Remicade Alert Centocor, Inc., a subsidiary of Johnson & Johnson, has added a boxed warning and a revised Warnings and Adverse Reactions section to the product labeling for RemicadeÒ (infliximab). In addition, Centocor, in conjunction with the U.S. Food and Drug Administration (FDA), recently issued two letters that advised health care professionals that certain patients taking Remicade may suffer serious adverse affects. Remicade is used, in combination with methotrexate, to treat CrohnÆs disease and rheumatoid arthritis (RA).1

Tuberculosis (TB) and other serious opportunistic infections including histoplasmosis, listeriosis, and pneumocystosis, have been reported in both clinical and post-marketing surveillance settings. Some of these infections have been fatal.2 The boxed warning was added as a result of 84 reported cases of TB in patients receiving Remicade between August 24, 1998 and June 30, 2001. Of the 84 cases, 14 patients died, although the primary cause of death was not always reported as TB. Most cases were diagnosed within seven months of the initiation of Remicade therapy, and most reported the use of concomitant immunosuppressive medications.2 The revised Warnings and Adverse Reactions section also states that the benefits and risks of Remicade therapy should be carefully considered in patients who have resided in regions where histoplasmosis is endemic.

Centocor has also alerted physicians to the potential adverse effects of Remicade in patients with congestive heart failure (CHF). Upon review of preliminary results of its ongoing phase 2 trial in 150 patients with moderate-to-severe (NYHA class III-IV) congestive heart failure, higher incidence of mortality and hospitalization for worsening heart failure were seen in patients treated with Remicade, especially those treated with the higher dose of 10 mg/kg. Seven of 101 patients treated with Remicade died, compared to no deaths in the 49 patients on placebo.2

AdvancePCS has communicated the most recent labeling change to physicians who have patients who have been identified through prescription drug claims as having a prescription filled recently for Remicade.

If you encounter a new prescription for Remicade or a request for a refill, please confirm that the patient consulted with his or her physician regarding the potential safety risks.

References1.Remicade®product information. Centocor Inc., August 2001. 2. U.S. Food and Drug Administration. 2001 Medical Product Safety Alerts: Remicade. Last update October 23, 2001. Available at: . Accessed October 29, 2001.

Rifampin and Pyrazinamide Alert

The Centers for Disease Control and Prevention (CDC), in cooperation with the American Thoracic Society, has issued revised treatment guidelines for latent tuberculosis infection (LTBI).

The revised guidelines limit the circumstances in which the combination of rifampin-pyrazinamide (RIF-PZA) is prescribed, and strengthen the level of patient counseling and monitoring recommended for LTBI treatment regimens.

For most individuals with LTBI, the new guidelines recommend a nine-month regimen of daily isoniazid (INH) as the preferred treatment. RIF-PZA may be used in selected cases and requires more intensive clinical and laboratory monitoring than previously recommended.1,2

The guidelines were revised after the CDC investigated cases of liver injury associated with RIF-PZA treatment. From February 12, 2001 through August 24, 2001, 21 patient cases of liver injury associated with a two-month RIF-PZA regimen were reported.1 Sixteen patients recovered and five died of liver failure.1

The CDC recommends that providers use RIF-PZA with caution, especially in those currently taking other medications that have been associated with liver injury, and in those with alcoholism.1,2

AdvancePCS has provided this information to physicians who have patients who recently filled a prescription for rifampin and pyrazinamide or the combination of RIF/INH/PZA.

If you encounter a patient presenting a new prescription or obtaining refills for these products, please inform him or her of the revised guidelines and suggest that the patient discuss them with their physician.

1. Update: fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations-United states, 2001. MMWR. 2001;50(34):733-735. Available at: 2. Backgrounder: severe and fatal injury connected to latent TB treatment (press release). Atlanta, GA: Centers for Disease Control and Prevention, Office of Communication; August 30, 2001. Available at:

Baycol Alert

Bayer Corporation has recently announced its decision to voluntarily withdraw BAYCOLÒ(cerivastatin) from the United States market.

BAYCOL, available in the United States since1997, is an HMG-CoA reductase inhibitor, a class of cholesterol-lowering medications commonly known as is “statins.”l While all statins have been associated with very rare reports of rhabdomyolysis, a serious potentially fatal adverse effect, cases of fatal rhabdomyolysis in association with the use of BAYCOL have been reported significantly more frequently than with other approved statins.1,2 The U.S. Food and Drug Administration (FDA) has received reports of 31 deaths in the United States due to severe rhabdomyolysis associated with the use of BAYCOL, 12 of which involved its use with another cholesterol-lowering drug, gemfibrozil (LOPID® and generics).1

Rhabdomyolysis is a condition that results in muscle cell breakdown and release of the contents of muscle cells into the bloodstream.1 Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, malaise, fever, dark urine, nausea, and vomiting.1 The pain may involve specific groups of muscles or may be generalized throughout the body.1 The more frequently involved muscle groups are the calves and lower back.1 In rare cases, the muscle injury is so severe that patients develop renal and other organ failure, which can be fatal.1 However, some patients may report no symptoms of muscle injury.1

For further information regarding the withdrawal of BAYCOL, pharmacists can contact Bayer

Customer Service at 1-800-758-9794 or the Drug Information Office at the FDA at 301-827-4573 or 1-888-INFO-FDA.1

AdvancePCS has responded to the withdrawal by alerting physicians to patients who have been identified through prescription drug claims as having a prescription filled recently for BAYCOL. Patients who are taking BAYCOL should consult with their physicians about switching to alternate medications to control their cholesterol levels.1 Patients taking BAYCOL who are experiencing muscle pain or are also taking gemfibrozil should discontinue BAYCOL immediately and consult their physician.1

If you encounter a new prescription for BAYCOL or a request for a refill, please inform the patient of its withdrawal and suggest that he or she consult with their physician about switching to alternate medications. Also, claims for BAYCOL now reject at the point-of-service with:

BAYER PRODUCT RECALL

Thank you for your assistance.

References:1Food and Drug Administration. Glaxo Wellcome decides to withdraw Lotronex from the market. FDA Talk Paper. November 28, 2000. Available at: l

2Bayer Pharmaceutical Division. Market withdrawal of Baycol (cerivastatin). August 8, 2001. Available at: HealthCare Letter-Baycol pull.pdf

Lotronex Alert

On November 28, 2000, Glaxo Wellcome informed the U.S. Food and Drug Administration (FDA), that it will voluntarily withdraw Lotronex® (alosetron) from the market.1 The FDA approved Lotronex on February 9, 2000 for the treatment of irritable bowel syndrome (IBS) in women.1

Since its approval, the FDA has received and reviewed 70 cases of serious post-marketing events, which include 49 cases of ischemic colitis and 21 cases of severe constipation.1 Of the total number of cases reported, 34 resulted in hospitalization without surgery, 10 required surgical procedures, and three resulted in death.1 Two additional reports of death, not classified as ischemic colitis or severe complications of constipation, have been received by the FDA.1

The FDA is advising patients taking Lotronex to contact their healthcare providers to discuss treatment alternatives.1 AdvancePCS has also responded to the market withdrawal by alerting physicians to patients who have been identified through prescription drug claims as having a prescription filled recently for Lotronex.

If you encounter a new prescription for Lotronex or a request for a refill, please inform the patient of its market withdrawal and suggest that he or she contact their physician to discuss treatment alternatives.

AdvancePCS appreciates your continued assistance.

References:1Food and Drug Administration. Glaxo Wellcome decides to withdraw Lotronex from the market. FDA Talk Paper. November 28, 2000. Available at: .

Phenylpropanolamine Alert

The Food and Drug Administration (FDA) recently issued a public health advisory concerning phenylpropanolamine (PPA) and increased risk of hemorrhagic stroke.

PPA is used as a decongestant in many over-the-counter (OTC) and prescription cough and cold medications and as an ingredient in OTC weight-loss products. Earlier this year, scientists at Yale University School of Medicine reported that taking PPA increases the risk of hemorrhagic stroke in women and that men may also be at risk.1 The increased risk of hemorrhagic stroke was detected among women using the drug for weight control and for nasal decongestion, specifically in the three days after initial use of the medication.1 Although the risk of hemorrhagic stroke is believed to be very low, the FDA believes that the use of PPA in these conditions does not warrant the increased risk to the patient and recommends that patients discuss alternative OTC and prescription products with their health care provider or pharmacist.1 The FDA is currently taking steps to remove PPA from all drug products and has requested that all drug companies discontinue marketing products containing PPA.1

Common OTC cough and cold products containing PPA include: Dimetapp Cold and Flu Caplets, Comtrex Liquigels, Coricidin-D tablets, Alka Seltzer Cough and Cold tablets, Robitussin-CF, Triaminic Syrup, Dimetapp products, and many others. Common OTC weight-loss products containing PPA include: Dexatrim and Acutrim products, Appedrine, and Permathene-16 Maximum Strength. Prescription cough and cold products containing PPA include: Entex, Entex LA, Hycomine syrup, Triaminic products, and many others.2

AdvancePCS has responded to the public health advisory by alerting physicians to patients who have been identified through prescription drug claims as having a prescription filled recently for a product containing phenylpropanolamine.

If you encounter a patient purchasing one of these products, please inform him or her of the public health advisory issued concerning phenylpropanolamine and increased risk of hemorrhagic stroke. In addition, AdvancePCS appreciates your assistance in recommending a therapeutic alternative to these patients.

References:1FDA Talk Paper: FDA issues public health warning on phenylpropanolamine. November 6, 2000. Available at: .2Drug Facts and Comparisons®. St Louis, MO: Facts and Comparisons; 2000:728, 730, 735, 746, 757, 782-783.

Propulsid Alert

Janssen Pharmaceutica, in consultation with the Food and Drug Administration (FDA), has voluntarily discontinued the marketing of Propulsid® (cisapride) Tablets and Suspension, indicated for the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophogeal reflux disease (GERD), as of July 14, 2000.

Propulsid has been associated with serious cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation.1 Consequently, Janssen has made Propulsid available only through an investigational limited access program.

Through a “Dear Health Care Provider” letter that was sent on April 12, 2000, Janssen encouraged physicians to reassess the need for Propulsid in each patient given the risks of the drug, and discuss, if needed, the possible use of alternative therapies. AdvancePCS also responded to the information by alerting physicians on two separate occasions to patients who have been identified through prescription drug claims as having had a prescription recently filled for Propulsid.

According to our records, there are still a significant number of claims being adjudicated for Propulsid. If you encounter a new prescription for Propulsid or a request for a refill, please inform the patient of its market withdrawal and suggest that he or she contact their physician, as the product will not be available through your pharmacy for much longer.

Janssen established the investigational limited access program for patients who fail other treatment options and who meet clearly defined eligibility criteria. Enrollment in this program began May 1, 2000. If you wish to obtain further information regarding the program, you may call Janssen toll-free at 877-795-4247.

Reference:1Janssen Pharmaceutica. Healthcare Provider letter. April 12, 2000. Available at: .