Updates from FDA
New Approval
SUZETRIGINE
(Journavx—Vertex Pharmaceuticals)
Drug class: Journavx is a sodium channel blocker.
Indication: Journavx is indicated for the treatment of moderate to severe acute pain in adults.
Recommended dosage and administration: Swallow Journavx tablets whole and do not crush or chew. The recommended starting dose is 100 mg orally and should be taken on an empty stomach,at least 1 hour before or 2 hours after food. Clear liquids such as water, apple juice, vegetable broth, tea, and black coffee may be consumed during this time. Starting 12 hours after the starting dose, take 50 mg of Journavx orally every 12 hours. Take these doses with or without food. Use Journavx for the shortest duration, consistent with individual patient treatment goals. Use of Journavx for the treatment of acute pain has not been studied beyond 14 days.
Common adverse effects: The most common adverse reactions are pruritus, muscle spasms, increased creatine phosphokinase, and rash.
Warnings and precautions: Concomitant use with strong CYP3A inhibitors is contraindicated. Reduce the Journavx dose when used concomitantly with moderate CYP3A inhibitors. Avoid food or drink containing grapefruit. Avoid Journavx with strong or moderate CYP3A inducers. If used concomitantly with sensitive CYP3A substrates or CYP3A substrates where minimal concentration changes may lead to loss of efficacy, dosage modifications may be necessary. Avoid use in patients with severe hepatic impairment. Use in patients with moderate hepatic impairment may increase the risk of adverse reactions. The recommended dosage is lower in patients with moderate hepatic impairment than those with normal hepatic function. Patients treated with Journavx and using hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should use an additional nonhormonal contraceptive method or an alternative hormonal contraceptive during concomitant use and for 28 days after Journavx discontinuation.
TREOSULFAN
(Grafapex—Medexus Pharma)
Drug class: Grafapex is an alkylating drug.
Indication: Grafapex is indicated for use in combination with fludarabine as a preparative regimen for allogenic hematopoietic stem cell transplantation in adult and pediatric patients 1 year of age and older with acute myeloid leukemia or myelodysplastic syndrome.
Recommended dosage and administration: The recommended dosage of Grafapex is 10 g/m2 body surface area per day as a 2-hour I.V. infusion, given on 3 consecutive days in conjunction with fludarabine before hematopoietic stem cell infusion.
Common adverse effects: The most common adverse reactions are musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, vomiting, increased GGT, increased bilirubin, increased ALT and AST, and increased creatinine.
Boxed warning: Grafapex causes severe and prolonged myelosuppression. Hematopoietic stem cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression. Monitor hematologic laboratory parameters.
Other warnings and precautions: Use of Grafapex is contraindicated in patients with a history of hypersensitivity to any component of the drug product. Monitor for signs of neurological adverse reactions and consider clonazepam prophylaxis in patients at higher risk for seizures. Keep skin clean and dry on days of Grafapex infusion and change occlusive dressings after infusion. Change diapers frequently during the 12 hours after each infusion of Grafapex. Injection site reactions and tissue necrosis may occur. If extravasation occurs, stop the infusion immediately and manage medically as required. There is an increased risk of a secondary malignancy with use of Grafapex. Avoid exceeding the recommended dosage as there is increased early morbidity and mortality at dosages higher than recommended. Monitor for adverse reactions if Grafapex is administered concomitantly with a CYP2C19 or CYP3A4 substrate where minimal concentration changes may lead to serious or life-threatening toxicities. Grafapex can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. Advise patients not to breastfeed during treatment.
New dosage forms
SITAGLIPTIN ORAL SOLUTION
(Brynovin—Azurity Pharmaceuticals)
Drug class: Brynovin is a dipeptidyl peptidase-4 inhibitor.
Indication: Bryovin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D. Brynovin is not recommended in patients with T1D. Brynovin has not been studied in patients with a history of pancreatitis.
Recommended dosage and administration: The recommended dose of Brynovin is 100 mg (4 mL) orally once daily. Brynovin can be taken with or without food. Dosage adjustment is recommended for patients with an eGFR less than 45 mL/min/1.73 m2. In patients with an eGFR greater than or equal to 30 mL/min/1.73 m2 to less than 45 mL/min/1.73 m2, the recommended dosage is 50 mg (2 mL) orally once daily. In patients with an eGFR of less than 30 mL/min/1.73 m2, the recommended dosage is 25 mg (1 mL) once daily.
Common adverse effects: The most common adverse reactions are upper respiratory tract infection, nasopharyngitis, and headache.
Warnings and precautions: Brynovin is contraindicated in patients with history of a serious hypersensitivity reaction to sitagliptin or any of the excipients in Brynovin, such as anaphylaxis or angioedema. There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue Brynovin. Consider the risks and benefits of Brynovin in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms of heart failure. Acute renal failure has been reported, sometimes requiring dialysis. Assessment of renal function is recommended prior to initiating Brynovin and periodically thereafter. There is an increased risk of hypoglycemia when Brynovin is used in combination with insulin or an insulin secretagogue. A lower dose of insulin or the insulin secretagogue may be required. Promptly stop Brynovin, assess for other potential causes, and institute appropriate monitoring and treatment if serious allergic and hypersensitivity reactions such as anaphylaxis, angioedema, and exfoliative skin conditions, including Stevens-Johnson syndrome, occur. Severe and disabling arthralgia has been reported in patients taking dipeptidyl peptidase-4 inhibitors. Consider Brynovin as a possible cause for severe joint pain and discontinue the drug if appropriate. Tell patients to report development of blisters or erosions while taking Brynovin. If bullous pemphigoid is suspected, discontinue the medication.
New indications
ACALABRUTINIB
(Calquence—Azurity Pharmaceuticals)
Drug class: Calquence is a kinase inhibitor.
Indication: Calquence is indicated in combination with bendamustine and rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation, for the treatment of adult patients with MCL who have received at least one prior therapy, and for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.
Recommended dosage and administration: The recommended dose of Calquence is 100 mg orally approximately every 12 hours. Swallow whole with water and with or without food. Do not break, open, or chew capsules. Manage toxicities using treatment interruption, dose reduction, or discontinuation. Avoid Calquence in patients with severe hepatic impairment.
Common adverse effects: The most common adverse reactions are diarrhea, upper respiratory tract infection, headache, musculoskeletal pain, lower respiratory tract infection, fatigue, decreased absolute neutrophil count, decreased absolute lymphocyte count, decreased platelets, and decreased hemoglobin.
Warnings and precautions: Monitor for signs and symptoms of infection and treat promptly. Monitor for bleeding and manage appropriately. Monitor complete blood counts regularly. Second primary malignancies have occurred, including skin cancers and other solid tumors. Advise patients to use sun protection. Monitor for symptoms of arrhythmias and manage. Monitor hepatic function throughout treatment. Avoid coadministration with strong CYP3A inhibitors or inducers. Dose adjustments may be recommended. Avoid coadministration with PPIs. Stagger dosing with H2-receptor antagonists and antacids. Calquence may cause fetal harm and dystocia. Advise patients not to breastfeed during treatment.
SOTORASIB
(Lumakras—Amgen)
Drug class: Lumakras is an inhibitor of the RAS GTPase family.
Indication: Lumakras is indicated as a single agent for KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy. Lumakras is also indicated in combination with panitumumab for the treatment of adult patients with KRAS G12C-mutated metastatic colorectal cancer, as determine by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Recommended dosage and administration: The recommended dose of Lumakras is 960 mg orally once daily. Swallow tablets whole with or without food.
Common adverse effects: The most common adverse reactions are diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, cough, rash, dry skin, stomatitis, decreased lymphyocytes, decreased hemoglobin, decreased calcium, decreased sodium, increased aspartate aminotransferase, increased alanine aminotransferase, increased alkaline phosphatase, increased urine protein, decreased magnesium, decreased potassium, and increased potassium.
Warnings and precautions: Monitor liver function tests every 3 weeks for the first 3 months of treatment then once monthly as clinically indicated. Consider administering systemic corticosteroids and withhold, reduce the dose, or permanently discontinue Lumakras if hepatotoxicity occurs. Monitor for new or worsening pulmonary symptoms as interstitial lung disease (ILD) or pneumonitis may occur. Immediately withhold Lumakras for suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. Avoid coadministration with PPIs and H2-receptor antagonists. If an acid-reducing agent cannot be avoided, administer Lumakras 4 hours before or 10 hours after a local antacid. Avoid coadministration with strong CYP3A4 inducers. Avoid coadministration with CYP3A substrates or P-gp substrates for which minimal concentration changes may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, adjust the substrate dosage as needed. ■