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verapamil (Isoptin, Calan, Verelan, Covera-HS, Iproveratril, Dilacorin, Cardioprotect)

Tradenames: Isoptin, Calan, Verelan, Covera-HS. Indications: 1) supraventricular tachycardia (SVT) 2) hypertension (HTN) 3) prophylaxis of cluster headaches 4) variant (Prinzmetal's) angina 5) left ventricular diastolic dysfunction 6) verapamil may preserve beta-cell function in patients with newly diagnosed type 1 diabetes [9] Contraindications: 1) sick sinus syndrome 2) AV nodal disease 3) wide-complex ventricular tachycardia 4) congestive heart failure (CHF) Dosage: 1) 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 2) HTN: start 80 mg PO TID, max 360 mg/day (extended release) 3) angina: 80-120 mg PO TID; max 480 mg/day Tabs: 40, 80, 120 mg. Sustained release forms: - Isoptin SR, Calan SR, Covera-HS, Verelan. - start 240 mg PO QD, max 480 mg/day. Tabs: 120, 180, 240 mg. Injection: 2.5 mg/mL (2 mL) Pharmacokinetics: 1) metabolized in the liver by cyt P450 3A4 - orally administered verapamil undergoes extensive 1st pass hepatic metabolism 2) norverapamil (N-demethylated metabolite) has some vaso- dilatory activity 2) 90% of the drug is bound to plasma proteins 3) elimination 1/2life is 4 hours, increased with long-term use & severe liver disease Monitor: - electrocardiogram for bradycardia Adverse effects: 1) not common (1-10%) - skin rash, bradycardia, AV block, CHF exacerbation, orthostatic hypotension, peripheral edema, constipation, dizziness, light-headedness, nausea, tiredness, weakness 2) uncommon (< 1%) - chest pain, galactorrhea, gingival hyperplasia, tachycardia, flushing 3) other - negative inotropic effect - eosinophilia (rare) - hepatic dysfunction (rare) 4) overdose: - tetrad of hypotension, bradycardia, hyperglycemia, metabolic acidosis Drug interactions: 1) beta adrenergic antagonists increase the risk for bradycardia or AV block; 2) digoxin: increased serum digoxin levels 3) carbamazepine: increased carbamazepine levels 4) lithium: decreased Li+ levels 5) theophylline: increased theophylline levels 6) verapamil increases plasma levels of digoxin & quinidine 7) any drug that inhibits cyt P450 3A4 may increase levels of verapamil 8) any drug that induces cyt P450 3A4 may diminish levels of verapamil 9) verapamil inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates Laboratory: 1) specimen: serum, plasma (EDTA, heparin) 2) methods: GC-MS, GLC, HPLC, fluorometry 3) interferences: fluorescent methods after oral administration unsatisfactory because of fluorescent metabolites Mechanism of action: 1) L-type Ca+2 channel blocker & a papaverine derivative 2) arteriolar vasodilating properties 3) slows AV nodal conduction & ventricular rate 4) 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 5) inhibits SLC22A5

Interactions

drug interactions drug adverse effects (more general classes)

Related

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

General

amine antiarrhythmic agent, Group IV calcium channel blocker (CCB) nitrile

Properties

MISC-INFO: elimination route LIVER 1/2life 2.4-14 HOURS therapeutic-range 100-500 NG/ML protein-binding 88-92% pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 90
  2. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  3. The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill pg 774
  4. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
  5. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  6. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  7. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  8. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  9. 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: 29988125 https://www.nature.com/articles/s41591-018-0089-4
  10. 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: 6355245 Free article

Component-of

trandolapril/verapamil (Tarka)