High Alert Drugs

Drug Manufacturers Consent to Oversight by Federal Agency Following Increased Scrutiny

June 4, 2014 | Lebowitz & Mzhen

Following a meningitis outbreak that was linked to a faulty drug, several custom drug manufacturers have recently consented to voluntary oversight by the FDA. According to a report by AZ Central, the manufacturers of custom drugs exist in a bit of a legal loophole. These manufacturers often create specific drug “cocktails” designed to treat very specific conditions.

These “shadow” drug makers, as the article refers to them, came under scrutiny after an outbreak of meningitis was linked to 64 deaths and over 700 illnesses. Under current law, these manufacturers are not regulated by the federal government. However, in 2012, there were two citations issued for unsanitary conditions and a faulty injection.

These specialty drugs, which are prescribed by doctors and filled at regular pharmacies like CVS or Walgreens, are often combinations of other approved drugs. However, since the manufactures operated somewhere between the smaller state-regulated compounding manufacturers and the large-scale drug manufacturers regulated by the FDA, it is unclear who is in charge of making sure these facilities are up to par with the governing safety standards in place.

Pharmaceutical Company’s Failure to Warn Did Not Cause Plaintiff’s Injury, Court Rules

April 29, 2014 | Lebowitz & Mzhen

A federal district court dismissed a lawsuit against a pharmaceutical company for alleged failure to warn, holding that any defect in the drug’s label did not influence the prescribing doctor’s decision regarding the drug. Parkinson v. Novartis Pharmaceuticals Corp., No. 3:12-cv-02089, opinion (D. Ore., Mar. 20, 2014). In a claim for damages caused by a manufacturer’s failure to warn of a hazardous condition or risk, a plaintiff must prove that the failure to warn was a proximate cause of their injuries. The “learned intermediary doctrine” often applies in cases involving pharmaceutical drugs, meaning that the question is whether the failure to warn influenced the prescribing physician, not the plaintiff. The plaintiff must prove that the physician would not have prescribed the drug, or would have done so in a different manner, had the manufacturer provided adequate warnings.

The plaintiff was diagnosed with stage IIIB breast cancer in January 2003. She underwent chemotherapy for about six months and then voluntarily stopped receiving treatment. In May 2005, she underwent radiation therapy on her pelvis to treat pain caused by the cancer, which by then had spread. She also had surgery on her legs because of bone damage. Her physician began administering monthly infusions of Aredia, a bisphosphonate used to treat bone damage in cancer patients, in June of that year. Bisphosphonates have been associated with an increase risk of osteonecrosis of the jaw (ONJ), a condition in which the jaw bone weakens and, in some cases, dies. Dental surgery may aggravate the condition in cancer patients receiving bisphosphonates.

The plaintiff’s physician testified in his deposition that he was aware of the risks associated with ONJ, but felt that they were outweighed by the benefits of the drug for the plaintiff. He also testified that he continues to prescribe Aredia and other bisphosphonate drugs. After the plaintiff had been receiving monthly Aredia infusions for over a year, the doctor switched her to Zometa, another bisphosphonate, in September 2006. The plaintiff saw a dentist in December 2006, reportedly the first time in five years. She then began experiencing tooth and jaw aches, and was eventually diagnosed with bisphosphonate-related ONJ in January 2008.

Nationwide Lipitor Lawsuits Consolidated in One Court for Pretrial Proceedings

April 22, 2014 | Lebowitz & Mzhen

The Judicial Panel on Multidistrict Litigation (JPML) has consolidated lawsuits filed around the country against the pharmaceutical company Pfizer under the style In Re Lipitor (Atorvastatin Calcium) Marketing, Sales Practices and Products Liability Litigation (No. II), No. MDL-2502. The cases involve allegations that the plaintiffs developed type 2 diabetes after taking the cholesterol-lowering drug marketed by Pfizer as Lipitor. As of April 15, 2014, the JPML has consolidated 464 claims in the U.S. District Court for the District of South Carolina. Consolidation is appropriate, according to federal statute, when multiple lawsuits involving common questions of fact are pending in multiple federal courts around the country, and a single court could efficiently handle various pretrial proceedings. 28 U.S.C. § 1407.

Atorvastatin, marketed under the brand name Lipitor, is part of the family of drugs known as statins, commonly used to reduce a patient’s cholesterol levels. Statins work by inhibiting an enzyme used by the liver to produce cholesterol. High cholesterol levels have been associated with an increased risk of heart disease, and statins have demonstrated the ability to prevent heart disease in high-risk patients. A paper published in the Lancet in February 2010 identified a slight risk of diabetes associated with statins, while a paper published in the January 2012 Archives of Internal Medicine found an increased risk of diabetes among postmenopausal women who take statins. These and other studies led to a series of lawsuits alleging that Lipitor caused plaintiffs to develop type 2 diabetes.

The U.S. Food and Drug Administration requested in August 2011 that Pfizer change the Lipitor label to include warnings about the risk of type 2 diabetes. The company changed the label in February 2012, but allegedly did not include specific warnings about the diabetes risk. The plaintiff in Jennings v. Pfizer, No. 1:14-cv-00096, complaint at 2 (D. Md., Jan. 13, 2014), describes the revised Lipitor label as “extremely vague.” The complaint in Gaines v. Pfizer, No. 1:14-cv-00170, complaint (D. Md., Jan. 22, 2014), alleges that Pfizer did not issue any warnings about the possible connection between Lipitor and type 2 diabetes before making the requested changes to the drug label. It further claims that, while the new label “warns in the most obtuse terms” about the risk of elevated blood sugar, it makes no direct warning about diabetes risk. Id. at 5.

FDA Approves Prescription-Based Antidote for Overdose of Heroin, Other Opioids

April 15, 2014 | Lebowitz & Mzhen

The U.S. Food and Drug Administration (FDA) approved a “hand-held auto-injector” device for use with known or suspected opioid overdoses. Abuse of opioids, a group of drugs that includes many prescription painkillers, is becoming a serious problem in the U.S., and the FDA claims that opioid overdose has surpassed automobile accidents as the nation’s leading cause of injury deaths. The device, marketed under the brand name Evzio, delivers an injection of naloxone hydrochloride to counter or reverse the effects of opioid overdose. The FDA has stated that it hopes the availability of the device with a prescription will help prevent overdose deaths in emergency situations.

Opioid analgesics are a family of opiate-based drugs commonly used in prescription painkillers. They are derived from the same source as heroin and several other illegal narcotics. Common opioids include codeine, hydrocodone, morphine, and oxycodone. Opioids can be very addictive, so they are tightly controlled by the government. According to the Centers for Disease Control and Prevention (CDC), 16,651 people died of drug overdoses involving opioids in 2010, the most recent year for which statistics are available. This number accounts for about seventy-five percent of all drug overdose deaths that year. Many overdoses involve legally-obtained prescription painkillers. The total number presumably includes intentional and accidental overdoses, as well as dosage errors by a physician or pharmacist.

Evzio, as approved by the FDA, is a handheld device that injects naloxone hydrochloride, an “opioid antagonist” that is a common treatment for opioid overdose. Emergency responders often carry naloxone-containing products for use with suspected overdose victims. Since Evzio is only available with a prescription, it must be obtained in advance of any emergency situation. It is recommended for family members and caregivers of people using opioid painkillers in case of overdose. The device provides verbal instructions for use once it is turned on. A single dose of naloxone, according to the FDA, does not last as long as a typical opioid, so it cautions that the device is not a substitute for medical attention. What the device can do is delay further injury or death due to an overdose until medical attention is available.

FDA Proposes New Guidelines Regarding Off-Label Promotion of Drugs

April 8, 2014 | Lebowitz & Mzhen

The U.S. Food and Drug Administration (FDA) recently issued draft revisions of pharmaceutical industry guidelines regarding “off-label” promotion of drugs. “Off-label” refers to information about uses of a drug that have not been formally approved by the FDA and are not included in its approved labeling. The agency has treated off-label promotion as “misbranding,” which can carry both civil and criminal penalties under the Food, Drug, and Cosmetics Act (FDCA). The Second Circuit Court of Appeals struck down the conviction of a pharmaceutical sales representative for conspiring to introduce a misbranded drug into interstate commerce, finding that the off-label promotion rule violated his First Amendment right to free speech. United States v. Caronia, 703 F.3d 149 (2nd Cir. 2012). The FDA’s proposed revisions, published in the Federal Register at 79 FR 11793 (Mar. 3, 2014), seek to apply a narrower set of restrictions on off-label promotion.

The FDCA generally prohibits “misbranding” of an approved drug. In a “Guidance for Industry” document published in January 2009, the FDA addressed the distribution of medical literature and other scientific publications regarding off-label uses of approved drugs. The FDA has strict labeling requirements for all approved drugs, including risks of side effects and complications and instructions for use. Off-label marketing of a drug, the FDA stated in the guidance document, constitutes unlawful misbranding of a drug because the drug’s label does not include “adequate directions for use,” as required by the FDCA. 21 U.S.C. § 352(f), 21 C.F.R. § 201.100(c)(1).

The defendant in Caronia was charged with conspiracy to introduce a misbranded drug, and introducing a misbranded drug, into interstate commerce. 21 U.S.C. § 331(a). If a defendant had the “intent to defraud or mislead,” the offense carries a maximum penalty of three years in prison, a $10,000 fine, or both. 21 U.S.C. § 333(a)(2). The case involved Xyrem, a central nervous system depressant with only two FDA-approved uses. The drug contains GHB, a powerful depressant commonly known as the “date rape drug,” making it one that the FDA closely watches.

Pharmacy Allegedly Dispenses Adult’s Prescription to Child with the Same Name, Resulting in Near-Fatal Drug Reaction

February 20, 2014 | Lebowitz & Mzhen

The family of a five-year old boy in the Chicago area is claiming that a case of mistaken identity resulted in the boy receiving the wrong medication and suffering a near-fatal reaction with possible long-term health effects. They have filed a negligence lawsuit in Cook County Circuit Court seeking $50,000 in damages. Pharmacies and the medical professionals they employ owe a duty of care to consumers to verify not only the type and dosage of medication dispensed, but also that the correct patient receives the correct medication.

The child reportedly had a routine checkup with a physician in January 2012. The doctor discussed allergy medication with the boy’s parents, but did not write a prescription at that time. A Walgreens pharmacy allegedly called the family two days later to tell them that their prescription was ready. Believing it to be the allergy medication they had discussed with the doctor, the boy’s mother picked the prescription up and began giving it to him according to the instructions on the bottle.

The lawsuit, filed in January 2014, states that the boy slept for almost two full days after taking the medication. When the child woke up, he exhibited unusual symptoms. His neck flared, leading his parents to call 9-1-1, but it soon subsided. The boy later fainted, so his parents took him to the doctor, who told them to go immediately to the hospital. The prescription that they thought was for allergies, they learned, was actually haloperidol, an antipsychotic medication intended for an adult with the same name as the child.

Similar Drug Names Can Cause Confusion, Catastrophe if Pharmacy Makes an Error

January 15, 2014 | Lebowitz & Mzhen

Confusion between two similarly-named drugs can be harmful or even fatal if the error is not detected quickly. An error could result from any number of circumstances, such as a pharmacist who misreads a doctor’s handwriting or a nurse who accidentally administers the wrong drug. The U.S. Food and Drug Administration has procedures for comparing new drug applications to existing drugs, but this does not guard against confusion regarding drugs that are already on the market. A pharmacy journal published an account last year of one such medication error at an oncology clinic, which fortunately did not result in any complications for the patient who received the wrong medication. A version of the drug she received, however, has been implicated in numerous injuries and lawsuits.

The journal Hospital Pharmacy included an account in its June 2013 issue of a fourteen year-old girl diagnosed with acute promyelotic leukemia (APL) who received the wrong medication for about four months. APL, according to the authors, can quickly turn fatal and requires immediate treatment. Her doctors prescribed an oral dose of trentinoin, a vitamin A derivative commonly prescribed in a topical form under the name Retin-A to treat and prevent acne. It is administered orally in 10-miligram capsules to treat APL. The same basic effect that treats acne can also fight cancer cells.

After completing a course of treatment, the patient returned to the hospital about a month later. Her doctors decided to do several rounds of outpatient intravenous chemotherapy and continue the oral trentinoin. A nurse in the oncology clinic, possibly unfamiliar with the drug, instead called in a prescription for isotrentinoin under the brand name Claravis. While similar to trentinoin, isotrentinoin is primarily used to treat severe acne. It was formerly marketed as Accutane, but the manufacturer discontinued the brand in 2009, allegedly in part because of lawsuits claiming harmful side effects.

Court Finds Failure to Warn and Design Defect Claims Preempted in Lawsuit Against Generic Antibiotic Manufacturer

January 8, 2014 | Lebowitz & Mzhen

A federal court dismissed most of the causes of action in a lawsuit alleging that a generic antibiotic caused a dangerous, potentially-fatal reaction. Wilson v. Amneal Pharmaceuticals, LLC, No. 1:13-cv-00333, order (D. Id., Dec. 31, 2013). The lawsuit asserted claims under Idaho state law, but the decision is similar to federal court decisions in other states involving generic drug manufacturers. Federal laws and regulations make recovery of damages difficult for injuries caused by generic drugs.

The plaintiff’s doctor prescribed Bactrim, a generic antibiotic manufactured by the defendant, Amneal Pharmaceuticals. After taking the medication for one week, the plaintiff reportedly developed Stevens-Johnson syndrome, a reaction to a medication or infection that causes painful rashes and blisters. It can be very difficult to treat, and in severe cases, can cause permanent injury or death. The plaintiff sued Amneal in state court, asserting seven causes of action including defective design, negligent manufacture, and failure to warn. Amneal removed the case to federal district court based on diversity jurisdiction. It attached various FDA documents to its answer, including formal approvals of changes to the drug label.

Amneal moved the court to take judicial notice of the documents it produced with its answer, and to dismiss the plaintiff’s complaint for failure to state a claim on which the court could grant relief. The plaintiff opposed the motion for judicial notice and moved the court to allow discovery to proceed. The court denied the plaintiff’s motion and granted the motion to take judicial notice. Judicial notice is proper, it held, when the evidence in question is widely available or a matter of public record. It found that all of the documents in question were easily obtainable online, and that no one disputed their authenticity. The court proceeded to decide the motion to dismiss without the introduction of any further evidence besides the pleadings.

Fosamax Plaintiff Receives $285,000 Verdict After Jury Trial

February 12, 2013 | Lebowitz & Mzhen

A plaintiff claiming that the drug Fosamax caused a painful jaw condition has won a $285,000 verdict against the drug’s manufacturer, Merck. Scheinberg v. Merck & Co., Inc., No. 1:2008-cv-04119 (S.D.N.Y., Feb. 5, 2013). While thousands of lawsuits related to Fosamax are currently pending, this is only the second case that a plaintiff was won at trial. Many cases have been consolidated into two federal district courts, one to hear cases alleging jaw injuries, and another to hear cases alleging femur injuries. Several days before the jury verdict in the Scheinberg case, an appellate court affirmed a verdict and a summary judgment order against a different Fosamax plaintiff in Secrest v. Merck, Sharp & Dohme Corp., No. 11-4358-cv (2nd Cir., Jan. 30, 2013).

Scheinberg filed suit against Merck in 2008, alleging that the drug Fosamax caused her to sustain jaw injuries. The drug was approved to treat osteoporosis in menopausal women. It has been linked to a heightened incidence of femur fractures and osteonecrosis of the jaw (ONJ), a painful condition affecting the jawbone and surrounding tissues. The sixty-nine year-old plaintiff alleges that she developed ONJ as a result of taking Fosamax, and that this caused complications after she had a tooth extracted.

The Judicial Panel on Multi-District Litigation began consolidating Fosamax lawsuits, transferring cases alleging ONJ to the Southern District of New York, and cases alleging femur injuries to the District of New Jersey. About 975 ONJ claims are pending in New York, along with 842 femur claims in New Jersey, and various claims in state courts. Scheinberg’s lawsuit asserted causes of action for the products liability theories of design defect and failure to warn of the risks of a dangerous product. Her suit is one of several “bellwether” cases that the judge has allowed to go to trial, to see how similar cases may turn out. Out of seven bellwethers that have gone to trial so far, Merck has won all but two.

Study Examines the Use of Antipsychotic Medications to Treat Children with ADHD

January 30, 2013 | Lebowitz & Mzhen

A study published last year examined the rate at which doctors prescribe antipsychotic medications for children diagnosed with attention deficit hyperactivity disorder, commonly known as ADHD or ADD. The researchers found a significant increase in the rate of prescriptions in recent years, and psychiatrists may now prescribe antipsychotics for children or adolescents with ADHD in one-third of all visits. The U.S. Food and Drug Administration (FDA) has not approved antipsychotic medications for ADHD in children, making it an “off-label” use. While this is not illegal per se, it raises concerns about known and unknown side effects and the risks of dangerous medication errors.

ADHD is a mental health condition that affects both children and adults, and can severely impact a child’s functioning in school and other activities. Symptoms include easy distraction, difficulty focusing, irritability, and difficulty remaining still. The most common pharmaceutical treatment for ADHD consists of stimulant drugs like Adderall and Ritalin. According to the Centers for Disease Control and Prevention (CDC), ADHD affects about 5.2 million children between the ages of three and seventeen, just over eight percent of all children in the U.S. in that age range. About twelve percent of boys and nearly five percent of girls in that age range have been diagnosed with ADHD.