GeneralPrior
to approval by the FDA, use of sildenafil was evaluated in over 3,700
patients who ranged from 19 to 87 years of age. Over 550 patients were
treated for at least 1 year. In placebo-controlled trials, the rate of
discontinuation of therapy due to adverse events associated with
sildenafil averaged 2.5%, which was not significantly different compared
with placebo (2.3%). The incidence of side effects has been
dose-dependent.
Nervous systemNervous
system side effects have included headache, observed in up to 16% of
patients. Other nervous system side effects have included dizziness in
2%, and, in less than 2%: ataxia, hypertonia, neuralgia, neuropathy,
paresthesias, tremor, vertigo, depression, insomnia, somnolence,
abnormal dreams, decreased reflexes, and hypesthesia. There have been
case reports of transient global amnesia and tonic-clonic seizures. Post
marketing experience has included reports of anxiety, seizure and
seizure recurrence.
CardiovascularCardiovascular
side effects have included flushing (vasodilation) in 10% and dizziness
in 2% of patients. Consistent with its known effects on the nitric
oxide/cGMP pathway, use of sildenafil has been shown to potentiate the
hypotensive effects of nitrates, and its administration to patients who
are concurrently taking organic nitrates is considered contraindicated.
The following cardiovascular side effects have been associated with the
use of sildenafil in less than 2% of patients: angina pectoris, AV
block, migraine, syncope, tachycardia, palpitation, hypotension,
postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac
arrest, heart failure, abnormal electrocardiogram, chest pain, and
cardiomyopathy.
Postmarketing studies have reported serious
cardiovascular events, including myocardial infarction, sudden cardiac
death, ventricular arrhythmia, cerebrovascular hemorrhage, transient
ischemic attack, and hypertension in temporal association with the use
of sildenafil. Most patients had preexisting cardiovascular risk
factors. Many of these events were reported to occur during or shortly
after sexual activity, and a few were reported to occur shortly after
the use of sildenafil without sexual activity. Others were reported to
have occurred hours to days after the use of sildenafil and sexual
activity. It has not been determined whether these events are related
directly to sildenafil, to sexual activity, to the patient's underlying
cardiovascular disease, to a combination of these factors, or to other
factors.
GastrointestinalGastrointestinal
side effects have included dyspepsia (7%) and diarrhea (3%). Less
common gastrointestinal side effects have included abdominal pain,
vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis,
esophagitis, stomatitis, dry mouth, abnormal liver function tests,
rectal hemorrhage, and gingivitis. Inhibition of contractile activity of
the esophagus has been reported in patients receiving sildenafil who
have idiopathic achalasia.
Results from a study of patients with
idiopathic achalasia given sildenafil therapy showed inhibition of
contractile activity of the esophageal musculature resulting in
decreased lower esophageal sphincter tone and residual pressure as well
as contraction amplitude.
RespiratoryRespiratory
system side effects have included nasal congestion (4%). Other
respiratory system side effects have included wheezing, dyspnea,
laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum
production, and cough.
GenitourinaryGenitourinary
side effects have included urinary tract infection in 3% of patients.
Less commonly, occurring in less than 2% of patients, cystitis,
nocturia, urinary frequency, breast enlargement, urinary incontinence,
abnormal ejaculation, genital edema, and anorgasmia have been reported.
Prolonged erection greater than 4 hours and priapism (painful erections
greater than 6 hours in duration) have been reported infrequently since
market approval of sildenafil. 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 could result. Acute priapism associated
with the use of sildenafil in a patient with sickle cell trait has been
reported.
OcularSildenafil
is selective for phosphodiesterase-5 (PDE5). It has lesser affinity for
other PDE isoenzymes, one of which is PDE6, an enzyme found in the
retina. This lower selectivity is thought to be the basis for
abnormalities related to color vision observed with higher doses or
plasma levels.Nonarteritic anterior ischemic optic neuropathy developed
in one eye within minutes to hours after ingestion of sildenafil. Four
of the five patients had no vascular risk factors for ischemic optic
neuropathy.
Ocular side effects have included mild and transient blue
or colored-tinged vision, sometimes associated with photosensitivity or
blurred vision. Less common ocular side effects (less than 2% of
patients) have included mydriasis, conjunctivitis, photophobia,
tinnitus, eye pain, deafness, ear pain, eye hemorrhage, cataract, and
dry eyes. Several cases of optic neuropathy have been associated with
sildenafil use.
DermatologicDermatologic
side effect have included rash which was reported in at least 2% of
patients. Other dermatologic side effects have included urticaria,
herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, and
exfoliative dermatitis.
HematologicHematologic side effects have included anemia and leukopenia.
MetabolicMetabolic
side effects have included thirst, peripheral and general edema, gout,
hyperglycemia, hypoglycemia (including hypoglycemia reactions), and
hypernatremia.
OtherOther side effects have included facial edema, shock, asthenia, pain, chills, and accidental falls and injuries.
MusculoskeletalMusculoskeletal
side effects have included arthritis, arthrosis, myalgia, tendon
rupture, tenosynovitis, bone pain, myasthenia, and synovitis.
PsychiatricPsychiatric side effects have included anecdotal reports and case studies of psychological disturbances and aggressive behavior.
Other
Other
side effects have included cases of sudden decrease or loss of hearing
reported post-marketing in temporal association with the use of PDE5
inhibitors, including sildenafil. In some cases, medical conditions and
other factors were reported that may have also played a role in the
otologic adverse events. In many cases, medical follow-up information
was limited. It is not possible to determine whether these reported
events are related directly to the use of sildenafil, to the patient's
underlying risk factors for hearing loss, a combination of these
factors, or to other factors
