Arthritis Drug May Cause Severe Reaction,
WebMDHealth.com, November 15, 2002, by Lisa Habib WebMD Medical News.  Since Bextra was introduced in March, Pharmacia, Bextra's manufacturer, has reported to the FDA serious and life-threatening skin and hypersensitivity reactions to the drug. These include cases of Stevens-Johnson syndrome, a rare and potentially deadly disorder characterized by inflammation of the mucous membranes of the mouth, throat, genitals, intestinal tract, and membrane lining the eyelids, which can lead to lesions and blisters.

FDA, PHARMACIA UPDATE BEXTRA LABEL WITH NEW WARNINGS
FDA and Pharmacia are advising health care professionals about new warnings and information in the product labeling of the drug Bextra (valdecoxib), a drug approved for treatment of osteoarthritis, rheumatoid arthritis and dysmenorrhea (menstrual pain). The labeling is being updated with new warnings following postmarketing reports of serious adverse effects including life-threatening risks related to skin reactions -- including Stevens Johnson Syndrome, and anaphylactoid reactions (serious allergic reactions). In addition, the labeling will state that the drug is contraindicated -- not to be used -- in patients allergic to sulfa containing products.
 

Friedman B, Orlet HK, Still JM, Law E.  Toxic epidermal necrolysis due to administration of celecoxib (Celebrex).  South Med J. 2002 Oct;95(10):1213-4.PMID: 12425513 [PubMed - indexed for MEDLINE]

Celebrex Web Site, Pharmacia Corp.
 

Celebrex Consumer Information, US Food and Drug Administration, Center for Drug Evaluation and Research
 

You and A: Arthritis Drugs, Washingtonpost.com, September 4, 2001
 

Safety of Arthritis Drugs in Question, WebMD, July 10, 2001
FDA Panel Rejects Celebrex's Marketing Request, USATODAY.com, February 8, 2001
 

Warning Letter to Pharmacia Corp. from US Food and Drug Administration, re: Celebrex (Celecoxib) Capsules (PDF), February 1, 2001
 

Marketing Rx, A NewsHour with Jim Leher Transcript, December 26, 2000
 

FDA Approves Celebrex for New Indication, US Food and Drug Administration, December 23, 1999
 

Approval Package: Celebrex (Celecoxib) Capsules, US Food and Drug Administration, Center for Drug Evaluation and Research, Application No. 21-156 & 20998/S007, Approval Date: December 23, 1999
 

FDA Approves First Drug in New Class of Painkillers, CNN.com, December 31, 1998
 

FDA Approves Celebrex for Arthritis, US Food and Drug Administration, December 31, 1998
 

Approval Package: Celebrex (Celecoxib) Capsules, US Food and Drug Administration, Center for Drug Evaluation and Research, Application No. 20-998, Approval Date: December 31, 1998

Parents of stricken girl sue makers of Children's Motrin SARATOGA PAIR CLAIM MEDICINE LEFT 9-YEAR-OLD UNABLE TO SEE, SPEAK, EAT
By Linda Goldston   Mercury News
The parents of a 9-year-old Saratoga girl have sued the makers of Children's Motrin, claiming the flu and pain medication caused the extreme allergic reaction that left their daughter, Kaitlyn Langstaff, unable to see, speak or eat. The lawsuit filed in U.S. District Court in San Jose also alleges that the manufacturer of the drug failed to adequately test it for over-the-counter use with children and failed to warn the public of potentially fatal reactions to Children's Motrin.

Children's Motrin (Ibuprofen) Oral Suspension, Junior Strength Motrin Chewable Tablet, Junior Strength Motrin Tablets & Drops, Company: McNeil Consumer Products Company
Application No.: 20-516/S4, 20-601/S2, 20-602/S3 & 20-603/S2, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Approval Date: August 13, 1999

Clinical aspects of skin reactions to NSAIDs., PubMed, National Library of Medicine, Scand J Rheumatology Suppl 1987;65:131-4, J.C. Roujeau.  Service de Dermatologie et Departement d' Immunologie, Hospital Henri Mondor, Universite Paris XII, Creteil, France.

Oxaprozin-induced pseudoporphyria., PubMed, National Library of Medicine, Arch Dermatology 1996 Dec;132(12):1519-20, Ingrish G, Rietschel RL.

Case report: oxaprozin and fatal toxic epidermal necrolysis., PubMed, National Library of Medicine,  J Burn Care Rehabilitation 1998 Jul-Aug;19(4):321-3, Chester N. Paul, MD; David W.  Voigt, MD; Kurt E. Clyne, MD; Sean L.  Hansen, BS.  Burn and Wound Center, Saint Elizabeth Community Health Center, Lincoln, Nebraska 68510, USA.

A case of Stevens-Johnson syndrome associated with oxaprozin therapy., PubMed, National Library of Medicine, The Journal of  Rheumatology 1998 Oct;25(10):2026-8, Mary J. Bell, MD, FRCPC, Assistant Professor, Division of Rheumatology, Faculty of Medicine, Research Scientist, Arthritis Community Research and Evaluation Unit and Laila D. Bishara, MD, Resident in General Internal Medicine, University of Toronto.   Department of Medicine, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.

Toxic epidermal necrolysis following treatment with oxaprozin., PubMed, National Library of Medicine, International Journal of Dermatology 1999 Mar;38(3):233-4, Carucci JA, Cohen DE.

February Arthritis Drugs Put a Hurt on Merck and Pfizer
The latest stock market action for both stocks appears to be a reaction to two articles published on line ahead of their inclusion in the Oct. 21 edition of the New England Journal of Medicine. In one editorial, Dr. Garret A. FitzGerald urged the Food and Drug Administration to examine all of the COX-2 drugs. FitzGerald is a medical researcher at the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania. "We must remember that the absence of evidence is not the evidence of absence," said FitzGerald, who has received consulting fees and research support from Merck.

Another New England Journal of Medicine article was written by a cardiologist, Dr. Eric J. Topol of the Cleveland Clinic, who has been a long-time critic of Vioxx. He called for a congressional investigation of the Vioxx approval process and the relationship between Merck and the Food and Drug Administration. "The senior executives at Merck and the leadership at the FDA share responsibility for not having taken appropriate action and not recognizing that they are accountable for public health," he charged.

February  Safety of All Cox-2 Drugs Questioned
FRIDAY, Oct. 8 (HealthDayNews) -- A week after drug giant Merck & Co. withdrew its arthritis drug Vioxx from the market, doubts are being raised about the safety of the two other approved medications in this class, Bextra and Celebrex.

In an article released Thursday by the New England Journal of Medicine, an expert with a long history of research in the cox-2 inhibitor class of medications said cardiovascular problems seen with Vioxx may yet surface with the other two drugs.

The problem, said Dr. Garrett A. FitzGerald, is that all cox-2 inhibitors suppress the production of a heart-protecting fat called prostaglandin I2.
"Vioxx, Celebrex and Bextra all have the same effect on this biochemical system. Therefore, until proven otherwise, evidence would suggest that this mechanism would involve all drugs in this class," explained FitzGerald, who is chairman of pharmacology at the University of Pennsylvania's Institute of Translational Medicine and Therapeutics.

FDA -- U.S. Department of Health & Human Services Dangerous Prescription
Watch the Full Program Online 
A look inside the FDA, its recent record, and
the debate over whether our nation's drug safety
system is broken.
Plus, FAQs and links for consumers.
 

FDA -- U.S. Department of Health & Human Services Dangerous Prescription
Watch the Full Program Online 
A look inside the FDA, its recent record, and
the debate over whether our nation's drug safety
system is broken.
Plus, FAQs and links for consumers.
 

Information about the Products the FDA Regulates
 

FDA's counsel accused of being too close to drug industry Daniel Troy, chief counsel to the US Food and Drug Administration, is under fire for inviting drug companies to inform him of lawsuits against them so the FDA could help in their defense.  Jeanne Lenzer New York  BMJ 2004;329:189 (24 July), doi:10.1136/bmj.329.7459.189;  Produced by BMJ Publishing Group Ltd of the BMA, assisted by Stanford University's HighWire Press.
 

February  FDA drug monitoring system probed
WASHINGTON (CBS.MW)-- The U.S Food and Drug Administration said on Friday that it has asked the Institute of Medicine to review how FDA monitors drugs after they hit the market.

February Why Drugs Need a Longer Look
The Vioxx fiasco signals the need for a returned FDA approval system, one that tracks more than short-term risks and side effects
Consumers can be excused if the Cox 2 painkiller debacle has left them scratching their heads. First, Merck (MRK ) pulled its Vioxx off the market after a study confirmed suspicions that it was linked to an increased risk of heart attack and stroke. Then, after rival Pfizer (PFE ) announced its Cox 2 Bextra drug also showed a higher risk of heart attack and stroke in patients who had just undergone a certain kind of heart surgery.
February New Worries About Drug Safety
NEW YORK - An internal survey conducted by the Food and Drug Administration (FDA) indicates that 66% of FDA scientists lacked confidence that the agency adequately monitors the safety of prescription drugs that are already on the market.

Arthritis Drugs Advisory Committee Meetings,  PDF Part 1 (pages 1 thru 100) of the Food and Drug Administration, Center for Drug Evaluation and Research, August 17, 2001
 

Continued ... Arthritis Drugs Advisory Committee Meetings, PDF Part 2 (pages 1 thru 59) of the Food and Drug Administration, Center for Drug Evaluation and Research, August 17, 2001
 

Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open-label study., PubMed, National Library of Medicine, Rheumatology (Oxford) 2002 Jun;41(6):631-7, Kiely PD, Johnson DM., Department of Rheumatology, St George's Healthcare NHS Trust, Blackshaw Road, London SW17 0QT, UK.

WHAT ARE NSAIDS?
NSAIDs, also called non-steroidal anti-inflammatory drugs, are medications used to reduce pain and swelling. About 20 are available with a prescription, and three are available over-the- counter. These include ibuprofen, naproxen and ketoprofen. The only difference between the over-the- counter and prescription versions is that the latter is available in higher dosages. Some examples of NSAIDs are Advil, Motrin, Aleve, Bayer, and Excedrin. NSAIDs can also be found in cold medications like Advil Cold and Sinus, Dimetapp Sinus, Motrin IB Sinus and Aleve Cold and Sinus. Acetaminophen, also sold as Tylenol, is not a NSAIDs.

Dilantin

WebMD

Forums.webmd.com/3/epilepsy-exchange

First timer here--question about Dilantin dose and side effects Calvin_and_Hobbes_Fan posted: Glad to have found this virtual community!

It's informative and reassuring on many levels. I'm not sure what the etiquette is here (details, length, etc.), but here is my story and question.

A couple of days after hitting my head I had a major seizure; I was put on Dilantin and have some continuing side effects. I won't bore you with details, but I have some short-term memory issues, occasional language problems (e.g., word substitutions when speaking), vivid dreams that wake me up, sore gums, and neuropathy and pain in the feet.

are all new symptoms for me. I've seen two neurologists. The only side effects of Dilantin they seem to recognize are strabismus, speech slurring, and staggering.

Only if those are pronounced, do they think action is necessary and then they advocate switching drugs. It's as if the drug acted via a threshold—all or nothing

It controls seizures and you have to live with the side effects; otherwise you should switch drugs. If the blood level of Dilantin is between 10 and 20 (preferably on the higher side), and you're not having seizures, then the dosage is fine.

doesn't make sense to me. I would think that a reduced dose could still control seizures and yet reduce side effects. But I'm not a doctor or a scientist.

My blood level of Dilantin has been fluctuating between 15 and 22. I'd like to see what would happen to the side effects if it were more like 10-15. (OTOH, I certainly don't want to risk another seizure or put my family through that again.)

So, here is my question:

. Did any of your neurologists sanction a dose reduction to control side effects—or did you have to switch drugs? And, for the resident neurologist,

2. Does Dilantin work in an all-or-nothing fashion?

Rising Prescription Drug Use Corresponds to Increase in Stevens Johnson Syndrome; SJS Foundation Issues

Warning Signs

Bextra Label Updated with Boxed Warning Concerning Severe Skin Reactions
With more than 40 percent of Americans taking at least one prescription drug (2004 CDC report), the potential for the deadly adverse drug reaction known as Stevens Johnson Syndrome (SJS) is increasing.

Described in many drug warning inserts as a "serious skin condition," SJS is actually a devastating reaction affecting the skin and mucous membranes, causing severe burning, blistering and sloughing of involved tissue. SJS commonly causes blindness and results in death in 10 to 30 percent of the cases.

An under-reported and under-recognized condition, people develop SJS from commonly prescribed drugs, including antibiotics, anti-convulsants,and non-steroidal inflammatory drugs (NSAIDS), including over-the-counter drugs such as adult and children ibuprofen products. Because many physicians and emergency facilities are not familiar with the symptoms, treatment is frequently delayed, further exacerbating the condition.

To recognize SJS in its earliest stage, the SJS foundation urges patients and physicians to watch for the following symptoms when taking medications:

-- Persistent fever
-- Burning or blistering of the mucous membranes, i.e.: eyes, ears, mouth, nose, genital area.
-- Rash, blisters or red splotches on skin
-- Flu-like symptoms
-- History of a reaction to prescribed drugs or over-the-counter medications.

In one estimate, SJS is reported to effect three to eight people per million per year in the U.S. However, the frequency could be much higher since only one percent of adverse drug reactions is reported, according to the Food and Drug Administration.

"SJS is not as rare as we are led to believe," said Jean McCawley, president of the SJS Foundation. "As prescription drug use increases, we are being contacted by increasing numbers of people. During the winter months, we learn of 15 new cases a week, and that's only people with Internet access."

About SJS Foundation

Founded in 1995, the Stevens Johnson Syndrome Foundation (Julie Foundation for allergic drug reactions) is a non-profit organization that provides information and support for victims, educates the medical community and encourages research in preventing adverse drug reactions. More information is available at www.sjsupport.org

Healing Well New Treatment for Acute Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are moderate and severe variations of the same adverse reaction (usually to drugs or mycoplasma pneumonia) which result in blistering and sloughing of skin and mucosal membranes, and carry a high risk of mortality
 

Stevens-Johnson syndrome plus toxic hepatitis due to ibuprofen, PubMed, National Library of Medicine, New York State Journal of Medicine July;78(8):1239-43, Sternlieb P, Robinson RM.  Nassau Hospital, Mineola, New York
 

Introital adenosis associated with Stevens-Johnson syndrome, PubMed, National Library of Medicine, Obstet Gynecol 1985 Jul;66(1):143-5, Marquette GP, Su B, Woodruff JD.
A 23-year-old woman presented with vulvar pain and dyspareunia 1.5 years after a Stevens-Johnson syndrome. A red friable lesion was identified at the vestibule and lower third of the vagina. The histologic diagnosis was adenosis with a tubal glandular epithelium. The possible histogenesis of this lesion is discussed with a review of the embryology of the lower genital tract.
 

Rehabilitative considerations for patients with severe Stevens-Johnson syndrome or toxic epidermal necrolysis. A case report.  PubMed, National Library of Medicine, J Burn Care Rehabil 1989 -Apr;10(2):167-71, K. McDonald, PT, B. Johnson, PT, J.K. Prasad, MD, and P. D. Thomas, PhD.  University of Michigan Medical Center, Physical Therapy Division, Ann Arbor 48109-0046.

Vitamin A in Stevens-Johnson Syndrome, PubMed, National Library of Medicine, Ann Ophthalmol 1989 Jun;21(6):209-10, Singer L, Brook U, Romem M, Fried D., Department of Ophthalmology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
 

Unusual manifestation of Stevens-Johnson syndrome involving the respiratory and gastrointestinal tract., PubMed, National Library of Medicine, Pediatrics 1992 Mar;89(3):429-32, Dean S. Edell, MD MPH; James J. Davidson; Andre A. Muelenaer, MD; Marc Majure, MD; Department of Pediatric Pulmonary, Duke University School of Medicine, Durham, NC.

Neuropathy in burn patients.>, PubMed, National Library of Medicine, Brain 1993 Apr;116 ( Pt 2):471-83, Sean Marquez; J. Jean E. Turley; Walter J. Peters; Department of Medicine, Division of Neurology and the Department of Surgery, Division of Plastic Surgery, Wellesley Hospital, Toronto, Canada.

Burn-associated peripheral polyneuropathy. A search for causative factors. PubMed, National Library of Medicine, American Journal Physical Medicine Rehabilitation 1995 Jan-Feb;74(1):28-32, Anthony J. Margherita, MD; Lawrence R. Robinson,MD; David M.Heimbach, MD; Vicki L. Fishfader,BS; Vicki A. Schneider, MS;  Dana Jones,BS.  Department of Rehabilitation Medicine, Harborview Medical Center/University of Washington School of Medicine, Seattle 98195.

Analysis of the Acute Ophthalmic Manifestations of the Erythema Multiforme/Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Disease Spectrum., PubMed, National Library of Medicine, Ophthalmology 1995 Nov;102(11):1669-76, William J. Power, FRCS, FRCOphth;  Mohammed Ghoraishi, MD;  Jesus Merayo-Lloves, MD;   Renato A. Neves, MD;  C. Stephen Foster, MD, FACS.  Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston 02114, USA.  Presented at the American Academy of Ophthalmology Annual Meeting.

Acute and Chronic Respiratory Complications of Toxic Epidermal Necrolysis., PubMed, National Library of Medicine, J Burn Care Rehabilitation 1996 May-Jun;17(3):237-40, R.A. McIvor, MD;  J. Zaidi, MD;  W. J. Peters, MD;  R.H.Hyland, MD.  Division of Respirology, University of Toronto, and the Ross Tilley Burn Centre, Wellesley Hospital, Toronto, Ontario, Canada.

Bronchiolitis obliterans in children with Stevens-Johnson syndrome: follow-up with high resolution CT. , PubMed, National Library of Medicine, Pediatrics Radiology 1996;26(1):22-5, M.J. Kim and K.Y. Lee.  Department of Diagnostic Radiology, Severance Hospital, 134 Seodaemoon-gu, Shinchon-dong, Seoul 120-752, Korea.

Vulvovaginal sequelae in toxic epidermal necrolysis., PubMed, National Library of Medicine, The Journal of Reproductive Medicine 1997 Mar;42(3):153-6, Eric Meneux, MD;  Bernard J. Paniel,MD; Florence Pouget,MD;  Jean Revuz,MD;  Jean-Claude Roujeau, MD;  Pierre Wolkenstein, MD.  Department of Gynecology, Centre Hopitalier Intercommunal, and the Department of Dermatology, Hospital Henri Mondor, Creteil, France.

Drug-associated acute-onset vanishing bile duct and Stevens-Johnson syndromes in a child.  PubMed, Srivastava M, Perez-Atayde A, Jonas MM.  Combined Program in Gastroenterology, Department of Medicine, Children's Hospital, Boston, Massachusetts, USA., Gastroenterology. 1998 Sep;115(3):743-6.PMID: 9721172.

Esophageal Involvement in Stevens-Johnson Syndrome., PubMed, National Library of Medicine, Endoscopy 2001 Jun;33(6):550-3, Lamireau T, Leaute-Labreze C, Le Bail B, Taieb A., Division of Pediatric Gastroenterology, Children's Hospital, Bordeaux, France.

thierry.lamireau@chu-bordeaux.fr.  Division of Pediatric Dermatology, Children's Hospital, Bordeaux, France, Laboratory of Pathology, Pellegrin's Hospital, Bordeaux, France.

Neuropathy after burn injury., PubMed, National Library of Medicine, J Burn Care Rehabilitation 2001 Sep-Oct;22(5):353-7; discussion 352, K. Kowalske, MD;  R. Holavanahalli, PhD; P. Helm, MD.  Department of Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center at Dallas, 75390-9055, USA.

Stevens-Johnson Syndrome and Cholestatic Hepatitis., PubMed, National Library of Medicine, Digestive Diseases and Sciences, Vol. 46, No. 11 (November 2001):2385-8, Michael S. Morelli, MD and Francis X. O'Brien, MD.  Department of Internal Medicine, Section of General Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.

Intravenous ulinastatin therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis in pediatric patients. Three case reports., PubMed, National Library of Medicine, Int Arch Allergy Immunol 2002 Jan;127(1):89-94, Inamo Y, Okubo T, Wada M, Fuchigami S, Hashimoto K, Fuchigami T, Takahashi S, Sawada S, Harada K, Department of General Pediatrics, Nihon University Nerima-Hikarigaoka Hospital, Nihon University School of Medicine, Tokyo, Japan. y-inamo@pb3.so-net.ne.jp

Effect of high-dose intravenous immunoglobulin therapy in Stevens-Johnson syndrome, Dermatology. 2003;207(1):96-9.
PMID: 12835566 [PubMed - indexed for MEDLINE]; Prins C, Vittorio C, Padilla RS, Hunziker T, Itin P, Forster J, Brocker EB, Saurat JH, French LE.  BACKGROUND:Stevens-Johnson syndrome (SJS) is a severe cutaneous drug reaction associated with considerable morbidity, possible transition to toxic epidermal necrolysis (TEN) and death in certain cases.

Use of intravenous immunoglobulin in children with Stevens-Johnson syndrome and toxic epidermal necrolysis: seven cases and review of the literature, Pediatrics. 2003 Dec;112(6 Pt 1):1430-6. Review. PMID: 14654625 [PubMed - indexed for MEDLINE]; Metry DW, Jung P, Levy ML.;  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are the most severe cutaneous reactions that occur in children.
 

More Evidence: Vioxx Increases Heart RisksHigh Doses Linked With Heart Attacks, Sudden Cardiac Death. By Jeanie Lerche Davis WebMD Medical News Reviewed By Michael Smith, MD on Thursday, August 26, 2004
In a new study, patients taking higher doses of Vioxx (more than 25 mg daily) had triple the risk of heart problems, including heart attacks and sudden cardiac death.

EXPENSIVE arthritis pills have not lived up to the hype    According to published research and interviews with arthritis doctors and drug specialists. Vioxx, which may be better for the stomach, appears to have a far worse side effect than over-the-counter drugs: an increased risk of heart attacks    By Judy Foreman, Globe Columnist | July 27, 2004  

Painkiller Vioxx Often Taken at Too High Dose   Evidence continues to grow that the popular pain reliever Vioxx may cause high blood pressure, swelling, and other health problems.  July 14, 2004 --  WebMDHealth Reviewed By Michael Smith, MD

>Vioxx Web Site, Merck & Co.

Vioxx Consumer Information, US Food and Drug Administration, Center for Drug Evaluation and Research
Merck Tangles with FDA on Marketing, Forbes.com, September 25, 2001

You and A: Arthritis Drugs, Washingtonpost.com, September 4, 2001
Safety of Arthritis Drugs in Question, WebMD, July 10, 2001
Marketing Rx, A NewsHour with Jim Leher Transcript, December 26, 2000
Approval Package: Vioxx (Rofecoxib) Tablets, US Food and Drug Administration, Center for Drug Evaluation and Research