Capivasertib Dosage

Medically reviewed by Drugs.com. Last updated on Feb 1, 2024.

Usual Adult Dose for Breast Cancer

400 mg orally twice a day for 4 days, followed by 3 days off
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• This drug should be administered in combination with fulvestrant; consult the manufacturer product information for fulvestrant for dosing information.
• Each dose of this drug should be given approximately 12 hours apart.
• Patients should be selected for treatment based on the presence of one or more of the following genetic alterations in tumor tissue: PIK3CA/AKT1/PTEN.
• In premenopausal and perimenopausal women, a luteinizing hormone-releasing hormone (LHRH) agonist should be administered according to current clinical practice standards.
• In men, consider administering a LHRH agonist according to current clinical practice standards.

Use: In combination with fulvestrant, for the treatment of 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-alteration 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.

Renal Dose Adjustments

Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): No dose adjustment recommended.
Severe renal dysfunction (CrCl 15 to 29 mL/min): Data not available; this population was not studied.

Liver Dose Adjustments

• Mild liver dysfunction (bilirubin less than or equal to the upper limit of normal [ULN] and AST greater than ULN OR bilirubin greater than 1 to 1.5 times ULN and any AST): No dose adjustment recommended.
• Moderate liver dysfunction (bilirubin greater than 1.5 to 3 times ULN and any AST): Caution recommended; monitor for adverse reactions due to potentially increased exposure.
• Severe liver dysfunction (bilirubin greater than 3 times ULN and any AST): Data not available; this population was not studied.

Dose Adjustments

General Dose Reduction Recommendations for Adverse Reactions:

• First dose reduction: 320 mg orally twice a day for 4 days, followed by 3 days off
• Second dose reduction: 200 mg orally twice a day for 4 days, followed by 3 days off
• This drug should be permanently discontinued in patients unable to tolerate the second dose reduction.

Dosage Modifications for Adverse Reactions:
HYPERGLYCEMIA:
If fasting glucose (FG) is greater than the upper limit of normal (ULN) to 160 mg/dL (8.9 mmol/L) OR hemoglobin A1C greater than 7%:

• Consider initiation or intensification of oral anti-diabetic treatment.

If FG is between 161 to 250 mg/dL (9 to 13.9 mmol/L):

• Treatment should be withheld until FG decreases to 160 mg/dL (8.9 mmol/L) or less.
• If recovery occurs in 28 days or less, treatment with this drug may be resumed at the same dose.
• If recovery occurs in more than 28 days, treatment with this drug may be resumed at one dose lower.

If FG is between 251 to 500 mg/dL (14 to 27.8 mmol/L):

• Treatment should be withheld until FG decreases to 160 mg/dL (8.9 mmol/L) or less.
• If recovery occurs in 28 days or less, treatment with this drug may be resumed at one dose lower.
• If recovery occurs in more than 28 days, treatment should be permanently discontinued.

If FG is greater than 500 mg/dL (27.8 mmol/L) OR life-threatening sequelae of hyperglycemia occurs at any FG level:

• Treatment with this drug should be permanently discontinued in the event of life-threatening sequelae of hyperglycemia OR if FG persists at 500 mg/dL (27.8 mmol/L) or greater after 24 hours.
• If FG is 500 mg/dL (27.8 mmol/L) or less within 24 hours, then the dose modifications for hyperglycemia based on FG level should be followed.

DIARRHEA:
Grade 2 severity:

• Treatment should be withheld until recovery to grade 1 or less.
• If recovery occurs in 28 days or less, treatment should be resumed at the same dose, or one dose lower as clinically indicated.
• If recovery occurs in more than 28 days, treatment should be resumed at one dose lower, as clinically indicated.
• For recurrence of grade 2 diarrhea, treatment should be resumed by one dose lower.

Grade 3 severity:

• Treatment should be withheld until recovery to grade 1 or less.
• If recovery occurs in 28 days or less, treatment should be resumed at the same dose, or one dose lower as clinically indicated.
• If recovery occurs in more than 28 days, treatment should be permanently discontinued.

Grade 4 severity:

• Treatment should be resumed permanently discontinued.

CUTANEOUS ADVERSE REACTIONS:
Grade 2 severity:

• Treatment should be withheld until recovery to grade 1 or less.
• Upon recovery, treatment should be resumed at the same dose.
• For persistent or recurrent grade 2 cutaneous reaction, treatment should be reduced by one dose lower.

Grade 3 severity:

• Treatment should be withheld until recovery to grade 1 or less.
• If recovery occurs in 28 days or less, treatment should be resumed at the same dose.
• If recovery occurs in more than 28 days, treatment should be resumed at one dose lower.
• For recurrent grade 3 cutaneous reaction, treatment should be permanently discontinued.

Grade 4 severity:

• Treatment should be permanently discontinued.

OTHER ADVERSE REACTIONS:
Grade 2 severity:

• Treatment should be withheld until recovery to grade 1 or less.
• Upon recovery, treatment may be resumed at the same dose.

Grade 3 severity:

• Treatment should be withheld until recovery to grade 1 or less.
• If recovery occurs in 28 days or less, treatment may be resumed at the same dose.
• If recovery occurs in more than 28 days, treatment may be resumed at one dose lower.

Grade 4 severity:

• Treatment should be permanently discontinued.

Dose Modifications for Concomitant Use of Strong and Moderate CYP450 3A Inhibitors:
STRONG CYP450 3A INHIBITORS:

• Concomitant use with strong CYP450 3A inhibitors should be avoided.
• If concomitant use cannot be avoided, the dosage of this drug should be reduced to 320 mg orally twice a day for 4 days, followed by 3 days off.
• After discontinuation of a strong CYP450 3A inhibitor, treatment with this drug may be resumed (after 3 to 5 half-lives of the inhibitor) at the same dosage that was taken prior to initiating the strong CYP450 3A inhibitor.

MODERATE CYP450 3A INHIBITORS:

• When used concomitantly with a moderate CYP450 3A inhibitor, the dosage of this drug should be reduced to 320 mg orally twice a day for 4 days, followed by 3 days off.
• After discontinuation of a moderate CYP450 3A inhibitor, treatment with this drug may be resumed (after 3 to 5 half-lives of the inhibitor) at the same dosage that was taken prior to initiating the moderate CYP450 3A inhibitor.

Precautions

CONTRAINDICATIONS:

• Severe hypersensitivity to either the active component or to any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer this drug twice a day (about 12 hours apart) at approximately the same times each day.
• May be taken with or without food.
• Swallow each tablet whole; do not chew, crush, or split tablets, or take tablets that are broken or cracked.
• If a dose is missed within 4 hours of the scheduled time, instruct the patient to take the missed dose.
• If a dose is missed more than 4 hours of the scheduled time, instruct the patient to skip the missed dose and take the next dose at its usual scheduled time.
• If a dose is vomited, instruct the patient not to take an additional dose and to take the next dose at its usual scheduled time.

Storage requirements:

• Store in original bottle at 20C to 25C (68F to 77F).
• Temperature excursions permitted to 15C to 30C (59F to 86F).

General:

• Information on FDA-approved tests for the detection of PIK3CA, AKT1, and PTEN alterations is available at: http://www.fda.gov/CompanionDiagnostics.

Monitoring:

• Dermatologic: For signs/symptoms of cutaneous reactions
• Gastrointestinal: For signs/symptoms of diarrhea
• Metabolic:
• Fasting blood glucose (prior to treatment; at least every 2 weeks [during first month] and then at least monthly thereafter prior to the scheduled dose; monitor more frequently in patients who experience hyperglycemia during treatment)
• Hemoglobin A1C (every 3 months)

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• This drug may cause hyperglycemia; monitor fasting blood glucose levels periodically during therapy.
• This drug may cause diarrhea; start antidiarrheal medication and increase oral fluids if diarrhea occurs.
• Contact your health care provider if you experience:
• Signs and symptoms of hyperglycemia
• Diarrhea during treatment
• New or worsening rash, erythematous and exfoliative skin reactions
• Inform your health care provider of all concomitant medications, including over-the-counter drugs.
• Do not consume grapefruit products while taking this drug.
• Breastfeeding is not recommended during treatment.
• Patients of childbearing potential:
• This drug may cause potential harm to a fetus.
• Notify your health care provider of a known/suspected pregnancy.
• Females: Use effective contraception during treatment and for 1 month after the last dose.
• Males (with female partners of reproductive potential): Use effective contraception during treatment and for 4 months after the last dose.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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