Nifedipine - Drug Monograph

Introduction

Nifedipine is a first-generation dihydropyridine calcium channel blocker widely used in cardiovascular medicine. Initially approved by the FDA in 1981, it remains a cornerstone therapy for various hypertensive and anginal conditions. As a potent arterial vasodilator, nifedipine reduces peripheral vascular resistance and myocardial oxygen demand through its effects on vascular smooth muscle.

Mechanism of Action

Nifedipine selectively inhibits the influx of calcium ions through L-type voltage-gated calcium channels in vascular smooth muscle and cardiac tissue. This inhibition prevents calcium-dependent contraction of smooth muscle cells, resulting in:

• Coronary and systemic arterial vasodilation
• Reduced peripheral vascular resistance
• Decreased afterload
• Improved coronary blood flow
• Reduced myocardial oxygen demand

The drug exhibits greater selectivity for vascular smooth muscle than cardiac muscle, resulting in more pronounced vasodilatory effects with minimal negative inotropic activity at therapeutic doses.

Indications

• Hypertension (chronic management)
• Vasospastic angina (Prinzmetal's angina)
• Chronic stable angina

• Raynaud's phenomenon
• Preterm labor (tocolysis)
• Achalasia
• Pulmonary hypertension

Dosage and Administration

• Immediate-release: 10-30 mg orally three times daily
• Extended-release: 30-90 mg orally once daily

• Immediate-release: 10-20 mg three times daily
• Maximum dose: 180 mg daily

• Hepatic impairment: Reduce initial dose by 50%
• Renal impairment: No initial adjustment required
• Geriatric patients: Start with lowest effective dose
• Avoid use in pregnancy unless benefit outweighs risk

• Immediate-release capsules: Swallow whole, do not crush or chew
• Extended-release tablets: Swallow whole, may be taken without regard to meals
• Avoid grapefruit juice (inhibits CYP3A4 metabolism)

Pharmacokinetics

Contraindications

• Hypersensitivity to nifedipine or other dihydropyridines
• Hypotension (systolic BP <90 mmHg)
• Severe aortic stenosis
• Unstable angina (except vasospastic angina)
• Acute myocardial infarction
• Cardiogenic shock
• Concomitant use with strong CYP3A4 inhibitors in patients with hypertension or CAD

Warnings and Precautions

• Peripheral edema (dose-dependent)
• Hypotension (especially with volume depletion)
• Exacerbation of angina (rare, with rapid titration)
• Heart failure (use cautiously in patients with systolic dysfunction)
• Hepatic impairment (reduce dose)
• Gastrointestinal obstruction (extended-release formulations)
• Withdrawal syndrome (avoid abrupt discontinuation)

Drug Interactions

• CYP3A4 inhibitors: Ketoconazole, itraconazole, clarithromycin (↑ nifedipine levels)
• CYP3A4 inducers: Rifampin, carbamazepine, phenytoin (↓ nifedipine levels)
• Beta-blockers: Increased risk of hypotension and heart failure
• Digoxin: ↑ digoxin levels (monitor closely)
• Magnesium sulfate: Risk of neuromuscular blockade
• Grapefruit juice: ↑ bioavailability and peak concentrations

• Fentanyl: Risk of severe hypotension
• Quinidine: ↓ quinidine levels
• Tacrolimus: ↑ tacrolimus levels
• Statins: Potential ↑ statin concentrations

Adverse Effects

• Peripheral edema (dose-dependent)
• Headache
• Dizziness
• Flushing
• Palpitations

• Nausea
• Constipation
• Fatigue
• Hypotension
• Tachycardia

• Myocardial infarction
• Heart failure exacerbation
• Severe hypotension
• Hepatotoxicity
• Gingival hyperplasia
• Stevens-Johnson syndrome

Monitoring Parameters

• Blood pressure and heart rate
• Liver function tests
• Renal function
• ECG (if cardiac disease suspected)

• Blood pressure (regular assessments)
• Heart rate
• Signs/symptoms of heart failure
• Peripheral edema
• Drug interactions and adherence
• Hepatic function (periodically)

• Angina symptoms (frequency and severity)
• Signs of hypotension (dizziness, syncope)
• Gingival health (long-term therapy)

Patient Education

• Take medication exactly as prescribed
• Do not stop abruptly without medical supervision
• Swallow extended-release tablets whole; do not crush or chew
• Avoid grapefruit and grapefruit juice
• Rise slowly from sitting/lying position to prevent dizziness
• Monitor for swelling in ankles/feet and report if severe
• Report chest pain, palpitations, or severe dizziness immediately
• Inform all healthcare providers about nifedipine use
• Keep regular follow-up appointments for blood pressure monitoring
• Be aware that headaches and flushing may diminish with continued use

• Maintain low-sodium diet
• Regular physical activity as tolerated
• Weight management
• Alcohol moderation
• Smoking cessation

References

1. FDA Prescribing Information: Nifedipine (2023) 2. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248 3. Hermann DD, et al. Dihydropyridine Calcium Channel Antagonists: A Class of Anti-Hypertensive Drugs. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 4. Elliott WJ, et al. Nifedipine: A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy, in Ischaemic Heart Disease, Hypertension and Related Cardiovascular Disorders. Drugs. 1985;30(3):182-274 5. McKeage K, et al. Nifedipine: A Review of its Use in the Management of Chronic Stable Angina Pectoris, Hypertension, and Raynaud's Phenomenon. Drugs. 2006;66(7):921-944 6. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012 7. Lexicomp Online, Lexi-Drugs. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc.; 2024