Updates from FDA
New drugs
FRUQUINTINIB
(Fruzaqla—Takeda Pharmaceuticals)
Drug class: Fruzaqla is a kinase inhibitor.
Indication: Fruzaqla is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine, oxaliplatin, and irinotecan based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.
Recommended dosage and administration: The recommended dose of Fruzaqla is 5 mg orally once daily with or without food for the first 21 days of each 28-day cycle.
Common adverse effects: The most common adverse reactions are hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia.
Warnings and precautions: Control BP prior to treatment and monitor during treatment. Manage with antihypertensive medications and adjustment of the dose of Fruzaqla, if necessary. Withhold, reduce dosage, or permanently discontinue Fruzaqla based on severity of hypertension. Closely monitor patients who are at risk for bleeding, as hemorrhagic events may occur. Withhold, reduce dosage, or permanently discontinue Fruzaqla based on severity and persistence of hemorrhage. Monitor for infection during treatment and withhold Fruzaqla during active infections. Do not start Fruzaqla in patients with active infections. Periodically monitor for GI perforation. Permanently discontinue Fruzaqla in patients who develop GI perforation or fistula. Monitor liver laboratory tests prior to the start of Fruzaqla and periodically during treatment as hepatotoxicity can occur. Withhold, dose reduce, or permanently discontinue based on severity. Monitor urine protein. Discontinue Fruzaqla for nephrotic syndrome. Palmar-plantar erythrodysesthesia may occur. Withhold Fruzaqla based on severity. Immediately discontinue Fruzaqla if posterior reversible encephalopathy syndrome is suspected and confirmed via MRI. Fruzaqla can cause impaired wound healing. Withhold for 2 weeks before major surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Fruzaqla after resolution of wound-healing complications has not been established. Initiation of Fruzaqla in patients with a recent history of thromboembolic events should be carefully considered. Discontinue Fruzaqla in patients who develop arterial thromboembolism. Fruzaqla contains FD&C Yellow No. 5 (tartrazine) and No. 6 (sunset yellow FCF) as color additives, which may cause allergic reactions, including bronchial asthma, in certain susceptible patients. Fetal harm may occur with use of Fruzaqla in pregnancy. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception. Advise patients not to breastfeed. Avoid concomitant use with strong or moderate CYP3A inducers.
REPOTRECTINIB
(Augtyro—Bristol Myers Squibb)
Drug class: Augtyro is a kinase inhibitor.
Indication: Augtyro is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).
Recommended dosage and administration: Select patients for the treatment of locally advanced or metastatic NSCLC based on the presence of ROS1 rearrangements in tumor specimens. The recommended dosage is 160 mg orally once daily for 14 days, then increase to 160 mg twice daily with or without food.
Common adverse effects: The most common adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness.
Warnings and precautions: Augtyro can cause CNS adverse reactions including dizziness, ataxia, and cognitive impairment. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue Augtyro based on severity. Monitor patients for new or worsening pulmonary symptoms indicative of interstitial lung disease or pneumonitis. Immediately withhold in patients with suspected interstitial lung disease or pneumonitis and permanently discontinue if diagnosis is confirmed. Monitor liver function tests every 2 weeks during the first month of treatment, and as clinically indicated thereafter, as hepatotoxicity may occur. Based on severity, withhold and then resume at the same or a reduced dose, or permanently discontinue. Monitor serum creatine phosphokinase (CPK) levels during treatment in patients reporting unexplained muscle pain, tenderness, or weakness. Based on severity of myalgia with CPK elevation, withhold and resume Augtyro at same or reduced dose upon improvement. Monitor serum uric acid levels prior to initiating and periodically during treatment as hyperuricemia can occur. Initiate treatment with urate-lowering medications as clinically indicated. Withhold and resume at the same or a reduced dose, or permanently discontinue based on severity. Promptly evaluate patients with signs or symptoms of skeletal fractures such as pain, changes in mobility, or deformity. Augtyro can cause embryo-fetal toxicity. Advise patients of reproductive potential of the potential risk to a fetus and to use an effective nonhormonal method of contraception. Advise patients not to breastfeed. Avoid concomitant use with strong and moderate CYP3A inhbitors, P-gp inhibitors, strong and moderate CYP3A inducers, hormonal contraceptives, and certain CYP3A substrates where minimal concentration changes can cause reduced efficacy.
CAPIVASERTIB
(Truqap—Astrazeneca)
Drug class: Truqap is a kinase inhibitor.
Indication: Truqap is indicated in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)–positive, human
epidermal growth factor receptor 2 (HER2)–negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations as detected by an FDA-approved test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.
Recommended dosage and administration: Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with Truqap based on the presence of one or more of the following genetic alterations in tumor tissue: PIK3CA/AKT1/PTEN. The recommended dosage is 400 mg orally twice daily with or without food for 4 days followed by 3 days off.
Common adverse effects: The most common adverse reactions are diarrhea, cutaneous adverse reactions, increased random glucose, decreased lymphocytes, decreased hemoglobin, increased fasting glucose, nausea, fatigue, decreased leukocytes, increased triglycerides, decreased neutrophils, increased creatinine, vomiting and stomatitis.
Warnings and precautions: Truqap is contraindicated in severe hypersensitivity to Truqap or any of its components. Hyperglycemia can occur. Evaluate blood glucose levels prior to starting and at regular intervals during treatment. Withhold, reduce dose, or permanently discontinue Truqap based on severity. Truqap caused diarrhea in most patients during clinical studies. Advise patients to increase oral fluids, start antidiarrheal treatment, and consult with a health care provider if diarrhea occurs while taking Truqap. Withhold, reduce dose, or permanently discontinue Truqap based on severity. Monitor for signs and symptoms of cutaneous adverse reactions. Withhold, reduce dosage of, or permanently discontinue Truqap based on severity. Truqap can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Advise patients not to breastfeed during treatment. Avoid concomitant use of Truqap with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce the Truqap dose. Reduce Truqap dose if used concomitantly with moderate CYP3A inhibitors. Avoid concomitant use with strong and moderate CYP3A inducers.
NIROGACESTAT
(Ogsiveo—Springworks Therapeutics)
Drug class: Ogsiveo is a gamma secretase inhibitor.
Indication: Ogsiveo is indicated for adult patients with progressing desmoid tumors who require systemic treatment.
Recommended dosage and administration: The recommended dosage of Ogsiveo is 150 mg orally twice daily until disease progression or unacceptable toxicity.
Common adverse effects: The most common adverse reactions are diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, dyspnea, decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium.
Warnings and precautions: Severe diarrhea can occur. Monitor and dose modify for grade 3–4 diarrhea. Female reproductive function and fertility may be impaired. Advise patients of the potential risk prior to treatment and monitor routinely.
Elevated AST and ALT can occur. Monitor AST and ALT regularly and modify dose as recommended. Perform dermatologic examination prior to initiation of Ogsiveo and routinely during treatment as nonmelanoma skin cancers may occur. Monitor phosphate and potassium regularly and modify dose accordingly. Ogsiveo can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. Advise patients not to breastfeed. Avoid concomitant use with strong or moderate CYP3A inhibitors and inducers. Avoid concomitant use with PPIs and H2-receptor antagonists. If concomitant use cannot be avoided, Ogsiveo administration can be staggered with antacids.
TAUROLIDINE AND HEPARIN
(Defencath—CorMedic Inc)
Drug class: Taurolidine is a thiadiazinane antimicrobial and heparin is an anticoagulant.
Indication: Defencath is indicated to reduce the incidence of catheter-related bloodstream infections in adult patients with kidney failure receiving chronic hemodialysis through a central venous catheter (CVC). The safety and effectiveness of Defencath have not been established for use in other populations.
Recommended dosage and admin-istration: Defencath catheter lock solution is for instillation into CVCs only and is not intended for systemic administration. Do not use Defencath as a catheter flush product. Withdraw a sufficient volume of Defencath catheter lock solution from the vial using a sterile needle and syringe to fill the catheter lumens. Use 3 mL or 5 mL single-dose vials to instill Defencath into each catheter lumen at the conclusion of each hemodialysis session. Defencath must be aspirated from the catheter and discarded prior to the initiation of the next hemodialysis session. Discard any unused portion of Defencath remaining in the vial.
Common adverse effects: The most common adverse reactions are hemodialysis catheter malfunction, hemorrhage/bleeding, nausea, vomiting, dizziness, musculoskeletal chest pain, and thrombocytopenia.
Warnings and precautions: Defencath is contraindicated in known heparin-induced thrombocytopenia and known hypersensitivity to taurolidine, heparin, the citrate excipient, or pork products. If heparin-induced thrombocytopenia occurs, discontinue Defencath and institute appropriate supportive measures. If a hypersensitivity reaction occurs, discontinue Defencath and institute appropriate supportive measures. ■