 3
- Infant monitoring: Breastfed infants should be monitored for drowsiness, hypotonia, and potential seizures 3
- Case report: One case reported an infant developing drowsiness, hypotonia, suspected seizures, and apnea when exposed through breastfeeding 3
Children
- Increased susceptibility: Children may be more susceptible to CNS depression than adults 2
- Hypertensive episodes: Children are particularly vulnerable to hypertensive episodes due to inability to take medication during gastrointestinal illnesses 2
Drug Interactions
- CNS depressants: Clonidine may potentiate effects of alcohol, barbiturates, or other sedating drugs 2
- Tricyclic antidepressants: May reduce the hypotensive effect of clonidine 2
- Neuroleptics: May induce or exacerbate orthostatic regulation disturbances 2
- Cardiac medications: Monitor heart rate when used with drugs affecting sinus node function or AV nodal conduction (e.g., digitalis, calcium channel blockers, beta-blockers) 2
- Beta-blockers: If discontinuing therapy, beta-blockers should be withdrawn several days before gradually discontinuing clonidine 2
Proper Discontinuation
- Gradual tapering: Dose should be reduced gradually over 2-4 days 2
- High discontinuation rate: Clonidine has a 40% discontinuation rate in clinical trials, higher than many other medications 1
Overdose Concerns
- Even small amounts (0.1 mg) have produced toxicity in children 2
- Symptoms include hypertension followed by hypotension, bradycardia, respiratory depression, hypothermia, and miosis 2
- Severe overdose may lead to apnea, coma, and seizures 2
Understanding these side effects is crucial for appropriate patient selection and monitoring during clonidine therapy, particularly given its designation as a last-line agent for hypertension due to its significant CNS side effect profile.