hydralazine (Apresoline) vs. clonidine (Catapres, Kapvay)

• Hydralazine and clonidine are used to treat high blood pressure.
• Hydralazine is also used to treat hypertensive crisis and congestive heart failure (CHF).
• Clonidine is also used off-label to treat alcohol withdrawal, smoking cessation, restless leg syndrome, Tourette’s syndrome, and opioid withdrawal.
• Hydralazine and clonidine belong to different drug classes. Hydralazine is a peripheral arterial vasodilator and clonidine is a central alpha-agonist.
• A brand name for hydralazine is Apresoline.
• Brand names for clonidine include Catapres, Catapres-TTS, and Kapvay.
• Side effects of hydralazine and clonidine that are similar include headache and constipation.
• Side effects of hydralazine that are different from clonidine include weight loss, nausea, vomiting, diarrhea, palpitations, rapid heartbeat chest pain (angina), paralytic ileus, low blood pressure, fluid retention (edema), shortness of breath, numbness and tingling of extremities, tremors, muscle cramps, psychotic reactions, difficulty urinating, blood disorders, hypersensitivity type reactions, nasal congestion, flushing, abnormal tear production, and conjunctivitis.
• Side effects of clonidine that are different from hydralazine include tiredness, lethargy, drowsiness, dry mouth, dizziness, fatigue, weakness, skin redness, itching, impotence, skin darkening, decreased sexual desire, and ejaculatory dysfunction.

Hydralazine is a peripheral arterial vasodilator used as an antihypertensive medication to treat high blood pressure, hypertensive crisis, and congestive heart failure (CHF). Hydralazine causes relaxation of blood vessels which carry blood away from the heart and towards the organs and tissues. Hydrazine affects calcium movement within blood vessels. Calcium is required for muscle contraction and therefore disturbances in calcium movement may cause smooth muscle relaxation in the blood vessels. Hydralazine is selective for arterioles (small arteries), and the overall effects of treatment include a decrease in arterial blood pressure, and peripheral vascular resistance.

Clonidine is a central alpha-agonist used to treat high blood pressure (hypertension). Clonidine is also used off-label to treat alcohol withdrawal, smoking cessation, restless leg syndrome, Tourette’s syndrome, and opioid withdrawal. Clonidine acts by stimulating receptors on nerves in the brain that reduces the transmission of messages from nerves in the brain to nerves in other areas of the body. As a result, it slows heart rate and reduces blood pressure.

Hydralazine

Common side effects of hydralazine are:

• headache,
• anorexia,
• nausea,
• vomiting,
• diarrhea,
• palpitations,
• tachycardia (rapid heartbeat), and
• angina pectoris (chest pain).

Other less commonly reported side effects include:

• constipation,
• paralytic ileus,
• low blood pressure,
• edema,
• paradoxical pressor response,
• dyspnea (shortness of breath),
• peripheral neuritis,
• numbness,
• tingling,
• tremors,
• muscle cramps,
• psychotic reactions,
• difficulty urinating,
• blood disorders,
• hypersensitivity type reactions,
• nasal congestion,
• flushing,
• abnormal tear production (lacrimation) , and
• conjunctivitis.

Clonidine

The most common side effects are:

• Tiredness
• Lethargy
• Drowsiness
• Constipation
• Dry mouth
• Headache
• Dizziness
• Fatigue
• Weakness

Other side effects include:

• Skin redness
• Itching
• Impotence
• Darkening of skin
• Decreased sexual desire
• Ejaculatory dysfunction
• Possible serious side effects include:
• Severe rebound high blood pressure
• Severe low blood pressure
• Slow heart rate
• Withdrawal symptoms
• Depression
• Angioedema
• Severe allergic reactions
• Slow heart rate
• Fainting
• Abnormal heart conduction

Severe rebound hypertension can occur following withdrawal from clonidine. This reaction is more likely to occur if clonidine is stopped suddenly (without a gradual dose reduction).

Symptoms of severe rebound high blood pressure can include:

• Increased salivation
• Nervousness
• Headache
• Heart palpitations
• Agitation
• Anxiety
• Sweating
• Nausea
• Muscle pain
• Abdominal pain

Slowly reducing the dose of this medication over several days will prevent these symptoms.

Hydralazine

Hypertension in adult patients:

• Start treatment at a low dose and increase gradually based on individual patient response. The usual recommended starting regimen is 10 mg orally four times daily for the first 2 to 4 days, increase to 25 mg four times daily for the remainder of the first week.
• For the second and subsequent weeks, increase dosage to 50 mg four times daily (increase dose by 10-25 mg/dose gradually every 2-5 days).
• The maximum daily dose used in clinical studies is 300 mg.

Congestive heart failure:

• The initial dose for treating heart failure is 10 to 25 mg orally 3 to 4 times daily.
• The usual dose is 225 to 300 mg daily in 3 to 4 divided doses.
• For pediatric hypertensive emergencies, the dose is 0.5 mg/Kg IV every 4 hours.

Clonidine

• The usual oral adult dose is 0.1–0.3 mg twice daily.
• The maximum oral dose is 2.4 mg daily.
• Topical patches should be applied to an area of hairless skin on the upper arm or torso, once every 7 days.
• When applying a new topical patch, a different area of skin should be used.

Hydralazine

Sympathomimetics such as:

• cocaine,
• dobutamine (Dobutrex),
• dopamine (Intropin),
• norepinephrine (Levophed),
• epinephrine (Adrenalin),
• metaraminol (Aramine),
• methoxamine,
• phenylephrine, (NeoSynephrine, Neofrin)
• phenylpropanolamine,
• ephedra (Ma Huang), and
• ephedrine may decrease the effectiveness of hydralazine.

Co-administration of these agents may block the anti-hypertensive benefits of hydralazine treatment.

Clonidine

This drug can increase the sedating effects of other medications that cause sedation. Such drugs include:

• Narcotic pain relievers
• Barbiturates
• Sedatives such as alprazolam (Xanax) and clonazepam (Klonopin)
• Ethanol

Tricyclic antidepressants, for example, amitriptyline (Elavil, Endep), imipramine (Tofranil), desipramine (Norpramin), and clomipramine (Anafranil), can block the blood pressure lowering effects of Catapres. This may cause blood pressure to rise.

Since this drug can reduce heart rate, it should be used cautiously in persons who are receiving any other medication that lowers heart rate such as beta-blockers, for example:

• atenolol (Tenormin)
• metoprolol (Lopressor)
• propranolol (Inderal)
• digoxin (Lanoxin)
• diltiazem (Cardizem)
• verapamil (Calan Covera HS)

Abnormal heart rhythms can occur with the combination of clonidine and verapamil.

Cyclosporine (Sandimmune, Neoral) concentrations in the blood can increase when clonidine is begun. This interaction could result in kidney damage from the increased levels of cyclosporine.

Nonsteroidal anti-inflammatory drugs (NSAIDs), for example, ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve), and nabumetone (Relafen) can reduce the antihypertensive effects of clonidine.

Cocaine, pseudoephedrine, phenylephrine, and phenylpropanolamine also can reverse the blood pressure lowering effects of clonidine.

Hydralazine

• Hydralazine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Hydralazine is classified as FDA pregnancy risk category C (Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks). It is used for treating high blood pressure during pregnancy.
• Hydralazine is excreted in breast milk. Hydralazine should be used cautiously in females who are breastfeeding if treatment is necessary.

Clonidine

• There are no adequate studies of this drug in during pregnancy
• It is excreted into breast milk and potentially could cause adverse effects in the infant.