What is the appropriate dosage and treatment regimen for Inderal (propranolol) in a patient with hypertension, angina, or migraines?

Inderal (Propranolol) Dosing and Treatment Guidelines

Hypertension Management

For hypertension, start with propranolol extended-release 80 mg once daily, titrating up to 120-160 mg once daily for adequate blood pressure control, with a maximum dose of 640 mg daily if needed. 1

Initial Dosing Strategy

• Begin with propranolol hydrochloride extended-release capsules 80 mg once daily, whether used alone or added to a diuretic 1
• The usual maintenance dosage is 120-160 mg once daily 1
• Time needed for full hypertensive response ranges from a few days to several weeks 1

Combination Therapy Considerations

• Beta-blockers like propranolol are recommended as part of a multi-drug regimen for patients with hypertension and compelling indications such as coronary artery disease, post-myocardial infarction, or diabetes 2
• For patients with hypertension and chronic stable angina, combine a beta-blocker with an ACE inhibitor or ARB and a thiazide diuretic (Class I, Level of Evidence A) 2
• Target blood pressure is <140/90 mmHg (Class I, Level of Evidence A), with lower targets (<130/80 mmHg) considered in select patients with CAD 2

Important Formulation Considerations

• Do not consider propranolol extended-release a simple mg-for-mg substitute for immediate-release propranolol tablets, as extended-release has different kinetics and produces lower blood levels 1
• Retitration may be necessary when switching formulations, especially to maintain effectiveness at the end of the 24-hour dosing interval 1

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Angina Pectoris Management

Start with propranolol extended-release 80 mg once daily for angina, gradually increasing at 3-7 day intervals until optimal response is obtained, with an average optimal dosage of 160 mg once daily. 1

Dosing Protocol

• Begin with 80 mg propranolol extended-release once daily 1
• Increase dosage gradually at three- to seven-day intervals until optimal response is obtained 1
• The average optimal dosage appears to be 160 mg once daily 1
• Dosages exceeding 320 mg per day have not been established as safe or effective in angina 1

Discontinuation Protocol

• If treatment is to be discontinued, reduce dosage gradually over a period of a few weeks to avoid rebound angina or myocardial infarction 1

Guideline-Based Recommendations

• Beta-blockers are mainstays of angina treatment, particularly in patients with prior MI 2
• Long-acting nitrates or calcium channel blockers can be prescribed when beta-blockers are contraindicated or cause unacceptable side effects (Class I, Level of Evidence B) 2
• If angina remains uncontrolled, add a long-acting dihydropyridine calcium channel blocker to the regimen of beta-blocker, ACE inhibitor, and thiazide diuretic (Class IIa, Level of Evidence B) 2

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Migraine Prophylaxis

For migraine prophylaxis, initiate propranolol extended-release 80 mg once daily, with the usual effective dose range of 160-240 mg once daily. 1

Dosing and Titration

• Initial dose: 80 mg propranolol extended-release once daily 1
• Usual effective dose range: 160-240 mg once daily 1
• Increase dosage gradually to achieve optimal migraine prophylaxis 1

Treatment Duration and Discontinuation

• If satisfactory response is not obtained within 4-6 weeks after reaching maximal dose, discontinue therapy 1
• Withdraw the drug gradually over several weeks, considering the patient's age, comorbidity, and dose 1

Important Drug Interaction

• Rizatriptan (Maxalt) is contraindicated with propranolol (Inderal), as propranolol significantly increases rizatriptan exposure 2
• Other triptans (sumatriptan, naratriptan, zolmitriptan) do not have this specific contraindication with propranolol 2

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Hypertrophic Subaortic Stenosis

The usual dosage for hypertrophic subaortic stenosis is 80-160 mg propranolol extended-release once daily. 1

• This indication showed improved NYHA class for most patients in uncontrolled series 1
• Oral propranolol 40-80 mg three times daily was associated with symptom improvement when followed for up to 17 months 1

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Critical Safety Considerations

Contraindications

• If beta-blockers are contraindicated or produce intolerable side effects, a nondihydropyridine calcium channel blocker (diltiazem or verapamil) may be substituted, but not if there is left ventricular dysfunction (Class IIa, Level of Evidence B) 2

Drug Interactions

• Propranolol increases warfarin bioavailability and prothrombin time; monitor INR closely 1
• Coadministration with lovastatin or pravastatin decreases their AUC by 18-23% but does not alter pharmacodynamics 1

Monitoring Parameters

• Monitor blood pressure and heart rate at each visit during titration 3
• Assess for signs of worsening heart failure or bronchospasm 4
• Target blood pressure reduction should be at least 20/10 mmHg, ideally to <140/90 mmHg 4

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Pharmacokinetic Considerations

Extended-Release Formulation Advantages

• Long-acting propranolol maintains therapeutic plasma concentrations throughout a 24-hour period with once-daily dosing 5, 6
• Terminal half-life is prolonged to 8-11 hours compared to conventional formulation due to slower absorption 6
• Peak drug concentrations are significantly lower and delayed compared to conventional propranolol 5, 7, 6
• Systemic bioavailability is 30-50% less than conventional formulation, possibly due to increased hepatic metabolism 6

Special Population Considerations

• Elderly patients may have higher plasma levels than younger patients; long-acting propranolol was well tolerated with minimal side effects in elderly hypertensive patients 7
• A single 160 mg dose of long-acting propranolol produces cardiac beta-adrenoceptor blockade throughout 24 hours without variability from multiple peak concentrations 5

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Common Pitfalls to Avoid

• Do not abruptly discontinue propranolol, as this can cause severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias 1
• Do not assume immediate-release and extended-release formulations are interchangeable; retitration is necessary when switching 1
• Do not exceed 320 mg daily for angina without clear evidence of benefit, as safety has not been established 1
• Do not combine beta-blockers with nondihydropyridine calcium channel blockers (diltiazem or verapamil) without caution, as this increases risk of bradyarrhythmias and heart failure (Class IIa, Level of Evidence B) 2