adagrasib
Krazati
Pharmaceutical company: Mirati Therapeutics
Pharmacologic classification: KRAS inhibitor
Therapeutic classification: Antineoplastic
AVAILABLE FORMS
Tablets: 200 mg
INDICATIONS AND DOSAGES
KRAS G12C-mutated locally advanced or metastatic non–small-cell lung cancer in patients who have received at least one prior systemic therapy
Adults: 600 mg PO b.i.d. until disease progression or unacceptable toxicity.
Adjust-a-dose: Refer to the manufacturer’s instructions for toxicity-related dosage adjustments. First dose reduction for adverse reactions is to 400 mg PO b.i.d.; second dose reduction is to 600 mg PO daily. Permanently discontinue drug if patients can’t tolerate 600 mg per day.
CONTRAINDICATIONS AND CAUTIONS
- This drug may increase the risk of QTc interval prolongation and risk for tachyarrhythmias, torsades de pointes, and sudden death. Avoid use in patients with congenital QT syndrome.
- Use cautiously in patients with heart failure, bradyarrhythmias, electrolyte abnormalities, and patients unable to avoid taking medication known to prolong the Qt interval.
- Safety and effectiveness haven’t been established in children.
- Dialyzable drug: Unlikely.
PREGNANCY-LACTATION-REPRODUCTION
- There are no available data on the use of this drug during pregnancy.
- Because of the potential for adverse reactions in a breastfed child, patients shouldn’t breastfeed during treatment and for 1 week after the last dose.
- This drug may impair fertility.
INTERACTIONS
Drug-drug. Drugs that prolong QT interval (amiodarone, levofloxacin, fluoxetine, haloperidol, methadone): May prolong the QT interval. Avoid use together.
Sensitive CYP2C9 or CYP2D6 substrates or P-glycoprotein substrates (warfarin, dextromethorphan, digoxin): May increase substrate level. Avoid use together where minimal concentration changes may lead to serious adverse reactions.
Sensitive CYP3A4 substrates (midazolam): May increase CYP3A substrate level. Avoid use together.
Strong CYP3A4 inducers (rifampin): May reduce adagrasib level. Avoid use together.
Strong CYP3A4 inhibitors (itraconazole): May increase adagrasib level. Avoid concomitant use until adagrasib concentrations have reached steady state (after approximately 8 days).
Drug-herb. St. John’s wort: May reduce adagrasib concentrations. Avoid use together.
ADVERSE REACTIONS
CNS: fatigue, dizziness, fever, mental status changes.
CV: edema, QT prolongation, heart failure, hypotension, pulmonary embolism.
GI: diarrhea, nausea, vomiting, constipation, abdominal pain, decreased appetite, GI bleeding, GI obstruction.
GU: abnormal kidney function.
Hematologic: anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia.
Hepatic: hepatotoxicity, increased liver enzymes, decreased albumin.
Metabolic: hyponatremia, hypokalemia, increased lipase, increased amylase, hypomagnesemia, dehydration, decreased weight.
Musculoskeletal: musculoskeletal pain, muscular weakness.
Respiratory: dyspnea, cough, pneumonia, interstitial lung disease, interstitial pneumonitis, hypoxia, pleural effusion, respiratory failure, pulmonary hemorrhage.
Other: sepsis, sudden death.
Reactions in bold italics are life-threatening.
Released: March 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer
olutasidenib
Rezlidhia
Pharmaceutical company: Rigel Pharmaceuticals, Inc.
Pharmacologic classification: Isocitrate dehydrogenase-1 (IDH1) inhibitor
Therapeutic classification: Antineoplastic
AVAILABLE FORMS
Capsules: 150 mg
INDICATIONS AND DOSAGES
Relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase-1 mutation
Adults: 150 mg PO b.i.d. until disease progression or unacceptable toxicity. If there is no disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.
Adjust-a-dose: Refer to the manufacturer’s instruction for toxicity-related dosage adjustments.
CONTRAINDICATIONS AND CAUTIONS
- Black Box Warning: Differentiation syndrome, which can be fatal, can occur. If differentiation syndrome is suspected, withhold drug and initiate corticosteroids and hemodynamic monitoring until symptoms resolve.
- This drug may increase the risk of hepatotoxicity. Use cautiously in patients with mild or moderate hepatic impairment. Use in patients with severe hepatic impairment hasn’t been established.
- Safety and effectiveness in children haven’t been established.
- Older adults have an increased risk of hepatotoxicity and hypertension compared to younger individuals.
- Dialyzable drug: Unknown.
PREGNANCY-LACTATION-REPRODUCTION
- This drug may cause fetal harm.
- It’s unknown if this drug is excreted in human milk. Patients shouldn’t breastfeed during and for 2 weeks after treatment.
INTERACTIONS
Drug-drug. Moderate or strong CYP3A inducers (phenytoin, dexamethasone, rifampin): May decrease olutasidenib levels. Avoid use together.
Sensitive CYP3A substrates (digoxin, sirolimus): May decrease levels of substrates. Avoid concomitant use; if unavoidable, monitor for loss of therapeutic effects of these drugs.
ADVERSE REACTIONS
CNS: fatigue, malaise, fever, headache.
CV: edema, hypertension.
GI: nausea, constipation, mucositis, diarrhea, abdominal pain, vomiting, decreased appetite, gallbladder disorders.
GU: increased creatinine.
Hematologic: leukocytosis, increased lymphocytes.
Hepatic: hepatotoxicity, elevated transaminases, increased bilirubin, increased alkaline phosphatase.
Metabolic: hypokalemia, hypophosphatemia, increased lipase, increased uric acid, hyponatremia.
Musculoskeletal: arthralgia.
Respiratory: dyspnea, cough.
Skin: rash.
Other: differentiation syndrome.
Reactions in bold italics are life-threatening.
Released: March 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer