Can Alprostadil cause erection increased?

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 placebo. 6.2 Post-marketing Experience The following additional adverse reactions have been reported during post approval use of CAVERJECT IMPULSE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Injury and procedural complication : device malfunction/failure, needle breakage, drug ineffective and drug effect decreased.

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 with an alcohol swab or sterile gauze for 5 minutes. 5.5 Cardiovascular Risk Related to Underlying Medical Conditions There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including CAVERJECT IMPULSE, generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. In addition, the evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. 5.6 Risks of Use in Combination with Other Vasoactive Medications Injected Intracavernosally The safety and efficacy of combinations of CAVERJECT IMPULSE and other vasoactive agents injected intracavernosally have not been established in clinical studies. The risks of prolonged erection, priapism, and hypotension may be increased. 5.7 Needle Breakage CAVERJECT IMPULSE uses a superfine (29 gauge) needle for administration. As with all superfine needles, the possibility of needle breakage exists. Needle breakage, with a portion of the needle remaining in the penis, has been reported and, in some cases, has required hospitalization and surgical removal. Careful instruction in proper patient handling and injection techniques may minimize the potential for needle breakage [see Dosage and Administration (2.3) and Adverse Reactions (6.2) ] . 5.8 Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol The preservative benzyl alcohol contained in CAVERJECT IMPULSE 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. CAVERJECT IMPULSE is not indicated for use in pediatric patients. 5.9 Counsel Patients About Sexually Transmitted Diseases The use of CAVERJECT IMPULSE offers no protection against sexually transmitted diseases. Counsel patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV).