Is it okay to take clonidine with metoprolol (Metoprolol)?

From the Guidelines

It is generally safe to take metoprolol and clonidine together, but this combination should only be used under close medical supervision. Both medications lower blood pressure through different mechanisms - metoprolol is a beta-blocker that reduces heart rate and cardiac output, while clonidine is a centrally-acting alpha-2 agonist that decreases sympathetic outflow from the brain. When used together, they can have additive blood pressure-lowering effects, which may be beneficial for difficult-to-control hypertension but also increases the risk of excessive blood pressure reduction.

Key Considerations

• Patients taking both medications should monitor their blood pressure regularly and be alert for symptoms of hypotension such as dizziness, lightheadedness, or fainting.
• Abruptly stopping either medication, especially clonidine, can cause rebound hypertension, so any dosage changes should be gradual and medically supervised 1.
• If you're currently taking one of these medications and your doctor is considering adding the other, be sure to discuss all other medications you're taking and any cardiovascular conditions you have.

Mechanism of Action

• Metoprolol works by blocking the effects of the hormone epinephrine, also known as adrenaline, and by slowing the heart rate and reducing its workload 1.
• Clonidine works by stimulating certain receptors in the brain, which reduces the sympathetic nervous system activity, leading to a decrease in blood pressure 1.

Potential Risks and Benefits

• The combination of metoprolol and clonidine may be beneficial for patients with difficult-to-control hypertension, but it also increases the risk of excessive blood pressure reduction.
• Patients should be closely monitored for signs of hypotension, such as dizziness, lightheadedness, or fainting.
• The potential benefits of this combination should be weighed against the potential risks, and patients should be carefully selected and monitored by their healthcare provider.

From the FDA Drug Label

Alpha-adrenergic Agents Antihypertensive effect of alpha-adrenergic blockers such as guanethidine, betanidine, reserpine, alpha-methyldopa or clonidine may be potentiated by beta-blockers including metoprolol. Beta-adrenergic blockers may also potentiate the postural hypotensive effect of the first dose of prazosin, probably by preventing reflex tachycardia On the contrary, beta adrenergic blockers may also potentiate the hypertensive response to withdrawal of clonidine in patients receiving concomitant clonidine and beta-adrenergic blocker. If a patient is treated with clonidine and metoprolol concurrently, and clonidine treatment is to be discontinued, stop metoprolol tartrate several days before clonidine is withdrawn Rebound hypertension that can follow withdrawal of clonidine may be increased in patients receiving concurrent beta-blocker treatment.

• Concomitant use: Metoprolol and clonidine can be taken together, but with caution.
• Key consideration: When discontinuing clonidine, metoprolol should be stopped several days before to avoid rebound hypertension.
• Clinical decision: It is okay to take clonidine with metoprolol, but careful monitoring and gradual discontinuation of clonidine are necessary to prevent adverse effects 2.

From the Research

Metoprolol and Clonidine Interaction

• The interaction between metoprolol and clonidine is not directly addressed in most of the provided studies, but there are some relevant findings:
  • A study from 1985 3 found that the combination of clonidine and beta-adrenoceptor blocking agents (including propranolol and atenolol) is an effective antihypertensive medication, and patients treated with it are apparently at no greater risk of serious cardiovascular incidents than those treated with other regimens.
  • Another study from 2019 4 mentions that mirtazapine can antagonize clonidine's hypotensive effect, but it does not provide information on the interaction between metoprolol and clonidine.
  • A study from 1979 5 compared the cardiovascular effects of centrally administered clonidine and adrenaline in anaesthetized rats, and found that metoprolol (a beta-antagonist) was effective against adrenaline-induced hypotension and bradycardia, but not against clonidine-induced hypotension and bradycardia.

Bradycardia Risk with Metoprolol

• A study from 2013 6 found that the risk of emergent bradycardia associated with metoprolol initiation is higher with the immediate-release formulation than the slow-release formulation.
• The same study 6 found that the incidence of emergent bradycardia was 19.1/1000 person-years overall, but was nearly twice as common in patients using the immediate-release formulation versus the slow-release formulation.

Hypotension Risk with Clonidine and Other Medications

• A study from 2025 7 found that the concomitant administration of tizanidine (a muscle relaxant) and lisinopril can cause profound hypotension, which is a rare but potentially life-threatening reaction.
• The study from 1985 3 found that the combination of clonidine and beta-adrenoceptor blocking agents can have a distinct antihypertensive effect, but it does not provide information on the risk of hypotension with this combination.