Capivasertib
FDA Drug Information • Also known as: Truqap
- Brand Names
- Truqap
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION TRUQAP (capivasertib) is a kinase inhibitor. The molecular formula for capivasertib is C 21 H 25 ClN 6 O 2 and the molecular weight is 428.92 g/mol. The chemical name of capivasertib is 4-amino- N -[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7 H -pyrrolo[2,3- d ]pyrimidin-4-yl)-4-piperidinecarboxamide. Capivasertib is a white to off-white powder with pH-dependent solubility. It is freely soluble in water at pH values below 1.2 and practically insoluble at pH values above 6.8. Capivasertib has the following structural formula: TRUQAP film-coated tablets are supplied for oral administration with 160 mg or 200 mg capivasertib. The tablets also contain croscarmellose sodium, dibasic calcium phosphate, magnesium stearate, and microcrystalline cellulose. The film coat contains the following inactive ingredients: copovidone, hypromellose, iron oxide black, iron oxide red, iron oxide yellow, medium chain triglycerides, polydextrose, polyethylene glycol 3350, and titanium dioxide. chemical structure
What Is Capivasertib Used For?
1 INDICATIONS AND USAGE TRUQAP, in combination with fulvestrant, is indicated for the treatment of adult patients with 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. TRUQAP is a kinase inhibitor indicated, in combination with fulvestrant for the treatment of adult patients with 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 -alterations 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. (1)
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with TRUQAP based on the presence of one or more of the following genetic alterations in tumor tissue: PIK3CA/AKT1/PTEN . ( 2.1 ) Recommended Dosage: 400 mg orally twice daily, with or without food, for 4 days followed by 3 days off. ( 2.3 ) 2.1 Patient Selection Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with TRUQAP, based on the presence of one or more of the following genetic alterations in tumor tissue: PIK3CA/AKT1/PTEN [see Clinical Studies (14) ] . Information on FDA-approved tests for the detection of PIK3CA, AKT1 , and PTEN alterations is available at: http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Evaluation Before Initiating TRUQAP Evaluate fasting blood glucose (FG) and hemoglobin A1C (HbA1C) prior to starting TRUQAP and at regular intervals during treatment [see Warnings and Precautions (5.1) ] . 2.3 Recommended Dosage and Administration The recommended dosage of TRUQAP, in combination with fulvestrant, is 400 mg orally twice daily (approximately 12 hours apart) with or without food, for 4 days followed by 3 days off. Continue TRUQAP until disease progression or unacceptable toxicity. TRUQAP dosing schedule for each week is provided in Table 1. Table 1: TRUQAP Dosing Schedule for Each Week Day 1 2 3 4 5 No dosing on day 5, 6 and 7. 6 7 Morning 2 x 200 mg 2 x 200 mg 2 x 200 mg 2 x 200 mg Evening 2 x 200 mg 2 x 200 mg 2 x 200 mg 2 x 200 mg Swallow TRUQAP tablets whole. Do not chew, crush, or split tablets prior to swallowing. Do not take tablets that are broken, cracked, or otherwise not intact. If a patient misses a dose within 4 hours of the scheduled time, instruct the patient to take the missed dose. If a patient misses a dose more than 4 hours of the scheduled time, instruct the patient to skip the dose and take the next dose at its usual scheduled time. If a patient vomits a dose, instruct the patient not to take an additional dose and take the next dose at its usual scheduled time. Refer to the fulvestrant Full Prescribing Information for recommended fulvestrant dosing information. For premenopausal and perimenopausal women, administer a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards. For men, consider administering a LHRH agonist according to current clinical practice standards. 2.4 Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are listed in Table 2. Permanently discontinue TRUQAP if unable to tolerate the second dose reduction. Table 2: Recommended Dose Reductions of TRUQAP for Adverse Reactions TRUQAP Dose and 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 The recommended dosage modifications for adverse reactions...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are also discussed in greater details in other sections of the labeling:
Hyperglycemia [see Warnings and Precautions (5.1) ] Diarrhea [see Warnings and Precautions (5.2) ] Cutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥20%), including laboratory abnormalities, were diarrhea, cutaneous adverse reactions, increased random glucose, decreased lymphocytes, decreased hemoglobin, increased fasting glucose, nausea, fatigue, decreased leukocytes, increased triglycerides, decreased neutrophils, increased creatinine, vomiting and stomatitis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population described in WARNINGS and PRECAUTIONS reflects exposure to TRUQAP 400 mg orally, twice a day for 4 days followed by 3 days off, in combination with fulvestrant, in 355 patients in CAPItello-291 until disease progression or unacceptable toxicity. Among the 355 patients who received TRUQAP, 52% were exposed for 6 months or longer, and 27% were exposed for greater than one year. In this safety population, the most common (≥ 20%) adverse reactions including laboratory abnormalities were diarrhea (72%), cutaneous adverse reactions (58%), increased random glucose (57%), decreased lymphocytes (47%), decreased hemoglobin (45%), increased fasting glucose (37%), nausea and fatigue (35% each), decreased leukocytes (32%), increased triglycerides (27%), decreased neutrophils (23%), increased creatinine (22%), vomiting (21%), and stomatitis (20%). CAPItello-291 The safety of TRUQAP was evaluated in CAPItello-291, a clinical trial including 288 adult patients (155 patients in TRUQAP with fulvestrant arm and 133 patients in placebo with fulvestrant arm) whose breast cancer had one or more PIK3CA/AKT1/PTEN -alterations [see Clinical Studies (14) ] . Among patients who received TRUQAP, 61% were exposed for 6 months or longer and 30% were exposed for greater than one year. Of the 155 patients who received TRUQAP with fulvestrant, the median age was 58 years (range 36 to 84); female (99%); White (48%), Asian (31%), Black (1.3%), American Indian/Alaska Native (0.6%), and other races (19%). Serious adverse reactions occurred in 18% of patients receiving TRUQAP with fulvestrant. The most common serious adverse reactions (≥ 1%) were cutaneous adverse reaction (3.9%), diarrhea and pneumonia (2.6% each), vomiting and pyrexia (1.9% each), hyperglycemia, hypersensitivity, fatigue, renal injury and second malignancy (1.3% each). Fatal adverse reactions occurred in 1.3% of patients who received TRUQAP with fulvestrant, including sepsis (0.6%), and acute myocardial infarction (0.6%). Permanent TRUQAP discontinuation due to an adverse reaction occurred in 10% of patients. The most common adverse reaction (≥ 2%) leading to permanent discontinuation of TRUQAP was cutaneous adverse reactions (6%). Dosage interruptions of TRUQAP due to an adverse reaction occurred in 39% of patients. Adverse reactions leading to dosage interruption in ≥ 2% of patients included cutaneous adverse reactions (14%), diarrhea (10%), pyrexia (4.5%), vomiting and nausea (3.2% each), and fatigue (2.6%). Dose reductions of TRUQAP due to adverse reactions occurred in 21% of patients receiving TRUQAP with fulvestrant. Adverse reactions leading to TRUQAP dose reductions in ≥ 2% of patients were diarrhea and cutaneous adverse reactions (8% each). The most common (≥ 20%) adverse reactions including laboratory abnormalities were diarrhea (77%), increased random glucose (58%), cutaneous adverse reaction (56%),...Drug Interactions
7 DRUG INTERACTIONS
Strong CYP3A Inhibitors : Avoid concomitant use. If concomitant use cannot be avoided, reduce TRUQAP dose. ( 2.5 , 7.1 ) Moderate CYP3A Inhibitors: Reduce TRUQAP dose. ( 2.5 , 7.1 ) Strong and Moderate CYP3A Inducers: Avoid concomitant use. ( 7.1 ) 7.1 Effects of Other Drugs on TRUQAP Table 6 describes drug interactions where concomitant use of another drug affects TRUQAP. Table 6: Drug Interactions with TRUQAP Strong CYP3A Inhibitors Clinical Impact Capivasertib is a CYP3A substrate. Strong CYP3A inhibitors increase capivasertib exposure [see Clinical Pharmacology (12.3) ], which may increase the risk of TRUQAP adverse reactions. Prevention or Management Avoid concomitant use with a strong CYP3A inhibitor. If concomitant use cannot be avoided, reduce the dose of TRUQAP and monitor patients for adverse reactions [see Dosage and Administration (2.5) ] . Moderate CYP3A Inhibitors Clinical Impact Capivasertib is a CYP3A substrate. Moderate CYP3A inhibitors increase capivasertib exposure [see Clinical Pharmacology (12.3) ], which may increase the risk of TRUQAP adverse reactions. Prevention or Management When concomitantly used with moderate CYP3A inhibitor, reduce the dose of TRUQAP and monitor patients for adverse reactions [see Dosage and Administration (2.5) ] . Strong and Moderate CYP3A Inducers Clinical Impact Capivasertib is a CYP3A substrate. Strong and moderate CYP3A inducers decrease capivasertib exposure [see Clinical Pharmacology (12.3) ], which may reduce the effectiveness of TRUQAP. Prevention or Management Avoid concomitant use of TRUQAP with strong or moderate CYP3A inducers.Contraindications
4 CONTRAINDICATIONS TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components. Severe hypersensitivity to TRUQAP or any of its components. (4)
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary TRUQAP is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy information. Based on findings in animals and mechanism of action, TRUQAP can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of TRUQAP in pregnant women. In an animal reproduction study, oral administration of capivasertib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality and reduced fetal weights at maternal exposures 0.7 times the human exposure (AUC) at the recommended dose of 400 mg twice daily ( see Data ). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of capivasertib up to 150 mg/kg/day during the period of organogenesis. Administration of capivasertib resulted in maternal toxicities (reduced body weight gain and food consumption, increased blood glucose) and adverse developmental outcomes, including embryo-fetal deaths (post-implantation loss), reduced fetal weights, and minor fetal visceral variations at a dose of 150 mg/kg/day (0.7 times the human exposure at the recommended dose of 400 mg twice daily based on AUC). In a pre- and post-natal assessment, pregnant rats received oral doses of capivasertib up to 150 mg/kg/day from gestation day 6 through at least lactation day 6. Administration of 150 mg/kg/day resulted in reduced litter and pup weights.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Table 8: TRUQAP 160 mg and 200 mg Tablets Strength Description Package Size and Type NDC Number TRUQAP 160 mg Beige film-coated, round, biconvex tablets debossed with ‘CAV’ above ‘160’ on one side and plain on the reverse supplied in HDPE bottle with child-resistant closure. Bottle of 64 tablets 0310-9500-01 TRUQAP 200 mg Beige film-coated, capsule-shaped, biconvex tablets debossed with ‘CAV 200’ on one side and plain on the reverse supplied in HDPE bottle with child-resistant closure. Bottle of 64 tablets 0310-9501-01 TRUQAP 160 mg Beige film-coated, round, biconvex tablets debossed with ‘CAV’ above ‘160’ on one side and plain on the reverse supplied in a blister with a child‑resistant closure. Each carton has 4 blister packs (64 tablets total)-each blister pack contains 16 tablets. 0310-9500-02 TRUQAP 200 mg Beige film-coated, capsule-shaped, biconvex tablets debossed with ‘CAV 200’ on one side and plain on the reverse supplied in a blister with a child‑resistant closure. Each carton has 4 blister packs (64 tablets total)-each blister pack contains 16 tablets. 0310-9501-02 Storage and Handling Store TRUQAP in original packaging to maintain stability at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense bottled TRUQAP tablets either in:
The original bottle. A USP equivalent tight container. Instruct patients to keep the unused tablets in the container at 20°C to 25°C (68°F to 77°F) and discard after 45 days.About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.