Access to new information regarding the safety profiles of old and newly marketed drugs is essential in optimizing patient care. Keeping abreast of these changes is of particular concern to the pharmacist. In 1999, several significant actions occurred in the United States, specifically drug market withdrawals and FDA notifications regarding significant changes to drug safety profiles. Part II summarizes important information posted on the FDA website after April 1999. Readers are encouraged to visit the particular website (specific URLs are provided) for more complete information.
Summary of Drug Market Withdrawals, Significant Drug Recalls and Changes in Drug Safety Profiles in the United States: May 1999 to December 1999 |
|
| Albuterol Inhaler | Sept 1999 A
single lot of albuterol metered dose inhaler aerosol 17 gm container was recalled after
one patient returned an inhaler that did not contain drug substance. The lot recalled was
No. 9-BBS-525 distributed by Warrick Pharmaceuticals. FDA Announcement: http://www.fda.gov/medwatch/safety/1999/albute.html |
| Astemizole (Hismanal) |
June 1999 Janssen
Pharmaceuticals notified health professionals and the FDA that astemizole was
voluntarily withdrawn from the United States market based on numerous drug interactions
and the availability of other alternatives in the same class. FDA Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS00961.html Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/hisman.htm |
| Beclomethasone (Vanceril) |
Dec 1999
Schering/Key recalled several lots of double strength (84 mcg) inhalation aerosol
canisters based upon the potential that a small number of canisters did not contain active
drug. Batch numbers included 9-DMT-157, -158, -160, -161 and –163. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/vancer1.htm |
| Capecitabine (Xeloda) |
June 1999 Roche
Laboratories cautioned all health professionals regarding the potential for a dispensing
error with orlistat (Xenical) and capecitabine (Xeloda) because of similar brand names.
Clinicians are encouraged to review the indications, appearance and dosages of both
products to avoid med errors. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/xenxel.pdf |
| Celecoxib (Celebrex) |
May 1999: Searle
and Pfizer notified health professionals of a new addition to product labeling under the
precaution heading regarding a significant interaction between celecoxib and warfarin.
This change was based on postmarketing reports of bleeding events, primarily in the
elderly, taking concurrent therapy. Anticoagulant monitoring is recommended, particularly
in the first few days after starting or changing the dose of celecoxib in patients also on
warfarin. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/celebr.htm FDA Announcement:http://www.fda.gov/cder/news/celebrex/qandas.htm |
| Cisapride (Propulsid) |
June 1999 Health
professionals were notified of two new contraindications (known family history of
congenital long QT syndrome and clinically significant bradycardia) added to the
contraindication and black box warning section of cisapride’s product labeling. In
addition, the coadministration of grapefruit juice and cisapride should be avoided based
on a kinetic study in healthy volunteers which demonstrated a significant increase in the
bioavailability of cisapride. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/propul.htm |
| Didanosine (Videx) |
Nov 1999 Bristol
Myers Squibb notified health professionals regarding revised warnings of fatal and
nonfatal pancreatitis associated with didanosine when used alone or in combination with
stavudine with or without hydroxyurea. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/videx.html |
| Ethanercept (Enbrel) |
May 1999 The FDA
and Immunex notified health care professionals regarding new postmarketing reports of
serious infections (including sepsis) associated with the use of ethanercept (Enbrel), a
recently marketed agent for moderate to severe rheumatoid arthritis. When initially
approved, labeling indicated that this drug should not be used in patients with sepsis and
discontinued if patient developed a serious infection. New labeling recommends that the
drug should not be started in patients with active infections and should be used with
caution in patients with history of recurring infections or predisposition to infections.
Since its approval in 11/98, ~30 of 25,00 treated patients have developed serious
infections (including sepsis) with six patients who died. Manufacturer's letter: http://www.fda.gov/medwatch/safety/1999/enbrel.htm FDA Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS00954.html |
| Flutamide (Eulexin) |
Sept 199: The FDA
and manufacturer notified health professionals regarding the addition of a boxed warning
of liver toxicity for patients taking flutamide. These changes were based on
post-marketing reports of hospitalization and rare deaths associated with liver failure
during flutamide therapy, typically within the first three months after therapy was
started. New recommendations include liver function monitoring at baseline (prior to
therapy), monthly for the first four months of therapy and periodically thereafter.
Flutamide therapy should be stopped or not started in patients with ALT values exceeding
twice the normal limits. Manufacturer's letter: http://www.fda.gov/medwatch/safety/1999/eulexi.htm |
| Gamma- Butryolactone |
May 1999 The FDA
warned the public regarding a new group of products, marketed as sleep aids, that have
been associated with at least three deaths and 122 reports of severe adverse reactions.
These products are chemically related to gamma butyrolactone (GBL) and gamma
hydroxybutryic acid (GHB). The FDA considers these products unapproved new drugs. FDA Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS00953.html |
| Grepafloxacin (Raxar) |
Nov 1999 The FDA
and Glaxo Wellcome announced that grepafloxacin was withdrawn from the US market based on
a small number of severe cardiovascular events possibly associated with its use. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/raxar.pdf |
| HIV Rapid Home Use Test
Kit (EZ Med Test) |
July 1999 The FDA
alerted health professionals and consumers regarding a FDA reviewed but unapproved HIV
home use testing kit which is sold over the Internet. The product was not approved due to
false negative results . FDA Announcement:http://www.fda.gov/medwatch/safety/1999/ezmedt.html |
| Immune Globulin – Intravenous (IVIG) | June 1999 A
MMWR publication reviewed 88 cases of renal insufficiency and failure associated with IVIG
therapy (1985-1998) with approximately 40% of patients requiring dialysis. High risk
patients for renal events during IVIG therapy include pre-existing renal disease,
diabetes, hypovolemia, sepsis, concomitant therapy with nephrotoxic agents, and those >
65 yrs. MMWR publication: http://www.cdc.gov/epo/mmwr/preview/mmwrhtml.mm4824A3.htm Sept 1999 The FDA recommended safety precautions to reduce the
potential risk of acute renal failure associated with IVIG including, ensuring normal
volume prior to administration, caution in patients with risk factors, using recommended
dosages, monitoring renal function and advising patients of symptoms suggestive of renal
failure. See specific guidelines at |
| Methotrexate (Rheumatrex) |
June 1999 Health
professionals were notified of new warnings including an increased risk of bone and soft
tissue necrosis after radiation therapy in patients taking methotrexate. In addition,
precautions included the potential development of painful plaque erosions when
methotrexate is used for psoriasis. The risk of hepatotoxicity may also be increased when
given with other hepatotoxic drugs. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/methot.htm |
| Nevirapine (Viramune) |
July 1999
Boehringer Ingelheim notified health professionals of an interaction between nevirapine
and methadone, possibly precipitating narcotic withdrawal syndrome because of decreased
methadone hepatic metabolism. The methadone dose may need to be increased when given
concurrently with nevirapine. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/viramu.htm |
| Pemoline (Cylert) |
June 1999: The FDA
notified health professionals regarding updated recommendations for liver function
monitoring and a patient Information/Consent Form with pemoline. Recommendations in the
black box warnings section of the package insert include: serum ALT (SGPT) determined at
baseline and every two weeks thereafter. The agent should be discontinued if clinical
signs of hepatic failure appear, if ALT values increase to clinically significant levels
or > 2 times upper limit of normal. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/cylert.htm Patient Consent Form: http://www.fda.gov/medwatch/safety/1999/cylertpi.htm |
| Pimozide (Orap) |
Sept 1999: The FDA
and Gate Pharmaceuticals notified health professionals of unexpected sudden deaths
possibly associated with high doses of pimozide (greater than 10 mg). A suggested
mechanism may be QT prolongation causing ventricular arrhythmias. Two sudden deaths were
reported after clarithromycin was added to high dose pimozide therapy. Because pimozide is
metabolized by cytochrome P450 3A, inhibitors of this isoenzyme system are NOW
CONTRAINDICATED with pimozide, including macrolides (clarithromycin, erythromycin), azole
antifungals (itraconazole, ketoconazole), protease inhibitors, nefazodone, and zileuton.
Patients should also be advised to avoid grapefruit juice. CYP 1A2 inhibitors may also
contribute to the metabolism of pimozide and inhibitors of this system should be avoided. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/orap.pdf |
| Pramipexole (Mirapax) |
Sept 1999: The FDA
and Pharmcia/Upjohn released an advisory regarding new safety information about
pramipexole, a dopamine agonist used to treat Parkinson's. Although somnolence is a
recognized side effect of this drug, instances of falling asleep without warning signs or
pre-existing excessive drowsiness have been reported, and in some cases have caused
automobile accidents. Some events have occurred as late as one year post treatment
initiation. Although general drowsiness may lessen with dose reduction, it is not known if
sudden sleep is dose related. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/mirape.htm |
| Rotavirus Vaccine (Rotashield) | July 1999:
The FDA announced a published report regarding 15 cases of intussusception among
infants who received the rhesus-based rotavirus vaccine (RotaShield) during Sept 1, 1998
to July 7, 1999. Of these reports 13 developed intussusception after the first dose of the
three dose series and 12 developed developed symptoms within one week of receiving any
dose. 13 also received other vaccinations concurrently. The CDC recommends postponing
administration of RotaShield to children scheduled to receive the vaccine before Nov 1999,
including those who have already begun the RotaShield series. CDC Announcement:http://www.cdc.gov/od/oc/media/pressrel/r990715.htm Oct 1999: Vaccine market withdrawal due to temporal
association between vaccine and the development of intussusception. |
| Thimerosal in Vaccines | July 1999 A joint
statement from the American Academy of Pediatrics (AAP) and Public Health Service (PHS)
was release regarding the thimerosal content in vaccines and the unacceptable cumulative
exposure to mercury in infants receiving recommended vaccinations. These groups with
vaccine manufacturers agreed to replace current thimerosal containing vaccines with
non-thimerosal products. MMWR publication: http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/mm4826a3.htm |
| Troglitazone (Rezulin) |
June 1999 The
FDA and manufacturer announced important changes in troglitazone labeling based on new
safety information (further evidence of sometimes fatal liver injury). Troglitazone is no
longer indicated for initial single agent therapy. Patients taking this product need to
have baseline liver tests performed prior to initiation of therapy, monthly during the
first year of therapy and quarterly thereafter. In addition, a new patient information
sheet will be available for distribution with EACH prescription dispensed. A new
indication will be added to labeling for use in combination with sulfonylureas and
metformin in patients who are not controlled with the combined use of these drugs. Manufacturer Letter: http://www.fda.gov/medwatch/safety/1999/rezuhp.htm FDA Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS00960.html New Patient Information: http://www.fda.gov/medwatch/safety/1999/safety99.htm#rezuhp |
| Trovafloxacin (Trovan) |
June 1999:
The FDA published a public health advisory regarding the risks of liver toxicity with
trovafloxacin (oral) and alatrovafloxacin (IV) based on several reports of rare severe
liver injuries leading to transplants and deaths. The FDA is recommending that Trovan be
used only in patients who meet the following criteria: 1)patients who have at least one of
several specified infections (hospital acquired), that are life or limb threatening, 2)
patients who begin therapy in inpatient health care facilities, or 3) even with new safety
announcements the benefit outweighs risk. In addition, the FDA is recommending that duration of therapy should not be longer than 14 days and should be discontinued if the patient exhibits signs of liver dysfunction. The FDA is advising that Trovan therapy will most likely begin as intravenous with oral follow-up. They are also emphasizing that oral therapy is not warranted for infections other than those specified. The manufacturer will be limiting distribution of product to hospitals and long term care facilities. See the following for more information: |
| Urokinase (Abbokinase)
|
July 1999: On
July 16, 1999, the FDA notified health professionals about the specifics of the
manufacturing deficiencies related to urokinase production processes, particularly
screening and testing of the mothers and donors of the human kidney cells used to produce
urokinase. FDA Update Announcement: http://www.fda.gov/bbs/topics/ANSWERS/ANS00964.html |
