Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
CAPIFLVS
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
This Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Treatment of hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations*, following disease progression on at least one endocrine-based hormonal therapy in the metastatic setting, OR disease recurrence/progression while on or within 12 months of completing adjuvant hormonal therapy
*confirmed by a validated test prior to treatment
(Refer to EAP for full details of funding criteria and exclusions.)
capivasertib
Exceptional Access Program
(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)
(EAP Website
)
fulvestrant
ODB - General Benefit
(fulvestrant)
(ODB Formulary
)
Cycle 1:
| capivasertib | 400 mg | PO | Twice daily; Days 1-4, 8-11, 15-18, 22-25* |
| fulvestrant | 500 mg | IM | Days 1 and 15 |
|
|
|||
| capivasertib | 400 mg | PO | Twice daily; Days 1-4, 8-11, 15-18, 22-25* |
| fulvestrant | 500 mg | IM | Day 1 |
Pre/perimenopausal women, or men, should also be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to local clinical practice.
*Give capivasertib twice daily for 4 days, followed by 3 days off each week.
Low – No routine prophylaxis; PRN recommended
- Also refer to CCO Antiemetic Recommendations.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Other Supportive Care:
- 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.
- Early consultation with a dermatologist is recommended due to risks of cutaneous reactions.
Doses should be modified according to the protocol by which the patient is being treated.
Refer to Interactions section for dosing recommendations when co-administered with strong or moderate CYP3A4 inhibitors.
Dosage with toxicity
Dose Modifications for Capivasertib:
| 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.
Dose Modifications for Fulvestrant:
|
Toxicity
|
Action
|
|
Hypersensitivity
|
Consider discontinuing if severe. |
|
Mild hepatotoxicity
|
Hold until recovery and then restart. |
|
Moderate to severe hepatotoxicity |
Discontinue.
|
Hepatic Impairment
Capivasertib:
| 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. |
Fulvestrant:
| Hepatic Impairment | Fulvestrant Dose |
|
Mild to Moderate |
Use with caution. No dose adjustment required. |
|
Severe |
Not studied. Use not recommended. |
Renal Impairment
| Creatinine Clearance (mL/min) | Capivasertib Dose | Fulvestrant Dose |
| ≥ 30 | No dose adjustment required. | No dosage adjustment required. |
| < 30 or ESRD | No data. Use not recommended. | Use with caution; no data. |
Dosage in the Elderly
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.
Refer to capivasertib, fulvestrant drug monograph(s) for additional details of adverse effects
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to capivasertib, fulvestrant drug monograph(s) for additional details
Capivasertib:
-
Avoid concomitant use with strong CYP3A4 inhibitors due to increased capivasertib exposure and/or toxicity.
-
If concomitant use of capivasertib and strong or moderate CYP3A4 inhibitor is required:
-
Administer 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, then resume the dose that was used prior to starting the inhibitor.
-
-
Avoid concomitant use with strong or moderate CYP3A4 inducers due to decreased exposure and/or efficacy of capivasertib.
-
Avoid concomitant use of capivasertib CYP3A4 sensitive* substrates, since capivasertib may increase the concentration and/or toxicity of these substrates. If they must be co-administered, adjust dosage of these substrates based on their product monographs.
-
Avoid concomitant use of capivasertib with sensitive* OATP1B1 and/or OATP1B3 substrates that are metabolized by CYP3A4, since capivasertib may increase the concentration and/or toxicity of these substrates. If they must be co-administered, adjust dosage for these substrates based on their product monographs.
-
Caution with concomitant use of capivasertib and sensitive* MATE1, MATE2K, or OCT2 substrates, since capivasertib may increase the concentration and/or toxicity of these substrates. Adjust dosage for these substrates according to their product monographs.
Fulvestrant:
- Fulvestrant may interfere with estradiol immunoassay measurements (falsely elevated estradiol levels) due to its structural similarity with estradiol.
*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).
Refer to capivasertib, fulvestrant drug monograph(s) for additional details
Administration
Capivasertib:
- 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.
- Do not administer a replacement dose if a dose is vomited. The next scheduled dose should be given on the next day.
- Ensure at least 8 hours between doses.
- Store at room temperature between 15°C to 30°C in original package.
Fulvestrant:
- Each dose consists of 2 pre-filled syringes (250 mg/5mL). Administer each pre-filled syringe as SLOW intramuscular injection (1-2 minutes per injection) into EACH buttock.
- Caution should be taken due to proximity of the sciatic nerve and large blood vessels.
- Administer according to local clinical practice guidelines.
- Store refrigerated at 2 to 8°C in original package.
Contraindications/Precautions
- Patients who have a hypersensitivity to capivasertib, fulvestrant or any of their components
- Fulvestrant is contraindicated in pregnant or lactating patients
Other Warnings / Precautions
- The safety of capivasertib has not been established in patients with certain medical conditions, including 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.
- Due to the route of administration, use fulvestrant with caution in patients with bleeding disorders or on anticoagulants.
- There is a potential osteoporosis risk due to fulvestrant's mechanism of action.
Pregnancy / Lactation
- This regimen is contraindicated for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
- Breastfeeding is contraindicated during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
- 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, hyperglycemia, injection site reactions, hypersensitivity, estrogen deprivation symptoms, thromboembolism, musculoskeletal 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
Suggested Clinical Monitoring
- Blood ketones; As clinically indicated for diabetic ketoacidosis
back to top
Capivasertib: Outpatient prescription for home administration
Fulvestrant: Outpatient prescription; drug administration according to local guidelines.
CADTH reimbursement recommendation: capivasertib. Canadian Journal of Health Technologies 2024 Sep;4(9).
Canada's Drug Agency reimbursement review: capivasertib. Canadian Journal of Health Technologies 2025 Jan;5(1).
Capivasertib drug monograph. Ontario Health (Cancer Care Ontario).
Fulvestrant drug monograph. Ontario Health (Cancer Care Ontario).
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):2058-70.
October 2025 Updated to full regimen monograph
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.