Diagnosis and Management of Infantile Hemangioma

acute myocardial infarction: 3 (Rate=0.035%), palpitation: 9 (Rate=0.106%), pulmonary edema:
1 (Rate=0.012%), syncope: 7 (Rate=0.083%), tachycardia: 8 (Rate=0.095%), presyncope: 1
(Rate=0.012%), and tachycardia ventricular: 2 (Rate=0.024%). 24 It is important to note that the
original FDA approval document only contains data for adult patients. Across five clinical trials,
patients applying the medication for 2 to 3 week cycles (n=665) experienced the following
adverse events most often: headache, local site reactions, fatigue and nausea. Patients using the
higher dose (3.75%) of Zyclara experienced local cite reactions more often.
Two clinical trials assessing the use of Zyclara® 2.5% and 3.75% in adult patients with
actinic keratosis were submitted in the original FDA approval document. 24 Patients age 36 to 90
applied the medication using one of two treatment cycles: 1) 3 weeks of treatment followed by 3
weeks of rest, 2) 3 weeks of treatment followed by 8 weeks of rest. Adverse events reported most
often in patients applying Zyclara® included: application site adverse events, fatigue, headache,
lymphadenopathy and influenza like illness.
Serious Adverse Events
Aldara® was studied in male and female patients (n=784) aged 15-77 (mean age 31.5) with
genital warts. Patients applied Aldara® three times a week for 16 weeks. 25 Some patients were
treated for up to 32 weeks if their warts were not cleared after the initial 16 weeks. Serious
adverse events reported in this study included: acute appendicititis (1), skull fracture (1),
increased depression/suicide attempt (1), suicide attempt/drug overdose (1), inferior mypcardial
infarction (1), pyelonephritis (1), pacemaker generator exchange (1), pancreatitis (1), cervical
cancer (1), exacerbation of depression (1), incomplete abortion (1), possible infection of GI tract
(1), and heroin addiction (1). In a similar study of male and female patients (n=943) age 16-78
(mean 31.2) with genital warts, 14 patients experienced serious adverse events including:
alteration in speech and sensation of spaciness (1), fracture of left clavicle (1); exacerbation of
eczema at non-wart site (1), rectal pain due to internal warts-remote site (1), nephrotic syndrome
(1), carcinoma of vulva (1), vulval pain (with anorexia and fatigue) (1), depression (1),
lymphangitis due to dog bite (1), axillary abscess (1), laryngeal cancer (1), vomiting and
abdominal pain (1), cholecystectomy (1), flu (1), tonsil abscess (1), metrorrhagia (1), and act
fetal distress (1).
The first clinical trial reviewed in the original FDA approval document for Zyclara® (GW01-
0702) had 227 patients complete the study. 24 Severe adverse events reported in patients applying
the 3.75% cream included: cerebrovascular accident, gout, and atrial fibrillation. Severe adverse
events reported in patients applying the 2.5% cream included: oral herpes, sinusitis, pneumonia,
application site infection, bacterial pneumonia, application site irritation, pruritic rash, procedural
pain, and cartilage injury. The second clinical trial (GW01-704) reported the following severe
adverse events in patients applying the 3.75% cream: influenza-like illness, chest pain, diarrhea,
vascular graft, and anxiety. Severe adverse events reported in patients applying the 2.75% cream
included: bronchiectasis, influenza-like illness twice, cheilitis, lymphadenopathy twice, angina
pectoris, atrial fibrillation, and arteriosclerosis.
Serious Adverse events reported across trials (n=160) of adult patients (mean age 64.4)
applying Zyclara® 2.5% cream for 2 weeks included: atrial fibrillation (1), chest pain (1),
pneumonia (2), acute myocardial infarction (1), non-cardiac chest pain (1), and ventricular
tachycardia (1). 24 Events reported in adult patients (n=160) applying Zyclara® 3.75% cream for
2 weeks included: cerebrovascular accident (1), atrial fibrillation (1), small intestine obstruction
(1), chest pain (1), anxiety (1), and diarrhea (1).
H-23