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capivasertib
Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3) and blocks the AKT signaling pathway. This inhibits phosphorylation of downstream AKT substrates involved in cellular processes, such as cell division, apoptosis, and glucose and fatty acid metabolism. Capivasertib reduced the growth of various cancer cell lines in vitro and inhibited tumour growth in vivo for ER+ breast cancer models with or without PIK3CA, AKT1, or PTEN alterations.
| Bioavailability |
29% |
| Peak plasma levels |
~1-2 hours after administration |
| Effects with food |
No clinically significant effect on exposure when given with food. AUCT and Cmax increased by up to 33% and 23%, respectively, depending on the fat and calorie content of the meal. A delay in Tmax of 1 hour was also observed under fed conditions. |
| Time to reach steady state |
Every 3rd and 4th dosing day of each week, starting from week 2 |
| PPB |
78% |
Capivasertib is mainly metabolized by CYP3A4 and UGT2B7 enzymes.
| Urine |
45% |
| Feces |
50% |
| Half-life |
~8 hours |
| Clearance |
21% |
- Breast cancer
Refer to the product monograph for a full list and details of approved indications
Emetogenic Potential:
The following table lists adverse effects that occurred in ≥ 2% of patients with HR positive, HER2-negative advanced or metastatic breast cancer treated with capivasertib and fulvestrant versus placebo and fulvestrant in a phase 3 study. It also includes severe, life-threatening and post-marketing adverse effects from other sources.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Dermatological | Erythema multiforme (2%) | E | |||
| Hand-foot syndrome | E | ||||
| Rash (47%) (17% severe) | E D L | ||||
| Gastrointestinal | Anorexia (11%) | E | |||
| Diarrhea (67%) (9% severe) | E | ||||
| Dry mouth (4%) | E | ||||
| Dyspepsia (3%) | E | ||||
| Mucositis (16%) (2% severe) | E | ||||
| Nausea, vomiting (27%) (1% severe) | E | ||||
| General | Fatigue (22%) | E | |||
| Fever (6%) | E | ||||
| Hematological | Anemia (4%) | E | |||
| Hypersensitivity | DRESS syndrome (<1%) | E | |||
| Hypersensitivity (<1%) | I E | ||||
| Metabolic / Endocrine | Glucose intolerance (<1%) | E | |||
| Hyperglycemia (14%) (2% severe) | E D | ||||
| ↓ K (2%) | E | ||||
| Other (<1%) Diabetic ketoacidosis | E | ||||
| Nervous System | Dysgeusia (6%) | E | |||
| Headache (5%) | E | ||||
| Renal | Creatinine increased (3%) | E | |||
| Other (1%) Acute kidney injury | E | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for capivasertib include diarrhea, rash, nausea/vomiting, fatigue, mucositis, hyperglycemia, and anorexia.
Severe hyperglycemia, including diabetic ketoacidosis (fatal in some cases), has been observed in patients treated with capivasertib. Comorbidities and concurrent treatments (e.g., dehydration, malnourishment, chemotherapy/steroids, sepsis) may increase the risk of progression from hyperglycemia to diabetic ketoacidosis, which can occur at any time during treatment with capivasertib. Among patients who experienced hyperglycemia, 12% were treated with insulin and 32% with metformin.
Severe diarrhea associated with dehydration and/or acute kidney injury was observed in patients treated with capivasertib. Coadministration with metformin may increase the frequency of diarrhea. Among patients who experienced diarrhea, 58% required antidiarrheal medications to manage symptoms.
Cutaneous adverse reactions were reported in patients treated with capivasertib, including severe reactions such as erythema multiforme (EM), palmar-plantar erythrodyesthesia and drug reaction with eosinophilia and systemic symptoms (DRESS). Among patients who experienced cutaneous adverse reactions, 39% were treated with topical corticosteroids and 22% with systemic steroids. Early consultation with a dermatologist is recommended.
Refer to protocol by which the patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Presence of one or more PIK3CA/AKT1/PTEN genetic alterations in patients with hormone receptor (HR) positive, HER2-negative advanced breast cancer should be confirmed by a validated test prior to starting treatment with capivasertib.
Control and correct abnormal glucose levels before starting treatment.
Patients should be advised to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea while on treatment.
Oral: 400 mg BID for 4 days, followed by 3 days off each week.
- Capivasertib should be co-administered with fulvestrant, refer to the fulvestrant Product Monograph for more information.
- Pre/perimenopausal women, or men, should also be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to local clinical practice.
Refer to Interactions section for dosing recommendations when co-administered with strong or moderate CYP3A4 inhibitors.
| Dose level | Capivasertib dose (mg, twice daily)* |
| 0 | 400 |
| -1 | 320 |
| -2 | 200 |
| -3 | Discontinue |
*Administered for 4 days, followed by 3 days off each week.
| Toxicity | Severity/Grade | Action |
| Hyperglycemia§† | Grade 1 Fasting Glucose (FG) >ULN - 8.9 mmol/L or HbA1C >7% |
No dose adjustment required. Consider initiating or intensifying oral anti-diabetic treatment. |
|
Grade 2 FG >8.9 - 13.9 mmol/L |
Continue capivasertib and initiate/increase oral anti-diabetic. If no improvement to Grade ≤1, hold*.
|
|
|
Grade 3 FG >13.9 - 27.8 mmol/L |
Hold.* Consult with an expert. Start or optimize anti-diabetic treatment as clinically indicated, according to local guidelines.
|
|
|
Grade 4 FG >27.8 mmol/L |
Hold. Consult with an expert. Start or optimize anti-diabetic treatment as clinically indicated, according to local guidelines.
|
|
| Life-threatening sequelae | Discontinue. | |
| Diabetic Ketoacidosis | Hold and investigate for any symptoms; discontinue if confirmed. | |
| Diarrhea | Grade 2 |
Hold.* Initiate or intensify anti-diarrheal treatment and monitor as clinically indicated.
|
| Grade 3 |
Hold.* Initiate or intensify anti-diarrheal treatment and monitor as clinically indicated.
|
|
| Grade 4 | Discontinue. | |
| Cutaneous Adverse Reactions | Grade 2 |
Start or increase topical steroid treatment. Optimize non-sedating antihistamine treatment. If no improvement, hold capivasertib. |
| Grade 3 |
Hold.* Manage appropriately (e.g. topical steroid of moderate/higher strength, non-sedating oral antihistamines, and/or systemic steroids).
|
|
| Grade 4 | Discontinue. | |
| Other Adverse Reactions | Grade 2 |
Hold.* Restart at same dose. |
| Grade 3 |
Hold.* Restart at same dose or at 1 dose level ↓, as clinically appropriate. |
|
| Grade 4 | Discontinue. |
§ Dose adjustments and management are based on pre-dose fasting glucose (FG) and/or HbA1c levels.
†If hyperglycemia develops, monitor at least twice weekly (on days on and off capivasertib) until FG decreases to baseline. During treatment with anti-diabetic medication(s), monitor FG at least once a week for 2 months, followed by once q2 weeks or as clinically indicated.
* Hold until recovery to ≤Grade 1.
| Bilirubin | AST | Capivasertib Dose | |
| ≤ULN | and | >ULN | No dose adjustment required. |
| >1 to 1.5 ULN | and | Any | |
| >1.5 to 3 ULN | and | Any | Limited data available. Administer only if benefit outweighs risk; monitor closely for signs of toxicity. |
| >3 ULN | and | Any | No data. Use not recommended. |
| Creatinine Clearance (mL/min) | Capivasertib Dose |
| ≥30 | No dose adjustment required. |
| <30 or ESRD | No data. Use not recommended. |
No dose adjustment is required for elderly patients aged ≥65 years. No clinically significant difference in efficacy was observed between patients ≥65 years of age and younger patients. Higher incidence of Grade ≥3 adverse reactions may be observed in patients ≥65 years old compared to younger patients.
No clinically significant differences in pharmacokinetics based on gender.
No clinically significant differences in pharmacokinetics between White and Asian patients. There is limited information available about other race/ethnicities.
The safety and efficacy of capivasertib have not been established in patients under 18 years of age.
- Administer capivasertib tablets with or without food.
- Swallow tablets whole with water. Do not chew, crush, dissolve, or divide tablets.
- If a dose is missed, it can be administered within 4 hours of the missed dose. If more than 4 hours, the dose should be skipped and the next dose should be given at the next planned time.
- Ensure at least 8 hours between doses.
- Do not administer a replacement dose if a dose is vomited. The next scheduled dose should be given on the next day.
- Store at room temperature between 15°C to 30°C in original package.
- Patients who have a hypersensitivity to this drug or any of its components
- The safety of capivasertib has not been established in patients with certain medical conditions, including with Type 1 diabetes, diabetes requiring insulin and/or those with a HbA1C of ≥8%, history of clinically significant cardiac disease, or symptomatic visceral disease, as these patients were excluded from the CAPItello-291 trial.
- Diabetic ketoacidosis (fatal in some cases), severe cutaneous reactions, and severe diarrhea associated with dehydration and/or acute kidney injury have been observed in patients treated with capivasertib.
Other Drug Properties:
-
Carcinogenicity:
No information available
-
Genotoxicity:
No
-
Mutagenicity:
No
-
Embryotoxicity:
Documented in animals
-
Fetotoxicity:
Documented in animals
-
Pregnancy:
Capivasertib is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 4 weeks after the last dose.
-
Breastfeeding:
Breastfeeding is not recommended during treatment.
-
Excretion into breast milk:
Documented in animals
-
Fertility effects:
Unknown
Capivasertib is mainly metabolized by CYP3A4 and UGT2B7 enzymes; however, UGT2B7 inhibitors (i.e. probenecid) are not predicted to have a clinically meaningful effect on capivasertib pharmacokinetics.
Capivasertib inhibits CYP2C9 (clinical significance not established), CYP2D6, CYP3A4 and UGT1A1. In vitro, capivasertib inhibited BCRP, OATP1B1, OATP1B3, OAT3, OCT2, MATE1 and MATE2K drug transporters.
Capivasertib is a substrate of P-glycoprotein (P-gp) transporter.
Sensitive substrates are substrates where minimal concentration changes due to enzyme/transporter inhibition may lead to serious adverse effects. Capivasertib can inhibit certain enzymes or transporters and increase sensitive substrate exposure. Generally, applicable inhibitors can increase sensitive substrate exposure (e.g. by 1.25 to <2-fold with weak inhibitors, 2 to <5-fold with moderate inhibitors, and ≥5-fold with strong inhibitors).
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Strong CYP3A4 inhibitors (e.g. clarithromycin, itraconazole, ritonavir, etc.) | ↑ capivasertib concentration and/or toxicity (e.g. itraconazole ↑ capivasertib exposure by 1.6-fold) | ↓ metabolism of capivasertib | Avoid concomitant use. If must co-administer, give capivasertib at 320 mg BID for 4 days, then 3 days off each week . Monitor for signs of toxicity. After discontinuation of the inhibitor wait for 3 half-lives (of the inhibitor), then resume the dose that was used prior to starting the inhibitor. |
| Moderate CYP3A4 inhibitors (e.g. aprepitant, erythromycin, verapamil, etc.) | ↑ capivasertib concentration and/or toxicity | ↓ metabolism of capivasertib | If given concomitantly, give capivasertib at 320 mg BID for 4 days, then 3 days off each week. Monitor for signs of toxicity. After discontinuation of the inhibitor wait for 3 half-lives (of the inhibitor), then resume the dose that was used prior to starting the inhibitor. |
| Strong or moderate CYP3A4 inducers (e.g. phenytoin, rifampin, dexamethasone, carbamazepine, St. John’s Wort, etc.) | ↓ capivasertib concentration and/or efficacy (e.g. enzalutamide ↓ capivasertib exposure by 40-50%) | ↑ metabolism of capivasertib | Avoid concomitant use. |
| CYP3A4 substrates (e.g. midazolam) | ↑ CYP3A4 substrates concentration and/or toxicity (e.g. ↑ midazolam AUC by 1.8-fold on day 4) | Capivasertib is a weak inhibitor of CYP3A4. | Avoid concomitant use with CYP3A4 sensitive substrates. If must co-administer, adjust dosage of these substrates based on their product monographs |
| OATP1B1 and/or OATP1B3 substrates, that are metabolized by CYP3A4 | ↑ OATP1B1, OATP1B3 substrate concentration and/or toxicity (theoretical; no clinically relevant effects on exposure of atorvastatin or rosuvastatin) | Capivasertib inhibits OATP1B1 and OATP1B3 in vitro; it may ↓ metabolism of OATP1B1, OATP1B3 substrates that are metabolized by CYP3A4. | Avoid concomitant use of sensitive substrates or adjust dosage for these substrates based on their product monographs. |
| MATE1, MATE2K, OCT2 substrates (e.g. procainamide) | ↑ MATE1, MATE2K, OCT2 substrates concentration and/or toxicity (theoretical; no meaningful interaction with metformin); transient ↑ in serum creatinine | Capivasertib inhibits MATE1, MATE2K, OCT2 transporters in vitro. | Caution when used concomitantly with sensitive substrates; adjust dosage of these substrates based on their product monographs. |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline, and at each visit |
Liver function tests |
Baseline, and at each visit |
Renal function tests |
Baseline, and at each visit |
Fasting glucose* (patients without diabetes) |
Baseline and at weeks 1, 2, 4, 6 and 8 after treatment start, then at least once a month thereafter. (Additional monitoring may be required within the first 2 weeks of treatment, as clinically indicated.) |
Fasting glucose (patients with diabetes) |
Baseline and daily for the first 2 weeks of treatment, then as frequently as needed to manage hyperglycemia. |
HbA1c |
Baseline, at week 4 (for patients with diabetes, pre-diabetes or hyperglycemia at baseline) and every 3 months |
Clinical toxicity assessment for diarrhea, rash, fatigue, and other GI effects. |
Baseline and at each visit |
*It is recommended to test fasting glucose pre-dose on Day 3 or 4 of the dosing week.
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
| Monitor Type | Monitor Frequency |
|---|---|
Blood ketones |
As clinically indicated for diabetic ketoacidosis |
Exceptional Access Program (EAP Website )
- capivasertib - For the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, based on criteria
NCI drug dictionary: capivasertib. Accessed February 24, 2025.
Prescribing Information: Truqap™ (capivasertib). AstraZeneca Pharmaceuticals LP. September 2024.
Product Information: Truqap™ (capivasertib). AstraZeneca AB. July 11, 2024.
Product Information: Truqap™ (capivasertib). AstraZeneca Pty Ltd. November 6, 2024.
Product Monograph: Truqap™ (capivasertib). AstraZeneca Canada Inc. January 3, 2025.
Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023 Jun 1;388(22):2058-2070. doi: 10.1056/NEJMoa2214131.
October 2025 New drug monograph
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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