Extended Pediatric Use for Pfizer/BioNTech’s COVID-19 Booster
The U.S. Food and Drug Administration (FDA) issued a new Emergency Use Authorization (EUA) on March 14, 2023, for the bivalent COVID-19 booster vaccine from Pfizer/BioNTech. Reformulated to be more effective for preventing infections with the BA.4 and BA.5 forms of COVID’s Omicron variant and still effective against other variations of the virus, it now is authorized for children between the ages of six months old and five years old. It can be administered as a booster at least two months after the child has had the third shot of the original vaccine formulation in the primary series of Pfizer/BioNTech vaccinations or it can replace the third primary inoculation for patients in the age group. For children receiving the bivalent vaccine as the last in their primary series, a fourth shot is not necessary. The bivalent vaccine also can be used for older patients. A Fact Sheet for Healthcare Providers about the new EUA is here. For more information about Pfizer/BioNTech’s COVID-19 vaccines, look here.
Livmarli Indication Expanded
Livmarli® (maralixibat – Mirum Pharmaceuticals) oral solution was approved by the FDA on March 13, 2023, for children as young as three months old. Originally approved in September 2021 for patients at least one year old, it is an ileal bile acid transporter (IBAT) inhibitor. It is the only drug currently indicated to treat patients who have cholestatic pruritus caused by Alagille syndrome (ALGS). Usually evident soon after birth, ALGS affects about 2,500 individuals in the U.S. It is caused by defective bile ducts and/or a lower-than-usual number of bile ducts (bile duct paucity), which cannot accommodate the normal flow of bile from the liver into the gallbladder. The resulting accumulation of bile damages the liver and leads to symptoms such as jaundice. Multiple organs — including blood vessels, the heart, and the kidneys – also may be affected. One common characteristic of ALGS is intensely itchy skin, which contributes to sleep disturbances and mental health issues. Scratching damages the skin and leaves many patients with scars. Livmarli lessens itching by blocking the intestinal reabsorption of bile acids, forcing more to be excreted and leaving less to recirculate. Initial dosing is 190mcg/kg/day. After one week, the maintenance dose increases to 380mcg/kg with a maximum of 28.5mg (3mL)/day. All doses should be taken one-half hour before the first food of the day. Patients taking it to need to have regular liver function tests. Livmarli may be associated with gastrointestinal (GI) side effects, such as diarrhea and vomiting, which may be severe enough to result in dehydration for some patients. Livmarli also may interfere with the absorption of vitamins A, D, E, and K; so patients may need supplemental vitamins. Here is the updated prescribing information.
New Pediatric Indication and Dose Forms for Tafinlar and Mekinist
Tafinlar® (dabrafenib) and Mekinist® (trametinib) were FDA-approved on March 16, 2023, for treating patients who are one year old or older and who need systemic therapy for low-grade gliomas that test positive for BRAF V600E mutations. With an estimated incidence of fewer than 2,000 pediatric cases per year, low-grade gliomas still are the most prevalent brain tumors in children. Up to one-fifth of them have BRAF V600 mutations. At the same time, oral solution forms of each drug were approved. In addition to 50mg and 75mg capsules, Tafinlar will be available as 10mg tablets to be dissolved in water for administration. Mekinist will be dispensed in bottles containing powder that has 0.05mg/mL once it is reconstituted, as well as in 0.5mg and 2mg tablets. For both, pediatric doses depend on the child’s weight with Tafinlar administered twice and Mekinist once daily. All doses should be given one hour or more before or two hours or more after food. In a clinical trial, children taking Tafinlar and Mekinist had an overall response rate (ORR) of 47% and an average progression-free survival (PFS) time of 20.1 months. Comparatively, patients receiving standard chemotherapy averaged an ORR of 11% and 7.4 months PFS. Side effects, including fever, rash, headache, GI issues, musculoskeletal pain, and fatigue, affected one-quarter or more of patients taking the Tafinlar/Mekinist regimen. Used together, the two drugs, which both are kinase inhibitors, also have indications to treat advanced melanoma, non-small cell lung cancer (NSCLC), and anaplastic thyroid cancer that have BRAF V600 mutations. They also are approved after previous therapy has failed to treat BRAF V600E-positive solid tumors for patients as young as six years old. Revised prescribing information is here for Tafinlar and here for Mekinist.
Illuccix Indication Broadened
An agent for imaging prostate cancer, Telix Pharmaceuticals’ Illuccix ® (kit for the preparation of gallium Ga 68 gozetotide injection), initially was approved by the FDA in December 2021. The prostate-specific membrane antigen (PSMA) is radiolabeled with gallium-68 (68Ga) gozetotide, which also is called PSMA-11, before a positron emission tomography (PET) imaging procedure. The recommended dose of between 111 MBq and 259 MBq is delivered in one quick intravenous (IV) injection. It should be given between 50 minutes and 100 minutes after mixing for patients whose prostate cancer is presumed to have metastasized or returned. Now, it also can be used during PSMA-guided PET imaging to identify patients who have metastatic prostate cancers that are most likely to be responsive to treatment with radioactive drugs. Like all radioactive pharmaceuticals, Illuccix is handled under precise conditions by imaging centers, hospitals, and nuclear pharmacies that have specifically trained staff, specialized equipment, and strict protocols for using and discarding radioactive substances. Complete prescribing information is here.
On March 1, 2023, Apotex recalled several lots and expiration dates of brimonidine tartrate 0.15% ophthalmic solution out of an abundance of caution, since caps to the dropper could be cracked or broken, leading to the product lacking sterility. Brimonidine is an alpha-adrenergic receptor agonist used to reduce intraocular pressure in patients who have glaucoma. When eye drops lack sterility, it could lead to adverse events or infections. Full information about the recall can be read here. Aprepitant
Through the Consumer Product Safety Commission (CPSC), Sandoz recalled two lots of unit-dose packaged aprepitant capsules, 125mg, on March 9, 2023. Although they were meant to be used in hospitals and nursing facilities, some packages unintentionally were dispensed by retail pharmacies. They are not child-resistant, raising the potential for accidental poisoning. Aprepitant is used to control nausea and vomiting – primarily for patients undergoing chemotherapy. Children ingesting it could have adverse effects such as drowsiness, dizziness, and headaches. For more information, the CPSC notice is here; and one with contact information from Sandoz is here.