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Clonidine

AEMPS

Central α2-adrenergic agonist

ATC code: C02AC01

Brand names: Catapres, Kapvay

Updated · Methodology

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

F

Stress and anxiety

Not recommended

Clonidine is an alpha-2 agonist used for hypertension (as a non-first-line drug) and for ADHD in children ( 2023 and 2019 guidelines). For acute stress or anxiety control in adults, clonidine is not used: no clinical studies of such use exist. The drug has serious risks: pronounced sedation, orthostatic hypotension (fall risk), paradoxical bradycardia, a severe rebound syndrome on abrupt discontinuation (sharp blood-pressure spike, sometimes above baseline, boxed warning), and formation of drug dependence. If clonidine was prescribed for stress, consider seeking a second opinion.

Sources

  1. AEMPS: Ficha técnica de Clonidina (2024)
  2. Cochrane: Valerian for anxiety disorders (2006)

ICD-10: F41.9 · ICD-11: 6B0Z

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Activates presynaptic α2 adrenoreceptors in brainstem → reduces central sympathetic tone → reduces BP and HR. Abrupt withdrawal causes rebound hypertension (often severe). Used in resistant HTN, ADHD in children, opioid withdrawal.

Safety

Contraindications

  • Hypersensitivity to clonidine
  • Severe bradycardia (sick sinus syndrome, 2nd–3rd degree AV block)
  • History of depression

Serious adverse effects

  • Rebound hypertension on abrupt discontinuation
  • Severe bradycardia and AV block
  • Depression

Common adverse effects

  • Dry mouth
  • Sedation and somnolence
  • Orthostatic hypotension
  • Constipation
  • Erectile dysfunction

Pregnancy: can you take Clonidine?

AEMPS summary of product characteristics (section 4.6): data on clonidine in pregnant women are limited, and as a precaution it is preferable to avoid it during pregnancy; if it is given, mother and child should be closely monitored. Clonidine crosses the placenta and may lower the fetal heart rate, and a transient rise in blood pressure in the newborn after delivery cannot be ruled out. There is no adequate experience on the long-term effects of prenatal exposure. Animal studies have shown embryofetal toxicity at clinically relevant doses.

Breastfeeding: can you take Clonidine?

Compatible with caution. Hale L3. Transfers into milk in meaningful amounts (RID about 7%); sedation and reduced weight gain may occur in the infant. AEMPS recommends choosing alternatives (labetalol, nifedipine) when possible.

Calculate RIDFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–drug interactions

10 pairs found. Sorted from critical to minor.

MajorAmitriptylineTricyclic antidepressants (TCA)

Mechanism

Tricyclic antidepressants, amitriptyline included, can counteract centrally acting antihypertensives such as clonidine (amitriptyline SmPC). The clonidine SmPC adds that the blood pressure lowering effect of clonidine may be reduced or lost entirely. The combination can also cause or worsen orthostatic dysregulation, a drop in blood pressure on standing (clonidine SmPC).

Symptoms

Blood pressure drifts above target: home and clinic readings are higher than before, and some patients get headache or dizziness. On standing, orthostatic hypotension can cause dizziness and weakness (clonidine labels).

Management

The combination is not recommended: the Spanish amitriptyline SmPC lists clonidine under combinations that are not recommended and advises reviewing all antihypertensive treatment while a tricyclic antidepressant is used. When reviewing it, keep in mind that clonidine may stop lowering blood pressure and that orthostatic dysregulation may get worse (clonidine SmPC). The clonidine label notes that a higher clonidine dose may be needed with tricyclic antidepressants. If clonidine is to be stopped, do not stop it abruptly: taper the dose over 2–4 days, otherwise blood pressure can rise quickly. In a patient also taking a beta-blocker, withdraw the beta-blocker gradually first and clonidine after it (clonidine SmPC).

Sources

Pair details →Amitriptyline →

MajorBisoprololSelective beta-adrenergic blockers

Mechanism

Abrupt clonidine withdrawal on a beta-blocker triggers a hypertensive crisis: the α2 effect is lost while β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop bisoprolol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensives: an ACE-I (enalapril) plus amlodipine without clonidine.

Sources

Pair details →Bisoprolol →

MajorCarvedilolAlpha and beta blocker (non-selective β + α1)

Mechanism

Clonidine is an α2-agonist that reduces sympathetic tone. Carvedilol blocks β-receptors plus α1-receptors. On abrupt clonidine withdrawal, the α2 effect is lost while carvedilol's β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop carvedilol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensive therapy: an ACE-I (enalapril) plus a calcium channel blocker (amlodipine) without clonidine.

Sources

Pair details →Carvedilol →

MajorDiltiazemCalcium channel blocker, non-DHP (benzothiazepine derivative)

Mechanism

Additive bradycardia and atrioventricular (AV) block. Clonidine lowers sympathetic tone and slows conduction; diltiazem directly blocks the AV node.

Symptoms

Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall and fracture risk.

Management

Avoid the combination, especially in older patients. Alternative calcium channel blockers in hypertension: amlodipine or nifedipine (no AV effect). Alternative to clonidine: an ACE-I or ARB with a diuretic.

Sources

Pair details →Diltiazem →

MajorMetoprololSelective β1-adrenoceptor blockers

Mechanism

Abrupt clonidine withdrawal on a beta-blocker triggers a hypertensive crisis: the α2 effect is lost while β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise. Additional additive bradycardia.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop metoprolol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensives: an ACE-I (enalapril) plus amlodipine without clonidine.

Sources

Pair details →Metoprolol →

MajorPropranololNon-selective beta blocker

Mechanism

Propranolol is a non-selective beta-blocker (β1 and β2). On abrupt clonidine withdrawal, additional β2-blockade amplifies the residual α1 effect, making the hypertensive crisis particularly severe.

Symptoms

Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.

Management

For planned clonidine withdrawal, stop propranolol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensives: an ACE-I plus amlodipine (without clonidine) or a selective beta-blocker (bisoprolol).

Sources

Pair details →Propranolol →

MajorSildenafilPhosphodiesterase type 5 inhibitors (PDE5)

Mechanism

Additive hypotensive effect. Sildenafil vasodilates by blocking phosphodiesterase-5; clonidine lowers blood pressure via central α2-agonism. Combined action can cause symptomatic hypotension.

Symptoms

Sudden blood pressure drop: postural dizziness, syncope. Particularly dangerous in older patients and in ischaemic heart disease.

Management

The combination is acceptable in stable hypertension. Cap sildenafil at 25 mg (instead of 50–100 mg). Warn the patient about orthostatic hypotension; take the first dose lying down.

Sources

Pair details →Sildenafil →

MajorVerapamilNon-dihydropyridine calcium channel blocker

Mechanism

Additive bradycardia and AV block. Clonidine lowers sympathetic tone; verapamil directly blocks the AV node.

Symptoms

Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall and fracture risk.

Management

Avoid the combination, especially in older patients. Alternative calcium channel blockers: amlodipine or nifedipine (no AV effect). Alternative to clonidine: an ACE-I or ARB with a diuretic.

Sources

Pair details →Verapamil →

ModerateAlprazolamBenzodiazepines. Short-to-medium-acting anxiolytics

Mechanism

Additive CNS depression and hypotension. Clonidine is a central α2-agonist with sedative effect; alprazolam is a GABAergic sedative.

Symptoms

Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk. Pronounced morning hypotension and bradycardia possible.

Management

On starting the combination, begin both at minimal doses with time-separated dosing (e.g. clonidine in the morning, alprazolam at bedtime). Avoid the combination in older patients — fall risk. In anxiety disorders with hypertension, alternative: a beta-blocker (metoprolol) plus buspirone.

Sources

Pair details →Alprazolam →

ModerateBudesonideInhaled corticosteroids (ICS)

Mechanism

Systemic budesonide retains sodium and water via mineralocorticoid effect, blunting clonidine's antihypertensive effect. Inhaled budesonide does not clinically affect BP.

Symptoms

On long-term systemic therapy: return or rise of blood pressure, leg oedema.

Management

For short systemic budesonide courses, no specific adjustment needed. For long-term therapy, check BP weekly in the first month. If BP rises, increase clonidine or add a diuretic. Inhaled budesonide with clonidine is unproblematic.

Sources

Pair details →Budesonide →

Label mentions49 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • MajorMethylphenidate
    «Insuficiencia renal: Catapresan no está recomendado para uso en niños y adolescentes debido a la escasez de datos sobre seguridad y eficacia. En particular, cuando clonidina se utiliza fuera de las…»

    AEMPS, section 4.4 · Open on CIMA

  • Moderatebeta blockersclass named in the label
    «Drug Interactions: 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…»

    FDA, section 7 · Open on DailyMed

  • Moderatecalcium channel blockersclass named in the label
    «Drug Interactions: 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…»

    FDA, section 7 · Open on DailyMed

  • Moderatedigitalisclass named in the label
    «Drug Interactions: 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…»

    FDA, section 7 · Open on DailyMed

  • ModerateDiltiazem
    «Drug Interactions: 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…»

    FDA, section 7 · Open on DailyMed

  • ModerateVerapamil
    «Drug Interactions: 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…»

    FDA, section 7 · Open on DailyMed

  • AINEclass named in the label
    «Fármacos que elevan la presión arterial o inducen una retención de sodio y agua, tales como fármacos antiinflamatorios no esteroideos, pueden reducir el efecto terapéutico de la clonidina.»

    AEMPS, section 4.5 · Open on CIMA

  • Amitriptyline
    «Drug Interactions: Amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see Toxicology ).»

    FDA, section 7 · Open on DailyMed

  • antagonistas del calcioclass named in the label
    «La reducción de la presión arterial inducida por clonidina puede ser potenciada además por administración simultánea de otros hipotensores. Ello puede ser de utilidad terapéutica en el caso de otros…»

    AEMPS, section 4.5 · Open on CIMA

  • antidepresivos tricíclicosclass named in the label
    «La administración simultánea de antidepresivos tricíclicos o neurolépticos con propiedades bloqueadoras alfa puede provocar o agravar una alteración de la regulación ortostática, mientras que el…»

    AEMPS, section 4.5 · Open on CIMA

  • antipsicóticosclass named in the label
    «La administración simultánea de antidepresivos tricíclicos o neurolépticos con propiedades bloqueadoras alfa puede provocar o agravar una alteración de la regulación ortostática, mientras que el…»

    AEMPS, section 4.5 · Open on CIMA

  • antipsychoticsclass named in the label
    «Drug Interactions: Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. If a patient receiving clonidine hydrochloride is also taking tricyclic…»

    FDA, section 7 · Open on DailyMed

  • barbituratesclass named in the label
    «Drug Interactions: Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. If a patient receiving clonidine hydrochloride is also taking tricyclic…»

    FDA, section 7 · Open on DailyMed

  • diuréticosclass named in the label
    «La reducción de la presión arterial inducida por clonidina puede ser potenciada además por administración simultánea de otros hipotensores. Ello puede ser de utilidad terapéutica en el caso de otros…»

    AEMPS, section 4.5 · Open on CIMA

  • Haloperidol
    «Drug Interactions: Based on observations in patients in a state of alcoholic delirium it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential…»

    FDA, section 7 · Open on DailyMed

  • inhibidores de la ECAclass named in the label
    «La reducción de la presión arterial inducida por clonidina puede ser potenciada además por administración simultánea de otros hipotensores. Ello puede ser de utilidad terapéutica en el caso de otros…»

    AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

  • MajorAmitriptyline
    «Bloqueantes neuronales adrenérgicos: Los antidepresivos tricíclicos pueden contrarrestar los efectos antihipertensivos de los antihipertensivos de acción central como la guanetidina, la betanidina…»

    AEMPS, section 4.5 · Open on CIMA

  • MajorBisoprolol
    «Antihipertensivos de acción central como clonidina y otros (ej. metildopa, moxonodina, rilmenidina): El uso concomitante de fármacos antihipertensivos de acción central puede empeorar la…»

    AEMPS, section 4.5 · Open on CIMA

  • MajorBisoprolol
    «DRUG INTERACTIONS: BISOPROLOL FUMARATE should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely…»

    FDA, section 7 · Open on DailyMed

  • MajorNebivolol
    «Antihipertensivos de acción central (clonidina, guanfacina, moxonidina, metildopa, rilmenidina): el uso concomitante de antihipertensivos de acción central puede empeorar la insuficiencia cardiaca a…»

    AEMPS, section 4.5 · Open on CIMA

  • MajorNebivolol
    «Hypotensive Agents: Do not use nebivolol tablets with other β-blockers. Closely monitor patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, because the added…»

    FDA, section 7 · Open on DailyMed

  • ModerateAmiodarone
    «DRUG INTERACTIONS: Negative Chronotropes digoxin, beta blockers, verapamil, diltiazem, clonidine, ivabradine Potentiates the electrophysiologic and hemodynamic effects of amiodarone, resulting in…»

    FDA, section 7 · Open on DailyMed

  • ModerateAmisulpride
    «Depresores del SNC: incluyendo narcóticos, analgésicos, antihistamínicos sedantes H1, barbitúricos, benzodiazepinas y otros ansiolíticos, clonidina y derivados.»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateAtenolol
    «Los betabloqueantes pueden exacerbar la hipertensión arterial de rebote que puede aparecer por la retirada de clonidina. En el caso de que se administre clonidina concomitantemente con…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateCarvedilol
    «Clonidina: La administración concomitante de clonidina con medicamentos con propiedades β-bloqueantes, puede aumentar la presión sanguínea y disminuir el ritmo cardiaco.»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateCarvedilol
    «Hypotensive Agents: Concomitant administration of clonidine with a β-blocker may cause hypotension and bradycardia. When concomitant treatment with a β-blocker and clonidine is to be terminated, the…»

    FDA, section 7 · Open on DailyMed

  • ModerateDiltiazem
    «Drug Interactions: Clonidine: Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Monitor…»

    FDA, section 7 · Open on DailyMed

  • ModerateGlimepiride
    «Drugs Affecting Glucose Metabolism: A number of medications affect glucose metabolism and may require glimepiride dose adjustment and particularly close monitoring for hypoglycemia or worsening…»

    FDA, section 7 · Open on DailyMed

  • ModerateMetoclopramide
    «Anticolinérgicos y derivados de la morfina: Depresores de SNC (derivados de la morfina, ansiolíticos, antihistamínicos H 1 sedantes, antidepresivos sedantes, barbitúricos, clonidina y relacionados)»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateMetoprolol
    «Clonidina: la reacción hipertensiva cuando se retira repentinamente clonidina puede estar potenciada por los beta-bloqueantes. Si el tratamiento concomitante con clonidina se va a suspender, la…»

    AEMPS, section 4.5 · Open on CIMA

  • ModeratePropranolol
    «Combinación no recomendada: En el caso que se administren ambos fármacos de forma concomitante, el betabloqueante deberá retirarse varios días antes de suspenderse la administración de clonidina. Si…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateSotalol
    «Clonidina: Los betabloqueantes pueden potenciar la hipertensión de rebote que se produce en ocasiones tras abandonar el tratamiento con clonidina; por consiguiente, la administración del…»

    AEMPS, section 4.5 · Open on CIMA

  • MinorTrazodone
    «Antihipertensivos: Dado que trazodona es sólo un inhibidor muy débil de la recaptación de noradrenalina y no modifica la respuesta de la presión sanguínea a la tiramina, la interferencia con la…»

    AEMPS, section 4.5 · Open on CIMA

  • Atenolol
    «Drug Interactions: Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the beta-blocker should be withdrawn…»

    FDA, section 7 · Open on DailyMed

  • Dexchlorpheniramine
    «U so concomitante contraindicado: -Asociaciones con otros depresores del sistema nervioso central (sedantes antidepresivos, barbitúricos, benzodiazepinas, clonidina y similares, hipnóticos, derivados…»

    AEMPS, section 4.5 · Open on CIMA

  • Glimepiride
    «Los antagonistas H2, betabloqueantes, clonidina y reserpina pueden dar lugar a una potenciación o disminución del efecto reductor de la glucosa en sangre.»

    AEMPS, section 4.5 · Open on CIMA

  • Insulin
    «DRUG INTERACTIONS: Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.»

    FDA, section 7 · Open on DailyMed

  • Insulin glargine
    «Los betabloqueantes, la clonidina, las sales de litio o el alcohol pueden potenciar o debilitar el efecto hipoglucemiante de la insulina. La pentamidina puede provocar hipoglucemia, que algunas veces…»

    AEMPS, section 4.5 · Open on CIMA

  • Insulin glulisine
    «Los betabloqueantes, clonidina, sales de litio o alcohol podrían potenciar o debilitar la actividad reductora del nivel de glucosa en sangre de la insulina. La pentamidina podría causar hipoglucemia…»

    AEMPS, section 4.5 · Open on CIMA

  • Labetalol
    «Para la retirada en pacientes que utilizan tanto betabloqueantes como clonidina, la interrupción gradual del betabloqueante debe realizarse varios días antes de la interrupción de la clonidina. Esto…»

    AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Clonidine used for?

Clonidine is evaluated for the following indications with varying evidence strength: Stress and anxiety (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Clonidine?

Common side effects of Clonidine (≥ 1 in 100): Dry mouth, Sedation and somnolence, Orthostatic hypotension, Constipation, Erectile dysfunction. See the Safety section for uncommon and serious reactions.

Is Clonidine safe during pregnancy?

AEMPS summary of product characteristics (section 4.6): data on clonidine in pregnant women are limited, and as a precaution it is preferable to avoid it during pregnancy; if it is given, mother and child should be closely monitored. Clonidine crosses the placenta and may lower the fetal heart rate, and a transient rise in blood pressure in the newborn after delivery cannot be ruled out. There is no adequate experience on the long-term effects of prenatal exposure. Animal studies have shown embryofetal toxicity at clinically relevant doses.

Is Clonidine compatible with breastfeeding?

Compatible with caution. Hale L3. Transfers into milk in meaningful amounts (RID about 7%); sedation and reduced weight gain may occur in the infant. AEMPS recommends choosing alternatives (labetalol, nifedipine) when possible.

Who should not take Clonidine?

Clonidine is contraindicated in: Hypersensitivity to clonidine; Severe bradycardia (sick sinus syndrome, 2nd–3rd degree AV block); History of depression. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

Other drugs in this group

Doxazosin, Hydralazine, Methyldopa, Moxonidine, Riociguat