Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
DARO
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.
For the treatment of high risk non-metastatic castration resistant prostate cancer (nmCRPC), in patients with ECOG status ≤ 2
(Refer to EAP for full details of funding criteria and exclusions)
darolutamide
Exceptional Access Program
(darolutamide - For the treatment of high risk non-metastatic castration resistant prostate cancer (nmCRPC) according to clinical criteria)
(EAP Website)
| darolutamide | 600 mg | PO | BID |
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Not applicable
Other Supportive Care:
- Optimize management of cardiovascular risk factors (e.g., hypertension, diabetes, or dyslipidemia).
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
| Dose Level | Darolutamide Dose |
| 0 | 600 mg BID |
| -1 | 300 mg BID |
| -2 | Discontinue |
| Toxicity | Action |
| Intolerable or > grade 3 | Hold or ↓ 1 dose level until symptoms improve. Then may resume at previous dose. |
| Drug-induced liver injury (DILI) | Discontinue. |
| Seizure | Consider discontinuing. |
Hepatic Impairment
During a pharmacokinetic (PK) study, patients with moderate hepatic impairment had a 1.9-fold higher darolutamide exposure.
| Hepatic Impairment | Darolutamide Dose |
| Mild (Child-Pugh class A) | No dose adjustment necessary |
| Moderate (Child-Pugh class B) | 300 mg BID |
| Severe (Child-Pugh class C) | Not studied |
Renal Impairment
During PK studies, patients with mild, moderate and severe renal impairment had a 1.1-,1.3- and 1.5-fold higher darolutamide exposure, respectively.
| Creatinine Clearance (mL/min) | Darolutamide Dose |
| > 30 | No dose adjustment necessary |
| 15 - 29* | 300 mg BID (limited data) |
| < 15** | Not studied |
*Not on hemodialysis
**Including patients with ESRD on dialysis
Dosage in the Elderly
No clinically relevant differences in safety or efficacy in patients ≥ 65 years of age. Compared to patients < 65 years of age, patients > 85 years of age had a 1.6-fold higher darolutamide exposure without associated greater toxicity.
Refer to darolutamide drug monograph(s) for additional details of adverse effects.
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Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to darolutamide drug monograph(s) for additional details.
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Avoid concomitant use when possible with combined P-gp and strong CYP3A4 inducers (e.g. rifampin) due to ↓ darolutamide concentration.
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Consider an alternative with less inhibition to combined P-gp, BCRP, and strong CYP3A4 inhibitors (e.g. itraconazole) due to ↑ risk of darolutamide toxicity. If co-administered, monitor closely.
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Avoid concomitant use when possible with BCRP substrates (e.g. rosuvastatin) due to ↑ risk of substrate toxicity. If co-administered, monitor closely; consider substrate dose reduction.
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Caution with concomitant use of OATP1B1 or OATP1B3 substrates (e.g. rosuvastatin) due to ↑ risk of substrate toxicity. Monitor for toxicity and consider substrate dose reduction.
Refer to darolutamide drug monograph(s) for additional details.
Administration
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Administer darolutamide with food.
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Tablets should be swallowed whole.
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If a dose is missed, patient may take as soon as possible. If it is close to the next dose, patient should not double the dose to make up for the missed dose.
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Store at room temperature (15°C to 30°C). Keep bottle tightly closed after opening. Once bottle is opened, darolutamide is stable for 3 months.
Contraindications
- Patients who are hypersensitive to this drug or any of its components.
Warnings/Precautions
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Patients with uncontrolled hypertension, recent stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft or CHF NYHA Class III or IV were excluded in clinical trials.
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Tablets contain lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
Pregnancy/Lactation
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Darolutamide is not indicated for use in females. It may cause harm to a developing fetus or lead to loss of pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for 3 months after the last dose.
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Patients who produce sperm should use a condom and not donate sperm during treatment, and for 3 months after the last dose.
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Excretion into breast milk: Unknown
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Fertility Effects: Probable
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
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CBC; Baseline and as clinically indicated
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Liver function tests; Baseline and as clinically indicated
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Renal function tests; Baseline and as clinically indicated
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PSA and radiographic disease progression; Baseline and as clinically indicated
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Clinical toxicity assessment for fatigue, seizures, musculoskeletal, dermatologic, GI and cardiovascular effects; At each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Darolutamide drug monograph. Ontario Health (Cancer Care Ontario).
Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2019;380:1235-46.
Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049.
March 2024 Updated Dose modifications section
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.