CAVERJECT STERILE

2 Recommended Dose and Dosage Adjustment 7 WARNINGS AND PRECAUTIONS, Fertility 12/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ..........................................................................................

2 TABLE OF CONTENTS ............................................................................................................ 2 PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................

4 1 INDICATIONS ............................................................................................................. 1 Pediatrics..................................................................................................................

2 Geriatrics .................................................................................................................. 4 2 CONTRAINDICATIONS ................................................................................................

4 4 DOSAGE AND ADMINISTRATION................................................................................ 1 Dosing Considerations ............................................................................................. 2 Recommended Dose and Dosage Adjustment ........................................................

3 Reconstitution .......................................................................................................... 4 Administration .........................................................................................................

6 5 OVERDOSAGE............................................................................................................ 7

). In patients infected with blood-borne diseases, this may increase the transmission of blood-borne diseases between partners. The safety and efficacy of combinations of CAVERJECT STERILE POWDER and other vasoactive agents have not been systematically studied.

Therefore, the use of such combinations is not recommended. CAVERJECT STERILE POWDER (alprostadil) Product Monograph Page 11 of 33 Reproductive Health: Female and Male Potential • Fertility CAVERJECT STERILE POWDER is not indicated for use in women (see 2 CONTRAINDICATIONS).

) (200 times the maximum human recommended dose of 60 microgram) did not have an adverse effect on the reproductive potential of the male rat (see 16 NON-CLINICAL TOXICOLOGY). • Function In man, prolonged erection and/or priapism are known to occur following intracavernosal administration of vasoactive substances (see 5 OVERDOSAGE and 7 WARNINGS AND PRECAUTIONS).

• Teratogenic Risk CAVERJECT STERILE POWDER is not indicated for use in women (see 2 CONTRAINDICATIONS). Respiratory The diluent that is used to reconstitute CAVERJECT STERILE POWDER contains benzyl alcohol, a preservative that has been associated with serious adverse events, including the “gasping syndrome”, and death in pediatric patients.

The minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys’ capacity to detoxify the chemical. Premature and low- birth weight infants may be more likely to develop toxicity.

Benzyl alcohol can cross the placenta. 1 Pregnant Women CAVERJECT STERILE POWDER is not indicated for use in women (see 2 CONTRAINDICATIONS). 2 Breast-feeding CAVERJECT STERILE POWDER is not indicated for use in women (see 2 CONTRAINDICATIONS).

3 Pediatrics Pediatrics (<18 years): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of CAVERJECT STERILE POWDER in pediatric patients has not been established; therefore, Health Canada has not authorized an indication for pediatric use (see 2 CONTRAINDICATIONS).

4 Geriatrics Geriatrics: No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use (see 2 CONTRAINDICATIONS). 1 Adverse Reaction Overview Local Adverse Events The following local adverse events were reported from controlled and uncontrolled clinical trials, including an uncontrolled 18 month safety study.

Local Event (reported in 1% of patients) No. (%) of Pts (N=1861) Penile Pain Pain after injection Pain at the injection site 696 580 370 (37) (31) (20) Prolonged erection (4-6 hr) 82 (4) Penile fibrosisa 55 (3) Injection site hematoma 63 (3) Penis disorderb 46 (3) Injection site ecchymosis 32 (2) Penile rash 21 (1) Penile edema 18 (1) a Includes generalized or deep fibrosis, penile curvature/deviation, and Peyronie's disease.

b Includes numbness, yeast infection, irritation, sensitivity, phimosis, pruritus, erythema, venous leak, penile skin tear, strange feeling in penis, burning sensation in penis and itch at tip of penis. Penile Pain Penile pain after intracavernosal administration of CAVERJECT STERILE POWDER (alprostadil) was reported at least once by 37% of patients in clinical studies of up to 18 months in duration.

The intensity of pain was rated mild or moderate in the majority of cases. Three percent of patients discontinued treatment because of penile pain. The frequency of penile pain was 2% in 294 patients who received 1 to 3 injections of placebo.

Prolonged Erection/Priapism In clinical trials, prolonged erection was defined as an erection that lasted for 4 to 6 hours; priapism was defined as an erection that lasted 6 hours or longer (see 7 WARNINGS AND PRECAUTIONS). CAVERJECT STERILE POWDER (alprostadil) Product Monograph Page 13 of 33 Hematoma/Ecchymosis The frequency of hematoma and ecchymosis was 3% and 2% respectively.

In most cases, hematoma/ecchymosis was judged to be a complication of a faulty injection technique. Accordingly, proper instruction of the patient in self-injection is of importance to minimize the potential of hematoma/ecchymosis (see 4 DOSAGE AND ADMINISTRATION).

Local events observed in <1% of the patients include: balanitis, lack of efficacy, injection site hemorrhage, injection site inflammation, injection site itching, injection site reaction, injection site swelling, injection site edema, trauma, urethral bleeding, urethral disorder, penile hematoma, penile warmth, priapism (>6 hr), numbness, yeast infection, irritation, sensitivity, phimosis, pruritus, erythema, venous leak, painful erection and abnormal ejaculation.

Systemic Adverse Events The following systemic adverse event information was derived from controlled and uncontrolled studies, including an uncontrolled 18 month safety study. Systemic Eventa by Body Systemb (reported in 1% of patients)c No.

(%) of Pts (N=1861) BODY AS A WHOLE Upper respiratory infection Flu syndrome Headache Traumad Localized paine Back pain Localized abdominal pain 245 76 42 37 33 32 22 10 (13) (4) (2) (2) (2) (2) (1) (<1) RESPIRATORY Sinusitis Nasal congestion Cough Bronchitis Pharyngitis 123 43 25 21 18 16 (7) (2) (1) (1) (1) (<1) UROGENITAL Prostatic disorderf Urinary tract infection Testicular pain Hematuria 121 28 16 16 10 (7) (2) (<1) (<1) (<1) CARDIOVASCULAR Hypertension 80 39 (4) (2) CAVERJECT STERILE POWDER (alprostadil) Product Monograph Page 14 of 33 CENTRAL NERVOUS Dizziness 66 22 (4) (1) DIGESTIVE Nausea Tooth abscess Diarrhea Dyspepsia 86 14 12 11 11 (5) (<1) (<1) (<1) (<1) SKIN AND APPENDAGES Rash 49 11 (3) (<1) a number (%) patients reporting the event, with patients reporting the same event more than once counted only once.

b number (%) patients reporting a […]

, Fertility 12/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ..........................................................................................

2 TABLE OF CONTENTS ............................................................................................................ 2 PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................

4 1 INDICATIONS ............................................................................................................. 1 Pediatrics..................................................................................................................

2 Geriatrics .................................................................................................................. 4 2 CONTRAINDICATIONS ................................................................................................

4 4 DOSAGE AND ADMINISTRATION................................................................................ 1 Dosing Considerations ............................................................................................. 2 Recommended Dose and Dosage Adjustment ........................................................

3 Reconstitution .......................................................................................................... 4 Administration .........................................................................................................

6 5 OVERDOSAGE............................................................................................................ 7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................ 8 7 WARNINGS AND PRECAUTIONS .................................................................................

1 Special Populations ................................................................................................ 1 Pregnant Women ............................................................................................. 2 Breast-feeding ..................................................................................................

3 Pediatrics.......................................................................................................... 4 Geriatrics ..........................................................................................................

12 8 ADVERSE REACTIONS............................................................................................... 1 Adverse Reaction Overview ................................................................................... 12 9 DRUG INTERACTIONS ..............................................................................................

2 Drug Interactions Overview ................................................................................... 3 Drug-Behavioural Interactions ............................................................................... 4 Drug-Drug Interactions ..........................................................................................

5 Drug-Food Interactions .......................................................................................... 6 Drug-Herb Interactions .......................................................................................... 7 Drug-Laboratory Test Interactions.........................................................................

15 10 CLINICAL PHARMACOLOGY ...................................................................................... 1 Mechanism of Action ....................................................................................... 2 Pharmacodynamics ..........................................................................................

3 Pharmacokinetics ............................................................................................. 17 11 STORAGE, STABILITY AND DISPOSAL ........................................................................ 18 12 SPECIAL HANDLING INSTRUCTIONS..........................................................................

18 PART II: SCIENTIFIC INFORMATION ..................................................................................... 19 13 PHARMACEUTICAL INFORMATION .......................................................................... 19 14 CLINICAL TRIALS ......................................................................................................

1 Trial Design and Study Demographics ............................................................. 20 15 MICROBIOLOGY ...................................................................................................... 20 16 NON-CLINICAL TOXICOLOGY ....................................................................................

20 PATIENT MEDICATION INFORMATION ................................................................................ 23 CAVERJECT STERILE POWDER (alprostadil) Product Monograph Page 4 of 33 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS CAVERJECT STERILE POWDER (alprostadil) is indicated for: • the intracavernosal treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.

Intracavernosal CAVERJECT STERILE POWDER may also be useful as an adjunct to diagnostic tests in the diagnosis of erectile dysfunction. 1 Pediatrics CAVERJECT STERILE POWDER is not indicated for pediatric use (See 2 CONTRAINDICATIONS).

2 Geriatrics Geriatrics: No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use. 2 CONTRAINDICATIONS CAVERJECT STERILE POWDER (alprostadil) is contraindicated in the following individuals: • Patients who are hypersensitive to this […]

). 2 Geriatrics Geriatrics: No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use. 2 CONTRAINDICATIONS CAVERJECT STERILE POWDER (alprostadil) is contraindicated in the following individuals: • Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • Patients who have any condition that may predispose them to priapism such as sickle cell anemia or trait, multiple myeloma or leukemia. • Patients with anatomical deformations of the penis, such as angulation, cavernosal fibrosis, Peyronie's disease.

• Patients with penile implants CAVERJECT STERILE POWDER should not be used in women or children and is not for use in newborns. CAVERJECT STERILE POWDER should not be used in men for whom sexual activity is inadvisable or contraindicated.