Pharmacology Watch

Escitalopram for Menopausal Hot Flashes

In this issue: Escitalopram for menopausal hot flashes, rifaximin for IBS without constipation, herpes zoster vaccination, antiepileptics drugs and fracture risk, and FDA Actions.

Escitalopram for hot flashes

Since the Women's Health Initiative was published in 2003, the use of hormone therapy for the treatment of postmenopausal hot flashes has dropped dramatically. Both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have been studied to relieve postmenopausal symptoms, but no agent has been conclusively shown to be effective. A new study suggests that escitalopram (Lexapro™) may offer some relief.

In a study recently published in the Journal of the American Medical Association, 205 menopausal women were randomized to 10-20 mg per day of escitalopram or matching placebo for 8 weeks. The primary outcome was the frequency and severity of hot flashes with the average hot flash frequency at nearly 10 per day at baseline. Escitalopram resulted in 1.41 fewer hot flashes per day compared to placebo (P < 0.001), although both the active drug group and placebo groups noted reductions. Escitalopram also reduced hot flash severity. There was no difference among women of different races, and the discontinuation rate was small. The authors concluded that escitalopram 10-20 mg per day compared with placebo resulted in fewer and less severe menopausal hot flashes at 8 weeks (JAMA 2011;305:267-274). Whether the same effect can be expected with racemic citalopram (Celexa™) is unknown.

Rifaximin for IBS without constipation

Rifaximin, an oral, nonsystemic (poorly absorbed) broad-spectrum antibiotic, may help relieve symptoms of irritable bowel syndrome according to two identically designed studies published in the New England Journal of Medicine. A total of 1060 patients who had IBS without constipation were randomized to rifaximin 550 mg three times daily for 2 weeks or matching placebo. The primary endpoint was a proportion of patients with adequate relief of global IBS symptoms; the secondary endpoint was relief of bloating. Significantly more patients in the rifaximin group had adequate relief of IBS symptoms during the first 4 weeks of treatment (40.7% vs 31.7%; P < 0.001), as well as improvement in bloating (40.2% vs 30.3%; P < 0.001). The incidence of adverse events was similar in the two groups. The authors concluded that among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of the IBS symptoms of bloating, abdominal pain, and loose or watery stools (N Engl J Med 2011;364:22-32).

An accompanying editorial points out that the benefit from rifaximin was sustained over 10 weeks after a short 2-week treatment course, but also points out that benefit of the drug was a mere 9%-12% improvement over placebo, barely clinically relevant. Still, for patients who have IBS without constipation who have not responded to other therapies, a single treatment cycle could be tried (N Engl J Med 2011;364:81-82).

Herpes zoster vaccination rates and incidence of shingles

The herpes zoster vaccine cuts the rate of shingles by 55% in the elderly population according to a new report in the Journal of the American Medical Association. Researchers at Kaiser Permanente in Southern California performed a retrospective cohort study of health plan members, 75,000 of whom were vaccinated against shingles (age 60 and older) and 225,000 age-matched controls who did not receive vaccine. The rate of herpes zoster was 6.4/1000 person-years in the vaccinated group and 13.0/1000 person-years in the unvaccinated group (hazard ratio, 0.45; 95% confidence interval, 0.42-0.48). Reduction in herpes zoster occurred in all age groups and among individuals with chronic disease. The rate of ophthalmic herpes zoster and hospitalizations for herpes zoster were also significantly reduced.

The authors of the study concluded that among immunocompetent community-dwelling adults age 60 and older, receipt of the herpes zoster vaccine was associated with a lower incidence of herpes zoster (JAMA 2011;305:160-166). The study is important because only 10% of those aged 60 and older received the shingles vaccine in 2009, whereas nearly one of three people in the United States will develop shingles in their lifetime.

Fracture risk with antiepileptic drugs

Most antiepileptic drugs (AEDs) are associated with an increased risk of nontraumatic fracture according to a retrospective match cohort study. Nearly 16,000 patients with a history of prior AED use (carphenazine, clonazepam, ethosuximide, felbamate, gabapentin, lamotrogine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproic acid, or vigabatrin) were compared to up to three matched controls each. Rates of fractures of the wrist, hip, and vertebrae were measured between 1996 and 2004. A significant increase in fracture risk was found for most AEDs, with an adjusted odds ratio of 1.24 for clonazepam to 1.91 for phenytoin. The only AED not associated with increased fracture risk was valproic acid.

The authors concluded that most AEDs are associated with an increased risk of nontraumatic fractures in individuals age 50 or older. They suggested that the risk of fracture with newer AEDs needs to be determined, as well as the effect of bone protective medications in this population (Arch Neurol 2011;68:107-112). The mechanism of increased fracture risk in patients using AEDs is unknown, but may be related to accelerated vitamin D catabolism, calcium absorption, or an effect on osteoblasts.

FDA Actions

The FDA has approved vilazodone hydrochloride for the treatment of depression in adults. The drug is a selective serotonin reuptake inhibitor as well as a partial agonist of the 5HT 1a receptor. The drug was approved in dosages of 10 mg, 20 mg, and 40 mg for major depressive disorder or major depression. Vilazodone is touted as having fewer sexual side effects than other antidepressants. It carries the same boxed warning as other antidepressant regarding suicidal thinking and behavior in children, adolescents, and young adults. Vilazodone will be marketed by Clinical Data Inc. as Viibryd™.

The FDA is limiting the amount of acetaminophen in combination prescription pain medications. The new requirement limits the amount of acetaminophen to 325 mg in each tablet or capsule. Common medications that will be affected include codeine (acetaminophen with codeine), oxycodone (Percocet®), and hydrocodone (Vicodin®). Over-the-counter acetaminophen products are not affected. This action is being taken to limit acetaminophen-related liver failure. It is felt that lowering the amount of acetaminophen in these products will have minimal effect on efficacy for treating pain. The change will be phased in over 3 years.

The FDA has approved a new transmucosal form of fentanyl for the treatment of breakthrough pain for adults with cancer. The drug is indicated for the management of breakthrough pain in patients with cancer ages 18 and older, who use opiate pain medication around the clock. Breakthrough pain is defined as pain that comes on suddenly for short periods of time and is not alleviated by the patient's normal pain management plan. Patients must be opioid-tolerant to qualify for use with transmucosal fentanyl. The drug is available only through a Risk Evaluation and Mitigation Strategy (REMS) program, which is intended to minimize risk of misuse, abuse, addiction, and overdose. Fentanyl sublingual tablets are available as 100 mcg, 200 mcg, 300 mcg, 400 mcg, 600 mcg, and 800 mcg strengths. Fentanyl sublingual tablets are marketed by ProStrakan Inc. under the trade name Abstral®.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Elliott reports no financial relationships to this field of study. Questions and comments, call: (404) 262-5468. E-mail: