Summary of Drug Market Withdrawals, Significant Drug Recalls and Changes in Drug Safety Profiles in the United States: January 2000 to August 2000

Jan 2000 Glaxo Wellcome notified health professionals regarding revised warnings in the product labeling about fatal hypersensitivity reactions to abacavir, initially manifesting as respiratory symptoms (e.g., cough, dyspnea, pharnygitis). Respiratory symptoms have occurred in approximately 20% of patients with hypersensitivity reactions, and may not be recognized, causing delay in diagnosis and increasing the risk of more severe or life-threatening reactions.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/ziagen.htm

July 2000 New information regarding hypersensitivity reactions with abacavir indicate that severe or fatal hypersensitivity reactions can occur within hours after abacavir therapy is restarted after therapy interruption. Reactions have also occurred in patients without a history of prior hypersensitivity reactions. If the reason for therapy interruption is unknown, hypersensitivity symptoms should be ruled out. If prior hypersensitivity reaction has occurred, abacavir should not be restarted.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/ziagen1.htm

Albuterol 
(Proventil)

March 2000 Schering/Key recalled several lots of inhalation aerosol canisters based upon the potential that a small number of canisters did not contain active drug. Batch numbers included 7-BBS-303 through 7-BBS-642, 8-BBS-500 through 8-BBS-826, and 9-BBS-500 through 9-BBS-832.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/proven1.htm

March 2000 Schering/Key recalled several lots inhalation aerosol canisters based upon the potential that a small number of canisters did not contain active drug. For the 42 mcg aerosol containers, batch numbers included 8-AMA-208 through 8-AMA-703 and 9-AMA-200 through 9-AMA-404. For the 84 mcg aerosol containers, batch numbers included 8-DMT-644 through 8-DMT-646 and 9-DMT-133 through 9-DMT-621.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/vancer.htm

Aug 2000 Glaxo Wellcome notified health professionals regarding reports of ischemic colitis or constipation possibly progressing to serious complications in association with of alosetron use. This product should not be used in patients with active or history of severe constipation, Crohn’s disease, or ulcerative colitis. Other contraindications also include active diverticulitis, or history of intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, ischemic colitis and/or adhesions.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/lotron.htm

May 2000 Glaxo Wellcome notified health professionals regarding the large amount of propylene glycol in amprenavir oral solution and the potential risk of toxicity. The oral solution is contraindicated in infants, children younger than 4 years, pregnant women, patients with renal/hepatic failure, and concurrent disulfiram or metronidazole therapy.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/agener.htm

July/Aug 2000 Bayer and Aventis voluntarily withdrew Kogenate lot numbers 670H071C and 670H076, and Helixate lot numbers 670H071E due to variable potency under certain storage conditions.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/kogena.htm

May 2000 The FDA notified health professionals regarding reports of severe nephrotoxicity associated with dietary supplements and/or herbal products containing aristolochic acids. Urothelial carcinomas have also been reported in patients with "Chinese herb nephropathy". A list of botanicals containing these products was provided.
FDA Announcement: http://vm.cfsan.fda.gov/~dms/ds-botl2.html
Botanical List: http://vm.cfsan.fda.gov/~dms/ds-bot2.html
FDA Letter to Industry: http://vm.cfsan.fda.gov/~dms/ds-botl1.html

Cisapride
(Propulsid)

Jan 2000 Janssen Pharmaceutica and the FDA notified health professionals regarding expanded boxed warnings requiring a 12 lead ECG and QTc < 450 milliseconds prior to initiation of cisapride therapy. This agent is also contraindicated in patients with electrolyte disorders. Revised labeling also included an expanded list of drug interactions.
Manufacturer's Letter: http://www.fda.gov/medwatch/safety/2000/propul.htm
FDA Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS00999.html

FDA Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS01007.html

Cyclosporine
(SangCya)

August 2000 A study in healthy volunteers has identified that SangCya is not bioequivalent to Neoral oral solution when mixed with apple juice. SangStat has voluntarily withdrawn the product (Class II recall action).
Manufacturer's Letter: http://www.fda.gov/medwatch/safety/2000/sangcy.htm

Didanosine
(Videx)

August 2000 The results of a recently completed clinical trial demonstrated that the 48-week virologic response of didanosine once daily was significantly lower than observed in the comparator arm. Therefore, the preferred dosing frequency of didanosine is twice-daily because there is more evidence to support the effectiveness of this dosing frequency.
Manufacturer's Letter http://www.fda.gov/medwatch/safety/2000/videx.htm

Divalproex
(Depakote)

July 2000 Abbott Labs notified health professionals regarding revised warnings of life-threatening and fatal pancreatitis associated with divalproex. Symptoms may rapidly progress to death.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/depako.htm

April 2000 Genentech recalled several lots of inhalation solutions based upon a potential packaging defect possibly resulting in ampule leakage.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/pulmoz.htm

March 2000 Amgen notified health professionals of bacteremia or pyrogenic reactions, which occurred in a dialysis unit after pooling of unused portions from single use (preservative free) vials for use in other patients.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/epogen.pdf

May 2000 Immunex and Wyeth-Ayerst encouraged health care professionals to properly instruct patients regarding product preparation to reduce patient difficulties with needle damage during vial stopper penetration.
Manufacturer's letter: http://www.fda.gov/medwatch/safety/2000/enbrel.htm

Jan 2000: Roche Labs notified health professionals regarding the revision of product labeling to reflect the risk of QT interval prolongation, ventricular tachycardia, and/or torsades de pointes, based on a recent trial in children undergoing outpatient dental surgery. Several revisions have occurred in the Contraindications, Warnings, Precautions, Adverse Reactions, Overdoses, and Dosing sections.
Manufacturer's letter http://www.fda.gov/medwatch/safety/2000/floxur.htm

March 2000: Wyeth-Ayerst Labs notified health professionals regarding the unavailability of floxuridine due to manufacturing issues.
Manufacturer's letter: http://www.fda.gov/medwatch/safety/2000/fluoth.htm

June 2000: InterMune Pharmaceuticals notified health professionals regarding a change in the potency determination of interferon gamma-1b from units to International Units. These changes did not affect the strength of the product.
Manufacturer's letter: http://www.fda.gov/medwatch/safety/2000/actimm.htm

June 2000 Glaxo Wellcome cautioned health professionals, especially pharmacists, regarding the potential for a dispensing error with lamotrigine (Lamictal) and terbinafine (Lamisil) because of similar brand names. Clinicians are encouraged to review the indications, appearance and dosages of both products to avoid medication errors.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/lamict.htm

March 2000 Smith Kline Beecham announced a change in the manufacturing site for Eskalith CR 450 mg tablets which does not effect bioequivalency. However, long term stability data is not available and requires prescription limits of 30 days.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/eskali.htm

Misoprostol
(Cytotec)

August 2000 Searle reminded health professionals that misoprostol administration in pregnant women is contraindicated due to abortificiant properties. Off-label use has been associated with several serious events including, but not limited to, maternal/fetal death, uterine hyperstimulation, rupture or perforation, severe vaginal bleeding, and/or retained placenta.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/cytote.htm

Feb 2000 Wyeth-Lederle notified health professionals of changes in storage conditions for the live poliovirus vaccine requiring storage in freezer (below 32^oF) for maximum shelf life. It is now recommended that the product be removed from the freezer immediately prior to use and thawed completely prior to administration.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/orimun.htm

Rabies Vaccine
(IMOVAX)

July 2000 Lot numbers P0313-3, P0030-2, and N1204-2 were recalled due to possible reduction in potency 24 months after manufacturing. Patients who were vaccinated with one of these lots for pre-exposure prophylaxis, and who remain at risk for rabies exposure, should either be tested for antibodies or be revaccinated.
Manufacturer Letter: http://www.fda.gov/cber/fprecalls/rabvac072800.htm

Jan 2000 Cangene Corp notified health professionals of reports of acute intravascular hemolysis (IVH) after Rh_oD Immune Globulin in D-positive patients with immune thrombocytopenic purpura (ITP). Possible cases of IVH have also occurred in other patients treated for ITP.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/winrho.html

Sodium Citrate
(triCitrasol)

April 2000 The FDA warned hospital pharmacies and hemodialysis units that this unapproved product, used to keep bloodlines open, may cause death when infused into patients. The FDA received a report of fatal cardiac arrest shortly after undiluted triCitrasol was infused into a hemodialysis permanent blood access catheter. Rapid/excessive infusion of citrate solutions can cause fatal heart rhythm disruption, seizures or bleeding due to loss of blood calcium.
FDA Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS01009.html

Feb 2000 The FDA notified health professionals regarding a significant drug interaction between St. John’s wort and indinavir. Indinavir plasma concentrations were reduced via cytochrome P450 inhibition by St. John’s wort. Based on this information, the concurrent use of St. John’s wort with other protease inhibitors or nonnuclesoide reverse transcriptase inhibitors is not recommended.
FDA Announcement: http://www.fda.gov/cder/drug/advisory/stjwort.htm

July 2000 Novartis notified health professionals regarding revisions in product labeling concerning dose related QTc interval prolongation. Based on this data, thioridazine is indicated only for schizophrenics who are refractory to other antipsychotics and is contraindicated with drugs known to prolong the QTc interval or inhibit cytochrome P450 2D6. Prior to therapy initiation, patients should have QTc interval < 450 milliseconds and normal values for ECG and serum potassium.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/mellar.htm

May 2000 Genentech notified health professionals regarding revisions in product labeling concerning reports of serious adverse events including, hypersensitivity, infusion and pulmonary reactions. In the majority of patients, reactions occurred after the first dose, during infusion or within 12 hours after the first infusion. Most fatal events occurred in patients with pre-existing pulmonary conditions.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/hercep.htm

March 2000 The FDA and Parke-Davis/Warner Lambert announced the market withdrawal of troglitazone based on postmarketing surveillance reports of severe liver toxicity.
FDA Announcement: http://www.fda.gov/bbs/topics/NEWS/NEW00721.html

Jan 2000: The FDA reminded health professionals regarding the safe and appropriate use of influenza drugs and that vaccination remains the primary method of prevention and control of influenza. In addition, caution was advised when prescribing zanamivir to COPD patients based on several postmarketing surveillance reports of respiratory deterioration after zanamivir inhalation
FDA Announcement: http://www.fda.gov/cder/drug/advisory/influenza.htm

July 2000 Glaxo Wellcome advised health professionals of revised product labeling including new warnings recommending that zanamivir should not be used as treatment in patients with underlying airway disease (e.g., COPD, asthma) due to reports of bronchospasm and respiratory decline. In addition, the FDA pregnancy category for this drug has been changed from B to C.
Manufacturer Letter: http://www.fda.gov/medwatch/safety/2000/relenz.htm