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APO-ENZALUTAMIDE is a brand name for Enzalutamide, supplied as a capsule. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: APO-ENZALUTAMIDE (enzalutamide capsules) is indicated for the treatment of patients with non-metastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk of metastasis (high-risk BCR) (see 14 CLINICAL TRIALS). APO-ENZALUTAMIDE is indicated for the treatment of patients with…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations APO-ENZALUTAMIDE is for use in patients with nm-CRPC, metastatic CRPC or m-CSPC who are maintaining treatment with a GnRH analogue or who have had previously undergone surgical castration. Patients started on enzalutamide capsules who are receiving a GnRH analogue should continue to receive a GnRH analogue.
Patients with nm-CSPC with high-risk BCR may be treated with APO-ENZALUTAMIDE with or without a GnRH analogue. 2 Recommended Dose and Dosage Adjustment The recommended dose of APO-ENZALUTAMIDE is 160 mg (four 40 mg capsules) as a single oral daily dose.
APO-ENZALUTAMIDE can be taken with or without food. Co-administration of APO-ENZALUTAMIDE with CYP2C8 inhibitors may increase the plasma exposure of enzalutamide and should be avoided if possible. In patients who must be co- administered a strong CYP2C8 inhibitor, reduce the APO-ENZALUTAMIDE dose to 80 mg once daily.
If a patient experiences ≥ Grade 3 toxicity or an intolerable side effect, withhold dosing for one week or until symptoms improve to ≤ Grade 2, then resume at the same or a reduced dose (120 mg or 80 mg), if warranted. 2 ng / mL) after 36 weeks of therapy.
0 ng / mL for patients who had prior primary radiation therapy. Enzalutamide capsules have been studied in nm-CPSC patients with high-risk BCR in combination with leuprolide (See 14 CLINICAL TRIALS). Caution is advised when using other GnRH analogues to treat patients with high-risk BCR due to potential differences in patterns of testosterone recovery, PSA expression, duration of treatment suspension and compliance to APO-ENZALUTAMIDE (Enzalutamide) Page 7 of 88 treatment.
There is a potential risk that rapid testosterone recovery after treatment suspension results in shorter treatment suspension duration.
Elderly patients:
No dose adjustment is necessary for elderly patients (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions).
Patients with hepatic impairment:
No dose adjustment is necessary for patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B or C. An increased drug half-life, however, has been observed in patients with severe hepatic impairment; see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions).
, Cardiovascular). 1% on the placebo plus ADT arm. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue APO- ENZALUTAMIDE for Grade 3 to 4 ischemic heart disease.
Patients with clinically significant cardiovascular disease, including recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure, except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension (resting systolic blood pressure > 170 mm Hg and / or diastolic blood pressure > 105 mm Hg) were excluded from the Phase 3 clinical trials (see 14 CLINICAL TRIALS).
Therefore, the safety of enzalutamide capsules in these patients has not been established. 5 msec (placebo-adjusted mean change from baseline) during weeks 5 to 25 of treatment when administered to metastatic CRPC patients with pre-dose ECG recordings (see 10 CLINICAL PHARMACOLOGY, Cardiac Electrophysiology).
4 msec observed at week 37. g. hypokalemia) or patients who are taking medications known to prolong the QT interval (see 9 DRUG-DRUG INTERACTIONS, Drugs APO-ENZALUTAMIDE (Enzalutamide) Page 10 of 88 that Cause QT / QTc Prolongation).
Hypertension:
Enzalutamide capsules was associated with increases in systolic and diastolic blood pressure and an increased risk of hypertension or worsening of pre-existing hypertension when administered to patients in the Phase 3 clinical trials (see 10 CLINICAL PHARMACOLOGY, Blood Pressure).
2% vs. 4%). Hypertension rarely led to discontinuation or dose modification and, in general, was not associated with major cardiovascular adverse sequelae. However, approximately 75% of patients with this adverse event required initiation of new antihypertensive treatment or increase in dose of prior therapy.
1. of the PM Guidance) or subsections that are not applicable at the time of the preparation of the most recent authorized product monograph are not listed. RECENT MAJOR LABEL CHANGES ...........................................................................................
2 TABLE OF CONTENTS .............................................................................................................. 2 PART 1: HEALTH PROFESSIONAL INFORMATION......................................................................
5 1 INDICATIONS .................................................................................................................. 1 Pediatrics ......................................................................................................................
2 Geriatrics ...................................................................................................................... 5 2 CONTRAINDICATIONS .....................................................................................................
5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ................................................................. 6 4 DOSAGE AND ADMINISTRATION ..................................................................................... 1 Dosing Considerations..................................................................................................
2 Recommended Dose and Dosage Adjustment ............................................................ 4 Administration.............................................................................................................. 5 Missed Dose .................................................................................................................
7 5 OVERDOSE ..................................................................................................................... 7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION, AND PACKAGING ..................................... 8 7 WARNINGS AND PRECAUTIONS ......................................................................................
APO-ENZALUTAMIDE is contraindicated in: • patients who are hypersensitive to enzalutamide or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.
• women who are or may become pregnant, or who are lactating. APO-ENZALUTAMIDE (Enzalutamide) Page 6 of 88
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Patients with renal impairment:
No dose adjustment is necessary for patients with mild or moderate renal impairment (calculated creatinine clearance (CrCL) values ≥ 30 mL / min; see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions). The effect of severe renal impairment on enzalutamide pharmacokinetics has not been studied.
Caution is advised in patients with severe renal impairment or end-stage renal disease (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions). Health Canada has not authorized an indication for pediatric use. 4 Administration APO-ENZALUTAMIDE capsules should be swallowed whole with a sufficient amount of water and can be taken with or without food.
Do not chew, dissolve or open the capsules. 5 Missed Dose If a patient misses taking APO-ENZALUTAMIDE at the usual time, the prescribed dose should be taken as close as possible to the usual time. If a patient misses a dose for a whole day, treatment should be resumed the following day with the usual daily dose.
5 OVERDOSE There is no antidote for APO-ENZALUTAMIDE. 8 days. It is unlikely that enzalutamide will be significantly removed by intermittent hemodialysis or continuous ambulatory peritoneal dialysis, owing to its large volume of distribution and low unbound free fraction.
Patients may be at increased risk of seizures following an overdose. For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X APO-ENZALUTAMIDE (Enzalutamide) Page 8 of 88 (1-844-764-7669).
Blood pressure should be measured at baseline and periodically during treatment. Treatment- emergent hypertension should be treated appropriately. Driving and Operating Machinery No studies on the effects on the ability to drive and use machines have been performed.
Ear/Nose/Throat Dysphagia Related to Product Size:
There have been reports of patients experiencing difficulty swallowing enzalutamide capsules, including reports of choking, due to product size. The swallowing difficulties were mostly reported with the capsule formulation. Advise patients to swallow the capsules whole with a sufficient amount of water.
Hepatic / Biliary / Pancreatic Mild, moderate or severe hepatic impairment (Child-Pugh Class A, B or C) had no significant effects on the pharmacokinetics of enzalutamide (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions).
Patients with baseline severe hepatic impairment (Child-Pugh C) were excluded from both the AFFIRM and PREVAIL trials. Immune Hypersensitivity reactions manifested by symptoms including, but not limited to face, tongue, lip and pharyngeal oedema have been observed with enzalutamide (see 8 ADVERSE REACTIONS, Post-Market Adverse Reactions).
Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue APO-ENZALUTAMIDE and promptly seek medical care. Permanently discontinue APO-ENZALUTAMIDE for serious hypersensitivity reactions. Monitoring and Laboratory Tests Monitoring for laboratory or clinical parameters should be conducted as per routine practice.
Blood pressure should be measured at baseline and periodically during treatment. APO-ENZALUTAMIDE (Enzalutamide) Page 11 of 88 Monitoring of ECG and serum electrolyte levels at baseline and during treatment should be considered for patients at risk for electrolyte abnormality and QTc prolongation.
Enzalutamide is a moderate inducer of CYP2C9. g. warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted. Patients with cardiac history should be assessed for active cardiac disease before starting therapy with APO-ENZALUTAMIDE.
Patients with nm-CSPC with high-risk BCR or nm-CRPC should be monitored for disease progression radiographically at the discretion of their treating physician in addition to serum Prostate Specific Antigen (PSA). 1%) of patients treated with enzalutamide capsules monotherapy reported radiographic progression without PSA progression.
PSA progression was defined as the date that a ≥25% increase and an absolute increase of ≥2 mcg / L (2 ng / mL) above the nadir (or baseline for participants with no PSA decline by Week 25) and that was confirmed by a second consecutive value at least 3 weeks later.
In the PROSPER trial, 104 out of 219 nm-CRPC patients treated with enzalutamide capsules in the PROSPER trial reported radiographic progression without PSA progression.
Musculoskeletal Bone Fractures:
APO-ENZALUTAMIDE is indicated for use in patients who are maintaining castration status through GnRH analogue therapy or surgical castration. In the Phase 3 clinical trials, a higher incidence of non- pathological bone fractures was reported in the […]
8 General .................................................................................................................................... 8 Carcinogenesis and Genotoxicity ............................................................................................
9 Cardiovascular ......................................................................................................................... 9 Driving and Operating Machinery .........................................................................................
10 Ear/Nose/Throat ................................................................................................................... 10 Hepatic / Biliary / Pancreatic.................................................................................................
10 APO-ENZALUTAMIDE (Enzalutamide) Page 3 of 88 Immune ................................................................................................................................. 10 Monitoring and Laboratory Tests ..........................................................................................
10 Musculoskeletal .................................................................................................................... 11 Neurologic .............................................................................................................................
12 Renal ..................................................................................................................................... 13 Reproductive Health .............................................................................................................
1 Special Populations .................................................................................................... 1 Pregnancy..............................................................................................................
2 Breastfeeding .......................................................................................... 3 Pediatrics................................................................................................ 4 Geriatrics ................................................................................................
14 8 ADVERSE REACTIONS .................................................................................................... 1 Adverse Reaction Overview ........................................................................................
2 Clinical Trial Adverse Reactions................................................................................... 3 Less Common Clinical Trial Adverse Reactions ........................................................... 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry, and Other Quantitative Data ......................................................................................................
5 Post-Market Adverse Reactions ................................................................................. 25 9 DRUG INTERACTIONS ...................................................................................................
2 Drug Interactions Overview ........................................................................................ 4 Drug-Drug Interactions ..............................................................................................
5 Drug-Food Interactions .............................................................................................. 6 Drug-Herb Interactions ..............................................................................................
7 Drug-Laboratory Test Interactions […]