Truven Health Analytics™ Micromedex® Solutions Clinical Content Updates
Quarter 1 2015
Selected New Drug Approvals
FDA Approvals – New Monographs and Patient Medication Instructions
Topic / Title
Implication
Atazanavir/cobicistat (Evotaz™)
Approved to treat HIV-1 infection in adults. The drug combines a protease inhibitor, atazanavir, with a pharmacokinetic
booster, cobicistat and is given concurrently with other antiretrovirals.
Carbidopa/levodopa (Duopa™)
Approved this enteral suspension form to treat motor fluctuations in advanced Parkinson disease. Because patients with
Parkinson disease have delayed and unpredictable emptying of the stomach which can affect absorption in the small
intestine, Duopa™ is administered directly into the small intestine for 16 continuous hours.
Carbidopa/levodopa (Rytary™)
Approved this extended-release capsule form to treat Parkinson disease, postencephalitic parkinsonism, and parkinsonism
associated with carbon monoxide or manganese intoxication in adults.
Ceftazidime/avibactam
Approved for use in adults who have limited or no alternative treatment options for complicated intra-abdominal infections
(Avycaz™)
or complicated urinary tract infections. This was designated as a qualified infectious disease product and given priority
review.
Darunavir/cobicistat
Approved to treat HIV-1 in combination with other antiretroviral agents for adults with no darunavir resistance-associated
(Prezcobix™)
mutations. Since darunavir and cobicistat are combined into a once-daily, fixed-dose tablet, the number of medications a
patient is required to take is reduced.
Edoxaban (Savaysa™)
Approved to help prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation and to treat DVT and
pulmonary embolism following 5 to 10 days of parenteral anticoagulant therapy.
Empagliflozin/linagliptin
Approved as an adjunct to diet and exercise to manage glycemic control in patients with type 2 diabetes. This once-daily
(Glyxambi®)
tablet is the first to combine a sodium glucose co-transporter-2 inhibitor with a dipeptidyl peptidase-4 inhibitor.
Ferric pyrophosphate (Triferic™) Approved to maintain hemoglobin in adults with hemodialysis-dependent chronic kidney disease. Ferric pyrophosphate is
the first non-IV iron replacement therapy and is mixed with bicarbonate concentrate and then administered via dialysate.
Insulin glargine (Toujeo®)
Approved for glycemic control in adults with type 1 or 2 diabetes as a once-daily, long-acting insulin.
Lenvatinib (Lenvima™)
Approved to treat progressive, differentiated thyroid cancer with disease progression after radioactive iodine therapy.
Levonorgestrel (Liletta™)
Approved to prevent pregnancy for up to 3 years. The Liletta™ IUD was developed to be a low-cost contraceptive option and
will be available both commercially and at a reduced cost in eligible public health clinics.
Meningococcal group B vaccine
Approved as a breakthrough therapy for meningitis B prophylaxis in patients aged 10 to 25 years. It is the second meningitis
(Bexsero®)
B vaccine to gain US approval to protect against Neisseria meningitides serogroup B which caused about 33% of reported
meningitis infections in the US in 2012 according to the CDC.
Olopatadine hydrochloride
(Pazeo™)
Palbociclib (Ibrance®)
Approved to treat seasonal eye allergies in adult and pediatric patients 2 years of age or older. It is instilled as a daily dose of
1 drop to each eye to relieve ocular itching for up to 24 hours.
Approved as breakthrough therapy for advanced metastatic breast cancer in postmenopausal women in combination with
letrozole.
Panobinostat (Farydak®)
Approved to treat multiple myeloma in patients who have received at least 2 prior regimens, including bortezomib and an
immunomodulatory agent. Panobinostat is to be used with bortezomib and dexamethasone. Panobinostat was granted
priority review, orphan product designation, and accelerated approval.
Parathyroid hormone,
Approved as an adjunct to calcium and vitamin D to treat hypocalcemia in patients with hypoparathyroidism. Natpara® is
recombinant (Natpara®)
available only through a REMS program and is FDA approved under orphan drug designation.
Pembrolizumab (Keytruda®)
Approved a solution formulation to treat unresectable or metastatic melanoma unresponsive to ipilimumab and, if BRAF
V600 mutation positive, a BRAF inhibitor. Previously, pembrolizumab was approved as a lyophilized powder for
reconstitution.
Perindopril arginine/amlodipine Approved to treat hypertension in adults. It is indicated for patients who may need combination therapy to control their
(Prestalia®)
hypertension or for whom monotherapy is ineffective.
Secukinumab (Cosentyx™)
Approved to treat adults with moderate to severe plaque psoriasis. The new biologic prevents inflammation by inhibiting
the action of interleukin-17A protein, offering an alternative to phototherapy or other systemic treatments.
EMA Approvals (not already approved by FDA) – New Monographs
Afamelanotide (Scenesse)
Indicated to prevent phototoxicity in adult patients with erythropoietic protoporphyria
Dasabuvir (Exviera)
Indicated to treat chronic hepatitis C in adults
New FDA-approved Indications – Revised Monographs and Patient Medication Instructions
Fluticasone propionate (Cutivate®) Expanded approval to include patients 3 months of age or older. Indicated for inflammatory and pruritic manifestations
of atopic dermatitis, fluticasone propionate lotion was previously approved for patients aged 1 year or older.
Gadobutrol (Gadavist®)
Now approved for use in patients younger than 2 years, including term neonates. Gadobutrol is the first gadoliniumbased contrast agent approved for this age group.
Lenalidomide (Revlimid®)
Expanded approval to include patients with newly diagnosed multiple myeloma (MM). Before this expanded indication,
treatment with lenalidomide required patients with MM to have undergone previous therapy.
Lisdexamfetamine dimesylate
Approved to treat binge eating disorder (BED) in adults. It is the first FDA approval for treatment of BED, but is not
(Vyvanse®)
approved or recommended for weight loss.
Ranibizumab (Lucentis®)
Approved to treat diabetic retinopathy (DR) in patients with diabetic macular edema. The FDA approved the use of
ranibizumab for DR under priority review and breakthrough therapy designation.
Drug Safety Updates
Drug Safety – Revised Monographs and Patient Medication Instructions
Multi-dose diabetes pen devices
In order to reduce the serious risk of infection, the US FDA announced it is requiring additional label warnings that multi-
dose pens are intended for single patient use only and should not be shared among patients.
New Off-label Indications
Alprostadil for radiographic contrast agent nephropathy prophylaxis (Class IIb, recommended in some)
Alteplase for the treatment of prosthetic cardiac valve thrombosis in pregnant women (Class IIb, recommended in some)
Edoxaban for postoperative deep vein thrombosis in arthroplasty of knee prophylaxis (Class IIb, recommended in some)
Magnesium sulfate as an adjunct for postoperative pain (Class IIb, recommended in some)
Mycophenolate mofetil – Lupus nephritis (guidelines & dosing)
Vitamin A to reduce the mortality and morbidity of measles infection (Class IIa, recommended in most)
Guideline Updates
ASCO deep venous thrombosis
Find updated information regarding ASCO DVT 2015 guidelines throughout drug monographs and the Venous
2015 guidelines
Thromboembolism in Patients with Cancer: Drug Therapy Guidelines Drug Consult.
2015 CDC/ACIP Immunization
guidelines
In Micromedex: Search on venous thromboembolism in patients with cancer: drug therapy guidelines to access related
drug content.
Find updated information regarding 2015 CDC/ACIP Immunization guidelines throughout drug monographs and the
Immunization of Adults 19 Years or Older—ACIP Recommendations Drug Consult.
2015 CDC/ACIP Immunization
guidelines
In Micromedex: Search on ACIP immunization to access related drug content.
Find updated information regarding 2015 CDC/ACIP Childhood Immunization guidelines throughout drug monographs
and the Childhood Immunization Schedule- United States 2015 Drug Consult.
In Micromedex: Search on ACIP childhood immunization to access related drug content.
Other Significant Updates – Drug
Flecanide vs vernakalant
Flecainide versus vernakalant for conversion of recent-onset atrial fibrillation.
Pharmacological cardioversion to sinus rhythm in patients with new-onset atrial fibrillation occurred within a median of
10 minutes with IV vernakalant, significantly faster than the 163 minutes required with oral flecainide. And, hospital stay
was significantly decreased in the vernakalant group (232 vs 409 minutes with flecainide).
In Micromedex, see the Comparative Efficacy section of the Drugdex Evaluation monographs for each drug for
additional details.
Other Significant Updates – Care Notes
90 New Care Notes
New patient instructions cover topics in the areas of adolescent diabetes management, adult overdose, edema,
emergency medicine, medicine refill, pelvic pain, and rib contusion. Several new pediatric health and disease prevention
topics were also written incorporating the American Academy of Pediatrics Bright Futures initiative materials.
73 Revised Care Notes
Topics have been revised to incorporate new evidence and new and updated clinical guideline recommendations from
the American Heart Association (AHA)/American College of Cardiology (ACC) guideline on Stable Ischemic Heart Disease,
AHA/American Stroke Assoc (ASA) guideline on the Primary Prevention of Stroke, American College of Physicians (ACP)
guideline on Nonsurgical Mgmt of Urinary Incontinence in Women, and the National Heart, Lung, and Blood Institute
(NHLBI) guideline on Sickle Cell Disease.
Other Significant Updates – Toxicology – New Monographs
Eliglustat
USES: is a glucosylceramide synthase inhibitor used orally for long-term treatment of adult patients with Gaucher disease type 1 who are CYP2D6 extensive
metabolizers, intermediate metabolizers or poor metabolizers.
PHARMACOLOGY: Acts as a substrate reduction therapy. In Gaucher disease, patients are deficient in acid beta-glucosidase, a lysosomal enzyme. This
deficiency leads to accumulation of glucosylceramide in lysosomal compartments of macrophages and formation of Gaucher cells (foam cells).
OVERDOSE: Limited data. Clinical events are anticipated to be an extension of events reported with therapeutic use.
MILD TO MODERATE TOXICITY: Gastrointestinal and CNS events are likely to occur. SEVERE TOXICITY: In a single-dose escalation study in healthy subjects, a
dose approximately equivalent to 21 times the recommended dose for Gaucher disease type 1 patients produced nausea, vomiting, hypotension, bradycardia,
and dizziness resulting in significant disequilibrium.
ADVERSE EFFECTS: COMMON (greater than 10% of patients): fatigue, headache, nausea, back pain, pain in extremities and upper abdominal pain.
Empagliflozin
USES: Is a sodium-glucose cotransporter 2 inhibitor used to improve glycemic control in adults with type 2 diabetes; indicated as an adjunct to diet and
exercise.
PHARMACOLOGY: Lowers the renal threshold for glucose and increases urinary glucose excretion by interfering with the reabsorption of renally-filtered
glucose across the tubular lumen of the proximal renal tubules; OVERDOSE: Toxicity following overdose has not been reported.
ADVERSE EFFECTS: COMMON (incidence rate of at least 5%): urinary tract infections and female genital mycotic infections. LESS COMMON: hypotension,
dyslipidemia, increased urination, increased thirst, nausea, renal impairment, an increase in hematocrit, arthralgia, upper respiratory tract infections, and male
genital mycotic infections. Ingestion of empagliflozin alone is not expected to cause severe hypoglycemia, but when combined with insulin or insulin
secretogogues, hypoglycemia may develop.
Idelalisib
USES: In combination with rituximab to treat relapsed chronic lymphocytic leukemia in adults when rituximab alone is appropriate therapy due to other
comorbidities.
PHARMACOLOGY: Is a kinase inhibitor that induces apoptosis and inhibits proliferation of malignant B-cells and primary tumor cells, resulting in inhibition of
chemotaxis and adhesion, and reduced cell viability; OVERDOSE: Overdose effects are anticipated to be an extension of adverse effects following therapeutic
doses.
ADVERSE EFFECTS: MOST COMMON (20% or greater): diarrhea, fatigue, nausea, cough, pneumonia, abdominal pain, fever, chills, and rash; MOST COMMON
LAB ABNORMALITIES (30% or greater): neutropenia, hypertriglyceridemia, hyperglycemia, and elevated ALT and AST; OTHER EFFECTS: Peripheral edema, night
sweats, hypoglycemia, hyponatremia, vomiting, gastroesophageal reflux disease, colitis, stomatitis, decreased appetite, urinary tract infection,
thrombocytopenia, neutropenia, decreased or increased lymphocyte count, decreased hemoglobin, acute allergic reactions, anaphylaxis, joint pain, asthenia,
headache, insomnia, nasal congestion, bronchitis, sinusitis, upper respiratory tract infection, dyspnea, sepsis, exfoliative dermatitis, toxic epidermal necrolysis,
intestinal perforation, hepatotoxicity, and pneumonitis.
Other Significant Updates – Toxicology – Updated Monographs
Military Nerve Agents
USES: Are organophosphate (OP) chemical compounds, probably the most poisonous of the known chemical warfare agents, and confer high lethality in
exposed populations, both military and civilians. Liquid or vapor exposure can cause death within minutes by inhibition of acetylcholinesterase function.
Exposure to relatively small amounts can be fatal.
TOXICOLOGY: Toxic effects are caused by the presence of excess acetylcholine. Toxicities are expressed by cholinergic overdrive at muscarinic, nicotinic, and
CNS cholinergic sites. The military nerve agents differ from other OPs in potency, tendency to produce rapid CNS effects, and, in the case of soman, by the
rapidity of "aging" of the OP-enzyme complex. After aging of AChE enzyme, oximes therapy will not be effective. At least two weeks is required for restoration
of AChE.
EPIDEMIOLOGY: These agents are particularly toxic following inhalation exposure, but can be absorbed following ingestion, dermal, or eye contact.
MILD TO MODERATE TOXICITY: Because AChE inhibition affects both muscarinic and nicotinic sites, a mixed nicotinic-muscarinic clinical picture is often present.
MUSCARINIC EFFECTS: Bradycardia, wheezing, bronchorrhea, sweating, salivation, miosis, vomiting and diarrhea, and urinary and fecal incontinence.
NICOTINIC EFFECTS: Tachycardia, mydriasis, muscle fasciculations, and hypertension. CNS EFFECTS: Anxiety and headaches. SEVERE TOXICITY: Death is a result
of respiratory failure due to increased work of breathing combined with respiratory muscle weakness, and/or CNS effects. MUSCARINIC EFFECTS: More severe
manifestations of signs listed above. Bronchospasm and bronchorrhea may severely impair both ventilation and oxygenation. NICOTINIC EFFECTS: More severe
manifestations of signs listed above. Fasciculations may progress to flaccid paralysis of skeletal muscles, including the diaphragm. CNS EFFECTS: Seizures, coma,
and central apnea.
Ticks
BACKGROUND: Are small arachnids found throughout the world, especially in warm, humid climates. There are approximately 900 species of ticks that are
divided into 3 families: Argasidae (soft ticks; 191 species), Ixodidae (hard ticks; 701 species) and Nuttalliellidae (Nuttalliella namaqua; only 1 species identified).
Tick bites can produce a local reaction and tick saliva can contain toxins. In addition, there are many infectious diseases that can be transmitted via tick bites.
TOXICOLOGY: Tick bites can often produce a dermal or inflammatory reaction at the site of injury. Ticks exert their toxic effects through several mechanisms.
Some ticks have a neurotoxin in their salivary glands that can cause paralysis.
EPIDEMIOLOGY: Tick bites occur commonly worldwide. Tick borne disease or illness is also common (eg, Lyme disease is the most commonly reported vector
borne disease in the US). Manifestations can range from mild local reactions to severe symptoms requiring hospitalization.
ADVERSE EFFECTS: Ticks may cause a dermal reaction or transmit other organisms and diseases in their bites. Most commonly, tick bites can produce a local
reaction. Hypersensitivity reactions may also occur after tick bites.
TICK BORNE DISEASE: There are many tick borne diseases, which include bacterial, viral, and protozoal illnesses. Many of these diseases have common
symptoms including fever, chills, headache, myalgias, arthralgias, fatigue, malaise, gastrointestinal symptoms, cough. Infrequent symptoms can include stiff
neck, confusion, mild hepatomegaly or jaundice. Rarely, serious manifestations such as encephalitis, aseptic meningitis, and pericarditis can occur.
TICK PARALYSIS: A rare disease that may cause ascending flaccid paralysis that may be confused with other neurologic conditions. It is caused by a toxin found
in the saliva of certain ticks, usually only a female tick of select genera. Patients usually recover within 24 hours of tick removal.
NeoFax - New Monographs and Calculators
factor XIII concentrate, human
NeoFax - Revised Monographs
acyclovir, albuterol, calcium - oral, calcium chloride 10%, calcium gluconate 10%, captopril, clonidine, dexamethasone, dornase alfa, enalapril maleate,
enalaprilat, epinephrine (adrenaline), fluconazole, hydralazine, ibuprofen, ibuprofen lysine, immune globulin (human), insulin, isoproterenol, levalbuterol,
levetiracetam, levothyroxine, lidocaine – antiarrhythmic, lidocaine – CNS, lorazepam, magnesium sulfate, methadone, metoclopramide, metronidazole,
micafungin, midazolam, milrinone, morphine, neostigmine, norepinephrine, octreotide, oseltamivir, pancuronium, papaverine, pentobarbital, phenobarbital,
phenytoin, piperacillin/tazobactam, pneumococcal 13-valent conjugate vaccine (PCV13), Poly-Vi-Sol® with iron MVI drops, potassium chloride, procainamide,
propranolol, protein C concentrate (human), quinupristin/dalfopristin, ranitidine, remifentanil, rifampin, rocuronium, sildenafil, sodium bicarbonate, sodium
glycerophosphate, sodium phenylacetate/sodium benzoate, sodium nitroprusside, tobramycin, Tri-Vi-Sol® MVI drops, varicella-zoster immune globulin, vitamin
D, Vi-Sol® multivitamin products
Pediatrics - New Monographs and Calculators
ecallantide; factor IX recombinant; factor XIII concentrate, human; fexofenadine; human papillomavirus 9-valent vaccine, recombinant; loperamide;
meningococcal vaccine, group B.
Pediatrics - Revised Monographs
acyclovir, albuterol, ampicillin/sulbactam, beclomethasone, bupropion, calcium - oral, calcium chloride 10%, calcium gluconate 10%, captopril, clonidine,
daptomycin, dexamethasone, dolutegravir, dornase alfa, enalapril maleate, enalaprilat, epinephrine (adrenaline), esomeprazole, fluconazole, fluoxetine,
fluticasone, foscarnet, guanfacine, hydralazine, hypertonic saline, ibuprofen, immune globulin (human), insulin, ivacaftor, levalbuterol, levetiracetam,
levothyroxine, lidocaine – antiarrhythmic, lidocaine – CNS, lisdexamfetamine, lisinopril, lorazepam, magnesium sulfate, meningococcal vaccine; group A, C, Y,
and W-135, meningococcal vaccine; group B, methadone, methotrexate, metoclopramide, metronidazole, micafungin, midazolam, milrinone, mixed grass
pollen allergen extract, morphine, multivitamin drops, neostigmine, norepinephrine, octreotide, oseltamivir, oxycodone, pancuronium, papaverine,
peginterferon alfa-2a, penicillin V potassium, pentobarbital, phenobarbital, phenytoin, piperacillin/tazobactam, pneumococcal 13-valent conjugate vaccine
(PCV13), potassium chloride, procainamide, propranolol, protein C concentrate (human), quinupristin/dalfopristin, ranitidine, remifentanil, rifabutin, rifampin,
rifapentine, rocuronium, sildenafil, sodium bicarbonate, sodium glycerophosphate, sodium phenylacetate/sodium benzoate, sodium nitroprusside,
tobramycin, varicella-zoster immune globulin, vitamin D