The treatment of atrial fibrillation includes anticoagulation, rate control, and rhythm control. New US guidelines for the management of atrial fibrillation have recently been published.

The FDA has approved a new oral solution of the calcium channel blocker nimodipine (Nymalize – Arbor) to reduce the severity of neurological deficits associated with vasospasm after subarachnoid hemorrhage from a ruptured intracranial aneurysm. An older formulation of nimodipine has been available for such use for many years.1

Since 1988, nimodipine has been available only in liquid-filled gel capsules (Nimotop, and generics) that a conscious patient could swallow intact. For unconscious patients, the package insert included instructions for use of a needle and syringe to aspirate the liquid from the capsules and inject it into a feeding tube. However, some healthcare providers mistakenly injected the nimodipine liquid into IV tubing instead; IV nimodipine can cause severe hypotension, cardiac arrest and death. In 2006, the FDA added a boxed warning to the labeling regarding the dangers of giving oral nimodipine intravenously, but errors continued to occur. In 2010, the FDA warned again that nimodipine should only be administered orally or through a nasogastric or gastric feeding tube.2

Nymalize, a 60 mg/20 mL solution, can be administered orally or through a nasogastric or gastric feeding tube. Use of the oral syringe supplied with the drug for administration through a feeding tube should prevent erroneous IV injection. No new clinical trials were required for approval of Nymalize.

1. Nimodipine for cerebral vasospasm after subarachnoid hemorrhage. Med Lett Drugs Ther 1989; 31:47.

2. FDA Drug Safety Communication: serious medication errors from intravenous administration of nimodipine oral capsules. Available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm220386.htm. Accessed August 6, 2013.

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The treatment of atrial fibrillation includes ventricular rate control, anticoagulation, conversion to normal sinus rhythm and maintenance of sinus rhythm. The choice of therapies that can achieve these goals is discussed in the text that follows. Some drugs are recommended here for indications that have not been approved by the FDA.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

The ability of grapefruit juice to increase serum concentrations of drugs was first discovered during a study of the effect of ethanol on felodipine (Plendil) pharmacokinetics. Double-strength grapefruit juice used to disguise the taste of ethanol resulted in higher than expected serum concentrations of felodipine (DG Bailey et al, Clin Invest Med 1989; 12:357).

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Reports of adverse interactions between drugs continue to accumulate. Recently, the FDA has expanded the recommendations on drug interactions found in the package inserts of new drugs.

Reports of increased mortality associated with calcium-channel blockers have caused concerns among patients taking these drugs and their physicians.

In a study of the interaction between alcohol and the calcium-channel blocker felodipine (Plendil), the grapefruit juice vehicle for the alcohol appeared to increase felodipine plasma concentrations. Subsequent studies have found that grapefruit juice increases plasma concentrations of several calcium-channel blockers and of some other drugs as well (DG Bailey et al, Clin Pharmacokinet, 26:91, 1994).