{ "meta": { "disclaimer": "Do not rely on openFDA to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. We may limit or otherwise restrict your access to the API in line with our Terms of Service.", "terms": "https://open.fda.gov/terms/", "license": "https://open.fda.gov/license/", "last_updated": "2026-05-12", "results": { "skip": 0, "limit": 1, "total": 1 } }, "results": [ { "spl_product_data_elements": [ "TRUQAP capivasertib CAPIVASERTIB CAPIVASERTIB MICROCRYSTALLINE CELLULOSE ANHYDROUS DIBASIC CALCIUM PHOSPHATE CROSCARMELLOSE SODIUM MAGNESIUM STEARATE HYPROMELLOSE, UNSPECIFIED COPOVIDONE K25-31 POLYETHYLENE GLYCOL 3350 POLYDEXTROSE MEDIUM-CHAIN TRIGLYCERIDES TITANIUM DIOXIDE FERRIC OXIDE YELLOW FERRIC OXIDE RED FERROSOFERRIC OXIDE WATER Beige Biconvex CAV;160 TRUQAP capivasertib CAPIVASERTIB CAPIVASERTIB MICROCRYSTALLINE CELLULOSE ANHYDROUS DIBASIC CALCIUM PHOSPHATE CROSCARMELLOSE SODIUM MAGNESIUM STEARATE HYPROMELLOSE, UNSPECIFIED COPOVIDONE K25-31 POLYETHYLENE GLYCOL 3350 POLYDEXTROSE MEDIUM-CHAIN TRIGLYCERIDES TITANIUM DIOXIDE FERRIC OXIDE YELLOW FERRIC OXIDE RED FERROSOFERRIC OXIDE WATER Beige Biconvex CAV200" ], "recent_major_changes": [ "Warnings and Precautions, Hyperglycemia ( 5.1 ) 02/2025" ], "indications_and_usage": [ "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 are provided in Table 3. Table 3: Recommended Dosage Modifications of TRUQAP for Adverse Reactions Adverse Reaction Severity Severity grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. TRUQAP Dosage Modification Hyperglycemia For the management of suspected or confirmed diabetic ketoacidosis (DKA) refer to section Warnings and Precautions (5.1). (Fasting Glucose [FG]) [see Warnings and Precautions (5.1) ] FG > ULN‑160 mg/dL or FG > ULN‑8.9 mmol/L or HbA1C > 7% Consider initiation or intensification of oral anti-diabetic treatment. FG 161‑250 mg/dL or FG 9‑13.9 mmol/L Withhold TRUQAP until FG decrease ≤ 160 mg/dL (or ≤ 8.9 mmol/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 251‑500 mg/dL or FG 14‑27.8 mmol/L Withhold TRUQAP until FG decrease ≤ 160 mg/dL (or ≤ 8.9 mmol/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 Withhold TRUQAP. For life-threatening sequelae of hyperglycemia or if FG persists at ≥ 500 mg/dL after 24 hours, permanently discontinue TRUQAP. If FG ≤ 500 mg/dL (or ≤ 27.8 mmol/L) within 24 hours, then follow the guidance in the table for the relevant grade Diarrhea [see Warnings and Precautions (5.2) ] 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 in > 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 in > 28 days, permanently discontinue TRUQAP. Grade 4 Permanently discontinue TRUQAP. Cutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] 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 [see Adverse Reactions (6.1) ] 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. 2.5 Dosage Modifications for Strong and Moderate CYP3A Inhibitors Avoid concomitant use with strong CYP3A inhibitors. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the dosage of TRUQAP to 320 mg orally twice daily for 4 days followed by 3 days off [see Drug Interactions (7.1) ] . When concomitantly used with a moderate CYP3A inhibitor, reduce the dosage of TRUQAP to 320 mg orally twice daily for 4 days followed by 3 days off. After discontinuation of a strong or moderate CYP3A inhibitor, resume the TRUQAP dosage (after 3 to 5 half-lives of the inhibitor) that was taken prior to initiating the strong or moderate CYP3A inhibitor." ], "dosage_and_administration_table": [ "
Table 1: TRUQAP Dosing Schedule for Each Week
Day12345No dosing on day 5, 6 and 7.67
Morning2 x 200 mg2 x 200 mg2 x 200 mg2 x 200 mg
Evening2 x 200 mg2 x 200 mg2 x 200 mg2 x 200 mg
", "
Table 2: Recommended Dose Reductions of TRUQAP for Adverse Reactions
TRUQAPDose and Schedule
First dose reduction320 mg twice daily for 4 days followed by 3 days off
Second dose reduction200 mg twice daily for 4 days followed by 3 days off
", "
Table 3: Recommended Dosage Modifications of TRUQAP for Adverse Reactions
Adverse Reaction SeveritySeverity grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.TRUQAP Dosage Modification
HyperglycemiaFor the management of suspected or confirmed diabetic ketoacidosis (DKA) refer to section Warnings and Precautions (5.1).(Fasting Glucose [FG])[see Warnings and Precautions (5.1)]FG > ULN‑160 mg/dL or FG > ULN‑8.9 mmol/L or HbA1C > 7%Consider initiation or intensification of oral anti-diabetic treatment.
FG 161‑250 mg/dL orFG 9‑13.9 mmol/LWithhold TRUQAP until FG decrease ≤ 160 mg/dL (or ≤ 8.9 mmol/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 251‑500 mg/dL or FG 14‑27.8 mmol/LWithhold TRUQAP until FG decrease ≤ 160 mg/dL (or ≤ 8.9 mmol/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/Lorlife-threatening sequelae of hyperglycemia at any FG levelWithhold TRUQAP. For life-threatening sequelae of hyperglycemia or if FG persists at ≥ 500 mg/dL after 24 hours, permanently discontinue TRUQAP. If FG ≤ 500 mg/dL (or ≤ 27.8 mmol/L) within 24 hours, then follow the guidance in the table for the relevant grade
Diarrhea [see Warnings and Precautions (5.2)]Grade 2Withhold 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 in > 28 days, resume at one lower dose as clinically indicated.For recurrence, reduce TRUQAP by one lower dose.
Grade 3Withhold 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 in > 28 days, permanently discontinue TRUQAP.
Grade 4Permanently discontinue TRUQAP.
Cutaneous Adverse Reactions [see Warnings and Precautions (5.3)]Grade 2Withhold TRUQAP until recovery to ≤ Grade 1.Resume TRUQAP at the same dose.Persistent or recurrent: reduce TRUQAP by one lower dose.
Grade 3Withhold 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 4Permanently discontinue TRUQAP.
Other Adverse Reactions [see Adverse Reactions (6.1)]Grade 2Withhold TRUQAP until recovery to ≤ Grade 1.Resume TRUQAP at the same dose.
Grade 3Withhold 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 4Permanently discontinue TRUQAP.
" ], "dosage_forms_and_strengths": [ "3 DOSAGE FORMS AND STRENGTHS Tablets: • 160 mg: beige film-coated, round, biconvex tablets debossed with ‘CAV’ above ‘160’ on one side and plain on the reverse. • 200 mg: beige film-coated, capsule-shaped, biconvex tablets debossed with ‘CAV 200’ on one side and plain on the reverse. Tablets: 160 mg and 200 mg (3)" ], "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)" ], "warnings_and_cautions": [ "5 WARNINGS AND PRECAUTIONS • Hyperglycemia: TRUQAP can cause hyperglycemia. Evaluate blood glucose levels prior to starting and at regular intervals during treatment. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.2 , 2.4 , 5.1 ) • Diarrhea: TRUQAP caused diarrhea in most patients. Advise patients to increase oral fluids, start antidiarrheal treatment, and consult with a healthcare provider if diarrhea occurs while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.4 , 5.2 ) • Cutaneous Adverse Reactions: Monitor for signs and symptoms of cutaneous adverse reactions. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.4 , 5.3 ) • Embryo-Fetal Toxicity: TRUQAP can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information. ( 5.4 , 8.1 , 8.3 ) 5.1 Hyperglycemia Severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes, can occur in patients treated with TRUQAP. Increased fasting glucose from baseline occurred in 37% of patients treated with TRUQAP, including 11% of patients with Grade 2 (FG > 160 to 250 mg/dL), 2% with Grade 3 (FG > 250 to 500 mg/dL), and 1.1% with Grade 4 (FG > 500 mg/dL) events. The median time to first occurrence of hyperglycemia was 15 days (range: 1 to 367). Dose reduction for hyperglycemia was required in 0.6% of patients and permanent discontinuation was required in 0.6% of patients. Diabetic ketoacidosis occurred in 0.3% of patients and diabetic metabolic decompensation in 0.6% of patients. In CAPItello-291, 12% (43/355) of patients who received TRUQAP had an anti-hyperglycemic medication regimen either initiated or changed during the study, including treatment with insulin in 4.8% (17/355) of patients. The safety of TRUQAP has not been established in patients with Type I diabetes or diabetes requiring insulin. Patients with insulin-dependent diabetes were excluded from CAPItello-291. Before initiating treatment with TRUQAP, test fasting glucose levels (FPG or FBG), HbA1C levels, and optimize fasting glucose. After initiating treatment with TRUQAP, monitor or self-monitor fasting glucose levels on Day 3 or 4 of the dosing week during weeks 1, 2, 4, 6 and 8; then monthly while on treatment with TRUQAP; and as clinically indicated. Monitor HbA1C levels every 3 months during treatment with TRUQAP and as clinically indicated. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of fasting glucose levels. For patients who experience hyperglycemia during treatment with TRUQAP, monitor fasting glucose at least twice weekly, on days on and off TRUQAP, until fasting glucose decreases to baseline levels. During treatment with anti-diabetic medications, monitor fasting glucose at least once a week for 2 months, followed by once every 2 weeks, or as clinically indicated. Consider consultation with a healthcare practitioner with expertise in the treatment of hyperglycemia and initiation of fasting glucose monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients of the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes. Withhold TRUQAP immediately when ketoacidosis is suspected. If ketoacidosis is confirmed, permanently discontinue TRUQAP. Based on the severity of the hyperglycemia, withhold, reduce dose, or permanently discontinue TRUQAP [see Dosage and Administration (2.4) ] . 5.2 Diarrhea Severe diarrhea associated with dehydration occurred in patients who received TRUQAP. Diarrhea occurred in 72% of patients. Grade 3 or 4 diarrhea occurred in 9% of patients. The median time to first occurrence was 8 days (range 1 to 519). In the 257 patients with diarrhea, 59% required anti-diarrheal medications to manage symptoms. Dose reductions were required in 8% of patients, and 2% of patients permanently discontinued TRUQAP due to diarrhea. In patients with Grade ≥ 2 diarrhea (n=93) with at least 1 grade improvement (n=89), median time to improvement from the first event was 4 days (range: 1 to 154). Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity [see Dosage and Administration (2.4) ] . 5.3 Cutaneous Adverse Reactions Cutaneous adverse reactions, which can be severe, including erythema multiforme (EM), palmar-plantar erythrodysesthesia, and drug reaction with eosinophilia and systemic symptoms (DRESS), occurred in patients who received TRUQAP. Cutaneous adverse reactions occurred in 58% of patients. Grade 3 or 4 cutaneous adverse reactions occurred in 17% of patients receiving TRUQAP. EM occurred in 1.7% of patients and DRESS occurred in 0.3% of patients. Dose reduction was required in 7% of patients and 7% of patients permanently discontinued TRUQAP due to cutaneous adverse reactions. The median time to onset of cutaneous adverse reactions was 13 days (range 1 to 575 days). Among the 204 patients with cutaneous adverse reactions, 44% (90/204) required corticosteroid treatment. Of these, 37% (76/204) were treated with topical corticosteroids and 19% (39/204) with systemic corticosteroids. In patients with Grade ≥ 2 cutaneous adverse reaction (n= 116) with at least 1 grade improvement (n=104), median time to improvement from the first event was 12 days (range 2 to 544). Monitor patients for signs and symptoms of cutaneous adverse reactions. Early consultation with a dermatologist is recommended. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity [see Dosage and Administration (2.4) ] . 5.4 Embryo-Fetal Toxicity Based on findings from animals and mechanism of action, TRUQAP can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . 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 dosage of 400 mg twice daily. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRUQAP and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRUQAP and for 4 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] . TRUQAP is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information." ], "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%), decreased lymphocytes (49%), decreased hemoglobin (47%), fatigue (38%), increased fasting glucose (37%), nausea and decreased leukocytes (35% each), increased triglycerides (30%), stomatitis (25%), decreased neutrophils (25%), and vomiting (21%). Adverse reactions and laboratory abnormalities are listed in Table 4 and Table 5, respectively. Table 4: Adverse Reactions ≥ 10% in Patients who Received TRUQAP with Fulvestrant [with a Difference Between Arms of ≥ 3%] in CAPItello-291 Adverse Reaction TRUQAP with Fulvestrant N=155 Placebo with Fulvestrant N=133 All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Gastrointestinal Disorders Diarrhea 77 12 19 0.8 Nausea 35 1.3 14 0.8 Stomatitis Includes other related terms. 25 1.9 5 0 Vomiting 21 1.9 7 0.8 Skin and Subcutaneous Tissue Disorders Cutaneous adverse reactions Cutaneous adverse reaction includes butterfly rash, dermatitis, allergic dermatitis, dry skin, eczema, erythema multiforme, hand dermatitis, palmar-plantar erythrodysesthesia syndrome, pruritus, rash, erythematous rash, maculo-papular rash, papular rash, skin discoloration, skin fissures, skin reaction, skin ulcer, urticaria, purpura, erythema and drug eruption. 56 15 16 0.8 General Disorders and Administration Site Conditions Fatigue 38 1.9 27 1.5 Metabolism and Nutrition Disorders Decreased appetite 17 0 8 0.8 Nervous System Disorders Headache 17 0 13 0.8 Infections and Infestations Urinary tract infection 14 0.6 5 0 Renal and Urinary disorders Renal injury Renal injury includes acute kidney injury, renal failure, renal impairment, glomerular filtration rate decreased, increased creatinine and proteinuria. 11 2.6 1.5 0.8 Clinically relevant adverse reactions occurring in < 10% of patients treated with TRUQAP included anemia, pyrexia, dysgeusia, dyspepsia, pneumonia, weight decreased, and hypersensitivity (including anaphylactic reaction). Table 5: Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients who Received TRUQAP with Fulvestrant [With a Difference Between Arms ≥3%] in CAPItello-291 Laboratory Abnormality TRUQAP with Fulvestrant The denominator used to calculate the rate varied from 129 to 155 based on the number of patients with a baseline value and at least one post-treatment value. Placebo with Fulvestrant The denominator used to calculate the rate varied from 109 to 131 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Glucose Metabolism Increased random glucose 58 9 17 0 Increased fasting glucose 37 0.6 29 0 Hematology Decreased lymphocytes 49 11 14 2.3 Decreased hemoglobin 47 2 22 2.3 Decreased leukocytes 35 0.6 23 0 Decreased neutrophils 25 1.9 16 0.8 Decreased platelets 12 1.9 6 0.8 Other Categories Increased triglycerides 30 0.7 22 0.9 Increased alanine aminotransferase 23 2.6 13 0 Electrolytes/Renal Decreased corrected calcium 19 0.6 8 0 Increased creatinine 19 1.3 4.6 0.8 Decreased potassium 17 4.5 8 0" ], "adverse_reactions_table": [ "
Table 4: Adverse Reactions ≥ 10% in Patients who Received TRUQAP with Fulvestrant [with a Difference Between Arms of ≥ 3%] in CAPItello-291
Adverse Reaction TRUQAP with Fulvestrant N=155Placebo with Fulvestrant N=133
All Grades %Grade 3 or 4 %All Grades %Grade 3 or 4 %
Gastrointestinal Disorders
Diarrhea 7712190.8
Nausea 351.3140.8
StomatitisIncludes other related terms. 251.950
Vomiting 211.970.8
Skin and Subcutaneous Tissue Disorders
Cutaneous adverse reactionsCutaneous adverse reaction includes butterfly rash, dermatitis, allergic dermatitis, dry skin, eczema, erythema multiforme, hand dermatitis, palmar-plantar erythrodysesthesia syndrome, pruritus, rash, erythematous rash, maculo-papular rash, papular rash, skin discoloration, skin fissures, skin reaction, skin ulcer, urticaria, purpura, erythema and drug eruption. 5615160.8
General Disorders and Administration Site Conditions
Fatigue381.9271.5
Metabolism and Nutrition Disorders
Decreased appetite 17080.8
Nervous System Disorders
Headache 170130.8
Infections and Infestations
Urinary tract infection 140.650
Renal and Urinary disorders
Renal injuryRenal injury includes acute kidney injury, renal failure, renal impairment, glomerular filtration rate decreased, increased creatinine and proteinuria.112.61.50.8
", "
Table 5: Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients who Received TRUQAP with Fulvestrant [With a Difference Between Arms ≥3%] in CAPItello-291
Laboratory Abnormality TRUQAP with FulvestrantThe denominator used to calculate the rate varied from 129 to 155 based on the number of patients with a baseline value and at least one post-treatment value.Placebo with FulvestrantThe denominator used to calculate the rate varied from 109 to 131 based on the number of patients with a baseline value and at least one post-treatment value.
All Grades (%)Grade 3 or 4 (%)All Grades (%)Grade 3 or 4 (%)
Glucose Metabolism
Increased random glucose589170
Increased fasting glucose370.6290
Hematology
Decreased lymphocytes4911142.3
Decreased hemoglobin472222.3
Decreased leukocytes350.6230
Decreased neutrophils251.9160.8
Decreased platelets121.960.8
Other Categories
Increased triglycerides300.7220.9
Increased alanine aminotransferase232.6130
Electrolytes/Renal
Decreased corrected calcium190.680
Increased creatinine191.34.60.8
Decreased potassium174.580
" ], "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." ], "drug_interactions_table": [ "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.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)].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.When concomitantly used with moderate CYP3A inhibitor, reduce the dose of TRUQAP and monitor patients for adverse reactions [see Dosage and Administration (2.5)].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. Avoid concomitant use of TRUQAP with strong or moderate CYP3A inducers.
Table 6: Drug Interactions with TRUQAP
Strong CYP3A Inhibitors
Clinical Impact
•
Prevention or Management
•
Moderate CYP3A Inhibitors
Clinical Impact
•
Prevention or Management
•
Strong and Moderate CYP3A Inducers
Clinical Impact
•
Prevention or Management
•
" ], "use_in_specific_populations": [ "8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 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. 8.2 Lactation Risk Summary TRUQAP is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for lactation information. There are no data on the presence of capivasertib or its metabolites in human milk or their effects on milk production or the breastfed child. Capivasertib was detected in the plasma of suckling rat pups ( see Data ). Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with TRUQAP. Data Animal Data In a pre- and post-natal assessment, when capivasertib was administered to maternal rats during the lactation period, capivasertib was detected in plasma of suckling rat pups on lactation day 7 to 8 [see Use in Specific Populations (8.1) ] . Plasma concentrations in pups were up to 0.6% of concentrations in maternal plasma in the 150 mg/kg/day group. 8.3 Females and Males of Reproductive Potential TRUQAP is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for contraception and infertility information. TRUQAP can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating TRUQAP [see Use in Specific Populations (8.1) ] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment with TRUQAP and for 1 month after the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRUQAP and for 4 months after the last dose. 8.4 Pediatric Use The safety and effectiveness of TRUQAP have not been established in pediatric patients. 8.5 Geriatric Use Of the 355 patients who received TRUQAP in CAPItello-291, 115 (32%) patients were ≥ 65 years of age and 24 (7%) patients were ≥ 75 years of age. No overall differences in the efficacy of TRUQAP were observed between patients ≥ 65 years of age and younger patients. Analysis of the safety of TRUQAP comparing patients ≥ 65 years of age to younger patients suggest a higher incidence of Grade 3 to 5 adverse reactions (57% versus 36%), dosage reductions (30% versus 15%), dose interruptions (57% versus 30%), and permanent discontinuations (23% versus 8%), respectively. 8.6 Renal Impairment No dosage modification is recommended for patients with mild to moderate (creatinine clearance (CLcr) 30 to 89 mL/min) renal impairment [see Clinical Pharmacology (12.3) ] . TRUQAP has not been studied in patients with severe (CLcr 15 to 29 mL/min) renal impairment. 8.7 Hepatic Impairment No dosage modification is recommended for patients with mild hepatic impairment (bilirubin ≤ upper limit of normal (ULN) and AST > ULN or bilirubin > 1 to 1.5x ULN and any AST) [see Clinical Pharmacology (12.3) ] . Monitor patients with moderate (bilirubin > 1.5 to 3x ULN and any AST) hepatic impairment for adverse reactions due to potential increased capivasertib exposure [see Warnings and Precautions (5.1 , 5.2 , 5.3) ] . TRUQAP has not been studied in patients with severe (bilirubin > 3x ULN and any AST) hepatic impairment." ], "pregnancy": [ "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." ], "pediatric_use": [ "8.4 Pediatric Use The safety and effectiveness of TRUQAP have not been established in pediatric patients." ], "geriatric_use": [ "8.5 Geriatric Use Of the 355 patients who received TRUQAP in CAPItello-291, 115 (32%) patients were ≥ 65 years of age and 24 (7%) patients were ≥ 75 years of age. No overall differences in the efficacy of TRUQAP were observed between patients ≥ 65 years of age and younger patients. Analysis of the safety of TRUQAP comparing patients ≥ 65 years of age to younger patients suggest a higher incidence of Grade 3 to 5 adverse reactions (57% versus 36%), dosage reductions (30% versus 15%), dose interruptions (57% versus 30%), and permanent discontinuations (23% versus 8%), respectively." ], "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" ], "clinical_pharmacology": [ "12 CLINICAL PHARMACOLOGY 12.1 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 . 12.2 Pharmacodynamics Exposure-Response Relationships The exposure-response relationship and time course of pharmacodynamic response for the effectiveness of capivasertib have not been fully characterized. Exposure-response relationships were observed for diarrhea (CTCAE Grade 2 to 4), rash (CTCAE Grade 2 to 4) and hyperglycemia (CTCAE Grades 3 or 4) at doses of 80 to 800 mg (0.2 to 2 times the approved recommended dosage). Cardiac Electrophysiology At the recommended TRUQAP dose, a mean increase in the QTc interval > 20 ms was not observed. 12.3 Pharmacokinetics Capivasertib pharmacokinetic parameters are presented as the mean [%coefficient of variation (%CV)], unless otherwise specified. The capivasertib steady-state AUC is 8,069 h·ng/mL (37%) and C max is 1,371 ng/mL (30%). Steady-state concentrations are predicted to be attained on the 3 rd and 4 th dosing day of each week, starting week 2. Capivasertib plasma concentrations are approximately 0.5% to 15% of the steady state C max during the off-dosing days. Capivasertib AUC and C max are proportional with dose over a range of 80 to 800 mg (0.2 to 2 times the approved recommended dosage). Absorption T max is approximately 1-2 hours. The absolute bioavailability is 29%. Effect of Food No clinically meaningful differences in capivasertib pharmacokinetics were observed following administration of TRUQAP with a high-fat meal (approximately 1,000 kcal; fat 60%) or a low-fat meal (approximately 400 kcal; fat 26%). Distribution The steady state oral volume of distribution is 1,847 L (36%). Capivasertib plasma protein binding is 78% and the plasma-to-blood ratio is 0.71. Elimination The half-life is 8.3 hours, and the steady-state oral clearance is 50 L/h (37% CV). Renal clearance was 21% of total clearance. Metabolism Capivasertib is primarily metabolized by CYP3A4 and UGT2B7. Excretion Following a single radiolabeled oral dose of 400 mg, the mean total recovery was 45% from urine and 50% from feces. Specific Populations No clinically significant differences in capivasertib pharmacokinetics were observed based on race/ethnicity (including White, Asian, Black, American Indian or Alaskan Native, and Native Hawaiian or Other Pacific Islander), sex (88% females), body weight (32 to 150 kg), age (26 to 87 years), mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin > 1 to 1.5x ULN), or mild to moderate renal impairment (CLcr 30 to 89 mL/min). The effect of moderate (bilirubin > 1.5 to 3x ULN and any AST) hepatic impairment is not fully characterized. TRUQAP has not been studied in patients with severe (bilirubin > 3x ULN and any AST) hepatic impairment or severe renal impairment (CLcr 15 to 29 mL/min). Drug Interaction Studies Clinical Studies and Model-Informed Approaches Effect of Strong and Moderate CYP3A Inhibitors on Capivasertib: Itraconazole (strong CYP3A4 inhibitor) is predicted to increase capivasertib AUC by up to 1.7-fold and C max by up to 1.4-fold. Erythromycin and verapamil (moderate CYP3A inhibitors) are predicted to increase capivasertib AUC by up to 1.5-fold and C max by up to 1.3-fold. Effect of Strong and Moderate CYP3A Inducers on Capivasertib: Rifampicin (strong CYP3A4 inducer) is predicted to decrease capivasertib AUC by 70% and C max by 60%. Efavirenz (moderate CYP3A4 inducer) is predicted to decrease capivasertib AUC by 60% and C max by 50%. Effect of UGT2B7 Inhibitors on Capivasertib: Probenecid (UGT2B7 inhibitor) is not predicted to have a clinically meaningful effect on capivasertib pharmacokinetics. Effect of Acid Reducing Agents on Capivasertib: Rabeprazole (gastric acid reducing agent) did not have a clinically meaningful effect on capivasertib pharmacokinetics. Effect of Capivasertib on CYP3A Substrates: Concomitant use of TRUQAP increased midazolam (CYP3A substrate) AUC by 1.8-fold on day 4 and by 1.2-fold on day 7. Effect of Capivasertib on CYP2D6 Substrates: TRUQAP is predicted to increase desipramine (CYP2D6 substrate) AUC by up to 2.1-fold on day 4. Effect of Capivasertib on CYP2C9 Substrates: Concomitant use of TRUQAP with warfarin (CYP2C9 substrate) is not predicted to have a clinically meaningful effect on warfarin pharmacokinetics. Effect of Capivasertib on UGT1A1 Substrates: TRUQAP is predicted to increase raltegravir (UGT1A1 substrate) AUC by up to 1.7-fold on day 4. In-Vitro Studies Capivasertib inhibits BCRP, OATP1B1, OATP1B3, OAT3, MATE1, MATE2-K, and OCT2." ], "mechanism_of_action": [ "12.1 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 ." ], "pharmacodynamics": [ "12.2 Pharmacodynamics Exposure-Response Relationships The exposure-response relationship and time course of pharmacodynamic response for the effectiveness of capivasertib have not been fully characterized. Exposure-response relationships were observed for diarrhea (CTCAE Grade 2 to 4), rash (CTCAE Grade 2 to 4) and hyperglycemia (CTCAE Grades 3 or 4) at doses of 80 to 800 mg (0.2 to 2 times the approved recommended dosage). Cardiac Electrophysiology At the recommended TRUQAP dose, a mean increase in the QTc interval > 20 ms was not observed." ], "pharmacokinetics": [ "12.3 Pharmacokinetics Capivasertib pharmacokinetic parameters are presented as the mean [%coefficient of variation (%CV)], unless otherwise specified. The capivasertib steady-state AUC is 8,069 h·ng/mL (37%) and C max is 1,371 ng/mL (30%). Steady-state concentrations are predicted to be attained on the 3 rd and 4 th dosing day of each week, starting week 2. Capivasertib plasma concentrations are approximately 0.5% to 15% of the steady state C max during the off-dosing days. Capivasertib AUC and C max are proportional with dose over a range of 80 to 800 mg (0.2 to 2 times the approved recommended dosage). Absorption T max is approximately 1-2 hours. The absolute bioavailability is 29%. Effect of Food No clinically meaningful differences in capivasertib pharmacokinetics were observed following administration of TRUQAP with a high-fat meal (approximately 1,000 kcal; fat 60%) or a low-fat meal (approximately 400 kcal; fat 26%). Distribution The steady state oral volume of distribution is 1,847 L (36%). Capivasertib plasma protein binding is 78% and the plasma-to-blood ratio is 0.71. Elimination The half-life is 8.3 hours, and the steady-state oral clearance is 50 L/h (37% CV). Renal clearance was 21% of total clearance. Metabolism Capivasertib is primarily metabolized by CYP3A4 and UGT2B7. Excretion Following a single radiolabeled oral dose of 400 mg, the mean total recovery was 45% from urine and 50% from feces. Specific Populations No clinically significant differences in capivasertib pharmacokinetics were observed based on race/ethnicity (including White, Asian, Black, American Indian or Alaskan Native, and Native Hawaiian or Other Pacific Islander), sex (88% females), body weight (32 to 150 kg), age (26 to 87 years), mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin > 1 to 1.5x ULN), or mild to moderate renal impairment (CLcr 30 to 89 mL/min). The effect of moderate (bilirubin > 1.5 to 3x ULN and any AST) hepatic impairment is not fully characterized. TRUQAP has not been studied in patients with severe (bilirubin > 3x ULN and any AST) hepatic impairment or severe renal impairment (CLcr 15 to 29 mL/min). Drug Interaction Studies Clinical Studies and Model-Informed Approaches Effect of Strong and Moderate CYP3A Inhibitors on Capivasertib: Itraconazole (strong CYP3A4 inhibitor) is predicted to increase capivasertib AUC by up to 1.7-fold and C max by up to 1.4-fold. Erythromycin and verapamil (moderate CYP3A inhibitors) are predicted to increase capivasertib AUC by up to 1.5-fold and C max by up to 1.3-fold. Effect of Strong and Moderate CYP3A Inducers on Capivasertib: Rifampicin (strong CYP3A4 inducer) is predicted to decrease capivasertib AUC by 70% and C max by 60%. Efavirenz (moderate CYP3A4 inducer) is predicted to decrease capivasertib AUC by 60% and C max by 50%. Effect of UGT2B7 Inhibitors on Capivasertib: Probenecid (UGT2B7 inhibitor) is not predicted to have a clinically meaningful effect on capivasertib pharmacokinetics. Effect of Acid Reducing Agents on Capivasertib: Rabeprazole (gastric acid reducing agent) did not have a clinically meaningful effect on capivasertib pharmacokinetics. Effect of Capivasertib on CYP3A Substrates: Concomitant use of TRUQAP increased midazolam (CYP3A substrate) AUC by 1.8-fold on day 4 and by 1.2-fold on day 7. Effect of Capivasertib on CYP2D6 Substrates: TRUQAP is predicted to increase desipramine (CYP2D6 substrate) AUC by up to 2.1-fold on day 4. Effect of Capivasertib on CYP2C9 Substrates: Concomitant use of TRUQAP with warfarin (CYP2C9 substrate) is not predicted to have a clinically meaningful effect on warfarin pharmacokinetics. Effect of Capivasertib on UGT1A1 Substrates: TRUQAP is predicted to increase raltegravir (UGT1A1 substrate) AUC by up to 1.7-fold on day 4. In-Vitro Studies Capivasertib inhibits BCRP, OATP1B1, OATP1B3, OAT3, MATE1, MATE2-K, and OCT2." ], "nonclinical_toxicology": [ "13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year rat carcinogenicity study, rats received oral doses up to 30 mg/kg/day in males and 75 mg/kg/day in females (approximately 0.2 times and 0.4 times the human exposure at the recommended dose based on AUC, respectively). While there were no statistically significant increases in tumors, there was an increase in malignant mesothelioma in the testis of male rats at 30 mg/kg/day, which is considered a rare tumor in the tested rat strain. Capivasertib was genotoxic in the in vivo rat bone marrow micronucleus assay through an aneugenic mechanism. Capivasertib was not mutagenic in vitro in a bacterial reverse mutation (Ames) assay or mouse lymphoma gene mutation assay. In repeat-dose toxicity studies up to 26 weeks duration in rats and 39 weeks duration in dogs, tubular degeneration in the testes and cellular debris in the epididymides were observed at oral capivasertib doses of 100 mg/kg/day in rats and 15 mg/kg/day in dogs (approximately 1 time the human exposure at the recommended dose of 400 mg twice daily based on AUC). In a male fertility study, capivasertib had no effect on fertility in male rats at oral doses up to 100 mg/kg/day following 10 weeks of treatment. Effects of capivasertib on female fertility have not been studied in animals. 13.2 Animal Toxicology and/or Pharmacology Oral administration of capivasertib for up to 2 years resulted in islet of Langerhans hypertrophy/ hyperplasia in the pancreas and lens degeneration in rats at doses ≥ 15 mg/kg/day (≥ 0.1 times the human exposure at the recommended dose based on AUC)." ], "carcinogenesis_and_mutagenesis_and_impairment_of_fertility": [ "13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year rat carcinogenicity study, rats received oral doses up to 30 mg/kg/day in males and 75 mg/kg/day in females (approximately 0.2 times and 0.4 times the human exposure at the recommended dose based on AUC, respectively). While there were no statistically significant increases in tumors, there was an increase in malignant mesothelioma in the testis of male rats at 30 mg/kg/day, which is considered a rare tumor in the tested rat strain. Capivasertib was genotoxic in the in vivo rat bone marrow micronucleus assay through an aneugenic mechanism. Capivasertib was not mutagenic in vitro in a bacterial reverse mutation (Ames) assay or mouse lymphoma gene mutation assay. In repeat-dose toxicity studies up to 26 weeks duration in rats and 39 weeks duration in dogs, tubular degeneration in the testes and cellular debris in the epididymides were observed at oral capivasertib doses of 100 mg/kg/day in rats and 15 mg/kg/day in dogs (approximately 1 time the human exposure at the recommended dose of 400 mg twice daily based on AUC). In a male fertility study, capivasertib had no effect on fertility in male rats at oral doses up to 100 mg/kg/day following 10 weeks of treatment. Effects of capivasertib on female fertility have not been studied in animals." ], "clinical_studies": [ "14 CLINICAL STUDIES The efficacy of TRUQAP with fulvestrant was evaluated in CAPItello-291 (NCT04305496), a randomized, double-blind, placebo-controlled, multicenter trial that enrolled 708 adult patients with locally advanced (inoperable) or metastatic HR-positive, HER2-negative (defined as IHC 0 or 1+, or IHC 2+/ISH-) breast cancer of which 289 patients had tumors with eligible PIK3CA/AKT1/PTEN -alterations. Eligible PIK3CA/AKT1 activating mutations or PTEN loss of function alterations were identified in the majority of FFPE tumor specimens using FoundationOne®CDx next-generation sequencing (n=686). All patients were required to have progression on an aromatase inhibitor (AI) based treatment in the metastatic setting or recurrence on or within 12 months of completing (neo) adjuvant treatment with an AI. Patients could have received up to two prior lines of endocrine therapy and up to 1 line of chemotherapy for locally advanced (inoperable) or metastatic disease. Patients were excluded if they had clinically significant abnormalities of glucose metabolism (defined as patients with diabetes mellitus Type 1, Type 2, requiring insulin treatment, or HbA1c ≥8% (63.9 mmol/mol)). Patients were randomized (1:1) to receive either 400 mg of TRUQAP (n=355) or placebo (n=353), given orally twice daily for 4 days followed by 3 days off treatment each week of 28-day treatment cycle. Fulvestrant 500 mg intramuscular injection was administered on cycle 1 days 1 and 15, and then at day 1 of each subsequent 28-day cycle. Patients were treated until disease progression, or unacceptable toxicity. Randomization was stratified by presence of liver metastases (yes vs. no), prior treatment with CDK4/6 inhibitors (yes vs. no) and geographical region (region 1: US, Canada, Western Europe, Australia, and Israel vs region 2: Latin America, Eastern Europe and Russia vs Region 3: Asia). The major efficacy outcomes were investigator-assessed progression-free survival (PFS) in the overall population, and in the population of patients whose tumors have PIK3CA/AKT1/PTEN -alterations evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Additional efficacy outcome measures were overall survival (OS), investigator assessed objective response rate (ORR) and duration of response (DoR). A statistically significant difference in PFS was observed in the overall population and the population of patients whose tumors have PIK3CA/AKT1/PTEN -alteration. An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN -alteration showed a HR of 0.79 (95% CI: 0.61, 1.02), indicating that the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN -alteration. Of the 289 patients whose tumors were PIK3CA/AKT1/PTEN -altered, the median age was 59 years (range 34 to 90); female (99%); White (52%), Asian (29%), Black (1%), American Indian/Alaska Native (0.7%), other races (17%) and 9% were Hispanic/Latino. Eastern Cooperative Oncology Group (ECOG) performance status was 0 (66%) or 1 (34%), and 18% were premenopausal or perimenopausal. Seventy-six percent of patients had an alteration in PIK3CA , 13% had an alteration in AKT1 , and 17% had an alteration in PTEN . All patients received prior endocrine-based therapy (100% AI based treatment and 44% received tamoxifen). Seventy-one percent of patients were previously treated with a CDK4/6 inhibitor and 18% received prior chemotherapy for locally advanced (inoperable) or metastatic disease. Efficacy results for PIK3CA/AKT1/PTEN -altered subgroup are presented in Table 7 and Figure 1. Results from the blinded independent review committee (BICR) assessment were consistent with the investigator assessed PFS results. Overall survival results were immature at the time of the PFS analysis (30% of the patients died). Table 7: Efficacy Results for CAPItello-291 (Patients with PIK3CA/AKT1/PTEN-Altered Tumors) TRUQAP with fulvestrant N=155 Placebo with fulvestrant N=134 Investigator-Assessed Progression-Free Survival (PFS) Number of events (%) 121 (78%) 115 (86%) Median, months (95%CI) 7.3 (5.5, 9.0) 3.1 (2.0, 3.7) Hazard ratio (95% CI) Stratified Cox proportional hazards model stratified by presence of liver metastases (yes vs no), and prior use of CDK4/6 inhibitors (yes vs no). 0.50 (0.38, 0.65) p-value Stratified log-rank test stratified by presence of liver metastases (yes vs no), and prior use of CDK4/6 inhibitors (yes vs no). <0.0001 Investigator-Assessed Confirmed Objective Response Rate (ORR) Patients with measurable disease 132 124 ORR (95% CI) 26% (19, 34) 8% (4, 14) Complete response rate 2.3% 0 Partial response rate 23% 8% Median DoR, months (95%CI) 10.2 (7.7, NC NC = not calculable ) 8.6 (3.8, 9.2) Figure 1: Kaplan-Meier Plot of Progression-Free Survival in CAPItello-291 (Investigator Assessment, Patients with PIK3CA/AKT1/PTEN -Altered Tumors) figure_1" ], "clinical_studies_table": [ "Number of events (%)Median, months (95%CI)Hazard ratio (95% CI)Stratified Cox proportional hazards model stratified by presence of liver metastases (yes vs no), and prior use of CDK4/6 inhibitors (yes vs no).p-valueStratified log-rank test stratified by presence of liver metastases (yes vs no), and prior use of CDK4/6 inhibitors (yes vs no).Patients with measurable diseaseORR (95% CI)Complete response ratePartial response rateMedian DoR, months (95%CI)
Table 7: Efficacy Results for CAPItello-291 (Patients with PIK3CA/AKT1/PTEN-Altered Tumors)
TRUQAP with fulvestrant N=155Placebo with fulvestrant N=134
Investigator-Assessed Progression-Free Survival (PFS)
121 (78%)115 (86%)
7.3 (5.5, 9.0)3.1 (2.0, 3.7)
0.50 (0.38, 0.65)
<0.0001
Investigator-Assessed Confirmed Objective Response Rate (ORR)
132124
26% (19, 34)8% (4, 14)
2.3%0
23%8%
10.2 (7.7, NCNC = not calculable)8.6 (3.8, 9.2)
" ], "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." ], "how_supplied_table": [ "
Table 8: TRUQAP 160 mg and 200 mg Tablets
StrengthDescriptionPackage Size and TypeNDC Number
TRUQAP 160 mgBeige 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 tablets0310-9500-01
TRUQAP 200 mgBeige 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 tablets0310-9501-01
TRUQAP 160 mgBeige 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 mgBeige 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
" ], "information_for_patients": [ "17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hyperglycemia Advise patients that TRUQAP can cause hyperglycemia and that they will need to monitor their fasting blood glucose periodically during therapy. Advise patients to contact their healthcare provider immediately for signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often, blurred vision, mental confusion, difficulty breathing, or increased appetite with weight loss) or ketoacidosis [see Warnings and Precautions (5.1) ] . Diarrhea Advise patients that TRUQAP can cause diarrhea and to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs while taking TRUQAP [see Warnings and Precautions (5.2) ] . Cutaneous Adverse Reactions Advise patients that TRUQAP can cause cutaneous adverse reactions and to contact their healthcare provider immediately to report new or worsening rash, erythematous and exfoliative skin reactions [see Warnings and Precautions (5.3) ] . Embryo-Fetal Toxicity • Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ] . Advise pregnant women and females of reproductive potential of the potential risk to a fetus. • Advise females of reproductive potential to use effective contraception during treatment with TRUQAP and for 1 month after the last dose [see Use in Specific Population (8.3) ] . • Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRUQAP and for 4 months after the last dose [see Use in Specific Populations (8.3) ] . • Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information. Lactation Advise women to not breastfeed during treatment with TRUQAP [see Use in Specific Populations (8.2) ] . Refer to the Full Prescribing Information of fulvestrant for lactation information. Dosing Instructions Instruct patients to take TRUQAP 2 times each day, at about the same times each day, for four days on and 3 days off, with or without food. Swallow the tablet(s) whole with water. Tablets should not be chewed, crushed, or split prior to swallowing. [see Dosage and Administration (2.3) ] . Instruct patients that if the dose is missed, it can be taken within 4 hours after the time it is usually taken. If more than 4 hours has passed, skip the dose. Take the next dose at the usual time. Instruct patients that if they vomit after taking the dose, an additional dose should not be taken. The next dose of TRUQAP should be taken at the usual time [ see Dosage and Administration (2.3) ] . Drug Interactions Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter medications, vitamins, and herbal products [see Drug Interactions (7.1) ] . Grapefruit may interact with TRUQAP. Patients should not consume grapefruit products while taking TRUQAP. Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 TRUQAP is a registered trademark of the AstraZeneca group of companies. ©AstraZeneca 2025" ], "spl_unclassified_section": [ "Patient Package Insert PATIENT INFORMATION TRUQAP ® (TRUE-cap) (capivasertib) tablets What is TRUQAP? TRUQAP is a prescription medicine used in combination with the medicine fulvestrant to treat adults who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that is advanced or that has spread to other parts of the body (metastatic), with an abnormal “ PIK3CA”, “AKT1”, or “PTEN” gene, and whose disease has progressed on or after endocrine therapy. Your healthcare provider will test your cancer for an abnormal “PIK3CA” , “AKT1” , or “PTEN” gene to make sure that TRUQAP is right for you. It is not known if TRUQAP is safe and effective in children. Do not take TRUQAP if you: Have had a severe allergic reaction to TRUQAP or are allergic to any of the ingredients of TRUQAP. See the end of this leaflet for a list of the ingredients in TRUQAP. Before you take TRUQAP, tell your healthcare provider about all of your medical conditions, including if you: • have a history of high levels of sugar in your blood or diabetes. • have a history of rash or other skin disorders. • have liver problems. • have any current infection. • are pregnant or plan to become pregnant. TRUQAP can harm your unborn baby. Females who are able to become pregnant: ∘ Your healthcare provider will check to see if you are pregnant before you start treatment with TRUQAP. ∘ You should use effective birth control during treatment with TRUQAP and for 1 month after the last dose. Talk to your healthcare provider about birth control methods that may be right for you during this time. ∘ If you become pregnant or think you are pregnant, tell your healthcare provider right away. Males with female partners who are able to become pregnant should use effective birth control during your treatment with TRUQAP and for 4 months after the last dose. If your female partner becomes pregnant, tell your healthcare provider right away. • are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with TRUQAP. Talk to your healthcare provider about the best way to feed your baby during treatment with TRUQAP. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. TRUQAP may affect the way other medicines work, and other medicines may affect how TRUQAP works. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. How should I take TRUQAP? • Take TRUQAP exactly as your healthcare provider tells you. • Do not change your dose or stop taking TRUQAP unless your healthcare provider tells you. • Take TRUQAP 2 times each day (about 12 hours apart) in the morning and evening, at about the same times each day. • Take TRUQAP for 4 days in a row, followed by 3 days not taking TRUQAP each week. • Take TRUQAP with or without food. • Swallow TRUQAP tablets whole with water. Do not chew, crush, or split the tablets. • Do not take any tablets that are broken, cracked, or that look damaged. • If you miss a dose of TRUQAP, you may still take it within 4 hours from the time you usually take it. If it has been more than 4 hours after you usually take your dose, skip that dose. Take the next dose at your usual time. Do not take 2 doses at the same time to make up for a missed dose. • If you vomit after taking a dose of TRUQAP, do not take an additional dose. Take your next dose at your usual time. • For women who have not reached menopause or are just starting menopause, your healthcare provider will prescribe a medicine called a luteinizing hormone-releasing hormone (LHRH) agonist to take with TRUQAP and fulvestrant. For men, your healthcare provider may prescribe a LHRH agonist to take with TRUQAP and fulvestrant. What are the possible side effects of TRUQAP? TRUQAP may cause severe side effects, including: • High blood sugar levels (hyperglycemia) - Hyperglycemia is common with TRUQAP and may be severe. Untreated severe hyperglycemia can lead to a condition called diabetic ketoacidosis that can happen in people treated with TRUQAP. Diabetic ketoacidosis is a serious condition that requires treatment in a hospital and that can lead to death. Your healthcare provider will monitor your blood sugar levels before you start and during treatment with TRUQAP. It is not known if TRUQAP is safe in people with type 1 diabetes or people who use insulin to treat their diabetes. Your healthcare provider will monitor your blood sugar levels more often if you have a history of diabetes. Tell your healthcare provider right away if you develop symptoms of hyperglycemia,: ∘ excessive thirst ∘ dry mouth ∘ more frequent urination than usual or a bigger amount of urine than normal ∘ blurred vision ∘ increased appetite with weight loss ∘ stomach area (abdominal) pain ∘ unusual tiredness ∘ confusion ∘ nausea ∘ vomiting ∘ fruity odor on breath ∘ dry or flushed skin ∘ difficulty breathing ∘ sleepiness • Diarrhea. Diarrhea is common during treatment with TRUQAP and may be severe. Severe diarrhea can lead to the loss of too much body water (dehydration). Tell your healthcare provider if you develop any signs of diarrhea, including loose or watery stool. Your healthcare provider will tell you to drink more fluids or take medicines to treat diarrhea. • Skin reactions. Skin reactions are common with TRUQAP and can be severe. Tell your healthcare provider or get medical help right away if you get a new or worsening rash, reddening of the skin, fever, blistering of the lips, eyes or mouth, blisters on the skin, skin peeling, or dry skin. Your healthcare provider may tell you to decrease your dose, temporarily stop your treatment, or completely stop your treatment with TRUQAP if you get certain serious side effects. The most common side effects of TRUQAP include: ∘ nausea ∘ tiredness ∘ vomiting ∘ mouth sores ∘ changes in certain blood tests These are not all of the possible side effects of TRUQAP. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1‑800-FDA-1088. What should I avoid while taking TRUQAP? • You should not drink grapefruit juice or eat grapefruit during treatment with TRUQAP. How should I store TRUQAP? • Store TRUQAP in original packaging at room temperature between 68°F to 77°F (20°C to 25°C). • Throw away (discard) TRUQAP after 45 days if the tablets are not kept in the original packaging. • TRUQAP comes in child resistant packaging. Keep TRUQAP and all medicines out of the reach of children. General information about the safe and effective use of TRUQAP. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TRUQAP for a condition for which it was not prescribed. Do not give TRUQAP to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TRUQAP that is written for health professionals. What are the ingredients in TRUQAP? Active ingredient: capivasertib. Inactive ingredients: copovidone, croscarmellose sodium, dibasic calcium phosphate, hypromellose, iron oxide black, iron oxide red, iron oxide yellow, magnesium stearate, medium chain triglycerides, microcrystalline cellulose, polydextrose, polyethylene glycol 3350, and titanium dioxide Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 TRUQAP is a registered trademark of the AstraZeneca group of companies. ©AstraZeneca 2025 For more information, go to https://www.TRUQAP.com or call 1-800-236-9933. If you still have questions, contact your healthcare provider. This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 02/2025" ], "spl_unclassified_section_table": [ "have a history of high levels of sugar in your blood or diabetes. have a history of rash or other skin disorders. have liver problems.have any current infection.are pregnant or plan to become pregnant. TRUQAP can harm your unborn baby.Females who are able to become pregnant:Your healthcare provider will check to see if you are pregnant before you start treatment with TRUQAP. You should use effective birth control during treatment with TRUQAP and for 1 month after the last dose. Talk to your healthcare provider about birth control methods that may be right for you during this time. If you become pregnant or think you are pregnant, tell your healthcare provider right away.Males with female partners who are able to become pregnant should use effective birth control during your treatment with TRUQAP and for 4 months after the last dose. If your female partner becomes pregnant, tell your healthcare provider right away. are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with TRUQAP. Talk to your healthcare provider about the best way to feed your baby during treatment with TRUQAP. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. TRUQAP may affect the way other medicines work, and other medicines may affect how TRUQAP works. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.Take TRUQAP exactly as your healthcare provider tells you.Do not change your dose or stop taking TRUQAP unless your healthcare provider tells you.Take TRUQAP 2 times each day (about 12 hours apart) in the morning and evening, at about the same times each day.Take TRUQAP for 4 days in a row, followed by 3 days not taking TRUQAP each week. Take TRUQAP with or without food. Swallow TRUQAP tablets whole with water. Do not chew, crush, or split the tablets. Do not take any tablets that are broken, cracked, or that look damaged.If you miss a dose of TRUQAP, you may still take it within 4 hours from the time you usually take it. If it has been more than 4 hours after you usually take your dose, skip that dose. Take the next dose at your usual time. Do not take 2 doses at the same time to make up for a missed dose. If you vomit after taking a dose of TRUQAP, do not take an additional dose. Take your next dose at your usual time.For women who have not reached menopause or are just starting menopause, your healthcare provider will prescribe a medicine called a luteinizing hormone-releasing hormone (LHRH) agonist to take with TRUQAP and fulvestrant. For men, your healthcare provider may prescribe a LHRH agonist to take with TRUQAP and fulvestrant.High blood sugar levels (hyperglycemia) - Hyperglycemia is common with TRUQAP and may be severe. Untreated severe hyperglycemia can lead to a condition called diabetic ketoacidosis that can happen in people treated with TRUQAP. Diabetic ketoacidosis is a serious condition that requires treatment in a hospital and that can lead to death. Your healthcare provider will monitor your blood sugar levels before you start and during treatment with TRUQAP. It is not known if TRUQAP is safe in people with type 1 diabetes or people who use insulin to treat their diabetes. Your healthcare provider will monitor your blood sugar levels more often if you have a history of diabetes. Tell your healthcare provider right away if you develop symptoms of hyperglycemia,:excessive thirstdry mouthmore frequent urination than usual or a bigger amount of urine than normalblurred visionincreased appetite with weight lossstomach area (abdominal) painunusual tirednessconfusion nauseavomitingfruity odor on breathdry or flushed skindifficulty breathingsleepinessDiarrhea. Diarrhea is common during treatment with TRUQAP and may be severe. Severe diarrhea can lead to the loss of too much body water (dehydration). Tell your healthcare provider if you develop any signs of diarrhea, including loose or watery stool. Your healthcare provider will tell you to drink more fluids or take medicines to treat diarrhea.Skin reactions. Skin reactions are common with TRUQAP and can be severe. Tell your healthcare provider or get medical help right away if you get a new or worsening rash, reddening of the skin, fever, blistering of the lips, eyes or mouth, blisters on the skin, skin peeling, or dry skin.Your healthcare provider may tell you to decrease your dose, temporarily stop your treatment, or completely stop your treatment with TRUQAP if you get certain serious side effects.The most common side effects of TRUQAP include:nauseatirednessvomitingmouth soreschanges in certain blood testsYou should not drink grapefruit juice or eat grapefruit during treatment with TRUQAP.Store TRUQAP in original packaging at room temperature between 68°F to 77°F (20°C to 25°C).Throw away (discard) TRUQAP after 45 days if the tablets are not kept in the original packaging.TRUQAP comes in child resistant packaging. Keep TRUQAP and all medicines out of the reach of children.
PATIENT INFORMATIONTRUQAP® (TRUE-cap)(capivasertib)tablets
What is TRUQAP?TRUQAP is a prescription medicine used in combination with the medicine fulvestrant to treat adults who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that is advanced or that has spread to other parts of the body (metastatic), with an abnormal “PIK3CA”, “AKT1”, or “PTEN” gene, and whose disease has progressed on or after endocrine therapy. Your healthcare provider will test your cancer for an abnormal “PIK3CA”, “AKT1”, or “PTEN” gene to make sure that TRUQAP is right for you.It is not known if TRUQAP is safe and effective in children.
Do not take TRUQAP if you:Have had a severe allergic reaction to TRUQAP or are allergic to any of the ingredients of TRUQAP. See the end of this leaflet for a list of the ingredients in TRUQAP.
Before you take TRUQAP, tell your healthcare provider about all of your medical conditions, including if you:
••••• ∘∘∘ •
How should I take TRUQAP?
••••••••••
What are the possible side effects of TRUQAP?TRUQAP may cause severe side effects, including:
•
∘∘∘∘∘∘∘
∘∘∘∘∘∘∘
••
 ∘∘∘
∘∘
These are not all of the possible side effects of TRUQAP. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1‑800-FDA-1088.
What should I avoid while taking TRUQAP?
•
How should I store TRUQAP?
•••
General information about the safe and effective use of TRUQAP.Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TRUQAP for a condition for which it was not prescribed. Do not give TRUQAP to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TRUQAP that is written for health professionals.
What are the ingredients in TRUQAP?Active ingredient: capivasertib.Inactive ingredients: copovidone, croscarmellose sodium, dibasic calcium phosphate, hypromellose, iron oxide black, iron oxide red, iron oxide yellow, magnesium stearate, medium chain triglycerides, microcrystalline cellulose, polydextrose, polyethylene glycol 3350, and titanium dioxide Distributed by: AstraZeneca Pharmaceuticals LPWilmington, DE 19850 TRUQAP is a registered trademark of the AstraZeneca group of companies.©AstraZeneca 2025For more information, go to https://www.TRUQAP.com or call 1-800-236-9933. If you still have questions, contact your healthcare provider.
" ], "package_label_principal_display_panel": [ "PRINCIPAL DISPLAY PANEL – 160mg tablets Rx Only NDC 03109500-01 TRUQAP™ (capivasertib) tablets 160mg 64 film-coated tablets AstraZeneca 160mg_label", "PRINCIPAL DISPLAY PANEL – 200mg tablet Rx only NDC 0310-9501-01 TRUQAP™ (capivasertib) tablets 200mg 64 film-coated tablets AstraZeneca 200mg_label" ], "set_id": "d698c106-2322-401e-b738-cbd83c843ecf", "id": "edd76d11-d12f-4042-bd30-a44c54b09580", "effective_time": "20251114", "version": "8", "openfda": { "application_number": [ "NDA218197" ], "brand_name": [ "TRUQAP" ], "generic_name": [ "CAPIVASERTIB" ], "manufacturer_name": [ "AstraZeneca Pharmaceuticals LP" ], "product_ndc": [ "0310-9500", "0310-9501" ], "product_type": [ "HUMAN PRESCRIPTION DRUG" ], "route": [ "ORAL" ], "substance_name": [ "CAPIVASERTIB" ], "rxcui": [ "2669972", "2669978", "2669980", "2669982" ], "spl_id": [ "edd76d11-d12f-4042-bd30-a44c54b09580" ], "spl_set_id": [ "d698c106-2322-401e-b738-cbd83c843ecf" ], "package_ndc": [ "0310-9500-01", "0310-9500-02", "0310-9501-01", "0310-9501-95", "0310-9501-02", "0310-9501-96" ], "is_original_packager": [ true ], "upc": [ "0303109501011" ], "unii": [ "WFR23M21IE" ] } } ] }