capivasertib
Truqap
Pharmaceutical company: AstraZeneca
Pharmacologic classification: Kinase inhibitor
Therapeutic classification: Antineoplastic agent
AVAILABLE FORMS
Tablets: 160 mg, 200 mg
INDICATIONS AND DOSAGES
Hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations following progression while on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy, in combination with fulvestrant
Adults: 400 mg PO b.i.d. (approximately 12 hours apart) for 4 days followed by 3 days off. Continue until disease progression or unacceptable toxicity occurs. Refer to the fulvestrant manufacturer's instructions for dosing information. For males and pre- and perimenopausal females, consider giving a luteinizing hormone-releasing hormone agonist according to standard clinical practice.
Adjust-a-dose: For adverse reactions, the first dose reduction is 320 mg b.i.d. for 4 days followed by 3 days off. The second dose reduction is 200 mg b.i.d. for 4 days followed by 3 days off. Permanently discontinue capivasertib if patient is unable to tolerate the second dose reduction. Refer to the manufacturer's instructions for toxicity-related dosage adjustments. If giving with a strong or moderate CYP3A inhibitor, reduce capivasertib dosage to 320 mg PO b.i.d. for 4 days followed by 3 days off. When the CYP3A inhibitor is discontinued, resume the capivasertib dosage given before initiation of the inhibitor after 3 to 5 half-lives of the inhibitor.
CONTRAINDICATIONS AND CAUTIONS
- Contraindicated in patients with severe hypersensitivity to capivasertib or any of its components.
- Severe hyperglycemia associated with ketoacidosis may occur. Safety and effectiveness in patients with type 1 diabetes or diabetes requiring insulin haven't been established.
- Cutaneous adverse reactions, such as erythema multiforme, palmar-plantar erythrodysesthesia and drug reaction with eosinophilia and systemic symptoms (DRESS), may occur and may be severe.
- This drug hasn't been studied in patients with creatinine clearance of 29 mL/minute or less, or bilirubin level more than 3 times the upper limit of normal (ULN) and any AST level.
- Use cautiously in patients with bilirubin level greater than 1.5 to 3 times the ULN and any AST level.
- Safety and effectiveness in children haven't been established.
- Dialyzable drug: Unknown.
PREGNANCY-LACTATION-REPRODUCTION
- This drug may cause fetal harm.
- Female patients of reproductive potential should use effective contraception during treatment and for 1 month after the last dose.
- Male patients with female partners of reproductive potential should use effective contraception during treatment and for 4 months after the last dose.
- It isn't known whether this drug appears in human milk. Because of the risk to a breastfed child, breastfeeding isn't recommended during treatment.
INTERACTIONS
Drug-drug. Moderate and strong CYP3A inducers (phenytoin, rifampin, efavirenz): May decrease capivasertib level and effectiveness. Avoid use together.
Moderate CYP3A inhibitors (erythromycin, fluconazole, verapamil): May increase capivasertib level and risk of adverse effects. Reduce capivasertib dosage and monitor patient.
Strong CYP3A inhibitors (clarithromycin, itraconazole): May increase capivasertib level and risk of adverse effects. Avoid use together. If concomitant use can't be avoided, reduce capivasertib dosage and monitor patient.
Drug-food. Grapefruit and grapefruit products: May increase drug level. Discourage use together.
ADVERSE REACTIONS
CNS: fatigue, headache, fever, dysgeusia.
GI: diarrhea, nausea, stomatitis, vomiting, decreased appetite, dyspepsia.
GU: UTI, increased creatinine level, kidney injury (acute kidney injury, kidney failure)
Hematologic: anemia, lymphocytopenia, leukopenia, neutropenia, thrombocytopenia.
Hepatic: increased ALT.
Metabolic: hyperglycemia, increased triglycerides, decreased corrected calcium, hypokalemia.
Respiratory: pneumonia.
Skin: cutaneous reactions (butterfly rash, dermatitis, allergic dermatitis, dry skin, eczema, erythema multiforme, palmar-plantar erythrodysesthesia syndrome, pruritis, erythematous rash, maculopapular rash, papular rash, skin discoloration, skin fissures, skin ulcer, urticaria, purpura, drug eruption).
Other: hypersensitivity reaction, second malignancy.
Reactions in bold italics are life-threatening.
Released: February 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
nirogacestat
Ogsiveo
Pharmaceutical company: SpringWorks Therapeutics
Pharmacologic classification: Gamma secretase inhibitor
Therapeutic classification: Antineoplastic
AVAILABLE FORMS
Tablets: 50 mg
INDICATIONS AND DOSAGES
Progressing desmoid tumors
Adults: 150 mg PO b.i.d. until disease progression or unacceptable toxicity occurs.
Adjust-a-dose: Refer to the manufacturer's instructions for toxicity-related dosage adjustments.
CONTRAINDICATIONS AND CAUTIONS
- This drug may increase the risk of liver toxicity, nonmelanoma skin cancer, and electrolyte abnormalities.
- Safety and effectiveness have not been established in children. Widening of the epiphyseal growth plate has occurred in children with open growth plates treated with nirogacestat.
- Dialyzable drug: Unlikely.
PREGNANCY-LACTATION-REPRODUCTION
- This drug may cause fetal harm.
- It's unknown if this drug is present in human milk. Because of the potential for serious adverse reactions on the breastfed child, breastfeeding is not recommended during treatment and for 1 week after the last dose.
- Patients should use effective contraception during treatment and for 1 week after the last dose.
- This drug may cause fertility impairment in males and females, and ovarian toxicity.
INTERACTIONS
Drug-drug. CYP2C19 substrates (carisoprodol, citalopram, diazepam, diphenhydramine, fluoxetine, omeprazole, pantoprazole, voriconazole): May decrease substrate level. Avoid use together if decreased level of substrate leads to decreased effectiveness. Refer to prescribing information for the substrate.
CYP3A substrates (midazolam, amitriptyline, clarithromycin, cyclosporin, docetaxel, etoposide, mirtazapine, paclitaxel, tacrolimus, tamoxifen): May increase substrate level. Avoid use together if minimal changes in level may lead to serious adverse reaction.
Gastric acid reducing agents (proton pump inhibitors, histamine-2 blockers): May decrease nirogacestat level. Avoid use together. If use cannot be avoided, give nirogacestat 2 hours before or 2 hours after antacid.
Moderate or strong CYP3A inducers (carbamazepine, phenobarbital, phenytoin, primidone, rifampin, efavirenz): May decrease nirogacestat level. Avoid use together.
Moderate or strong CYP3A inhibitors (amiodarone, cimetidine, itraconazole, clarithromycin, diltiazem, fluconazole, erythromycin, ketoconazole, lopinavir, nefazodone, voriconazole, verapamil): May increase nirogacestat level. Avoid use together.
Drug-food. Grapefruit products, Seville oranges, starfruit: May increase nirogacestat level. Discourage use together.
ADVERSE REACTIONS
CNS: fatigue, headache.
EENT: epistaxis.
GI: diarrhea, nausea, stomatitis, abdominal pain.
GU: ovarian toxicity, glycosuria, proteinuria.
Hepatic: increased AST and ALT levels.
Metabolic: hypophosphatemia, hypokalemia.
Respiratory: cough, URI, dyspnea.
Skin: rash, alopecia, folliculitis, skin abscesses with scarring, nonmelanoma skin cancer.
Other: flulike illness.
Reactions in bold italics are life-threatening.
Released: February 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer