The Food and Drug Administration (FDA) will fund systematic research on the safety of medications used during pregnancy in collaboration with private research entities, the agency announced in late December 2009.
Because of ethical concerns, it is very difficult to conduct prospective, controlled clinical trials to study the effects of medications used during pregnancy. Currently, the FDA classifies the pregnancy risk level of medications largely on the basis of animal studies and anecdotal reports. The proposed research program will systematically analyze health outcomes of mothers and babies in the naturalistic setting. A network of 11 health care sites will generate a large amount of health care data before and after birth on women who take prescription medications during pregnancy and those who do not and their newborns. The endeavor involves the HMO Research Network (HMORN), Kaiser Permanente, and Vanderbilt University. HMORN is a consortium of 16 health maintenance organizations that have the capability and experience to conduct research.
Exposure to valproic acid and divalproex during pregnancy increases the risk of major birth defects, the FDA warned in a public announcement this past December. The birth defects include neural tube defects, craniofacial defects, and cardiovascular malformations. The agency urged health care professionals to inform their pregnant patients and patients who may become pregnant about these risks and that "women of childbearing potential should only use valproate if it is essential to manage their medical condition." In addition, pregnant women who must use valproate or other antiepileptic drugs are encouraged to enroll in the North American Antiepileptic Drug Pregnancy (NAAED) Registry at <www.aedpregnancyregistry.org>. The NAAED Registry has reported a major malformation rate of 10.7 percent (95 percent confidence interval, 6.3 percent-16.9 percent) in children born to women who had been exposed to an average of 1,000 mg/day of valproic acid monotherapy during pregnancy. This rate was four times the malformation rate in children with prenatal exposure to other antiepileptic drugs.
Details about the safety warning for valproate are posted at <www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm192649.htm>.
Olanzapine long-acting injection was approved by the FDA for the treatment of schizophrenia in adults, Eli Lilly and Co. announced last December. The suspension is administered through intramuscular injection every two or four weeks.
The injection had undergone several rounds of FDA review in the past few years, including at a Psychopharmacologic Advisory Committee meeting in February 2008. The agency had been reluctant to approve the injection because of a rare but potentially serious adverse event, known as postinjection delirium/sedation syndrome (PDSS), during clinical trials. Symptoms include sedation, which may range from mild drowsiness to loss of consciousness or coma, and delirium, confusion, disorientation, agitation, anxiety, and other cognitive impairment. In clinical trials, patients with PDSS generally recovered within 72 hours.
According to the company's most recent data, PDSS was reported in about 2 percent of patients involving <0.1 percent of total number of injections. Most of the PDSS events occurred within the first three hours after an injection, but delayed events have been reported as well.
The distribution of olanzapine long-acting injection is limited to prescribers, health care facilities, and patients who enroll in a patient-care program. The injection must be given at a health care facility where emergency care is available, and the patient must remain there for at least three hours afterward.
The prescribing information and patient medication guide for olanzapine long-acting injection can be accessed at <www.zyprexarelprevv.com/index.jsp>.
The FDA approved quetiapine extended-release tablets for the adjunctive treatment of major depressive disorder in combination with antidepressants, according to an AstraZeneca announcement this past December. However, the agency rejected the company's other applications, which had asked the drug be approved as an acute and long-term monotherapy treatment for major depressive disorder.
In late December 2009, the FDA rejected Pfizer's new drug application for pregabalin as a monotherapy for generalized anxiety disorder (GAD), citing insufficient data to support this indication. The agency is still reviewing an application for the drug as an adjunctive treatment for GAD. Pregabalin is approved for treatment of fibromyalgia, neuropathic pain, and partial seizures.
The safety information in the labels of venlafaxine and desvenlafaxine was revised in November 2009. Flulike symptoms upon discontinuation of venlafaxine was added to the precautions section. "Skin and subcutaneous tissue disorder-angionedema" was added to the adverse-reactions section for desvenlafaxine.
In December 2009, the safety information in the label for quetiapine extended-release tablets was revised. New information and data on hyperglycemia, hyperlipidemia, weight gain, increased blood pressure, and potential for cognitive and motor impairment and suicide were added to the warnings and precautions section.
Safety labeling was also revised for topiramate tablets and capsules. A new subsection in warnings and precautions states that antiepileptic drugs including topiramate should be gradually withdrawn when discontinued to minimize seizure potential. In addition, patients taking topiramate should be told to seek immediate medical attention if they experience any sign of eye disorders.
Safety-related drug labeling changes can be accessed at <www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm>.
An orexin receptor antagonist known as almorexant showed promise in a phase 3 clinical trial for the treatment of insomnia, according to Actelion, a Swiss company developing the drug. In the trial, almorexant was significantly better than placebo in reducing waking after sleep onset as measured by polysomnography and self-reports. Orexins are a type of neuropeptides produced by specialized neurons in the hypothalamus and are involved in regulating the sleep-wake cycle. Almorexant is an oral drug that penetrates the blood-brain barrier and reversibly blocks orexin receptors. Orexins may play a role in other neurological functions such as reward seeking, food consumption, and metabolism.
A new drug application was submitted to the FDA for the antipsychotic drug lurasidone, developed by the Japanese company Dainippon Sumitomo Pharma, for the acute treatment of schizophrenia, the company announced in January. Lurasidone binds with high affinity to dopamine D2; serotonin 5-HT7, 5-HT2A, and 5-HT1A; and norepinephrine alpha2C receptors.
Last December Jazz Pharmaceuticals announced the submission of a new drug application to the FDA for sodium oxybate for the treatment of fibromyalgia. Sodium oxybate is approved in the United States for the treatment of excessive daytime sleepiness and cataplexy associated with narcolepsy.
GlaxoSmithKline has already paid nearly $1 billion to settle lawsuits regarding its antidepressant drug paroxetine, Bloomberg.com reported last December. Many of these cases involve claims that associated the drug with suicide, addiction, and birth defects.
The European Commission announced in January that it began to investigate Lundbeck A/S for possible antitrust violations. The company is suspected of having blocked generic versions of its antidepressant citalopram from entering the European market after the patent expired in 2003.