Prescription Drug Spending per Person: Insurance or Government Health Program Versus Out-of-Pocket Costs, 2004–19

Prescription Drug Spending per Person, 2004–19*

*Data from Switzerland and the United Kingdom were not available for 2004–09.

Baycol (Cerivastatin)

Date of Approval: 1998

Date of Removal: August 2001

Manufacturer: Bayer A.G.

Medical Use: cholesterol reduction

Cause for Recall: rhabdomyolysis (breakdown of muscle fibers that results in myoglobin being released into the bloodstream), which led to kidney failure. The drug caused 52 deaths (31 in the U.S.) worldwide and 385 nonfatal cases, with most requiring hospitalization. Of those deaths, 12 were related to taking this drug in combination with gemfibrozil (Lopid). [85]

Belviq, Belviq XR (Lorcaserin)

Date of Approval: 2012

Date of Removal: February 13, 2020

Manufacturer: Eisai Inc.

Medical Use: weight loss

Cause for Recall: potential cancer risk. The FDA stated, “We are taking this action because we believe that the risks of lorcaserin outweigh its benefits based on our completed review of results from a randomized clinical trial assessing safety.” [68] [80]

Bextra (Valdecoxib)

Date of Approval: November 1, 2001

Date of Removal: April 7, 2005

Manufacturer: G.D. Searle & Co.

Medical Use: NSAID (pain relief)

Cause for Recall: serious cardiovascular adverse events (such as death, MI, stroke); increased risk of serious skin reactions (such as toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme); gastrointestinal bleeding. The FDA determined that Bextra showed no advantage over other NSAID pain relievers on the market. [72]

Cylert (Pemoline)

Date of Approval: 1975

Date of Removal: October 2010

Manufacturer: Abbott Laboratories

Medical Use: central nervous system stimulant to treat ADHD/ADD

Cause for Recall: liver toxicity. The FDA added a box warning to Cylert in 1999, alerting doctors and patients to the potential of liver damage, which prompted the manufacturer to stop production of the drug. [49] [71]

Darvon & Darvocet (Propoxyphene)

Date of Approval: 1955

Date of Removal: November 19, 2010

Manufacturer: Xanodyne

Medical Use: opioid pain reliever

Cause for Recall: serious toxicity to the heart; between 1981 and 1999 there were more than 2,110 deaths reported. The U.K. banned Darvon & Darvocet in 2005. The FDA was petitioned in 1978 and again in 2006 to ban the drug by the group Public Citizen. [74] [91] [101]

DBI (Phenformin)

Date of Approval: 1959

Date of Removal: November 1978

Manufacturer: Ciba-Geigy

Medical Use: antidiabetic

Cause for Recall: lactic acidosis (low pH in body tissues and blood and a buildup of lactate) in patients with diabetes

DES (Diethylstibestrol)

Date of Approval: 1940

Date of Removal: 1971

Manufacturer: Grant Chemical Co.

Medical Use: synthetic estrogen to prevent miscarriage, premature labor, and other pregnancy complications

Cause for Recall: clear cell adenocarcinoma (cancer of the cervix and vagina), birth defects, and other developmental abnormalities in children born to women who took the drug while pregnant; increased risk of breast cancer, higher risk of death from breast cancer; risk of cancer in children of mothers taking the drug, including raised risk of breast cancer after age 40; increased risk of fertility and pregnancy complications, early menopause, testicular abnormalities; potential risks for third-generation children (the grandchildren of women who took the drug). Studies in the 1950s showed the drug was not effective at preventing miscarriages, premature labor, or other pregnancy complications. [87] [93]

Duract (Bromfenac)

Date of Approval: July 1997

Date of Removal: June 26, 1998

Manufacturer: Wyeth-Ayerst Laboratories

Medical Use: pain killer

Cause for Recall: 4 deaths; 8 patients requiring liver transplants; 12 patients with severe liver damage. Duract was labeled for maximum use of 10 days, but patients often received or took more than ten days’ worth of pills; all cases of death and liver damage involved patients taking pills for longer than ten days. [76] [103]

Ergamisol (Levamisole)

Date of Approval: May 8, 1989

Date of Removal: 2000

Manufacturer: Janssen Pharmaceutica

Medical Use: worm infestation; colon and breast cancers; rheumatoid arthritis

Cause for Recall: neutropenia (a type of low white blood cell count), agranulocytosis (a type of low white blood cell count), and thrombotic vasculopathy (blood clots in blood vessels) which results in retiform purpura (a purple discoloration of the skin that can sometimes require reconstructive surgery). Levamisole is still used to treat animals with worm infestations in the U.S. It has also been found in street cocaine to increase euphoric qualities. [55] [96]

Hismanal (Astemizole)

Date of Approval: 1988

Date of Removal: August 13, 1999

Manufacturer: Janssen Pharmaceutica

Medical Use: antihistamine

Cause for Recall: slowed potassium channels in the heart that could cause torsade de pointes (TdP; a heart condition marked by a rotation of the heart’s electrical axis) or long QT syndrome (LQTS; prolonged QT intervals)

Lotronex (Alosetron)

Date of Approval: February 9, 2000

Date of Removal: November 28, 2000

Manufacturer: Prometheus Laboratories, Inc.

Medical Use: irritable bowel syndrome (IBS) in women

Cause for Recall: 49 cases of ischemic colitis (inflammation and injury of the large intestine); 21 cases of severe constipation (10 requiring surgery); 5 deaths; mesenteric ischemia (inflammation and injury of the small intestine). Lotronex was reintroduced to the U.S. market in 2002 with restricted indication. [62] [108] [90]

Meridia (Sibutramine)

Date of Approval: November 1997

Date of Removal: October 2010

Manufacturer: Knoll Pharmaceuticals

Medical Use: appetite suppressant

Cause for Recall: increased cardiovascular and stroke risk. In September 30, 2004, testimony before a U.S. Senate committee, FDA reviewer David Graham listed Meridia with Crestor, Accutane, Bextra, and Serevent as drugs whose sales should be limited or stopped because of their danger to consumers, calling the drugs “another Vioxx.”

Merital & Alival (Nomifensine)

Date of Approval: 1982

Date of Removal:

Manufacturer: Hoechst AG

Medical Use: antidepressant

Cause for Recall: haemolytic anemia; some deaths due to immunohemolytic anemia

Micturin (Terodiline)

Date of Approval: August 1989

Date of Removal: September 13, 1991

Manufacturer: Forest Labs

Medical Use: bladder incontinence

Cause for Recall: QT prolongation and potential for cardiotoxicity

Mylotarg (Gemtuzumab Ozogamicin)

Date of Approval: May 2000

Date of Removal: June 21, 2010

Manufacturer: Wyeth-Ayerst Laboratories

Medical Use: acute myeloid leukemia (AML; a bone marrow cancer)

Cause for Recall: increased risk of death and veno-occlusive disease (obstruction of veins) [65]

Omniflox (Temafloxacin)

Date of Approval: January 31, 1992

Date of Removal: June 5, 1992

Manufacturer: Abbott Laboratories

Medical Use: antibiotic for pneumonia, bronchitis, and other respiratory tract infections; prostatitis and other genitourinary tract infections; skin ailments

Cause for Recall: three deaths; severe low blood sugar; hemolytic anemia and other blood cell abnormalities; kidney dysfunction (half of the cases required renal dialysis); allergic reactions, including some causing life-threatening respiratory distress. [79] [94]

Palladone (Hydromorphone hydrochloride, extended-release)

Date of Approval: January 2005

Date of Removal: July 13, 2005

Manufacturer: Purdue Pharma

Medical Use: narcotic painkiller

Cause for Recall: high levels of Palladone could slow or stop breathing or cause coma or death; combining the drug with alcohol use could lead to rapid release of hydromorphone, in turn leading to potentially fatally high levels of drugs in the system. [75]

Permax (Pergolide)

Date of Approval: 1988

Date of Removal: March 29, 2007

Manufacturer: Valeant

Medical Use: Parkinson’s disease

Cause for Recall: heart valve regurgitation (a condition that causes the valves to not close tightly, which allows blood to flow backward over the valve) in the mitral, tricuspid, and aortic heart valves, which can result in shortness of breath, fatigue, and heart palpitations. Permax is still available in the U.S. for veterinary use, specifically for pituitary pars intermedia hyperplasia or equine Cushing’s Syndrome (ECS) in horses. [61] [84]

Pondimin (Fenfluramine)

Date of Approval: 1973

Date of Removal: September 15, 1997

Manufacturer: Wyeth-Ayerst

Medical Use: appetite suppressant

Cause for Recall: 30 percent of patients prescribed the drug had abnormal echocardiograms; 33 cases of rare valvular disease in women; 66 additional reports of heart valve disease. Pondimin was better known as “Fen-Phen” when prescribed with Phentermine. [60] [77]

Posicor (Mibefradil)

Date of Approval: June 1997

Date of Removal: June 1998

Manufacturer: Roche Laboratories

Medical Use: calcium channel blocker (used to treat hypertension)

Cause for Recall: fatal interactions with at least 25 other drugs (e.g., common antibiotics, antihistamines, cancer, and cholesterol drugs), including astemizole, cisapride, terfenadine, lovastatin, and simvastatin. Posicor was found by the FDA to offer no significant benefit over other antihypertensive or antianginal drugs, which made the risks of drug interactions “unreasonable.” Patients immediately switching from Posicor to another calcium channel blocker were at increased risk of going into shock within 12 hours of the drug switch. [102]

Propulsid (Cisapride)

Date of Approval: 1993

Date of Removal: July 14, 2000

Manufacturer: Janssen Pharmaceutica

Medical Use: severe nighttime heartburn associated with gastroesophageal reflux disease (GERD)

Cause for Recall: more than 270 cases of serious cardiac arrythmias (including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation) reported between July 1993 and May 1999, with 70 being deaths. Propulsid is also banned in India (2011) but is available for limited use in Europe. It is still available for use in animals in the U.S. and Canada. [73]

PTZ and Metrazol (Pentylenetetrazol)

Date of Approval: 1934

Date of Removal: 1982

Manufacturer: unknown

Medical Use: convulsive therapy for schizophrenia and other psychiatric conditions

Cause for Recall: uncontrollable seizures; pulled muscles; fractured bones; spine fractures in as many as 42 percent of patients. [58]

Quaalude (Methaqualone)

Marketed as Optimal, Sopor, Parest, Somnafac, and Bi-Phetamine T

Date of Approval: 1962

Date of Removal: 1985

Manufacturer: William H. Rorer Inc. & Lemmon Company

Medical Use: sedative and hypnotic

Cause for Recall: mania; seizures; vomiting; convulsions; death. Methaqualone was originally tested in India as a malaria treatment (it was ineffective). The drug is now a schedule 1 drug in the United States (like heroin, marijuana, and LSD).

Raplon (Rapacuronium)

Date of Approval: 1999

Date of Removal: March 27, 2001

Manufacturer: Organon Inc.

Medical Use: nonpolarizing neuromuscular blocker (used in anesthesia)

Cause for Recall: bronchospasms and unexplained deaths [78]

Raptiva (Efalizumab)

Date of Approval: 2003

Date of Removal: April 8, 2009 (not completely withdrawn until June 8, 2009)

Manufacturer: Genentech

Medical Use: psoriasis

Cause for Recall: progressive multifocal leukoencephalopathy (PML; a rare and usually fatal disease that causes inflammation or progressive damage of the white matter in multiple locations of the brain). [70]

Raxar (Grepafloxacin)

Date of Approval: 1997

Date of Removal: November 1, 1999

Manufacturer: Glaxo Wellcome

Medical Use: antibiotic for bacterial infections

Cause for Recall: cardiac repolarization; QT interval prolongation; ventricular arrhythmia (torsade de pointes) [81]

Redux (Dexfenfluramine)

Date of Approval: 1996

Date of Removal: September 15, 1997

Manufacturer: Wyeth-Ayerst

Medical Use: appetite suppressant

Cause for Recall: 30 percent of patients prescribed the drug had abnormal echocardiograms; 33 cases of rare valvular disease in women; 66 additional reports of heart valve disease. Redux is better known as “Fen-Phen” when prescribed with Phentermine. [60] [77]

Rezulin (Troglitazone)

Date of Approval: January 29, 1997

Date of Removal: March 21, 2000

Manufacturer: Parke-Davis/Warner Lambert

Medical Use: antidiabetic and anti-inflammatory

Cause for Recall: at least 90 liver failures; at least 63 deaths. About 35,000 personal injury claims were filed against the manufacturer. [83] [107]

Selacryn (Tienilic acid)

Date of Approval: May 2, 1979

Date of Removal: 1982

Manufacturer: SmithKline

Medical Use: blood pressure

Cause for Recall: hepatitis; 36 deaths; at least 500 cases of severe liver and kidney damage. Anphar Labs (which developed the drug in France and sold rights to sell in the U.S. to SmithKline) sent a report to SmithKline in April 1979 (translated in May 1979 into English from French) stating that Selacryn damaged livers. On December 13, 1984, SmithKline Beckman plead guilty to “14 counts of failing to file reports with the drug agency of adverse reactions to Selacryn and 20 counts of falsely labeling the drug with a statement that there was no known cause-and-effect relationship between Selacryn and liver damage.” [51]

Seldane (Terfenadine)

Date of Approval: 1985

Date of Removal: February 1, 1998

Manufacturer: Hoechst Marion Roussel

Medical Use: antihistamine

Cause for Recall: life-threatening heart problems when taken in combination with other drugs (specifically erthromycin (an antibiotic) and ketoconazole (an antifungal). Seldane was not considered an imminent threat. The FDA pulled Seldane from the market because Allegra and Allegra D were produced by the same company and were deemed safer by the FDA. [54]

Trasylol (Aprotinin)

Date of Approval: 1993 (used without FDA approval since the 1960s)

Date of Removal: November 5, 2007 (marketing suspension request to phase it out of the market); May 14, 2008 (manufacturer announced complete removal from the market)

Manufacturer:Bayer

Medical Use: antifibrinolytic to reduce blood loss during surgery

Cause for Recall: increased chance of death, serious kidney damage, congestive heart failure, and strokes. On February 8, 2006, the FDA issued a public heath advisory to surgeons who perform heart bypasses, alerting them to possible fatal side effects. [64] [65] [66]

Vioxx (Rofecoxib)

Date of Approval: May 20, 1999

Date of Removal: September 30, 2004

Manufacturer: Merck

Medical Use: NSAID (pain relief)

Cause for Recall: increased risk of heart attack and stroke; linked to about 27,785 heart attacks or sudden cardiac deaths between May 20, 1999 and 2003. Ads for Vioxx featured Olympic gold medalists, including Dorothy Hamill. Vioxx was prescribed to more than 20 million people.

Xigris (Drotrecogin alfa activated)

Date of Approval: November 2001

Date of Removal: October 25, 2011

Manufacturer: Eli Lilly & Company

Medical Use: severe sepsis and septic shock

Cause for Recall: no survival benefit [63] [92] [95] [99]

Zantac (Ranitidine)

Date of Approval: 1983 (prescription), 2004 (over the counter)

Date of Removal: April 2021

Manufacturer: Sanofi

Medical Use: heartburn

Cause for Recall: potential N-Nitrosodimethylamine (NDMA) amounts above appropriate levels. According to the FDA, “NDMA is classified as a probable human carcinogen (a substance that could cause cancer).” [67] [98]

Zelmid (Zimelidine)

Date of Approval: 1982

Date of Removal: 1982 (withdrawn by the FDA before being released in the U.S. market)

Manufacturer: Astra AB

Medical Use: antidepressant

Cause for Recall: Guillain–Barré syndrome; higher risk of suicide

Zelnorm (Tegaserod maleate)

Date of Approval: July 24, 2002

Date of Removal: March 30, 2007

Manufacturer: Novartis

Medical Use: irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in women younger than age 55

Cause for Recall: higher chance of heart attack, stroke, and unstable angina (heart or chest pain). The FDA permitted restricted use of Zelnorm on an emergency basis (with prior case-by-case authorization from the FDA) on July 27, 2007. [50] [82]