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Mrx CLINICAL ALERT MRx FEBRUARY 2018 CLINICAL ALERT YOUR MONTHLY SOURCE FOR DRUG INFORMATION HIGHLIGHTS FDA APPROVES FIRST NETs. At month 20, the study reported a RADIOACTIVE AGENT 79% lower risk of disease progression EDITORIAL FOR NEUROENDOCRINE or death with Lutathera compared to TUMORS (NET) control. Median progression-free survival STAFF (PFS) was 8.5 months in the control The Food and Drug Administration (FDA) group and had not been reached in the approved the first peptide receptor Lutathera group. Overall response rate EDITOR IN CHIEF radionuclide therapy (PRRT), which with Lutathera was 18% compared to Maryam Tabatabai delivers radionuclides directly to tumor 3% with control. The most common PharmD cells. Lutathera™ (lutetium Lu 177 grade 3 or 4 adverse events reported dotatate) was granted Priority review more often with Lutathera included and Orphan drug status; it is approved to lymphopenia and vomiting. EXECUTIVE EDITOR treat adults with somatostatin receptor- Carole Kerzic positive gastroenteropancreatic NETs The recommended dose of Lutathera is RPh (GEP-NETs), including foregut, midgut, 7.4 GBq administered intravenously (IV) and hindgut NET. over 30 minutes every 8 weeks for a total DEPUTY EDITORS of 4 doses. It is given in conjunction with Stephanie Christofferson NETs originate in neuroendocrine cells octreotide LAR 30 mg intramuscular (IM) PharmD of the body. Symptoms, which may or 4 to 24 hours after each Lutathera dose. may not be associated with hormonal Advanced Accelerator Applications is Jessica Czechowski hypersecretion, are not typically preparing for launch of Lutathera in the PharmD experienced early in the disease course US, with delivery directly to hospitals and may mimic other conditions; hence, and treatment centers. Lara Frick over 50% of patients have metastatic PharmD, BCPS, BCPP disease upon diagnosis. Incidence AMERICAN COLLEGE OF of NETs has risen markedly since the CARDIOLOGY (ACC) HEART Raquel Holmes 1970s. It is estimated that over 12,000 RPh, MHM, AAHIV people in the United States (US) are FAILURE (HF) DECISION diagnosed with a NET each year, most PATHWAY Leslie Pittman often in the lungs, gastrointestinal (GI) PharmD tract, and pancreas. The ACC developed an Expert Consensus Decision Pathway to facilitate optimal The usual first-line systemic therapy for treatment of patients with reduced somatostatin receptor positive GI NETs ejection fraction (HFrEF); this document include a somatostatin analogue, such is a compliment to the ACC consensus as octreotide or lanreotide, to control guideline for HF management. The new hormonal secretion and tumor growth. pathway focuses on pharmacologic Approval of Lutathera was based, in treatment of chronic ambulatory HFrEF, part, on the pivotal NETTER-1 trial that and discusses medication initiation compared Lutathera plus standard-dose and titration, as well as challenges of octreotide long-acting release (LAR) to care. Key recommendations include high-dose octreotide LAR alone (control) starting therapy with an angiotensin- in 229 patients with midgut metastatic converting enzyme inhibitor (ACEI) Download at: magellanrx.com| FEBRUARY 2018 ® or angiotensin II receptor blocker (ARB), if congestion INJECTABLE VARUBI HYPERSENSITIVITY is present, versus an evidence-based beta blocker, in ALERT patients with adequate resting HF and less congestion; use of an angiotensin receptor-neprilysin inhibitor The FDA is alerting the public of post-marketing reports of (ARNI) after an ACEI or ARB; and addition of ivabradine serious hypersensitivity reactions, including anaphylaxis in select patients in sinus rhythm. HFrEF management in and anaphylactic shock (some requiring hospitalization), specific populations, such as African American, elderly, associated with injectable rolapitant (Varubi). This substance and frail patients is also discussed. P/neurokinin 1 (NK1) receptor antagonist is indicated to prevent delayed nausea and vomiting associated The pathway reviews challenges faced with HF with cytotoxic chemotherapy. Rolapitant injection is management including the high rate of nonadherence administered IV over 30 minutes within 2 hours before (up to 50%) to prescribed multiple medications. While chemotherapy on day 1 of each cycle. Hypersensitivity dose titration may increase drug tolerability, studies reactions have occurred during or soon after the infusion, show that strategies, such as integration of care, mobile most within the first few minutes of administration. The healthcare, and patient education regarding their illness FDA is advising healthcare professionals (HCPs) to assess and prescribed medications, may improve mortality and patient history of hypersensitivity to any component of decrease hospital admissions. ACC emphasizes that the product (including soybean oil) or other allergens achieving target doses leads to the best HFrEF outcomes. that may have cross-reactivity. HCPs must be vigilant Factors that hinder the use of optimal treatment, including for signs of hypersensitivity both during and after the comorbidities, cost of care, and treatment adherence, rolapitant infusion. Symptoms of anaphylaxis can include should be addressed. Finally, care should focus on both wheezing or difficulty breathing; swelling of the face or the patients’ symptoms and functional capacity, as well throat; hives or flushing; itching; abdominal cramping, as improving cardiac function. abdominal pain, or vomiting; back or chest pain; and hypotension or shock. Anaphylaxis has not been reported IV SALINE SOLUTION SHORTAGE with the rolapitant oral tablet formulation. On January 16, 2018, the FDA provided an update on the BOXED WARNING REMOVED FOR serious shortage of sodium chloride 0.9% (saline) injection COMBINATION ASTHMA THERAPY bags currently experienced at healthcare facilities across the US. Saline bags, used for IV drug administration, have The FDA concluded that treatment of asthma with long- been in intermittent short supply since 2014. The impact acting beta agonists (LABA) in combination with inhaled of Hurricane Maria on Puerto Rico, where many medical corticosteroids (ICS) does not lead to significantly more products are produced, has greatly worsened this supply serious asthma-related adverse effects than treatment dilemma. The Agency also noted that the 2017-2018 flu with ICS alone. This determination is based on results of season has been more severe than typically experienced, 4 large clinical safety trials with 41,297 asthma patients resulting in an increase in demand for IV saline fluids and (1 study included children aged 4 to 11 years) who further exacerbation of the shortage. were treated with combination LABA/ICS therapy for 6 months. Results revealed that the addition of a LABA In an effort to resolve the saline fluid shortage, the FDA is to ICS therapy does not cause a significant increase in assisting manufacturing facilities in Puerto Rico to operate the risk of serious asthma outcomes compared to ICS at full capacity. Other steps taken include temporarily alone, and that the combination is more effective in allowing the import of IV saline products from facilities reducing asthma attacks. Consequently, the Agency outside the US (e.g., Baxter and B. Braun foreign facilities), removed the boxed warning for asthma-related death encouraging increased production at existing facilities, from the labeling of ICS/LABA combination products and expediting the approval process for IV saline products that are indicated for asthma. Select combination ICS/ (Fresenius Kabi, Grifols Laboratories). LABA products are also used to treat chronic obstructive pulmonary disease (COPD). The boxed warning regarding Manufacturers are allocating IV saline products to providers, the increase in risk of asthma-related death with use of based on historical use, until supply improves. The FDA also LABAs alone to treat asthma will remain in the labeling has received accounts of institutions rationing weakened for single-component LABA agents. supply and/or repackaging or compounding IV saline fluids, using empty IV containers, in order to provide the prescribed end-volume to the patient. As a result, the Agency is also monitoring supply of empty IV containers. 2 | FEBRUARY 2018 DRUG INFORMATION HIGHLIGHTS • Based on an extensive review and key expert opinion, • The first oral poly (ADP-ribose) polymerase (PARP) the FDA determined that the risks of slowed or difficult inhibitor has been approved for the treatment of breast breathing, misuse, abuse, addiction, overdose, and cancer. Under Priority review, olaparib (Lynparza®) death associated with opioid-containing cough and tablets received a new indication to treat patients with cold products outweigh their benefits in patients < 18 deleterious or suspected deleterious germline BRCA- years of age; therefore, the Agency is limiting their use mutated (gBRCAm), human epidermal growth factor to adults only. The FDA is requiring a boxed warning receptor 2 (HER2)-negative metastatic breast cancer about these risks be added to the product label; other who have previously been treated with chemotherapy warnings will also be added that are consistent with in the neoadjuvant, adjuvant, or metastatic setting. prescription opioid pain medicines. Alternative cough Patients with hormone receptor (HR)-positive breast and cold products for pediatrics include over-the-counter cancer should have been treated with a prior endocrine (OTC) dextromethorphan and prescription benzonatate. therapy or be considered inappropriate for endocrine The Agency is
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