Atrial fibrillation (AF) is the most common arrhythmia in the world. Risk factor modification, anticoagulation, rhythm control, and rate control are the four pillars of its management. American College of Cardiology/American Heart Association (ACC/AHA) guidelines on management of AF were updated recently.

Treatment of atrial fibrillation includes anticoagulation, rate control, and rhythm control. US guidelines were recently updated.

Direct-to-consumer advertisements continue to urge patients who take warfarin (Coumadin, and others) for atrial fibrillation to ask their doctors about the benefits of one or another of the newer oral anticoagulants.

Warfarin-related bleeding, especially intracranial hemorrhage, can be catastrophic. Several products are available to reverse warfarin’s anticoagulant effect.

Osteoporosis is characterized by low bone mass with microarchitectural disruption and skeletal fragility that results in an increased risk of fracture. The diagnosis has traditionally been established by bone densitometry, which is generally reported in terms of standard deviations (SD) from mean values in young adults (T score). The World Health Organization (WHO) has defined normal bone mineral density (BMD) for women as a value within one SD of the young adult mean. Values 2.5 SD (T score -2.5) or more below the mean are defined as osteoporosis. The WHO has developed a computerized model (FRAX) that predicts the 10-year probability of hip fracture based on clinical risk factors and BMD at the femoral neck.

A reader expressed disappointment that our recent listing of “Some Warfarin Drug Interactions”1 did not include acetaminophen. Perhaps it should have. Acetaminophen can increase the anticoagulant effect of warfarin, particularly with continued use, but it does so inconsistently. The mechanism of this interaction has not been established, but may be related to an acetaminophen metabolite inhibiting vitamin K-epoxide reductase, the target for warfarin’s anticoagulant effect.2

Patient susceptibility varies, possibly on a genetic basis; occasional use of acetaminophen generally has little or no effect on the international normalized ratio (INR) in patients on chronic warfarin therapy, but in some, even a few grams of the drug may cause a dramatic increase in INR. One study in healthy subjects found no effect of acetaminophen 4 g per day for 2 weeks, while another study in patients with the same acetaminophen dose for the same period of time found a moderate increase in INR.3,4 It might be prudent to monitor INR in patients on chronic warfarin therapy more closely than usual when they take more than 2 g per day of acetaminophen for more than a few days.

1. Pharmacogenetic-based dosing of warfarin. Med Lett Drugs Ther 2008; 50:39.
2. HH Thijssen et al. Paracetamol (acetaminophen) warfarin interaction: NAPQI, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle. Thromb Haemost 2004; 92:797.
3. D Kwan et al. The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 1999; 39:68.
4. I Mahe et al. Paracetamol: A haemorrhagic risk factor in patients on warfarin. Br J Clin Pharmacol 2005; 59:371.

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Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy. Studies suggest that when used for the appropriate seizure type, antiepileptic drugs are roughly equivalent in efficacy. The choice of a drug is usually based on factors such as ease of use, adverse effects and cost.

Warfarin sodium (Coumadin, and others) and other coumarin anticoagulants prevent thrombosis, but patient response is highly variable and overanticoagulation can lead to hemorrhage. Genotyping patients for single nucleotide polymorphisms (SNPs) that affect coumarin metabolism and sensitivity may help clinicians estimate the therapeutic warfarin dose. The FDA has added a note to warfarin labeling recommending lowrange doses for patients with such genetic variations. Commercial tests for these variants are now available and cost about $500 per test.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only for adjunctive therapy are probably also effective as monotherapy. Many of the drugs used to treat epilepsy interact with each other (see table beginning on page 63) and with other drugs; for interactions with other drugs, see The Medical Letter Handbook of Adverse Drug Interactions, 2003. The treatment of status epilepticus is not included here.