What is the recommended dosing for Nifedipine (Calcium Channel Blocker) extended release in a patient with hypertension or angina, considering factors such as age, kidney function, and liver function?

Nifedipine Extended-Release Dosing

For hypertension and angina, initiate nifedipine extended-release at 30 mg once daily and titrate upward to 30-90 mg once daily based on blood pressure response, with a maximum dose of 180 mg daily for angina. 1

Standard Dosing Recommendations

Hypertension

• Starting dose: 30 mg once daily 2, 3, 1
• Maintenance dose: 30-90 mg once daily 4, 2, 3
• Titration: Increase dose gradually based on blood pressure response; allow at least 4 weeks between dose adjustments to observe full therapeutic effect 3
• Dose-proportional response: The area under the curve (AUC) is dose proportional from 30-90 mg when given as extended-release tablets 1

Angina Pectoris

• Dosing range: 30-180 mg once daily of extended-release formulation 4, 2, 3
• Higher doses may be required: Up to 180 mg daily can be used for angina management 4, 3

Critical Safety Considerations

Formulation-Specific Warnings

• Avoid immediate-release nifedipine: Immediate-release formulations (30-90 mg daily in divided doses) must be avoided unless administered with concomitant beta-blockade due to increased risk of adverse cardiovascular events 4, 2, 3
• Do not substitute three 30 mg tablets for one 90 mg tablet: Three 30 mg extended-release tablets result in substantially higher peak concentrations (Cmax 29% greater) than a single 90 mg tablet and should not be considered interchangeable 1
• Two 30 mg tablets may be interchanged with one 60 mg tablet without significant pharmacokinetic differences 1

Contraindications

• Severe left ventricular dysfunction or pulmonary edema: Avoid all calcium channel blockers in these patients 4, 2
• Advanced aortic stenosis: Nifedipine is contraindicated 4

Special Population Adjustments

Elderly Patients (Age >60 years)

• Initiate at low doses and titrate cautiously: Elderly patients have 36% higher mean Cmax and 70% greater average plasma concentrations compared to younger patients 1
• Prolonged elimination half-life: Elimination half-life is 6.7 hours in elderly versus 3.8 hours in young subjects, with decreased clearance (348 mL/min vs 519 mL/min) 1
• Start at 30 mg once daily and monitor closely for hypotension, dizziness, and falls 4, 2

Hepatic Impairment

• Use with extreme caution: Patients with liver cirrhosis have longer elimination half-life and higher bioavailability than healthy volunteers 1
• Initiate at lowest dose (30 mg once daily) and titrate slowly with close monitoring 1
• Protein binding may be greatly reduced in hepatic impairment, increasing free drug concentration 1

Renal Impairment

• Exercise caution: While significant pharmacokinetic alterations have not been reported in hemodialysis or peritoneal dialysis patients with immediate-release formulations, absorption from extended-release tablets could be modified by renal disease 1
• Protein binding may be greatly reduced in renal impairment 1
• No specific dose adjustment required based on available data, but monitor closely 1

Administration Guidelines

Food Effects

• Avoid high-fat meals at time of dosing: Administration immediately after a high-fat meal increases peak plasma concentration by 60% and prolongs time to peak concentration, though AUC remains unchanged 1
• Consistent timing recommended: Take at the same time each day, preferably under fasting conditions for more predictable plasma levels 1

Drug Interactions

• Avoid grapefruit juice: Co-administration results in up to 2-fold increase in AUC and Cmax due to inhibition of CYP3A4-related first-pass metabolism 1
• CYP3A4 interactions: Drugs that inhibit or induce CYP3A4 may alter first-pass metabolism or clearance of nifedipine 1

Common Adverse Effects

Dose-dependent vasodilatory effects are the primary side effects and include: 4, 2, 3

• Peripheral edema
• Headache
• Dizziness and flushing
• Hypotension
• Nausea and constipation

These effects are generally mild to moderate, transient, and diminish with continued treatment. 5

Clinical Pearls

Combination Therapy

• Most hypertensive patients require combination therapy: Use submaximal doses of two drugs rather than maximal doses of a single drug to achieve larger blood pressure responses with fewer side effects 3
• Combines effectively with beta-blockers or ACE inhibitors for enhanced blood pressure control 3
• In unstable angina/NSTEMI: Patients already taking beta-blockers appeared to benefit from addition of nifedipine (risk ratio 0.68) 4

Monitoring

• Trough/peak ratios: Range from 41-78% for diastolic and 46-91% for systolic blood pressure, indicating sustained 24-hour efficacy 1
• Blood pressure measurements should be obtained 24 hours post-dose to assess trough effectiveness 1
• Monitor for orthostatic hypotension: Particularly in elderly patients, as baroreceptor response to blood pressure changes is decreased 4

Hypertensive Emergencies

• Not recommended for acute hypertensive emergencies: For emergencies, use intravenous nicardipine (initial 5 mg/h, increasing every 5 minutes by 2.5 mg/h to maximum 15 mg/h) instead 4