Updates from FDA
APhA Staff
New drugs
DOXECITINE AND DOXRIBTIMINE
(Kygevvi—UCB)
Drug class: Both doxecitine and doxribtimine are pyrimidine nucleosides.
Indication: Kygevvi is indicated for the treatment of thymidine kinase 2 deficiency in adults and pediatric patients with an age of symptom onset on or before 12 years.
Recommended dosage and administration: Obtain ALT and AST levels in all patients prior to treatment initiation. The recommended starting dosage is 260 mg/kg/day (130 mg doxecitine and 130 mg doxribtimine) and the recommended intermediate dosage is 520 mg/kg/day (260 mg of doxecitine and 260 mg of doxribtimine). The recommended maintenance dosage is 800 mg/kg/day (400 mg doxecitine and 400 mg doxribtimine). Titrate to the next dosage level based on tolerability after a minimum of 2 weeks at the current dosage level. Administer Kygevvi orally in three equally divided doses with food. Use Kygevvi only with the ZX2000 administration kit.
Common adverse effects: The most common adverse reactions are diarrhea, abdominal pain, vomiting, and increased ALT and AST.
Warnings and precautions: Obtain baseline AST, ALT, and bilirubin levels prior to treatment initiation with Kygevvi. If signs or symptoms consistent with liver injury are observed, interrupt treatment. Consider permanently discontinuing Kygevvi if signs or symptoms consistent with liver injury persist or worsen. Monitor patients yearly and as clinically indicated. Reduce Kygevvi dosage or interrupt treatment based on severity of diarrhea and vomiting. If persistent severe diarrhea or vomiting occurs, consider discontinuing Kygevvi permanently.
PLOZASIRAN
(Redemplo—Arrowhead Pharmaceuticals Inc)
Drug class: Redemplo is an apolipoprotein C-III directed small interfering ribonucleic acid.
Indication: Redemplo is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome.
Recommended dosage and administration: The recommended dosage of Redemplo is 25 mg injected subcutaneously once every 3 months. Inject Redemplo subcutaneously into the front of the thigh or abdomen. The outer area of the upper arm can be used as an injection site if a health care provider or caregiver administers the injection.
Common adverse effects: The most common adverse reactions are hyperglycemia, headache, nausea, and injection site reaction.
SEVABERTINIB
(Hyrnuo—Bayer Healthcare)
Drug class: Hyrnuo is a kinase inhibitor.
Indication: Hyrnuo is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Recommended dosage and administration: Select patients for treatment with Hyrnuo based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations. The recommended dosage is 20 mg orally twice daily with food until disease progression or unacceptable toxicity. Swallow tablets whole.
Common adverse effects: The most common adverse reactions are diarrhea, rash, paronychia, stomatitis, nausea, decreased potassium, decreased lymphocytes, decreased sodium, increased lipase, increased amylase, increased ALT and increased AST.
Warnings and precautions: If diarrhea occurs, instruct patients to start an antidiarrheal treatment, and to increase their fluid and electrolyte intake. Interrupt, reduce the dose, or permanently discontinue Hyrnuo based on severity. Monitor liver function tests at baseline prior to administration, every 2 weeks during the first month, and then monthly thereafter as clinically indicated. Monitor patients for new or worsening symptoms indicative of interstitial lung disease or pneumonitis, and discontinue Hyrnuo if diagnosis is confirmed. Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose, or permanently discontinue Hyrnuo based on severity. Monitor amylase and lipase regularly during treatment. Interrupt, reduce the dose, or permanently discontinue Hyrnuo based on severity. Hyrnuo can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. Avoid concomitant use with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce Hyrnuo dosage. If used concomitantly with moderate CYP3A inhibitors, monitor patients for increased adverse reactions. Avoid concomitant use with strong or moderate CYP3A inducers and with CYP3A substrates where minimal increases in concentration may lead to serious adverse reactions unless otherwise recommended in the prescribing information of the CYP3A substrate. Refer to the prescribing information for P-gp substrates where minimal increases in concentration may lead to serious adverse reactions. Advise patients not to breastfeed during treatment with Hyrnuo.
New indications
SEMAGLUTIDE
(Wegovy—Novo Nordisk)
Drug class: Wegovy is a GLP-1 receptor agonist.
Indication: Wegovy is indicated in combination with a reduced calorie diet and increased physical activity to reduce the risk of major adverse CV events in adults with established CV disease and either obesity or overweight, to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with obesity and adults with overweight in the presence of at least one weight-related comorbid condition, and for the treatment on noncirrhotic metabolic dysfunction–associated steatohepatitis (MASH), with moderate to advanced liver fibrosis in adults. The indication for MASH is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial. Coadministration with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended.
Recommended dosage and administration: Administer Wegovy once weekly as an adjunct to diet and increased physical activity, on the same day each week, at any time of day, with or without meals. Inject subcutaneously in the abdomen, thigh, or upper arm. In patients with T2D, monitor blood glucose prior to starting and during Wegovy treatment. Initiate at 0.25 mg once weekly for 4 weeks. Then follow the dosage escalation schedule, titrating every 4 weeks to achieve the maintenance dosage. For patients with MASH, the maintenance dosage of Wegovy is 2.4 mg once weekly. If patients do not tolerate 2.4 mg once weekly, the dosage can be decreased to 1.7 mg once weekly. For all other Wegovy indications, the maintenance dosage is either 2.4 mg or 1.7 mg once weekly.
Common adverse effects: The most common adverse reactions are nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distention, eructation, hypoglycemia in patients with T2D, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis.
Boxed warning: In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans as the human relevance of semaglutide-induced rodent C-cell tumors has not been determined. Wegovy is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Counsel patients regarding the potential risk of medullary thyroid carcinoma and symptoms of thyroid tumors.
Other warnings and precautions: Acute pancreatitis has been observed in patients treated with GLP-1s, including Wegovy. Discontinue promptly if pancreatitis is suspected. Acute gallbladder disease has occurred in clinical trials. If cholelithiasis is suspected, gallbladder studies and clinical follow up are indicated. Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing the dose of insulin or insulin secretagogue may be necessary. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms. Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. Wegovy use has been associated with GI adverse reactions, sometimes severe. Wegovy is not recommended in patients with severe gastroparesis. Anaphylactic reactions and angioedema have been reported postmarketing. Discontinue Wegovy if suspected and promptly seek medical advice. Diabetic retinopathy complications in patients with T2D has been reported in trials. Patients with a history of diabetic retinopathy should be monitored. Monitor heart rate at regular intervals. Monitor for depression or suicidal thoughts. Discontinue Wegovy if symptoms develop. Pulmonary aspiration during general anesthesia or deep sedation has been reported in patients receiving GLP-1s undergoing elective surgeries or procedures. Instruct patients to inform health care providers about any planned surgeries or procedures. Wegovy delays gastric emptying and may impact absorption of concomitantly administered oral medications. Wegovy may cause fetal harm. For patients receiving Wegovy for CV risk reduction or weight reduction, discontinue Wegovy when pregnancy is recognized. For patients with MASH, use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Discontinue Wegovy at least 2 months before a planned pregnancy because of the long half-life of semaglutide. ■
FDA removes boxed warnings on hormone replacement therapy
On November 10, 2025, FDA initiated the removal of broad boxed warnings from hormone replacement therapy products for menopause. In the early 2000s, FDA applied these boxed warnings after a study found a statistically nonsignificant increase in the risk of breast cancer diagnosis. However, the average age of women in the study was 63 years, over 10 years past the average age of a woman experiencing menopause. Additionally, study participants were given a hormone formulation that is no longer in common use.
After a comprehensive review of scientific literature, an expert panel held in July 2025, and a public comment period, FDA is working with companies to update the language in product labeling to remove references to risks of CV disease, breast cancer, and probable dementia. Boxed warnings for endometrial cancer for systemic estrogen-alone products will not be removed.
FDA’s labeled recommendation will be to start hormone replacement therapy within 10 years of menopause onset or before age 60 years for systemic hormone replacement therapy. FDA is also approving two new drugs to expand the treatment options that are available for menopause symptoms. The first approval is for a generic version of Premarin (conjugated estrogens), and the second approved is for a nonhormonal treatment for moderate to severe vasomotor symptoms, such as hot flashes, that are associated with menopause. ■