Med Check

In November the Food and Drug Administration (FDA) approved Vyvanse (lisdexamfetamine dimesylate) capsules for the treatment of adolescents aged 13 to 17 diagnosed with attention-deficit/hyperactivity disorder (ADHD). The amphetamine-containing medication was first granted FDA approval in 2007 for the treatment of ADHD in children aged 6 to 12 and in 2008 for adults. The updated prescribing information is posted at <www.accessdata.fda.gov/drugsatfda_docs/label/2010/021977s016s018s019s021lbl.pdf>.

In November the FDA released the findings of its second annual Final Report on the Post-Marketing Requirement/Post-Marketing Commitment (PMR/PMC) Backlog Review. The report, which includes data from January through December 2009, details the status of drug manufacturers' postmarketing and safety trials, also called phase 4 trials, of already-approved FDA drugs. It can be accessed at <www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/ucm232850.htm>.

The prescribing information for Paxil, Paxil CR (paroxetine) immediate- and extended-release tablets, and the oral suspension formulation was updated in October 2010. The revised labeling advises clinicians about the risk of a fracture in patients on paroxetine who present with unexplained bruising, swelling, bone pain, and/or tenderness and have low bone-mineral density. In these patients, a bone fracture may occur even if there appears to have been minimal injury to the bone.

The precautions section of each paroxetine formulation also has been updated to note a drug interaction with the opioid medication fentanyl. This interaction may put patients at risk for serotonin syndrome, since both drugs affect similar serotonergic neurotransmitter systems in the brain. Symptoms of this possible interaction may result in changes in mental status, autonomic instability, or GI symptoms.

The manufacturer also reports that there has been at least one postmarketing report of restless leg syndrome that developed while the patient was taking paroxetine. Although it is not known whether paroxetine causes restless leg syndrome, this information was added to the prescribing information.

The updated prescribing information for paroxetine controlled-release tablets is posted at <www.accessdata.fda.gov/drugsatfda_docs/label/2010/020936s041lbl.pdf>. The updated prescribing information for paroxetine immediate-release tablets and oral-suspension products is posted at <www.accessdata.fda.gov/drugsatfda_docs/label/2010/020031s063,020710s027lbl.pdf>.

In October 2010 the FDA reported that Pfizer Inc./Wyeth Pharmaceuticals Inc. updated the patient medication guide for Pristiq (desvenlafaxine succinate) extended-release tablets to reflect safety-labeling changes. Pristiq, a serotonin-norepinephirne reuptake inhibitor (SNRI), is approved for the treatment of anxiety, depression, and mood disorders.

The revised prescribing information cautions prescribers to be aware of the possibility of symptoms consistent with neuroleptic malignant syndrome (NMS) or the serotonin syndrome that may occur when switching patients to desvenlafaxine. In general, NMS-like reactions are rare, but serious adverse side effects may occur when stopping particular medications that act on the serotonergic neurotransmitter systems in the brain. Some such medications include the SNRI, SSRI, and monoamine oxidase inhibitor (MAOI) classes of medications. However, NMS-like reactions have also been reported to occur when simply switching patients from their current antidepressant to desvenlafaxine, according to the manufacturer. This may even occur in instances where drug therapy is being switched from venlafaxine, which is also an SNRI, to desvenlafaxine. The manufacturer recommends that to decrease the chances of discontinuation symptoms occurring when switching from one medication to desvenlafaxine, a gradual reduction of the previous antidepressant is recommended. However, serotonin symptoms may also occur when taking other medications that act on the serotonergic neurotransmitter systems.

According to the prescribing information, changes to the medication guide for patients describe the symptoms of the serotonin syndrome or NMS-like reactions that may occur when taking desvenlafaxine. It also advises patients to notify their doctor if they think they may be taking other medications such as “triptans” for migraines, tricyclic antidepressants, lithium, SSRIs, SNRIs, antipsychotic medications, metoclopramide, silbutramine, tramadol, St. John's wort, MAOIs, the antibiotic medication linezolid, and supplements that contain tryptophan, which may trigger symptoms of the serotonin syndrome or NMS-like reactions.

The updated desvenlafaxine medication guide, located at the end of the prescribing information for the medication, is posted at <www.accessdata.fda.gov/drugsatfda_docs/label/2010/021992s013lbl.pdf>.

Cephalon Inc. is updating the prescribing information for Provigil (modafinil) and Nuvigil (armodafinil) tablets as a result of the FDA approval of the medications in the Risk Evaluation and Mitigation Strategies (REMS) program.

The REMS program was established under the Food and Drug Administration Amendments Act (FDAAA) of 2007 to the Federal Food, Drug, and Cosmetic Act. The FDAAA gives the FDA the authority to evaluate and monitor all newly and already approved medications to prove that they are safe, their benefits outweigh their risks, and the risks are being communicated to prescribers and consumers. The FDA can require manufacturers to provide additional communication and medication guides to prescribers and patients or enact other safeguards such as restricted use.

Although the medications have an existing warning in the product labeling alerting prescribers to the risk of hypersensitivity and rash, including Stevens-Johnson syndrome, patients will now receive a REMS medication guide. Both medications are indicated for the treatment of obstructive sleep apnea, shift-work disorder, and narcolepsy in adults.

The modafinil and armodafinil prescriber materials are posted at <www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM232054.pdf>. The modafinil medication guide is posted at <www.provigil.com/media/PDFs/medication_guide.pdf>. The armodafinil medication guide is posted at <www.nuvigil.com/media/Medication_Guide.pdf>.

In October 2010 GlaxoSmithKline agreed to pay $750 million in civil penalties and criminal fines in a case involving a manufacturing plant in Cidra, Puerto Rico. It was found that several adulterated medications, including Paxil CR (paroxetine hydrochloride) extended-release tablets, were allowed to be produced at the plant between 2001 and 2005. Although there have been no reports of medications produced at the plant affecting patient safety, the plant has been closed since 2009 due to a decrease in demand for the medications manufactured there.

The U.S. Supreme Court plans to hear arguments in the first quarter of 2011 in a case between Stanford University and a division of Roche Holding AG that may impact the research patent rights of universities that use federal funds. The lawsuit, filed against the drug manufacturer, involves patent rights on the clinical tests that are used to determine the effectiveness of AIDS therapies for patients. The Court's ruling may impact future relationships that drug companies have with universities and the federal government. The case under consideration is the Board of Trustees of the Leland Stanford Junior University vs. Roche Molecular Systems.

Otsuka Pharmaceutical Co. Ltd. announced in a press release last month that the U.S. District Court for the District of New Jersey has upheld the company's patent-exclusivity rights for Abilify (aripiprazole). As a result, any generic products containing aripiprazole cannot be sold in the United States until April 2015 at the earliest, the Japanese company stated. Teva Pharmaceutical Industries Ltd., Novartis AG's Sandoz, and other generic-drug manufacturers had challenged the company's patent exclusivity of the drug. The medication is co-marketed in the United States by Bristol-Myers Squibb.