Caverject Impulse

1 INDICATIONS AND USAGE CAVERJECT IMPULSE is a prostaglandin E1 agonist indicated • For the treatment of erectile dysfunction ( 1.1 ) • As an adjunct to other diagnostic tests in the diagnosis of erectile dysfunction ( 1.2 ). 1.1 Erectile Dysfunction CAVERJECT IMPULSE is indicated for the treatment of erectile dysfunction. 1.2 Diagnostic Test CAVERJECT IMPULSE is indicated as an adjunct to other diagnostic tests in the diagnosis of erectile dysfunction.

2 DOSAGE AND ADMINISTRATION • Determine the most suitable dose and presentation of CAVERJECT to use. Use a new syringe for each dose of CAVERJECT ( 2.1 ). • Administer first intracavernosal injections in the health care provider’s office and titrate the dose for each patient to the lowest effective dose ( 2.1 ). • Instruct the patient on proper use and assess that they are well trained in the self-injection technique prior to initiation of at-home use ( 2.1 ). • Recommended dosage for erectile dysfunction ( 2.2 ): o Erectile dysfunction of vasculogenic, psychogenic, or mixed etiology: Initiate dosing with 2.5 mcg o Erectile dysfunction of pure neurogenic etiology (spinal cord injury): Initiate dosing with 1.25 mcg • Follow dose titration procedures for each type of erectile dysfunction and determine the maintenance dosage for patient home use in the health care provider’s office ( 2.2 ). • The recommended frequency of injection is no more than 3 times weekly, with at least 24 hours between each dose ( 2.2 ). • While on self-injection treatment, the patient should visit the prescribing health care provider’s office every 3 months to assess the efficacy and safety of the therapy ( 2.1 ). • Follow procedure for CAVERJECT IMPULSE syringe preparation ( 2.3 ). • Follow the procedure for CAVERJECT IMPULSE administration ( 2.4 ). • To diagnose erectile dysfunction (pharmacologic testing), inject CAVERJECT IMPULSE intracavernosally and monitor patients for the occurrence of an erection ( 2.2 ). 2.1 Important Dosage and Administration Instructions • Alprostadil is available in different strengths and presentations. Determine the most suitable dose and presentation for each patient. Use a new syringe for each dose of CAVERJECT. • Titrate the dose of CAVERJECT IMPULSE for each patient to the lowest effective dose. • CAVERJECT IMPULSE doses greater than 60 mcg are not recommended. • Administer the first doses of CAVERJECT IMPULSE in the health care provider’s office by medically trained personnel. • Instruct the patient on proper use and assess that they are well trained in the self-injection technique prior to initiation of home use. Refer to the Patient Information and Instructions for Use. • Re-evaluate patients regularly (every 3 months or as clinically appropriate) and determine if dosage adjustments are needed. 2.2 Recommended Dosage for Erectile Dysfunction Erectile Dysfunction of Vasculogenic, Psychogenic, or Mixed Etiology. • Initiate dosing with 2.5 mcg of CAVERJECT IMPULSE intracavernousally as recommended [see Dosage and Administration 2.4 ] . • If there is a partial response at 2.5 mcg, administer another dose of 2.5 mcg within 1 hour. • During titration, no more than 2 doses should be given within a 24-hour period. • If additional titration is required, administer doses in increments of 5 to 10 mcg at least 24 hours apart. • The optimal dose should produce an erection suitable for intercourse that does not exceed a duration of 1 hour. • The patient must stay in the health care provider’s office until complete detumescence occurs. Repeat the titration as necessary until the optimal dose is achieved. Doses greater than 60 mcg are not recommended. Erectile Dysfunction of Pure Neurogenic Etiology (Spinal Cord Injury): • Initiate dosing with 1.25 mcg of alprostadil using CAVERJECT. • If there is a partial response, administer another dose of CAVERJECT of 1.25 mcg within 1 hour. • No more than 2 doses during initial titration should be given within a 24-hour period. • If additional titration is required, administer a dose of 5 mcg at least 24 hours later. • The optimal dose should produce an erection suitable for intercourse that does not exceed a duration of 1 hour. • The patient must stay in the health care provider’s office until complete detumescence occurs. Repeat the titration as necessary until the optimal dose is achieved. Doses greater than 60 mcg are not recommended. Maintenance Dosage for Patient Home Use: • Once the dos…

5 WARNINGS AND PRECAUTIONS • Prolonged erection and priapism have occurred in patients receiving CAVERJECT. To minimize the chances of this occurring, titrate CAVERJECT IMPULSE slowly to the lowest effective dose ( 2.1 ). Advise patients to seek immediate medical assistance for an erection that persists longer than 4 hours ( 5.1 ). • Penile fibrosis has occurred in patients receiving CAVERJECT. Follow patients regularly to detect signs of penile fibrosis. Discontinue in patients who develop penile angulation or cavernosal fibrosis ( 5.2 ). • Hypotension - injections of CAVERJECT IMPULSE can lead to increased peripheral blood levels of alprostadil, especially in patients with significant corpora cavernosa venous leakage. Avoid use in patients with known cavernosal venous leakage ( 5.3 ). • Injection site bleeding may occur in patients taking anticoagulants, such as warfarin or heparin. Compress the site of injection with an alcohol swab or sterile gauze for 5 minutes ( 5.4 ). • Cardiovascular risk related to underlying medical conditions - Underlying treatable medical causes of erectile dysfunction should be diagnosed and treated prior to initiation of therapy ( 5.5 ). • Risks of use in combination with other vasoactive medications injected intracavernosally - Safety and efficacy of combinations of CAVERJECT and other vasoactive agents have not been systematically studied. Use of such combinations is not recommended ( 5.6 ). • Risk of needle breakage – A superfine needle is used for CAVERJECT IMPULSE and cases of needle breakage have been reported. Careful instruction in proper patient handling and injection techniques may minimize this risk ( 5.7 ). • Benzyl alcohol – Serious and fatal adverse reactions can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved formulations in infusion solutions, including CAVERJECT IMPULSE. CAVERJECT IMPULSE is not indicated in neonates and infants ( 5.8 ). • Counsel patients about sexually transmitted diseases . Counsel patients about the protective measures necessary to guard against sexually transmitted disease including the Human Immunodeficiency Virus (HIV) ( 5.9 ). 5.1 Prolonged Erection and Priapism Prolonged erection, defined as erection lasting between 4 to 6 hours in duration, occurred in 4% of 1,861 patients treated up to 18 months in studies of CAVERJECT. The incidence of priapism (erections lasting more than 6 hours in duration) was 0.4%. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result. To minimize the chances of prolonged erection or priapism, titrate CAVERJECT IMPULSE to the lowest effective dose [ see Dosage and Administration (2.1 ]. In addition, do not use CAVERJECT IMPULSE in patients who have conditions that predispose them to priapism, such as sickle cell anemia or sickle cell trait, multiple myeloma, or leukemia [see Contraindications (4) ] . 5.2 Penile Fibrosis The overall incidence of penile fibrosis reported in clinical studies with CAVERJECT was 3%. In one self-injection clinical study where duration of use was up to 18 months, the incidence of penile fibrosis was 7.8%. Physical examination of the penis should be performed periodically to detect signs of penile fibrosis. Treatment with CAVERJECT IMPULSE should be discontinued in patients who develop penile angulation or cavernosal fibrosis. 5.3 Hypotension Intracavernous injections of CAVERJECT IMPULSE can increase peripheral blood levels of alprostadil which can result in hypotension. Avoid use of CAVERJECT IMPULSE in patients with known cavernosal venous leakage. 5.4 Injection Site Bleeding When Used with Anticoagulants Patients on anticoagulants, such as warfarin or heparin, may have increased propensity for injection site bleeding after intracavernosal injection with CAVERJECT IMPULSE. Compress the site of injection…

4 CONTRAINDICATIONS CAVERJECT IMPULSE is contraindicated: • in men who have a known hypersensitivity to the drug [see Adverse Reactions (6.1) ] • in men who have conditions that predispose them to priapism, such as sickle cell anemia or sickle cell trait, multiple myeloma, or leukemia [see Warnings and Precautions (5.1) ] • for the treatment of erectile dysfunction in men with fibrotic conditions of the penis, such as anatomical deformation, angulation, cavernosal fibrosis, or Peyronie's disease [see Warnings and Precautions (5.2) ] • in men with penile implants. • Known hypersensitivity to the drug ( 4 ). • Men who have conditions that predispose them to priapism, such as sickle cell anemia or sickle cell trait, multiple myeloma, or leukemia ( 4 ). • Treatment of erectile dysfunction in men with fibrotic conditions of the penis, such as anatomical deformation, angulation, cavernosal fibrosis, or Peyronie's disease ( 4 ). • Men with penile implants ( 4 ).

7 DRUG INTERACTIONS The potential for pharmacokinetic drug-drug interactions between alprostadil and other agents administered orally or intracavernosally has not been formally studied [see Warnings and Precautions (5.6) ] .

8.1 Pregnancy CAVERJECT IMPULSE is not indicated for use in females.

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: • Prolonged Erection and Priapism [see Warnings and Precautions (5.1) ] • Penile Fibrosis [see Warnings and Precautions (5.2) ] Most common (≥10%) adverse reactions: penile pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at (1-800-438-1985 and www.pfizer.com ) or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. CAVERJECT IMPULSE was evaluated in 87 patients in an open-label crossover study of 6 weeks treatment duration that compared the formulation of alprostadil for injection contained in CAVERJECT IMPULSE with the formulation contained in CAVERJECT. Doses used in this study ranged from 2.5 mcg to 20 mcg. Adverse reactions reported for the CAVERJECT IMPULSE formulation included: penis disorder (4.6%), prolonged erection (1.1%), injection site erythema (1.1%), rash (1.1%), dizziness (1.1%), and hematospermia (1.1%). Penis disorder included penile pain, post-injection pain, and pain with erection. CAVERJECT IMPULSE was also evaluated in 63 patients in a single-dose, double-blind, crossover study that compared CAVERJECT IMPULSE with CAVERJECT. Doses used in this study ranged from 2.5 mcg to 20 mcg. Adverse reactions reported for the CAVERJECT IMPULSE formulation included: penile pain (1.6%) and pruritus (1.6%). In addition to the adverse reactions observed for CAVERJECT IMPULSE in these two studies, the following adverse reactions have been reported in clinical studies of CAVERJECT: Local Adverse Reactions: Local adverse reactions derived from 1861 patients in clinical studies of CAVERJECT, including an 18-month, open-label study, are shown in Table 1. Table 1. Local Adverse Reactions Reported by ≥ 1% of Patients Treated with CAVERJECT for up to 18 Months Penile pain 37% Prolonged erection 4% Penile fibrosis 3% Injection site hematoma 3% Penis disorder Penis disorder includes: numbness, irritation, sensitivity, pruritus, erythema, skin tear, discoloration, itching. 3% Injection site ecchymosis 2% Penile rash 1% Penile edema 1% The following local adverse reactions were reported in < 1% of patients: injection site hemorrhage, injection site inflammation, injection site itching, injection site swelling, injection site edema, urethral bleeding, penile warmth, numbness, irritation, sensitivity, pruritus, erythema, painful erection, and abnormal ejaculation. In these studies, no local adverse reactions were reported in the 294 patients who received placebo, except for penile pain (2%). Penile Pain: In the majority of the cases, penile pain was rated mild or moderate in intensity. Three percent of patients discontinued treatment because of penile pain Prolonged Erection/Priapism: 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. In clinical studies, the frequency of prolonged erection after CAVERJECT was 4%, while the frequency of priapism was 0.4% [see Warnings and Precautions (5.1) ]. Penile Hematoma/Ecchymosis: In clinical studies, the frequency of penile hematoma and ecchymosis was 3% and 2%, respectively. Systemic Adverse Reactions : Systemic adverse reactions reported by ≥ 1% of subjects in clinical studies of CAVERJECT included: dizziness (1%). The following systemic adverse reactions were reported in < 1% of patients: testicular pain, scrotal edema, hematuria, pelvic pain, hypotension, vasodilation, vasovagal reaction, diaphoresis, rash, and non-application site pruritus. Three patients (0.2%) discontinued due to symptomatic hypotension. No systemic adverse reactions were reported in the 294 patients who received pl…