6 ADVERSE REACTIONS
The following are discussed in more detail in other sections of the labeling:
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- Prolonged Erection and Priapism [see Warnings and Precautions (5.1)]
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- Penile Fibrosis [see Warnings and Precautions (5.2)]
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.
| |
Penile pain | 37% |
Prolonged erection | 4% |
Penile fibrosis | 3% |
Injection site hematoma | 3% |
Penis disorder* | 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)].
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.