CaverJect Impulse

Erectile Dysfunction

CAVERJECT IMPULSE is indicated for the treatment of erectile dysfunction.

Diagnostic Test

CAVERJECT IMPULSE is indicated as an adjunct to other diagnostic tests in the diagnosis of erectile dysfunction.

Caverject Impulse (alprostadil) for injection contains sterile, freeze-dried alprostadil for reconstitution and sterile bacteriostatic water in a prefilled dual chamber glass cartridge. It is available in 10 mcg and 20 mcg strengths.

CAVERJECT IMPULSE should not be used:

• 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.

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)]

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 Sterile Powder. 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 Sterile Powder. 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 Sterile Powder:

Local Adverse Reactions: Local adverse reactions derived from 1861 patients in clinical studies of CAVERJECT Sterile Powder, including an 18-month, open-label study, are shown in Table 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 intracavernosal administration of CAVERJECT Sterile Powder 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 Sterile Powder 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 placebo.

Post-marketing Experience

The following additional adverse reactions have been reported: device malfunction/failure, drug ineffective and drug effect decreased.

Pregnancy

CAVERJECT IMPULSE is not indicated for use in females.

Lactation

CAVERJECT IMPULSE is not indicated for use in females.

Pediatric Use

CAVERJECT IMPULSE is not indicated for use in pediatric patients [see Warnings and Precautions (5.8)].

Geriatric Use

A total of 341 subjects included in clinical studies were 65 and older. No overall differences in safety and effectiveness were observed between these subjects and younger subjects, and the other reported clinical experience has not identified differences in responses between elderly and younger patients.

CAVERJECT IMPULSE contains alprostadil a synthetic form of prostaglandin E1 (PGE1) and is designated chemically as (11α,13E,15S)-11,15-dihydroxy-9-oxoprost-13-en-1-oic acid. The molecular weight is 354.49.

Alprostadil is a white to off-white crystalline powder with a melting point between 115° and 116°C. Its solubility at 35°C is 8000 micrograms (mcg) per 100 milliliter double distilled water.

The structural formula of alprostadil is represented below:

CAVERJECT IMPULSE is available as a disposable, single-dose, dual chamber syringe system. The system includes a glass cartridge which contains sterile, freeze-dried alprostadil in the front chamber and sterile bacteriostatic water for injection in the rear chamber. The alprostadil is reconstituted with the sterile bacteriostatic water just before injection. CAVERJECT IMPULSE is available in two strengths for intracavernosal administration:

10 microgram – The reconstituted solution has a volume of 0.64 mL. The delivered volume, 0.5 mL, contains 10 micrograms (mcg) of alprostadil, 324.7 mcg of alpha cyclodextrin, 45.4 mg of lactose, 23.5 mcg of sodium citrate, and 4.45 mg of benzyl alcohol.

20 microgram – The reconstituted solution has a volume of 0.64 mL. The delivered volume, 0.5 mL, contains 20 micrograms (mcg) of alprostadil, 649.3 mcg of alpha cyclodextrin, 45.4 mg of lactose, 23.5 mcg of sodium citrate, and 4.45 mg of benzyl alcohol.

During manufacture, the pH of the alprostadil for injection was adjusted with hydrochloric acid and/or sodium hydroxide before lyophilization.

Caverject Impulse®

Dual Chamber System
alprostadil for injection

10 micrograms

KEEP OUT OF REACH OF CHILDREN

Pharmacia & Upjohn Co
DIVISION OF PFIZER INC, NY, NY 10017
MADE IN BELGIUM

8Q3129

LOT/EXP

Pfizer

Caverject Impulse®
alprostadil for injection

10 micrograms

NDC 0009-5181-01
Contains 2 of NDC 0009-5181-10

For intracavernosal use only
Dual Chamber System

Contains 2 single dose injection systems
Diluent Contains Benzyl Alcohol

Rx only

Pfizer

Caverject Impulse®
alprostadil for injection

20 micrograms

NDC 0009-5182-01
Contains 2 of NDC 0009-5182-11

For intracavernosal use only
Dual Chamber System

Contains 2 single dose injection systems
Diluent Contains Benzyl Alcohol

Rx only

Applies to alprostadil: compounding powder, injectable kit, injectable powder for injection, injectable solution, transurethral suppository

General

The most common side effects were penile pain, local bleeding, fever, urethral pain, urethral burning, apnea, and flushing.[Ref]

Genitourinary

Very common (10% or more): Penile pain (up to 36%), urethral pain (13%), urethral burning (12%)
Common (1% to 10%): Prolonged erection greater than 4 hours, penile angulation, penile fibrosis, cavernous body fibrosis, Peyronie's disease, penis disorder, prostate disorder, testicular pain, urethral bleeding/spotting and other minor urethral abrasions, vaginal burning/itching
Uncommon (0.1% to 1%): Priapism, scrotal erythema, dysuria, hematuria, pollakiuria, micturition urgency, urethral hemorrhage, balanitis, phimosis, ejaculation disorder, scrotal disorder, scrotal pain, testicular swelling, testicular edema, scrotal edema, spermatocele, testicular disorder, testicular mass, penile hemosiderin deposits, swelling of the preputium or the glans, perineal pain, painful erection
Rare (less than 0.1%): Urinary tract infection
Frequency not reported: Anuria, abnormal ejaculation, penile deviations, penile warmth, urinary frequency/urinary urgency/impaired urination[Ref]

Cardiovascular

Very common (10% or more): Flushing (10.1%)
Common (1% to 10%): Bradycardia, hypotension, tachycardia, cardiac arrest, edema, hematoma, hypertension, myocardial infarction, abnormal ECG
Uncommon (0.1% to 1%): Vascular fragility, supraventricular extrasystoles, vein disorder, vasodilatation, peripheral vascular disorder, peripheral edema, swelling of the leg veins
Frequency not reported: Congestive heart failure, hyperemia, second degree heart block, shock, spasm of the right ventricle infundibulum, supraventricular tachycardia, ventricular fibrillation, rapid pulse, pneumopericardium, ventricular hypertrophy, tachyphylaxis, ductus arteriosus histological changes, venous leak, cardiac arrhythmias, postural hypotension, changes in blood pressure, vagal shock, vasovagal reactions, myocardial ischemia[Ref]

Local

Very common (10% or more): Local bleeding (15%)
Common (1% to 10%): Injection site hematoma, injection site burning, sensation of tension in the penis, injection site pain
Uncommon (0.1% to 1%): Injection site hemorrhage, injection site edema, injection site inflammation, injection site mass, injection site pruritus, injection site swelling and reddening, injection site irritation, injection site anesthesia, injection site warmth
Frequency not reported: Localized pain[Ref]

Respiratory

Very common (10% or more): Apnea (12%)
Common (1% to 10%): Upper respiratory tract infection, sinusitis, rhinitis
Frequency not reported: Bradypnea, bronchial wheezing, hypercapnia, respiratory depression, respiratory distress, tachypnea, hypoplastic lungs, pneumothorax[Ref]

Other

Very common (10% or more): Fever (14%)
Common (1% to 10%): Sepsis, influenza-like symptoms, pain, accidental injury
Uncommon (0.1% to 1%): Asthenia
Rare (less than 0.1%): Vertigo
Frequency not reported: Hypothermia, jitteriness, non-generalized weakness[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, leg pain, pelvic pain, muscle spasms
Uncommon (0.1% to 1%): Exostosis
Frequency not reported: Hyperextension of the neck, stiffness, cortical proliferation of the long bones, microcephaly, leg cramps[Ref]

Metabolic

Common (1% to 10%): Hypokalemia, hypertriglyceridemia, hypercholesterolemia, hyperglycemia
Frequency not reported: Hypoglycemia, hyperkalemia[Ref]

Nervous system

Common (1% to 10%): Seizures, headache, dizziness
Uncommon (0.1% to 1%): Syncope, hypoesthesia, hyperesthesia, presyncope
Frequency not reported: Cerebral bleeding, lethargy, numbness, collapse, amnesia, cerebrovascular accident[Ref]

Dermatologic

Common (1% to 10%): Ecchymosis, erythema, skin disorder
Uncommon (0.1% to 1%): Rash, pruritus, hyperhidrosis
Rare (less than 0.1%): Urticaria
Frequency not reported: Diaphoresis, sensitivity, irritation, non-application site pruritus[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, inguinal hernia
Uncommon (0.1% to 1%): Obstruction gastric, gastric mucosal hypertrophy, nausea, dry mouth
Frequency not reported: Gastric regurgitation, peritonitis[Ref]

Immunologic

Common (1% to 10%): Infection
Uncommon (0.1% to 1%): Fungal infection, common cold
Rare (less than 0.1%): Anaphylactic/anaphylactoid reactions[Ref]

Hematologic

Common (1% to 10%): Disseminated intravascular coagulation
Uncommon (0.1% to 1%): Blood creatinine increased
Very rare (less than 0.01%): Thrombocytopenia
Frequency not reported: Anemia, bleeding, hypochromic anemia[Ref]

Ocular

Common (1% to 10%): Abnormal vision
Uncommon (0.1% to 1%): Mydriasis[Ref]

Hepatic

Frequency not reported: Hyperbilirubinemia, biliary atresia[Ref]

Renal

Frequency not reported: Polycystic kidneys, renal failure[Ref]

Psychiatric

Frequency not reported: Hyperirritability[Ref]

Some side effects of Caverject Impulse may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.