verapamil (Isoptin, Calan, Verelan, Covera-HS, Iproveratril, Dilacorin, Cardioprotect)
Jump to navigation
Jump to search
Introduction
Tradenames: Isoptin, Calan, Verelan, Covera-HS.
Indications
- supraventricular tachycardia (SVT)
- hypertension (HTN)
- prophylaxis of cluster headaches
- variant (Prinzmetal's) angina
- left ventricular diastolic dysfunction
- verapamil may preserve beta-cell function in patients with newly diagnosed type 1 diabetes[9]
Contraindications
- sick sinus syndrome
- AV nodal disease
- wide-complex ventricular tachycardia
- congestive heart failure (CHF)
Dosage
- SVT: 0.1-0.3 mg/kg up to 5-10 mg IV over 2 minutes; may repeat with 10 mg (0.15 mg/kg) in 30 minutes if arrhythmia is not terminated
- HTN: start 80 mg PO TID, max 360 mg/day (extended release)
- angina: 80-120 mg PO TID; max 480 mg/day
Tabs: 40, 80, 120 mg.
Sustained release forms:
Tabs: 120, 180, 240 mg.
Pharmacokinetics
- metabolized in the liver by cyt P450 3A4
- orally administered verapamil undergoes extensive 1st pass hepatic metabolism
- norverapamil (N-demethylated metabolite) has some vaso- dilatory activity
- 90% of the drug is bound to plasma proteins
- elimination 1/2life is 4 hours, increased with long-term use & severe liver disease
elimination via liver
1/2life = 2.4-14 hours
protein binding = 88-92 %
Monitor
Adverse effects
- not common (1-10%)
- skin rash, bradycardia, AV block, CHF exacerbation, orthostatic hypotension, peripheral edema, constipation, dizziness, light-headedness, nausea, tiredness, weakness
- uncommon (< 1%)
- other
- negative inotropic effect
- eosinophilia (rare)
- hepatic dysfunction (rare)
- overdose:
- drug adverse effects of calcium channel blockers
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of antihypertensive agents
Drug interactions
- beta adrenergic antagonists increase the risk for bradycardia or AV block;
- digoxin: increased serum digoxin levels
- carbamazepine: increased carbamazepine levels
- lithium: decreased Li+ levels
- theophylline: increased theophylline levels
- verapamil increases plasma levels of digoxin & quinidine
- any drug that inhibits cyt P450 3A4 may increase levels of verapamil
- any drug that induces cyt P450 3A4 may diminish levels of verapamil
- verapamil inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
- drug interaction(s) of antiarrhythmic agents in combination with diuretics
- drug interaction(s) of calcium channel blockers with ARBs
- drug interaction(s) of calcium channel blockers with ACE inhibitors
- drug interaction(s) of calcium channel blockers with diuretics
- drug interaction(s) of calcium channel blockers with erythromycin
- drug interaction(s) of calcium channel blockers with clarithromycin
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of beta-adrenergic receptor antagonists with calcium channel blockers
- drug interaction(s) of simvastatin, verapamil & grapefruit
- drug interaction(s) of NSAIDs & antihypertensives
Laboratory
- specimen: serum, plasma (EDTA, heparin)
- methods: GC-MS, GLC, HPLC, fluorometry
- interferences: fluorescent methods after oral administration unsatisfactory because of fluorescent metabolites
Mechanism of action
- L-type Ca+2 channel blocker & a papaverine derivative
- arteriolar vasodilating properties
- slows AV nodal conduction & ventricular rate
- greater negative inotropic effect than nifedipine (an N-type Ca+2 channel blocker) or diltiazem (another L-type Ca+2 channel blocker, limiting its use in patients with significant left ventricular systolic dysfunction
- inhibits SLC22A5
More general terms
Additional terms
Component of
References
- ↑ Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 90
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill pg 774
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Ovalle F, Grimes T, Xu G et al. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med 2018 Aug; 24:1108. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29988125 https://www.nature.com/articles/s41591-018-0089-4
- ↑ Enyeart JJ, Price WA, Hoffman DA, Woods L. Profound hyperglycemia and metabolic acidosis after verapamil overdose. J Am Coll Cardiol. 1983 Dec;2(6):1228-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/6355245 Free article