Dosing
Adult Dose
:Important Note:
Orphan drug designation:
Treatment of pediatric (children less than 17 years of age)
pulmonary arterial hypertension
Erectile dysfunction:
25 to 100 mg (50 mg
usual dose
) ORALLY 1 hour (range 0.5 to 4 hours) prior tosexual activity
; Maximum frequency of administration once dailyPulmonary arterial hypertension:
5 or
20 mg
orally 3 times daily; give doses approximately 4 to 6 hours apart2.5 Or
10 mg
IV bolus injection 3 times daily.Pediatric Dose
:Important Note:
Orphan drug designation:
Treatment of pediatric (children less than 17 years of age)
pulmonary arterial hypertension
General Dosage Information:
Sildenafil use
; especially chronic treatment; is not recommended in children;sildenafil
not indicatedfor use
in pediatric patients; safety and effectiveness not established.Pulmonary arterial hypertension:
0.5 mg/kg orally once the night before and the morning of congenital heart disease surgery; IV 0.4 mg/kg administered after removal of aortic cross clamp; followed by a continuous IV infusion over 24 hours (total 1.6 mg/kg); then 0.5 mg/kg orally with termination of IV infusion (off-label dosage).
Indications
FDA-LABELED INDICATIONS:Erectile dysfunction
Pulmonary arterial hypertension
NON-FDA LABELED INDICATONS:
Antidepressant drug adverse reaction – Sexual dysfunction
Depression –
Erectile dysfunction
Diabetes mellitus –
Erectile dysfunction
Dialysis procedure –
Erectile dysfunction
Drug-induced impotence
Erectile dysfunction
– Generalized atherosclerosisErectile dysfunction
– Lower urinary tract symptoms; In combination with alfuzosinErectile dysfunction
– Parkinson diseaseErectile dysfunction
– Peyronie diseaseErectile dysfunction
– ProstatectomyErectile dysfunction
– Radiation therapyErectile dysfunction
– Resection of rectumErectile dysfunction
– Spina bifidaErectile dysfunction
– Spinal cord injuryFemale sexual arousal disorder
Persistent
pulmonary hypertension
of the newbornSecondary Raynaud phenomenon
Sexual dysfunction – Spinal cord injury
Mechanism of Action
Sildenafil citrate
is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE5) in smooth muscle; where PDE5 is responsible for degradation of cGMP.Sildenafil citrate
increases cGMP within vascular smooth muscle cells resulting in relaxation and vasodilation. In patients withpulmonary hypertension
; this leads to vasodilation of the pulmonary vascular bed and; to a lesser degree; vasodilation in the systemic circulation. In patients witherectile dysfunction
;sildenafil citrate
enhances the effect of nitric oxide (NO) by inhibiting PDE5 in the corpus cavernosum. When sexual stimulation causes local release of NO; inhibition of PDE5 bysildenafil citrate
causes increased levels of cGMP resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosumAdverse Effect
Common:Dermatologic:
Erythema (
pulmonary arterial hypertension
; 6%)Flushing (
erectile dysfunction
; 10% to 19%;pulmonary arterial hypertension
; 10%)Gastrointestinal:
Indigestion (
erectile dysfunction
; 3% to 17%;pulmonary arterial hypertension
; 13%)Neurologic:
Headache (
erectile dysfunction
; 16% to 28%;pulmonary arterial hypertension
; 46%)Insomnia (
erectile dysfunction
; less than 2%;pulmonary arterial hypertension
; 7%)Ophthalmic:
Visual disturbance (
erectile dysfunction
; 1% to 11%)Respiratory:
Epistaxis (
pulmonary arterial hypertension
; 3% to 9%)Nasal congestion (
erectile dysfunction
; 4% to 9%)Rhinitis (
pulmonary arterial hypertension
; 4%)Serious:
Cardiovascular:
Cardiovascular morbidity
Myocardial infarction
Sickle cell anemia
with vasoocclusive crisisOphthalmic:
Non-arteritic ischemic optic neuropathy
Retinal hemorrhage (
pulmonary hypertension
, 1.4% to 1.9%)Otic:
Decreased hearing
Sudden onset (
erectile dysfunction
, less than 2%)Sudden hearing loss (
erectile dysfunction
, less than 2%)Reproductive:
Priapism, Prolonged erection of penis
Contraindication
Concurrent regular or intermittentuse of organic nitrates
in any formConcomitant
use with
HIV protease inhibitors or elvitegravir/cobicistat/tenofovir/emtricitabine (whenused for
pulmonary arterial hypertension
)Concomitant
use with riociguat
or any other guanylate cyclase stimulatorHypersensitivity to sildenafil
or any of its componentsInteraction
Nitrates:Concomitant
use of sildenafil
with nitrates in any form is contraindicatedRitonavir and other Potent CYP3A Inhibitors :
Concomitant
use of sildenafil
with ritonavir and other potent CYP3A inhibitors is not recommendedOther drugs that reduce blood pressure:
Alpha blockers. In drug-drug interaction studies,
sildenafil
(25 mg
,50 mg
, or100 mg
) and the alpha-blocker doxazosin (4 mg or 8 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy. In these study populations, mean additional reductions of supine systolic and diastolic blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, respectively, were observed. Mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were also observed. There were infrequent reports of patients who experienced symptomatic postural hypotension. These reports included dizziness and light-headedness, but not syncope.Amlodipine When
sildenafil 100 mg
oral was co-administered with amlodipine, 5 mg or10 mg oral
, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic.Monitor blood pressure when co-administering blood pressure lowering
drugs with sildenafil
Phamacokinetics
Absorption:Bioavailability: 41%
Time for Maximum Plasma concentration (Tmax): 30 to 120 minutes
Effect of food; high fat meal: mean delay in Tmax of 60 minutes; mean reduction in Cmax of 29%
Distribution:
Volume of Distribution (Vd):
Adults: 105 L
Neonates: 22.4 L or 456 L/70 kg
Protein binding: Plasma: 96% (sildenafil and N-desmethyl metabolite)
Metabolism:
Hepatic: CYP3A4 (major) and CYP2C9 (minor)
Metabolite: active N-desmethyl metabolite;accounts for 20% of
sildenafil pharmacologic effects
Excretion:
Fecal: 80% as metabolites
Renal: 13% as metabolites
Dialyzable: no (hemodialysis)
Elimination:
Sildenafil citrate: 4 hours
N-desmethyl metabolite: 4 hours
Precaution
Cardiovascular:Cardiac failure or coronary artery disease causing unstable angina
Use
not recommended whensexual activity
is inadvisable due to patient cardiovascular status Conditions adversely affected by vasodilatory effects (eg, resting hypotension, fluid depletion; left ventricular outflow obstruction, or autonomic dysfunction)Hypertension (blood pressure greater than 170/110 mmHg) or resting hypotension (blood pressure less than 90/50 mmHg)
Myocardial infarction; stroke, or life-threatening arrhythmia within the last 6 months
Pediatric patients with
pulmonary arterial hypertension
;use
not recommended due to lack of efficacy oflow-dose sildenafil
and an increased risk of mortality for high- vs low-dose therapyPulmonary hypertension
secondary tosickle cell anemia
; increased risk of veno-occlusive crisis requiring hospitalizationPulmonary veno-occlusive disease; pulmonary vasodilators may significantly worsen cardiovascular status;
use
not recommended.Hepatic:
Hepatic impairment; dose adjustment recommended.
Renal:
Renal impairment, severe (CrCl less than 30 mL/min); dose adjustment recommended.
Ophthalmic:
Sudden vision loss in one or both eyes; discontinue
use of all phosphodiesterase type 5 inhibitors
and seek medical careNon-arteritic anterior ischemic optic neuropathy (NAION) has been reported; increased risk with previous NAION or crowded optic disk
Retinitis pigmentosa;
use
with caution.Otic:
Sudden decrease or loss of hearing; discontinue
use of phosphodiesterase
type 5 inhibitors and seek prompt medical care.Other:
Anatomical deformation of the penis (eg, angulation, cavernosal fibrosis, or Peyronie disease) or conditions that predispose to priapism (eg,
sickle cell anemia
, multiple myeloma, or leukemia); risk of priapism may be increasedElderly patients (older than 65 years); dose adjustment recommended
Prolonged erection greater than 4 hours and priapism have been reported; immediately treat priapism
Concomitant use:
Concurrent
use with other phosphodiesterase
5 inhibitors is not recommendedConcomitant
use
with strong CYP3A inhibitors is not recommended.Pregnancy Category
Fetal Risk Cannot Be ruled outBreast Feeding
Infant Risk Cannot be ruled outMonitoring
Erectile dysfunction:Improved erectile response is indicative of efficacy
Pulmonary arterial hypertension:
Improvement in signs and symptoms of
pulmonary arterial hypertension
(dyspnea or fatigue, chest pain, or near syncope) exercise capacity, and WHO functional classification, and a decrease in the rate of clinical worsening are indicative of efficacyHow to Take or Administration
Intravenous:(
Pulmonary arterial hypertension
)Administer as an IV bolus injection 3 times a day.
Oral:
(
Erectile dysfunction
)Take approximately 1 hour (from 30 minutes to 4 hours) before
sexual activity
(
Pulmonary arterial hypertension
)Take tablets or
oral suspension doses
approximately 4 to 6 hours apart; do not mix oral suspension with flavorings or other medicationsDosage Form
Intravenous Solution:10 MG/12.5 ML
Oral Tablet:
20 MG
25 MG
50 MG
100 MG
Oral Powder for Suspension:
10 MG/1 ML
Treatment
MANAGEMENT OF MILD TO MODERATE TOXICITY:The vast majority of
sildenafil overdoses
requires only supportive care; activated charcoal is indicated if patients present shortly after ingestion. Treat headache; facial flushing; dizziness and general weakness with IV fluids. Hypotension and tachycardia are generally mild and well tolerated and usually respond to IV fluids.MANAGEMENT OF SEVERE TOXICITY:
Patients who experience respiratory compromise or significant CNS depression require early endotracheal intubation for airway protection. While activated charcoal is indicated in these cases; is should be performed only in patients who can protect their airway or who are intubated. Patients with persistent hypotension despite intravenous fluids require vasopressors; theoretically alpha agonists norepinephrine and phenylephrine may be more effective
Toxicology
ADULT:Adults who ingest less than 800 mg typically have symptoms consistent with therapeutic dosing. A 56-year-old man reportedly intentionally ingested
6500 mg of sildenafil
and initially developed severe vomiting and complaints of blurred vision. Upon admission 24 hours later; his serum level was 22.2mcg/mL (higher than previously reported in fatal and non fatal cases). Symptoms were managed with supportive care and he recovered completely. However; one adult developed rhabdomyolysis after ingesting250 mg of sildenafil
and improved with supportive care. In another case; a young adult developed recurrent tonic-clonic seizures after misusingsildenafil 100 mg
; no intervention was needed. Doses in excess of 2000 mg have caused hypotension and tachycardia. Fatalities are exceedingly rare.PEDIATRIC:
A 2-year-old developed persistent facial flushing; painful transient penile engorgement; bilateral rhonchi; and diarrhea after ingesting approximately 1.5 pills (75 mg) of
sildenafil
.Patient Counselling or Clinical Teaching
Advise patient to report an erection that persists longer than 4 hoursInstruct patient to report a sudden decrease or loss of hearing or vision
For
erectile dysfunction
;side effects
may include flushing; dyspepsia; nausea; headache; angina; and dizzinessFor
pulmonary hypertension
; side effects may include epistaxis; headache; dyspepsia; flushing; insomnia; erythema; dyspnea; and rhinitisFor
erectile dysfunction
; counsel patient to take drug prior tosexual activity
; but not more than once per dayInstruct patient taking for
pulmonary hypertension
not to take forerectile dysfunction
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