This year, the FDA is on pace to approve about 38 new medications. Here is a look at 5 of those.
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 2 of this series covers new endocrinology and gastroenterology medications.
The FDA approved etelcalcetide on February 7, 2017, to treat secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. This medication is a calcimimetic, a drug that mimics the action of calcium by activating the calcium-sensing receptors on the parathyroid gland. It binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby decreasing parathyroid hormone levels (PTH).1,2
Standard dosing of etelcalcetide is initially a 5 mg IV bolus 3 times per week at the end of hemodialysis. This dose may be titrated in 2.5 mg or 5 mg increments no more frequently than every 4 weeks to a dose that maintains PTH levels within the recommended target range and corrected serum calcium within the normal range. The maximum maintenance dose is 15 mg 3 times per week, and the minimum maintenance dose is 2.5 mg 3 times per week. This drug is not to be administered if hemodialysis is missed and should be resumed following the next hemodialysis session.2
The most common adverse effects of etelcalcetide include decreases in blood calcium levels/hypocalcemia, muscle spasms, nausea/vomiting/diarrhea, headache, and parasthesia. Other warnings/precautions include adynamic bone disease, cardiovascular effects, such as QT prolongation and ventricular arrhythmia secondary to hypocalcemia, and gastrointestinal (GI) bleeding.2
Etelcalcetide is the first therapy approved for secondary HPT in adult patients with CKD in 12 years and the only calcimimetic that can be administered intravenously by the dialysis health care team 3 times a week at the end of a hemodialysis session.3 This is advantageous because it puts the medication in the hands of the health care provider and can help ensure that the patient receives the therapy he or she needs.
QTERN (dapagliflozin plus saxagliptin)
The FDA approved QTERN (dapagliflozin 10mg plus saxagliptin 5 mg) on February 28, 2017, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Specifically, this is indicated for those who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin.4
QTERN is a combination of 2 antihyperglycemic agents: dapagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, and saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor.
Dapagliflozin acts by inhibiting SGLT2 in the proximal renal tubules, which reduces reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose (RTG). This reduction of filtered glucose reabsorption and lowering of RTG results in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.4,5
Saxagliptin acts by inhibiting the DPP-IV enzyme resulting in prolonged active incretin levels. Incretin hormones regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production.4,6
QTERN is dosed once daily (dapagliflozin 10mg + saxagliptin 5mg) and should only be started in those who have already demonstrated toleration to dapagliflozin 10 mg.6,7
The most common adverse effects of this medication (> 5% of those studied) include upper respiratory tract infections, urinary tract infections, and dyslipidemias. QTERN is contraindicated in patients with a prior serious hypersensitivity to either dapagliflozin or saxagliptin as well as those with moderate to severe renal impairment (eGFR <45 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis.7
Naldemedine is a peripherally acting m-opioid receptor antagonist approved for the treatment of opioid-induced constipation (OIC).8 OIC is defined characterized by reduced bowel movement frequency, development or worsening of straining to pass bowel, a sense of incomplete evacuation, or harder stool consistency, after initiating opioid therapy.9
Naldemedine is dosed once orally in a 0.2 mg tablet. Clinical trials for naldemedine focused on patients that had at least 4 weeks of opioid usage. It may be less effective for patients with less than 4 weeks of opioid exposure.9 [MB7] Naldemedine has a similar mechanism of action to naloxegol and mehtylnaltrexone, but it does not require renal or hepatic dosing like the others. The most common adverse effects of naldemedine are abdominal pain, diarrhea, and nausea and vomiting.9
The FDA approved plecanatide on January 19, 2017, to treat chronic idiopathic constipation (CIC).10 A CIC diagnosis is given to those who experience constipation with no structural or biochemical explanation.10
Plecanatide is a once-daily, orally dosed 3 mg tablet.11 Plecanatide[MB1] binds to and activates guanylate cyclase-C receptors on the luminal surface of intestinal epithelium. Intra- and extracellular cGMP concentrations are increased, leading to chloride and bicarbonate secretion into the lumen. Intestinal fluid is subsequently increased.11 Linaclotide and plecanatide share similar mechanisms of action, but plecanatide users experienced a lower rate [MB2] of diarrhea in its clinical trials.11,12
The most common adverse effect of plecanatide is diarrhea. It also carries a black box warning for the risk of serious dehydration in pediatric patients and is not approved for use in people younger than 18.11 Plecanatide carries a price of about $424 for 30 tablets.12
Xermelo (telotristat ethyl)
The FDA approved telotristat ethyl on February 28, 2017, in combination with somatostatin analog (SSA) therapy, such as octreotide, to treat adults with carcinoid syndrome diarrhea that SSA therapy alone has inadequately controlled. This approval provides patients who have carcinoid syndrome diarrhea with another option for adjunctive therapy.13
Carcinoid syndrome is a cluster of symptoms sometimes seen in people with carcinoid tumors. Most carcinoid tumors are found in the GI tract. The tumors in these patients release excess amounts of the hormone serotonin, resulting in diarrhea.13
Telotristat ethyl is a small molecule inhibitor of tryptophan hydroxylase (TPH). TPH converts tryptophan to 5-hydroxytryptophan and ultimately to serotonin and is the rate-limiting enzyme in serotonin synthesis. By decreasing the production of peripheral serotonin, the result is a reduction in the frequency of carcinoid syndrome diarrhea.14 This medication is available as an oral tablet and is dosed 250 mg by mouth 3 times daily, in addition to a SSA.15
The most common adverse effects of telotristat ethyl include headache, nausea, increased levels of the liver enzyme gamma-glutamyl transferase, depression, accumulation of fluid causing swelling (peripheral edema), flatulence, decreased appetite, and fever. This medication may also cause constipation.14,15 A 28-day supply (84 tablets) costs about $6200.14
This article was written with Christopher Robinson and Charles Vawters, 2018 PharmD Candidates at the Harrison School of Pharmacy at Auburn University.
1. CenterWatch. Parsabiv (etelcalcetide). centerwatch.com/drug-information/fda-approved-drugs/drug/100184/parsabiv-etelcalcetide. Accessed October 12, 2017.
2. Parsabiv [prescribing information]. Thousand Oaks, CA: KAI Pharmaceuticals, Inc; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/208325Orig1s000Lbledt.pdf. Accessed October 12, 2017.
3. FDA approves Amgen's Parsabiv (etelcalcetide), first new treatment in more than a decade for secondary hyperparathyroidism in adult patients on hemodialysis [news release]. Thousand Oaks, CA: February 7, 2017. prnewswire.com/news-releases/fda-approves-amgens-parsabiv-etelcalcetide-first-new-treatment-in-more-than-a-decade-for-secondary-hyperparathyroidism-in-adult-patients-on-hemodialysis-300403804.html. Accessed October 12, 2017.
4. CenterWatch. QTERN (dapagliflozin and saxagliptin). centerwatch.com/drug-information/fda-approved-drugs/drug/100188/qtern-dapagliflozin-and-saxagliptin-. Accessed October 12, 2017.
5. Dapagliflozin. 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/4927422
6. Saxagliptin. 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/1822220
7. QTERN [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals, LP; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/209091s000lbl.pdf. Accessed October 12, 2017.
8. FDA. Drug trials snapshots. fda.gov/Drugs/InformationOnDrugs/ucm550343.htm. Updated April 5, 2017. Accessed October 12, 2017.
9. Symproic [prescribing information]. Florham Park, NJ: Shionogi, Inc; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/208854s000lbl.pdf. Accessed October 12, 2017.
10. FDA approves Trulance for chronic idiopathic constipation [news release]. January 19, 2017. fda.gov/newsevents/newsroom/pressannouncements/ucm537725.htm. Accessed October 12, 2017.
11. Trulance [prescribing information]. New York, NY: Synergy Pharmaceuticals, Inc; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/208745lbl.pdf. Accessed October 12, 2017.
12. Linacoltide. In: Lexi-Comp Online, Lexi-Drugs [internet]. Hudson, OH: Wolters Kluwer Health/Lexi-Comp, Inc. c2017 [cited October 2, 2017].
13. FDA approves Xermelo for carcinoid syndrome diarrhea [news release]. February 28, 2017. fda.gov/newsevents/newsroom/pressannouncements/ucm544035.htm. Accessed October 12, 2017.
14. Telotristat ethyl. In: Lexi-Comp Online, Lexi-Drugs [news release]. Hudson, OH: Wolters Kluwer Health/Lexi-Comp, Inc. c2017 [cited October 2, 2017]. online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6442587.
15. Xermelo [prescribing information]. The Woodlands, TX: Lexicon Pharmaceuticals, Inc; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/208794s000lbl.pdf. Accessed October 12, 2017.