Celiprolol

Usage

Celiprolol is prescribed for the management of mild to moderate hypertension (high blood pressure). It is also used to treat angina pectoris (chest pain due to reduced blood flow to the heart).

It is pharmacologically classified as a cardioselective beta-blocker with partial beta-2 agonist activity, and a vasodilator.

Celiprolol’s mechanism of action involves blocking beta-1 adrenergic receptors in the heart, reducing heart rate and cardiac output, thus lowering blood pressure. Its partial beta-2 agonist activity contributes to vasodilation, further aiding in blood pressure reduction.

Alternate Names

Celiprolol is also known as Celiprolol hydrochloride. Brand names include Celectol and Selectol.

How It Works

Pharmacodynamics: Celiprolol primarily blocks beta-1 adrenergic receptors in the heart, decreasing heart rate, myocardial contractility, and atrioventricular conduction velocity. This leads to a decrease in cardiac output and blood pressure. Its partial beta-2 agonist activity causes vasodilation, further lowering peripheral resistance and blood pressure.

Pharmacokinetics: Celiprolol is well-absorbed orally. Peak plasma concentrations are reached within 1-3 hours. It is extensively metabolized in the liver, primarily by CYP2D6. Elimination is primarily through renal excretion. The half-life is 4-5 hours in individuals with normal renal function, and slightly longer in those with end-stage renal disease.

Mode of Action: Celiprolol competitively binds to beta-1 adrenergic receptors, preventing the binding of endogenous catecholamines like norepinephrine and epinephrine. This reduces sympathetic stimulation of the heart, leading to the aforementioned effects on heart rate, contractility, and conduction.

Elimination Pathways: Celiprolol is eliminated primarily through renal excretion, with approximately 10% excreted unchanged. Hepatic metabolism plays a significant role, involving CYP2D6.

Dosage

Standard Dosage

Adults:

Initial dose: 200 mg orally once daily, taken in the morning.

Maintenance dose: If the response is inadequate after 2-4 weeks, the dose may be increased to 400 mg once daily. The maximum recommended dose is 400 mg once daily.

Children:

Celiprolol is not recommended for use in children.

Special Cases:

• Elderly Patients: Start with the standard adult dose but monitor closely due to potential age-related decline in renal and hepatic function. Dosage adjustments may be required.

• Patients with Renal Impairment:

  • Creatinine clearance 15-40 mL/minute: Reduce the dose by half (100-200 mg daily).
  • Creatinine clearance <15 mL/minute: Celiprolol is not recommended.

• Patients with Hepatic Dysfunction: Patients with hepatic impairment should be carefully monitored. Dosage reduction may be necessary.

• Patients with Comorbid Conditions: Caution should be exercised in patients with well-controlled congestive heart failure, diabetes mellitus, or a history of psoriasis. Close monitoring is required.

Clinical Use Cases

Celiprolol’s clinical use is primarily focused on hypertension and angina pectoris. It is not typically used in clinical scenarios like intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations.

Dosage Adjustments

Dosage adjustments may be necessary based on renal or hepatic function, patient response, and the presence of comorbid conditions.

Side Effects

Common Side Effects:

Headache, dizziness, fatigue, somnolence, insomnia, hot flushes, asthenia, nausea, diarrhea.

Rare but Serious Side Effects:

Bradycardia, hypotension, bronchospasm, allergic skin reactions, visual disturbances, depression, SLE-like symptoms, heart failure, signs of psychosis.

Long-Term Effects:

Long-term side effects are not well-established, but may include worsening of pre-existing diabetes, increased thirst, excessive urination, weight loss.

Adverse Drug Reactions (ADR):

Severe bradycardia, hypotension, heart failure, bronchospasm, angioedema, anaphylaxis.

Contraindications

• Hypersensitivity to celiprolol.
• Second or third-degree atrioventricular block (unless a pacemaker is present).
• Severe bradycardia (≤50 beats per minute).
• Decompensated heart failure.
• Cardiogenic shock.
• Acute episodes of asthma.
• Hypotension (systolic blood pressure less than 100 mmHg).
• Untreated pheochromocytoma.
• Sick sinus syndrome.
• Late stages of peripheral arterial occlusive disease and Raynaud’s syndrome.
• Concomitant use with theophylline.

Drug Interactions

Celiprolol can interact with various medications, including:

• Other beta-blockers (additive effects).
• Calcium channel blockers (increased risk of bradycardia and hypotension).
• Antiarrhythmics (enhanced negative inotropic and chronotropic effects).
• Clonidine (exacerbated rebound hypertension upon withdrawal).
• Digitalis glycosides (increased AV conduction time).
• Hydrochlorothiazide, chlorthalidone, and theophylline (reduced celiprolol bioavailability).
• Dihydropyridine calcium channel blockers (increased risk of hypotension and heart failure).
• Mefloquine (bradycardia)
• Drugs that inhibit P-glycoprotein (e.g. verapamil, erythromycin, clarithromycin, ciclosporin, quinidine, ketoconazole, itraconazole) increase plasma concentrations of celiprolol
• CYP450 inducers/inhibitors can alter celiprolol metabolism.
• NSAIDs may decrease the antihypertensive effect.
• Alcohol (increased orthostatic hypotensive effect).

Pregnancy and Breastfeeding

Celiprolol’s safety during pregnancy has not been fully established. Use only if the potential benefits outweigh the risks. Beta-blockers can reduce placental perfusion. Breastfeeding is not recommended while taking celiprolol due to the risk of neonatal bradycardia and hypoglycemia.

Drug Profile Summary

• Mechanism of Action: Cardioselective beta-blocker with partial beta-2 agonist activity.
• Side Effects: Headache, dizziness, fatigue, bradycardia, hypotension.
• Contraindications: Severe bradycardia, decompensated heart failure, cardiogenic shock, hypersensitivity, concomitant use with theophylline.
• Drug Interactions: Other beta-blockers, calcium channel blockers, antiarrhythmics, clonidine, digitalis glycosides, theophylline, dihydropyridines, CYP450 inducers/inhibitors.
• Pregnancy & Breastfeeding: Use with caution during pregnancy; breastfeeding not recommended.
• Dosage: 200-400 mg once daily.
• Monitoring Parameters: Blood pressure, heart rate, ECG.

Popular Combinations

Celiprolol may be combined with diuretics for the treatment of hypertension when monotherapy is insufficient.

Precautions

Pre-screening for allergies, heart conditions, renal/hepatic impairment is essential. Avoid abrupt withdrawal. Patients should be cautious when driving or operating machinery due to potential dizziness and fatigue.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Celiprolol?

A: The initial dose is 200 mg once daily. This can be increased to 400 mg daily if needed. Dosage adjustments are required for renal impairment.

Q2: What are the common side effects of Celiprolol?

A: Common side effects include headache, dizziness, fatigue, and gastrointestinal disturbances.

Q3: What are the contraindications for Celiprolol?

A: Celiprolol is contraindicated in patients with severe bradycardia, decompensated heart failure, cardiogenic shock, hypersensitivity, or concomitant use with theophylline.

Q4: How does Celiprolol interact with other medications?

A: Celiprolol interacts with various medications, including other beta-blockers, calcium channel blockers, antiarrhythmics. Consult a drug interaction database for detailed information.

Q5: Can Celiprolol be used during pregnancy and breastfeeding?

A: Celiprolol’s safety during pregnancy is not fully established. Breastfeeding is not recommended.

Q6: How long does it take for Celiprolol to start working?

A: The onset of action is typically within 1-2 hours, but full therapeutic effect may take several weeks.

Q7: What should patients do if they miss a dose of Celiprolol?

A: Take the missed dose as soon as remembered, unless it’s close to the next dose. Do not double the dose.

Q8: Should Celiprolol be taken with food?

A: Celiprolol should be taken on an empty stomach, either one hour before meals or two hours after meals.

Q9: Can Celiprolol be used in patients with renal impairment?

A: Yes, but the dosage needs to be reduced for moderate renal impairment. Celiprolol is not recommended for severe renal impairment (CrCl <15 mL/min).

Q10: What should I monitor in patients taking Celiprolol?

A: Monitor blood pressure, heart rate, and ECG regularly. Be vigilant for signs of bradycardia, hypotension, or other adverse effects.