Sildenafil (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Antihypertensive
Peripheral Vasodilator
Erectile dysfunction Agent
Phosphodiesterase Type 5 Inhibitor
Vasodilator

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 to sexual activity; Maximum frequency of administration once daily

Pulmonary arterial hypertension:
5 or 20 mg orally 3 times daily; give

doses

approximately 4 to 6 hours apart
2.5 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 indicated for

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 INDICATIONS:
Antidepressant drug adverse reaction - Sexual dysfunction
Depression - Erectile dysfunction
Diabetes mellitus - Erectile dysfunction
Dialysis procedure - Erectile dysfunction
Drug-induced impotence
Erectile dysfunction - Generalized atherosclerosis
Erectile dysfunction - Lower urinary tract symptoms; In combination with alfuzosin
Erectile dysfunction - Parkinson disease
Erectile dysfunction - Peyronie disease
Erectile dysfunction – Prostatectomy
Erectile dysfunction - Radiation therapy
Erectile dysfunction - Resection of rectum
Erectile dysfunction - Spina bifida
Erectile dysfunction - Spinal cord injury
Female sexual arousal disorder
Persistent pulmonary hypertension of the newborn
Secondary 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 with pulmonary hypertension; this leads to vasodilation of the pulmonary vascular bed and; to a lesser degree; vasodilation in the systemic circulation. In patients with erectile 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 by sildenafil citrate causes increased levels of cGMP resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum

ADVERSE 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 vaso occlusive crisis

Ophthalmic:
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 intermittent

use of

organic nitrates in any form
Concomitant

use with

HIV protease inhibitors or elvitegravir/cobicistat/tenofovir/emtricitabine (when used for pulmonary arterial hypertension)
Concomitant use with riociguat or any other guanylate cyclase stimulator

Hypersensitivity to sildenafil

or any of its components

INTERACTION:
Nitrates:
Concomitant

use of sildenafil

with nitrates in any form is contraindicated

Ritonavir and other Potent CYP3A Inhibitors:
Concomitant

use of sildenafil

with ritonavir and other potent CYP3A inhibitors is not recommended

Other drugs that reduce blood pressure:
Alpha blockers. In drug-drug interaction studies, sildenafil (25 mg, 50 mg, or 100 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 or 10 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

Major:
Cannabis (theoretical)
Ceritinib (theoretical)
Clarithromycin (theoretical)
Conivaptan (theoretical)
Dihydrocodeine (probable)
Fluconazole (theoretical)
Fosnetupitant (theoretical)
Idelalisib (theoretical)
Itraconazole (probable)
Lumacaftor (theoretical)
Nefazodone (probable)
Netupitant (theoretical)
Simeprevir (theoretical)
Telithromycin (probable)
Voriconazole (probable)

Moderate:
Alfuzosin (probable)
Bosentan (established)
Bunazosin (probable)
Ciprofloxacin (probable)
Delavirdine (probable)
Doxazosin (probable)
Erythromycin (probable)
Etravirine (probable)
Ketoconazole (probable)
Moxisylyte (probable)
Nebivolol (probable)
Prazosin (probable)
Rifapentine (probable)
Silodosin (established)
Tamsulosin (probable)
Terazosin (probable)
Trimazosin (probable)

Contraindicated:
Amprenavir (theoretical)
Amyl Nitrite (theoretical)
Atazanavir (theoretical)
Boceprevir (theoretical)
Cobicistat (theoretical)
Darunavir (theoretical)
Erythrityl Tetranitrate (established)
Fosamprenavir (theoretical)
Indinavir (probable)
Isosorbide Dinitrate (established)
Isosorbide Mononitrate (established)
Lopinavir (theoretical)
Molsidomine (theoretical)
Nelfinavir (theoretical)
Nitroglycerin (established)
Nitroprusside (theoretical)
Pentaerythritol Tetranitrate (established)
Propatyl Nitrate (established)
Riociguat (theoretical)
Ritonavir (established)
Saquinavir (established)
Telaprevir (theoretical)
Tipranavir (theoretical)

PHARMACOKINETICS:
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 when sexual 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 of

low-dose sildenafil

and an increased risk of mortality for high- vs

low-dose therapy

Pulmonary hypertension secondary to sickle cell anemia; increased risk of veno-occlusive crisis requiring hospitalization
Pulmonary 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 care
Non-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 increased
Elderly 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 recommended
Concomitant use with strong CYP3A inhibitors is not recommended.

PREGNANCY CATEGORY:
Fetal Risk Cannot Be ruled out

BREAST FEEDING:
Infant Risk Cannot be ruled out

MONITORING:
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 efficacy

HOW 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 medications

DOSAGE 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

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 ingesting

250 mg of sildenafil

and improved with supportive care. In another case; a young adult developed recurrent tonic-clonic seizures after misusing sildenafil 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.

TREATMENTS:
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

PATIENT COUNSELING OR CLINICAL TEACHING:
Advise patient to report an erection that persists longer than 4 hours
Instruct 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 dizziness
For pulmonary hypertension; side effects may include epistaxis; headache; dyspepsia; flushing; insomnia; erythema; dyspnea; and rhinitis
For erectile dysfunction; counsel patient to take drug prior to sexual activity; but not more than once per day
Instruct patient taking for pulmonary hypertension not to take for erectile dysfunction




Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only information about medicine.