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nifedipine (Procardia, Adalat)

Tradenames: Procardia, Adalat. Verapamil is the preferred agent in this class. Indications: 1) hypertrophic cardiomyopathy 2) hypertension 3) variant (Prinzmetal's angina) 4) chronic, stable angina (see ACTION trial) 5) Raynaud's phenomenon 6) easing passage of urinary calculus [6] Contraindications: 1) myocardial ischemia/infarction 2) NOT for use in controlling ventricular response to atrial fibrillation -> does NOT block AV nodal conduction Dosage: Start 10 mg PO TID, max 120 mg/day. Tabs: 10 & 20 mg. Hypertensive urgency: - 10 mg SL or PO (bite & swallow) followed by 10 mg PO hourly until BP reduction achieved. Sustained release: Procardia XL, Adalat CC. - Do Not crush, split or chew tablets - Hypertension: 30-60 mg PO QD, max 120 mg/day. - Angina: 30 mg QD, max 180 mg/day. Tabs: 30, 60, 90 mg. Storage: - store Procardia in its original container - must be protected from light & moisture - product labeling for generics does not instruct to dispense in original container Pharmacokinetics: 1) 90% of dose is absorbed from GI tract 2) extensive 1st pass metabolism 3) metabolized in the liver by cyt P450 3A4 -> polymorphism of metabolism 4) bioavailablity is increased in patients with cirrhosis 5) protein binding 92-98%, decreased in patients with renal or hepatic failure Adverse effects: 1) common (> 10%) - dizziness - lightheadedness - giddiness - flushing - heat sensation - headache - weakness - nausea - heartburn 2) less common (1-10%) - muscle cramps, tremor, peripheral edema, nervousness, mood changes, palpitations, dyspnea, cough, nasal congestion, sore throat, orthostatic hypotension 3) uncommon (< 1%) - tachycardia, syncope, sweating, fever/chills, dermatitis, urticaria, diarrhea, constipation, gingival hyperplasia, thrombocytopenia, leukopenia, anemia, purpura, arthritis, increased antinuclear antibody (ANA), blurred vision, transient blindness, shortness of breath 4) short acting nifedipine - reflex tachycardia, especially when used with nitrates - adverse effects in myocardial ischemia/infarction - negative inotropic effects 5) proteinuria: nifedipine dilates both glomerular afferent & efferent arterioles & increases vascular permeability 6) nifedipine has anti-platelet effects that may increase bleeding time. 7) urinary retention (relaxation of bladder smooth muscle) [8] 8) gingival hyperplasia in 20% of elderly [9] - may appear 1-9 months after initiation of therapy & - may resolve slowly when nifedipine is discontinued 9) photosensitivity - increased risk of lip cancer [11] * In contrast to clonidine, nifedipine is well tolerated by most patients. It does not cause Na+ retention. Drug interactions: 1) beta blockers may increase risk of CHF 2) anesthetic doses of fentanyl may cause hypotension 3) concurrent administration of cimetidine may increase nifedipine level 4) nifedipine may increase serum levels of: a) phenytoin b) digoxin c) quinidine 5) severe hypotension may occur during surgery in combination with fentanyl 6) IV Mg+2 may result in neuromuscular blockade & hypotension 7) any drug that inhibits cyt P450 3A4 may increase levels of nifedipine -> grapefruit juice may increase nifedipine levels 8) any drug that induces cyt P450 3A4 may diminish levels of nifedipine Laboratory: 1) specimen: serum, plasma (EDTA) 2) methods: GLC, HPLC 3) interferences: -> nifedipine may be displaced from protein binding sites by plasticizers in collection devices Mechanism of action: 1) L-type Ca+2 channel blocker 2) potent arterial & coronary artery dilating properties 3) reflex increase in sympathetic tone 4) does NOT block AV nodal conduction Clinical trials: - ACTION trial

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

calcium channel blocker (CCB) dihydropyridine

Properties

MISC-INFO: elimination route LIVER PO-absorption 5-20 MIN 1/2life 2-6 HOURS protein-binding 96-98% elimination by hemodialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill pg 774
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary - non formulary drug request
  6. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  7. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  8. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  9. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
  10. Prescriber's Letter 11(9): 2004 Use of Nifedipine or Tamsulosin for Kidney Stones Detail-Document#: 200911 (subscription needed) http://www.prescribersletter.com
  11. Friedman GD et al Antihypertensive Drugs and Lip Cancer in Non-Hispanic Whites Archives of Internal Medicine, August 2012 PMID: 22869299 http://archinte.jamanetwork.com/article.aspx?articleid=1307567
  12. Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: 300622 (subscription needed) http://www.prescribersletter.com