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New FDA Drug Approvals - April 2023


bexagliflozin

Brenzavvy

Pharmaceutical company: TheracosBio

Pharmacologic classification:Sodium-glucose cotransporter 2 (SGLT2) inhibitor

Therapeutic classification:Antidiabetic

AVAILABLE FORMS

Tablets: 20 mg

INDICATIONS AND DOSAGES

As adjunct to diet and exercise to improve glycemic control in type 2 diabetes

Adults: 20 mg PO once daily in the morning.

CONTRAINDICATIONS AND CAUTIONS

  • Contraindicated in patients hypersensitive to this drug or any of its components and in patients on dialysis.
  • This drug isn’t recommended in patients with eGFR less than 30 mL/min/1.73 m2 or type 1 diabetes mellitus. This drug has not been studied in severe hepatic impairment and isn’t recommended for use in this population.
  • This drug may increase the risk of ketoacidosis. Use cautiously in patients with pancreatic insulin deficiency, caloric restriction, and alcohol use.
  • Use cautiously in patients predisposed to need for amputation, including those with prior amputation, peripheral vascular disease, neuropathy, or diabetic foot ulcers. This drug may increase the risk of lower limb amputation due to infection, gangrene, ischemia, or osteomyelitis.
  • This drug may cause a decrease in intravascular volume and cause symptomatic hypotension or acute transient changes in creatinine. Older adults, those with impaired kidney function (eGFR less than 60 mL/min/1.73 m2), low systolic blood pressure, or taking loop diuretics may be at increased risk. Acute kidney injury, some requiring hospitalization and dialysis, has been reported in patients receiving SGLT2 inhibitors.
  • SGLT2 inhibitors (including bexagliflozin) may increase the risk of UTI, including urosepsis and pyelonephritis.
  • Necrotizing fasciitis of the perineum (Fournier’s gangrene), a rare, serious, life-threatening necrotizing infection requiring urgent surgical intervention, has been reported in patients receiving SGLT2 inhibitors.
  • This drug may increase the risk of genital mycotic infection. Patients with a history of genital mycotic infection or who are uncircumcised are at greater risk.
  • The safety and effectiveness in children haven’t been established.
  • Dialyzable drug: Unknown.

PREGNANCY-LACTATION-REPRODUCTION

  • There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.
  • Use of this drug isn’t recommended during the second and third trimesters of pregnancy based on animal data.
  • There is no information regarding the presence of this drug in human milk, effects on the breastfed infant or on milk production. This drug may increase the risk of adverse reactions in a breastfed infant. Use isn’t recommended while breastfeeding.

INTERACTIONS

Drug-drug. Insulin and insulin secretagogues (glimepiride, glyburide, sulfonylurea agents): Increases the risk of hypoglycemia. When used together, decrease the insulin or insulin secretagogue dose as needed.

Lithium: May decrease lithium level. Monitor lithium level more frequently upon initiation and discontinuation of bexagliflozin.

UGT enzyme inducers (rifampicin, phenobarbital): May decrease bexagliflozin level and its efficacy. Consider adding another antihyperglycemic agent if necessary.

ADVERSE REACTIONS

GI: thirst.

GU: increased urination,genital mycotic infection, UTI, vaginal pruritus, increased serum creatinine, decreased eGFR.

Metabolic: volume depletion, hypoglycemia.

Musculoskeletal: lower limb amputation.

Skin: rash.

Other: sepsis.

Reactions in bold italics are life-threatening.

Released: April 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer


elacestrant

Orserdu

Pharmaceutical company: Stemline Therapeutics, Inc.

Pharmacologic classification:Estrogen receptor antagonist

Therapeutic classification:Antineoplastic

AVAILABLE FORMS

Tablets: 86 mg, 345 mg

INDICATIONS AND DOSAGES

Estrogen receptor-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Postmenopausal females and adult males: 345 mg PO once daily until disease progression or unacceptable toxicity.

Adjust-a-dose: Refer to the manufacturer’s instructions for toxicity-related dosage adjustments. Reduce the dose to 258 mg once daily for patients with moderate hepatic impairment (Child-Pugh B). Avoid use in patients with severe hepatic impairment (Child-Pugh C). Avoid concomitant use with strong or moderate CYP3A4 inducers and inhibitors.

CONTRAINDICATIONS AND CAUTIONS

  • Avoid use in severe hepatic impairment (Child-Pugh C).
  • Safety and effectiveness have not been established in children.
  • Dialyzable drug: Unknown.

PREGNANCY-LACTATION-REPRODUCTION

  • Based on findings in animals and its mechanism of action, this drug can cause fetal harm.
  • Females of reproductive potential and males with female partners of reproductive potential should use effective contraception during treatment and for 1 week after the last dose.
  • There are no data on the presence of this drug in human milk, its effects on milk production, or the breastfed child. Patients shouldn’t breastfeed during treatment and for 1 week after the last dose.
  • Based on findings from animal studies, this drug may impair fertility.

INTERACTIONS

Drug-drug. BCRP substrates (rosuvastatin), p-glycoprotein substrates (digoxin): May increase the substrate level and the risk of adverse reactions. Reduce the dosage of the substrate per its product labeling.

Strong and moderate CYP3A4 inducers (rifampin, efavirenz): May decrease elacestrant level and its effectiveness. Avoid use together.

Strong and moderate CYP3A4 inhibitors (itraconazole, fluconazole): May increase elacestrant level and the risk of adverse reactions. Avoid use together.

ADVERSE REACTIONS

CNS: fatigue, headache, insomnia, dizziness.

EENT: stomatitis.

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, decreased appetite, gastroesophageal reflux disease.

Hepatic: abnormal liver function tests.

Musculoskeletal: musculoskeletal pain.

Metabolic: increased cholesterol, increased triglycerides, hyponatremia, increased creatinine.

Hematologic: decreased hemoglobin.

Respiratory: cough, dyspnea.

Skin: rash.

Other: hot flush.

Reactions in bold italics are life-threatening.

Released: April 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer


lenacapavir

Sunlenca

Pharmaceutical company: Gilead Sciences, Inc.

Pharmacologic classification:Capsid inhibitor

Therapeutic classification:Antiretroviral

AVAILABLE FORMS

Injection: 463.5 mg/1.5 mL single-dose vial

Tablets: 300 mg

INDICATIONS AND DOSAGES

HIV-1 infection in combination with other antiretrovirals, in heavily treatment-experienced patients with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations

Initiation option 1

Adults: 927 mg subcut and 600 mg PO once on day 1. Then 600 mg PO once on day 2. Then begin maintenance regimen.

Initiation option 2

Adults: 600 mg PO once daily on days 1 and 2. Then 300 mg PO once on day 8.

Then 927 mg subcut once on day 15. Then begin maintenance regimen.

Maintenance regimen

Adults: 927 mg subcut every 6 months (26 weeks) from the date of last injection. May give within 2 weeks before or after the 6 month target date.

CONTRAINDICATIONS AND CAUTIONS

  • Use cautiously in patients with severe hepatic impairment or kidney failure with replacement therapy.
  • Immune reconstitution syndrome may occur in patients treated with combination antiretroviral therapy. Autoimmune disorders (Grave disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) may occur with immune reconstitution syndrome.
  • Nonadherence to the medication regimen could lead to loss of virologic response and development of resistance.
  • Safety and effectiveness in children have not been established.
  • Dialyzable drug: Unlikely.

PREGNANCY-LACTATION-REPRODUCTION

  • Insufficient data on use in pregnancy is available to determine risk.
  • Health care providers are encouraged to register patients in the Antiretroviral Pregnancy Registry at 1-800-258- 4263.
  • The Centers for Disease Control and Prevention recommends those with HIV-1 infection not to breastfeed. It’s unknown whether this drug is present in breast milk.

INTERACTIONS

Alert:Lenacapavir has the potential for significant interactions with many drugs. Consult a drug interactions resource for additional information.

Drug-drug. Alert: Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin): May decrease lenacapavir levels and increase risk for resistance. Use with carbamazepine or phenytoin is contraindicated. Use with oxcarbazepine or phenobarbital isn’t recommended. Consider use of alternative anticonvulsants.

Alert: Antimycobacterials (rifabutin, rifampin, rifapentine): May decrease lenacapavir levels and increase risk for resistance. Use with rifampin is contraindicated. Use with rifabutin or rifapentine isn’t recommended.

Antiretroviral agents (atazanavircobicistat, atazanavirritonavir, efavirenz, nevirapine, tipranavirritonavir): May alter lenacapavir level.Use of efavirenz, nevirapine, or tipranavir–ritonavir may decrease lenacapavir levels and increase risk for resistance. Use with atazanavir–cobicistat or atazanavir–ritonavir may increase lenacapavir levels. Concomitant administration with any of these agents isn’t recommended.

Combined P-glycoprotein (P-gp), UGT1A1, and strong CYP3A inhibitors (cobicistat, atazanavir): May significantly increase lenacapavir levels. Use together isn’t recommended.

Corticosteroids, systemic (dexamethasone, hydrocortisone/cortisone): may increase systemic corticosteroid levels and increase risk of Cushing syndrome and adrenal suppression. Initiate with lowest starting dose and titrate carefully while monitoring for safety.

CYP3A substrates: Lenacapavir may increase the exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last subcut dose of lenacapavir, increasing the risk of adverse reactions. See prescribing information of sensitive CYP3A substrate for dosing with moderate inhibitors of CYP3A.

Digoxin: May increase digoxin levels. Use cautiously and monitor digoxin therapeutic concentration.

Direct oral anticoagulants (rivaroxaban, dabigatran, edoxaban): May increase direct oral anticoagulants. Refer to the anticoagulant prescribing information for administration with combined moderate CYP3A and P-gp inhibitors.

Ergot derivatives (dihydroergotamine, ergotamine, methylergonovine): May increase levels of ergot derivatives. Use together isn’t recommended.

HMG-CoA reductase inhibitors (lovastatin, simvastatin): May increase levels of these statins. Initiate statins at lowest starting dose and titrate carefully while monitoring for safety.

Midazolam (oral), triazolam: May increase levels of these drugs. Use cautiously together.

Moderate CYP3A inducers (efavirenz): May significantly decrease lenacapavir levels and increase risk of resistance to lenacapavir. Use together isn’t recommended.

Naloxegol: May increase naloxegol level. Avoid use together; if unavoidable, decrease dosage of naloxegol and monitor for adverse reactions.

Narcotic analgesic for treatment of opioid dependence (buprenorphine, methadone): Effects of coadministration are unknown. Carefully titrate the dose of buprenorphine or methadone to desired effect; use the lowest possible initial or maintenance dose. In patients currently taking buprenorphine or methadone, a dose adjustment may be needed when lenacapavir is started. Monitor clinical signs and symptoms.

Narcotic analgesics metabolized by CYP3A (fentanyl, oxycodone): May increase levels of these narcotics. Monitor closely for effects and adverse reactions.

PDE-5 inhibitors (sildenafil, tadalafil, vardenafil): When used for pulmonary arterial hypertension, use with lenacapavir and tadalafil isn’t recommended. When used for erectile dysfunction, refer to the prescribing information of PDE5 inhibitors for dose recommendations.

Strong CYP3A inducers (rifampin): May significantly decrease lenacapavir levels and increase risk of resistance to lenacapavir. Use together is contraindicated.

Tramadol: May increase tramadol levels. Consider a decrease in tramadol dose.

Drug-herb. St. John’s wort: May decrease lenacapavir levels. Use together is contraindicated.

ADVERSE REACTIONS

GI: nausea.

GU: elevated creatinine levels, glycosuria, proteinuria.

Hepatic: increased AST, ALT, and direct bilirubin levels.

Metabolic: hyperglycemia.

Skin: injection site reactions (swelling, pain, discomfort, erythema, nodule, induration, pruritus, extravasation, mass, hematoma, edema, ulcer).

Reactions in bold italics are life-threatening.

Released: April 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer


pirtobrutinib

Jaypirca

Pharmaceutical company: Eli Lilly and Company

Pharmacologic classification:Kinase inhibitor

Therapeutic classification:Antineoplastic

AVAILABLE FORMS

Tablets: 50 mg, 100 mg

INDICATIONS AND DOSAGES

Relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a BTK inhibitor

Adults: 200 mg PO once daily until disease progression or unacceptable toxicity occurs.

Adjust-a-dose:Refer to the manufacturer’s instructions for toxicity-related dosage adjustments. If severely reduced GFR (eGFR 15 to 29 mL/min) and the current dose is 200 mg once daily, reduce the dose to 100 mg once daily; otherwise reduce the dose by 50 mg. If the current dosage is 50 mg once daily, discontinue the drug. If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the pirtobrutinib dose by 50 mg. If the current dosage is 50 mg once daily, interrupt pirtobrutinib treatment for the duration of strong CYP3A inhibitor use. After discontinuation of a strong CYP3A inhibitor for 5 half-lives, resume the pirtobrutinib dose taken prior to initiating the inhibitor. If concomitant use with a moderate CYP3A inducer is unavoidable and the current dosage of pirtobrutinib is 200 mg once daily, increase the dose to 300 mg. If the current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg.

CONTRAINDICATIONS AND CAUTIONS

  • Fatal and serious bacterial, viral, fungal, and opportunistic infections have occurred. Consider prophylaxis (vaccinations, antimicrobials) in patients at increased risk for infections.
  • Fatal and serious hemorrhage has occurred. Consider withholding the drug for 3 to 7 days pre- and post-surgery depending upon the type of surgery and risk of bleeding.
  • Use cautiously in patients with cardiac risk factors (hypertension, previous arrhythmias); this drug may increase the risk of development of atrial fibrillation or flutter.
  • Use cautiously in older adults.
  • Safety and effectiveness of this drug have not been established in children.
  • Dialyzable drug: Unlikely.

PREGNANCY-LACTATION-REPRODUCTION

  • Based on animal studies, this drug can cause fetal harm.
  • Females of reproductive potential should use effective contraception during treatment and for 1 week after the last dose.
  • There are no data on the presence of this drug in human milk or the effects on the breastfed child or milk production. Patients shouldn’t breastfeed during treatment and for 1 week after the last dose.

INTERACTIONS

Drug-drug. Antithrombotic agents (heparin, warfarin, apixaban): May increase risk of bleeding. Use cautiously together.

CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP3A (midazolam), P-glycoprotein (digoxin), or BCRP (rosuvastatin) substrates: May increase level of sensitive substrates and the risk of substrate-related adverse reactions. Follow recommendations for sensitive substrates provided in their product labeling.

Strong CYP3A inhibitors (itraconazole): May increase pirtobrutinib level and risk of adverse reactions. Avoid use together. If unavoidable, reduce the pirtobrutinib dose.

Strong or moderate CYP3A inducers (rifampin, bosentan, efavirenz): May decrease pirtobrutinib level and efficacy. Avoid use together. If concomitant use is unavoidable, increase the dose of pirtobrutinib.

Drug-lifestyle. Sunlight: May increase risk of new skin cancer or other cancers. Use sun protection.

ADVERSE REACTIONS

CNS: fatigue, fever, peripheral neuropathy, dizziness.

CV: edema, hemorrhage, atrial fibrillation, atrial flutter.

GI: diarrhea, constipation, abdominal pain, nausea.

GU: increased creatinine level,

Hematologic: bruising, anemia, neutropenia, thrombocytopenia, lymphocytopenia, transient lymphocytosis.

Hepatic: increased transaminases, increased alkaline phosphatase.

Metabolic: hypocalcemia, hypokalemia, hyponatremia, hyperkalemia, increased lipase.

Musculoskeletal: musculoskeletal pain, arthritis, arthralgia.

Respiratory: dyspnea, cough, pneumonia, upper respiratory infection, pleural effusion.

Skin: rash.

Other: sepsis, infection, second primary malignancy.

Reactions in bold italics are life-threatening.

Released: April 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer

 

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