capivasertib

High Alert

Hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with ≥1 PIK3CA/AKT1/PTEN-alteration following progression on ≥1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 mo of completing adjuvant therapy (in combination with fulvestrant).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Severe renal impairment;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Insulin-dependent diabetes;
Diabetes, obesity, elevated fasting glucose (>160 mg/dL), elevated A1c, concurrent use of corticosteroids, or infection;
Moderate hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: dermatitis, dry skin, eczema, pruritus, rash, skin discoloration, urticaria, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, palmar-plantar erythrodysesthesia

Endo: hyperglycemia, DIABETIC KETOACIDOSIS

F and E: hypocalcemia, hypokalemia, dehydration

GI: ↓appetite, ↑liver enzymes, diarrhea, nausea, stomatitis, vomiting

GU: ↑serum creatinine, urinary tract infection

Hemat: anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia

Metab: hypertriglyceridemia

Neuro: fatigue, headache

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including itraconazole, may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use necessary, ↓ capivasertib dose.
Moderate CYP3A4 inhibitors, including erythromycin and verapamil, may ↑ levels and risk of toxicity; ↓ capivasertib dose.
Strong CYP3A4 inducers, including rifampin, and moderate CYP3A4 inducers, including efavirenz, may ↓ levels and effectiveness; avoid concurrent use.

Availability ⬆ ⬇

Tablets: 160 mg; 200 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 400 mg twice daily for 4 days, followed by 3 days off; continue until disease progression or unacceptable toxicity. Concurrent use with strong or moderate CYP3A4 inhibitor: 320 mg twice daily for 4 days, followed by 3 days off; continue until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as an inhibitor of all three isoforms of serine/threonine kinase AKT (AKT1, AKT2, and AKT3) and inhibits phosphorylation of downstream AKT substrates.

Therapeutic effects:

Improved progression-free survival and decreased spread of breast cancer.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 29% absorbed following oral administration.

Distribution: Extensively distributed to extravascular tissues.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 and UGT2B7. 45% excreted in the urine; 50% in the feces.

Half-Life: 8.3 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr	12 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patient to immediately contact health care provider if symptoms of hyperglycemia (↑ thirst, ↑ hunger with weight loss, ↑ urination), diarrhea, dehydration, or skin changes occur.
Rep: May cause fetal harm. Advise women of reproductive potential and male partners of women of reproductive potential to use effective contraception during therapy and for 1 mo (women) and 4 mo (female partners) after last dose. Advise patient to notify health care provider of known or suspected pregnancy and to avoid breastfeeding.

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Indications ⬇