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P T. 2013;38(6): 313-320, 351

New Drugs/Drug News/New Medical Devices June 2013

NEW DRUGS

Simbrinza Decreases Ocular Pressure

Brinzolamide 1.0%/brimonidine tartrate 0.2% ophthalmic suspension (Simbrinza, Alcon/Novartis) has been approved to reduce elevated intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. Simbrinza was found to decrease elevated IOP by 21% to 35%.

This is the only fixed-dose combination therapy for glaucoma in the U.S. that does not include a beta blocker.

For more information, please see this month’s Pharmaceutical Approval Update column on page 323.

Sources: The Pharma Letter, April 22, 2013; Novartis, April 19, 2013

Xofigo for Advanced Prostate Cancer

Radium-223 dichloride (Xofigo, Bayer/Algeta ASA) is indicated for men with symptomatic metastatic castration-resistant prostate cancer that has spread only to bone after medical or surgical therapy has been given to lower testosterone levels. Reviewed under the FDA’s priority program, the agent was approved more than 3 months ahead of schedule.

Previously known as alpharadin, this radiopharmaceutical agent binds with minerals in bone to deliver radiation directly to bone tumors, limiting damage to surrounding healthy tissues. The product is given once a month by intravenous (IV) injection. Radium, which is taken up by osteoblasts, then emits alpha radiation; this causes double-strand DNA breaks that eradicate prostate cancer cells at the site of increased bone turnover induced by the cancer.

Radium-223 dichloride produces minimal myelosuppression, is well tolerated, and shows an overall survival benefit.

Sources: FDA, GlobalData, and WebMD, May 15, 2013

Breo Ellipta for COPD

A once-daily inhaled drug, Breo Ellipta (GlaxoSmithKline/Theravance), has been approved to treat chronic obstructive pulmonary disease (COPD). The fluticasone furoate/vilanterol combination powder is used for the long-term maintenance of airflow obstruction in patients with COPD, chronic bronchitis, and emphysema.

Breo Ellipta contains 100 mcg of the corticosteroid fluticasone furoate (Flonase), a nasal spray used in the treatment of allergic rhinitis, and 25 mcg of vilanterol, which was not previously approved by the FDA. The new product is delivered in a dry powder via an inhaler.

In April, an FDA advisory committee voted 9–4 to approve the indications for long-term maintenance and decreased exacerbations; however, the panelists expressed concerns that vilanterol—the long-acting beta-agonist (LABA) component—provided nearly all of the clinical benefit; fluticasone provided less benefit. Some committee members also questioned the increased risk of pneumonia and bone fractures associated with the drug. In the end, the panelists agreed that once-daily use could improve medication adherence.

A boxed warning mentions that LABAs can increase the risk of asthma-related deaths. Breo Ellipta is not approved for the treatment of asthma, acute bronchospasm, or sudden breathing problems.

Similar combinations include fluticasone propionate/salmeterol (Advair Diskus) and budesonide/formoterol fumarate dihydrate (Symbicort), which are used twice daily.

Sources: FDA and MedPage Today, May 10, 2013

Liptruzet for LDL-Cholesterol

The FDA has approved an ezetimibe–atorvastatin combination (Liptruzet, Merck) for the treatment of elevated low- density lipoprotein-cholesterol (LDL-C) levels in patients with primary or mixed hyperlipidemia. The absorption of cholesterol is inhibited in the digestive tract by ezetimibe (Zetia, Merck/Schering), and the production of cholesterol in the liver is inhibited with atorvastatin (Lipitor, Pfizer).

Liptruzet is sold as a once-daily tablet containing 10 mg of ezetimibe combined with 10, 20, 40, or 80 mg of atorvastatin. The dose range is 10/10 mg per day through 10/80 mg per day.

The recommended starting dose is 10/10 mg or 10/20 mg taken once daily or 10/40 mg once daily for patients whose goal is a reduction of LDL-C levels by more than 55%. The tablets can be taken at any time of day, with or without food.

Sources: FreshNews.com, The Wall Street Journal, and MedPage Today, May 3, 2013

Kcentra Reverses Bleeding

A prothrombin complex concentrate (PCC; Kcentra, CSL Behring) has been approved for the urgent reversal of vitamin K antagonist anticoagulation in adults with acute major bleeding. PCC is made from the pooled plasma of healthy donors. It is only the second product to be approved for this use in the U.S.

No blood-group typing or thawing is necessary, and the product can be administered more quickly than plasma. The volume of PCC is significantly lower than plasma at recommended doses, providing an alternative for patients who cannot tolerate the volume of plasma required to reverse vitamin K antagonist anti-coagulation.

The new drug contains factors II, VII, IX, and X, all of which are low in patients receiving warfarin (Coumadin, Bristol-Myers Squibb) or other vitamin K antagonists. If a patient is wounded or needs emergency surgery, the anticlotting effects of warfarin must be reversed quickly to prevent major bleeding.

A boxed warning refers to the risk of blood clots associated with PCC. It is uncertain whether PCC might also be a suitable reversal agent for the new oral anticoagulants, such as rivaroxaban (Xarelto, Janssen), dabigatran (Pradaxa, Boehringer Ingelheim), and apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), for which there are no specific reversal antidotes.

Sources: FDA, April 29, 2013; MedPage Today, April 30, 2013

Generic Approvals

Oral Contraceptive (Pirmella)

Lupin Pharmaceuticals, Inc., has received final approval from the FDA to sell Pirmella 7/7/7 and Pirmella 1/35 (norethindrone and ethinyl estradiol tablets), a generic version of Janssen’s Ortho-Novum tablets.

Sources: Money Control and Business Standard, April 26, 2013

Cefadroxil for Infections

Aurobindo Pharma may now sell generic cefadroxil oral suspension in strengths of 250 mg/5 mL and 500 mg/5 mL to treat bacterial infections. The product is the generic equivalent of formerly trademarked Duricef (Warner Chilcott) in the same strengths.

Source: Business Standard, April 26, 2013

Injectable Metoclopramide

The FDA has approved the second drug to be offered by BD Rx, a subsidiary of Becton, Dickinson and Company, in its BD Simplist line of prefilled injectables. Metoclopramide, an antiemetic agent, is the generic form of Reglan Intravenous (Wyeth/Pfizer). The product is designed to minimize the number of steps involved in the vial-and-syringe-injection sequence, thereby reducing the potential risk of medication errors and enhancing patient safety.

Sources: The Pharma Letter, April 23, 2013; www.bd.com; www.bdrxinc.com

Fenofibrate for Hyperlipidemia

Mylan Pharmaceuticals has received the FDA’s final approval for its Abbreviated New Drug Application (ANDA) for fenofibrate tablets, 48 mg and 145 mg. This product is the generic version of AbbVie Inc.’s TriCor tablets.

Fenofibrate is indicated as an adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B and to increase high-density lipoprotein cholesterol in adults with primary hypercholesterolemia or mixed dyslipidemia. It is also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia. In a controlled trial of patients with type-2 diabetes, however, the 145-mg dose was not found to reduce coronary heart disease morbidity and mortality rates.

Source: Mylan, May 17, 2013

Two Companies Launch Zolmitriptan for Migraine

Mylan has received the FDA’s approval for its NDA for zolmitriptan tablets, 2.5 mg and 5 mg. This product is the generic version of Zomig (IPR Pharmaceuticals/AstraZeneca) and is indicated for the acute treatment of migraine with or without aura in adults.

The tablets are meant to be used only when a diagnosis of migraine has been established. If a patient does not respond after the first dose, the clinician should reconsider the diagnosis before administering the drug to the patient again.

Zolmitriptan is not indicated for the prevention of migraine attacks or cluster headaches.

Zydus Cadila, based in India, is launching zolmitriptan orally disintegrating tablets upon receiving final approval from the FDA. The product will be sold in strengths of 2.5 mg and 5 mg in the U.S.

Sources: Mylan, May 15, 2013, http://investor.mylan.com; The Economic Times, May 16, 2013, http://articles.economictimes.indiatimes.com

NEW INDICATIONS

Amitiza for Opioid-Induced Constipation

Lubiprostone (Amitiza, Sucampo/Takeda) has been approved to treat opioid-induced constipation in patients with chronic non-cancer pain. A dose of 24 mcg twice daily was previously approved to treat chronic idiopathic constipation in adults. A dose of 8 mcg twice daily is also indicated for the treatment of irritable bowel syndrome with constipation in women 18 years of age and older.

Sucampo is studying the use of lubiprostone for pediatric constipation.

Sources: Bloomberg News, April 23, 2013; www.amitiza.com

Sustiva in HIV-Infected Children

Efavirenz (Sustiva, Bristol-Myers Squibb) has been approved to treat children 3 months to 3 years of age with HIV-1 infection. The drug can be given once daily, and a capsule sprinkle is included for young patients who cannot swallow tablets. Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), was originally approved in the U.S. in 1998 to treat children 3 years of age or older with HIV infection who weighed at least 10 kg.

Efavirenz is not recommended for children younger than 3 months of age or who weigh less than 3.5 kg, because the drug’s safety, pharmacokinetic properties, and antiretroviral activity have not been evaluated in these age and weight groups. There is also a risk of HIV resistance if the drug dose is insufficient.

Sources: FDA and Bristol-Myers Squibb, May 3, 2013

Two Agents for Juvenile Arthritis

Actemra

Tocilizumab (Actemra, Genentech) is now indicated for the treatment of polyarticular juvenile idiopathic arthritis in children 2 years of age and older. The drug can be used alone or with methotrexate.

Tocilizumab was the first humanized interleukin-6 receptor antagonist approved for adults with active, moderate-to-severe rheumatoid arthritis (RA) who responded inadequately to one or more disease-modifying antirheumatic drugs. Previously approved for patients with active systemic juvenile idiopathic arthritis (SIJA), tocilizumab is also approved for RA in adults.

Source: Genentech, April 30, 2013

Ilaris

Canakinumab (Ilaris, Novartis) has been approved for the treatment of active SJIA in patients 2 years of age and older. This medication is a selective, fully human monoclonal antibody that inhibits interleukin-1 (IL-1) beta. Excessive production of IL-1 beta plays a role in inflammation.

Canakinumab is the first IL-1 beta inhibitor approved for SJIA. It is given as a once-monthly subcutaneous injection. SJIA can affect children as young as age 2 years and can continue into adulthood.

This approval marks the second indication of canakinumab for patients with autoimmune inflammatory conditions. In 2009, it was approved for both children and adults with cryopyrin-associated periodic syndrome (CAPS), a rare, lifelong, genetic disorder with debilitating symptoms. In 2011, however, an FDA advisory committee declined to approve this drug for gout, citing safety concerns. Canakinumab is also approved in other countries for the treatment of refractory gouty arthritis and CAPS.

Sources: Novartis, May 10, 2013 and Fierce Biotech, June 22, 2011

Tarceva for Lung Metastases

Erlotinib (Tarceva, Genentech/OSI) has been approved as a first-line treatment for patients with metastatic non– small-cell lung cancer (NSCLC) who have certain mutations in the EGFR (endothelial growth factor receptor) gene. A companion diagnostic test for erlotinib is discussed on page 319.

Erlotinib was originally approved in November 2004 to treat patients with locally advanced or metastatic NSCLC after failure of at least one previous chemotherapy regimen. In 2010, the FDA approved erlotinib as a maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease had not progressed after four cycles of platinum-based first-line chemotherapy.

Source: FDA, May 14, 2013

Simponi for Ulcerative Colitis

Golimumab (Simponi), a biologic drug, may be used to treat moderate-to-severe ulcerative colitis. The expanded indication for golimumab, an inhibitor of tumor necrosis factor (TNF), applies to ulcerative colitis patients who have not responded to other approved therapies or who require continuous steroid treatment.

Golimumab was previously approved for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

The new approval was based on two clinical trials.

Drugs currently approved for ulcerative colitis include steroids and salicylic acid derivatives as well as anti-TNF biologic agents such as infliximab (Remicade, Janssen Ortho Biotech) and adalimumab (Humira, AbbVie).

Source: FDA, May 15, 2013

NEW FORMULATIONS

Oxycodone Tablet Redesigned to Reduce Misuse

The FDA has approved a new formulation of the opioid analgesic oxycodone HCl (OxyContin, Purdue Pharma) as a means of decreasing the potential for abuse of the drug.

The potency, label, and dosage recommendations are not being changed, but the tablet is redesigned so that it cannot be as easily cut, broken, chewed, crushed, or dissolved, thus making it less likely to be abused by snorting. Although abuse might be decreased, it will probably not be completely prevented. Purdue is not permitted to market the tablet as tamper-resistant.

Because the drug was approved as a timed-release pain medication, the original marketing of OxyContin did include safety claims. This led to widespread overprescribing of the original formulation.

Purdue is required to conduct a post-marketing study to determine the extent to which the new formulation reduces abuse and misuse of this opioid.

The FDA is also requiring a Risk Evaluation and Mitigation Strategy (REMS), including a medication guide.

Source: FDA, April 5, 2013

Procysbi, an Orphan Drug For Cystine Buildup

Cysteamine bitartrate (Procysbi, Raptor) has been granted an orphan product designation by the FDA to treat nephropathic cystinosis in patients 6 years of age and older. This is a revised formulation of Mylan’s Cytagon, which was approved in 1994.

Cystinosis, a rare genetic condition, causes an amino acid (cystine) to accumulate, potentially leading to urinary losses of sugar, proteins, and salts. Nephropathic cystinosis is the most severe form of the condition. Procysbi is discussed in the Pharmaceutical Approval Update column on page 324.

Sources: FDA, April 30, 2013; Pharma Times Online, May 1, 2013

Nymalize Oral Solution For Brain Hemorrhage

On May 10, the FDA approved a new nimodipine oral solution (Nymalize, Arbor Pharmaceuticals) to treat patients with subarachnoid hemorrhage.

Before this approval, nimodipine was available only as a liquid-filled gel capsule. Because the product is commonly administered by a nasogastric tube, health care providers extracted the product from the gel capsule with a syringe. This resulted in accidental administrations of nimodipine intravenously instead of via the intended enteral (oral) syringe.

Over the years, serious and sometimes fatal consequences resulted from intra- venous (IV) injection of the liquid contents of oral nimodipine capsules. IV administration intended for oral use can result in death, cardiac arrest, hypotension, and other heart-related complications. In August 2010, the FDA alerted health care professionals about the risks of IV administration of nimodipine from oral capsules. In 2006, a boxed warning was added to the drug’s label to warn against such use.

With Nymalize, there is no need for a needle, which was considered a causative factor in past medication errors.

The application for Nymalize received a fast-track designation and a priority review based on the potential for the oral formulation to decrease medication errors.

Sources: FDA and News Medical, www.news-medical.net, May 14, 2013

DRUG NEWS

Compounding Pharmacy Recalls Eye Products

On April 17, 2013, Balanced Solutions Compounding Pharmacy in Florida voluntarily recalled all lots of its unexpired ophthalmic products. An FDA inspection of the facility revealed poor practices and conditions, which raised concerns about sterility and possible microbial contamination of the solutions, injectables, and ophthalmologic agents. A chromium chloride injection sample was contaminated with gram-negative bacteria, although Sphingobacterium thalpophilum does not usually cause infection in humans. No adverse events related to the recall had been reported.

Source: FDA, April 21, 2013

Recall Expanded At NuVision Pharmacy

The FDA has alerted health care providers about a lack of sterility assurance of all sterile drug products made and distributed by NuVision Pharmacy of Dallas, Texas. The FDA recommends that these products should not be administered to patients.

The FDA based the expanded alert on a recent inspection of the NuVision Dallas facility. The investigators had observed poor sterile production practices.

In April, NuVision recalled methylcobalamin injection and lyophilized injection products because of concerns about the quality control processes identified during the FDA inspection. The FDA received reports of adverse events in patients, including fever, flu-like symptoms, and soreness at the injection site. The agency was not aware of any additional reports associated with other sterile products from NuVision.

Source: FDA, May 18, 2013

Liver Warning for Samsca

Tolvaptan (Samsca, Otsuka) should be used for no more than 30 days, and it should not be prescribed for patients with underlying liver disease. The drug, which is used to treat low serum sodium levels, can cause liver injury, potentially leading to the need for a liver transplant. The updated label includes information about limiting the duration of therapy and notes a contraindication for patients with cirrhosis.

Last January, Otsuka notified physicians that the drug was linked to elevated hepatic enzymes three times the upper limit of normal (ULN) and elevated bilirubin above twice the ULN.

Source: MedPage Today, April 30, 2013

OxyContin: No Generic Versions Allowed

The reformulation of oxycodone (Oxy-Contin, Purdue Pharma) (see page 315) is intended to prevent the opioid agent from being cut, broken, chewed, crushed, or dissolved in order to release more of the medication. Because original OxyContin provides the same therapeutic benefits as reformulated OxyContin but poses an increased potential for certain types of abuse, the FDA is not approving any abbreviated New Drug Applications for generic versions that rely on the approval of original OxyContin.

First approved in 1995, the product was often manipulated to defeat its extended-release properties. In 2010, a reformulated version was approved and was designed to be more difficult to misuse or abuse.

Source: FDA, April 16, 2013

Opana: Generic Versions Allowed

Because the original formulation of Endo Pharmaceuticals’ extended-release oxymorphone (Opana ER), which lacked abuse-resistant mechanisms, was not pulled from the market for safety reasons, the FDA said that generic versions based on that formula will be permitted.

In response to a citizen’s petition from Endo, the FDA denied the company’s requests to block generic formulations. Endo pulled its original version of Opana from the market in March 2012 after reformulating it with abuse-deterrent technology, similar to how long-acting oxycodone (OxyContin, Purdue Pharma) was reformulated in 2010. (Because original OxyContin was pulled from the market for safety reasons, generic formulations based on that formula are not allowed. Purdue voluntarily withdrew the original OxyContin formulation from the market after the abuse-deterrent version became available in 2010.)

Endo had tried to block generic approvals based on Opana’s original formulation and even claimed that the first version of the product was unsafe. If the FDA had declared that the earlier version was withdrawn for safety reasons, the agency would have required the withdrawal of generic competitors. One company, Impax Labs, has been shipping generic Opana based on the original formulation since Endo’s patent expired at the beginning of this year.

The FDA, disagreeing with Endo about Opana’s alleged safety advantages, pointed out that abuse-deterrent products can still be tampered with.

Endo said that it was extremely disappointed with the FDA’s decision, which could mean $120 million less in revenue for the rest of 2013.

Sources: MedPage Today, May 10, 2013; The Philadelphia Inquirer, May 14, 2013

FDA Designations

Fast Track Status for KB001A

The FDA has granted a fast-track designation to Sanofi Pasteur’s KB001A, which is intended to protect against bacterial pneumonia caused by Pseudomonas aeruginosa in patients receiving mechanical ventilation.

Most P. aeruginosa infections primarily affect the respiratory system and pose a serious problem because of the bacterium’s resistance to antibiotics. Sanofi Pasteur and KaloBios are conducting a phase 1 trial of the monoclonal antibody in the U.S. and have started planning a phase 2b study.

KB001A is a “humaneered” antibody fragment that blocks a virulence mechanism on the bacterium’s external surface, relieving inflammation. KB001A does not contribute to broad-spectrum bacterial resistance.

Sources: Sanofi/KaloBios and The Pharma Letter, April 23, 2013

Orphan Drug Status for XEN402

Teva and Xenon have received an orphan drug designation for XEN402, an investigational agent that is being developed for the treatment of pain associated with erythromelalgia, a form of blood-vessel inflammation. This rare autosomal dominant condition is characterized by spontaneous or easily evoked attacks of burning pain in the feet and hands, typically associated with elevated skin temperature and erythema. Symptoms are usually experienced after exercise, prolonged standing, exposure to heat, or changes in humidity.

Source: The Pharma Letter, April 23, 2013

Cancer Risk With Nexterone

In a large-scale retrospective study from Taiwan, men who took amiodarone (Nexterone, Baxter) to treat cardiac arrhythmias, particularly over a long period of time, had a 20% increased risk of cancer. The risk was even higher (46%) when cumulative doses exceeded 180 days annually.

Since its approval by the FDA in 1985, amiodarone has been associated with pulmonary fibrosis, skin cancer, and thyroid malignancies. Because the drug is fat-soluble and degrades slowly, large amounts can accumulate in soft tissues over a long period of time.

In the Taiwan study, researchers analyzed data from 6,418 patients who had received a prescription for the drug between 1997 and 2008. Median patient age was 70 years, and median follow-up was 2.57 years. Comorbidities included hypertension (76%), heart failure (47%), chronic obstructive pulmonary disease (44%) and diabetes (39%). A total of 288 cancers were identified during the almost 22,000 person-years of follow-up.

There was a 10% increase in risk for all cancers among patients who received amiodarone. Among men, the risk was elevated among 20- to 60-years-olds and those older than 80 years of age. Women did not appear to be at increased risk. The researchers suggested that the drug might be cleared more quickly in women.

Sources: Cancer, April 8, 2013 (online); Clinical Advisor; Science Daily

PML and Fumarate Agents

Two cases of progressive multifocal leukoencephalopathy (PML) have been reported in European patients who received oral dimethyl fumarate, which is used in the treatment of multiple sclerosis (MS).

PML was documented in one patient in the Netherlands and another in Germany after several years of treatment with European formulations of the drug, long available as psoriasis treatments. Both patients had psoriasis, although the Dutch patient had neurological symptoms leading to a diagnosis of possible MS 6 months before PML was detected.

Biogen Idec said that it was aware of two other cases of PML in patients taking drugs containing dimethyl fumarate, both involving its European product sold as Fumaderm. However, Fumaderm contains other active ingredients and those patients had additional confounding factors as well.

PML has also been a problem with the MS drug natalizumab (Tysabri, Biogen Idec) since its approval in 2004. Some cases have also been reported with rituximab (Rituxan, Genentech). Until now, however, PML had not been reported with any of the newer oral drugs used in MS. In addition to the new FDA-approved formulation of dimethyl fumarate (BG-12, Tecfidera), others include fingolimod (Gilenya, Novartis) and teriflunomide (Aubagio, Genzyme/Sanofi).

Biogen Idec claims that other compounds that are administered along with dimethyl fumarate can complicate the interpretation of these cases. In the case of Fumaderm, one of those patients was also taking methotrexate and steroids and the other had been taking efalizumab (Raptiva, Genentech/Merck Serono), also linked to PML.

Overall, PML has been rare in patients receiving drugs containing dimethyl fumarate. Patients also had long periods of lymphopenia before PML developed.

No cases of PML have been seen with the FDA-approved formulation, which has no active ingredients other than dimethyl fumarate.

Sources: N Engl J Med 2013;368:1657–1661; MedPage Today, April 24, 2013

Chemotherapy Problematic for Elderly Breast Cancer Patients

Women older than 75 years of age who have stage I breast cancer have similar prospects for survival as younger women do. If the cancer is stage II or III, however, it is less likely that their therapy will be adequate or appropriate. Findings reported from Swedish Cancer Institute in Seattle, Washington, underscore the need to find effective therapies for those patients, the researchers say.

Data from 2,329 women with breast cancer, 65 to 94 years of age, were reviewed. Of the women, 956 (41%) were age 75 or older and 60% of those had stage I tumors. Most of the women had undergone either lumpectomy with radiation (698), mastectomy with radiation (108), or mastectomy without radiation (120) as the initial treatment. Of the 716 women who saw an oncologist, 106 were recommended chemotherapy and 88 received it. Of 18 patients who declined adjuvant chemotherapy, 13 received radiation therapy in addition to surgery.

Of the 88 women receiving chemotherapy, 74 received standard chemotherapy and 14 received nonstandard chemotherapy because of their age or comorbidities. Most of the women (81%) completed standard therapy, but 18 who could not tolerate it were switched to nonstandard treatment. Patients discontinued adjuvant therapy because of complications (thrombocytopenia, neuropathy, neutropenia, and hyponatremia), personal choice, and disease progression. One woman died of causes not related to treatment.

Women older than age 75 are rarely included in clinical trials because of the high prevalence of comorbid conditions and a higher risk of death. In fact, women in this age group were more likely to refuse treatment and less likely to complete treatment because of complications. Only 69% of patients who received an initial reduced or nonstandard treatment regimen completed therapy, and many presumably healthier patients starting standard chemotherapy regimens had to be switched to a reduced dosage or had to stop therapy because of complications. Even so, 28% of patients who started with standard therapy and switched to a nonstandard regimen did not complete therapy.

Survival rates for stage I patients were excellent, regardless of age. Most of these patients received either no adjuvant systemic therapy or hormone-only adjuvant therapy. Many authors have proposed that older women are undertreated. In this study, women who saw an oncologist were more likely to receive adjuvant hormonal therapy. However, the researchers assume that even oncologists were reluctant to recommend chemotherapy for higher-stage cancer because of patients’ comorbidities.

In the study, however, no patients died of complications related to treatment, suggesting that if flexibility is used, severe complications of therapy could be avoided or at least mitigated. The researchers cited a study in which a significant portion of patients 65 to 78 years of age received intensive doses with manageable toxicity levels, although 24% required hospitalization for complications. The researchers emphasize the need to find safe and effective treatments that can be tolerated by older adults to bring their stage II and III survival rates into line with those of younger patients.

Source: J Geriatr Oncol 2013;4:148–156

Simvastatin May Reduce Exercise Benefits

Statins are often suggested to lower cholesterol and prevent heart disease in patients with obesity, diabetes, and metabolic syndrome. However, researchers at the University of Missouri–Columbia found that simvastatin, previously sold as Zocor (Merck), hindered the positive effects of exercise for obese and over-weight adults.

“Fitness is a proven predictor of longevity and health because it protects people from a variety of chronic diseases,” according to Dr. John Thyfault, Associate Professor of Nutrition and Exercise Physiology at the university. He said that if patients start exercising and taking statins at the same time, statins appear to block exercise from improving fitness levels.

Cardiologists often want to prescribe statins to all patients over a certain age whether or not they have metabolic syndrome; these drugs also are recommended for people with type-2 diabetes. Dr. Thyfault recommends that cardiologists weigh the benefits and risks of statins more closely in light of this new information.

He commented, “Statins have been used for only 15 to 20 years, so we don’t know what the long-term effects of statins will be on aerobic fitness and overall health. If the drugs cause complications with improving or maintaining fitness, not everyone should be prescribed statins.”

Dr. Thyfault and his team measured cardiorespiratory fitness in 37 previously sedentary, obese individuals, 25 to 59 years of age, with low fitness levels. The participants followed the same exercise regimen for 12 weeks; 18 of the 37 people also took 40 mg of simvastatin daily.

Participants in the exercise-only group increased their cardiorespiratory fitness by an average of 10%, whereas those taking statins improved by only 1.5%. Skeletal muscle mitochondrial content decreased by 4.5% in the statin group, whereas the exercise-only group experienced a 13% increase, a normal response following exercise training.

Research is needed to determine whether lower doses of simvastatin or other statins also affect people’s exercise outcomes and thus their risk for diseases such as type-2 diabetes.

Sources: J Am Coll Cardiol, April 10, 2013 (online); University of Missouri News Bureau, May 15, 2013; http://munews.missouri.edu

Valproate in Pregnancy May Raise Child’s Autism Risk

Pregnant women who take valproate sodium (Depacon, AbbVie) might be increasing the risk of autism and its spectrum disorders in their children. In a population-based study from Denmark, in utero exposure to the drug was associated with a five-fold elevated risk of autism and a three-fold elevated risk of autism spectrum disorder. The risks remained after adjustments were made for epilepsy and psychiatric disease in the mothers. Valproate is indicated for migraine prevention, seizure control, and manic and mixed episodes in bipolar disorder.

The American Academy of Neurology recommends that pregnant women avoid taking valproate, when possible, because of cognitive and physical birth defects for children exposed in utero. Women of childbearing age should be informed of the risks to the fetus before valproate is prescribed.

In children of mothers with epilepsy, the risk of autism was 2.9 times higher with valproate exposure, with an absolute risk of 2.95% versus 1.02% among all others in the cohort not exposed to the drug. The risk for offspring exposed to valproate during gestation appeared elevated if the mother was not taking the drug for epilepsy.

In May, the FDA issued a warning for pregnant women to avoid valproate products—valproate sodium (Depacon), divalproex sodium (Depakote, AbbVie), valproic acid (Depakene, AbbVie), and Stavzor (Noven), and their generic counterparts—because of a finding of lower intelligence scores in children at age 6.

Sources: FDA, May 6, 2013; JAMA 2013;309:1696–1703; MedPage Today, April 23, 2013

Revised Guidelines For Diabetes Therapy

New guidelines from the American Society of Endocrinologists emphasize a tailored approach to treating type-2 diabetes while maintaining the use of an algorithm-based model. The new algorithm involves every FDA-approved class of medications for managing hyperglycemia while still considering individual age and comorbidities. The guidance is published in a form more representative of a slide presentation, with various colors representing evidence for risks and benefits.

Monotherapy, dual therapy, or triple therapy, based on initial glycosylated hemoglobin (HbA1c), is recommended. Monotherapy could include metformin (Glucophage, Bristol-Myers Squibb), glucagon-like peptide-1 (GLP-1) agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors, as well as alpha-glucosidase inhibitors. These first-line therapies carry minimal risk. However, caution is urged for sodium glucose co-transporter 2 (SGLT-2) drugs, thiazolidinediones (TZDs), and sulfonylureas in this setting.

Dual therapy might consist of metformin or another first-line agent, plus any of the three other FDA-approved monotherapy agents, in addition to colesevelam (Welchol, Sankyo Pharma) or bromocriptine (Cycloset, VeroScience). Caution is urged for TZDs, SGLT-2 drugs, basal insulin, and sulfonylureas in this setting. Recommendations are similar for triple therapy.

Incretins received a positive recommendation despite concerns about pancreatitis and pancreatic tumors. The evidence regarding pancreatic disease with GLP-1 agonists or DPP-4 inhibitors is anecdotal so far.

Tailoring glycemic targets should be based on several factors, although 6.5% for HbA1c remains the optimal goal. The guidance also includes recommendations for reducing cardiovascular risks, excess weight, and prediabetes. The new anti-obesity medications lorcaserin (Belviq, Arena) and phentermine/topiramate (Qsymia, Vivus) appear to reduce blood glucose levels almost as much as oral diabetes agents.

Sources: Endocrine Pract 2013;19(2); 327–336; MedPage Today, April 23, 2013

DEVICE NEWS

Companion Diagnostic Test For Lung Cancer

The FDA has approved the Cobas EGFR Mutation Test (Roche Molecular Systems), a companion diagnostic for the cancer drug erlotinib (Tarceva, Genentech/OSI). This is the first FDA-approved companion diagnostic that detects epidermal growth factor receptor (EGFR) gene mutations. These mutations are present in approximately 10% of non–small-cell lung cancers (NSCLCs).

The test is being approved with an expanded use for erlotinib as a first-line treatment for patients with metastatic NSCLC.

Source: FDA, May 14, 2013

Class I Recall: Deep Brain Stimulation Kit

On February 2013, Medtronic, Inc., issued an Urgent Medical Device Correction notification to alert physicians about the potential for damage to deep brain stimulation (DBS) leads associated with the use of the lead cap provided in its DBS lead kits and dystonia therapy kits. Medtronic had received reports of damage to DBS leads from twisting of the connector within the lead cap during the surgical procedure. A manufacturing change intended to address the issue is under FDA review.

Source: FDA, May 2, 2013

Tool Identifies Counterfeit Antimalarial Drugs

To help identify counterfeit or sub-standard antimalarial drugs, the FDA has developed a counterfeit detection device called CD-3. If the antimalarial medications have insufficient or no active ingredients, adequate treatment is prevented, potentially leading to resistant strains of the parasite.

The FDA is working with the Skoll Global Threats Fund, the U.S. Pharmacopeia, the National Institutes of Health, the Centers for Disease Control and Prevention, and the multiagency President’s Malaria Initiative, led by the U.S. Agency for International Development. The partnership will focus on testing the use of the CD-3 in Africa and Southeast Asia. The FDA has also signed a letter of intent with Corning, Inc., to refine the tool for eventual manufacture on a larger scale.

The hand-held, battery-operated tool illuminates a product with various wavelengths of light that compare an unverified product with an authentic sample. The CD-3 has been in use since 2010 and has also been used to screen cosmetics, foods, medical devices, and cigarettes for authenticity of ingredients.

Sources: FDA and The Wall Street Journal, April 24, 2013

NEW MEDICAL DEVICES

Marvin M. Goldenberg, PhD, RPh, MS

Name: Vitra Multispot Laser

Manufacturer: Quantel Medical, Clermont-Ferrand, France

Approval Date: March 20, 2013

Purpose: The laser is used to lower the risk of vision loss resulting from new blood vessel growth in a procedure called photocoagulation. As blood vessels form at the back of the eye as a part of proliferative diabetic retinopathy, vitreous hemorrhage can blur vision. In extreme cases, patients can only distinguish light from dark in the affected eye. It may take a few days to months or even years for the blood to clear within the eye.

Description: Photocoagulation is usually performed in the office. The Vitra Multispot laser is used to cauterize the ocular blood vessels. Using the traditional 532-nm green wavelength, the surgeon can quickly perform the procedure.

The laser is compatible with Haag-Streit–type slit lamps, including the new Quantel light-emitting diode (LED) slit lamp on the wheelchair-access table.

Benefit: The Vitra laser is designed to benefit the growing number of patients with diabetes. It provides a less painful method of treating diabetic eye disease. Pattern scanning and solid-state green laser technologies are combined in a compact, portable platform. The interface is easy to use and cost-effective.

Sources: www.quantel-medical.com; http://optics.org

Name: Enseal G2 Cordless Tissue Sealer

Manufacturer: Ethicon Endo-Surgery, Cincinnati, Ohio

Approval Date: March 20, 2013

Purpose: Enseal technology is used in colorectal, gynecological, bariatric, and general surgery. The cordless tissue sealer provides uniform compression, controls temperature, and minimizes thermal spread.

Description: As the first of its kind, the bipolar energy device maintains excellent tissue sealing while simplifying setup and use. The device produces seal-burst pressures exceeding 240 mm Hg with 0.804 reliability with 95% confidence. This self-contained sealer includes the generator and power source.

Benefit: The cordless design enables surgeons to accomplish procedures during which speed and range of motion may be critical. No assembly is required, and there is a minimal risk of cord entanglement with other devices in the operating room. Batteries are encapsulated for quick use. Surgeons are provided with more choices to find the best fit for their procedures and patients.

Sources: www.medgadget.com; www.ethicon.com

Name: VivaSight DL Airway Management System

Manufacturer: ETView Medical Ltd., Tel Aviv, Israel

Approval Date: March 30, 2013

Purpose: The FDA approved a 510(k) Premarketing Notification Application for the VivaSight DL system. The device provides continuous airway visualization during thoracic procedures when one lung must be isolated in patients undergoing thoracic, cardiac, vascular, or esophageal surgery.

Description: The VivaSight platform was previously known as TVT. The single-use, disposable device consists of a dual-lumen airway ventilation tube with a continuous, high-resolution video airway imaging system that enables airway control and lung isolation during surgery. During the procedure, the clinician can temporarily visualize the patient’s airway with a fiberoptic bronchoscope. Repeated imaging and partial blocking of the airway are often needed to maintain lung isolation.

Benefit: The need for imaging with the fiberoptic bronchoscope(6) is eliminated during surgery. More than 1.9 million procedures involving lung isolation are performed worldwide annually.

Sources: www.etview.com; Today’s Medical Developments, www.onlinetmd.com, May 6, 2013

Recall

Hospira of Lake Forest, Illinois, has recalled all GemStar infusion systems made and distributed from February 1999 through April 2013. The lightweight, single-channeled device is designed for use in homes, hospitals, or locales where electronic infusion is required.

The GemStar system is indicated for intravenous (IV), arterial, subcutaneous, and short-term epidural infusions and parenteral administration of general IV fluids, drugs, nutritional foods, and blood products.

The device was recalled because damage from battery leakage has the potential to cause the device to shut off without warning. If this occurs, therapy can be delayed or interrupted.

Power can be lost when the pump loses contact with the batteries, when components on the middle printed wire assembly (PWA) fail, or when the middle PWA does not receive appropriate signals from elsewhere in the pump.

Inappropriate or missing input signals can result from contamination, corrosion, electronic defects, or keypad problems, disrupting the turn on/turn off signals.

Source: FDA, March 18, 2013, www.fda.gov