Share on Facebook
Share on Twitter
Share on LinkedIn
Share by Email
Print
Truqap Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Tabs—64
Manufacturer
Generic Availability
NO
Mechanism of Action
Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3) and inhibits phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA).
In vitro, capivasertib reduced growth of breast cancer cell lines including those with relevant PIK3CA or AKT1 mutations or PTEN alteration. In vivo, capivasertib alone and in combination with fulvestrant inhibited tumor growth of mouse xenograft models including estrogen receptor positive breast cancer models with alterations in PIK3CA, AKT1, and PTEN.
Truqap Indications
Indications
In combination with fulvestrant, for the treatment of patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer with 1 or more PIK3CA/AKT1/PTEN-alterations as detected by an FDA-approved test following progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.
Truqap Dosage and Administration
Adult
Confirm presence with ≥1 of PIK3CA/AKT1/PTEN genetic alterations in tumor tissue. Swallow whole. 400mg twice daily (approx. 12hrs apart) for 4 days, followed by 3 days off. Continue until disease progression or unacceptable toxicity. For premenopausal and perimenopausal women: give a luteinizing hormone-releasing hormone (LHRH) agonist; for men: consider giving a LHRH agonist. Concomitant strong CYP3A (if unavoidable) or moderate CYP3A inhibitors: 320mg twice daily for 4 days, followed by 3 days off. After discontinuation of a strong or moderate CYP3A inhibitor, resume Truqap (after 3–5 half-lives of the inhibitor) at the previous dose. Dose modifications for adverse reactions: see full labeling.
Children
Not established.
Other Modifications
Dosage Modifications for Adverse Reactions
- First dose reduction: 320mg twice daily for 4 days followed by 3 days off.
- Second dose reduction: 200mg twice daily for 4 days followed by 3 days off.
- If unable to tolerate the second dose reduction, permanently discontinue Truqap.
Hyperglycemia (fasting glucose [FG])
- FG > ULN of 160mg/dL or FG >ULN of 8.9mmol/L or HbA1C >7%:
- Consider initiation or intesification of oral antidiabetic treatment.
- FG 161–250mg/dL or FG 9–13.9mmol/L:
- Withhold Truqap until FG decrease ≤160mg/dL (or ≤8.9mmol/L). If recovery occurs in ≤28 days, resume Truqap at same dose. If recovery occurs in >28 days, resume Truqap at one lower dose.
- FG 251–500mg/dL or FG 14–27.8mmol/L:
- Withhold Truqap until FG decrease ≤160mg/dL (or ≤8.9mmol/L). If recovery occurs in ≤28 days, resume Truqap at one lower dose. If recovery occurs in >28 days, permanently discontinue Truqap.
- FG >500 mg/dL or FG >27.8 mmol/L or life-threatening sequelae of hyperglycemia at any FG level:
- For life-threatening sequelae of hyperglycemia or if FG persists at ≥500mg/dL after 24 hours, permanently discontinue Truqap. If FG ≤500mg/dL (or ≤27.8 mmol/L) within 24 hours, then follow the guidance in the table for the relevant guide.
Diarrhea
- Grade 2: Withhold Truqap until recovery to ≤Grade 1. If recovery occurs in ≤28 days, resume Truqap at same dose or one lower dose as clinically indicated. If recovery occurs >28 days, resume at one lower dose as clinically indicated. For recurrence, reduce Truqap by one lower dose.
- Grade 3: Withhold Truqap until recovery to ≤Grade 1. If recovery occurs in ≤28 days, resume Truqap at same dose or one lower dose as clinically indicated. If recovery occurs >28 days, permanently discontinue Truqap.
- Grade 4: Permanently discontinue Truqap.
Cutaneous Adverse Reactions
- Grade 2: Withhold Truqap until recovery to ≤Grade 1. Resume Truqap at the same dose. Persistent or recurrent: reduce Truqap by one lower dose.
- Grade 3: Withhold Truqap until recovery to ≤Grade 1. If recovery occurs in ≤28 days, resume Truqap at same dose. If recovery occurs in >28 days, resume Truqap at one lower dose. For recurrent Grade 3: permanently discontinue Truqap.
- Grade 4: Permanently discontinue Truqap.
Other Adverse Reactions
- Grade 2: Withhold Truqap until recovery to ≤Grade 1. Resume Truqap at the same dose.
- Grade 3: Withhold Truqap until recovery to ≤Grade 1. If recovery occurs in ≤28 days, resume Truqap at same dose. If recovery occurs in >28 days, resume Truqap at one lower dose.
- Grade 4: Permanently discontinue Truqap.
Strong and Moderate CYP3A Inhibitors
- Avoid concomitant use with strong CYP3A inhibitors. If unavoidable, reduce Truqap dose to 320mg orally twice daily for 4 days followed by 3 days off.
- When concomitantly used with a moderate CYP3A inhibitor, reduce Truqap dose to 320mg orally twice daily for 4 days followed by 3 days off.
- After discontinuing strong or moderate CYP3A inhibitor, resume Truqap dose (after 3 to 5 half-lives) that was taken prior to initating the CYP3A inhibitor.
Truqap Contraindications
Not Applicable
Truqap Boxed Warnings
Not Applicable
Truqap Warnings/Precautions
Warnings/Precautions
Risk for severe hyperglycemia associated with ketoacidosis. Obtain fasting blood glucose (FG) prior to initiation, at least every 2 weeks during the 1st month, and at least once a month thereafter. Obtain HbA1c prior to initiation and monitor every 3 months. History of diabetes and risk factors for hyperglycemia (eg, obesity, elevated FG >160mg/dL, HbA1c ≥ULN, intercurrent infections, concomitant systemic corticosteroids): monitor FG more frequently. Severe diarrhea associated with dehydration; monitor. Monitor for cutaneous adverse reactions (eg, erythema multiforme, palmar-plantar erythrodysesthesia, DRESS). Moderate hepatic impairment: monitor. Severe renal or hepatic impairment: not studied. Embryo-fetal toxicity. Advise to use effective contraception during and for 1 month (females of reproductive potential) or 4 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended.
Truqap Pharmacokinetics
Absorption
Tmax: ~1 to 2 hours. Absolute bioavailability: 29%.
Distribution
Steady state volume of distribution: 1847 L. Plasma protein bound: 22%.
Elimination
Fecal (50%), renal (45%). Half-life: 8.3 hours. Steady state oral clearance: 50 L/h. Renal clearance: 21% of total clearance.
Truqap Interactions
Interactions
Potentiated by strong CYP3A inhibitors (eg, itraconazole); avoid concomitant use; if unavoidable, reduce Truqap dose and monitor. Potentiated by moderate CYP3A inhibitors (eg, erythromycin, verapamil); reduce Truqap dose and monitor. Antagonized by strong or moderate CYP3A inducers (eg, rifampicin, efavirenz); avoid concomitant use.
Truqap Adverse Reactions
Adverse Reactions
Diarrhea, cutaneous adverse reactions, nausea, fatigue, vomiting, stomatitis, lab abnormalities (increased random glucose, increased fasting glucose, decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased neutrophils, increased triglycerides, increased creatinine).
Truqap Clinical Trials
Truqap Note
Not Applicable
Truqap Patient Counseling
Cost Savings Program
Images
