Rachel Meyers, PharmD

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

The past year has seen several new drugs for orphan diseases including 2 for Duchenne muscular dystrophy (DMD), a new combination drug for cystic fibrosis (CF), an anticonvulsant for Dravet syndrome (DS), and 2 potentially disease modifying drugs for sickle cell anemia (SCA).

ADAKVEO (CRIZANLIZUMAB) AND OXBRYTA (VOXELOTOR)

In November 2019 the US Food and Drug Administration (FDA) approved 2 therapies for SCA. Adakveo is a monoclonal antibody which binds to P-selectin, blocking interactions with its ligands including P-selectin glycoprotein ligand 1.

 The binding of P-selectin on the surface of activated endothelium and platelets prevents interactions between endothelial cells, platelets, leukocytes, and erythrocytes. Results from SUSTAIN 2 demonstrated a decreased rate of vaso-occlusive pain crises. Adakveo is approved for patients aged 16 years and older, given as a 30-minute IV infusion at weeks 0, 2, and 4, and then every 4 weeks.

Oxbryta inhibits polymerization of hemoglobin S, thus increasing its affinity for oxygen.

 a significantly higher percentage of patients in the Oxbryta group demonstrated a hemoglobin response, defined as an increase of at least 1.0 g/dL. Oxbryta is approved for patients aged 12 years and older and is an oral tablet given once daily.

VYONDYS 53 (GOLODIRSEN) AND VILTEPSO (VILTOLARSEN)

Two new medications for the treatment of DMD represent an advance in the treatment of this disease. Both Vyondys 53 and Viltepso bind to exon 53 of the dysfunctional dystrophin pre-messenger RNA, resulting in the skipping of exon 53.

 This allows for the production of a dystrophin protein, shorter than normal, but usable. The gene mutations that result in DMD vary: not all patients have mutations amenable to exon skipping. It is estimated that 8% of patients have mutations amenable to the skipping of exon 53.

 A similar mechanism is used for Exondys 51 (eteplirsen), which was approved in 2016 and skips exon 51. On the horizon is casimersen, which skips exon 45 – a new drug application is currently under consideration.

In August of 2020, a therapy for the treatment of spinal muscular atrophy (SMA) was approved, making it the third drug for this disease in less than 4 years. Evrysdi works by increasing inclusion of exon 7 in survival motor neuron 2 (SMN2) messenger ribonucleic acid transcripts, thus creating full length SMN protein. Trials in both infant-onset SMA and later-onset SMA were conducted to investigate efficacy.

 Patients in the infant-onset trial demonstrated a higher rate of sitting independently compared to typical disease progression. With this treatment, viability without permanent ventilatory assistance for children aged 23 months or older was higher than typical disease progression.

 Motor function scores compared to baseline were improved in patients with later-onset SMA.

 Evrysdi is the first oral medication for SMA.

Valtoco is an intranasal diazepam, approved for the acute treatment of seizures in patients aged 6 years and older. Devices of 5 mg, 7.5 mg, and 10 mg are available and each Valtoco device contains 1 spray; doses of 5 mg and 10 mg are given with 1 spray of the 5 mg and 10 mg device respectively. Doses of 15 mg and 20 mg are given with 1 spray from each of 2 devices of 7.5 mg (15 mg dose) and 10 mg (20 mg dose).

 A second dose may be given at least 4 hours after the initial dose.

ADVIL DUAL ACTION WITH ACETAMINOPHEN (IBUPROFEN AND ACETAMINOPHEN)

The new over-the-counter analgesic combination with ibuprofen and acetaminophen is the first of its kind in the United States. There is potential for overdose should patients use it in combination with acetaminophen or ibuprofen alone. A trial in pediatric patients aged 2-12 years is ongoing.

Fiasp, a faster-onset version of insulin aspart, was approved in 2018 for use in adults, and is now approved for patients aged 2 years and older. It is formulated with niacinamide, which increases the rate of absorption, resulting in an onset about 5 minutes earlier than the original insulin aspart formulation. Results from the onset 7 trial demonstrated non-inferiority to insulin aspart in hemoglobin A1c reduction from baseline and change in 1-hour postprandial glucose in patients aged 1 to less than 18 years.

 Fiasp is approved for use in basal-bolus regimens, subcutaneous pumps, and intravenous use under the supervision of a healthcare professional.

Originally approved in 2015 for the treatment of heart failure in adults, Entresto has now been granted approval for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.

 This approval was based on 12-week results from the 52-week PANORAMA-HF trial, which compares Entresto with enalapril. Although the results were not statistically different between groups, improved outcomes were seen with Entresto.

Treatment options for COVID-19 in pediatric patients remain limited. Veklury (remdesivir) was granted an Emergency Use Authorization (EUA) for the treatment of COVID-19 in adults and children by the FDA in May of 2020.

 A clinical trial of Veklury in children is ongoing. Veklury is available in a concentrated solution and lyophilized powder, both for intravenous injection.

 The manufacturer only recommends use of the lyophilized powder for patients 3.5 kg to less than 40 kg due to the higher amount of sulfobutylether-β-cyclodextran sodium salt in the concentrated solution for injection, resulting in a higher toxicity.

Convalescent plasma has also been granted an EUA from the FDA and is being used in the treatment of children and adults with COVID-19.

The impact of the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act continues to benefit children’s health.

Rachel Meyers, PharmD

Articles

What’s new in children’s drugs

New drugs for children in 2019-2020