capivasertib

kap-EYE-va-SER-tib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

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).

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.

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.

(plasma concentrations)

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

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.

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

F and E: hypocalcemia, hypokalemia, dehydration, ketoacidosis

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

GU: ↑serum creatinine, urinary tract infection

Hemat: anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia

Metab: ↓appetite, hypertriglyceridemia

Neuro: fatigue, headache

Drug-drug:

Strong CYP3A4 inhibitors, including itraconazole, may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use unavoidable, ↓ 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.

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.

Tablets: 160 mg; 200 mg

Monitor for signs and symptoms of diarrhea and dehydration. At first signs of diarrhea,advise patient to ↑ oral fluid intake and start antidiarrheal therapy.If Grade 2 or 3,withhold therapy until recovery to ≤Grade 1. If recovery occurs in ≤28 days, resume at same or one lower dose as clinically indicated. If recovery occurs in >28 days or recurrence occurs, resume at one lower dose for Grade 2 or permanently discontinue for Grade 3.If Grade 4,permanently discontinue capivasertib.
Monitor skin for erythema, rash, and urticaria. If Grade 2,withhold therapy until recovery to ≤Grade 1; then resume at same dose. If symptoms persist or recur, resume at one lower dose. If Grade 3,withhold therapy until recovery to ≤Grade 1. If recovery occurs in ≤28 days, resume at same dose. If recovery occurs in >28 days, resume at one lower dose.For recurrent Grade 3 or Grade 4,permanently discontinue capivasertib.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Monitor CBC with differential, triglycerides, and creatinine periodically during therapy.
Evaluate fasting blood glucose (FBG) and A1c prior to therapy. During 1st mo, evaluate FBG every 2 wk and at least once monthly starting from the 2nd mo prior to scheduled dose. Monitor FBG more frequently in patients with diabetes mellitus and at ↑ risk for hyperglycemia. Monitor A1c every 3 mo.If hyperglycemia occurs,monitor FBG at least twice weekly until ↓ to normal level. Consider consultation with health care professional experienced in treating hyperglycemia for therapy with antihyperglycemics. If FBG > upper limit of normal (ULN) 160 mg/dL, or A1c >7%, consider initiation or intensification of oral diabetic therapy. If FBG 161–250 mg/dL,withhold therapy until FBG ≤ 160 mg/dL. If recovery occurs in ≤28 days, resume at same dose. If recovery occurs in >28 days, resume at one lower dose. If FBG 251–500 mg/dL, withhold therapy until FBG ≤160 mg/dL. If recovery occurs in ≤28 days, resume at one lower dose. If recovery occurs in >28 days, permanently discontinue capivasertib. If FBG >500 mg/dL or life-threatening sequelae at any FBG level,discontinue capivasertib permanently if persists >24 hr. If FBG ↓ to ≤500 mg/dL within 24 hr and considered Grade 2 or 3, withhold therapy until recovery to ≤ Grade 1; then resume at same dose. If recovery occurs in >28 days, resume at one lower dose. If Grade 4, permanently discontinue capivasertib.

Dose reduction schedule:First dose reduction:320 mg twice daily for 4 days followed by 3 days off. Second dose reduction,200 mg twice daily for 4 days followed by 3 days off. If patient unable to tolerate 200 mg twice daily regimen,permanently discontinue capivasertib.
Take with or without food. DNC: Swallow tablets whole. Do not chew, crush, or split tablets prior to swallowing.Do not take tablets that are broken or otherwise not intact.
If a dose is missed, take within 4 hr of scheduled time; otherwise, skip that dose and take at the next scheduled time. If a patient vomits a dose, instruct not to take an additional dose; take the next dose at its usual time.
Administer a luteinizing hormone-releasing hormone (LHRH) agonist for premenopausal and perimenopausal females, and consider administration of LHRH agonist to males, according to current clinical practice standards.

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

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

Truqap

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US Brand Names ⬆