Med Check

On September 1, the Food and Drug Administration (FDA) warned the public that serious allergic reactions have been reported with the use of the antipsychotic Saphris (asenapine maleate). A search of the FDA's Adverse Event Reporting System database identified 52 cases of Type I hypersensitivity reactions linked to Saphris use. The hypersensitivity reactions included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, and rash. In several cases, these reactions occurred after the first dose.

The Contraindications, Warning and Precautions, Adverse Reactions, and Patient Counseling Information sections of Saphris's label have been revised to include information about this risk and to inform health care professionals that Saphris should not be used in patients with a hypersensitivity to the drug. The FDA advised health care professionals to educate patients on the symptoms of an allergic reaction and to seek help immediately if they experience any of these symptoms while taking Saphris.

Transcept Pharmaceuticals announced September 14 that it is working to resolve issues with the FDA concerning its new drug application (NDA) seeking approval of Intermezzo (zolpidem tartrate sublingual tablet) for use as needed for insomnia treatment when a middle of the night awakening is followed by difficulty returning to sleep. Transcept received a complete response letter from the FDA in July regarding resubmission of the Intermezzo NDA. In a September 14 meeting with Transcept, the FDA generally agreed with a Transcept proposal to reduce the recommended Intermezzo dose for women from 3.5 mg to 1.75 mg and to keep the recommended Intermezzo dose for men at 3.5 mg. The proposal also includes new instructions stating that Intermezzo should be taken only if patients have at least four hours of bedtime remaining and that patients should refrain from driving for at least one hour after arising and until five hours after taking the medication.  

Based on discussion with the FDA, Transcept does not plan to conduct additional studies prior to resubmitting the Intermezzo NDA. The FDA has informed Transcept that if the resubmission is adequately concise in summarizing morning zolpidem levels and shows evidence that the levels are safe given the proposed labeling, it may be able to consider the resubmission as a two-month, Class 1 review under FDA guidelines.

Transcept and Purdue Pharmaceutical Products have entered into a collaborative agreement for development and commercialization of Intermezzo in the United States.

Lupin Pharmaceuticals announced on August 31 that it had received final FDA approval for its abbreviated new drug application for tramadol hydrochloride extended-release tablets, 100 mg, 200 mg, and 300 mg strengths. Tramadol ER is a centrally acting synthetic analgesic in an extended-release formulation (the generic equivalent to Ortho-McNeil's Ultram ER tablets) and is indicated for moderate to moderately severe chronic pain in adults who require around-the-clock pain treatment for an extended period.  

On September 7, the U.S. Drug Enforcement Administration (DEA) used its emergency scheduling authority to temporarily control three synthetic stimulants (mephedrone; 3,4 methylenedioxypyrovalerone; and methylone). The DEA said the action was necessary to protect the public from the hazard posed by these dangerous chemicals. This action will make possessing and selling these chemicals or the products that contain them illegal for at least one year while the DEA and the Department of Health and Human Services further study whether these chemicals should be permanently controlled.

A Notice of Intent to temporarily control the stimulants was published in the Federal Register September 7. In the near future the DEA intends to publish in the Federal Register a Final Order to temporarily control these chemicals for at least 12 months, with the possibility of a six-month extension. The final order will designate these chemicals as Schedule I substances, the most restrictive category, which is reserved for unsafe, highly abused substances with no currently accepted medical use in the United States.

The Federal Register notice is posted at <www.deadiversion.usdoj.gov/fed_regs/rules/2011/fr0908.htm>.

On September 6, Sagent Pharmaceuticals announced FDA approval of its haloperidol injection, an antipsychotic medication. Sagent's haloperidol will be offered in 5 mg per mL single-dose and 50 mg per 10 mL multidose, latex-free vials. As with all products in Sagent's portfolio, haloperidol features the company's PreventIV Measures color-coded packaging and labeling designed to aid in reducing medication errors. Sagent expects to launch the product in the fourth quarter of the year. Haloperidol is indicated for use in schizophrenia and for control of tics and vocal utterances of Tourette's disorder.

The FDA informed health care professionals and patients on August 24 that the antidepressant Celexa (citalopram hydrobromide (also marketed in generic formulations) should no longer be used at doses greater than 40 mg per day because it can cause prolongation of the QT interval and lead to abnormal heart rhythm, including Torsade de Pointes. Studies did not show a benefit in the treatment of depression at daily doses higher than 40 mg. Previously, the citalopram drug label stated that certain patients may require a dose of 60 mg per day. 

The citalopram label has been revised to include the new dosage and usage recommendations, as well as information about the potential for QT interval prolongation and Torsade de Pointes.

Janssen Pharmaceuticals announced August 26 that the FDA has approved Nucynta ER, an oral analgesic taken twice daily, for management of moderate to severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period.

Johnson & Johnson Pharmaceutical Research and Development and Grünenthal, a privately owned pharmaceutical company based in Germany, conducted the double-blind, randomized, active and/or placebo-controlled phase 3 studies that evaluated the efficacy and safety of Nucynta ER for treatment of moderate to severe chronic low back pain and painful diabetic peripheral neuropathy. Safety was also evaluated in more than 1,100 patients with moderate to severe chronic pain over a one-year period.

BioDelivery Sciences International announced positive preliminary results on September 6 from its phase 1 study assessing the pharmacokinetics of a BioErodible MucoAdhesive (BEMA) formulation of buprenorphine/naloxone. The company is trying to develop a high-dose formulation of buprenorphine combined with the abuse-deterrent agent naloxone for treatment of opioid dependence.

This study assessed buprenorphine and naloxone absorption profiles from the BEMA formulation versus Suboxone, the FDA approved and currently marketed opioid dependence product. Study results showed the ability of the BEMA formulation to meet the key pharmacokinetic goal of delivering plasma concentrations of buprenorphine in the range needed to treat opioid dependence while minimizing the exposure of naloxone. The company expects to submit an NDA for BEMA buprenorphine/naloxone in the second half of 2012.

On September 5, Evotec and Roche announced a worldwide agreement for development and commercialization of Evotec's EVT 302, a potent inhibitor of monoamine oxidase type B (MAO-B) in patients with Alzheimer's disease. Under the terms of the agreement, Roche will pay Evotec an upfront fee of $10 million. Evotec could receive further development and commercial milestone payments of up to $820 million, as well as royalties on sales. Roche will initiate studies in 2012 to demonstrate proof of concept and will be responsible for all clinical development, manufacturing, and commercialization activities.