UWMC/HMC Drug Alerts!

Dated 8/23/2001: As of May 2001, the Pregnancy/Lactation, Adverse Reactions, and several other sections of the package insert have been revised to reflect serious safety-related issues and to incorporate "geriatric" information. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

AMIODARONE (Cordarone®): PEDIATRIC PRECAUTIONS

Dated 06/08/01: Health care practitioners are alerted to two changes to the Cordarone (amiodarone) prescribing information. Amiodarone has been used off-label to treat arrhythmias in pediatric patients. Amiodarone IV has been found to leach out plasticizers (such as DEHP) from IV tubing (including PVC tubing). The degree of leaching increases when infusing the drug at higher concentrations and lower flow rates than recommended in the package insert. An expert panel recentlu concluded that based on data from animal studies, there so concern that exposure to DEHP may adversely affect male reproductive tract development during fetal, infant, and toddler stages of development if the exposure in these stages is several fold higher than in adults, a situation that might be associated with intensive medical procedures such as those used in critically ill infants. The maximum anticipated exposure to DEHP following IV administration of amiodarone under conditions of pediatric administration was calculated to produce a safety margin of between about twofold and sevenfold. In order to reduce the potential exposure of such pediatric patients to placticizers, alternative methods of dosing and administration should be considered. Secondly, Cordarone IV contains the preservative benzyl alcohol. Practitoners are reminded that a "gasping syndrome" (sudden onset of gasping respiration, hypotension, bradycardia, cardiovascular collapse and death) in neonates can occur following administration of IV solutions containing benzyl alcohol. (Dear Doctor Letter)

AMITRIPTYLINE (Elavil®): LABELING CHANGES

Dated 06/15/01: As of March 2001, the labeling has been revised to to reflect serious safety-related issues (drug interaction with cisapride). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

ANTIOXIDANT VITAMINS AND ZINC: REDUCED RISK OF MACULAR DEGENERATION

Dated 10/15/2001: Findings from a nationwide clinical trial reported that high levels of antioxidant vitamins and zinc significantly reduce the risk of advanced age-related macular degeneration and its accompanying vision loss. These same nutrients were found to have no significant effect on the progression or development of cataracts. Details of this clinical trial, the Age-Related Eye Disease Study (AREDS), sponsored by the National Eye Institute, can be found at the National Library of Medicine web site.

AZITHROMYCIN (Zithromax®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Dosage/Administration section of the package insert has been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

BICLUTAMIDE (Casodex®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Warnings (hepatitis), Pregnancy, and Adverse Reactions (respiratory) sections of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

BUPROPION (Buspar®): GERIATRIC LABELING & OTHER LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Drug Interactions section of the package insert has been been revised to reflect serious safety-related issues (new information about inhibitors and inducers of CYP3A4) and to incorporate "geriatric" information. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

BUPROPION (Zyban®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Clinical Pharmacology and Adverse Reactions sections of the package insert have been revised to reflect serious safety-related issues (use in patients with COPD). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.
Dated 2/22/01: As of November 2000, the Clinical Pharmacology and Precautions (including information on drug interaction with cimetidine, information on allergic reactions, and information on dosing for patients with renal/hepatic impairment) sections of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

CAPECITABINE (Xeloda®)

Dated 11/01/01: INTERACTION WITH ANTICOAGULANTS: Health care practitioners are alerted to a potentially serious drug interaction between warfarin and capecitabine (Xeloda®), an antineoplastic agent, indicated for the treatment of colorectal and breast cancer. Clinically significant increases in prothrombin time and INR have been seen in patients stabilized on anticoagulants at the time capecitabine therapy was instituted. It is recommended that patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy have their INR and prothrombin time monitored frequently in order to adjust the anticoagulant dose as needed. (Revised product labeling)
Dated 7/13/01: LABELING CHANGES: As of April 2001, the labeling has been extensively revised to reflect serious safety-related issues. Prescribers are urged to contact the company (Hoffman LaRoche) for a copy of the new labeling.

CEFUROXIME (Ceftin®) : PEDIATRIC LABELING

Dated 05/17/01: As of February 2001, the package insert has been revised to incorporate "pediatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

CERIVASTATIN (Baycol®)

Dated 6/26/01: REVISED PRESCRIBING INFORMATION: The prescribing information for Baycol (cerivastatin), used for the treatment of hyperlipidemia, has been updated. Revisions were made following reports in the post-marketing period of muscle weakness and rhabdomyolysis in patients taking the drug. A large number of these reports involved patients receiving cerivastatin in a manner inconsistent with the product labeling: this involved concurrent gemfibrozil therapy or the administration of cerivastatin at a starting dose of 0.8mg. Prescribers are reminded that: 1) The starting dose for cerivastatin is 0.4mg, regardless of previous lipid therapy. Beginning therapy at doses above the 0.4mg starting dose increases the risk of myopathy and rhabdomyolysis. In patients with significant renal impairment (CrCl <60mL/min/1.73m2) lower starting doses are recommended. The maximum effect of the drug is seen within 4 weeks and lipid determinations should be performed at this time and the dose adjusted based on patient response. Only patients requiring further lipid adjustment should be titrated to 0.8mg. 2) The combined use of cerivastatin and gemfibrozil is contraindicated due to a risk for rhabdomyolysis and concurrent use should not occur under any circumstances. 3) Patients taking cerivastatin or any other statin should be reminded to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by fever or malaise. (Dear Doctor Letter)
Dated 06/15/01: LABELING CHANGES: As of March 2001, the Clinical Pharmacology (metabolism and cytochrome P450 enzymes) and Drug Interactions (omeprazole and cyclosporine) sections of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

CHLORPROMAZINE (Thorazine®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the labeling has been extensively revised to reflect serious safety-related issues. Prescribers are urged to contact the company (GlaxoSmithKline) for a copy of the new labeling.

CLONAZEPAM (Klonopin®): GERIATRIC LABELING

Dated 7/13/2001: As of April 2001, the package insert has been revised to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

DANGEROUS DRUG ABBREVIATIONS/DOSE EXPRESSIONS: MAJOR CAUSE OF MEDICATION ERRORS

Dated Sept 2001: One of the major causes of medication errors is the ongoing use of potentially dangerous abbreviations and dose expressions. Underlying factors contributing to many of these errors are illegible or confusing handwriting by clinicians and the failure of health care providers to communicate clearly with one another. Because medication safety and the identification, prevention and timely reporting of medication errors are of primary importance to the Joint Commission, this issue of Sentinel Event Alert specifically addresses medication errors related to the use of dangerous abbreviations and dose expressions used in prescribing medications. (JCAHO Sentinel Event Alert)

DEFEROXAMINE (Desferal®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the labeling has been extensively revised to reflect serious safety-related issues. Prescribers are urged to contact the company (Novartis) for a copy of the new labeling.

DOBUTAMINE: GERIATRIC LABELING

Dated 8/23/2001: As of May 2001, the package insert has been revised to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

DOPAMINE: PEDIATRIC LABELING

Dated 7/13/2001: As of April 2001, the package insert has been revised to incorporate "pediatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

DROPERIDOL (Inapsine®): FATAL CARDIAC ARRHYTHMIAS

Dated 12/4/2001: A "black box" warning has been added to the labeling information for droperidol (Inapsine), a tranquilizer used as a premedication for anesthesia, as treatment for nausea after anesthesia, and for sedation of agitated patients. This medication previously carried a warning about cases of sudden death at high doses(greater than 25mg) in patients at risk for cardiac arrhythmias. Current research has shown QT prolongation within minutes after injection of a dose of the drug at the upper end of the labeled dose range. Prolonged QT is a concern because it can potentially cause fatal heart arrhythmias known as torsades de pointes. In the past year there have been reports of torsades de pointes occurring following droperidol administration within or below the currently labeled dose range. Additionally there have been reports of sudden death or other serious cardiac adverse effects. (Dear Doctor Letter), (FDA Talk Paper)

EFAVIRENZ (Sustiva®): LABELING CHANGES

Dated 2/22/01: As of November 2000, the Precautions section of the package insert has been revised to reflect serious safety-related issues (updated information on breastfeeding). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

ELECTROLYTE SOLUTION (Plasma-Lyte®): GERIATRIC LABELING

Dated 05/17/01: As of February 2001, the package insert has been revised to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

ENALAPRIL (Vasotec®): PEDIATRIC LABELING

ENOXAPARIN (Lovenox®): LABELING CHANGES

Dated 2/22/01: As of November 2000, the Warnings, Adverse Reactions, and Dosage/Administration sections of the package insert have been revised to reflect serious safety-related issues (thrombocytopenia). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

EPOETIN ALFA (Epogen®)/Filgastim (Neupogen®): PRODUCT TAMPERING

Dated 2/13/01: FDA reports 3 incidents of product tampering involving vials of Epogen (epoetin alfa) and Neupogen (filgastim). The flip caps of the vials were removed and the contents of the vials extracted. The contents were replaced with varying amounts of an aqueous solution and the vials were resealed in an apparent effort to conceal product theft. In the reported instances, the tampering was discovered before the product was used. Health care practitioners are warned that if vials of Epogen or Neupogen appear to have been opened, have crusty white deposits around the stopper, appear to contain discolored or cloudy fluid, particulate matter, volumes less or greater than expected, or if the labels appear worn, the product should not be used. Practitioners are urged to call the manufacturer (Amgen), if they suspect product tampering. (FDA Talk Paper)

FAMCICLOVIR (Famvir®): LABELING CHANGES

Dated 06/15/01: As of March 2001, the Microbiology section of the package insert has been updated with information on drug resistance. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

FENTANYL (Duragesic®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the Clinical Pharmacology, Drug Interactions, Adverse Reactions, and Dosage/Administration sections of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

FLUOXETINE (Prozac®): LABELING CHANGES

Dated 2/22/01: As of November 2000, the Contraindications (thioridazine), Warnings (lupus-like syndrome, laryngospasm), Precautions (sumatriptan), and Adverse Reactions section of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

FLUTAMIDE (Eulexin®): LABELING CHANGES

Dated 06/15/01: As of March 2001, the Warnings section of the package insert has been updated to include information stating that this drug should not be used in women. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

FLUTICASONE (Flovent®): GERIATRIC LABELING

Dated 06/15/01: As of March 2001, the package insert has been revised to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

GENTUZUMAB (Mylotarg®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Boxed Warning and Warnings sections of the package insert have been revised to reflect serious safety-related issues (hepatotoxicity and the use of this drug with other chemotherapeutic agents). As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.
Dated 05/17/01: As of February 2001, the Boxed Warning section of the package insert has been revised with information on hypersensitivity reactions and hepatotoxicity. Additionally, the Warnings, Adverse Reactions, and Dosage/Administration sections have been updated with this information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

HYDROXYUREA (Droxia/Hydrea®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the Warnings section of the package insert has been revised to reflect serious safety-related issues (pregnancy). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.
Dated 05/17/01: As of February 2001, the Warnings, Precautions, and Adverse Reactions sections of the package insert have been revised to include updated information on hepatitis, pancreatitis, and peripheral neuropathy associated with/or without the use of other antiretroviral agents. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

HYDROXYZINE (Atarax®): GERIATRIC LABELING

HYDROXYZINE (Vistaril®): GERIATRIC LABELING

IBUTILIDE (Corvert®): GERIATRIC LABELING

INDINAVIR (Crixivan®): GERIATRIC LABELING & OTHER LABELING CHANGES

Dated 06/15/01: As of March 2001, the package insert has been updated with information on a drug interaction with sildenafil and to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

INFLIXIMAB (REMICADE®)

ADVERSE CARDIAC EFFECTS (Dated 10/18/2001): Health care practitioners are alerted to potential adverse effects of infliximab in patients with congestive heart failure (CHF). Infliximab is a biological therapeutic product used to treat rheumatoid arthritis and Crohn's disease. Upon review of preliminary results from an ongoing trial in 150 patients with moderate to severe congestive heart failure, higher rates of hospitalization for worsening heart failure and mortality were seen in patients treated with the medication. Of 101 patients treated with infliximab, seven died compared to no deaths among 49 patients on placebo. Based on the preliminary data from this trial, the following precautionary measures are recommended: a) Do not initiate therapy in patients with congestive heart failure. b) Patients with CHF currently receiving chronic infliximab treatment should be reevaluated and therapy stopped in patients whose CHF is worsening. c) Treatment discontinuation should be considered in patients with stable concomitant CHF, especially in those who have not had a significant clinical response to infliximab therapy. If a decision is made to continue treatment, cardiac status should be monitored closely. (Dear Doctor Letter)
SERIOUS OPPORTUNISTIC INFECTIONS (Dated 10/5/2001): FDA notifies health care providers about the occurrence of tuberculosis and other serious opportunistic infections (histoplasmosis, listeriosis, and pneumocystosis) occurring in patients after treatment with infliximab (Remicade®). Infliximab is a biological therapeutic product used to treat rheumatoid arthritis and Crohn's disease. Worldwide, 84 cases of infliximab-associated tuberculosis have been reported in the last 3 years. Of these 84 cases, 14 deaths occurred and many cases were disseminated or extrapulmonary at the time of clinical presentation. The majority of tuberculosis cases were diagnosed within seven months of the start of infliximab therapy and most patients were using concomitant immunosuppressive agents. Increased risk of infection associated with tumor necrosis factor inhibition (TNF) is consistent with the known effects of TNF on macrophage activation and granuloma formation. The manufacturer has added a Boxed Warning to the labeling for this product. (Dear Doctor Letter)

INTERFERON ALFA-2B/RIBAVIRIN (Rebetron®)

GERIATRIC LABELING & OTHER LABELING CHANGES (Dated 06/15/01): As of March 2001, the Warnings (bone marrow toxicity) and Adverse Reactions (hearing disorders) sections of the package insert have been updated to reflect serious safety-related issues and to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.
LABELING CHANGES (Dated 05/17/01): As of February 2001, the Boxed Warning in the package insert has been revised to include new information on use in pregnancy. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

IRINOTECAN (Camptosar®): DEATHS HALT 2 CLINICAL TRIALS

Dated 5/18/01: Following the deaths of 28 patients with colorectal cancer, 2 clinical trials of Camptosar (irinotecan) have been halted. This information was included in a letter to the editor released early by the New England Journal of Medicine. In the first trial (included patients with metastatic colon cancer and compared irinotecan with oxaliplatin, both used in combination with fluorouracil and leucovorin), 12 of the 14 patients who died had several common symptoms including dehydration (due to nausea, diarrhea, and vomiting), neutropenia, and sepsis (alone or in combination with shock). Of the 14 deaths, 13 occurred during the first cycle of chemotherapy or shortly thereafter. After the deaths are reviewed, the trial may reopen using lower doses of irinotecan. In the second trial (included patients with stage III colon cancers that had been resected, and used the drug with and without fluorouracil and leucovorin), patients who died also experienced coagulation-related problems (3 cases of pulmonary emboli and one case each of MI, CVA, and bowel ischemia and/or infarct). Irinotecan was approved last year as first-line therapy for metastatic colon cancer. In their letter, the authors state that "many oncologists have now adopted it as a standard of care." And they conclude that although irinotecan, used in combination with fluorouracil and leucovorin should remain a treatment option, they caution that they have found "an excessive rate of early deaths."(NEJM Letter)

IRON DEXTRAN (Infed®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the Boxed Warning and Adverse Reactions sections of the package insert have been revised to reflect serious safety-related issues (anaphylaxis). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

ISOTRETINOIN (Accutane®): NEW SAFETY COMMUNICATION TOOLS

Dated 2/5/01: Health care providers are notified of the availability of new safety information communications tools for Accutane (isotretinoin), a drug indicated for the treatment of severe nodular acne. A Medication Guide emphasizes key safety issues (including updated pregnancy and psychiatric information) and must be distributed by the pharmacist to every isotretinoin patient each time a prescription is dispensed. The Informed Consent/Patient Agreement document replaces the current consent form and must be completed and signed by the prescriber and each isotretinoin patient before receiving the medication. (Dear Doctor letter), (Medication Guide), (Information Consent Form)

ITRACONAZOLE (Sporanox®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the package insert has been revised to reflect serious safety-related issues (congestive heart failure and renally impaired patients, hepatotoxicity, and menstrual disorders). Numerous drugs have been added to the Drug Interactions section of the package insert and information on itraconazole as a CYP3A4 inhibitor has been added. A statement has been added to the Indications/Usage section advising that prior to initiating treatment, patients should be tested to confirm the diagnosis of onychomycosis. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line. at the URL indicated.

KETAMINE (Ketalar®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Adverse Reactions (anaphylaxis) section of the package insert has been updated and a section on Drug Abuse and Dependence has been added. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

KETOROLAC (Acular®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the labeling has been extensively revised to reflect serious safety-related issues. Prescribers are urged to contact the company (Allergan) for a copy of the new labeling.

LACTATED RINGER'S: GERIATRIC LABELING & OTHER LABELING CHANGES

Dated 2/22/01: As of November 2000, the Contraindications section of the package insert has been revised to reflect serious safety-related issues and to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

LAMIVUDINE (Epivir®): GERIATRIC LABELING & OTHER LABELING CHANGES

Dated 06/15/01: As of March 2001, the package insert has been revised with information regarding patients coinfected with HIV and hepatitis B virus and to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

LAMOTRIGINE (LAMICTAL)

DISPENSING ERRORS (Dated 12/6/2001): Health care prescribers are alerted to continuing reports of dispensing errors involving the anticonvulsant drug LAMICTAL (lamotrigine). Nameonfusion with other medications such as Lamisil, lamivudine, Ludiomil, labetolol, and Lomotil is an ongoing problem. Patients with a seizure disorder who do not receive prescribed lamotrigine (Lamictal) to control seizures could be at risk for developing serious consequences such as status epilepticus. Additionally, patients who receive lamotrigine (Lamictal) by mistake may be placed at unnecessary risk of adverse effects such as serious rash. The URLs below provide additional information about what health care practitioners can do to reduce the potential for dispensing errors. Dear Doctor Letter, (Dear Pharmacist Letter)
GERIATRIC LABELING (Dated 8/23/2001): As of May 2001, the package insert has been revised to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

LANSOPRAZOLE (Prevacid®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Clinical Studies section of the package insert has been updated with information on the treatment of erosive esophagitis. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

LINEZOLID (Zyvox®)

MYELOSUPPRESSION WARNING (Dated 3/02/01): Health care practitioners are alerted to reports of myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) in patients taking the antibiotic linezolid (Zyvox). In cases where the outcome was known, when linezolid was discontinued, the affected hematologic parameters have risen towards the pretreatment levels. The following information has been added to the Warnings section of the package insert: a) Complete blood counts should be monitored weekly in patients who receive linezolid, particularly in those who receive the drug for longer than 2 weeks, those with pre-existing myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy, b) Discontinuation of therapy with linezolid should be considered in patients who develop or have worsening myelosuppression. (Dear Doctor letter)
LABELING CHANGES (Dated 05/17/01): As of February 2001, the Warnings, Precautions, and Adverse Reactions sections of the package insert have been updated with information on myelosuppression. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

LIPOKINETIX, a dietary supplement: ADVERSE HEPATIC EFFECTS

Dated 11/19/2001: Health care practitioners are alerted by FDA about a dietary supplement, Lipokinetix, promoted for weight loss that may present a serious public health risk. FDA has received reports involving at least six people who developed acute hepatitis and/or liver failure while using this product. In these cases, no other cause for liver disease was identified and no pre-existing medical conditions that would predispose the users to liver injury were identified. The onset of liver injury was observed between two weeks and three months after starting the dietary supplement. Lipokinetix contains norephedrine (phenylpropanolamine), caffeine, yohimbine, diiodothyronine, and sodium usniate. FDA has issued a warning to consumers advising them to stop using the product and to report symptoms such as nausea, weakness or fatigue, fever, abdominal pain, or any change in skin color to their health care provider. FDA urges health care providers to review their cases of hepatitis in order to determine if any may be related to the use of this dietary supplement by their patients.

LITHIUM (Lithobid Slow Release®)--EXPIRATION DATE CHANGE

Dated 11/7/01: The expiration dating (or shelf life) for Lithobid Slow Release tablets has increased to 18 months. The August 2000 recommendations to prescribe and dispense 30-day quantities of the product (due to manufacturer has increased to 18 months. The August 2000 recommendations to prescribe and dispense 30-day quantities of the product (due to manufacturer need to locate a new source for its raw material, lithium carbonate) are no longer relevant. Health care practitioners should prescribe and fill prescriptions in their usual manner. (Dear Doctor Letter)

LOOK-ALIKE, SOUND-ALIKE DRUG NAMES: POTENTIAL FACTOR IN MEDICATION ERRORS

Dated May 2001: One potential contributing factor for medication errors is the existence of look-alike, sound-alike drug names. Because medication safety and the identification, prevention and timely reporting of medication errors are of primary importance to the Joint Commission, this issue of Sentinel Event Alert specifically addresses the topic of look-alike, sound-alike drug names and how they can potentially contribute to medication errors in prescribing. (JCAHO Sentinel Event Alert)

MEROPENEM (Merrem®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the package insert has been updated to include new information on a drug interaction with valproic acid and the Adverse Reactions/Post Marketing Experience sections have been extensively updated. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

METFORMIN (Glucophage®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the Clinical Pharmacology and Dosage/Administration sections of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.
Dated 05/17/01: As of February 2001, the labeling has been extensively revised to reflect serious safety-related issues. Prescribers are urged to contact the company (Bristol-Myers Squibb) for a copy of the new labeling.

METHOTREXATE

LABELING CHANGES (Dated 8/23/2001): As of May 2001, the Indications/Usage and Dosage/Administration sections of the package insert have been revised to reflect serious safety-related issues (hepatotoxicity and the use of this drug with other chemotherapeutic agents). As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.
PEDIATRIC LABELING (Dated 2/22/01): As of November 2000, the package insert has been revised to incorporate "pediatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

MICONAZOLE CREAM/SUPPOSITORIES: DANGEROUS DRUG INTERACTION

Dated 3/05/01: Health care practitioners are advised that women who take a warfarin anticoagulant and use a miconazole cream or suppository may be at risk for developing an increased prothrombin time, international normalized ratio (INR), and bleeding. FDA has received reports of 2 adverse reactions indicating abnormal blood clotting tests in women who took anticoagulant therapy and used vaginal miconazole concomitantly for 3 days. In addition to the abnormal tests, one of the women developed bruises, bleeding gums, and a nosebleed. Two articles in the medical literature report cases of a probable warfarin interaction with vaginal miconazole. Miconazole, an antifungal agent is available by prescription and over-the-counter in different forms such as creams and suppositories and is used to treat vaginal yeast infections. The interaction of systemically administered miconazole with warfarin is well established, and is included in the warfarin labeling. Because of the concerns raised by the recent reports of an interaction with vaginally administered miconazole with warfarin, health care practitioners and patients should be aware that patients who need to use both products simultaneously should be appropriately monitored. The product labeling for OTC miconazole preparations have been updated to reflect this new information. (FDA Science Background), (FDA Talk Paper)

MIDAZOLAM (Versed®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Warnings and Drug Interactions sections of the package insert have been updated with information on saquinavir. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

MILRINONE (Primacor®): LABELING CHANGES

Dated 2/22/01: As of November 2000, the Adverse Reactions section has been revised to reflect serious safety-related issues (liver function test abnormalities). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

MIRTAZAPINE (Remeron®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Precautions section of the package insert has been revised to reflect serious safety-related issues (phenylketonuria). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

MORPHINE (MS Contin®): GERIATRIC LABELING

NALTREXONE (Reva®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Contraindications section of the package insert has been revised with regards to patients currently dependent on opioids, including those currently maintained on opiate agonists [e.g., methadone or LAAM (levo-alpha-acetyl-methadol)]. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

NEFAZODONE (Serzone®): LABELING CHANGES

Dated 06/15/01: As of March 2001, the Adverse Reactions section of the package insert has been updated with information on hyponatremia and thrombocytopenia. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

NELFINAVIR (Viracept®): LABELING CHANGES

Dated 7/13/01: As of April 2001, the Drug Interactions section of the package insert has been revised to reflect serious safety-related issues (P450 isoform CYP3A). As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

NEO CONCEPT ALLER RELIEF: DANGEROUS PRODUCT CONTAMINATION

Dated 1/10/01: A recall has been issued for Neo Concept Aller Relief (BMK International) an OTC herbal product. The product has been found to contain trace amounts of aristolochic acid a potent carcinogen and nephrotoxin found in certain plants and botanicals. Products that contain aristolochic acid have been associated with cases of kidney failure in Europe and the use of aristolochic acid containing products has also been linked to a increased risk of kidney cancer inpeople who have consumed it. (Press Release)

NEVIRAPINE (Viramune®)

POSTEXPOSURE PROPHYLAXIS SERIOUS ADVERSE EFFECTS (Dated 01/05/01): Following 2 recent reports of life-threatening hepatotoxicity (one case requiring liver transplantation) in health-care workers taking nevirapine for postexposure prophylaxis (PEP) after occupational HIV exposure, FDA reviewed MedWatch reports to characterize nevirapineassociated PEP toxicity over a 3 year period. During this time period, 22 cases of serious adverse events related to nevirapine taken for PEP were reported. These events included: hepatotoxicity (12), skin reaction (14), and rhabdomyolysis (1). The results of this review indicate that healthy persons taking abbreviated 4-week nevirapine regimens for PEP are at risk for serious adverse events. Clinicians should use recommended PEP guidelines and dosing instructions to reduce the risk for serious adverse events. (MMWR article)
LABELING CHANGES (Dated 2/22/01): As of November 2000, the labeling has been extensively revised to reflect serious safety-related issues. Prescribers are urged to contact the company (Boehringer Ingelheim) for a copy of the new labeling.

OLANZEPINE (Zyprexa®): LABELING CHANGES

Dated 2/22/01: As of November 2000, the Indications/Usage, Clinical Pharmacology, and Dosage/Administration sections of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

OPRELVEKIN (Neumega®): PAPILLEDEMA IN CHILDREN

Dated 8/24/01: Practitioners are notified that preliminary data from a safety and pharmacokinetic study in 47 children has identified papilledema as a dose-limiting adverse reaction in the pediatric population treated with oprelvekin. Of the 16 children in the study who received 100 mcg/kg/day, 4 developed papilledema. None of the 9 children who received 75 mcg/kg/day developed papilledema, but given the small population size, the true incidence at this dose may be as high as 33%. There are no controlled clinical studies that have established a safe and effective dose of oprelvekin in the pediatric population. Therefore, use of this drug in children, especially those <12 years should be restricted to controlled clinical trial settings with closely monitored safety assessments. (Dear Doctor letter)

OXYCODONE (OxyContin®): RISING POPULARITY AS A STREET DRUG

Dated 1/08/01: A recent article in Time magazine describes the disturbing rise in the popularity of oxycodone, a leading treatment for chronic pain, as a street drug across the nation. Officials fear that this narcotic analgesic may succeed crack cocaine on the street. Drug abusers crush the OxyContin to remove the time-release coating and then snort or inject it to generate a heroin-like euphoria. Arecent survey in Virginia indicated that 20% of high school students and 10% of middle school students know about OxyContin and how to obtain it. Several states have reported increases in pharmacy break ins, home invasion robberies, drugstore parking lot holdups, and prescription forging activities that may be related to the rising demand for OxyContin on the street. Prescribers are alerted to the increasing popularity of this commonly prescribed medication as a drug of abuse.

PANTOPRAZOLE (Protonix®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Dosage/Administrative section of the package insert has been updated with information on the treatment of erosive esophagitis. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

PAROXETINE (Paxil®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Contraindications, Warnings, and Precautions sections of the package insert have been updated with new information regarding an interaction with thioridazine. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

PHYTONADIONE (Aquamephyton®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Warnings and Adverse Reactions sections of the package insert have been revised with information on intravenous and intramuscular use of phytonadione. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

PROCHLOPERAZINE (Compazine®): LABELING CHANGES

PROMETHAZINE (Phenergan®): GERIATRIC LABELING

PROPRANOLOL (Inderide/Inderide LA®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Precautions section of the package insert has been updated with information on lactation. As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

PROTON PUMP INHIBITORS: DANGEROUS INSTRUCTIONS

Dated 11/26/2001: A commonly written sig for proton pump inhibitors could be harmful to patients. Oftentimes instructions for these medications are written as follows: "Take one tablet (or capsule) daily half an hour prior to meals." Patients may interpret this as "One tablet half an hour before EACH meal." In this case, the medication would end up being taken 3 times per day, instead of once per day. It is recommended that these instructions be rewritten as follows: "Take one tablet each day. Take 30 minutes prior to a meal." Health care practitioners are also urged to reinforce the proper directions by providing patients with adequate verbal counseling. (Dear Doctor Letter)

PYRIDOSTIGMINE (Mestinon®): MANUFACTURING CHANGE

Dated 10/00: The manufacturer (ICN Pharmaceuticals) of Mestinon Timespan tablets for myasthenia gravis has transferred manufacturing responsibilities to their plant in Canada. All previous batches of the formulation were produced in the United States. Usually FDA would not approve of a change in manufacturing location without evidence that the in vivo performance of the newly manufactured product was similar to that of the previously approved product. These studies have not been performed, and, therefore, there is no assurance that this new product will perform similarly to the old product in the body. Because the previous formulation is no longer available, the FDA has permitted marketing of the product manufactured in Canada because there are some patients whose myasthenia can be managed successfully only with this dosage form. Health care providers should notify patients of this situation, and if the decision is made to continue to prescribe this new tablet, patients should be observed closely for any changes in their clinical condition.

RANITIDINE (Zantac®): GERIATRIC LABELING

RIVASTIGMINE (Exelon®): REPORT OF SEVERE VOMITING/ESOPHAGEAL RUPTURE

Dated 1/26/01: Following a report of severe vomiting with esophageal rupture that occurred in a patient taking Exelon (rivastigmine), a drug indicatedfor the treatment of dementia, revisions have been made to the package insert. These changes provide guidelines for reinitiating therapy in patients who have interrupted treatment with rivastigmine to reduce the risk of severe vomiting. To reduce the possibility of severe vomiting in patients who have interrupted rivastigmine therapy for longer than several days, treatment should be reinitiated with the lowest daily dose. After reinitiating therapy, patients should be titrated back to their maintenance dose as described in the Dosage/Administration section of the package insert. The case of severe vomiting with esophageal rupture occurred after reinitiation of patient treatment at an inappropriate single dose of 4.5mg of rivastigmine following an interruption of treatment for eight weeks. Health care providers are urged to consult the revised Warnings, Precautions, and Dosage/Administration sections of the package insert for the detailed revisions. (Dear Doctor letter)

ROSIGLITAZONE (Avandia®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Warnings, Precautions and Adverse Reactions sections of the package insert have been extensively revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

SALMETEROL (Serevent®): LABELING CHANGES

Dated 8/23/2001: As of May 2001, the Adverse Reactions section of the package insert has been revised to reflect serious safety-related issues (oropharyngeal irritation). As the package inserts available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

SAQUINAVIR (Fortovase®/Invirase®): GERIATRIC LABELING & OTHER LABELING CHANGES

(Dated 2/22/01): As of November 2000, the Drug Interactions (lovastatin, simvastatin, sildenafil), Pregnancy/Lactation, Dosage/Administration, and Precautions sections of the package insert have been revised to reflect serious safety-related issues and to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

SERTRALINE (Zoloft®)

GERIATRIC LABELING & OTHER LABELING CHANGES (Dated 05/17/01): As of February 2001, the Precautions (renal effects) section of the package insert has been revised to reflect serious safety-related issues and to incorporate "geriatric" information. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.
LABELING CHANGES (Dated 2/22/01): As of November 2000, the Adverse Reactions section of the package insert has been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

SIBUTRAMINE (Meridia®): LABELING CHANGES

Dated 05/17/01: As of February 2001, the Clinical Studies (effects on blood pressure) and Dosage/Administration sections of the package insert have been revised to reflect serious safety-related issues. As the package insert available from the pharmacy may not be current, prescribers are urged to review the changes on-line.

SIMVASTATIN (Zocor®): GERIATRIC LABELING

Dated 2/22/01: As of November 2000, the pac