Nifedipine SR: Definition and Clinical Significance
Nifedipine SR (sustained-release) refers to an extended-release formulation of the calcium channel blocker nifedipine that is designed for less frequent dosing compared to immediate-release preparations, typically administered once or twice daily rather than three times daily. 1
Pharmaceutical Characteristics
SR formulations utilize specialized drug delivery technology to provide controlled release of nifedipine over an extended period:
- The sustained-release tablets contain nifedipine in a matrix that allows gradual drug release, achieving peak plasma concentrations at approximately 2.5-5 hours with a second smaller peak at 6-12 hours post-dose 1
- The elimination half-life of nifedipine SR is approximately 7 hours, compared to only 2 hours for immediate-release capsules 1
- Bioavailability of SR formulations ranges from 84-89% relative to immediate-release tablets 1
- Available dosage strengths include 30 mg, 60 mg, and 90 mg tablets for once-daily administration 1
Pharmacokinetic Advantages
The SR formulation produces more stable plasma concentrations with reduced peak-to-trough fluctuations:
- Once-daily dosing with SR tablets results in decreased fluctuations in plasma nifedipine concentrations compared to three-times-daily dosing with immediate-release capsules 1
- Mean peak plasma concentration following a 90 mg SR tablet under fasting conditions is approximately 115 ng/mL 1
- The SR formulation demonstrates lower maximum plasma concentrations (Cmax) compared to immediate-release (54.46 vs. 107.45 ng/mL), with significantly longer time to peak concentration (Tmax of 2.97 vs. 1.13 hours) 2
Clinical Implications and Safety
The critical distinction between SR and immediate-release nifedipine has profound safety implications, particularly in acute coronary syndromes:
- Immediate-release nifedipine should NOT be administered to patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) in the absence of beta-blocker therapy 3
- Immediate-release nifedipine causes a dose-related increase in mortality in patients with coronary artery disease and harm in acute coronary syndromes 3
- Rapid-release, short-acting dihydropyridines like immediate-release nifedipine must be avoided in the absence of concomitant beta blockade due to increased adverse potential 3
- Short-acting nifedipine has been associated with dose-dependent detrimental effects on mortality in patients with coronary artery disease 3
Tolerability Profile
SR formulations demonstrate improved tolerability compared to immediate-release preparations:
- Sustained-release nifedipine formulations are generally better tolerated than conventional formulations, particularly regarding reflex tachycardia 4
- Adverse effects are dose-related and mainly associated with vasodilatory action, including headache, flushing, and dizziness, which are typically mild to moderate and transient 4
- Both SR and immediate-release formulations display comparable safety profiles overall, but SR allows less frequent administration 2
Dosing Considerations
Important caveats exist regarding dose interchangeability:
- Two 30 mg SR tablets may be interchanged with a single 60 mg SR tablet 1
- However, three 30 mg tablets result in substantially higher Cmax values than a single 90 mg tablet and should NOT be considered interchangeable 1
- The area under the curve (AUC) is dose proportional over the 30-90 mg range, but peak concentrations for 90 mg given as three 30 mg tablets are 29% greater than predicted 1
Clinical Applications
SR formulations are effective for multiple cardiovascular indications:
- Treatment of mild to moderate hypertension with once or twice-daily dosing 5, 4
- Management of stable and variant angina pectoris 4
- Long-acting calcium channel blockers including SR nifedipine are recommended for patients with coronary artery spasm 3
- SR formulations permit reduced dosing frequency, improving patient compliance 4