New treatment for age-related macular degeneration approved in U.S. December 21, 2004
New medication approved for mucositis associated with cancer treatment December 16, 2004
FDA approves single-dose bacterial vaginosis treatment December 16, 2004
Savient wins approval for osteoarthritis medication December 8, 2004
New drug approved in U.S. for treatment of overactive bladder November 29, 2004
British drugmaker wins U.S. approval for phosphate binder October 28, 2004
Facial wrinkle filler wins approval in U.S. October 15, 2004
Treatments for radiation contamination approved by the FDA August 12, 2004
FDA approves Sculptra for the treatment of facial lipoatrophy in HIV patients August 4, 2004
FDA approves new drug for treatment of alcoholism August 2, 2004
Antidiarrheal approved for use in adults July 26, 2004
Watson Pharmaceuticals announces launch of new acute pain product June 18, 2004
Low-dose osteoporosis prevention patch granted FDA approval June 10, 2004
U.S. FDA approves new treatment for postoperative pain June 7, 2004
FDA approves new drug for myelodysplastic syndrome May 24, 2004
New treatment for Parkinson's disease approved by FDA April 22, 2004
Rapid-acting insulin analog wins FDA approval April 20, 2004
FDA approves extended-release generic oxycodone hydrochloride March 26, 2004
Novartis wins approval for drug to prevent organ rejection March 4, 2004
FDA approves ImClone drug for colorectal cancer February 13, 2004
FDA approves new menopause therapy from Solvay February 11, 2004
Anika wins FDA approval for new osteoarthritis treatment February 6, 2004
New COPD treatment approved in the U.S. February 3, 2004
Insomnia drug from Sepracor approved December 21, 2004
Lens stain approved for use in cataract surgery December 21, 2004
FDA approves Combunox tablet for the treatment of acute, moderate to severe pain December 16, 2004
Shire's extended-release Equetro approved in U.S. for bipolar disorder December 14, 2004
FDA approves first monoclonal antibody treatment for MS November 30, 2004
New treatment for lung cancer approved in U.S. November 22, 2004
Serono wins U.S. approval for infertility treatment October 18, 2004
FDA grants approval for Schwarz Pharma Parkinson's drug August 31, 2004
FDA approves Lilly's Cymbalta for the treatment of depression August 5, 2004
Two new fixed-dose HIV drug combinations approved by the FDA August 3, 2004
New cholesterol drug approved in the U.S. July 27, 2004
FDA approves 12-hour dose of codeine cough suppressant June 29, 2004
New treatment for overactive bladder wins FDA approval June 9, 2004
New glaucoma treatment approved in U.S. June 9, 2004
FDA grants approval for new travelers' diarrhea treatment May 27, 2004
FDA approves new filler for facial wrinkles April 22, 2004
FDA approves nasal aerosol from Aventis for allergic rhinitis April 22, 2004
New class of antibiotics approved by FDA April 5, 2004
FDA approves treatment for secondary hyperparathyroidism in dialysis patients March 9, 2004
Angiogenesis inhibitor approved to treat colorectal cancer February 27, 2004
First injectable treatment of acetaminophen poisoning appoved by FDA February 11, 2004
Alimta first drug approved to treat rare type of cancer February 6, 2004
Pfizer drug approved to treat hypertension and high cholesterol February 3, 2004
December 21, 2004
ST. LOUIS (MD Consult) - On December 16, 2004, Sepracor Inc announced that the U.S. Food and Drug Administration (FDA) has approved Lunesta (eszopiclone), formerly referred to as Estorra, 1-, 2-, and 3-mg tablets for the treatment of insomnia. Insomnia can include difficulty falling asleep as well as difficulty maintaining sleep through the night. The recommended dosing to improve sleep onset or maintenance is 2 or 3 mg for adult patients (aged 18-64 years) and 2 mg for older adult patients (aged 65 and older). The 1-mg dose is for sleep onset in older adult patients whose primary complaint is difficulty falling asleep.
Data from a landmark, long-term (6-month), double-blind, placebo-controlled safety and efficacy study in 788 patients were reviewed by the FDA as part of the new drug application for eszopiclone and served as a basis for the FDA's decision to not limit Lunesta's indication to short-term use. Sepracor's 6-month study was the first of its kind for a prescription nonbenzodiazepine for the treatment of insomnia.
"Unlike all other available prescription sleep aids, which are generally indicated for short-term use, eszopiclone has been studied and approved for use when longer-term treatment is needed," said Andrew Krystal, M.D., Director of the Sleep Disorder Research Laboratory and Insomnia Program at Duke University Medical Center, Durham, NC. "The six-month, double-blind, placebo-controlled study of eszopiclone provides unprecedented evidence of sustained efficacy. There were statistically significant improvements in patient-reported measures of sleep onset and sleep maintenance versus placebo for the entire duration of the study with no evidence of tolerance."
Lunesta is indicated for patients who have difficulty falling asleep as well as for those who are unable to sleep through the night.
Sepracor will continue to study Lunesta in patients suffering from insomnia. The company will also continue to evaluate Lunesta for the treatment of insomnia in patients suffering from depression or pain, and in women who are experiencing the effects of perimenopause.
The Lunesta new drug application contained information from a total of 24 clinical trials, which included more than 2,700 adult and older adult (aged 65 and older) subjects and more than 60 preclinical studies. Sepracor conducted 6 randomized, placebo-controlled phase III studies for the treatment of chronic or transient insomnia in both adult and older adult patients and included these studies as part of the application, which served as the basis for the FDA's approval of Lunesta.
According to Lunesta's manufacturer, an estimated 100 million adult Americans have either chronic or occasional insomnia. Symptoms of insomnia include difficulty falling asleep, awakening frequently during the night, waking up too early, an inability to fall back to sleep, or awakening feeling unrefreshed. Insomnia can be a serious condition. If left untreated, it may become progressively worse and can potentially affect a person's emotional, mental, and physical health.
The U.S. market for prescription sleep products, not including off-label use of central nervous system agents for the treatment of insomnia, was approximately $2.1 billion between November 2003 and October 2004, representing a 20% increase over the same period the previous year, according to IMS Health information.
It is important to note that because sleep disturbances may be caused by underlying physical or psychiatric disorders, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric or medical illness that should be evaluated.
Patients should only take Lunesta when they are prepared to get a full night of sleep. Until they know how they will react to the medication, patients should not drive or operate machinery when taking it.
Sepracor's corporate headquarters are located in Marlborough, Mass. The company plans to make the product available in January 2005.
Prescription information is available at sepracor.com.
December 21, 2004
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) announced on December 20, 2004, it had approved Macugen (pegaptanib sodium injection), a new therapy to slow vision loss in people with the eye disease neovascular (wet) age-related macular degeneration (AMD). Pegaptanib is a selective vascular endothelial growth factor (VEGF) antagonist.
AMD, a retinal disease causing severe and irreversible vision loss, is a major cause of blindness in persons older than 55 years. Untreated, the majority of eyes affected with wet AMD may become functionally blind. Wet AMD, which accounts for approximately 10% of AMD, is caused by the growth of abnormal leaky blood vessels that eventually damage the area of the eye responsible for central vision, which is essential for most fine-detail visual activities, including reading, driving, and recognizing faces.
The safety and efficacy of Macugen was studied in 2 trials in patients with wet AMD for 2 years. Patients treated with Macugen exhibited a significant decrease in vision loss in both trials. Serious adverse events related to the injection procedure included infections, retinal detachment, and traumatic cataract. Other frequently reported adverse events in patients treated with Macugen were eye irritation, eye pain, hemorrhage under the conjunctiva, and blurred vision.
The new drug application for Macugen was received and approved in 6 months. Macugen therapy is being co-developed by Eyetech Pharmaceuticals, Inc, and Pfizer Inc. Eyetech and Pfizer will co-market the product in the United States.
For more details on Macugen, including full prescribing information, visit macugen.com.
December 21, 2004
ST. LOUIS (MD Consult) - On December 16, 2004, the U.S. Food and Drug Administration (FDA) announced the approval of Vision Blue (trypan blue ophthalmic solution). Vision Blue is the first product approved in the United States for staining the anterior lens capsule during cataract surgery.
The use of Vision Blue will enhance the ability of ophthalmologists to remove white cataracts, a very advanced mature cataract (typically seen in countries where medical care is not widely available), by allowing the surgeon to see the capsule as it is cut and removed. Clean cuts in the capsule are known to reduce some of the risks associated with the surgical removal of a cataract. Over 1.4 million people have cataract surgery each year in the United States, although only a small portion of these cataracts are mature white cataracts.
Cataract development is a normal process of aging, but cataracts can also develop from eye injuries, medications, or certain diseases, such as diabetes. The lens focuses light rays on the retina—the layer of light-sensing cells lining the back of the eye—to produce a sharp image. When the lens becomes cloudy, light rays cannot pass through it easily, and vision is blurred. Surgery is the only way to remove a cataract. Selective staining of the anterior lens capsule with Vision Blue makes it easier to visualize, manipulate, and remove the cloudy lens through a surgical incision.
The safety and effectiveness of Vision Blue has been established in pediatric patients. No overall differences in safety and effectiveness have been observed between elderly and younger patients.
The adverse reactions from the use of Vision Blue are generally self-limited and of short duration. They include discoloration of intraocular lenses and staining of the posterior lens capsule and the vitreous.
DORC International of the Netherlands is the manufacturer of Vision Blue. For more information, visit dorc.nl.
December 16, 2004
ST. LOUIS (MD Consult) - On December 15, 2004, the U.S. Food and Drug Administration (FDA) approved a new intravenous biologic product, Kepivance (palifermin) to help reduce the chance that certain cancer patients, those with blood cancers undergoing chemotherapy and radiation in preparation for bone marrow transplants, will develop mucositis. Palifermin also shortens the duration of the condition.
Mucositis is a common complication of the high-dose chemotherapy and radiation therapy regimens associated with bone marrow transplant. Patients with mucositis have difficulty eating and swallowing. In the most severe form of the condition, patients cannot eat or drink at all and must receive nutrition and fluid replacement intravenously.
Palifermin is a manufactured version of a naturally occurring human protein called keratinocyte growth factor (KGF). KGF stimulates the growth of cells in the skin and on the surface layer of the mouth, stomach, and colon. Palifermin, like the natural KGF, also stimulates cells on the surface layer of the mouth to grow. This is thought to lead to faster replacement of these cells when killed by the cancer treatments and is believed to speed up the healing process of mouth ulcers.
In a study of 212 patients with leukemia or lymphoma who were receiving high doses of chemotherapy and radiation treatments associated with bone marrow transplantation, 98% of the patients who did not receive palifermin developed severe mucositis compared with 63% of those who received the drug. Also, for those who received the drug, severe mucositis lasted an average of 3 days, compared with 9 days for those receiving a placebo.
Palifermin was given intravenously for 3 days before cancer treatment began and 3 days after treatment.
The most common adverse effects of palifermin were skin rash, unusual sensations in the mouth (such as tingling), and increases in blood proteins suggesting pancreatic irritation. No serious adverse effects have been reported related to use of palifermin. Palifermin has not yet been shown to be safe and effective in patients being treated for forms of cancer other than leukemia or lymphoma.
Kepivance is manufactured by Amgen Inc of Thousand Oaks, Calif.
December 16, 2004
ST. LOUIS (MD Consult) - Forest Laboratories, Inc, announced on November 19, 2004, that Combunox (oxycodone hydrochloride and ibuprofen) tablets (CII) was approved by the U.S. Food and Drug Administration (FDA) for the short-term management of acute, moderate to severe pian. Combunox is the first fixed-dose combination of the opioid oxycodone hydrochloride (5 mg) and the nonsteroidal anti-inflammatory drug ibuprofen (400 mg). The manufacturer expects to make Combunox available in the United States early next year.
Combunox combines oxycodone, which is generally considered to be up to 1.5 times more potent than hydrocodone and nearly 10 times more potent than codeine as a narcotic analgesic, with ibuprofen at its typical analgesic dose. The clinical benefit of Combunox is attributed to the distinct actions of each component.
The FDA approved Combunox based on a review of efficacy data from 3 double-blind placebo-controlled trials. In these trials, Combunox provided significantly greater pain relief than oxycodone 5 mg alone, ibuprofen 400 mg alone, or placebo. Pooled data from the complete safety database, which included multiple-dose study, found Combunox to be safe and well tolerated.
Acute pain is generally caused by injury or surgery and is the most common reason why patients seek medical attention (25 million Americans annually), stated Forest in a November 2004 press release. In addition to unnecessary suffering, inadequately controlled acute pain causes complications that can increase the length of hospital stays, rehospitalization rates, and outpatient visits.
More information on Combunox, including prescribing information and details regarding its availability, can be accessed by visiting Combunox.com or by calling 1-800-678-1605, ext. 7301.
December 16, 2004
ST. LOUIS (MD Consult) - KV Pharmaceutical Company announced on December 2, 2004, that it had received approval from the U.S. Food and Drug Administration (FDA) to market Clindesse (clindamycin phosphate) Vaginal Cream, 2%, a single-dose prescription cream therapy indicated to treat bacterial vaginosis.
Clindesse is the first approved single-dose therapy for patients with bacterial vaginosis, the most common form of vaginitis. The 1-dose product was demonstrated in clinical trials to effectively treat bacterial vaginosis and its symptoms with results equivalent to 7 days' treatment with another vaginal cream. Currently, other approved bacterial vaginosis treatments require a course of 3 to 10 doses.
A spokesperson for KV announced the company's expectation that the new single-dose therapy would help increase patient compliance with treatment. Clindesse is expected to launch in January 2005.
Bacterial vaginosis is believed to represent nearly half of all vulvovaginal infections. Accurate diagnosis of bacterial vaginosis by a physician can be difficult because more than 50% of patients may be asymptomatic. Additionally, it is widely believed that patients may inaccurately self-diagnose and therefore improperly treat bacterial vaginosis and other vaginal infections. Numerous articles in peer-reviewed journals cite the association of bacterial vaginosis with other conditions, including pelvic inflammatory disease, preterm labor, and a number of other gynecologic and obstetric complications.
Clindesse is contraindicated in persons with a history of hypersensitivity to clindamycin, lincomycin, or any of the other components of this vaginal cream, as well as persons with a history of regional enteritis, ulcerative colitis, or "antibiotic-associated" colitis.
Clindesse contains mineral oil that may weaken latex or rubber products such as condoms or contraceptive diaphragms. Therefore, the use of such barrier contraceptives is not recommended concurrently or for 5 days after treatment with Clindesse. During this time, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clindamycin. Orally and parenterally administered clindamycin has been associated with severe colitis. Therefore, it is important to consider this diagnosis in patients who experience diarrhea subsequent to the administration of Clindesse, even though there is minimal systemic absorption of clindamycin from the vagina with administration of Clindesse Vaginal Cream.
In clinical trials (n = 368), the most frequent reported adverse events were vaginosis fungal (14.1%), vulvovaginal pruritus (3.3%), and headache (2.7%).
For further information about St Louis-based KV Pharmaceutical Company and its products, visit kvpharmaceutical.com.
December 14, 2004
ST. LOUIS (MD Consult) - On December 13, 2004, Shire Pharmaceuticals Group PLC announced that the U.S. Food & Drug Administration (FDA) had approved Equetro (extended-release carbamazepine capsules), previously known as SPD417, for the treatment of patients with bipolar disorder.
Bipolar disorder is among the 6 leading mental disorders worldwide, according to the World Health Organization. Each year, it is estimated that more than 2 million American adults-about 1% of the population aged 18 years and older-are afflicted with bipolar disorder, also known as manic depression. Of the 750,000 currently diagnosed, about 650,000 are receiving treatment. Approximately $1.9 billion is spent in the United States on treatment of this disease annually, and this is expected to grow to $2.4 billion by 2007, according to Shire.
Bipolar disorder is characterized by episodes of mania and depression, with periods of normal mood in between. The disorder can have devastating effects on a person's life, although proper diagnosis and early treatment can usually alter the course of the illness. Equetro is indicated for the treatment of acute manic and mixed episodes associated with bipolar I disorder.
Equetro significantly reduces the manic symptoms in patients with bipolar disorder. Additionally, in clinical trials, patients treated with the product demonstrated no clinically significant weight gain or increase in blood glucose levels, thereby creating an effective tolerability profile. Available in 100-, 200-, and 300-mg dosage strengths, Equetro is the only carbamazepine formulation proven effective for treatment of bipolar disorder.
An analysis was undertaken to study pooled data from 2 identically designed, 3-week, double-blind, placebo-controlled phase III trials of Equetro monotherapy in patients initially requiring hospitalization. Each trial involved 443 patients aged 18 to 76 years with a DSM-IV diagnosis of bipolar disorder (current episode manic or mixed) who were randomly assigned to receive double-blind treatment with either Equetro or placebo.
The pooled analysis revealed that, by the end of the trials, both manic and mixed patients receiving Equetro experienced significant reductions in Young Mania Rating Scale total scores as well as significant improvements in Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores. Also, Equetro-treated mixed patients experienced total score improvements on the Hamilton Depression Rating Scale. Investigators measured the safety and tolerability of Equetro by measuring participants' weight, blood glucose levels, cholesterol levels, and interval between heartbeats, as well as adverse event monitoring. The results of pooled data analysis were presented November 18, 2004, at the 17th annual U.S. Psychiatric and Mental Health Congress in San Diego, Calif.
As Richard H. Weisler, MD, adjunct professor of psychiatry at University of North Carolina at Chapel Hill School of Medicine, adjunct assistant professor of psychiatry and behavioral sciences at Duke University Medical Center, and primary investigator of the Equetro clinical trials commented, "Equetro demonstrates significant reduction of manic symptoms in both manic and mixed patients as early as the first week of treatment. Equetro showed improvement in treating depressive symptoms in mixed patients who suffer both significant depression and mania at the same time."
Equetro has a formulation patent that runs until 2011, and Shire will have 3 years' access to market exclusivity under the U.S. Hatch-Waxman Act. The medication will be available for prescribing in the United States in the first quarter of 2005.
Shire also markets carbamazepine extended release under the trade name Carbatrol. Carbatrol is indicated in the United States for the treatment of partial and generalized seizure disorders, as well as trigeminal neuralgia.
For further information, visit the manufacturer's Web site at shire.com.
December 8, 2004
ST. LOUIS (MD Consult) - Savient Pharmaceuticals, Inc, announced on December 7, 2004, it had received approval from the U.S. Food and Drug Administration (FDA) for Nuflexxa (1% sodium hyaluronate). Nuflexxa is indicated for the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy and simple analgesics (eg, acetaminophen).
Nuflexxa is the first and only non–avian-derived hyaluronic acid (HA) approved in the United States. It is a product of Bio-Technology General (Israel) Ltd, a subsidiary of Savient.
Savient is in the process of completing a supplement to the labeling to support room temperature storage versus the refrigerated expiration dating approved by the FDA. The supplement is expected to be submitted early in the first quarter of 2005.
The U.S. Centers for Disease Control and Prevention and the Arthritis Foundation report that the number of Americans with arthritis or chronic joint symptoms in 2002 was estimated to be 70 million (1 in 3 adults), twice the prevalence present in 1985. According to a study recently published by Millennium Research Group, in 2004 the U.S. market for HA treatments of osteoarthritis is approximately $350 million, an increase of 11% from 2003.
Savient's drug is also approved in Europe, where it will be marketed under the brand name Euflexxa.
For more information about Savient and its products, visit savientpharma.com.
November 30, 2004
ST. LOUIS (MD Consult) - On November 23, 2004, the U.S. Food and Drug Administration (FDA) licensed a new biologic approach to treat relapsing forms of multiple sclerosis (MS) to reduce the frequency of symptom flare-ups or exacerbations of the disease. MS is a chronic, often disabling disease of the brain and spinal cord.
Natalizumab, the new product, is a monoclonal antibody bioengineered from part of a mouse antibody to closely resemble a human antibody. It is being marketed under the tradename Tysabri. The product is given intravenously once a month in a physician's office.
According to the Multiple Sclerosis Association of America, approximately 350,000 individuals have been diagnosed with MS in the United States, with an estimated 10,000 new cases diagnosed each year. The most common form of MS at the time of initial diagnosis is a relapsing-remitting form, in which acute symptoms or worsening of neurologic function (referred to as "relapses," "attacks," or "exacerbations") occur intermittently. The symptoms can diminish or disappear for months or years between relapses.
Although the cause of MS is unknown, it is widely considered to be an autoimmune disease in which a person's immune system attacks the brain, spinal cord, or both. Tysabri appears to work by binding to these immune system cells, thus preventing them from traveling to the brain where they can cause damage.
Antibodies are proteins produced by a person's immune system to fight foreign substances, such as infections. Monoclonal antibodies, such as natalizumab, can be produced in large quantities in cell culture in a laboratory setting. They can be designed to bind to proteins on the body's normal cells. By recognizing and attaching to these proteins, monoclonal antibodies can interfere with (or alter) normal or abnormal cellular responses. In this way, monoclonal antibodies may be useful in the treatment of certain diseases such as MS.
The approval of Tysabri is based on positive results seen in patients after 1 year of treatment. This product received accelerated approval because it appears to provide substantial benefit for patients with a serious disease. As part of that approval, the manufacturer has committed to continuing its trials of this product for another year.
Tysabri was evaluated for safety and efficacy in 2 ongoing randomized, double-blind, placebo-controlled trials in patients with relapsing forms of MS. In the first clinical trial of the product's safety and efficacy, the drug reduced the frequency of relapses by 66% relative to placebo.
In a second trial, patients who had been treated with Avonex (interferon beta-1a), an approved treatment for MS, but who had experienced 1 or more relapses while on Avonex, were randomly assigned to receive Tysabri or placebo. Avonex was continued throughout the study for both groups. In this trial, natalizumab reduced the frequency of relapses by 54% relative to placebo.
The most frequently reported serious adverse reactions were infections, including pneumonia, temporary hypersensitivity reactions (such as rash, fever, low blood pressure, and chest pain), depression, and gallstones. These serious adverse reactions were uncommon. Common adverse reactions were generally mild and included non-serious infections (such as vaginal, urinary tract, lower respiratory tract, gastrointestinal system infections), headache, depression, joint pains, and menstrual disorders.
Tysabri is marketed by Biogen Idec, Inc, of Cambridge, Mass, and Elan Pharmaceuticals, Inc, of Dublin, Ireland.
November 29, 2004
ST. LOUIS (MD Consult) - On November 22, 2004, GlaxoSmithKline and Yamanouchi announced that Vesicare (solifenacin succinate) had been approved by the U.S. Food and Drug Administration for the treatment of overactive bladder (OAB) with symptoms of urgency, frequency, and urge incontinence. In clinical studies, 5- and 10-mg doses of Vesicare showed clinical and statistical improvements in all symptoms of OAB. Specifically, once-daily Vesicare was found to significantly reduce the number of incontinence episodes for patients during a 12-week study period.
Although OAB affects an estimated 17 to 20 million persons in the United States, few understand that is a treatable condition. Many mistakenly believe this is a natural part of aging, are embarassed to discuss it, or believe there is no treatment option available.
Therefore, patients gradually develop coping behaviors to manage their symptoms. These coping mechanisms include restricting fluids, carrying extra clothing, "mapping" bathroom locations, or even choosing not to leave the house. None of these behaviors, however, are clinically proven to be successful in treating the symptoms of OAB.
The debilitating effects of OAB exact not only a physical, social, and emotional toil on patients, but a financial one as well. It is estimated that costs related to OAB were nearly $14 billion in the United States in 2000, similar to that of gynecologic and breast cancers, osteoporosis, or arthritis.
Clinical Trial Results
The approval of Vesicare was based on clinical findings from 4 double-blind, 12-week, randomized, placebo-controlled, parallel-group, multicenter trials involving more than 3,000 patients with symptoms of urgency, frequency, and/or urge incontinence.
Once-daily Vesicare 5 and 10 mg showed statiscally and clinically significant improvement in all major symptoms of OAB. Reduction in the number of incontinence episodes was also significantly greater with Vesicare 5 and 10 mg (P < .001) compared with placebo. Vesicare has approximately a 50-hour half-life. Also, once-daily Vesicare demonstrated 24-hour control of OAB symptoms.
Across all 4 studies, the efficacy of once-daily administration of 5 or 10 mg of Vesicare was consistent across patient age and gender. The most common adverse effects were dry mouth (5 mg, 10.9%; 10 mg, 27.6% vs placebo, 4.2%), constipation (5 mg, 5.4%; 10 mg, 13.4% vs placebo, 2.9%), and blurred vision (5 mg, 3.8%; 10 mg, 4.8% vs 1.8%).
Vesicare is indicated for the treatment of OAB with symptoms of urgency, frequency, and urge incontinence. The recommend dose of Vesicare is 5 mg once-daily. As with other anticholinergic agents, Vesicare is contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and in patients who have demonstrated hypersensitivity to the drug substance or other components of the product. Vesicare should be administered with caution to patients with bladder outflow obstruction, decreased gastrointestinal motility, controlled narrow-angle glaucoma, and reduced renal or hepatic function.
Vesicare is being copromoted by Japanese pharmaceutical company Yamanouchi and GlaxoSmithKline, which is headquartered in the United Kingdom.
For more information, visit vesicare.com.
November 22, 2004
ST. LOUIS (MD Consult) - On November 19, 2004, the U.S. Food and Drug Administration (FDA) announced the approval of Tarceva (erlotinib) tablets as a single-agent treatment for locally advanced or metastatic non–small cell lung cancer (NSCLC), the most common form of lung cancer in the United States. Tarceva is being approved as a treatment for patients whose cancer has continued to progress despite other treatments, including at least 1 prior chemotherapy regimen.
The mechanism of action by which Tarceva exerts its clinical benefit is not fully understood. However, Tarceva was developed to block growth stimulatory signals in cancer cells. These signals are mediated in part by enzymes called tyrosine kinsases, which are associated with a human epidermal growth factor receptor (EGFR). The drug has shown improved survival in patients with locally advanced or metastatic NSCLC. Tarceva received "fast track" status from the FDA during its development.
Safety and efficacy were demonstrated in a randomized trial involving 731 patients, comparing Tarceva with placebo. The primary end point in this trial was survival. The median overall survival was 6.7 months in the Tarceva group compared with 4.7 months in the placebo group.
In about one third of the patients, tumor cells were examined to see whether they had high or low levels of EGFR. Among the approximately 55% who had high EGFR, the effect on survival was much greater than it was in people with low EGFR levels. The relationship will be explored further in the future.
Common adverse effects reported with Tarceva in clinical trials were diarrhea, rash, nausea, and vomiting. Tarceva may cause fetal harm when administered to pregnant women.
The FDA reviewed the application for Tarceva using the "rolling review" procedures that are available to new drug applications designated as being on the fast track. In rolling review, the FDA starts reviewing specific components of a drug approval application even before all the application components have been submitted to the agency. For Tarceva, the first piece of the application was submitted in January 2004 and the last portion in July 2004.
Cancer of the lung and bronchus is the second most common cancer among both men and women and is the leading cause of cancer death in both sexes in the United States. NSCLC is the most common type of lung cancer, accounting for almost 80% of cases.
The drug will be manufactured by OSI Pharmaceuticals, Inc, and distributed by Genentech, Inc, of South San Francisco, Calif.
October 28, 2004
ST. LOUIS (MD Consult) - On October 27, 2004, Shire Pharmaceuticals Group PLC announced it had received approval from the U.S. Food and Drug Administration (FDA) for Fosrenol (lanthanum carbonate), a phosphate binder that reduces elevated blood levels of phosphate in patients with end-stage renal disease (ESRD).
According to Shire, fewer than one third of patients with ESRD are able to medically control phosphorus levels. Fosrenol works by binding to dietary phosphate in the gastrointestinal tract; once bound, the Fosrenol/phosphate complex cannot pass through the intestinal lining into the bloodstream and is eliminated from the body. As a consequence, overall phosphate absorption from the diet is decreased significantly.
Shire has conducted an extensive clinical research program involving nearly 2,000 patients treated with Fosrenol, some of whom have been treated for 36 months or more. This study demonstrated that Fosrenol is an effective phosphate binder with a well-established safety profile for long-term use.
In its press release announcing the approval of Fosrenol, Shire stated that there are currently over 1 million patients on dialysis worldwide, and the number is estimated to be increasing by approximately 8% per year. Up to 80% of patients have high phosphate levels. If left untreated, high phosphate levels can lead to diseases of the heart and blood vessels; these may be fatal.
Fosrenol will be available in the United States in 250-mg and 500-mg strengths. Most patients will require a total daily dose of 1,500 to 3,000 mg to reduce phosphate levels to less than 6.0 mg/dL. Fosrenol is formulated as a chewable tablet that need not be accompanied by water to be swallowed, an important benefit for ESRD patients who have to restrict fluid intake.
Chronic kidney failure is complicated by hyperphosphatemia caused by the inability of the kidneys (and dialysis) to filter out excess phosphate from food. Even with a low-phosphate diet, as many as 80% of Europe's 225,000 and the United States' 269,000 dialysis patients develop hyperphosphatemia and need treatment with a phosphate-binder. The most well-known consequences of hyperphosphatemia are a range of bone diseases that can cause bone pain, skeletal deformities, and fractures. Hyperphosphatemia is also associated with the development of cardiovascular disease, which accounts for nearly 50% of all deaths in dialysis patients. Ironically, some currently available phosphate binders—although they help control phosphate levels—can worsen these complications. Aluminium-based phosphate binders are associated with severe bone toxicity, whereas calcium-based binders contribute to cardiovascular disease by promoting calcification in the heart and blood vessels.
The drug's manufacturer anticipates that Fosrenol will be available in pharmacies before the end of 2004.
For further information, visit the shire.com.
October 18, 2004
ST. LOUIS (MD Consult) - Swiss biotechnology company Serono announced on October 15, 2004, that the U.S. Food and Drug Administration (FDA) had approved Luveris (lutropin alfa for injection) for concomitant use with Gonal-f (follitropin alfa for injection) for stimulation of follicular development in infertile hypogonadotropic hypogonadal women with profound luteinizing hormone (LH) deficiency (LH < 1.2 IU/L).
Hypogonadotropic hypogonadism is a rare endocrine deficiency. Women with hypogonadotropic hypogonadism are unable to produce the hormones needed for full development of follicles in the ovaries, ovulation, and growth of the lining of the uterus sufficient to support implantation of a fertilized egg and early pregnancy.
Luveris is the first approved recombinant human form of LH, a naturally occurring fertility hormone.
"Luveris, in conjunction with Gonal-f, helps individualize treatment for a special population of infertile patients," said Zev Rosenwaks, MD, Director, Center for Reproductive Medicine and Infertility at New York Weill Cornell. "It provides an option for women who specifically do not produce or secrete LH." Luveris has received orphan drug designation from the FDA Office of Orphan Products Development.
Adverse effects may occur with the use of infertility drugs and therefore should only be prescribed by physicians who are thoroughly familiar with infertility problems and their management. Ovarian hyperstimulation syndrome (OHSS) with or without vascular and pulmonary complications can occur with the use of infertility drugs. Reports of multiple births have been associated with gonadotropin treatments. The most common adverse effects in women using Luveris include headache, abdominal pain, nausea, OHSS, breast pain, and ovarian cyst.
Serono offers a toll-free educational service called Fertility LifeLines (866-538-7879) to patients and health care providers who would like additional information on Luveris and other Serono products. In addition, full prescribing information can be found at www.seronousa.com.
October 15, 2004
ST. LOUIS (MD Consult) - On October 13, 2004, Inamed Corporation and Genzyme Corporation announced that the U.S. Food and Drug Administration (FDA) has granted market approval for Hylaform Plus (hylan-B gel). This large-particle hyaluronic acid-based dermal filler is indicated for the correction of moderate to severe facial wrinkles and folds.
Hylaform Plus is a clear, colorless product that comprises a larger mean hyaluronic gel acid particle size than the companies' previously approved dermal filler, Hylaform.
Hylaform Plus was developed and is manufactured by Genzyme Corporation, a biotechnology company headquartered in Cambridge, Massachusetts, USA. California-based Inamed is Genzyme's worldwide marketing and distribution partner for Hylaform Plus.
More information on Hylaform gel can be found at inamed.com/products/facial/us/physician/hylaform/information.html.
August 31, 2004
ST. LOUIS (MD Consult) - German pharmaceutical company Schwarz Pharma announced on August 30, 2004, it had won approval from the U.S. Food and Drug Administration (FDA) to market its orally dissolving Parkison’s disease treatment, Parcopa (carbidopa-levodopa), in the United States.
Patients with Parkison’s disease experience symptoms such as morning rigidity or "off" periods—episodes of decreased movement or complete immobility—that can make dosing problematic. Unlike conventional carbidopa-levodopa, Parcopa dissolves rapidly in the mouth. They can be swallowed with or without water and are available in various flavors.
Parcopa is indicated in the treatment of the symptoms of idiopathic Parkison’s disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism that may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.
Parcopa is available in the same strengths and has the same dosage schedule as conventional Sinemet(carbidopa-levodopa) tablets. The most common adverse effects include involuntary movements and nausea. Each 10 mg/100 mg tablet and each 25 mg/100 mg tablet contain phenylalanine 3.4 mg. Each 25 mg/250 mg tablet contains phenylalanine 8.4 mg.
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with Parcopa. These inhibitors must be discontinued at least 2 weeks before therapy with Parcopa is initiated. The latter may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (eg, selegiline hydrochloride).
Parcopa is contraindicated in patients with known hypersensitivity to any component of this drug and in patients with narrow-angle glaucoma. Because levodopa may activate a malignant melanoma, Parcopa should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.
For more full prescribing information about Parcopa, visit parcopa.com.
August 12, 2004
ST. LOUIS (MD Consult) - On August 11, 2004, the U.S. Food and Drug Administration (FDA) announced the approval of 2 drugs, pentetate calcium trisodium injection (Ca-DTPA) and pentetate zinc trisodium injection (Zn-DTPA), for treating certain kinds of radiation contamination. The FDA is approving these drugs as part of its effort to provide the American public with protection against nuclear accidents as well as deliberate acts of aggression.
The FDA has determined that Ca-DTPA and Zn-DTPA are safe and effective for treating internal contamination with plutonium, americium, or curium. The drugs increase the rate of elimination of these radioactive materials from the body.
These substances have been used for several decades as investigational drugs to treat patients in radiation contamination emergencies. To encourage submission of new drug applications for these products, the FDA announced in September 2003 specific conditions and findings under which the 2 drugs could be approved through new drug applications. Until today, there had been no approved drug products for the treatment of internal contamination with plutonium, americium, or curium.
Internal contamination with plutonium, americium, or curium can occur through a variety of routes including ingestion, inhalation, or direct contact through wounds. The goal of treatment with Ca-DTPA and Zn-DTPA is to enhance the removal of these radioactive contaminants and therefore the risk of possible future biological effects including the development of certain cancers, which may occur years after exposure.
Release of plutonium, americium, and curium could occur from laboratory or industrial accidents or through intentional disbursement using a radiation dispersal device, commonly known as a "dirty bomb."
Ca-DTPA and Zn-DTPA should not be administered simultaneously. If both products are available, Ca-DTPA should be given as the first dose. If additional treatment is needed, treatment should be switched to Zn-DTPA. This treatment sequence is recommended because Ca-DTPA is more effective than Zn-DTPA during the first 24 hours after internal contamination. After the initial 24 hours, Zn-DTPA and Ca-DTPA are similarly effective. Ca-DTPA and Zn-DTPA are usually administered into the bloodstream; however, in people whose contamination occurs only by inhalation, Ca-DTPA or Zn-DTPA can be administered by nebulized inhalation.
The primary adverse effect of Ca-DTPA is the loss of certain essential nutritional metals such as zinc, which can be replaced by taking oral zinc supplements. Although Zn-DTPA may also decrease the levels of certain nutritional metals, the effect is less than with Ca-DTPA. In addition, breathing difficulties have been noted in some individuals treated by inhalation therapy with these products.
The sponsor of Ca-DTPA and Zn-DTPA is Hameln Pharmaceuticals, GmbH, of Hameln, Germany.
More information about the FDA's efforts to counteract bioterrorism is available at fda.gov/oc/opacom/hottopics/bioterrorism.html.
August 5, 2004
ST. LOUIS (MD Consult) - On August 4, 2004, Eli Lilly and Company announced that the U.S. Food and Drug Administration had approved Cymbalta (duloxetine hydrochloride) for the treatment of major depressive disorder.
Cymbalta, a balanced and potent reuptake inhibitor of serotonin and norepinephrine, has been studied in more than 6,000 adults with major depression worldwide. Its approval gives health care professionals a new option for treating the broad range of emotional and physical symptoms of depression. Today, only 25% to 35% of patients treated for depression in clinical studies experience relief from all of their disease symptoms.
"Because of its dual action on serotonin and norepinephrine, Cymbalta offers physicians a new opportunity to help patients with depression, particularly those who experience the common physical symptoms of the disease, such as vague aches and pains," said Dr. Stephen Stahl, chairman of the Neuroscience Education Institute and adjunct professor of psychiatry at the University of California at San Diego School of Medicine.
Neurotransmitters are believed to help regulate a person's emotions and sensitivity to pain. Researchers believe that, if these neurotransmitters are out of balance, a person may become depressed and may be more likely to feel painful physical symptoms. The combination of emotional and painful physical effects of depression can have a tremendous negative impact on a person’s quality of life.
Lilly demonstrated Cymbalta's effectiveness for treating major depression with data from 4 placebo-controlled clinical studies, all in adults. The safety and efficacy of Cymbalta in children have not been studied. Cymbalta was studied in a dose range of 40 to 120 mg per day, and the recommended daily dose is 60 mg. In clinical trials, Cymbalta was safe and effective.
Depression can be associated with periods during which symptoms worsen or thoughts of suicide emerge, especially at the initiation of antidepressant drug therapy and whenever a change in dose is made. Patients and their families should watch for these symptoms as well as for anxiety, agitation, panic, difficulty sleeping, irritability, hostility, aggressiveness, impulsivity, restlessness, overexcitement, and hyperactivity. Patients and their families should be encouraged to call their health care providers if any of these symptoms are severe or occur suddenly.
Persons who are allergic to duloxetine hydrochloride or any other ingredients in Cymbalta should not receive the medication. Persons taking thioridazine or a monoamine oxidase inhibitor should not take Cymbalta. It also should not be administered to patients with hepatic insufficiency, end-stage renal disease, or uncontrolled, narrow-angle glaucoma. Cymbalta ordinarily should not be prescribed to patients with substantial alcohol use. Women who are pregnant should talk with their physicians before taking Cymbalta. Nursing while taking Cymbalta is not recommended.
In clinical studies, the most common adverse effects were nausea, dry mouth, constipation, decreased appetite, fatigue, sleepiness, and increased sweating.
For full patient information, visit cymbalta.com.
August 4, 2004
ST. LOUIS (MD Consult) - On August 3, 2004, the U.S. Food and Drug Administration approved Sculptra, an injectable filler to correct facial fat loss in persons with human immunodeficiency virus (HIV).
Sculptra is the first treatment approved for a condition known as lipoatrophy, or facial wasting, a sinking of the cheek, eye, and temple areas of the face caused by the loss of fat tissue under the skin, which can affect HIV patients.
Sculptra is an injectable form of poly-L-lactic acid, a biodegradable, biocompatible, synthetic polymer from the alpha-hydroxy-acid family that has been widely used for many years in dissolvable stitches, bone screws, and facial implants.
The FDA approval of Sculptra was based on data from 4 studies, totaling 277 HIV-positive patients with severe facial lipoatrophy. The patients, who were all being treated with antiretroviral drugs, were primarily white men, and most were aged 41 to 45 years. Patients were given 3 to 6 injections of Sculptra at 2-week intervals and were followed for 2 years.
Skin thickness measurements and serial photographs from clinical studies were assessed, as well as other data submitted by the manufacturer, Dermik Laboratories, of Berwyn, Pa. Analysis indicated that the product significantly improved facial appearance and was safe for restoration and/or correction of shape and contour deficiencies resulting from facial fat loss in patients with HIV/AIDS. Sculptra was shown to produce significant increases in dermal thickness (up to 2 to 3 times baseline values), adding volume to facial tissue and restoring shape to areas of the face with fat loss.
After an initial treatment series, repeated treatments may be needed to maintain the correction.
Most adverse events were related to the injection itself and included nodules, redness, swelling, and bruising in the injection area.
The studies also demonstrated significant improvement in quality of life and measures of anxiety and depression, conditions which can be associated with lipoatrophy.
Sculptra should only be used in patients with HIV by health care providers who are fully familiar with the product training materials provided by Dermik and the entire product package insert. The use of the product for other indications, such as to treat wrinkles, has not been approved by the FDA. Sculptra should not be used in anyone who is allergic to any of the product's components.
As a condition of approval, Dermik has agreed to conduct an open-label registry study of 100 patients for 5 years to evaluate Sculptra's long-term safety. The study will include at least 30 women and 30 persons with dark skin.
August 3, 2004
ST. LOUIS (MD Consult) - On August 2, 2004, the US Food and Drug Administration announced the approval of 2 fixed-dose combination (FDC) antiretroviral drug products for use with other antiretroviral agents for the treatment of HIV-1 infection. The FDCs are Glaxo SmithKline’s Epzicom (abacavir/lamivudine) and Gilead Sciences’ Truvada (tenofovir disoproxil/emtricitabine).
These FDC approvals are important because they provide simplified dosing regimens: 1 pill, once daily, for the component of multidrug therapy represented by these FDCs.
Truvada (tenofovir disoproxil/emtricitabine)
Truvada is a FDC of the antiretroviral drugs tenofovir disoproxil fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg, both of which are approved individually under the brand names of Viread and Emtriva, respectively.
The approval of Truvada is based on bioequivalence studies demonstrating similar pharmacokinetic parameters of the combination product as compared with the individual products and safety and efficacy data that exist for both components individually. Efficacy results from studies using the combination of TDF and lamivudine (3TC) are being extrapolated to support the use of the TDF/FTC combination.
Truvada should be considered as an alternative to TDF and 3TC for treatment-naïve patients who might benefit from a once-a-day regimen.
Epzicom (abacavir/lamivudine)
Epzicom is a FDC of the antiretroviral drugs abacavir sulfate 600 mg and lamivudine 300 mg, both of which are approved individually under the brand names of Ziagen and Epivir, respectively.
Epzicom is being approved on the basis of a large, well-controlled clinical study that showed that abacavir dosed once daily had a similar antiviral effect as abacavir dosed twice daily, both in conjunction with lamivudine and efavirenz.
An important safety issue to note when dealing with abacavir-containing products, including Epzicom, is abacavir-hypersensitivity reaction. Previous clinical trials showed that there is a possibility of this hypersensitivity reaction occurring in approximately 8% of the patients. Epzicom should be discontinued a soon as a hypersensitivity reaction is suspected. Epzicom or other abacavir-containing products must not be restarted after a hypersensitivity reaction, because more severe symptoms can occur within hours and may include life-threatening hypotension and death.
August 2, 2004
ST. LOUIS (MD Consult) - On July 29, 2004, the US Food and Drug Administration approved the drug Campral (acamprosate) for the treatment of alcohol-dependent persons seeking to continue to remain alcohol-free after they have stopped drinking. Campral may not be effective for patients who are actively drinking at the start of treatment or for patients who abuse other substances in addition to alcohol.
Alcoholism (also called alcohol dependence) is a disease. The consequences of alcohol misuse are serious and, in many cases, life threatening. Heavy drinking can increase the risk for certain cancers, especially those of the liver, esophagus, throat, and larynx. Heavy drinking can also cause liver cirrhosis, immune system problems, brain damage, and harm to the fetus during pregnancy. Chronic alcoholism continues to be a widespread and debilitating disorder that places a tremendous burden on society in terms of healthcare costs, lost wages, and personal suffering.
Although its mechanism of action is not fully understood, Campral is thought to act on the brain pathways that are related to alcohol abuse. Campral was demonstrated to be safe and effective by multiple placebo-controlled clinical studies involving alcohol-dependent patients who had already been withdrawn from alcohol (ie, detoxified). Campral proved superior to placebo for maintaining abstinence as indicated by a greater percentage of acamprosate-treated subjects being assessed as continuously abstinent throughout treatment. Campral is not addictive and was generally well tolerated in clinical trials. The most common adverse events reported for patients taking Campral included headache, diarrhea, flatulence, and nausea.
Treatment with Campral should be part of a comprehensive management program that includes psychosocial support.
The sponsor of Campral is Lipha Pharmaceuticals, Inc, in Lyon, France.
July 27, 2004
ST. LOUIS (MD Consult) - Merck/Schering-Plough Pharmaceuticals announced on July 23, 2004, that the U.S. Food and Drug Administration had approved Vytorin (ezetimibe/simvastatin) for the treatment of high levels of low-density lipoprotein (LDL) cholesterol in patients with primary hypercholesterolemia or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough. Vytorin is the first and only product approved to treat the 2 sources of cholesterol by inhibiting the production of cholesterol in the liver and blocking the absorption of cholesterol in the intestine, including cholesterol from food. Vytorin has been approved for use in patients at the following doses: 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg.
In a 12-week, multicenter, double-blind, placebo-controlled clinical study of 1,528 patients with LDL cholesterol levels of 145 to 250 mg/dL, Vytorin provided LDL cholesterol reductions of 52% at the recommended starting dose (10/20 mg), 55% at the 10/40-mg dose, and 60% at the maximum dose (10/80 mg). Vytorin is administered as a once-daily tablet and should be taken in the evening with or without food.
In a 24-week, multicenter, randomized, double-blind, active-controlled, forced titration study of 788 patients, Vytorin (doses ranging from 10/10 to 10/80 mg) was compared with atorvastatin monotherapy (doses ranging from 10 to 80 mg). The average LDL cholesterol levels at baseline across treatment groups ranged from 179 to 181 mg/dL. At each pre-specified dose comparison, Vytorin lowered LDL cholesterol to a significantly greater degree than atorvastatin. At the recommended usual starting doses, Vytorin 10/20 mg lowered LDL cholesterol by 50% versus 37% for atorvastatin 10 mg and 44% for atorvastatin 20 mg. The impact on clinical outcomes of these differences in lipid-altering effects is unknown.
In the 12-week study of 1,528 patients with LDL cholesterol levels of 145 to 250 mg/dL, those taking Vytorin experienced significantly greater LDL cholesterol reductions compared with simvastatin. Vytorin 10/20 mg achieved a 52% LDL cholesterol reduction compared with reductions of 34% and 41%, respectively, for simvastatin 20 and 40 mg (typical starting doses for simvastatin). No incremental benefit of Vytorin on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established.
Results from a phase III, multicenter, randomized, double-blind controlled study of 710 patients showed that, after 5 weeks of treatment, Vytorin 10/20 mg lowered LDL cholesterol by 53% compared with a 38% reduction with simvastatin 20 mg. This greater LDL cholesterol reduction resulted in 83% of patients treated with Vytorin 10/20 mg achieving the study LDL cholesterol goal of less than 100 mg/dL as compared with 46% of patients taking simvastatin 20 mg.
Patients in this study were randomly assigned to 1 of 4 treatment groups for 23 weeks: Vytorin (10/10, 10/20, or 10/40 mg) or simvastatin 20 mg. All 710 patients enrolled in the study had LDL cholesterol levels of 130 mg/dL or more (mean across treatment arms, 165-174 mg/dL) and coronary heart disease (CHD) or CHD risk equivalents as defined by the National Cholesterol Education Program/Adult Treatment Panel III.
Cholesterol in the blood is derived from two sources—production by the body and absorption from the small intestine. The most widely prescribed cholesterol-lowering medications, statins, work in the liver to reduce cholesterol production and increase clearance of cholesterol from the bloodstream. Vytorin inhibits absorption of cholesterol in the small intestine while also reducing cholesterol synthesis in the liver, leading to clearance of cholesterol from the bloodstream.
Vytorin is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and non-HDL cholesterol and to increase HDL cholesterol in patients with primary (heterozygous familial and nonfamilial) hypercholesterolemia or mixed hyperlipidemia. Vytorin is also indicated for the reduction of elevated total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.
Vytorin is a prescription medicine and should not be taken by people who are hypersensitive to any of its components. It should also not be taken by anyone with active liver disease or unexplained persistent elevations of serum transaminases. In addition, women who are of childbearing age (unless highly unlikely to conceive), nursing, or pregnant should not take this medication.
Muscle pain, tenderness, or weakness in people taking Vytorin should be reported to a doctor promptly because these could be signs of a serious adverse effect. The administration of Vytorin should be discontinued if myopathy is diagnosed or suspected. To help avoid serious adverse effects, patients should talk to their doctors about medicine or food they should avoid while taking Vytorin. In 3 placebo-controlled, 12-week trials, the incidence of consecutive elevations (≥3 × upper limits of normal [ULN]) in serum transaminases was 1.7% overall for patients treated with Vytorin and 2.6% for patients treated with Vytorin 10/80 mg. In controlled long-term (48-week) extensions that included both newly treated and previously treated patients, the incidence of consecutive elevations (≥3 × ULN) in serum transaminases was 1.8% overall and 3.6% for patients treated with Vytorin 10/80 mg. These elevations in transaminases were generally asymptomatic, were not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment. Doctors should perform blood tests before and periodically during treatment with Vytorin when clinically indicated to check for liver problems. People taking Vytorin 10/80 mg should receive an additional liver function test prior to and 3 months after titration and periodically during the first year.
Due to the unknown effects of increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, this medication is not recommended for these patients. The safety and effectiveness of Vytorin with fibrates have not been established; therefore, coadministration with fibrates is not recommended. Caution should be exercised when initiating treatment in patients taking cyclosporine and in patients with severe renal insufficiency.
The recommended starting dose for Vytorin is 10/20 mg. Patients requiring LDL cholesterol reductions greater than 55% can initially be given a dose of 10/40 mg. Patients requiring less aggressive LDL cholesterol reductions can be started at 10/10 mg.
The dose of Vytorin should be limited to 10/10 mg daily in patients taking cyclosporine and 10/20 mg daily in patients taking amiodarone or verapamil.
Vytorin has been evaluated for safety in more than 3,800 patients in clinical trials and was generally well tolerated at all doses. In clinical trials, the most commonly reported adverse effects, regardless of cause, included headache (6.8%), upper respiratory tract infection (3.9%), myalgia (3.5%), influenza (2.6%), and extremity pain (2.3%).
Merck/Schering-Plough Pharmaceuticals is a joint venture between Merck & Co, Inc, and Schering-Plough Corporation. The company develops and markets new prescription medicines in cholesterol management in the United States. The collaboration was expanded to include worldwide markets (excluding Japan).
July 26, 2004
ST. LOUIS (MD Consult) - Romark Laboratories announced on July 22, 2004, that the U.S. Food and Drug Administration (FDA) has approved Alinia (nitazoxanide) tablets for treating diarrhea caused by Giardia lamblia in patients 12 years of age and older. The Alinia tablets received a priority review from the FDA.
The FDA also extended the approved uses of Alinia for oral suspension to include diarrhea caused by G lamblia in patients 12 years of age and older. The suspension was approved by the FDA late in 2002 for treating children 1 through 11 years of age with diarrhea caused by G lamblia and Cryptosporidium parvum, another common cause of persistent diarrhea.
Giardia, the most prevalent cause of intestinal protozoan infection in the United States, is a common cause of persistent diarrhea, a condition defined as diarrhea lasting more than 7 days. The U.S. Centers for Disease Control and Prevention estimate there are as many as 2.5 million cases of giardiasis each year. People contract this type of infection from person-to-person contact, day care centers, public water supplies, swimming pools and other recreational water, animals, and contaminated foods.
Alinia, a first-in-class antiprotozoal drug, is a well-tolerated, 3-day course of treatment that is administered twice daily. The New Drug Applications for Alinia tablets and oral suspension were designated for priority review by the FDA. This classification is reserved for products considered to be significant improvements compared with currently marketed products in the treatment, diagnosis, or prevention of a disease.
In placebo-controlled clinical studies in adults, Alinia tablets and oral suspension were 83% to 100% effective in resolving diarrhea and related symptoms. The adverse events experienced by patients receiving Alinia were not significantly different from those receiving a placebo. The most common adverse events reported, regardless of causality assessment, were abdominal pain (6.7%), diarrhea (4.3%), headache (3.1%), and nausea (3.1%).
Alinia 3-Day Therapy Packs will be available in pharmacies in September 2004. Each Alinia 3-Day Therapy Pack will contain a full course of therapy for adults and adolescents, 6 Alinia (nitazoxanide) tablets of 500 mg. Alinia tablets will also be supplied in bottles of 60 tablets.
Alinia (nitazoxanide) for oral suspension, 100 mg/5 mL, is currently available in pharmacies. The suspension is useful for children and for adults who may be unable to swallow tablets.
A Romark representative stated that studies are underway to evaluate the efficacy of Alinia as a treatment in a variety of other gastrointestinal infections. He also noted that lost productivity and medical costs associated with diarrheal illnesses in the United States have been estimated at up to $23 billion/yr. There are an estimated 375 million diarrheal illnesses in the United States per year, resulting in 73 million physician consultations, 1.8 million hospitalizations, and 3,100 deaths.
Alinia for oral suspension is indicated for patients 1 through 11 years of age for the treatment of diarrhea caused by C parvum. Alinia for oral suspension and Alinia tablets have not been shown to be superior to placebo for the treatment of diarrhea caused by C parvum in HIV-infected or immunodeficient patients. The safety and effectiveness of Alinia for oral suspension or Alinia tablets for the treatment of diarrhea caused by C parvum in patients 12 years of age and older have not been established.
Romark Laboratories is a privately owned, research-based pharmaceutical company based in Tampa, Fla. For more information on Alinia, visit alinia.com.
June 29, 2004
ST. LOUIS (MD Consult) - Celltech Group, a biotechnology company based in the United Kingdom, announced on June 23, 2004, it had received approval from the U.S. Food and Drug Administration (FDA) for Codeprex (codeine polistirex/chlorpheniramine polistirex) Extended-Release Suspension CIII. Codeprex is the first codeine-based cough suppressant to provide 12-hour dosing.
Codeprex is indicated for the temporary relief of cough that may occur with the common cold or inhalation of irritants, for the temporary relief of runny nose, sneezing, itching of the nose or throat, as well as for treatment of itchy watery eyes due to hay fever, other upper respiratory allergies, or allergic rhinitis. Codeprex is expected to be available in retail pharmacies by the fourth quarter of 2004.
Codeprex is contraindicated in persons with sensitivity to codeine or chlorpheniramine. Codeprex should be used with caution in patients with persistent or chronic cough, as occurs with smoking, asthma, or emphysema, or with cough accompanied by excessive phlegm. Caution is also advised when prescribing to patients with narrow-angle glaucoma or prostatic hypertrophy. The possibility of tolerance or dependence, particularly in patients with a history of drug abuse, should be considered. Common adverse effects may include drowsiness, confusion, dizziness, nausea, constipation, dry mouth, headache, and allergic reactions.
Codeprex is not recommended for use in children under 6 years of age.
For full prescribing information for Codeprex, visit celltechgroup.com/Products/PI/LR428_COL.pdf.
June 10, 2004
ST. LOUIS (MD Consult) - On June 16, 2004, Watson Pharmaceuticals, Inc., announced the launch of Reprexain CIII (5 mg hydrocodone bitartrate/200 mg ibuprofen tablets), a new prescription pain medication for the short-term (generally less than 10 days) management of acute pain.
Watson is launching Reprexain with Interpharm Holdings, Inc. Interpharm will manufacture and supply the product to Watson, who will market, sell, and distribute the product in the United States.
Reprexain addresses a market opportunity by combining 5 mg hydrocodone, the most commonly prescribed dose of hydrocodone, with 200 mg of ibuprofen, the leading prescribed nonsteroidal anti-inflammatory drug (NSAID). Combining both central and peripheral analgesic action, Reprexain offers patients a balanced approach to the management of acute pain. In addition, Reprexain offers physicians Schedule III prescribing convenience.
Reprexain is not indicated for the treatment of conditions such as osteoarthritis or rheumatoid arthritis. Reprexain should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Serious gastrointestinal toxicity, such as inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, with or without warning symptoms, can occur in patients taking NSAIDs. The most common reported adverse effects with Reprexain include headache, somnolence, constipation, nausea, dizziness, and dyspepsia. Hydrocodone may impair mental and/or physical abilities. These effects may be additive with alcohol and other central nervous system depressants.
Complete prescribing information for Reprexain is available at reprexain.com.
June 15, 2004
ST. LOUIS (MD Consult) - On May 28, 2004, Indevus Pharmaceuticals, Inc, announced the U.S. Food and Drug Administration (FDA) had approved Sanctura (trospium chloride tablets). The drug is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Sanctura, a quarternary ammonium compound, belongs to a class of anticholinergic compounds known as muscarinic receptor antagonists. These compounds relax smooth muscle tissue found in the bladder, thus decreasing bladder contractions. Overactive or unstable detrusor muscle function is believed to be the cause of overactive bladder.
The FDA approval of Sanctura was based on a review of data from clinical studies conducted in the United States and Europe involving approximately 3,000 subjects. Sanctura was well tolerated, and the most commonly reported adverse effects in phase III U.S. clinical trials were dry mouth (20.1% for Sanctura vs 5.8% for placebo) and constipation (9.6% vs 4.6%). Patients who have urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, or hypersensitivity to Sanctura should not use this medication.
Sanctura has been extensively studied and is currently marketed as a prescription drug product in Europe for the treatment of overactive bladder/urinary incontinence. Indevus licensed exclusive U.S. rights to Sanctura from Madaus AG, a German pharmaceutical company, in late 1999.
The product launch of Sanctura is anticipated to take place during the third calendar quarter of 2004.
Complete prescribing information for Sanctura is available at indevus.com.
June 10, 2004
ST. LOUIS (MD Consult) - Berlex, the U.S. affiliate of German company Schering AG, announced on June 9, 2004, that the U.S. Food and Drug Administration (FDA) had approved Menostar (estradiol transdermal system) 14 µg/d for the prevention of osteoporosis.
Menostar is a clear, dime-sized, once-a-week patch that delivers half the amount of medication administered in the lowest dose of transdermal estrogen therapy previously available for postmenopausal osteoporosis prevention. This transdermal patch delivers such a low dose of plant-derived estrogen that it can be used in women with or without a uterus.
"In a 2-year clinical study, Menostar, with a very low dose of estrogen, did not increase the risk of endometrial hyperplasia among women with a uterus. Therefore, this patch does not require a daily or monthly concomitant progestin," said Marie Foegh, MD, Vice President of Medical Affairs for Berlex Laboratories.
The extent of estrogen deficiency in postmenopausal women may predetermine osteoporosis risk. Women with low estrogen syndrome, or those with trace or undetectable estrogen levels (estradiol levels < 5 pcg/mL), are at a 2.5 times greater relative risk for osteoporosis and debilitating bone and hip fractures compared with other postmenopausal women. In addition, women with trace or undetectable levels of estrogen combined with high concentrations of sex hormone–binding globulin (SHBG) are at up to 8 times greater relative risk for developing osteoporosis, according to a Berlex press release.
To assess the efficacy and safety of Menostar, the FDA reviewed data from a 2-year, randomized, multicenter, placebo-controlled clinical trial of 417 postmenopausal women aged 60 to 80 years. After 2 years, Menostar increased lumbar spine bone mineral density (BMD) by 3% over baseline (P < .001) and 2.6% over placebo (P < .001). In addition, Menostar increased hip BMD by 0.84% over baseline (P < .001) and 1.6% over placebo (P < .001). In the clinical trial, the safety and tolerability profile of Menostar was comparable to placebo; the most frequently reported adverse effects were application site irritation, joint pain, and leukorrhea. Results of the study indicate that Menostar does not cause clinically significant endometrial hyperplasia. Therefore, stated Berlex, this patch does not require a daily or monthly concomitant progestin to protect against endometrial cancer among women with an intact uterus. In this study, there was no difference in the number of incidents of breast cancer, blood clots, or cardiovascular events in the active group over placebo.
"Our study of Menostar showed that with nearly half of the lowest dose of estrogen currently available in a patch for osteoporosis prevention—about one quarter of the standard doses used for osteoporosis prevention—bone density increased to a clinically and statistically significant degree," said Bruce Ettinger, MD, Clinical Professor of Medicine at the University of California, San Francisco, and lead investigator the study. "Menostar can be especially beneficial for women with extremely low estrogen by bringing their levels up just a little bit."
Transdermal delivery allows for estrogen delivery directly into the bloodstream through the skin, and therefore the hormone is not metabolized by the liver. A "first-pass effect" through the liver with oral delivery has been shown to cause increases in SHBG, triglycerides, and C-reactive protein.
Despite its prevalence and debilitating effects on women's health, osteoporosis continues to be underrecognized and undertreated in postmenopausal women. According to the National Osteoporosis Foundation, as many as 8 million women suffer from osteoporosis, and another 22 million women have bone density deficiency, putting them at risk for bone fracture and associated complications. In fact, 24% of women 50 years and older who suffer a hip fracture die within a year of the fracture.
Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses.
Estrogens with and without progestins should not be used for the prevention of cardiovascular disease.
The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50-79 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo.
The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen-alone therapy, such as Menostar.
Estrogens and estrogen/progestin therapy should not be used in persons with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; blood clots; stroke or myocardial infarction; known or suspected pregnancy; or liver dysfunction or disease. Menostar should not be used in patients with known hypersensitivity to its ingredients.
For full prescribing information, visit berlex.com/html/products/pi/fhc/Menostar_PI.pdf.
June 9, 2004
ST. LOUIS (MD Consult) - On June 7, 2004, ISTA Pharmaceuticals, Inc., announced the U.S. Food and Drug Administration (FDA) had approved the New Drug Application for its medication Istalol (timolol maleate ophthalmic solution) 0.5% for the treatment of glaucoma.
Istalol is a once-daily, liquid, topical solution of timolol, a beta-blocking agent indicated for the treatment of glaucoma. ISTA holds exclusive marketing rights to Istalol in the United States under an agreement with Senju Pharmaceutical Co., Ltd., which developed the product in Japan.
In September 2002, Senju submitted the NDA for Istalol to the FDA based on data from a phase I clinical study and a multicenter phase III clinical trial completed in the United States. In the clinical trials, once-daily Istalol showed efficacy and safety comparable to twice-daily timolol maleate ophthalmic solution, which is the leading beta-blocker indicated for the treatment of glaucoma in the United States. The advantages of Istalol include enhanced corneal penetration, as demonstrated in animal studies, and once-daily administration. Other formulations of timolol currently on the market are commonly prescribed as twice-daily solutions or gel formulations. Gel formulations, in particular, have been shown to cause blurring of patients' vision.
According to a statement issued by the President and Chief Executive Officer of ISTA, Istalol will be released to the market later in the summer of 2004.
ISTA is a specialty pharmaceutical company focused on the development and commercialization of ophthalmic products. For more information, please visit the company's Web site at istavision.com.
June 7, 2004
ST. LOUIS (MD Consult) - On May 19, 2004, SkyePharma PLC and Endo Pharmaceuticals announced that the U.S. Food and Drug Administration had approved SkyePharma's DepoDur for the treatment of pain after major surgery. Previously referred to as DepoMorphine, DepoDur is a single-dose sustained-release injectable formulation of morphine.
DepoDur is a single-dose extended-release injectable formulation of morphine sulphate. DepoDur uses SkyePharma's proprietary DepoFoam technology and is supplied as a ready-to-use suspension. It is given as a single epidural injection before or during surgery and provides pain relief for up to 48 hours after surgery. There is no need for an in-dwelling catheter for continuous infusion, thereby overcoming a major drawback to the otherwise theoretically desirable epidural route of administration for opioid analgesics.
DepoDur is designed for the control of pain after major surgery. SkyePharma and Endo expect that the medication's main use will be in control of postoperative pain in hospitalized patients undergoing major surgical procedures requiring general or regional anesthesia such as major abdominal surgery, orthopedic surgery, and cesarean section. Currently there are an estimated 6 million such procedures occurring every year in the United States and 5 million in Europe
After a major surgical operation, the level of pain is usually very high for the first 1 to 2 days, but the intensity of pain gradually subsides; by the end of the second day, pain can normally be satisfactorily controlled with oral analgesics. For the immediate postoperative period, opioid analgesics like morphine (used alone or in combination with other nonopioid analgesics) are likely to remain the "gold standard" for relief of severe acute pain. However, the relatively short duration of pain relief with opioids means that they require either continuous infusion or patient-controlled analgesia. Both of these approaches require the patient to have an in-dwelling epidural or intravenous catheter. Such catheters can fall out or interfere with patient mobility and are a potential source of infections. Epidural catheters are also contraindicated with concomitant use of anticoagulants because of the risk of bleeding in the spinal column that can potentially result in paralysis. There is a growing trend toward routine use of anticoagulants in patients undergoing orthopedic surgery to prevent the formation of blood clots.
DepoDur is supplied in a 2-mL vial containing a 10-mg/mL suspension in sterile saline and is administered as a single-dose epidural injection at the lumbar level before surgery (or after clamping of the umbilical cord during cesarean section). The recommended dose is 10 mg for cesarean section, 10 to 15 mg for lower abdominal surgery, and 15 mg for major orthopedic surgery of the lower extremities. Some patients may benefit from a dose of 20 mg. It should be appreciated that, as with all opioids, the incidence of serious adverse respiratory events is dose related. Respiratory depression is the chief hazard of all opioid preparations and occurs more frequently in elderly or debilitated patients. For elderly patients (older than 65 years), the low end of the dosing range for DepoDur is recommended together with vigilant perioperative monitoring.
SkyePharma has completed seven clinical trials of DepoDur. The phase IIb and phase III clinical development program for DepoDur involved 4 separate pain models and included more than 1,000 patients. In the two phase III trials, in hip surgery and lower abdominal surgery, DepoDur demonstrated extended dose–related analgesia and achieved its primary end point (superiority over study comparators in terms of total demand for opioid analgesics after surgery) with a high degree of statistical significance (P < .0001 and P = .0003, respectively). DepoDur also achieved statistical significance on several secondary end points. Importantly, statistical significance was achieved for the current pain intensity scores at rest and with activity over a 48-hour period and for the ratings of overall pain control.
In two related phase IIb trials, DepoDur was significantly better than study comparators in the cesarean section study (P = .0209) and approached statistical significance in the knee arthroplasty study (P = .0902), which used a novel end point: time-weighted pain intensity recall score over 48 hours. DepoDur achieved a high degree of statistical significance in total demand for opioid analgesics after surgery (P = .001), a secondary end point in this trial but the primary end point in the 3 other studies.
In all 4 of these studies, the safety profile of DepoDur was typical for an epidural opioid agent. As with all opioid preparations, respiratory depression is the chief hazard associated with DepoDur. The most common adverse events reported during clinical trials were decreased oxygen saturation, hypotension, urinary retention, vomiting, constipation, nausea, pruritus, pyrexia, anemia, headache, and dizziness.
According to an Endo spokesperson, the company expects to bring DepoDur to the market by the end of 2004, provided that sufficient inventory is available.
For more information, visit skyepharma.com or endo.com.
May 27, 2004
ST. LOUIS (MD Consult) - On May 26, 2004, Salix Pharmaceuticals, Ltd, announced that the U.S. Food and Drug Administration (FDA) had granted marketing approval for 200-mg Xifaxan (rifaximin) tablets for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients 12 years of age and older. Xifaxan is a nonsystemic (<0.4% of the drug absorbed into the bloodstream), gastrointestinal-selective, oral antibiotic.
Dr. Art Kamm, Senior Vice President of Research and Development and Chief Development Officer at Salix, stated, "In clinical trials, Xifaxan was shown to be effective in shortening the duration of diarrhea for the most common cause of this disease, noninvasive strains of E coli. Unlike systemically absorbed anti-infective agents, Xifaxan's beneficial effect was achieved with minimal systemic absorption thus reducing the potential for development of systemic antimicrobial resistance and other systemic concerns such as drug–drug interactions. Additionally, Xifaxan's tolerability profile was comparable to that observed with placebo."
"Travelers' diarrhea represents a significant risk to U.S. citizens traveling to foreign countries, and can affect as many as fifty percent of travelers depending upon their destination. Currently, systemic antibiotics are commonly prescribed to treat travelers' diarrhea. Systemic antibiotic therapy, unfortunately, can be associated with limitations such as the development of bacterial resistance outside the gastrointestinal tract and decreased tolerability. In light of this fact, practitioners are encouraged by the observation that nonabsorbed antibiotics, like Xifaxan, demonstrate potential to overcome the limitations associated with systemic antibiotic therapy," stated Dr. Herbert L. DuPont, Director of the Center for Infectious Disease at the Houston School of Public Health and the Chief of Internal Medicine at St. Luke's Episcopal Hospital. "Xifaxan offers physicians an alternative that is not only an appropriate and effective antibiotic for the most common cause of travelers' diarrhea, but also is a much-needed option that will help preserve the efficacy of systemic antibiotics for the treatment of systemic infections."
Xifaxan (rifaximin) tablets are indicated for the treatment of patients (12 years of age and older) with travelers' diarrhea caused by noninvasive strains of E coli. Xifaxan should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than E coli. The use of Xifaxan should be discontinued if diarrhea symptoms get worse or persist more than 24 to 48 hours, and alternative antibiotic therapy should be considered.
In clinical trials, Xifaxan was generally well tolerated. The most common adverse effects (vs placebo) were flatulence, 11.3% (vs 19.7%); headache, 9.7% (vs 9.2%); abdominal pain, 7.2% (vs 10.1 %); and rectal tenesmus, 7.2% (vs 8.8%).
Xifaxan is expected to be available to physicians and patients in August 2004. Salix is evaluating Xifaxan's potential for the treatment of other gastrointestinal-related diseases.
Salix, headquartered in Raleigh, NC, licensed rifaximin from Alfa Wassermann S.p.A. More than 500 million tablets of rifaximin have been sold/distributed in Italy since its approval in that country in 1987. Currently, rifaximin is approved in 17 countries worldwide.
For full prescribing information on Xifaxan tablets and other Salix products, please visit salix.com.
May 24, 2004
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) announced on May 19, 2004, the approval of Vidaza (azacitidine) injection, the first effective treatment for patients with myelodysplastic syndrome (MDS). The agency gave the product Fast Track Status and a priority review.
"By restoring normal growth and differentiation of bone marrow cells, this new treatment will offer a much needed option for patients suffering from this rare illness that, in some cases, has been found to progress to leukemia, a type of cancer. The agency continues to make approvals of these types of remarkable treatments one of its highest priorities," said Dr. Lester M. Crawford, Acting FDA Commissioner.
MDS is a collection of disorders in which the bone marrow does not function normally and not enough normal blood cells are produced. MDS may develop after treatment with drugs or radiation therapy for other diseases, or it may develop without any known cause. Some forms of MDS can progress to acute myeloid leukemia, a type of cancer in which too many white blood cells are made.
Vidaza is an orphan product. Orphan products are developed to treat rare diseases or conditions that affect fewer than 200,000 people in the United States. The Orphan Drug Act provides a 7-year period of exclusive marketing to the first sponsor who obtains marketing approval for a designated orphan drug.
It is estimated that between 7,000 and 12,000 new cases of MDS are diagnosed each year in the United States. Although the disease can occur in all age groups, the highest prevalence is in people older than 60 years of age. Typical symptoms include weakness, fatigue, infections, easy bruising, bleeding, and fever. Patients with MDS may need red blood cell and platelet transfusions, as well as antibiotic therapy for infections.
Vidaza is thought to work by restoring normal growth and differentiation of bone marrow cells.
The safety and effectiveness of Vidaza, in the treatment of all subtypes of MDS, were established in a randomized, controlled trial and in two non-randomized studies in a total of 268 patients. About 15% of patients in the 3 trials had complete or partial responses to azacitidine. Responses consisted of complete or partial normalization of blood counts and of immature cell percentages in the bone marrow. In responders, the need for transfusions was eliminated.
The most common adverse events reported in clinical trials included nausea, anemia, thrombocytopenia, diarrhea, fatigue, irritation at the injection site, and constipation.
The sponsor and distributor of Vidaza is Pharmion Corporation, based in Boulder, Colo.
April 26, 2004
ST. LOUIS (MD Consult) - On April 23, 2004, Inamed Corporation and Genzyme Corporation announced that the U.S. Food and Drug Administration (FDA) had granted market approval for Hylaform (Hylan-B gel), a hyaluronic acid–based dermal filler that is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).
No pretreatment skin test is required, and the company stated that shipments of Hylaform gel are anticipated to begin right away.
Hylaform gel is a colorless gel made from purified hyaluronic acid, a naturally occurring substance (complex sugar) found in all living organisms. Hyaluronic acid is chemically, physically, and biologically similar in all species. In the skin, hyaluronic acid fills the space between collagen and elastin fibers, replenishing the natural volume lost during aging while delivering essential nutrients and hydration. The body naturally absorbs Hylaform gel over time.
Hylaform gel was developed and is being manufactured by Cambridge, Mass–based Genzyme Corporation. Inamed, based in Santa Barbara, Calif, is Genzyme's worldwide marketing and distribution partner for Hylaform.
"Hylaform gel is a new option for patients looking for effective, non-surgical aesthetic facial treatment," said Ellen Gendler, MD, a Hylaform U.S. clinical trial investigator. "Hylaform demonstrated a favorable safety profile in clinical studies, which is supported by extensive worldwide post-marketing data. While redness, bruising, and swelling are common adverse events seen with the use of [hyaluronic acid] dermal fillers, those associated with Hylaform were primarily mild. My patients reported great satisfaction with results and no downtime from the treatment. I think Hylaform will quickly become a staple in my practice, especially as we begin to use multiple dermal filler products to replace the collagen and hyaluronic acid lost as skin ages."
At both this year's 62nd annual meeting of the American Academy of Dermatology and the recent annual meeting of the American Society for Aesthetic Plastic Surgery, physicians highlighted an emerging trend toward the combination use of dermal filler products such as collagen and hyaluronic acid–based products to achieve optimal aesthetic results.
Hylaform gel is indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds). The most commonly reported adverse events encountered during the Hylaform clinical study included erythema, bruising, and swelling, which typically were mild in severity and procedure related.
The safety and effectiveness of combination use of collagen and hyaluronic acid products have not been evaluated in clinical studies.
Full prescribing information for Hylaform is available through Inamed Corporation. Contact the company at 800-624-4261 or Inamed.com.
April 22, 2004
ST. LOUIS (MD Consult) - On April 22, 2004, Mylan Laboratories Inc announced that its branded-drug subsidiary, Bertek Pharmaceuticals Inc, received approval from the U.S. Food and Drug Administration (FDA) to market Apokyn (apomorphine hydrochloride injection). Apokyn is indicated for the acute, intermittent treatment of hypomobility, "off" episodes ("end-of-dose wearing off" and unpredictable "on/off" episodes) associated with advanced Parkinson's disease.
Apokyn provides patients with an effective treatment to use during an "off" episode. "Off" episodes are debilitating periods of partial loss of movement or total immobility experienced by patients with advanced Parkinson's disease. As Parkinson's disease progresses, patients begin to experience immobilizing "off" episodes despite treatment with drugs used to increase or replace dopamine. Apokyn is not used to prevent "off" episodes, and it does not replace other Parkinson's disease medications, but rather, it treats an existing "off" episode when it occurs. As an acute, rescue treatment, Apokyn helps patients experiencing a debilitating "off" episode to walk, talk, or move around more easily. The intensity, duration, and frequency of "off" episodes vary for each sufferer. Patients with Parkinson's disease lose motor control during "off" episodes, making routine tasks such as walking and even speaking extremely difficult. Patients with Parkinson's disease (or their caregivers) administer the medication via injection under the skin.
In clinical trials conducted by North Carolina–based Bertek, Apokyn was effective in improving an overall measurement of patient movement. "The data from clinical trials show that Apokyn, when used in conjunction with standard pharmacological therapies for Parkinson's disease, has the ability to provide relief from an 'off' episode," said Dr. James H. Sherry, Vice President of Clinical Affairs at Bertek Pharmaceuticals Inc.
The effectiveness of Apokyn for the acute treatment of "off" episodes associated with advanced Parkinson's disease was established in 3 randomized controlled clinical trials. Patients who received Apokyn demonstrated statistically significant improvement in their unified Parkinson's disease rating scale part III (UPDRS) motor score at 20 minutes after the administration of the drug compared with a placebo injection. The UPDRS is used by researchers and clinicians around the world to measure disease severity in patients.
Apokyn should not be used by patients who are being treated with certain drugs to treat nausea and vomiting or irritable bowel syndrome. These medications (including, for example, ondansetron, granisetron, dolasetron, palonosetron, and alosetron) are called 5HT3 antagonists or blockers. In addition, Apokyn should not be used by patients who have an allergic reaction to the drug or its ingredients (notably, sodium metabisulfite). Apokyn should be injected under the skin only, not into a vein. Because this medication can cause severe nausea and vomiting, it is taken with an oral medicine that helps to prevent these effects. Apokyn may lower blood pressure (orthostatic hypotension), cause fainting, and increase the risk of falling. At recommended doses, minimal increases in QTC were observed. Caution should be used when prescribing apomorphine with drugs that prolong the QT/QTC interval. Some patients treated with Apokyn may get sleepy during the day or fall asleep without warning while doing everyday activities. The most common adverse effects of Apokyn are yawning, dyskinesias, nausea or vomiting, sleepiness, dizziness, runny nose, hallucinations, fluid retention, chest pain, increased sweating, flushing, and an unusually pale complexion.
According to a press release from Mylan, Apokyn will be available by July 2004. The medication has orphan drug status, a federal designation to indicate the drug's exclusive use in treating a condition affecting fewer than 200,000 people in the United States.
For more information, contact Mylan Laboratories by mail at 1500 Corporate Drive, Suite 400, Canonsburg, PA 15317 USA, by telephone at 724-514-1800, or via the Internet at www.mylan.com.
April 22, 2004
ST. LOUIS (MD Consult) - On April 15, 2004, French pharmaceutical company Aventis announced the U.S. Food and Drug Administration (FDA) has approved Nasacort HFA (triamcinolone acetonide) Nasal Aerosol for the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in adults and children aged 6 years and older. Nasacort HFA Nasal Aerosol is the first intranasal corticosteroid dry-aerosol formulation approved in the United States that contains hydrofluoroalkane (HFA) rather than chlorofluorocarbons (CFCs).
Nasacort HFA Nasal Aerosol replaces Nasacort Nasal Inhaler, which was taken off the market in July 2003 to comply with U.S. Environmental Protection Agency and FDA requirements intended to protect the ozone layer. These requirements mandated the removal of nasal inhalers containing CFCs from U.S. markets.
In placebo-controlled clinical trials, the most commonly reported adverse effects were sneezing, headache, nasal irritation, and rhinitis.
Aventis corporate headquarters are in Strasbourg, France. The company's prescription drug business is conducted in the United States by Aventis Pharmaceuticals Inc, which is headquartered in Bridgewater, New Jersey. For more information, please visit aventis-us.com.
April 20, 2004
ST. LOUIS (MD Consult) - On April 16, 2004, the U.S. Food and Drug Administration (FDA) approved Apidra (insulin glulisine [rDNA origin] injection), a rapid-acting insulin analog, for the treatment of adult patients with diabetes mellitus for the control of hyperglycemia. Apidra is a recombinant DNA human insulin analog that has a more rapid onset and a shorter duration of action than regular human insulin after subcutaneous administration.
Apidra, manufactured by Strasbourg, France–based Aventis, is designed for the treatment of type 1 and type 2 diabetes, to cover mealtime blood sugar spikes. In combination with Lantus (insulin glargine [rDNA origin] injection), a 24-hour basal insulin also made by Aventis, Apidra provides a synergistic approach to total glucose control.
Diabetes is a chronic, widespread condition in which the body does not produce or properly use insulin, the hormone needed to convert glucose (sugar) into energy. People with diabetes may need different types of insulin at certain times of the day and at different stages of the progression of their diabetes to help them manage their blood glucose levels. Rapid-acting insulins can be taken shortly before or after a meal to control the peaks in blood glucose levels that happen immediately after eating.
Controlling blood sugar levels is an important key to fighting the current diabetes epidemic. In the United States, more than 18 million people have diabetes, including an estimated 5 million who remain undiagnosed. At the same time, approximately 60% of those diagnosed are not in control of their disease. According to the American Diabetes Association, the optimal control goal for people with diabetes is an A1C level of less than 7%. The A1C test measures blood glucose levels over a 2- to 3-month period. The United Kingdom Prospective Diabetes Study showed that using insulin in the treatment of type 2 diabetes can—when combined with oral medications, diet, and exercise—help people with diabetes achieve and maintain tight glucose control, helping to reduce their risk of blindness, amputation, kidney failure, stroke, and heart attack.
Apidra has been studied in clinical trials in adult patients with type 1 and type 2 diabetes. It is designed to be injected within 15 minutes before a meal or within 20 minutes after starting a meal. It is intended to be given by subcutaneous injection or by continuous subcutaneous pump infusion.
Hypoglycemia is the most common adverse effect of insulin therapeutic medications, including Apidra. Adverse events commonly associated with human insulin therapy include allergic reactions, injection site reaction, lipodystrophy, pruritus, and rash.
For more information, on Apidra, please visit aventis.com.
April 5, 2004
ST. LOUIS (MD Consult) - On April 2, 2004, Strasbourg, France–based Aventis announced that the U.S. Food and Drug Administration (FDA) has approved its drug Ketek (telithromycin) tablets to treat acute exacerbation of chronic bronchitis, acute bacterial sinusitis, and mild to moderate community-acquired pneumonia, including those infections caused by multi-drug resistant Streptococcus pneumoniae, in patients age 18 and older. Ketek is the first in a new class of antibiotics known as ketolides and was specifically designed to treat community-acquired respiratory tract infections (RTIs).
"Physicians . . . need a new therapeutic option to treat their patients suffering from mild to moderate RTIs, especially since approximately one third of Streptococcus pneumoniae (the most common pathogen causing RTIs) are resistant to commonly used first line antibiotics," said Frank Douglas, MD, PhD, Executive Vice President and Chief Scientific Officer at Aventis.
"Ketek's innovative mechanism of action selectively targets common respiratory pathogens, including resistant strains, without significant effects on bacteria not normally involved in RTIs. This may be an important factor in minimizing the development of antibiotic resistance, a critical public health concern and one that I've seen in my clinical practice," added Paul Iannini, MD, Chairman, Department of Medicine, Danbury Hospital, and Clinical Professor of Medicine, Yale University.
In clinical trials with Ketek, the most commonly reported adverse effects were nausea, headache, dizziness, vomiting, and diarrhea.
For more information, visit aventis.com.
March 26, 2004
ST. LOUIS (MD Consult) - On March 23, 2004, the U.S. Food and Drug Administration (FDA) released a statement approving generic oxycodone hydrochloride extended-release tablets.
According to the statement, oxycodone hydrochloride extended-release products, such as OxyContin and its generic versions, are important options for the management of moderate-to-severe chronic pain, such as that associated with cancer and various other illnesses. The FDA's approval of two generic oxycodone hydrochloride products should make this safe and effective medicine available at a lower cost to patients suffering from moderate to severe chronic pain.
At the same time, the FDA recognizes that oxycodone extended-release tablets present a potential for abuse, misuse, and diversion. For this reason, the FDA has secured the agreement of the manufacturers of the generic products to have in place, before marketing, risk management plans that are consistent with the innovator product's plan.
Decades of experience with generic drug approvals suggest that, when the first generic versions of an innovator drug reach the market, the use of that drug does not increase overall. Rather, demand tends to remain steady, with an increasing proportion of market share being held by the generic versions.
Earlier this month, the Office of National Drug Control Policy, the Drug Enforcement Agency, and the FDA announced a coordinated strategy to confront the illegal diversion and abuse of prescription drugs. This coordinated strategy includes:
This announcement incorporates the education of medical professionals and consumers and outreach to pharmacies, pharmaceutical manufacturers, and businesses involved in Internet commerce, as well as increased investigation and enforcement activities.
When used correctly, opioids play a very important role in the management of pain. The FDA's job is to maximize the potential benefits that patients receive from these drugs, while at the same time minimizing the risks associated with these products.
In approving these generic products, the FDA is seeking to balance the need for effective pain management therapies for the more than 10 million Americans who suffer from chronic pain with the prevention of misuse, abuse, and diversion of prescription drugs.
March 9, 2004
ST. LOUIS (MD Consult) - On March 8, 2004, California biotechnology company Amgen Inc announced the U.S. Food and Drug Administration (FDA) had approved its drug Sensipar (cinacalcet HCl). This first-in-class oral calcimimetic is indicated for the treatment of secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) who are receiving dialysis and for the treatment of elevated calcium levels (hypercalcemia) in patients with parathyroid carcinoma.
Nearly all of the more than 300,000 patients receiving dialysis in the United States have secondary HPT. The disease can develop early during the course of CKD and continues to progress as kidney function declines. Untreated secondary HPT is characterized by abnormal calcium and phosphorus levels and is associated with serious consequences, including cardiovascular morbidity.
Sensipar meets a significant medical need in patients with secondary HPT. "It is the only available therapy that allows practitioners to reduce parathyroid hormone [PTH] while lowering calcium-phosphorus product, which is consistent with the National Kidney Foundation [NKF]'s Kidney Disease Outcomes Quality Initiative [K/DOQI] clinical practice guidelines for bone metabolism and disease in chronic kidney disease," said Beth Seidenberg, MD, chief medical officer and senior vice president of global development at Amgen.
The NKF's K/DOQI clinical practice guidelines are a response to the strong correlation between these biochemical parameters and morbidity and mortality in the CKD population.
Secondary HPT is characterized by elevations in PTH, calcium, and phosphorus levels. If the disease is left untreated, patients with secondary HPT develop bone disease, bone pain and fractures, and vascular and soft tissue calcifications, which are frequently associated with an increased risk of hospitalization and death.
Before the approval of Sensipar, the only available medical treatments for patients with secondary HPT were phosphate binders and vitamin D sterols, which may elevate calcium and phosphorus levels. As a consequence, treatment is frequently interrupted; this can result in inadequate control of PTH. Sensipar provides targeted treatment of secondary HPT with its unique mechanism of action that acts directly on the calcium-sensing receptor, the primary regulator of PTH.
"With cincacalcet HCl now available, there is no question that there is a large number of patients who need this therapy right away. We have a lot of patients whose disease is very poorly controlled and in our attempt to control their disease, we are producing side effects that are completely unacceptable," said Geoffrey Block, MD, a lead investigator for the phase 3 trials and director of clinical research at Denver Nephrologists, PC. "In the clinical trials I have done with cinacalcet HCl, I have been astounded by how well this drug can control PTH, lower calcium, and lower phosphorus. Patients for the first time are achieving levels of phosphorus that they recognize will protect their health over the long term.
Sensipar provides significant improvement over traditional therapy by bringing multiple parameters into the target range recommended by the NKF's K/DOQI clinical practice guidelines.
"Achieving the new K/DOQI guidelines has been challenging with existing therapies, and has required clinicians to make tough decisions regarding therapeutic goals," said Brian Pereira, MD, president and chief executive officer at the New England Health Care Foundation and professor of medicine at Tufts-New England Medical Center. "Sensipar gives the nephrology community an important new tool to help dialysis patients suffering from secondary HPT to achieve all 4 therapeutic target goals."
Patients with parathyroid carcinoma have a rare, serious cancer of the parathyroid gland resulting in excess secretion of PTH, a form of primary HPT. The disease is complicated by elevated calcium levels in the blood. High calcium levels can lead to anxiety, depression, nausea, vomiting, bone fractures, kidney stones, and in some cases, coma. Surgical removal of the parathyroid gland is the only curative therapy for this disease but is not successful in all cases. Sensipar was shown to reduce high levels of calcium in patients with parathyroid carcinoma. With approximately 500 patients developing parathyroid carcinoma each year, Sensipar was granted orphan designation.
In clinical trials in patients with secondary HPT who were receiving dialysis, Sensipar was safe and effective in reducing PTH, calcium-phosphorus product, calcium, and phosphorus in a broad range of patients regardless of age, sex, race, years receiving dialysis, or disease severity. Sensipar was effective in patients receiving vitamin D as well as those not receiving vitamin D.
Clinical studies involving more than 1,100 patients showed tha