warnings and cautions
5 WARNINGS AND PRECAUTIONS • Prolonged erection and priapism have occurred in patients receiving CAVERJECT. To minimize the chances of this occurring, titrate CAVERJECT 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 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 ). • Needle breakage: A superfine needle is used for administration of CAVERJECT 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. CAVERJECT 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 to the lowest effective dose [see Dosage and Administration (2.1) ]. In addition, do not use CAVERJECT 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 should be discontinued in patients who develop penile angulation or cavernosal fibrosis. 5.3 Hypotension Intracavernous injections of CAVERJECT can increase peripheral blood levels of alprostadil which can result in hypotension. Avoid use of CAVERJECT 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. 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, 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 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 Separate needles should be used for reconstitution and administration. A superfine needle is used for administration of CAVERJECT. 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 Preservative When reconstituted using the recommended diluent, the solution contains benzyl alcohol. Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved formulations in infusion solutions, including CAVERJECT. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. CAVERJECT is not indicated for use in pediatric patients. 5.9 Counsel Patients about Sexually Transmitted Diseases The use of CAVERJECT 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).