This year, the FDA is on pace to approve about 38 new medications. Here is a look at 6 of these.
This year, the FDA is on pace to approve about 38 new medications. Additions to the drug market this year cover a variety of diseases and ailments providing prescribers with more options and the ability to optimize drug therapy. Part 4 of this series covers new medications for immunology, infectious diseases, and musculoskeletal conditions.
Odactra (house dust mite allergen extract)
The FDA approved Odactra on March 1, 2017, and it is the first sublingual allergen extract for the treatment of dust mite allergies.1 House dust mite allergies stem from a reaction to tiny bugs found in house dust. These mites are too small to be seen with the naked eye and are found in bedding, upholstered furniture, and carpeting. People with dust mite allergies experience coughing, runny noses, nasal itching, nasal congestion, sneezing, and itchy eyes upon exposure.1 Odactra works by exposing the patient to house dust mite allergens, which gradually train the immune system to reduce the frequency and severity of the allergic reactions. Odactra exhibits convenience when compared with other allergy immunotherapy treatments, as it is not administered as an injection.1 Odactra is dosed in a 12 SQ-HDM (propriety measurement used by the manufacturer) tablet that is to be taken once daily.2 The patient is to place 1 tablet under the tongue and allow it to dissolve, without swallowing for 1 minute. No food or drinks should be consumed for at least 5 minutes after administration. The first tablet is taken under the supervision of a physician with experience in the diagnosis and treatment of allergic diseases. If the patient tolerates the first dose, Odactra can be taken at home thereafter. All patients receiving Odactra should also be prescribed auto-injectable epinephrine in case of a severe hypersensitivity reaction.2 Oral itching (61%), mouth edema (20%), local pruritus (52%), and throat irritation (67%) were the most common adverse effects seen in clinical trials. Patients with severe or uncontrolled asthma, history of any severe systemic allergic reaction, history of any severe local reaction after taking any sublingual allergen immunotherapy, or history of eosinophilic esophagitis should not take Odactra, as reactions are the basis of its black box warning.2
Sarilumab, approved by the FDA on May 22, 2017, is a monoclonal antibody that targets interleukin-6 (IL-6) receptors to treat moderate-to-severe rheumatoid arthritis. It binds to IL-6 receptors to inhibit the receptor mediated signaling that results in the production of the inflammatory cytokine, IL-6.3-4 Sarilumab is available in single-dose, prefilled syringes, containing doses of 150 mg or 200 mg. The recommended dose is 200 mg every 2 weeks, given as a subcutaneous injection. Sarilumab can be used concurrently with methotrexate or non-biologic DMARDs. The 150-mg dose is used once every 2 weeks while managing neutropenia, thrombocytopenia, or elevated liver enzymes.4 Sarilumab should not be initiated in patients with an absolute neutrophil count less than 2000/mm3, platelet count less than 150,000/mm,3 or if liver enzymes are greater than 1.5 times the upper limits of normal. If patients experience an ANC 500 to 1000, a platelet count 50,000 to 100,000, or ALT 3 to 5 times the upper limits of normal, Sarilumab should be held. If the patients’ lab values increase out of these ranges, sarilumab can be resumed at 150 mg per dose. The most common adverse effects are neutropenia, increased liver enzymes, injections site erythema, upper respiratory and urinary tract infections.4
Infections and Infectious Diseases
Delafloxacin is a fluoroquinolone antibiotic that received FDA approval on June 19, 2017, for the treatment of skin and skin structure infections.5,6 Approval of delafloxacin was based on 2 phase 3 trials, in which both the oral and IV formulations as monotherapy proved to be statistically noninferior to the combination of vancomycin plus aztreonam at the FDA primary endpoint of early clinical response at 48 to 72 hours.
Delafloxacin is unique when compared with other agents in the fluoroquinolone class in its coverage of methicillin-resistant Staphylococcus aureus.5 Like other fluoroquinolones, delafloxacin inhibits DNA gyrase (topoisomerase II), and topoisomerase IV enzymes, which are required for bacterial DNA replication, transcription, repair, and recombination. Delafloxacin also demonstrates concentration-dependent bactericidal activity against both gram-positive and gram-negative bacteria in vitro.5,6 Delafloxacin is available as a tablet and as a solution for IV infusion. Recommended dosing for the IV infusion is 300 mg (diluted to 250 mL of NS or D5W) over 60 minutes every 12 hours for 5 to 14 days. The recommended dose for oral administration is a 450 mg tablet by mouth every 12 hours for 5 to 14 days. This discrepancy in oral versus IV dosing is due to an estimated oral bioavailability of about 58% to 59%.6,7 Use of this medication is not recommended in patients with end-stage renal disease (defined as eGFR of < 15 ml/min/1.73 m2). In patients with severe renal impairment (eGFR of 15-29 ml/min/1.73 m2), the IV dosage of this medication should be reduced to 200 mg every 12 hours, while the oral dosage does not require any adjustment.6 The most common adverse effects (>2% compared to placebo) include nausea, diarrhea, headache, transaminase elevations, and vomiting. Clostridium difficile-associated diarrhea is also a warning/precaution to consider when giving/taking this medication. Delafloxacin also has black box warnings for exacerbations of myasthenia gravis, as well as potentially irreversible tendonitis/tendon rupture.6
Benzndiazole was approved and designated as an orphan drug on September 21, 2017, through the FDA’s Accelerated Approval Pathway.8 Benznidazole is an antiprotozoal that inhibits the synthesis of DNA, RNA, and proteins within the Trypanosoma cruzi (T cruzi). T cruzi is the parasite that is responsible for Chagas disease. It is transmitted through contact with feces of certain insects, blood transfusions, or from mother to child during pregnancy. Chagas disease can cause serious heart illnesses and affect swallowing and digestion. It is estimated that there are 300,000 cases of Chagas disease in the United States.8 Benznidazole is indicated to treat patients 2 to 12 years of age. It comes in tablet form and is dosed as 5 to 7.5 mg/kg/day in 2 divided doses for 60 days. It has an off-label indication for the treatment of patients ≥12 years of age and is dosed at 5 to 7 mg/kg/day in 2 divided doses for 60 days.9
The most common adverse effects seen with benznidazole are allergic dermatitis, peripheral neuropathy, anorexia and weight loss, and insomnia. Benznidazole is the only medication approved for the treatment of Chagas disease in the United States. It is only available from the from the CDC via the existing investigational new drug protocol.9
Vabomere (meropenem and vaborbactam)
The FDA approved Vabomere on August 29th, 2017, to treat complicated urinary tract infections (cUTI), including pyelonephritis.10 It is a combination of the carbapenem, meropenem, and the beta-lactamase inhibitor, vaborbactcm. The addition of vaborbactam, a non-suicidal beta lactamase inhibitor, extends the spectrum of activity of meropenem to include some extended spectrum beta lactamase-producing and carbapenemase=producing bacteria. Vabomere is formulated for intravenous use only and is supplied in a 2-gram powder consisting of 1 gram of each component.1 The recommended dosage for a cUTI is 4 grams every 8 hours for less than or equal to 14 days. Vabomere requires the dosing interval to be extended to 12 hours in patients with an eGFR of 15 to 29 mL/min/1.73m2. The dose should be adjusted to 1 gram every 12 hours in patients with an eGFR ≤15 mL/min/1.73m2. The TANGO clinical trials showed that about 98.4% of patients treated with Vabomere exhibited cure or improvement in symptoms, accompanied by a negative urine culture test. By comparison, the piperacillin/tazobactam combination produced those same outcomes in 94.3% patients.11 Common adverse reactions include headache and infusion site reaction. The rate of these adverse effects is not known because the patients were given levofloxacin on the 15th day of treatment during the clinical trials.11
The FDA approved deflazacort on February 9, 2017, for the treatment of Duchenne muscular dystrophy (DMD) in patients 5 years and older. DMD is an X-linked recessive disorder, also called pseudohypertrophic muscular dystrophy, and has an incidence of about 1 per 5200 live-born males. Glucocorticoids are a mainstay of therapy that aid in the slowing of the progression of the disease. However, deflazacort demonstrated a significantly greater change in average muscle strength in a phase 3 trial when compared with the more traditional prednisone.12,13
Deflazacort is a systemic corticosteroid prodrug that is supplied as a tablet and as an oral suspension. Its active metabolite, 21-desDFZ, acts on the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The exact mechanism of its therapeutic effects in patients with Duchenne muscular dystrophy is unknown.14 Deflazacort comes in 6 mg, 18 mg, 30 mg, and 36 mg tablets and a 22.75 mg/mL oral suspension. Standard dosing of deflazacort is usually 0.9 mg/kg PO once daily. This dose should be rounded up to the nearest possible dose when using tablets and rounded up to the nearest tenth of a mL when using the oral suspension. If given concomitantly with a CYP3A4 inhibitor, such as azithromycin or cimetidine, the dose should be reduced by one-third of the usual dose.14 The most common adverse effects of deflazacort (> 10% when compared with placebo) include erythema, cushingoid appearance, hirsutism, weight gain and obesity, abdominal pain, increased appetite, pollakiuria, cough, and upper respiratory tract infections.14,15 The general cost of this medication is between $4700 and $8700 for 30 tablets.15
This article was written with Christopher Robinson and Charles Vawters, 2018 PharmD Candidates at the Harrison School of Pharmacy at Auburn University.
1. FDA approves Odactra for house dust mite allergies [news release]. March 1, 2017. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm544330.htm. Accessed October 13, 2017.
2. Odactra [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc; 2017. fda.gov/downloads/biologicsbloodvaccines/allergenics/ucm544382.pdf. Accessed October 13, 2017.
3. Sanofi and Regeneron receive FDA approval for Kevzara in rheumatoid arthritis. FDANews. fdanews/com/articles/181927-sanofi-and-regeneron-receive-fda-approval-for-kevzara-in-rheumatoid-arthritis. Published May 26, 2017. Accessed October 13, 2017.
4. Kevzara [prescribing information]. Bridgewater, NJ: sanofi-aventis U.S., LLC; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/761037s000lbl.pdf. Accessed October 13, 2017.
5. CenterWatch. Baxdela (delafloxacin) tablets and injection. centerwatch.com/drug-information/fda-approved-drugs/drug/100207/baxdela-delafloxacin-tablets-and-injection. Accessed October 13, 2017.
6. Baxdela [prescribing information]. Lincolnshire, IL: Melinta Therapeutics, Inc; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/208610s000,208611s000lbl.pdf. Accessed October 13, 2017.
7. Delafloxacin. In: Lexi-Comp Online, Lexi-Drugs [internet]. Hudson, OH: Wolters Kluwer Health/Lexi-Comp, Inc. c2017 [cited October 2, 2017]. online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6507092.
8. FDA approves first U.S. treatment for Chagas disease [news release]. August 29, 2017.
fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm573942.htm. Accessed October 13, 2017.
9. CDC. Parasites — American Trypanosomiasis (also known as Chagas disease). cdc.gov/parasites/chagas/health_professionals/tx.html. Updated August 31, 2017. Accessed October 13, 2017.
10. FDA approves new antibacterial drug [news release]. August 29, 2017.
fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm573955.htm. Accessed October 13, 2017.
11. Vabomere [prescribing information]. Teramo, Italy: Facta Farmaceutici, S.p.A.; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/209776lbl.pdf. Accessed October 13, 2017.
12. Amato AA, Brown RH, Jr. Muscular dystrophies and other muscle diseases. In: Kasper DL, Fauci AS, Longo DL, et al, eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill; 2014.
13. FDA approves drug to treat Duchenne muscular dystrophy [news release]. February 9, 2017. fda.gov/newsevents/newsroom/pressannouncements/ucm540945.htm. Accessed October 13, 2017.
14. Emflaza [prescribing information]. Northbrook, IL: Marathon Pharmaceuticals, LLC. 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/208684s000,208685s000lbl.pdf. Accessed October 13, 2017.
15. Deflazacort. In: Lexi-Comp Online, Lexi-Drugs [internet]. Hudson, OH: Wolters Kluwer Health/Lexi-Comp, Inc. c2017 [cited October 2, 2017]. online.lexi.com/lco/action/doc/retrieve/docid/patch_f/4854435