FDA Okays First Single-Entity Extended-Release Hydrocodone.


The US Food and Drug Administration (FDA) has approved the first single-entity extended-release formulation of hydrocodone bitartrate (Zohydro ER, Zogenix Inc) for the management of pain severe enough to require daily around-the-clock long-term treatment and for which alternative options are inadequate.

“Zohydro ER, a Schedule II controlled substance under the Controlled Substances Act, is the first FDA-approved single-entity (not combined with an analgesic such as acetaminophen) and extended-release hydrocodone product,” a statement from FDA released today notes.

“Zohydro ER will offer prescribers an additional therapeutic option to treat pain, which is important because individual patients may respond differently to different opioids.”

This formulation belongs to the class of extended-release/long-acting (ER/LA) opioids, the statement notes. “Due to the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with ER/LA opioid formulations, Zohydro ER should be reserved for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain,” the FDA release said.

It is not approved for as-needed pain relief.

In addition, the labeling approved for this drug conforms to updated labeling requirements for all ER/LA opioids announced by the FDA on September 10 and reported at that time by Medscape Medical News, the first opioid to be labeled in this way, the statement notes.

“The new class of labeling and stronger warnings will more clearly describe the risks and safety concerns associated with ER/LA opioid analgesics, along with the appropriate use of these medications,” the FDA said. “These warnings are expected to improve the safety of all such medicines by encouraging more appropriate prescribing, patient monitoring, and patient counseling practices.”

Schedule II drugs can be dispensed only by prescription, and no refills are allowed. Stringent record-keeping, reporting, and physical security requirements are also in place for these substances.

The FDA will require postmarketing studies of this agent to assess the “known serious risks of misuse, abuse, increased sensitivity to pain (hyperalgesia), addiction, overdose, and death associated with long-term use beyond 12 weeks,” the FDA release said. “These studies will also be required for other ER/LA opioid analgesics.”

Safety of this new formulation of hydrocodone is based on clinical studies that have included more than 1100 patients with chronic pain. Efficacy is based on a clinical study that enrolled more than 500 patients with chronic low back pain and showed a significant improvement in chronic pain vs placebo.

It will also be part of the ER/LA Opioids Analgesics risk evaluation and mitigation strategy (REMS) approved in 2012. The REMS requires companies to make educational programs on how to safety prescribe these agents to healthcare professionals and provide medication guides and patient counseling documents with information on safe use, storage, and disposal of ER/LA opioids.

The most common adverse effects of this single-entity hydrocodone are constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting, and pruritus.

In December 2012, FDA’s Anesthetic and Analgesic Drug Advisory Committee of independent experts voted 11 to 2, with 1 abstention, to recommended against approval of this agent for the treatment of moderate to severe chronic pain.

Most panel members voted that the drug had met regulatory requirements for safety and efficacy, as indicated by their responses to questions on efficacy and safety. However, for the last question voted on — “Based on the data presented and discussed today, do the efficacy, safety and risk-benefit profile of Zohydro ER support the approval of this application?” — most had negative responses.

The main concern of those voting against approval was that the potential for abuse of these agents; because the product does not include acetaminophen, they feared the potential for abuse might be even greater.

FDA Directs ADHD Drug Manufacturers to Notify Patients about Cardiovascular Adverse Events and Psychiatric Adverse Events.


“An FDA review of reports of serious cardiovascular adverse events in patients taking usual doses of ADHD products revealed reports of sudden death in patients with underlying serious heart problems or defects, and reports of stroke and heart attack in adults with certain risk factors.”

“Another FDA review of ADHD medicines revealed an increased risk  for drug-related psychiatric adverse events, such as hearing voices, becoming suspicious for no reason, or becoming manic, even in patients who did not have previous psychiatric problems. ”

The medicines that are the focus of the revised labeling and new Patient Medication Guides include the following 15 products:

  • · Adderall (mixed salts of a single entity amphetamine product) Tablets
  • · Adderall XR (mixed salts of a single entity amphetamine product) Extended-Release Capsules
  • · Concerta (methylphenidate hydrochloride) Extended-Release Tablets
  • · Daytrana (methylphenidate) Transdermal System
  • · Desoxyn (methamphetamine HCl) Tablets
  • · Dexedrine (dextroamphetamine sulfate) Spansule Capsules and Tablets
  • · Focalin (dexmethylphenidate hydrochloride) Tablets
  • · Focalin XR (dexmethylphenidate hydrochloride) Extended-Release Capsules
  • · Metadate CD (methylphenidate hydrochloride) Extended-Release Capsules
  • · Methylin (methylphenidate hydrochloride) Oral Solution
  • · Methylin (methylphenidate hydrochloride) Chewable Tablets
  • · Ritalin (methylphenidate hydrochloride) Tablets
  • · Ritalin SR (methylphenidate hydrochloride) Sustained-Release Tablets
  • · Ritalin LA (methylphenidate hydrochloride) Extended-Release Capsules
  • · Strattera (atomoxetine HCl) Capsules

FDA Approves Extended-Release Once-Daily Epilepsy Drug.


An oral once-daily extended release formulation of topiramate (Trokendi XR) for the treatment of epilepsy has received final approval from the US Food and Drug Administration (FDA), according to an announcement from Supernus Pharmaceuticals Inc.

The specialty pharmaceutical company said the product should be available in pharmacies over the next few weeks. It is indicated for initial monotherapy in patients 10 years of age and older with partial-onset or primary generalized tonic-clonic seizures, adjunctive therapy in patients 6 years of age and older with partial-onset or primary generalized tonic-clonic seizures, and adjunctive therapy in patients 6 years of age and older with seizures associated with Lennox-Gastaut syndrome.

“We are very excited about the approval of Trokendi XR and its upcoming launch,” said Jack Khattar, chief executive officer, president and director of Supernus, in a press statement. “This is excellent news for Supernus, its shareholders, and patients with epilepsy. We remain committed to the epilepsy community and very much look forward to now having two products, Trokendi XR and Oxtellar XR, available to patients.”

The approval letter states that the FDA has completed its review of the application and that Trokendi XR is approved effective August 16 for use as recommended in the agreed-upon labeling, according to the statement that appears on the Supernus Web site.

The company noted that the product will be available in 25-mg, 50-mg, 100-mg, and 200-mg extended-release capsules.

The FDA granted a waiver for certain pediatric study requirements and a deferral for submission of postmarketing pediatric pharmacokinetic assessments that are due in 2019, followed by clinical assessments in 2025, according to the press release.

Oxtellar XR (extended-release oxcarbazepine) received FDA approval in late 2012 and was introduced in the United States earlier this year. Oxtellar XR is indicated for adjunctive therapy in the treatment of partial seizures in adults and in children aged 6 to 17 years.

Source: medscape.com

FDA Taking Closer Look at Extended-Release Generics .


The failure of an extended-release form of generic Wellbutrin (bupropion) to perform as well as its brand-name counterpart has prompted the FDA to take a closer look at the way all extended-release generics are made, reports the New York Times.

“This has actually prompted us to change our policy,” Gregory P. Geba, director of the FDA’s office of generic drugs, told the Times in an interview.

While generic drugs are required to have the same active ingredient as brand-name versions, critics say that manufacturers of generics do not always succeed in designing ways to deliver extended-release formulations, and the FDA has been slow to act on this.

The 300-mg formulation of extended-release bupropion made by Impax Laboratories was pulled from the market in October after an FDA analysis found that it was not therapeutically equivalent to Wellbutrin XL 300 mg.

Source:  New York Times