Updates from FDA
APhA Staff
New drugs
ACALABRUTINIB MALEATE
(Calquence—AstraZeneca)
Drug class: Acalabrutinib maleate is a kinase inhibitor.
Indication: Calquence is indicated for the treatment of adult patients with mantle cell lymphoma who have received at least one prior therapy or have chronic lymphocytic leukemia or small lymphocytic lymphoma.
Recommended dosage and administration: The recommended dose is 100 mg orally every 12 hours. The tablet should be swallowed whole with water and with no regard to food.
Common adverse effects: The most common adverse reactions in patients taking Calquence are anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain.
Warnings and precautions: Calquence should be avoided in patients with severe hepatic impairment. Avoid coadministration with strong CYP3A inhibitors. Reduce the dosage of Calquence if it is coadministered with moderate CYP3A inhibitors. Avoid coadministration with strong CYP3A inducers, but if coadministration is unavoidable increase the dosage of Calquence. Calquence should not be used during pregnancy as it may cause fetal harm and dystocia. Patients taking Calquence should be advised not to breastfeed. Monitor for signs and symptoms of infection, bleeding, and symptoms of arrhythmias. Blood counts should be monitored regularly. Secondary malignancies have occurred, including skin cancers and other solid tumors. Advise patients to use sun protection.
New indications
IBRUTINIB
(Imbruvica—Pharmacyclics)
Drug class: Ibrutinib is a kinase inhibitor.
Indication: Imbruvica is indicated for the treatment of adult patients with mantle cell lymphoma who have received at least one prior therapy, adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma with 17p deletion, adult patients with Waldenstrom macroglobulinemia, adult patients with marginal zone lymphoma who require systemic therapy and have received at least one prior anti-CD20–based therapy, and adult and pediatric patients age 1 year or older with chronic graft versus host disease after failure of one or more lines of systemic therapy.
Recommended dosage and administration: For treatment of marginal zone lymphoma and mantle cell lymphoma, the recommended dosage is 560 mg taken orally once daily. For treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma, the recommended dosage is 420 mg taken orally once daily. For treatment of chronic graft versus host disease in patients 12 years and older, the recommended dosage is 420 mg taken orally once daily. For treatment of chronic graft versus host disease in patients 1–12 years old, the recommended dosage is 240 mg/m2 taken orally once daily and should not to exceed a dose of 420 mg. Tablets or capsules should be taken orally with a glass of water.
Common adverse effects: The most common adverse reactions in patients with B-cell malignancies are thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, and bruising. The most common adverse reactions in adult or pediatric patients with chronic graft-versus-host disease are fatigue, anemia, bruising, diarrhea, thrombocytopenia, musculoskeletal pain, pyrexia, muscle spasms, stomatitis, hemorrhage, nausea, abdominal pain, pneumonia, and headache.
Warnings and precautions: Patients should be advised not to breastfeed while taking Imbruvica. Avoid use of Imbruvica in patients with severe hepatic impairment. In patients with mild or moderate hepatic impairment, reduce the dose of Imbruvica. If coadministered with CYP3A inhibitors, the Imbruvica dose should be modified. Avoid coadministration with strong CYP3A inducers. Monitor for bleeding, fever, infections, symptoms of arrhythmias and cardiac failure, and blood pressure elevation. Check complete blood counts monthly. Secondary malignancies have occurred in patients, including skin cancers and other carcinomas. Assess baseline risks for tumor lysis syndrome and treat appropriately. Imbruvica can cause fetal harm and females of reproductive potential should be advised of the potential risk to a fetus and to use effective contraception.
New formulations
MIDAZOLAM
(Midazolam—Rafa Laboratories)
Drug class: Midazolam is a benzodiazepine.
Indication: Midazolam injection is indicated for the treatment of status epilepticus in adults.
Recommended dosage and administration: The recommended dose is a single 10 mg dose, administered by intramuscular injection using the prefilled autoinjector. It should be injected into the mid-outer thigh.
Common adverse effects: The most common adverse reactions in patients with status epilepticus were upper airway obstruction, agitation, and pyrexia.
Black box warning: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and/or death. The use of midazolam exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and/or death.
If midazolam is used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal symptoms, which can be life-threatening.
Other warnings and precautions: Midazolam should not be used in patients who have previously shown hypersensitivity to midazolam. Serious cardiorespiratory adverse reactions have occurred after administration of midazolam. Agitation can occur. If administered concomitantly with central nervous system depressants, patients may be at an increased risk of hypoventilation, airway obstruction, desaturation, and/or apnea. Some patients have experienced impaired cognitive function after administration of midazolam, so the operation of hazardous machinery or a motor vehicle should be avoided until the drug’s effects have subsided. Patients with open-angle glaucoma may need to have their ophthalmologic status evaluated following treatment with midazolam injection. Midazolam injection is not recommended in patients with narrow-angle glaucoma. Use of midazolam during pregnancy can result in neonatal sedation or withdrawal.
KONVOMEP
(Omeprazole and sodium bicarbonate—Azurity Pharmaceuticals)
Drug class: Omeprazole is a proton pump inhibitor.
Indication: Konvomep is indicated in adults for treatment of active benign gastric ulcer and reduction of risk of upper GI bleeding in critically ill patients.
Recommended dosage and administration: Konvomep dosing is based on the omeprazole content. The recommended dosage for treatment of active benign gastric ulcer is 40 mg (20 mL) once daily for 4 to 8 weeks. The recommended dosage for reduction of risk of upper GI bleeding in critically ill patients is 40 mg initially followed by 40 mg 6–8 hours later and 40 mg once daily thereafter for 14 days.
Common adverse effects: The most common adverse reactions are headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence.
Warnings and precautions: Konvomep is contraindicated in patients with a known hypersensitivity to any components of the formulation or patients receiving products containing rilpivirine. Symptomatic response to Konvomep does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. Monitor for acute tubulointerstitial nephritis. Sodium content should be taken into consideration when treating patients on a sodium-restricted diet. Avoid in patients with Bartter syndrome, hypokalemia, hypocalcemia, and/or problems with acid-base balance. Therapy may be associated with an increased risk of
C. difficile–associated diarrhea. Long-term and multiple daily dose therapy may be associated with an increased risk for osteoporosis-related fractures. Discontinue therapy at the first signs or symptoms of severe cutaneous adverse reactions. Avoid concomitant use with clopidogrel, St. John’s wort, or rifampin. Daily long-term use may lead to malabsorption of cyanocobalamin and hypomagnesemia. Concomitant use of Konvomep with methotrexate may elevate or prolong serum concentrations of methotrexate or its metabolite, possible leading to toxicity. Monitor for fundic gland polyps.
New combination
AUVELITY
(Dextromethorphan hydrobromide and bupropion hydrochloride—Axsome Therapeutics)
Drug class: Dextromethorphan hydrobromide is an uncompetitive N-methyl D-aspartate receptor antagonist and sigma-1 receptor agonist. Bupropion hydrochloride is an aminoketone and CYP450 2d6 inhibitor.
Indication: Auvelity is indicated for the treatment of major depressive disorder in adults.
Recommended dosage and administration: Starting dosage is one tablet (45 mg dextromethorphan hydrobromide/105 mg bupropion hydrochloride) once daily in the morning.
After 3 days, increase to the maximum recommended dosage of one tablet twice daily, separated by at least 8 hours. Do not exceed 2 doses within the same day. Tablets should be swallowed whole. For patients with moderate renal impairment, the dose should be one tablet by mouth once daily in the morning. In patients who metabolize CYP2D6 poorly, the dose should be one tablet by mouth once daily in the morning.
Common adverse effects: The most common adverse reactions seen in patients taking Auvelity are dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.
Black box warning: There is an increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. All patients should be closely monitored for clinical worsening and emergence of suicidal thoughts and behaviors.
Other warnings and precautions: Treatment with Auvelity is contraindicated in patients with seizure disorder; a current or prior diagnosis of bulimia or anorexia nervosa; abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs; patients taking an MAOI or within 14 days of discontinuing an MAOI; or a known hypersensitivity to bupropion, dextromethorphan, or other components of Auvelity. Use of Auvelity is not recommended in breastfeeding patients. Use should be avoided in those with severe renal or hepatic impairment. Seizure risk is dose-related. Auvelity can increase blood pressure and cause hypertension. Patients should be screened for bipolar disorder as use of Auvelity can cause activation of mania or hypomania. Instruct patients to contact a health care provider if psychosis and other neuropsychiatric reactions occur. Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. Auvelity may cause dizziness. Patients should be monitored for serotonin syndrome. Pregnant patients should be advised of potential risk to a fetus. ■