FDA Approval Summary: Margetuximab plus Chemotherapy for Advanced or Metastatic HER2-Positive Breast Cancer.

On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Approval was based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab with trastuzumab, in combination with chemotherapy. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review. SOPHIA demonstrated a 0.9-month difference in median PFS between the two treatment arms [5.8 vs. 4.9 months, respectively; stratified HR, 0.76 (95% confidence interval: 0.59-0.98; P = 0.0334)]. Overall survival (OS) was immature at the data cut-off date of September 10, 2019. Infusion-related reactions (IRR) are an important safety signal associated with margetuximab plus chemotherapy. In SOPHIA, 13% of patients treated with margetuximab plus chemotherapy reported IRRs, of which 1.5% were grade 3. The most commonly reported adverse drug reactions (>10%) with margetuximab in combination with chemotherapy were fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, IRR, palmar-plantar erythrodysesthesia, and extremity pain. Overall, the favorable risk-benefit profile for margetuximab when added to chemotherapy supported its approval for the intended indication.

U.S. Public Health Service Commissioned Corps pharmacists: making a difference in advancing the nation's health.

OBJECTIVE: To describe how U.S. Public Health Service (PHS) pharmacists serving in jobs that are normal for them, but considerably different than those found in the private sector, are making a difference in advancing the nation's health. SUMMARY: Pharmacists who serve in the Commissioned Corps of PHS fill roles that are considerably different than their counterparts in the private sector. Their work takes them out from behind the counter and into the world. Pharmacy officers advance the health and safety of the nation by their involvement in the delivery of direct patient care to medically underserved people, national security, drug vigilance, research, and policy-making endeavors. PHS pharmacists fill essential public health leadership and service roles throughout the U.S. Department of Health and Human Services (HHS) and certain non-HHS federal agencies and programs. The Health Resources and Services Administration, National Institutes of Health, Federal Bureau of Prisons, Indian Health Service, Food and Drug Administration, and U.S. Coast Guard are among the many federal agencies in which pharmacy officers are assigned. CONCLUSION: In each setting, PHS pharmacists find traditional roles augmented with assignments and challenges that broaden the scope of their practice.

Concurrent use of statins and amiodarone.

OBJECTIVE: To estimate the concurrent use between statins and amiodarone in context with published case reports of drug-interaction-induced rhabdomyolysis. DESIGN: Retrospective analysis of a longitudinal prescription claims database for concurrent prescriptions of statins and amiodarone dispensed during 2006. PATIENTS, PARTICIPANTS: The study population includes an unprojected annual number of patients who filled a prescription for an HMG CoA reductase inhibitor or simvastatin-containing products or lovastatin-containing products or Lipitor (atorvastatin) or Caduet (amlodipine/atorvastatin) concurrently with brand and generic forms of amiodarone during 2006. The concurrency analysis was used to provide context for published case reports of rhabdomyolysis/myopathy related to simvastatin and amiodarone concurrent use. MAIN OUTCOME MEASURE: Episodes of concurrent use between statins and amiodarone. RESULTS: Findings from this analysis indicate noteworthy amiodarone and statin concurrency (44%) when based on amiodarone patient volume. Atorvastatin had the greatest level of concurrency (23.5%) with amiodarone followed by simvastatin (13.3%). Proportionality based on amiodarone patient volume shows a greater level of concurrency with 20 mg (6%) and 40 mg (5.5%) simvastatin strengths compared with other simvastatin strengths. CONCLUSION: Clinicians should be vigilant in monitoring the regimens of patients prescribed a statin with drugs that may increase the risk of myopathy. In particular, since nearly half of the patients prescribed amiodarone may also be prescribed a statin, then addition of amiodarone or changes in statin dose should trigger a drug regimen review and patient level monitoring. Clinicians should avoid simvastatin doses greater than 20 mg per day in patients taking amiodarone.

Use of Proprietary Names by Prescribers for Generic Products.

BACKGROUND: Proprietary names are often used when prescribing drug products in the United States. The purpose of this study is to describe prescribers' use of proprietary names for generic products, branded-generic names, on prescription orders and to identify prescribing practice trends to inform the development and evaluation of new proprietary names. METHODS: To identify Abbreviated New Drug Application (ANDA) with branded-generic names approved between January 2003 and December 2012, we utilized the database provided by the FDA Office of Communications, Drugs@FDA . A national outpatient retail prescription database, IMS's Vector One: National (VONA) was used to identify prescribing trends by examining data for branded-generic names identified in Drugs@FDA as they were written on prescriptions for years 2003 to 2012, the last year of data collection for VONA. IMS Health, IMS National Sales Perspectives (IMS NSP) was used to retrieve the date that product sales were first reported (launch date). RESULTS: Our search of Drugs@FDA identified 65 distinct branded-generic names approved between January 2003 and December 2012. Data show that most of these products with branded-generic names are written on prescriptions and sold to pharmacies within a year of FDA approval. In some cases, the use of branded-generic names persists for up to 9 years after drug approval. CONCLUSION: This descriptive study confirmed that branded-generic names are used in prescribing. Thus, evaluation of orthographic and phonetic similarities between proposed proprietary names and branded-generic names is necessary when formulating and evaluating new proprietary names.

Use of antidiabetic drugs in the U.S., 2003-2012.

OBJECTIVE: To describe market trends for antidiabetic drugs, focusing on newly approved drugs, concomitant use of antidiabetic drugs, and effects of safety concerns and access restrictions on thiazolidinedione use. RESEARCH DESIGN AND METHODS: Nationally projected data on antidiabetic prescriptions for adults dispensed from U.S. retail pharmacies were extracted from IMS Health Vector One National and Total Patient Tracker for 2003-2012 and from Encuity Research Treatment Answers and Symphony Health Solutions PHAST Prescription Monthly for 2012. RESULTS: Since 2003, the number of adult antidiabetic drug users increased by 42.9% to 18.8 million in 2012. Metformin use increased by 97.0% to 60.4 million prescriptions dispensed in retail pharmacies in 2012. Among antidiabetic drugs newly approved for marketing between 2003 and 2012, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin had the largest share with 10.5 million prescriptions in 2012. Rosiglitazone use plummeted to <13,000 prescriptions dispensed in retail or mail-order pharmacies in 2012. Concomitancy analyses showed that 44.9% of metformin use was for monotherapy. Between 33.4 and 48.1% of sulfonylurea, DPP-4 inhibitor, thiazolidinedione, and glucagon-like peptide 1 analog use was not accompanied by metformin. CONCLUSIONS: The antidiabetic drug market is characterized by steady increases in volume, and newly approved drugs experienced substantial uptake, especially DPP-4 inhibitors. The use of rosiglitazone has been negligible since restrictions were put in place in 2011. Further study is needed to understand why one-third to one-half of other noninsulin antidiabetic drug use was not concomitant with metformin use despite guidelines recommending that metformin be continued when other agents are added to treatment.

Use of prescription antiobesity drugs in the United States.

STUDY OBJECTIVE: To examine national trends in prescription antiobesity drug use in the United States. DESIGN: Data analysis. DATA SOURCE: The IMS Health Vector One National and Total Patient Tracker and Encuity Research Treatment Answers databases, the Source Healthcare Analytics Source Lx database, and IMS LifeLink database. MEASUREMENTS AND MAIN RESULTS: National drug use estimates from 1991-2011 were extracted from the IMS Health Vector One National database, and patient characteristics from 2008-2011 were extracted from the Vector One Total Patient Tracker and Encuity Research Treatment Answers databases. The Source Healthcare Analytics Source Lx database was used to examine duration of antiobesity drug use from 2002-2011, with a sensitivity analysis performed using the IMS LifeLink database. In 2011, approximately 2.74 million patients used antiobesity drugs, predominantly phentermine (2.43 million patients). The use of prescription orlistat and sibutramine was relatively uncommon. Eighty-five percent of antiobesity drug users were female, 62% were aged 17-44 years, and 4.5% had a body mass index of ≤ 24.9 kg/m(2) . Duration of use was generally short and most patients only had one episode of antiobesity drug use during the observation period. The longest episode of use was 30 days or less in 47-58% of patients. Approximately one quarter of the patients used antiobesity drugs for longer than 90 days, including phentermine and other amphetamine congeners whose labels recommend short-term use, not exceeding "a few weeks." Only 1.3-4.2% of antiobesity drug users used them for longer than 1 year. Concomitant use of two or more prescription weight-loss drugs was generally uncommon, although phentermine was dispensed during 13-16% of benzphetamine, diethylpropion, or phendimetrazine episodes of use. CONCLUSION: Phentermine dominated the prescription weight-loss market. Despite the indication of short-term use for amphetamine congeners, duration of use was similar to other antiobesity drugs. Nevertheless, the reasons for and implications of the limited duration of use observed with all prescription antiobesity drugs deserve further investigation.

U.S. utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic.

BACKGROUND: The 2009 H1N1 influenza pandemic in the United States occurred from April 2009 to April 2010. The 2009 H1N1 influenza virus was susceptible to neuraminidase inhibitors (oseltamivir and zanamivir). OBJECTIVES: To characterize the 2009 H1N1 influenza pandemic in the United States from April 2009 to April 2010 using weekly influenza antiviral prescription utilization data and the CDC's weekly reports of the number of visits for influenza-like-illnesses by the Influenza Sentinel Provider Surveillance Network. METHODS: A proprietary outpatient data source used by the FDA, which captures adjudicated U.S. prescription claims for select influenza antiviral drugs, was used to conduct this analysis. Data were extracted weekly and analyzed for surveillance during the pandemic. Results were compiled at the end of the pandemic. RESULTS: Oseltamivir has dominated the U.S. influenza antiviral market share of dispensed prescriptions since approval in October 1999 and was the primary influenza antiviral drug used during the 2009 H1N1 influenza pandemic. However, commercial availability of the suspension formulation of oseltamivir was reduced by high demand during the pandemic. Dispensed prescription trends of other influenza antiviral medications studied followed that those of oseltamivir, even antivirals for which the 2009 H1N1 strains showed resistance. CONCLUSION: Weekly prescription utilization of all influenza antivirals used to treat influenza during the seasonal influenza outbreak followed the same trend of weekly reports of the number of visits for influenza-like-illnesses (ILI) by the Influenza Sentinel Provider Surveillance Network. The ILI epidemic curve resembled dispensed antiviral prescription trends (both overall and stratified by age), providing some corroboration for the surveillance data.

Linezolid-associated peripheral and optic neuropathy in children.

OBJECTIVE: Peripheral neuropathy (PN) and optic neuropathy (ON) associated with linezolid use are described in the adult literature; however limited information is available in pediatrics. The purpose of this communication is to summarize pediatric cases of linezolid-associated neuropathy and to increase awareness of these neurologic side effects so that clinicians can most appropriately balance the benefits and risks of linezolid in the pediatric population. METHODS: A search of the FDA Adverse Events Reporting System was performed for all pediatric cases of neuropathy from April 2000-2009. AERS includes both inpatient and outpatient data. Inpatient utilization patterns for linezolid were also assessed from January 2000 to December 2008. RESULTS: Eight pediatric cases of linezolid-associated neuropathy were identified. Treatment duration ranged from 4 weeks to 1 year. Five patients had PN alone, one had only ON and two had both. Symptoms of PN included pain, numbness, weakness, and paresthesias. Symptoms of ON included decreased visual acuity and color vision. Three children had other adverse events associated with linezolid including acidosis, anemia, and leukopenia. Outcomes were reported in 5 cases. Resolution of symptoms occurred between 2 weeks and 6 months after discontinuation of linezolid. Utilization data showed that during the study period, overall inpatient utilization of linezolid had increased. CONCLUSIONS: While linezolid may be used to treat serious infections often needing extended courses of therapy, potential safety concerns should be kept in mind. In the circumstance of prolonged use of linezolid in children, it is likely that more cases of neuropathy may occur.