Pooja Shah, PharmD, BCPPS

We are continuing to observe the effects of federal legislation, including the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, which have increased the number of clinical trials conducted in children. This article summarizes recent (October 2020 to September 2021) labeling changes, new dosage forms, and new drugs that have potential for use in children. Table 1 includes information on newly approved drugs indicated for use in pediatric patients, whereas Table 2 lists newly approved drugs for adults with the potential for use in pediatric patients. Table 3 describes new dosage forms for medications, and Table 4 lists labeling changes to existing drugs with implications for pediatric patients.

There have been major advancements in the treatment and prevention of COVID-19. Thus far, only remdesivir

 (Veklury) has received FDA approval for treatment of COVID-19 in adults and children 12 years and older, but its use in younger children is permitted only under an emergency use authorization (EUA). COVID-19 Vaccine, mRNA

 (Comirnaty) received approval as a vaccine for COVID-19 in adults and children 16 years and older and is available under an EUA for children 5 to 15 years old. More treatments and vaccines for younger children are expected to receive EUAs in the coming months, which may subsequently lead to full approvals.

There has been a continuing trend in the development of drugs for orphan diseases affecting pediatric patients, such as lonafarnib (Zokinvy) or progeria, casimersen (Amondys 45) for Duchenne muscular dystrophy, fosdenopterin (Nulibry) for molybdenum cofactor deficiency type A, and avalglucosidase alfa-ngpt (Nexviazyme) for Pompe disease.

Additional developments include 2 treatments for infection caused by Zaire ebolavirus, ansuvimab-zykl (Ebanga) and atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb). Both are approved for patients as young as neonates born to mothers who have tested positive for Ebola on reverse transcriptase polymerase chain reaction tests. Both Ebanga and Inmazeb were studied in the PALM trial, which was conducted during the 2018-2019 Ebola outbreak in the Democratic Republic of the Congo.

 For Ebanga, the 28-day mortality was 35.1% compared with 49.7% in its comparator control group. The 28-day mortality was 33.5% in the Inmazeb group compared with 51.3% in its comparator control group.

Some new alternatives to commonly used medications have also emerged. Dasiglucagon (Zegalogue) is a new treatment for severe hypoglycemia that is available as a pre-filled syringe or an autoinjector. In a clinical trial, Zegalogue was reported to raise blood glucose by at least 20 mg/dL in approximately 10 minutes compared with 12 minutes for traditional glucagon.

 Two new treatments for attention-deficit/hyperactivity disorder (ADHD) have also been approved. Serdex-methylphenidate and dexmethylphenidate (Azstarys) is a stimulant that contains an immediate-release dexmethylphenidate component in addition to serdex-methylphenidate, which is a prodrug of dexmethylphenidate.

 Serdex-methylphenidate is metabolized to dexmethylphenidate throughout the day, allowing for once-daily dosing. Viloxazine (Qelbree) is available as a nonstimulant, once-daily extended-release capsule.

 Both of these new treatment options for ADHD are available as capsules, which can be swallowed whole or opened and sprinkled on applesauce; Azstarys may also be sprinkled in water.

This year, we have continued to observe drug labeling changes that include more of the younger pediatric patient population. These updates help increase the tools available for practitioners to administer these drugs safely and effectively in this vulnerable patient population.

Morphine in children has been considered off-label despite the high rates of use described in pediatric patients.

 Labeling information is finally available for morphine as an intravenous continuous infusion and as an oral solution. Morphine oral solution (2 mg/mL and 4 mg/mL) is now indicated for pediatric patients aged 2 to 17 years with acute pain severe enough to require an opioid analgesic when alternative treatments are inadequate.

 Safety and efficacy in this age group are supported by extrapolation from clinical evidence in adults and supportive data from an open-label safety and pharmacokinetic study in pediatric patients aged 2 to 17 years with postoperative acute pain. The recommended initial dosage is 0.3 mg/kg/dose orally, based on pharmacokinetic modeling and simulation, which will be equivalent to the maximum concentration of 10 mg in adult patients. With regard to safety, adverse effects are expected to be similar to those observed in adults. Morphine continuous intravenous infusion is now approved for pain in patients of all age groups. Use of morphine continuous intravenous infusion for pain management in pediatric patients is supported by evidence from randomized controlled studies in pediatric patients.

Additional pain medications that have expanded indications in the pediatric population include diclofenac potassium (Zipsor). The labeling has been expanded to include safety and effectiveness in pediatric patients aged 12 to 17 years, offering this population an alternative nonopioid pain medication.

 This indication was based on extrapolation of efficacy from studies in adult patients combined with pharmacokinetic and safety data from 2 open-label studies with a combined 49 patients aged 12 to 17 years and an active-controlled study in 76 pediatric patients aged 12 to 16 years.

Bupivacaine liposome (Exparel) is a postoperative local anesthetic with labeling updated to include a single-dose infiltration to contribute to postsurgical local analgesia in pediatric patients 6 years and older.

 This indication was based on the results of the phase 3 PLAY study, which included 98 pediatric patients undergoing spinal or cardiac surgeries. A dose of 4 mg/kg produced pharmacokinetics and safety outcomes similar to those in adult patients. This updated indication provides an alternative to opioids for postoperative pain control.

Many of the drug labeling changes in 2021 have focused on expanding indications to include younger pediatric patients. Although initial FDA approvals in pediatric patients often include adolescent patients, these medications are often used in the younger populations. Below are highlights of updates for expanded indications in children.

Brivaracetam (Briviact) is an anticonvulsant with a mechanism similar to that of levetiracetam; it binds specifically to synaptic vesicle protein 2A, but with a 15- to 30-fold higher affinity compared with levetiracetam. Brivaracetam oral and intravenous formulations are now indicated in patients 1 month or older for the treatment of partial-onset seizures.

 This indication was based on the results of an open-label follow-up pediatric study, in which an estimated 71.4% and 64.3% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year and 2 years, respectively.

Dalbavancin (Dalvance) is a unique glycopeptide antibiotic that is approved in all pediatric patients from birth.

 It is indicated for the treatment of acute bacterial skin and soft tissue infections caused by gram-positive bacteria, including methicillin-resistant 

. It is the first single-dose option for this indication and is administered as a 30-minute infusion. This approval was based on a multicenter, open-label, randomized, active-controlled trial that was conducted in pediatric patients aged 3 months to 18 years with bacterial skin and soft tissue infections. The study compared single-dose or 2-dose dalbavancin against a comparator regimen that included intravenous vancomycin for methicillin-resistant gram-positive infections or intravenous oxacillin or flucloxacillin for methicillin-susceptible gram-positive infections.

Another antimicrobial agent that recently received expanded age indications is peramivir

 (Rapivab). Based on the results of a randomized, open-label, active-controlled study comparing peramivir and oseltamivir in 97 patients aged 6 months to 17 years with acute uncomplicated influenza, the label was updated to include pediatric patients 6 months and older. There was a comparable time between the oseltamivir and peramivir groups to alleviation of symptoms and time to recovery of normal temperature. The recommended dose based on this study is 12 mg/kg/dose for patients 6 months to 12 years of age.

As the need for pediatric dosage forms expands, pharmaceutical companies have begun exploring options beyond oral liquids. Three medications have been approved as “oral pellets” in the past year: dabigatran etexilate (Pradaxa), sofosbuvir/ velpatasvir (Epclusa), and glecaprevir/pibrentasvir (Mavyret). Pradaxa, originally approved in 2010 for the treatment and prevention of venous thromboembolism in adults, is now approved for pediatric patients aged 3 months to less than 12 years for the same indications.

 As the first direct-acting oral anticoagulant approved for use in the pediatric population, Pradaxa offers an alternative to injectable anticoagulants and warfarin. The oral pellets approved for this age group are available in packets of 20 mg, 30 mg, 40 mg, 50 mg, 110 mg, and 150 mg. The packet is opened and the pellets mixed in a soft food, such as baby rice cereal prepared with water or apple sauce; the pellets should not be mixed with milk or milk-containing foods. A spoon is then used to administer the dose. It should be noted that these pellets should not be administered with an oral syringe or through a feeding tube. Epclusa and Mavyret, both approved for the treatment of hepatitis C infection in children as young as 3 years, are also now available as oral pellets packaged in packets.

 It is important to read the instructions for use carefully, as only certain types of foods can be used to mix the pellets. For both Epclusa and Mavyret, it is important that the child not chew the pellets, as this will produce a bad taste.

We continue to see improvements in drug labeling for children and new dosage forms, which will help improve care for this patient population. New vaccines for the prevention of pneumococcal disease in adults may eventually receive approval in children. Novel pediatric-friendly oral dosage forms, such as oral pellets, may continue to become available for new drugs seeking approval for pediatric use. The coming months should see more approvals in the area of COVID-19. The continuing growth of clinical trials and approvals in children combined with the expansion of drug labeling to include children has been encouraging for pediatric practitioners.

1. Veklury. Prescribing Information. Gilead Sciences; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214787Orig1s000lbl.pdf

2. Comirnaty. Prescribing Information. Pfizer Inc.; 2021. Accessed October 24, 2021. 

https://www.fda.gov/media/151707/download

3. Mulangu S, Dodd LE, Davey RT, Jr., et al. A randomized, controlled trial of ebola virus disease therapeutics. 

4. Pieber TR, Aronson R, Hovelmann U, et al. Dasiglucagon: a next-generation glucagon analog for rapid and effective treatment of severe hypoglycemia results of phase 3 randomized double-blind clinical trial. 

5. Azstarys. Prescribing Information. Corium, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212994s000lbl.pdf

6. Qelbree. Prescribing Information. Supernus Pharmaceuticals Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211964s000lbl.pdf

7. Shah SS, Hall M, Goodman DM, et al. Off-label drug use in hospitalized children. 

8. Morphine Sulfate Oral Solution. Prescribing Information. Hikma Pharmaceuticals USA Inc.; 2021. Accessed October 24, 2021. 

https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=19a17354-8ae9-48cf-ad52-cc774ca801be

9. Morphine Sulfate Injection USP. Prescribing Information. Hospira Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202515s025lbl.pdf

10. US Food and Drug Administration. Pediatric Labeling Changes. Accessed October 1, 2021. 

https://www.fda.gov/science-research/pediatrics/pediatric-labeling-changes

11. Zipsor. Prescribing Information. Assertio Therapeutics, Inc.; 2009. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022202s013s014lbl.pdf

12. Exparel. Prescribing Information. Pacira Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021. 

https://www.exparel.com/hcp/prescribing-information.pdf

13. Briviact. Prescribing Information. UCB, Inc.; 2021. Accessed October 24, 2021. 

14. Dalvance. Prescribing Information. Allergan USA, Inc.; 2021. Accessed October 24, 2021. 

https://media.allergan.com/actavis/actavis/media/allergan-pdf-documents/product-prescribing/Dalvance_Final_PI_10_2018.pdf

15. Rapivab. Prescribing Information. BioCryst Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021. 

https://www.rapivab.com/themes/rapivab/pdf/Rapivab-Prescribing-Information.pdf

16. Pradaxa. Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214358s000lbl.pdf

17. Epclusa. Prescribing Information. Gilead Sciences, Inc.; 2021. Accessed October 24, 2021. 

https://www.gilead.com/-/media/files/pdfs/medicines/liver-disease/epclusa/epclusa_pi.pdf

18. Mavyret. Prescribing Information. AbbVie Inc.; 2021. Accessed October 24, 2021. 

https://www.rxabbvie.com/pdf/mavyret_pi.pdf

19. Orladeyo. Prescribing Information. BioCryst Pharmaceuticals, Inc.; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214094s000lbl.pdf

20. Imcivree. Prescribing Information. Rhythm Pharmaceuticals, Inc.; 2020. Accessed October 24, 2021. 

https://www.rhythmtx.com/IMCIVREE/prescribing-information.pdf

21. Oxlumo. Prescribing Information. Alnylam Pharmaceuticals, Inc.; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214103lbl.pdf

22. Zokinvy. Prescribing Information. Eiger BioPharmaceuticals, Inc..; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213969s000lbl.pdf

23. Inmazeb. Prescribing Information. Regeneron Pharmaceuticals, Inc.; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761169s000lbl.pdf

24. Ebanga. Prescribing Information. Ridgeback Biotherapeutics, LP; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761172s000lbl.pdf

25. Multrys. Prescribing Information. American Regent, Inc.; 2021. Accessed October 24, 2021. 

https://americanregent.com/media/3146/ref-1835_multrys-insert-in9302-rev-6-2021.pdf

26. Danyelza. Prescribing Information. Y-mAbs Therapeutics, Inc.; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761171lbl.pdf

27. Gavreto. Prescribing Information. Genentech, Inc.; 2021. Accessed October 24, 2021. 

https://www.gene.com/download/pdf/gavreto_prescribing.pdf

28. Klisyri (tirbanibulin) [package insert]. Exton, PA: Almirall, LLC; 2021.

29. Evkeeza. Prescribing Information. Regeneron Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761181s000lbl.pdf

30. Amondys 45. Prescribing Information. Sarepta Therapeutics, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213026lbl.pdf

31. Nulibry. Prescribing Information. Origin Biosciences, Inc.; 2021. Accessed October 24, 2021. 

https://www.nulibry.com/pdfs/nulibry-prescribing-information-v2.pdf

32. Zegalogue. Prescribing Information. Zealand Pharma A/S; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214231s000lbl.pdf

33. Tembexa. Prescribing Information. Chimerix, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdf

34. Fexinidazole. Prescribing Information. sanofi-aventis U.S. LLC; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214429s000lbl.pdf

35. Rezurock. Prescribing Information. Kadmon Pharmaceuticals, LLC; 2021. Accessed October 24, 2021. 

https://rezurockhcp.com/full-prescribing-information.pdf

36. Bylvay. Prescribing Information. Albireo Pharma, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215498s000lbl.pdf?utm_medium=email&utm_source=govdelivery

37. Nexviazyme. Prescribing Information. Genzyme Corporation; 2021. Accessed October 24, 2021. 

https://products.sanofi.us/nexviazyme/nexviazyme.pdf

38. Skytrofa. Prescribing Information. Ascendis Pharma, Inc.; 2021. Accessed October 24, 2021. 

https://ascendispharma.us/products/pi/skytrofa/skytrofa_pi.pdf

39. Ryplazim. Prescribing Information. Prometic Bioproduction Inc; 2021. Accessed October 24, 2021. 

https://www.fda.gov/media/149806/download

40. Brexafemme. Prescribing Information. Scynexis, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214900s000lbl.pdf

41. Bronchitol. Prescribing Information. Chiesi USA, Inc.; 2020. Accessed October 24, 2021. 

https://resources.chiesiusa.com/Bronchitol/BRONCHITOL_PI.pdf

42. Sutab. Prescribing Information. Braintree Laboratories, Inc.; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213135s000lbl.pdf

43. Lupkynis. Prescribing Information. Aurinia Pharmaceuticals Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213716s000lbl.pdf

44. Saphnelo. Prescribing Information. AstraZeneca Pharmaceuticals LP; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761123s000lbl.pdf

45. Korsuva. Prescribing Information. Vifor (International) Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214916s000lbl.pdf

46. Loreev XR. Prescribing Information. Almatica Pharma LLC; 2021. Accessed October 24, 2021. 

https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=227734c1-bf01-9607-73ea-5a1f38a89bd9&version=1

47. Vaxneuvance. Prescribing Information. Merck & Co., Inc.; 2021. Accessed October 24, 2021. 

https://www.merck.com/product/usa/pi_circulars/v/vaxneuvance/vaxneuvance_pi.pdf

48. Prevnar 20. Prescribing Information. Pfizer Inc.; 2021. Accessed October 24, 2021. 

http://labeling.pfizer.com/ShowLabeling.aspx?id=15428

49. Xofluza. Prescribing Information. Genentech USA, Inc.; 2021. Accessed October 24, 2021. 

https://www.gene.com/download/pdf/xofluza_prescribing.pdf

50. Thyquidity. Prescribing Information. VistaPharm, Inc.; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214047s000lbl.pdf

51. Hetlioz. Prescribing Information. Vanda Pharmaceuticals Inc.; 2020. Accessed October 24, 2021. 

52. Xolair. Prescribing Information. Genentech, Inc.; 2021. Accessed October 24, 2021. 

https://www.gene.com/download/pdf/xolair_prescribing.pdf

53. Myrbetriq Granules. Prescribing Information. Astellas Pharma US, Inc.; 2021. Accessed October 24, 2021. 

https://astellas.us/docs/Myrbetriq_WPI.pdf

54. Kloxxado. Prescribing Information. Hikma Specialty USA Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212045s000lbl.pdf

55. Noxafil PowderMix. Prescribing Information. Merck & Co., Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214770s000,205053s012,205596s012lbl.pdf

56. Verkazia. Prescribing Information. Santen Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214965s000lbl.pdf

57. Rylaze. Prescribing Information. Jazz Pharmaceuticals Ireland Limited; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761179s000lbl.pdf

58. Twyneo. Prescribing Information. Sol-Gel Technologies Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214902s000lbl.pdf

59. Semglee. Prescribing Information. Mylan Pharmaceuticals Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761201Orig1s000lbl.pdf

60. Bridion. Prescribing Information. Merck & Co., Inc.; 2021. Accessed October 24, 2021. 

https://www.merck.com/product/usa/pi_circulars/b/bridion/bridion_pi.pdf

61. Toviaz. Prescribing Information. Pfizer Inc.; 2021. Accessed October 24, 2021. 

http://labeling.pfizer.com/showlabeling.aspx?id=540

62. Diovan. Prescribing Information. Novartis Pharmaceuticals Corporation; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021283s058lbl.pdf

63. Natroba. Prescribing Information. ParaPRO LLC; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022408Orig1s010lbl.pdf

64. Evekeo ODT. Prescribing Information. Arbor Pharmaceuticals, LLC; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209905Orig1s001lbl.pdf

65. Vyxeos. Prescribing Information. Jazz Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209401s006lbl.pdf

66. Trintellix. Prescribing Information. Takeda Pharmaceuticals America, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204447s024lbl.pdf

67. Botox. Prescribing Information. Allergan, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103000s5320lbl.pdf

68. Xeomin. Prescribing Information. Merz Pharmaceuticals, LLC; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125360s093lbl.pdf

69. Saxenda. Prescribing Information. Novo Nordisk Inc.; 2020. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206321s011lbl.pdf

70. Prograf. Prescribing Information. Astellas Pharma US, Inc.; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/050708s053,050709s045,210115s005lbl.pdf

71. Trikafta. Prescribing Information. Vertex Pharmaceuticals Incorporated; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212273s008lbl.pdf

72. Cystic Fibrosis Foundation. CFTR Modulator Types. Accessed November 8, 2021. 

https://www.cff.org/Research/Developing-New-Treatments/CFTR-Modulator-Types/

73. Cosentyx. Prescribing Information. Novartis Pharmaceuticals Corporation; 2021. Accessed October 24, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125504s043lbl.pdf

Articles

This past year has seen several important new drug approvals and labeling updates for children. Here is what you should know.

What’s new in children’s drugs

Off-label use of medication in pediatric patients has varied from 25% to 85%.

 Federal legislation including the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) have increased the number of clinical trials conducted in children and led to expanded labeling for these patients. This article summarizes recent (November 2018 to September 2019) labeling changes, new dosage forms, and new drugs that have potential for use in children.

Table 1 includes information on new dosage forms and Table 2 lists new biologics with pediatric indications. Table 3 lists labeling changes to existing drugs.

In May 2019, the US Food and Drug Administration (FDA) approved the first nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern in patients aged 12 years and older with epilepsy.

 The nasal spray comes in a single dose of 5 mg of midazolam, and each package contains 2 spray units. The sprayer should not be primed prior to use as this will cause loss of the dose. The caregiver should administer a dose into one nostril, and if the seizure continues beyond 10 minutes, a second dose with a new spray unit may be given.

Many patients with refractory epilepsy have used intranasal midazolam compounded in compounding pharmacies; unlike Nayzilam, these products typically have multiple doses. Nayzilam is a single dose, similar to Diastat (rectal diazepam gel) that has been on the market since 1997.

BAQSIMI (GLUCAGON NASAL SPRAY) AND GVOKE (GLUCAGON AUTOINJECTOR AND PREFILLED SYRINGE)

Glucagon has been available in a subcutaneous kit for many years and has been the mainstay of emergency treatment for hypoglycemic emergencies. Recently, the FDA approved Baqsimi nasal spray (July 2019)4 and the Gvoke HypoPen and Gvoke PFS (September 2019),

 both of which will provide glucagon in a ready-to-use form. Glucagon in liquid form was previously not stable at room temperature and the traditional kit requires the user to reconstitute the powder with a diluent using a needle and syringe. These steps can be intimidating and difficult, especially for a user who is experiencing a hypoglycemic emergency.

Baqsimi is available as a 3-mg intranasal device that contains one dose. The 3-mg dose is indicated for ages 4 years and older and is administered into one nostril. If no response is seen in 15 minutes, a second dose may be administered. Packages containing 1 or 2 devices are available.

Gvoke is available as an autoinjector (Gvoke HypoPen) and prefilled syringe (Gvoke PFS) in 2 dose strengths. Adults and children aged 12 years and older as well as children aged younger than 12 years who weigh 45 kg or greater should receive 1 mg. Children aged younger than 12 years who weigh less than 45 kg should receive 0.5 mg. Both the autoinjector and prefilled syringe should be administered subcutaneously and are single use. If no response is seen in 15 minutes, another dose should be administered. Package sizes of 1 and 2 autoinjectors or prefilled syringes are available.

Both Baqsimi and Gvoke contain instructions to call for emergency assistance immediately after administration.

Legislation to improve studies of medications in the pediatric patient population has increased the number of drug studies conducted in pediatric patients. However, this data often lags behind the drug’s initial complete evaluation in larger clinical trials. Here we present a review of both new drugs for pediatric patients and selected new drug approvals with high potential for pediatric use.

Xenleta is a first in-class antibiotic approved in August 2019 for the treatment of community-acquired pneumonia in patients aged older than 18 years. It works by inhibition of protein synthesis of the 50S bacterial ribosome and preventing the binding of transfer RNA for peptide transfer. In clinical studies, it has demonstrated similar rates of clinical success in patients treated with moxifloxacin with or without linezolid.9 Pediatric studies are expected to be completed in 2024.

Accrufer is an oral capsule approved in July 2019 and used for the treatment of low iron stores in adult patients.

 Pediatric studies in patients aged 1 month to younger than 10 years for pharmacokinetics and pharmacodynamics to confirm the dosing used in the efficacy and safety study are expected to be completed by January 2022.

RECARBRIO (IMIPENEM, CILASTATIN, RELEBACTAM)

This antibiotic combination is approved to treat complicated urinary tract and complicated intra-abdominal infections in adult patients. An open-label, single-dose study evaluating pharmacokinetics, safety, and tolerability from birth to age 18 years is expected to be completed by 2021 and a randomized trial will be completed by 2024.

ZOLGENSMA (ONASEMNOGENE ABEPARVOVEC-XIOI)

Zolgensma is a gene therapy indicated for treatment in children aged younger than 2 years with spinal muscular atrophy (SMA).

 Spinal muscular atrophy is caused by the lack of the survival motor neuron (SMN) protein due to an autosomal recessive mutation in the 

 gene. The lack of the SMN protein causes slow degeneration of the lower motor neurons in the spinal cord and brainstem leading to symmetric significant progressive muscle atrophy and weakness. This weakness spreads to all skeletal muscle resulting in mortality.

Onasemnogene abeparvovec-xioi is a recombinant adeno-associated virus vector-based gene therapy that delivers a normal copy of the SMN gene allowing replication of the normal protein. Unlike the alternative therapy for SMA, nusinersen, this is a one-time infusion. Significant adverse effects include acute serious liver injury, and close monitoring of liver function is recommended until 3 months after the infusion. Furthermore, there is a recommendation to administer systemic corticosteroids to all patients (prednisone 1 mg/kg/day once daily) for at least 30 days after infusion. As therapies for SMA are extremely limited, this is a life-changing option for these patients. The cost is reported to be $2.1 million per dose, making it one of the most expensive drugs on the market.

EPINEPHRINE MULTIDOSE INHALER (PRIMATENE MIST)

Primatene Mist is an over-the-counter (OTC) multidose inhaler for asthma. Many practitioners may remember this product, which was removed from the market in 2011 due to the carbonated fluorocarbons (CFCs) in the propellant. In November 2018, Primatene Mist formulated with hydrofluoroalkanes (HFAs) as a propellant was approved for OTC use for asthma.

 Its indication is for adults and pediatric patients aged 12 years and older for the temporary relief of mild symptoms of intermittent asthma. The labeling does include a warning that it is for temporary relief of mild symptoms of intermittent asthma and that patients should see a doctor if they are feeling worse, are not better in 20 minutes, need more than 8 inhalations in 24 hours, or have more than 2 asthma attacks in 1 week.

The year 2019 has seen major advances for pediatric therapeutics in the quest to identify better medicines for children. Here is a summary of what is new from these last months.

Pooja Shah, PharmD, BCPPS

Articles

What’s new in children’s drugs

Pediatric clinical trials lead to new drugs, updates in 2019