Updates from FDA
APhA Staff
New Formulations
DAPAGLIFLOZIN/METFORMIN
(Xigduo XR—AstraZeneca Pharmaceuticals)
Drug class: Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and metformin is a biguanide.
Indication: Xigduo XR has been approved as an add-on therapy to help improve glycemic control for type 2 diabetes since 2014. In 2019, it gained additional approval to help reduce the risk of hospitalization for heart failure in patients with type 2 diabetes who had established cardiovascular disease or who had multiple risk factors for cardiovascular disease. In February 2022, it gained the additional indication to reduce risk of cardiovascular death and hospitalization for use in patients with heart failure (NYHA Class II–IV) with reduced ejection faction.
Recommended dosage and administration: Xigduo XR is available in several different dapagliflozin/metformin dose combinations: 5 mg dapagliflozin/500 mg metformin HCl, 5 mg dapagliflozin/1,000 mg metformin HCl, 10 mg dapagliflozin/500 mg metformin HCl, and 10 mg dapagliflozin/1,000 mg metformin HCl. Initial dose is dependent on whether the patient is already taking dapagliflozin as well as the dose and formulation of metformin they are taking. For patients who are starting this medication to initiate dapagliflozin for an indication related to heart failure, the initial daily dose of dapagliflozin should be 10 mg. Xigduo XR should only be taken once daily in the morning, should be taken with food, and should only be used by patients who have type 2 diabetes. Use is contraindicated in patients who have an eGFR less than 30 mL/min/1.73 m2. See full prescribing information for entire list of dose combinations and recommendations.
Common adverse effects: Nasopharyngitis, urinary tract infection, diarrhea, headache, female genital mycotic infection.
Black box warning: Increased risk of metformin-associated lactic acidosis.
Other warnings and precautions: Risk of volume depletion, ketoacidosis, urosepsis and pyelonephritis, hypoglycemia, necrotizing fasciitis of the perineum, vitamin B12 deficiency, and genital mycotic infections. See full prescribing information for more in-depth information and monitoring parameters.
New drug
MITAPIVAT
(Pyrukynd—Agios Pharmaceuticals, Inc.)
Drug class: Pyruvate kinase activator. Pyrukynd is indicated as a treatment for hemolytic anemia in patients with pyruvate kinase deficiency.
Recommended dosage and administration: Pyrukynd is available as 5 mg, 20 mg, and 50 mg tablets. Pyrukynd tablets should be taken twice daily by mouth and can be taken with or without food. The initial dose of Pyrukynd is 5 mg twice daily. After 4 weeks at the 5 mg dose, the dose can be increased to 20 mg twice daily if hemoglobin (Hb) level is below normal range or if the patient has required a transfusion within the last 8 weeks. If the dose is increased to 20 mg twice daily, the dose can be increased to 50 mg twice daily if the patient has been taking the 20 mg dose for 4 weeks and Hb is still low, or if the patient has required a transfusion within the last 8 weeks. Pyrukynd should be discontinued if no benefit has been shown after 24 weeks. If therapy with Pyrukynd is discontinued, the patient should follow a tapering schedule to prevent the risk of acute hemolysis (see full prescribing information for a dose tapering schedule based on the patient’s dosage regimen). Patients who have moderate or severe hepatic impairment should not use Pyrukynd. Pyrukynd is primarily metabolized by CYP3A4; see prescribing information for dose adjustments based on potential drug–drug interactions.
Common adverse effects: Decreased estrone and estradiol in male patients, increased urate levels, back pain, arthralgia.
Warnings and precautions: Increased risk of acute hemolysis if Pyrukynd is discontinued abruptly.
FILGRASTIM-AYOW
(Releuko—Kashiv BioSciences, LLC)
Drug class: Leukocyte growth factor.
Indication: Releuko is a newly approved medication that is biosimilar to Neupogen. It is indicated to decrease the incidence of infection caused by febrile neutropenia in patients who are receiving myelosuppressive anticancer treatment to reduce the time to neutrophil recovery and duration of fever in patients undergoing chemotherapy for acute myeloid leukemia; reduce the duration of neutropenia and neutropenia-related effects in patients receiving myeloablative chemotherapy and bone marrow transplantation; and reduce the incidence and duration of clinical effects of severe neutropenia in patients who have symptoms and have congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.
Recommended dosage and administration: Releuko can be administered as a subcutaneous injection or as an intravenous infusion. The dose and administration instructions are dependent on the indication. See full prescribing information for specific instructions.
Common adverse effects: Fever, pain, rash, cough, shortness of breath, bloody nose, diarrhea.
Warnings and precautions: Risk of fatal splenic rupture, acute respiratory distress syndrome, serious allergic reactions, fatal sickle cell crisis, glomerulonephritis, myelodysplastic syndrome and acute myeloid leukemia, and thrombocytopenia. Patients should be monitored closely and therapy should be adjusted or discontinued as necessary.
FDA approves first-in-class drug-eluting contact lens
ACUVUE Theravision with ketotifen is a daily wear contact lens that is indicated for the prevention of ocular itch due to allergic conjunctivitis and correction of refractive ametropia. Patients must be able to wear contact lenses and cannot have more than 1 D of astigmatism. The contacts contain ketotifen, an H1 histamine receptor antagonist. A new set of lenses should be used each day. Lenses should be removed and discarded prior to sleeping. The most commonly reported adverse effects of ACUVUE Theravision with ketotifen are eye irritation and eye pain.
Condom for anal intercourse receives FDA authorization
In February 2022, FDA granted authorization to market condoms indicated for anal intercourse. The ONE Condom is the first condom to receive an FDA authorization specifically for anal intercourse. ONE Condoms are composed of natural rubber latex, available in 54 different sizes, and should be used with a lubricant that is compatible with condoms. FDA authorization was based on a clinical trial published in eClinicalMedicine in December 2019. The trial enrolled 252 men who have sex with men and 252 men who have sex with women and assessed condom failure rate by having trial participants document slippage and/or breakage of condoms during both anal and vaginal intercourse. The overall goal of the trial was to provide data to regulatory agencies showing that condoms used for anal sex are both safe and effective at preventing HIV infections and sexually transmitted diseases. The total condom failure rate for anal intercourse was 0.68%. Courtney Lias, PhD, director of the FDA’s Office of GastroRenal, ObGyn, General Hospital, and Urology Devices in the Center for Devices and Radiological Health states that “this authorization helps us accomplish our priority to advance health equity through the development of safe and effective products that meet the needs of diverse populations.”
Biosimilar refresher
Biosimilars are FDA-approved products that do not have a clinically meaningful difference from the originally approved biologic.
The reference product refers to the biologic that was originally approved by FDA. Interchangeable products are biosimilar products that meet additional FDA requirements and may be substituted at the pharmacy in a similar way as with a generic drug without consulting the prescriber.
For more information about biologics, biosimilars, and interchangeable products, see our practice resource Biologics and Biosimilar Drug Products: Pharmacist Guide to Patients’ Frequently Asked Questions or take our Show You Know quiz about biosimilars on the APhA website.
Jardiance now approved for patients with heart failure
Jardiance (empagliflozin, Boehringer Ingelheim) was originally approved in 2014 as an add-on therapy for glycemic control for patients with type 2 diabetes. In February 2022, it gained its most recent approval to be used to reduce the risk of cardiovascular death and hospitalization in adults with heart failure. Previously, this indication was limited to heart failure patients with a reduced ejection fraction. The initial recommended dose of 10 mg Jardiance by mouth once daily in the morning remains the same.