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Truven Health Analytics™ Micromedex® Solutions Clinical Content Updates
Quarter 2 2015
Selected New Drug Approvals
FDA Approvals – New Monographs and Patient Medication Instructions
Topic / Title
Implication
Albuterol sulfate (ProAir®
New breath-actuated inhaler approved to treat or prevent bronchospasm induced by reversible obstructive airway disease
RespiClick)
and to prevent exercise-induced bronchospasm in patients 12 years or older. The new delivery device offers an alternative
administration option that does not require hand-breath coordination.
Anthrax immune globulin
Approved in combination with antibacterial agents to treat inhalational anthrax in adult and pediatric patients. The drug
intravenous, human
was produced under a developmental contract with the Biomedical Advanced Research and Development Authority and will
(Anthrasil™)
be stockpiled by the federal government for possible future anthrax emergencies.
Cholic acid (Cholbam®)
Approved under the FDA’s Rare Pediatric Disease Priority Review program to treat bile acid synthesis and peroxisomal
disorders in patients older than 3 weeks. In clinical trials of almost 20 years' duration, improvement in liver function and
maintained survival were observed in 64% of patients with bile acid synthesis disorders and in 46% of patients with
peroxisomal disorders.
Deferasirox (Jadenu™)
New oral tablet dose form, approved to treat chronic iron overload due to blood transfusions in patients 2 years or older
and chronic iron overload in non-transfusion-dependent thalassemia syndromes in patients 10 years or older. As the first
once-daily oral iron chelator, Jadenu™ simplifies daily treatment options for patients.
Desoxycholic acid (Kybella™)
Approved to improve the appearance of moderate to severe submental fat; its use is limited to the submental region of the
body.
Dinutuximab (Unituxin™)
Approved as the first IV injection for use in pediatric patients with high-risk neuroblastoma who achieved at least a partial
response to previous first-line treatment. Administered as part of a combination therapy, it carries a boxed warning for
infusion reactions and severe neuropathic pain.
DTaP-IPV (Quadracel™)
Approved for immunization against diphtheria, tetanus, pertussis, and poliomyelitis in children ages 4 to 6 years of age. It
can be given as a fifth DTaP dose and as a fourth or fifth IPV dose, reducing the number of vaccines needed.
Fibrinogen thrombin, human
Topical powder spray approved for use with an absorbable gelatin sponge to help control bleeding during surgery when
(Raplixa™)
standard techniques are ineffective or impractical.
Glatiramer (Glatopa™)
Approved as the first generic version of glatiramer. Originally approved in 1996 under the brand name Copaxone®,
glatiramer subQ injection is used to treat patients with relapsing forms of multiple sclerosis.
Ivabradine (Corlanor®)
Approved to treat stable patients with chronic heart failure and to reduce the risk of hospitalization for worsening.
Isavuconazonium sulfate
Approved as an orphan drug to treat invasive aspergillosis or mucormycosis infections in adults. This azole antifungal which
(Cresemba®)
is available as oral capsules and IV powder for solution was also designated as a qualified infectious disease product and was
given priority review.
Levetiracetam (Elepsia™ XR)
New ER tablet dose form approved for adjunctive therapy to treat partial onset seizures in patients 12 years or older with
epilepsy. Because most patients with epilepsy require levetiracetam doses between 1000 mg and 3000 mg, this new ER
tablet will come in 1000- and 1500-mg strengths. Previously, the highest available strength was 750 mg.
EMA Approvals (not already approved by FDA) – New Monographs
Safinamide (Xadago)
Approved to treat adult patients with mid-to late-stage fluctuating idiopathic Parkinson disease as add-on therapy to a
stable dose of levodopa alone or in combination with other PD drugs.
New FDA-approved Indications – Revised Monographs and Patient Medication Instructions
Aflibercept (Eylea®)
Now approved to treat diabetic retinopathy in adults with diabetic macular edema
Asenapine (Saphris®)
Expanded approval to include treatment of pediatric patients aged 10 to 17 years with manic or mixed episodes
associated with bipolar I disorder. Asenapine is the first atypical antipsychotic approved for this indication in pediatric
patients.
Fluticasone/vilanterol (Breo®
Expanded approval to include treatment of asthma in adult patients. Originally approved in 2013 for patients with airflow
Ellipta®)
obstruction or COPD, it is available in 2 once-daily strengths. Fluticasone/vilanterol is not indicated for acute
bronchospasm.
Ivacaftor (Kalydeco®)
New oral granule dose form and expanded approval to include treatment of pediatric patients aged 2 to 5 years who
have cystic fibrosis (CF) caused by 1 of 10 mutations in the CF transmembrane conductance regulator gene. Previously
approved as an oral tablet for adults and children 6 years or older, the new oral granules can be taken by mixing in soft
foods or liquids.
Nivolumab (Opdivo®)
Now approved to treat patients with metastatic squamous non-small cell lung cancer with progression on or after
platinum-based chemotherapy.
OnabotulinumtoxinA (Botox®)
Expanded approval to include treatment of adults with upper limb spasticity in their thumb flexors. Additionally, the
maximum 3-month cumulative dose was increased from 360 to 400 units.
Pomalidomide (Pomalyst®)
Now approved for use in combination with dexamethasone for treatment of multiple myeloma.
Ramucirumab (Cyramza®)
Expanded approval to include treatment, in combination with FOLFIRI, of metastatic colorectal cancer in treatmentexperienced patients.
Drug Safety Updates
Drug Safety – Revised Monographs and Patient Medication Instructions
Bendamustine (Treanda®)
The US FDA warns that bendamustine solution be administered only with polypropylene syringes with metal needles and
polypropylene hubs or closed system transfer devices (CSTDs) that have been confirmed compatible with the solution.
Before administering Treanda® solution with a CSTD, confirm compatibility with Teva US Medical Information or with the
CSTD manufacturer. Alternatively, 25-mg or 100-mg lyophilized powder for solution may be reconstituted and
Ferumoxytol (Feraheme®)
Testosterone products
Varenicline (Chantix®)
administered via any CSTD
A new black box warning has been added to the ferumoxytol labeling due to the possibility for serious, potentially fatal,
allergic reactions with IV iron replacement therapy.
The US FDA cautioned that prescription testosterone products are approved only for men with low levels due to certain
medical conditions and not due to aging. The FDA also reports a potential increased heart attack and stroke risk with
testosterone use. Manufacturers of prescription testosterone products are required to change their labeling to clarify the
approved use and to inform of the possible increased cardiovascular risk.
The US FDA warned that varenicline can change a patient's reaction to alcohol. In addition, rare accounts of seizures and
an increased risk of neuropsychiatric side effects have been reported. Patients taking varenicline should limit their
alcohol intake and seek medical attention immediately in the event of a seizure.
New Off-label Indications
Colchicine for post-pericardiotomy syndrome; prophylaxis (Class IIb, recommended in some)
In a randomized study (N=360), postpericardiotomy syndrome (PPS) occurred in significantly fewer patients initiated on 1 month of colchicine treatment
beginning on postoperative day 3 (8.9%) compared with placebo (21.1%); 85% of reported cases occurred during the first month postsurgery. Adverse events
were not different between treatment groups. In a second study (N=360) in which colchicine was initiated 48 to 72 hours preoperatively and continued for 1
month, PPS was reported in 19.4% of the colchicine-treated patients compared with 29.4% of placebo-treated patients. Gastrointestinal adverse effects were
reported in significantly more colchicine-treated patients (14.4% vs 6.7%), but treatment discontinuation rates were similar between groups.
Rivaroxaban for acute coronary syndrome, recent - cardiovascular event risk; prophylaxis (Class IIb, recommended in some)
In the 63% of patients from ATLAS ACS 2 - TIMI 51 who had a stent prior to the study or received one as part of the study, rivaroxaban 2.5 mg twice daily was
associated with a significant 39% reduction in definite or probable stent thrombosis compared with placebo (thrombosis incidence, 1.5% vs 1.9%). In patients
receiving dual antiplatelet therapy, benefit in the combined 2.5- and 5-mg rivaroxaban groups was seen during active dual therapy and before thienopyridine
discontinuation. Patients receiving dual antiplatelet therapy and rivaroxaban 2.5 mg twice daily had a significant 44% reduction in cardiovascular mortality
(mortality rate, 1.35% vs 2.27% with placebo). Rivaroxaban 5 mg twice daily was not associated with any significant thrombosis reduction or mortality benefit.
Pentoxifylline for the treatment of non-alcoholic fatty liver (Class IIb, recommended in some)
In a meta-analysis of randomized and cohort studies (N=147; 5 studies) and of randomized studies (N=157; 5 studies), pentoxifylline significantly decreased ALT
and AST compared with placebo in selected studies (total of 4 studies; 2 studies analyzed were the same) of patients with nonalcoholic fatty liver disease
(NAFLD). There was no significant difference in total cholesterol, triglycerides, and interleukin-6. Body mass index, steatosis scores, and fibrosis, as well as
tumor necrosis factor-alpha, were significantly improved with pentoxifylline compared with placebo in 1 meta-analysis, but not the other. Lobular
inflammation and NAFLD activity scores were significantly reduced in both analyses.
Guideline Updates
2015 Diabetes Mellitus Guidelines
Diabetes mellitus: Guidelines for Drug Therapy Drug Consult updated.
In Micromedex, enter 2015 diabetes mellitus guidelines in the search box to access the diabetes mellitus drug therapy
guidelines Dashboard.
Other Significant Updates – Drug
Aclidinium vs tiotropium
Both aclidinium bromide and tiotropium improved forced expiratory volume in 1 second (FEV1) 24-hour AUC (postmorning dose) at week 6 compared with placebo in patients with stable moderate-to-severe COPD (N=414). Both
treatments were also significantly better than placebo for FEV1 AUC(12 to 24 hours) and FEV1 AUC(0 to 12 hours); there
was no significant difference between the 2 active treatments.
Aripiprazole
The US FDA approved the first generic versions of Abilify® (aripiprazole) to treat schizophrenia and manic or mixed
episodes of bipolar disorder. Aripiprazole is available as tablets in multiple strengths.
Corticosteroids
Corticosteroid-Induced Hypersensitivity Reactions Drug Consult updated.
Glimepiride vs vildagliptin
Glycemic control was improved by vildagliptin or glimepiride added to metformin in patients with inadequately
controlled type 2 diabetes (N=167), but vildagliptin was more effective for improvements in body weight and some
measures of insulin sensitivity and lipidemia when compared for use in treating type 2 diabetes mellitus.
Influenza virus vaccine (subvirion)
A high-dose, trivalent, inactivated influenza vaccine (Fluzone® High-Dose) was 22% more effective in preventing flu(Fluzone® High-Dose)
associated illness and 22% more effective at preventing flu-related hospital admissions compared with a standard dose.
This FDA-funded study included more than 2.5 million patients 65 years or older during the 2012 to 2013 flu season.
Ticagrelor (Brilinta®)
Approved new administration option, may now be crushed and added to water for oral or nasogastric tube
administration. This new option addresses the needs of patients who cannot swallow pills whole, especially in emergency
settings.
Other Significant Updates – Toxicology – New Monographs
Alphavirus Infections
Alphavirus belongs to the family Togaviridae. These viruses are transmitted via mosquito bites resulting in widespread and potentially serious epidemics. This
management is limited to a discussion of alphaviruses of human importance (Chikungunya, Mayaro, O'Nyong-Nyong, Sindbis, and the Eastern, Western, and
Venezuelan equine encephalitis); MILD TO MODERATE TOXICITY: ARTHRALGIC ALPHAVIRUSES: These diseases (ie, Chikungunya, Mayaro, O'Nyong-Nyong, and
Sindbis) are usually self-limiting with acute symptoms that can last up 2 weeks. Symptoms usually include the abrupt onset of fever followed by malaise,
headache, rash, arthralgia, joint swelling, and muscle pain; SEVERE TOXICITY: ENCEPHALITIC ALPHAVIRUSES: Eastern equine encephalitis is rarely observed in
humans, but it is the most virulent of all the encephalitic alphaviruses with a case-fatality rate of 50% to 70%. Systemic infection appears similar to other
alphaviruses (ie, fever, chills, malaise, arthralgia and myalgia). The encephalitic form occurs abruptly in children while older children and adults develop
symptoms (eg, fever, headache, irritability, restlessness, drowsiness, vomiting, diarrhea, cyanosis, seizures, and coma) a few days after systemic illness
Nintedanib (Ofev®)
Approved to treat idiopathic pulmonary fibrosis in adult patients; OVERDOSE: Overdose data are limited but in general OD effects are anticipated to be an
extension of adverse effects at therapeutic doses. One patient, who received a dose of 600 mg daily (2 times recommended daily dose) for 21 days,
experienced nasopharyngitis that resolved without an onset of any other reported clinical effect; ADVERSE EFFECTS: Most common include nausea, vomiting,
diarrhea, abdominal pain, decreased appetite, decreased weight, elevated liver enzymes, hypertension, and headache; Infrequent/others include arterial
thromboembolic events, myocardial infarction, hypothyroidism, bleeding, gastrointestinal perforation, pneumonia, and bronchitis.
Suvorexant (Belsomra®)
Approved to treat insomnia due to difficulty falling asleep and/or staying asleep and is a Schedule IV controlled substance; OVERDOSE: In clinical trials,
volunteers administered morning doses of up to 240 mg of suvorexant developed dose-dependent increases in frequency and duration of somnolence.
ADVERSE EVENTS: Somnolence was the most common and was more likely to occur in females compared with males. Women were also twice as likely as men
to experience the following adverse events: headache, dry mouth, abnormal dreams, cough and upper respiratory tract infections; SERIOUS EVENTS: CNS
depressant effects of suvorexant may impair daytime wakefulness, driving skills and may increase the risk of falling asleep while driving. Coadministration with
other CNS depressants can increase the risk of CNS depression. Abnormal thinking and behavioral changes have developed in patients using hypnotics like
suvorexant. In clinical studies, a dose-dependent increase in suicidal ideation has been self-reported in patients receiving suvorexant.
Other Significant Updates – Toxicology – Updated Monographs
Benzyl Cyanide
 Added primary literature (Beckerman et al, 2009; Lee et al, 2007; and Borron et al, 2007) to lab and diagnostic tests
 Added case report (Weng et al, 2004) to cyanide levels after hydroxocobalamin
Cobalt
Updates made throughout, including:
 Added summary to range of toxicity
 Added therapeutic use for adults and children
NeoFax - New Monographs and Calculators
antihemophilic factor (recombinant) plasma/albumin free, colistin
NeoFax - Revised Monographs
acyclovir, albuterol, alteplase, amiodarone, Aquadeks, darbepoetin alfa, digoxin, DT/Td vaccine, DTaP vaccine, haemophilus B (HiB) conjugate
vaccine, hepatitis B vaccine (recombinant), HiB conjugate/hepatitis B combination vaccine, ibuprofen, immune globulin (human), Infuvite®
Pediatric, insulin, lansoprazole, levalbuterol, meropenem, morphine, omeprazole, pneumococcal 13-valent conjugate vaccine (PCV13), poliovirus
vaccine enhanced-inactivated, propranolol, rotavirus vaccine (Rotarix®), rotavirus vaccine (Rotateq®), tham acetate, tobramycin, vaccination
schedule ACIP- 2015, vancomycin, vecuronium, vitamin D.
Pediatrics - New Monographs and Calculators
alendronate, antihemophilic factor (recombinant) plasma/albumin free, colistin, finafloxacin, loratadine, olanzapine, pimecrolimus, sucralfate
Pediatrics - Revised Monographs
abacavir, acyclovir, albuterol, alteplase, amiodarone, amoxicillin/clavulanate, Aquadeks, azelastine, azelastine/fluticasone, baclofen, bupropion,
darbepoetin alfa, deferasirox, dexmedetomidine, digoxin; DT/Td vaccine, DTaP vaccine, duloxetine, filgrastim, guanfacine, haemophilus B (HiB)
conjugate vaccine, hepatitis A vaccine, hepatitis B vaccine (recombinant), HiB conjugate/hepatitis B combination vaccine, human papillomavirus
(HPV) vaccine, human papillomavirus 9-valent vaccine, recombinant, ibuprofen, immune globulin (human), influenza virus vaccine, Infuvite®
Pediatric, insulin, isoniazid, ivacaftor, lamotrigine, lansoprazole, levalbuterol, levofloxacin, measles, mumps, rubella (MMR) virus vaccine, live,
meningococcal vaccine, group B, meningococcal vaccine, group a, c, y, and w-135; meningococcal/HiB conjugate combination vaccine,
meropenem, morphine, nitroglycerin, omeprazole, oxybutynin, pantoprazole, pneumococcal 13-valent conjugate vaccine (PCV13), pneumococcal
polysaccharide vaccine (PPSV23), poliovirus vaccine enhanced-inactivated, propranolol, rifapentine, ropivacaine, rotavirus vaccine (Rotarix®),
rotavirus vaccine (Rotateq®), TDaP vaccine, tham acetate, tobramycin, vaccination schedule ACIP- 2015, vancomycin, varicella virus vaccine, live,
vecuronium, vitamin D, voriconazole