Sildenafil is a medication primarily used to treat erectile dysfunction and pulmonary arterial hypertension. It works by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which regulates blood flow in the penis. By blocking PDE5, sildenafil increases blood flow to the penis during sexual stimulation, resulting in improved erectile function. For pulmonary arterial hypertension, sildenafil relaxes the blood vessels in the lungs, allowing blood to flow more easily, thus reducing the workload on the heart.

Sildenafil (Revatio, Viagra) is a class of drugs called phosphodiesterase inhibitors. It causes vasodilation of the pulmonary vessels and penis. Thus, it is used in the treatment of erectile dysfunction in males and pulmonary hypertension in males and females. The efficacy of sildenafil in women with sexual dysfunction has not been established.

Sildenafil (Revatio, Viagra) Uses:

• Erectile dysfunction:
  • Viagra: Treatment of erectile dysfunction (ED)
• Pulmonary arterial hypertension:
  • Revatio: Treatment of pulmonary arterial hypertension (PAH) (WHO Group I; efficacy established predominately in patients with WHO/NYHA functional class II and III) in adults to improve exercise ability and delay clinical worsening.
• Off Label Use of Sildenafil in Adults:
  • Achalasia/Esophageal motility disorders;
  • Persistent pulmonary hypertension after recent left ventricular assist device placement;
  • Raynaud phenomenon

Sildenafil (Viagra) Dose in Adults

Sildenafil (Viagra) Dose in the treatment of Erectile dysfunction:

• Usual dose: Start with 50 mg once a day. You take it by mouth about 1 hour before you plan to have sex. But you can take it anytime between 30 minutes to 4 hours before sex.
• Dosing range: Your doctor might adjust your dose depending on how you respond. It can vary from 25 mg to 100 mg once a day.
• Maximum dose: The highest amount you should take in a day is 100 mg.

Sildenafil Dose in the treatment of pulmonary arterial hypertension (PAH) (Revatio):

For Intravenous (IV) Use:

• You might get either 2.5 mg or 10 mg three times a day through a vein.

For Oral Use:

• Start with 20 mg to 40 mg three times a day by mouth.
• Your doctor may increase the dose up to a maximum of 80 mg three times a day if you're not responding well to the lower dose.

Keep in mind:

• Always follow your doctor's instructions precisely.
• The dosages might vary based on your individual needs and response.
• The maximum dose according to manufacturer's labeling is 20 mg three times a day, but your doctor may adjust this based on your specific situation.

Sildenafil (Revatio, Viagra) Dose in the treatment of Raynaud phenomenon (off-label):

• Take 50 mg of sildenafil by mouth twice a day.
• Clinical trials lasted for up to 4 weeks.

For patients already taking alpha-blockers:

• Start with a lower dose of 25 mg of Viagra.

When using potent CYP34A inhibitors like itraconazole or ketoconazole, or erythromycin:

• Consider starting with a lower dose of 25 mg.
• If you're taking protease inhibitors, the maximum dose is 25 mg every 48 hours.

Sildenafil (Viagra) Dose in Childrens

Note:

• In pediatric patients (1 to 17 years of age) with PAH, increased mortality risk was associated with long-term use (>2 years) at dose levels of 0.88 to 2.5 mg/kg/dose administered three times a day.
• Use of Revatio, especially chronic use, is not advised in pediatric patients because of dose-dependent increased mortality risk reported in trials; however, situations may exist in which the benefit-risk profile of Revatio may make its use, with close monitoring, acceptable in individual pediatric patients, for example, when other treatment options are limited.
• Oral suspensions may be available in multiple concentrations (commercially available: 10 mg/mL; extemporaneous preparation: 2.5 mg/mL);
• dosing should be presented in mg of sildenafil;
• use extreme caution when verifying product formulation and calculation of dose volumes.

Sildenafil (Revatio, Viagra) Dose in the treatment of pulmonary hypertension:

For Infants:

• Start with either 0.25 mg/kg per dose every 6 hours or 0.5 mg/kg per dose every 8 hours.
• Adjust the dose as needed, with a maximum reported dose range of 1 to 2 mg/kg per dose every 6 to 8 hours.

For Children and Adolescents under 18 years old:

• The dosage depends on weight:
  • 8 to 20 kg: 10 mg three times daily
  • More than 20 kg to 45 kg: 20 mg three times daily
  • More than 45 kg: 40 mg three times daily

Important Points:

• For children, it's crucial not to increase the dosage beyond these recommendations.
• Higher doses and long-term use can increase the risk of mortality.
• These dosage recommendations are based on studies showing effectiveness in improving exercise capacity, functional class, and hemodynamic status.
• It's estimated that these doses will achieve specific serum concentrations needed for effectiveness while minimizing risks.

Sildenafil (Revatio, Viagra) Dose in the treatment of Pulmonary hypertension due to congenital heart surgery (postoperative):

Oral (or through a nasogastric tube) for Infants, Children, and Adolescents:

• Start with 0.5 mg/kg per dose when admitted to the intensive care unit (ICU).
• Increase the dose by 0.5 mg/kg every 4 to 6 hours, up to a maximum of 2 mg/kg per dose, as tolerated.
• When mechanical ventilation is discontinued, sildenafil therapy can be gradually reduced over 5 to 7 days.
• The dosing is based on various studies showing a reduction in pulmonary arterial pressures and prevention of severe pulmonary hypertension. Different studies used different doses ranging from 0.35 mg/kg per dose to 0.9 mg/kg per dose four times daily.

Intravenous (IV) for Infants over 60 days and Children:

• A loading dose is given over 5 minutes, with a range of 0.04 to 0.35 mg/kg.
• This is followed by a maintenance infusion, with reported ranges of 0.015 to 0.4 mg/kg per hour, continued for 24 to 72 hours.
• Different dosages were used in a trial aiming for specific serum concentrations. Patients who received sildenafil had lower pulmonary artery pressure, shorter mechanical ventilation duration, ICU stay, and hospitalization compared to those who received a placebo.

Important Points:

• Dosages can vary depending on the patient's age, condition, and response to treatment.
• Sildenafil may be tapered off gradually after discontinuing mechanical ventilation.
• IV administration may be used in specific cases, with dosages tailored to achieve desired serum concentrations.

Sildenafil Dose in the treatment of Pulmonary hypertension, facilitation of inhaled nitric oxide (iNO) wean (in patients who have not previously failed iNO wean): 

For Infants and Children up to 15 months old:

• Oral administration: A single dose of 0.4 mg/kg (with a range of 0.3 to 0.5 mg/kg) given once, 60 minutes before discontinuing inhaled nitric oxide (iNO).
• This dosage is based on a study involving infants and young children, aiming to facilitate the transition from iNO therapy.

Regarding special considerations:

• There are no specific pediatric recommendations for dosage adjustments in patients taking alpha blockers. Consultation with a healthcare provider is necessary.
• For patients taking potent CYP3A4 inhibitors (such as itraconazole or ketoconazole), it's not recommended to use sildenafil alongside these medications. Additionally, the concurrent use of sildenafil with protease inhibitors is contraindicated.

Pregnancy Risk Category: B

• Sildenafil, a medication known for widening blood vessels, has been found to pass through the placenta in studies.
• Researchers are exploring its potential use in pregnancy-related issues due to its ability to relax the uterus.
• However, using sildenafil in pregnant women is not recommended outside of controlled clinical studies, as early data from research on its use for fetal growth restriction showed adverse effects in newborns.
• Limited information is available regarding its safety and effectiveness for treating pulmonary arterial hypertension (PAH) during pregnancy, a condition that poses serious risks such as heart failure, stroke, and maternal/fetal death if left untreated.
• Women with PAH are advised against becoming pregnant to mitigate these risks.

Use Sildenafil while breastfeeding

• Sildenafil, a medication used for pulmonary arterial hypertension (PAH), has been detected in breast milk.
• A case report discussed the presence of sildenafil and its metabolite, desmethylsildenafil, in breast milk after a mother used it for PAH treatment.
• This finding suggests that sildenafil can pass from mother to infant through breastfeeding.

Sildenafil (Revatio, Viagra) Dose in Kidney Disease:

• If a person's creatinine clearance (CrCl) is equal to or greater than 30 mL/minute, no adjustment to the sildenafil dosage is needed.
• If CrCl is less than 30 mL/minute, for Revatio, no dosage adjustment is necessary.
• But for Viagra, it's recommended to start with a lower dose of 25 mg to ensure safety. Adjusting the dosage based on renal function helps to prevent potential side effects and ensures the medication is appropriately metabolized by the body.

Sildenafil (Revatio, Viagra) Dose in Liver disease:

• For individuals with mild to moderate impairment (Child-Pugh classes A and B), no dosage adjustment is necessary for Revatio. However, for Viagra, it's advisable to consider starting with a lower dose of 25 mg to ensure safety.

• In cases of severe impairment (Child-Pugh class C), specific dosage adjustments for Revatio are not provided in the manufacturer's labeling as it hasn't been studied. Similarly, for Viagra, it's recommended to start with a lower dose of 25 mg. Adjusting the dosage based on liver function helps minimize the risk of adverse effects and ensures the medication is metabolized effectively.

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Side effects such as flushing, myalgia, diarrhea, and visual disturbances may be increased with adult doses exceeding 100 mg/24 hours)

Common Side Effects of Sildenafil (Revatio, Viagra):

• Cardiovascular:
  • Flushing
• Central Nervous System:
  • Headache
• Gastrointestinal:
  • Dyspepsia
• Ophthalmic:
  • Visual Disturbance
• Respiratory:
  • Epistaxis

Less Common Side Effects of Sildenafil (Revatio, Viagra):

• Central Nervous System:
  • Insomnia
  • Dizziness
  • Paresthesia
• Dermatologic:
  • Erythema
  • Skin Rash
• Gastrointestinal:
  • Diarrhea
  • Gastritis
  • Nausea
• Genitourinary:
  • Urinary Tract Infection
• Hepatic:
  • Increased Liver Enzymes
• Neuromuscular & Skeletal:
  • Myalgia
  • Back Pain
• Respiratory:
  • Nasal Congestion
  • Exacerbation Of Dyspnea
  • Nasal Congestion
  • Rhinitis
  • Sinusitis
• Miscellaneous:
  • Fever

Contraindications to Sildenafil (Revatio, Viagra):

• Sildenafil is contraindicated in individuals with hypersensitivity to sildenafil or any component of the formulation, those using organic nitrates regularly or intermittently (like nitroglycerin), and those taking riociguat, a guanylate cyclase stimulator.
• Additionally, protease inhibitors, such as atazanavir, darunavir, fosamprenavir, and others, when used concurrently with sildenafil for pulmonary artery hypertension (PAH), are contraindicated according to the manufacturers' recommendations.
• In Canada, Viagra is contraindicated in individuals with a prior episode of non-arteritic anterior ischemic optic neuropathy (NAION).
• Similarly, Revatio is contraindicated in those with a prior episode of NAION, concurrent use with potent CYP3A4 inhibitors like ketoconazole or itraconazole, pulmonary hypertension secondary to sickle cell anemia, severe hepatic impairment, recent history of stroke or MI, life-threatening arrhythmia, coronary artery disease causing unstable angina, and severe hypotension (blood pressure <90/50 mm Hg) at initiation.

Warnings and precautions

Color discrimination:

• Sildenafil may lead to dose-dependent impairment of color discrimination.
• Caution is advised in patients with retinitis pigmentosa, as some may have genetic disorders affecting retinal phosphodiesterases, although safety information specific to this population is not available.

Hearing loss:

• Sudden decrease or loss of hearing, sometimes accompanied by symptoms like ringing in the ears (tinnitus) and dizziness, has been reported with the use of sildenafil.
• However, it's important to note that a direct relationship between sildenafil therapy and hearing loss hasn't been conclusively established.

Hypersensitivity

• Hypersensitivity reactions to sildenafil, including rash, hives (urticaria), and severe allergic reactions like anaphylaxis and anaphylactic shock, have been reported.
• If you experience any signs of a hypersensitivity reaction while taking sildenafil, such as a rash or difficulty breathing, seek immediate medical attention.

Hypotension

• Sildenafil can cause decreases in blood pressure due to its vasodilator effects.
• It's important to use caution in patients with conditions like aortic stenosis or hypertrophic obstructive cardiomyopathy, as well as those already on antihypertensive therapy or with resting low blood pressure (less than 90/50 mm Hg).
• Patients with fluid depletion or autonomic dysfunction may also be more sensitive to the hypotensive effects of sildenafil.
• Before starting treatment, patients should be hemodynamically stable, and the lowest possible dose should be used.
• Blood pressure should be monitored, especially when combining sildenafil with medications that lower blood pressure.
• Drinking substantial amounts of alcohol can increase the risk of low blood pressure and orthostatic hypotension.
• Therefore, patients should avoid or limit alcohol consumption while taking sildenafil.
• Lower levels of alcohol intake haven't been linked to significant changes in blood pressure or an increase in orthostatic symptoms.

Priapism

• Priapism, which is a prolonged and painful erection lasting longer than 6 hours, has been reported rarely with the use of sildenafil.
• Patients should be educated about this potential side effect and advised to seek medical assistance if they experience an erection lasting longer than 4 hours.
• Prompt medical attention is crucial to prevent complications associated with priapism, such as tissue damage and permanent erectile dysfunction.

Vision loss:

• Sudden loss of vision in one or both eyes, including permanent vision loss, may occur with the use of sildenafil and could be a sign of a condition called nonarteritic anterior ischemic optic neuropathy (NAION).
• Risk factors for NAION include a history of vision loss, a crowded optic disc (low cup-to-disc ratio), coronary artery disease, diabetes, hypertension, high cholesterol levels, smoking, and being over 50 years old.
• If a patient experiences sudden vision loss while taking sildenafil, they should stop the medication immediately and seek medical attention.
• While a direct relationship between sildenafil therapy and vision loss hasn't been conclusively determined, it's important to prioritize patient safety and address any potential concerns promptly.

Anatomical penis deformation:

• Sildenafil should be used with caution in patients who have anatomical deformities of the penis, such as angulation, cavernosal fibrosis, or Peyronie's disease.
• These conditions may increase the risk of complications or discomfort during erections.

Bleeding disorders:

• Sildenafil should be used cautiously in patients with bleeding disorders, as its safety in such individuals has not been firmly established.
• In vitro studies have indicated a potential decrease in platelet aggregation with sildenafil use.
• This suggests that sildenafil may affect blood clotting, although the clinical significance of this effect remains uncertain.

Cardiovascular disease

• Sildenafil should be used cautiously in patients with cardiovascular disease.
• This includes individuals with low blood pressure (hypotension, defined as less than 90/50 mm Hg), uncontrolled high blood pressure (hypertension, defined as greater than 170/110 mm Hg), recent history of stroke or heart attack (within the last 6 months), life-threatening arrhythmias, cardiac failure, or coronary artery disease leading to unstable angina.
• Safety and effectiveness of sildenafil have not been specifically studied in these patient populations.
• Additionally, caution is advised in patients with left ventricular outflow obstruction, such as aortic stenosis.

Predisposing conditions to priapism

• Sildenafil should be used with caution in patients who have conditions that may predispose them to priapism, such as sickle cell anemia, multiple myeloma, or leukemia.
• Priapism is a prolonged and painful erection that can occur as a rare side effect of sildenafil.
• All patients taking sildenafil should be instructed to seek immediate medical attention if they experience an erection that persists for more than 4 hours, as priapism requires prompt treatment to prevent potential complications, such as tissue damage and permanent erectile dysfunction.

Hepatic impairment

• Patients with hepatic impairment should use Viagra (sildenafil) with caution.
• It's advisable to start with the lowest dose available, which is typically 25 mg.
• This caution is necessary because hepatic impairment can affect how the body metabolizes medications, potentially leading to increased drug levels and a higher risk of side effects.
• By starting with a lower dose, healthcare providers aim to minimize the risk of adverse reactions while still providing effective treatment for erectile dysfunction.

Peptic ulcer disease:

• Sildenafil should be used with caution in patients with active peptic ulcer disease.
• The safety of sildenafil in this population has not been firmly established.
• Peptic ulcer disease involves open sores in the lining of the stomach or small intestine, and sildenafil may potentially exacerbate these ulcers or interfere with healing.

PAH:

• It's important to avoid suddenly stopping sildenafil monotherapy for pulmonary arterial hypertension (PAH), as this could lead to a worsening of the condition.
• While the effectiveness of sildenafil in adult patients has been established through short-term studies lasting 12 to 16 weeks, the safety of long-term use remains uncertain.
• In pediatric patients, a long-term trial showed increased mortality rates in higher dose groups (ranging from 20 to 80 mg three times daily, depending on weight) after two years of use.
• These findings emphasize the need for careful monitoring and evaluation of the risks and benefits of sildenafil therapy, particularly in long-term treatment plans for PAH.

Pulmonary venoocclusive disease

• Sildenafil is not recommended for use in patients with pulmonary veno-occlusive disease (PVOD) as it has not been studied in this population.
• If pulmonary edema occurs during treatment for pulmonary arterial hypertension (PAH) with sildenafil, healthcare providers should consider the possibility of PVOD.
• Pulmonary veno-occlusive disease is a rare condition characterized by narrowing or blockage of the blood vessels in the lungs, leading to increased pressure in the pulmonary arteries.
• The use of sildenafil in patients with PVOD may worsen symptoms and lead to complications, so caution is advised in this population.

Renal impairment

• Patients with renal impairment should use Viagra (sildenafil) with caution, as dose adjustment may be necessary.
• In cases of severe renal dysfunction, with a creatinine clearance (CrCl) less than 30 mL/minute, it is advisable to start with the lowest dose available, typically 25 mg.
• Renal impairment can affect how the body processes medications, potentially leading to increased drug levels and an increased risk of side effects.

Sickle cell anemia

• In patients with sickle cell anemia, treating pulmonary hypertension with sildenafil may increase the likelihood of hospitalizations for the management of vaso-occlusive crises.
• The effectiveness and safety of sildenafil in treating pulmonary hypertension secondary to sickle cell disease have not been firmly established.
• Given the potential risks.

Sildenafil: Drug Interaction

Risk Factor C (Monitor therapy)
Alcohol (Ethyl)	May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors.
Alpha1-Blockers (Uroselective)	May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors.
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Blood Pressure Lowering Agents	Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Blood Pressure Lowering Agents.
Bosentan	May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan.
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May increase the serum concentration of Sildenafil.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Etravirine	May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Management: No empiric dosage adjustments are recommended with concomitant therapy; however, dose of the phosphodiesterase inhibitor may need to be altered based on clinical response.
Fluconazole	May increase the serum concentration of Sildenafil.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Grapefruit Juice	May increase the serum concentration of Sildenafil.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Lorcaserin	May enhance the adverse/toxic effect of Phosphodiesterase 5 Inhibitors. Specifically, the risk of developing priapism may be increased.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Sapropterin	May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Simeprevir	May increase the serum concentration of Phosphodiesterase 5 Inhibitors.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Risk Factor D (Consider therapy modification)
Alpha1-Blockers (Nonselective)	Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Alpha1-Blockers (Nonselective). Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended.
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary hypertension should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, starting adult dose should be reduced to 25 mg. Maximum adult dose with ritonavir or cobicistat is 25 mg per 48 hours.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Erythromycin (Systemic)	May increase the serum concentration of Sildenafil. Management: For pulmonary arterial hypertension, US label recommends no dose adjustment and Canadian label recommends reducing to 20 mg twice/day. For erectile dysfunction, consider using a lower starting dose of 25 mg in patients who are also taking erythromycin.
Itraconazole	May increase the serum concentration of Sildenafil. Management: Concurrent itraconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent itraconazole.
Ketoconazole (Systemic	May increase the serum concentration of Sildenafil. Management: Concurrent ketoconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent ketoconazole.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Nefazodone	May increase the serum concentration of Sildenafil.
Posaconazole	May increase the serum concentration of Sildenafil. Management: Concurrent posaconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent posaconazole.
Protease Inhibitors	May increase the serum concentration of Sildenafil. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease inhibitors (adult doses). Contraindicated if sildenafil being used for pulmonary arterial hypertension.
Saquinavir	May increase the serum concentration of Sildenafil. Management: Used for PAH: no dose adjustment recommended per US label, Canadian label recommends decrease to 20 mg twice/day. Used for ED: consider a lower starting dose of 25 mg with concurrent saquinavir.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Telithromycin	May increase the serum concentration of Sildenafil.
Voriconazole	May increase the serum concentration of Sildenafil. Management: Concurrent voriconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent voriconazole.
Risk Factor X (Avoid combination)
Alprostadil	Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil.
Amyl Nitrite	Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Amyl Nitrite.
Clarithromycin	May increase the serum concentration of Sildenafil.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Dapoxetine	May enhance the orthostatic hypotensive effect of Phosphodiesterase 5 Inhibitors.
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Molsidomine	May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors.
Nitroprusside	Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Nitroprusside.
Phosphodiesterase 5 Inhibitors	May enhance the adverse/toxic effect of other Phosphodiesterase 5 Inhibitors.
Riociguat	Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Riociguat.
Vasodilators (Organic Nitrates)	Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Vasodilators (Organic Nitrates).

Monitoring parameters:

• Blood Pressure and Pulse: Keep an eye on blood pressure and pulse when using sildenafil alongside medications that lower blood pressure. This helps ensure that blood pressure doesn't drop too low.
• Pulmonary Edema: Watch out for signs of pulmonary edema, which is fluid buildup in the lungs. If pulmonary edema occurs, it needs prompt attention to prevent complications.

How to administer Sildenafil (Revatio, Viagra)?

Oral Administration:

• Revatio: Take doses at least 4 to 6 hours apart, regardless of food intake. Shake the oral suspension well for at least 10 seconds before giving the dose. Do not mix it with any other medication or flavoring agent.
• Viagra: Take with or without food, 30 minutes to 4 hours before sexual activity.

Intravenous (IV) Administration:

• Revatio: Administer as an IV bolus.

Mechanism of action of sildenafil (Revatio, Viagra):

Erectile Dysfunction:

• Sildenafil doesn't directly cause penile erections but enhances the response to sexual stimulation.
• During sexual arousal, nitric oxide (NO) is released in the corpus cavernosum (spongy tissue in the penis).
• NO activates guanylate cyclase enzyme, increasing cyclic guanosine monophosphate (cGMP) levels.
• This leads to smooth muscle relaxation and increased blood flow to the penis, causing an erection.
• Sildenafil inhibits phosphodiesterase type 5 (PDE-5), which degrades cGMP, thus prolonging its effects.
• When sexual stimulation occurs, sildenafil helps maintain higher cGMP levels, promoting smooth muscle relaxation and blood flow to the penis.
• It's important to note that sildenafil doesn't cause erections on its own; sexual stimulation is still necessary.

Pulmonary Arterial Hypertension (PAH):

• In PAH, sildenafil inhibits PDE-5 in the smooth muscle of pulmonary blood vessels.
• PDE-5 normally breaks down cGMP, but sildenafil's inhibition allows cGMP levels to rise.
• Increased cGMP concentration leads to relaxation of pulmonary blood vessels (vasodilation).
• This vasodilation reduces pressure in the pulmonary circulation, and to a lesser extent, in the systemic circulation.

Onset of Action:

• For erectile dysfunction, it takes approximately 60 minutes for sildenafil to take effect.

Peak Effect on Decreasing Blood Pressure:

• When taken orally, the peak effect occurs 1 to 2 hours after administration.

Duration of Action:

• In treating erectile dysfunction, sildenafil's effects typically last 2 to 4 hours, while its impact on lowering blood pressure lasts less than 8 hours.

Absorption:

• Sildenafil is rapidly absorbed, but absorption slows down when taken with a high-fat meal. Both tablet and suspension forms are bioequivalent.

Distribution:

• Sildenafil distributes into tissues. In neonates, the total volume of distribution is 22.4 L, while in adults, it's 105 L.

Protein Binding:

• In neonates, about 93.9% of sildenafil and its metabolite are bound to plasma proteins. In adults, this binding is around 96%.

Metabolism:

• Sildenafil is primarily metabolized in the liver by the enzyme CYP3A4, with a minor route involving CYP2C9.
• The major metabolite, desmethylsildenafil, has about 50% of the activity of sildenafil.

Bioavailability:

• The mean oral bioavailability of sildenafil is 41%, but it can vary between 25% and 63%.
• It may be higher in patients with pulmonary arterial hypertension (PAH) compared to healthy individuals.

Half-life:

• In adults, sildenafil's half-life is approximately 4 hours. For neonates, the half-life ranges from 47.7 to 55.9 hours.
• The active metabolite, desmethylsildenafil, has a half-life of around 4 hours in adults and 11.9 hours in neonates.

Time to Peak:

• When taken on an empty stomach, sildenafil reaches peak levels in the blood within 30 to 120 minutes, with a median of 60 minutes.
• This time is delayed by 60 minutes when taken with a high-fat meal.

Excretion:

• Sildenafil and its metabolites are primarily excreted in feces (about 80%) and urine (about 13%).

Clearance:

• Clearance of sildenafil is reduced in patients with hepatic cirrhosis or severe renal impairment. It may also be lower in patients with PAH compared to healthy volunteers.
• Clearance in newborns is significantly lower initially but approaches adult values by the first week of life. Clearance of the active metabolite is reduced in patients with severe renal impairment.

International Brand Names of Sildenafil:

• Revatio
• Viagra
• ACT Sildenafil
• AG-Sildenafil
• APO-Sildenafil
• APO-Sildenafil R
• AURO-Sildenafil
• GD Sildenafil
• JAMP-Sildenafil
• M-Sildenafil
• Mar-Sildenafil
• MINT-Sildenafil
• MYL-Sildenafil
• NRA-Sildenafil
• PMS-Sildenafil
• PMS-Sildenafil R
• Priva-Sildenafil
• PRZ-Sildenafil
• RAN-Sildenafil
• Revatio
• RIVA-Sildenafil
• SANDOZ Sildenafil
• TEVA-Sildenafil
• TEVA-Sildenafil R
• VANSildenafil
• Viagra
• Acmegra
• Adegra
• Adonix
• Aladin
• Amfidor
• Andagra
• Andros
• Androz
• Androz 100
• Aphrodil
• Avigra
• Avixar
• Azulsix
• Balcoga
• Baleoga
• Blugral
• Bultis Film
• Caprenafil
• Cilafil
• Conegra
• Cupid
• Daygra
• Direktan
• Dragul
• Ecriten
• Edegra
• Edyfil
• Ejertol
• Elonza
• Ereccil
• Erecstar
• Erectil
• Erectol
• Erilin
• Ernafil
• Eroton
• Eroxim
• Ezequel
• Facsid
• Fexion
• For MR.
• Fortera Orally Soluble Film
• Freeya
• Funcional
• Grandipam
• Granpidam
• Happigra Gran
• Hippigra
• Hydenex
• Idilico
• Immense
• Iqnyde
• Ivagra
• Kamagra
• Katora
• Lekap
• Maxigra
• Mysildecard
• Neo-Up
• Nipatra
• Olvion
• Orisild
• Osigra
• Pahtension
• Palpal Chew Tab
• Patrex
• Penegra
• Please
• Pramil
• Pulmolan
• Remenafil
• Revatio
• Rigix
• Ripol
• Sanbenafil
• Seregra
• Serivia Gran
• Sidegra
• Sidena
• Silagra
• Silatio
• Silchemo
• Sildava
• Sildefil
• Sildegra
• Sildenon
• Sildera
• Sildex
• Silvie
• Supra
• Tagazepin
• Tarim
• Tigerfil
• Tonafil
• Topgra
• V-Gra
• Varonil
• Vasigra
• Viagra
• Viajoy
• Viasin Powder
• Viner
• Vivic
• Vizarsin
• Willmon-100
• Wingora
• X-cite
• Xcite
• Xex
• Zilden
• Zwagra

Sildenafil Brand Names in Pakistan:

• Viagra