Updates from FDA
APhA Staff
New Formulations
SIPONIMOD
(Mayzent—Novartis Pharmaceuticals)
Drug class: Sphingosine 1-phosphate (S1P) receptor modulator.
Indication: Mayzent is indicated for patients who have relapsing forms of multiple sclerosis (MS).
Recommended dosage and administration: Mayzent is taken once daily by mouth. For most individuals, the daily maintenance dose is 2 mg. For patients who have a CYP2C9 *1/*3 or CYP2C9 *2/*3 genotype, the maintenance dose is decreased to 1 mg once daily.
Prior to initiating therapy, all patients must undergo screening to assess CYP2C9 genotype, have a complete blood count, an ophthalmic evaluation, a cardiac evaluation, a full review of vaccination status, and liver function tests.
The new labeling has been updated to include specifics regarding the CYP2C9 genotype and the impact it has on the metabolism of siponimod. Patients with specific genotypes could contraindicate use or require a dose adjustment. For example, use is contraindicated in patients who are homozygous for CYP2C9*3. Updated labeling also includes new vaccine recommendations as well as drug interactions.
Common adverse effects: Headache, hypertension, and elevated liver transaminases.
Warnings and precautions: Increased risk of infections, macular edema, transient decrease in heart rate, decline in pulmonary function, cutaneous malignancies, increased blood pressure, and fetal risk.
New Patient Population
METHOTREXATE INJECTION
(Methotrexate Injection—Accord Healthcare)
Drug class: Folate analog metabolic inhibitor.
Indication: Methotrexate injection is indicated for adult and pediatric patients with acute lymphoblastic leukemia, non-Hodgkin lymphoma, and osteosarcoma. In March 2022, it gained the additional patient population of pediatric patients for use in non-Hodgkin lymphoma. When being used for acute lymphoblastic leukemia and osteosarcoma, it should be part of a combination chemotherapy regimen. Methotrexate injection is NOT indicated for non-oncology diseases.
Recommended dosage and administration: Methotrexate injection should only be used intravenously. Recommended dosage is dependent on the indication. See full prescribing information for indication-specific dosing.
Common adverse effects: Ulcerative stomatitis, leukopenia (low white-blood cell count), nausea, abdominal pain.
Black box warning: Increased risk of embryo-fetal toxicity; all patients of reproductive age should be counseled on using effective contraception during and after treatment. Increased risk of serious adverse reactions—patients should be monitored for nervous system, kidney, liver, bone marrow, gastrointestinal tract, lung, and skin abnormalities and medication should be discontinued, if necessary. If patient has had a hypersensitivity reaction to methotrexate, its use is contraindicated.
Additional warnings and precautions: Increased risk of serious infections, secondary malignancies, tumor lysis syndrome, and infertility. Methotrexate affects the immune system; immunizations that are given during methotrexate therapy may be ineffective and live vaccines are not recommended.
New Dosage Form
ABACAVIR/DOLUTEGRAVIR/ LAMIVUDINE TABLETS FOR ORAL SUSPENSION
(Triumeq PD—ViiV Healthcare)
Drug class: Abacavir and lamivudine are nucleoside analogue reverse transcriptase inhibitors. Dolutegravir is an integrase strand transfer inhibitor (INSTI).
Indication: Triumeq PD is indicated for the treatment of adult and pediatric patients who have HIV-1 infections and weigh at least 10 kg. It should not be used in patients who have resistance-associated integrase substitutions or are clinically suspected to have INSTI resistance.
Recommended dosage and administration: Triumeq PD is a newly approved dosage form of the previously approved Triumeq. It is recommended that pediatric patients who weigh between 10 kg and 25 kg use the Triumeq PD dosage form and that all patients who weigh 25 kg or greater take the original Triumeq formulation. Triumeq PD tablets for oral suspension contain 60 mg abacavir, 5 mg dolutegravir, and 30 mg of lamivudine. For patients who weigh 10 kg to less than 14 kg, the recommended dose is 4 tablets once daily. For patients who weigh 14 kg to less than 20 kg, the recommended dose is 5 tablets once daily. For patients who weigh 20 kg to less than 25 kg, the recommended dose is 6 tablets once daily. Triumeq PD tablets for oral suspension should be dispersed in 20 mL of drinking water in the cup supplied by the manufacturer. The suspension should be swirled until no lumps remain and should be administered once the tablets have been fully dispersed and within 30 minutes of mixing. Prior to starting Triumeq PD therapy, patients should be screened for the HLA-B*5701 allele as well as hepatitis B virus (HBV) infection.
Common adverse effects: Insomnia, headache, fatigue.
Black box warning: Risk of fatal hypersensitivity reactions, particularly in patients who carry the HLA-B*5701 allele, use of Triumeq PD is contraindicated in patients who carry the HLA-B*5701 allele. Triumeq PD should never be started or reinitiated in patients who have had a previous hypersensitivity reaction to any abacavir-containing medication. All patients should be tested for HBV infection prior to therapy initiation because there is an increased risk of emergence of lamivudine-resistant HBV.
Additional warnings and precautions: Products containing dolutegravir increase risk of hepatoxicity, patients should be monitored for hepatotoxicity while using Triumeq PD. There is also a risk of lactic acidosis and severe hepatomegaly with steatosis. Patients who have the potential to get pregnant should receive a pregnancy test prior to therapy initiation and should be counseled on proper contraception due to the risk of embryo-fetal toxicity. It is also important to note that Triumeq tablets and Triumeq PD tablets for oral suspension are not interchangeable.
DONEPEZIL TRANSDERMAL SYSTEM
(Adlarity—Corium Inc.)
Drug class: mTOR inhibitor immunosuppressant.
Indication: Hyftor is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients who are at least 6 years old.
Recommended dosage and administration: Hyftor is 0.2% sirolimus topical gel that is applied topically to the affected area twice daily. For patients aged 6 to 11 years, the maximum daily dosage is 600 mg (or 2 cm). For patients who are 12 years and older, the maximum daily dosage is 800 mg (or 2.5 cm). Hyftor should be stored in the refrigerator and is for topical use only. If patients do not have improvement after 12 weeks of treatment, treatment discontinuation should be considered.
Common adverse effects: Dry skin, application site irritation, pruritis, acne, acneiform dermatitis, ocular hyperemia, skin hemorrhage, and skin irritation.
Warnings and precautions: Increased risk of hypersensitivity reaction, serious infection, malignancy, hyperlipidemia, interstitial lung disease, embryo-fetal toxicity, and male infertility. (Note that all of these have been observed with oral sirolimus formulations and should be monitored with topical sirolimus application.)
DONEPEZIL TRANSDERMAL SYSTEM
(Adlarity—Corium Inc.)
Drug class: Acetylcholinesterase inhibitor.
Indication: Adlarity is indicated for the treatment of mild, moderate, and severe dementia caused by Alzheimer disease.
Recommended dosage and administration: Adlarity will be available as 5 mg/day and 10 mg/day transdermal patches and should be applied once weekly. The initial dose of Adlarity is 5 mg/day and can be increased to 10 mg/day after 4 to 6 weeks of treatment with the 5 mg/day dose. Patients who have been taking donepezil 5 mg orally for at least 4 to 6 weeks can start on either the 5 mg/day patch or the 10 mg/day patch. Adlarity transdermal patches should be applied to clean, dry skin and left on for 7 days. Patients do not need to take the patch off prior to bathing/showering, swimming, or being in the sun, but saunas and hot tubs should be avoided. If a patch falls off before 7 days is up, a new patch should be applied. Additionally, the patches should be stored in the refrigerator. Adlarity patches should be removed from the refrigerator and brought to room temperature prior to application. Once the patch has been removed from the refrigerator, it must be applied within 24 hours.
As with other transdermal patches, application site should be rotated and the patches should not be applied to broken or irritated skin.
Common adverse effects: Nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia.
Warnings and precautions: Cholinesterase inhibitors such as Adlarity may increase or exaggerate muscle relaxation during anesthesia and have vagotonic effects that lead to an increased risk of bradycardia or heart block. Additionally, cholinesterase inhibitors should be used with caution in patients who have asthma or COPD. Cholinomimetics such as Adlarity may also increase the risk of bladder outflow obstructions and have the potential to cause generalized convulsions. ■