New Drug Approvals in Pediatrics


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

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.

There have been major advancements in the treatment and prevention of COVID-19. Thus far, only remdesivir1 (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, mRNA2 (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.3 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.4

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.5 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.6

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.

Labeling changes

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.7 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.8 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.9,10

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.10,11

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.10,12 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.10,13

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.14 It is indicated for the treatment of acute bacterial skin and soft tissue infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. 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 peramivir10,15 (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.

New dosage forms

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.16

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.17,18 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.

This article originally appeared on Contemporary Pediatrics.


  1. Veklury. Prescribing Information. Gilead Sciences; 2020. Accessed October 24, 2021.
  2. Comirnaty. Prescribing Information. Pfizer Inc.; 2021. Accessed October 24, 2021.
  3. Mulangu S, Dodd LE, Davey RT, Jr., et al. A randomized, controlled trial of ebola virus disease therapeutics. N Engl J Med. 2019;381(24):2293-2303.
  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. Diabetes Care. 2021.
  5. Azstarys. Prescribing Information. Corium, Inc.; 2021. Accessed October 24, 2021.
  6. Qelbree. Prescribing Information. Supernus Pharmaceuticals Inc.; 2021. Accessed October 24, 2021.
  7. Shah SS, Hall M, Goodman DM, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007;161(3):282-290.
  8. Morphine Sulfate Oral Solution. Prescribing Information. Hikma Pharmaceuticals USA Inc.; 2021. Accessed October 24, 2021.
  9. Morphine Sulfate Injection USP. Prescribing Information. Hospira Inc.; 2021. Accessed October 24, 2021.
  10. US Food and Drug Administration. Pediatric Labeling Changes. Accessed October 1, 2021.
  11. Zipsor. Prescribing Information. Assertio Therapeutics, Inc.; 2009. Accessed October 24, 2021.
  12. Exparel. Prescribing Information. Pacira Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021.
  13. Briviact. Prescribing Information. UCB, Inc.; 2021. Accessed October 24, 2021.
  14. Dalvance. Prescribing Information. Allergan USA, Inc.; 2021. Accessed October 24, 2021.
  15. Rapivab. Prescribing Information. BioCryst Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021.
  16. Pradaxa. Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc.; 2021. Accessed October 24, 2021.
  17. Epclusa. Prescribing Information. Gilead Sciences, Inc.; 2021. Accessed October 24, 2021.
  18. Mavyret. Prescribing Information. AbbVie Inc.; 2021. Accessed October 24, 2021.
  19. Orladeyo. Prescribing Information. BioCryst Pharmaceuticals, Inc.; 2020. Accessed October 24, 2021.
  20. Imcivree. Prescribing Information. Rhythm Pharmaceuticals, Inc.; 2020. Accessed October 24, 2021.
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