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E. Fougera & Co., a division of Nycomed, has received the FDA’s approval for the first generic equivalent of Imiquimod Cream 5%. This product is rated AB-equivalent to Graceway’s Aldara and can be substituted for all indications.
The original approval was granted to 3M in 1997. Imiquimod is an immune response modifier designed to treat actinic keratosis, superficial basal cell carcinoma, and external genital warts. Serious adverse effects have resulted in the need to revise the label’s warnings.
Source: Nycomed, February 25, 2010, www.fougera.com
The FDA has approved the first generic version of Flomax capsules 0.4 mg (tamsulosin HCl) to treat men with benign prostatic hyperplasia (BPH). Symptoms of prostate enlargement include a weak urinary stream, urgency, leaking or dribbling, and frequent urination, especially at night. BPH rarely causes symptoms before age 40, but more than half of men in their 60s and as many as 90% of men older than 70 years of age have symptoms of BPH.
The prescribing information and the safety warnings for the generic version are the same as those for Flomax capsules.
Source: FDA, March 2, 2010
Canyon Pharmaceuticals has announced the launch of desirudin for injection (Iprivask), the first direct thrombin inhibitor (DTI) approved in the U.S. by the FDA for preventing deep vein thrombosis (DVT). It was approved in 2003 in the U.S., but it is available only now. Iprivask has been used for 10 years in Europe, where it is known as Revasc.
In clinical trials, Iprivask was found to be superior to both heparin and enoxaparin (Lovenox, Sanofi-Aventis) for preventing proximal DVT and major venous thromboembolic embolism (VTE) after elective hip replacement surgery. VTE is a common postsurgical complication and is associated with increased hospital costs, length of stay, morbidity, and mortality.
Administered as a fixed subcutaneous (SQ) dose, Iprivask is considered easier to use than intravenous (IV) agents and may be a safer alternative for DVT prophylaxis.
Iprivask does not pose a risk for thrombocytopenia or heparin-induced thrombocytopenia; it is relatively short-acting and is easy to monitor. It is modeled after hirudin, an anticoagulant found in the saliva of medicinal leeches. However, it must be used with caution in patients with renal impairment.
Source: Canyon, March 1, 2010, www.canyonpharma.com
Shire’s velaglucerase alfa for injection (VPRIV) has been approved to treat children and adults with type-1 Gaucher disease. This rare genetic disorder affects people who do not produce enough of an enzyme called glucocerebrosidase. The new product is an alternative to imiglucerase (Cerezyme, Genzyme), which has been in short supply.
Type-1 is the most common form of the disease and is more prevalent among Jews of Eastern European descent. In patients lacking the enzyme, harmful amounts of a certain lipid can build up in the liver, spleen, bones, bone marrow, and nervous system, resulting in the inability of cells and organs to function properly.
The FDA’s approval of velaglucerase replacement therapy was based on a priority review of data from 3 clinical studies of 82 patients four years of age and older, some of whom had previously received imiglucerase.
The recommended velaglucerase regimen is 60 IU/kg every other week as a one-hour IV infusion.
Adverse events have been infusion-related and have included headache, dizziness, hypotension, hypertension, nausea, fatigue, asthenia, and pyrexia. Infusion reactions were generally mild and occurred most frequently during the first six months of therapy in treatment-naive patients. Children were more likely than adults to experience rash, upper respiratory tract infection, prolonged partial thromboplastin time, and pyrexia.
Sources: FDA, March 2, 2010; Medscape, March 1, 2010
The FDA has approved Covidien’s New Drug Application for hydromorphone HCl (Exalgo) extended-release tablets. A boxed warning mentions the potential for abuse.
This once-daily Schedule II agent is indicated for the management of moderate-to-severe pain in opioid-tolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period of time.
Patients considered opioid-tolerant are those who are taking at least 60 mg/day of oral morphine, 25 mcg/hour of transdermal fentanyl, 30 mg/day of oral oxycodone, 8 mg/day of oral hydromorphone, 25 mg/day of oral oxymorphone, or an equianalgesic dose of another opioid for a week or longer.
Hydromorphone HCl has been used in treating chronic pain for more than 80 years, but the extended-release formulation is new. Alza’s osmotic delivery system is designed to release the opioid at a controlled rate and to help minimize the peaks and troughs that are sometimes experienced by patients who are prescribed products that are taken at more frequent intervals.
Exalgo is contraindicated in opioid non-tolerant patients; those with mild, acute, postoperative, or temporary pain; patients with compromised respiration, those with a narrowed or obstructed gastrointestinal tract; and those with a hypersensitivity to hydromorphone and sulfites. The drug is not recommended for patients who have taken monoamine oxidase inhibitors within the previous 14 days. Tablets should be swallowed whole.
A Risk Evaluation and Mitigation Strategy (REMS) will be included. Covidien’s development partner is CombinatoRx, Inc.
Sources: Covidien and Street Insider. com, March 2, 2010
AP24534, an investigational pan–bcr-abl inhibitor made by Ariad Pharmaceuticals, has been granted orphan drug designation by the FDA and the European Medicines Agency. In the U.S., the drug is indicated for patients with chronic myeloid leukemia (CML) and Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). In the U.S. and European Union, its orphan designation is for CML and ALL.
In preclinical studies, AP24534 demonstrated inhibition of kinase targets associated with acute myeloid leukemia (AML) as well as proliferation and angiogenesis in multiple solid tumors.
Source: Ariad, March 1, 2010
ImmunoGen’s IMGN901 compound has received an orphan drug designation when used to treat patients with Merkel cell carcinoma (MCC). The European Union also granted an orphan medicinal product designation for the treatment of MCC.
IMGN901 is designed to kill cancer cells that express CD56, a protein. MCC is an aggressive neuroendocrine cancer of the skin that typically occurs on the head and neck, most often in individuals of European ancestry.
Approximately 2,000 new cases of MCC are diagnosed in the U.S. each year, and the incidence is increasing. The company plans to begin pivotal testing in 2011.
Source: ImmunoGen, March 8, 2010
Bayer HealthCare Pharmaceuticals has announced the approval of an orphan drug designation for ciprofloxacin dry powder inhaler to manage pulmonary infection caused by Pseudomonas aeruginosa in patients with cystic fibrosis. A similar designation has already been granted by the European Medicines Agency.
This investigational agent combines the powder (formulated by Novartis) with a delivery inhaler. The product is in phase 2 development.
Patients with cystic fibrosis have thickened respiratory secretions that are difficult to clear, thus increasing the risk of infection and inflammation.
Source: Bayer, March 11, 2010
The FDA has approved carglumic acid tablets (Carbaglu, Orphan Europe) to treat excessive levels of ammonia in the blood. N-acetylglutamate synthase (NAGS) deficiency is a rare genetic disorder that can manifest soon after birth. The deficiency and the resulting hyperammonemia can be fatal if they are not detected and treated rapidly. DNA testing can confirm the diagnosis.
The drug’s safety was evaluated in 23 patients who were treated for periods ranging from six months to 21 years. Carbaglu reduced blood ammonia levels within 24 hours and normalized levels within three days. Most patients appeared to maintain normal plasma ammonia levels with long-term treatment.
Carbaglu should be administered only by physicians with experience in treating metabolic disorders. The recommended initial dose for acute hyperammonemia is 100 to 250 mg/kg per day. Other ammonia-lowering therapies with Carbaglu during episodes of acute hyperammonemia are recommended. Dose adjustments may be needed according to the patient’s ammonia levels and symptoms.
Source: FDA, March 18, 2010
Olmesartan medoxomil tablets (Benicar, Daiichi Sankyo) are now approved for the treatment of hypertension in children and adolescents 6 to 16 years of age. The approval was based on study data from a phase 3 clinical trial involving pediatric patients.
This angiotensin II receptor blocker is already indicated for adults with elevated BP. For more information on the pediatric indication, please see this month’s Pharmaceutical Approval Update feature, page 218.
The FDA has approved botulinum toxin type A (Botox, Allergan) to treat spasticity in the flexor muscles of the elbow, wrist, and fingers in adults. Spasticity is common after stroke, traumatic brain injury, or the progression of multiple sclerosis.
Botox temporarily blocks connections between nerves and muscles, resulting in a temporary paralysis of the spastic muscle. The tightness and stiffness of the muscles can lead to pain, difficulty in performing activities of daily living, and changes in physical appearance.
A boxed warning notes that the effects of the toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism, such as swallowing and breathing difficulties that can be life-threatening.
Botox has not been shown to be safe or effective for other upper-limb muscles; spasticity in the legs; or fixed contractures, which affect range of motion.
Source: FDA, March 9, 2010
Triptorelin pamoate 2.5 mg for injectable suspension has been approved. This twice-yearly version of Trelstar (Watson Pharmaceuticals) is a palliative therapy for advanced prostate cancer.
A gonadotropin-releasing hormone (GnRH) agonist, the drug suppresses testosterone production for six months. Developed by the Debiopharm Group and first approved in the U.S. in 2000, Trelstar is also available in one-month (3.75-mg) and three-month (11.25-mg) forms. The new, longer-acting formulation can be stored at room temperature.
The product is administered with a thin needle and is associated with little injection-site pain.
Source: Watson, March 11, 2010
A new version of Wyeth’s Pneumococcal 7-valent conjugate vaccine (diphtheria CRM197 protein) (Prevnar 7) has been approved. Prevnar 13 is indicated for the prevention of pneumococcal illnesses, such as ear infections, sepsis, and meningitis, in infants and young children.
The vaccine is the first product to win FDA approval since Pfizer acquired Wyeth last year. Prevnar 13 is designed to reduce the risk of infection by 13 strains of pneumococcal disease in children five years old and younger. Prevnar 13 adds protection against six additional strains of bacterial infection compared with Prevnar 7. In the U.S., children receive four injections. Children who have not been fully vaccinated with the original Prevnar can finish their schedule with the new vaccine.
Infections from pneumococcal disease dropped dramatically after Prevnar 7 was released in 2000, but infections began rising again in 2005 with the development of new variants of the disease.
Prevnar 13 costs about $100 per dose, or 30% over the previous vaccine. Pfizer plans to file an indication for adults in the U.S. and Europe and to expand into countries where Prevnar 7 has not yet been sold.
The vaccine is discussed in the Pharmaceutical Approval Update feature on page 217.
Sources: The Wall Street Journal, February 24, 2010; Philadelphia Inquirer, February 25, 2010; Associated Press
The FDA has added a black-box warning to the labeling for clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis), an anticoagulant. The drug may be less effective in people who cannot metabolize the drug to convert it to its active form. These “poor metabolizers” might not receive the drug’s full benefit and may remain at risk for a heart attack, stroke, or death from cardiovascular disease. The FDA had added this warning to the label in May 2009, but after reviewing more data, the agency decided to highlight the risk in a boxed warning.
Source: FDA, March 12, 2010
The FDA has approved a name change for Takeda’s heartburn drug Kapidex (dexlansoprazole) to avoid confusion with two other agents, Casodex (bicalutamide, AstraZeneca) and Kadian (morphine sulfate, Actavis Kadian LLC). The new name for Kapidex is Dexilant. A new National Drug Code (NDC) number will be assigned.
Since Kapidex was approved in January 2009, there have been dispensing errors because of confusion with other drugs. Kapidex is a proton pump inhibitor, Casodex is used to treat advanced prostate cancer, and Kadian is an opioid analgesic.
Source: FDA, March 4, 2010
New approval. The FDA has approved Boston Scientific’s Express LD Iliac Pre-mounted Stent System for use in iliac arteries. In patients with atherosclerotic iliac disease, plaque has built up within the arteries that supply blood to the legs, resulting in poor blood flow and leg pain. The disease can be treated with medication, surgery or angioplasty. The stent design offers physicians a less invasive alternative to surgery. This balloon-expandable stent has received CE Mark approval and is approved for iliac use in international markets.
Source: Boston Scientific, March 11, 2010
Charges against Guidant. Guidant LLC, a subsidiary of Boston Scientific Corp., has been charged with criminal violations of the Federal Food, Drug, and Cosmetic Act related to safety problems with some of its implantable defibrillators. Because the device delivers an electrical shock to the heart in an effort to return the heartbeat to a normal rate, if it does not operate properly when needed, the patient can die within minutes.
According to the information filed in federal district court in St. Paul, Minnesota, Guidant concealed information from the FDA regarding catastrophic failures in some of its lifesaving devices. The charges were filed following a four-year investigation into the company’s handling of short-circuiting failures of three models of implantable cardioverter defibrillators: Ventak Prizm 2 DR (Model 1861) and Contak Renewal (Models H135 and H155). Guidant issued safety advisories about the failures in June 2005.
Source: U.S. Department of Justice, February 25, 2010; www.justice.gov/opa/pr/2010/February/10-civ-202.html
Name: TIGR Matrix Surgical Mesh
Manufacturer: Novus Scientific Pte. Ltd., Canton, Mass./Singapore
Approval Date: February 5, 2010
Purpose: The mesh is used to reinforce weak soft tissues such as hernias.
Description: A dual-fiber design provides an initial high-strength, high-stability configuration, with gradually increasing compliance over time as the product is resorbed. The 100% resorbable, synthetic matrix is warp-knitted from two different resorbable fibers that degrade at different rates after implantation. The macroporous structure enables reliable tissue repair.
Benefit: Permanent synthetic material is widely used, but the permanent implant of an inert material can result in long-term complications. Not all resorbable materials are suitable for all patients because the short degradation period restricts their use as sole components of resorbable surgical meshes. The new technology fills a gap in the market for patients needing a ventral, incisional, or inguinal hernia repair and may avoid the long-term complications associated with permanent synthetic meshes.
The mesh is designed to retain its mechanical strength for at least six months, yielding better compliance because of its dual fiber construction. The matrix gradually degrades; like other natural by-products, it is absorbed and excreted. As the world’s first long-term resorbable matrix, it represents a significant breakthrough.
Name: Dyna-Link Spinal System/Presidio Spinal Plating System
Manufacturer: Life Spine, Hoffman Estates, Ill.
Approval Date: January 28, 2010
Purpose: This stand-alone device is indicated for use in spinal surgery.
Description: The spinal system accommodates two types of screws, and the thoracolumbar plating system features multiple types of low-profile implants. The device combines a surgical-grade titanium component and an Invibio Peek Optima interbody cage. Either fixed or variable angle screws can be used to control compression on the interbody device. The two systems incorporate an innovative, zero-step locking mechanism and use comprehensive instrumentation. Up to four screws can be accommodated for optimal torsional resistance.
Benefit: The instrumentation is designed to reduce the number of surgical steps and intraoperative complexity.
Name: ProGel Pleural Air Leak Sealant
Manufacturer: NeoMend, Inc., Irvine, Calif.
Approval Date: January 14, 2010
Purpose: Surgeons performing open resection of lung tissue use ProGel to seal air leaks on pulmonary tissue after sutures or staples are used to close the incision. After a lung tumor is removed, air leaks can develop around the sutures or staples that were used. The surgeon usually closes an air leak by suturing and stapling tissue or applying a surgical mesh over the leak. In some patients, lung tissue is so fragile that the surgeon might not try to use these usual closure methods.
In addition to the standard surgical closure methods, the sealant can be used to close lung tissue.
Description: ProGel sealant is composed of human serum albumin and a polyethylene glycol cross-linker that forms a clear flexible gel on mixing.
Benefit: The sealant is sprayed or painted on the lung tissue. In clinical studies, 35% of patients treated with ProGel and standard surgical closure were free of any air leaks upon hospital discharge, in contrast to 14% of patients treated with standard techniques alone. ProGel also reduced the number of air leaks occurring during surgery. The incidence and severity of side effects for both treatment groups were similar; however, the total number of kidney-related adverse events was higher in the ProGel patients (9.5%) than in the controls (3.8%).
Precautions: ProGel should not be used in patients who are allergic to human blood proteins or who have renal impairment. It should not be used after surgery for open or closed defects of the branches of the airway that lead to the lung because of a possible increased incidence of undesired air passageways between the lung and the tissue surrounding the lung.