[1][69][239] It is recommended that a lower initial sildenafil dose (25 mg) be considered in patients with ED receiving potent CYP3A4 inhibitors such as erythromycin. No pharmacokinetic interaction has been observed to date between azithromycin (500 mg daily for 3 days) and sildenafil. [1][138][239] Therefore, no dosage adjustments are required in patients receiving these drugs concomitantly. In a clinical trial combining a single dose of sildenafil (50 mg) and aspirin (150 mg), sildenafil did not potentiate the aspirin-induced increase in bleeding time. In an in vitro human platelet study, sildenafil potentiated the antiaggregatory effect of sodium nitroprusside.
Dosage And Administration
[1][69][239] It is recommended that a lower initial sildenafil dose (25 mg) be considered in patients with ED receiving potent CYP3A4 inhibitors such as erythromycin. No pharmacokinetic interaction has been observed to date between azithromycin (500 mg daily for 3 days) and sildenafil. [1][138][239] Therefore, no dosage adjustments are required in patients receiving these drugs concomitantly. In a clinical trial combining a single dose of sildenafil (50 mg) and aspirin (150 mg), sildenafil did not potentiate the aspirin-induced increase in bleeding time. In an in vitro human platelet study, sildenafil potentiated the antiaggregatory effect of sodium nitroprusside.
IV Administration
The possibility that concomitant administration of rifampin, a potent CYP3A4 inducer, could decrease plasma concentrations of sildenafil should be considered. Additive hypotensive effects can occur if riociguat is used concomitantly with PDE type 5 inhibitors. [1][247] In a study in patients with pulmonary arterial hypertension (PAH) who were receiving stable dosages of sildenafil (20 mg 3 times daily), administration of single doses of riociguat resulted in additive hemodynamic effects. [247] A high rate of drug discontinuance generally has been observed among patients receiving combination therapy with sildenafil and riociguat; at least one death, possibly related to the combined use of these drugs, has been reported. Because of the risk of hypotension, concomitant use of sildenafil and riociguat is contraindicated. The possibility that concomitant administration of rifampin, a potent CYP3A4 inducer, could decrease plasma concentrations of sildenafil should be considered. Additive hypotensive effects can occur if riociguat is used concomitantly with PDE type 5 inhibitors. [1][247] In a study in patients with pulmonary arterial hypertension (PAH) who were receiving stable dosages of sildenafil (20 mg 3 times daily), administration of single doses of riociguat resulted in additive hemodynamic effects.
- Sildenafil can sometimes cause flushing and nasal congestion.
- It is not a cure for erectile dysfunction, only a treatment option.
- Psychological factors can also affect erectile performance alongside medication.
- Sildenafil may sometimes interact with foods that contain high fat content.
- Regular exercise and stress management can complement treatment with sildenafil.
- The medication should be stored safely out of children's reach.
- Reporting side effects to a healthcare provider is important for safety.
- Sildenafil is typically started at a low dose, gradually increased if needed.
- It is important to follow the prescribed timing for medication intake.
- Discontinuing sildenafil should be discussed with a healthcare professional.
[247] A high rate of drug discontinuance generally has been observed among patients receiving combination therapy with sildenafil and riociguat; at least one death, possibly related to the combined use of these drugs, has been reported. Because of the risk of hypotension, concomitant use of sildenafil and riociguat is contraindicated.
| Year | Milestone | Description |
|---|---|---|
| 1989 | Discovery of Sildenafil | Originally researched for angina |
| 1996 | First clinical trials for ED | Revealed benefits for erectile function |
| 1998 | FDA approval for erectile dysfunction treatment | First oral pill approved |
| 2003 | Launch of generic sildenafil in various markets | Increased accessibility |
The safety and efficacy of sildenafil in combination with other treatments for ED have not been established, and therefore such combined therapy currently is not recommended by the manufacturer. [67] No pharmacokinetic interaction has been observed between warfarin, a CYP2C9 substrate, and sildenafil. Sildenafil is a selective inhibitor of phosphodiesterases (PDEs), with the greatest selectivity for PDE type 5, the principal isoenzyme of PDE involved in the metabolism of cyclic guanosine monophosphate (cGMP) to GMP in the corpora cavernosa of the penis. [1][2][4][5][7][8][10][24][27][33][41][42][54][56][57][67][87][88][91][131] Sildenafil has no direct relaxant effect on isolated human corpora cavernosa of the penis, but enhances the effect of nitric oxide by inhibiting PDE type 5-mediated hydrolysis of cGMP. [1][2][4][5][7][8][10][33][41][42][127][131] During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpora cavernosa. [1][2][4][56][67][91][131] By selectively inhibiting PDE type 5, sildenafil causes accumulation of cGMP in various tissues. [1][2][4][5][31][33][34][41][42][56][57][67][91][131] Because sildenafil potentiates the accumulation of cGMP rather than stimulating its production, the drug is effective only when cGMP production in the penis is increased by sexual arousal. [34][91][131] Sildenafil at recommended doses has no effect on erectile function in the absence of sexual stimulation. [1][4][33][34][91][127][130][131][132] Sildenafil also exhibits some activity against other PDE isoenzymes. [1][4][5][31][44][57][67][87][88] In vitro, sildenafil is about 10 times more active against PDE type 5 than against PDE type 6, greater than 70-80 times more active against PDE type 5 than against PDE type 1, greater than 1000 times more active against PDE type 5 than against PDE types 2 and 4, and 4000 times more active against PDE type 5 than against PDE type 3. [1][4][27][31][45][52][55][57][67][87][88] The duration of erectile responsiveness (i.e., the time period in which adequate sexual stimulation can produce an erection) with oral sildenafil has been reported to be approximately 2 hours, with some penile responsiveness persisting for up to 4 hours after oral administration. [1] In the largest clinical study published to date, the onset and duration of action of oral sildenafil were not reported.
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[33][34] In most other placebo-controlled studies in which improvement in erection was determined by penile plethysmography, the erectile effect was determined at a fixed time of 60 minutes after an oral dose of the drug. Sildenafil is rapidly absorbed following oral administration; the mean absolute bioavailability is 41% (range, 25-63%).
Before Using
[1][4][27][31][45][52][55][57][67][87][88] The duration of erectile responsiveness (i.e., the time period in which adequate sexual stimulation can produce an erection) with oral sildenafil has been reported to be approximately 2 hours, with some penile responsiveness persisting for up to 4 hours after oral administration. [1] In the largest clinical study published to date, the onset and duration of action of oral sildenafil were not reported. [33][34] In most other placebo-controlled studies in which improvement in erection was determined by penile plethysmography, the erectile effect was determined at a fixed time of 60 minutes after an oral dose of the drug. Sildenafil is rapidly absorbed following oral administration; the mean absolute bioavailability is 41% (range, 25-63%). [1][4][56][67][91][116][249] Although studies indicate that more than 90% of an oral sildenafil dose is absorbed from the GI tract, the drug undergoes extensive metabolism in the GI mucosa during absorption and on first pass through the liver, with only about 40% of a dose reaching systemic circulation unchanged.
Who Should NOT Take Sildenafil
[1][4][56][67][91][116][131][249] Pharmacokinetics of the drug (as determined by peak plasma concentrations or AUC) are dose proportional over the single-dose range of 1.25-200 mg.[1][4][56][91][116][131] Peak plasma concentrations of sildenafil and its active N-desmethyl metabolite are achieved within 30-120 (median: 60) minutes following oral administration in fasting adults. [1][4][91][127][130][249] Administration with a high-fat meal delays GI absorption, with a reduction in peak plasma concentrations of about 29% and a delay in time to peak plasma concentrations of about 60 minutes; the extent of absorption is not affected. Sildenafil appears to be widely distributed in the body. [1][4][67][116][131] Sildenafil and its major circulating N-desmethyl metabolite are each approximately 96% bound to plasma proteins; protein binding reportedly is independent of plasma concentration. [1][67][91][116][131] Sildenafil is distributed to a limited extent in semen following oral administration, with less than 0.001% of a single dose appearing in semen 90 minutes after dosing in healthy individuals. [1][4][56][67][91][116][249] Although studies indicate that more than 90% of an oral sildenafil dose is absorbed from the GI tract, the drug undergoes extensive metabolism in the GI mucosa during absorption and on first pass through the liver, with only about 40% of a dose reaching systemic circulation unchanged. [1][4][56][67][91][116][131][249] Pharmacokinetics of the drug (as determined by peak plasma concentrations or AUC) are dose proportional over the single-dose range of 1.25-200 mg.[1][4][56][91][116][131] Peak plasma concentrations of sildenafil and its active N-desmethyl metabolite are achieved within 30-120 (median: 60) minutes following oral administration in fasting adults. [1][4][91][127][130][249] Administration with a high-fat meal delays GI absorption, with a reduction in peak plasma concentrations of about 29% and a delay in time to peak plasma concentrations of about 60 minutes; the extent of absorption is not affected. Sildenafil appears to be widely distributed in the body. [1][4][67][116][131] Sildenafil and its major circulating N-desmethyl metabolite are each approximately 96% bound to plasma proteins; protein binding reportedly is independent of plasma concentration. [1][67][91][116][131] Sildenafil is distributed to a limited extent in semen following oral administration, with less than 0.001% of a single dose appearing in semen 90 minutes after dosing in healthy individuals. [1][67] Such concentrations are unlikely to sildenafil online ireland cause any effects in sexual partners exposed to the semen.
Accessing Viagra in Malaysia
[1]Instruct the patient to seek medical attention immediately if they take too much sildenafil. [1]Inform patients of the risk of symptomatic low blood pressure (e.g., dizziness, lightheadedness, fainting). [1] Monitor blood pressure when administering sildenafil in combination with blood pressure lowering drugs (e.g., α-adrenergic blocking agents). [1]Advise patients to take sildenafil with or without food 1 hour or, if needed, 30 minutes to 4 hours before sexual activity. [1] Inform patients that taking sildenafil with a high-fat meal may cause delayed onset. [67] Plasma sildenafil concentrations appear to decline in a biphasic manner following oral administration, with a terminal elimination half-life of about 4 hours (range: 3-5 hours). [1][4][67][91][116][127][130][131] Sildenafil is metabolized principally via hepatic cytochrome P-450 (CYP) microsomal isoenzymes 3A4 (major route) and 2C9 (minor route). [1][26][67][91][131] Plasma concentrations of the active N-desmethyl metabolite are approximately 40% of those observed with sildenafil, and the metabolite reportedly accounts for about 20% of sildenafil's pharmacologic activity.
Sildenafil Pricing in India
[1][67] Such concentrations are unlikely to sildenafil online ireland cause any effects in sexual partners exposed to the semen. [67] Plasma sildenafil concentrations appear to decline in a biphasic manner following oral administration, with a terminal elimination half-life of about 4 hours (range: 3-5 hours). [1][4][67][91][116][127][130][131] Sildenafil is metabolized principally via hepatic cytochrome P-450 (CYP) microsomal isoenzymes 3A4 (major route) and 2C9 (minor route). [1][26][67][91][131] Plasma concentrations of the active N-desmethyl metabolite are approximately 40% of those observed with sildenafil, and the metabolite reportedly accounts for about 20% of sildenafil's pharmacologic activity. [1][67][131] The N-demethylated metabolite, the major circulating metabolite, has a phosphodiesterase selectivity profile similar to that of sildenafil and an in vitro potency for PDE type 5 of approximately 50% of the parent drug.
Insurance Information
[1][116][131] Sildenafil is eliminated mainly in the feces as metabolites following oral administration. [1][67][91][116][131] In healthy adults and those with ED, approximately 80% of an oral dose is excreted as metabolites in feces and 13% is excreted in urine. Importance of instructing patients to read the manufacturer's patient information before starting sildenafil therapy and each time their prescription is refilled. [1]Instruct patients to avoid contraindicated medications such as regular and/or intermittent use of organic nitrates, organic nitrites (e.g., ''poppers''), and riociguat. [1]Inform patients that sildenafil is marketed for erectile dysfunction (Viagra) and pulmonary arterial hypertension (Revatio®). [1][67][131] The N-demethylated metabolite, the major circulating metabolite, has a phosphodiesterase selectivity profile similar to that of sildenafil and an in vitro potency for PDE type 5 of approximately 50% of the parent drug. [1][116][131] Sildenafil is eliminated mainly in the feces as metabolites following oral administration.
- Do not take sildenafil if you have a history of heart attack or stroke.
- Women and children should not use sildenafil products.
- The medication can cause temporary vision disturbances, including blue-tinted vision.
- Always consult a healthcare provider before starting sildenafil therapy.
- Use caution when driving or operating machinery after taking sildenafil.
- Sildenafil is contraindicated in people with hypersensitivity to the drug.
- Some users report improved erectile function within 15 minutes.
- It is essential to stay hydrated, but avoid consuming large amounts of alcohol.
- Men with certain health conditions should undergo a medical exam before use.
- Overuse or misuse of sildenafil can lead to serious health complications.
[1][67][91][116][131] In healthy adults and those with ED, approximately 80% of an oral dose is excreted as metabolites in feces and 13% is excreted in urine. Importance of instructing patients to read the manufacturer's patient information before starting sildenafil therapy and each time their prescription is refilled.
What is Sildenafil for Erectile Dysfunction?
[1]Advise patient to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. [1]Inform patients of other important precautionary information. Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. [1]Instruct patients to avoid contraindicated medications such as regular and/or intermittent use of organic nitrates, organic nitrites (e.g., ''poppers''), and riociguat. [1]Inform patients that sildenafil is marketed for erectile dysfunction (Viagra) and pulmonary arterial hypertension (Revatio®). [1] Advise patients taking Viagra® not to take Revatio® or other PDE type 5 inhibitors. [1]Advise patients of the potential for sildenafil to augment the blood pressure lowering effect of α-adrenergic blocking agents (e.g., doxazosin) and anti-hypertensive medications (e.g., amlodipine) and concomitant administration may lead to symptomatic hypotension in some patients. [1]Inform patients taking sildenafil for erectile dysfunction and with potential for cardiac risk of sexual activity (e.g., patients with preexisting cardiovascular risk factors) to refrain from further activity and seek medical attention immediately if they experience symptoms (e.g., chest pain, dizziness, nausea) upon initiation of sexual activity.
How to Take Sildenafil Correctly for Erectile Dysfunction
The safety and efficacy of sildenafil in combination with other treatments for ED have not been established, and therefore such combined therapy currently is not recommended by the manufacturer. [67] No pharmacokinetic interaction has been observed between warfarin, a CYP2C9 substrate, and sildenafil. Sildenafil is a selective inhibitor of phosphodiesterases (PDEs), with the greatest selectivity for PDE type 5, the principal isoenzyme of PDE involved in the metabolism of cyclic guanosine monophosphate (cGMP) to GMP in the corpora cavernosa of the penis. [1][2][4][5][7][8][10][24][27][33][41][42][54][56][57][67][87][88][91][131] Sildenafil has no direct relaxant effect on isolated human corpora cavernosa of the penis, but enhances the effect of nitric oxide by inhibiting PDE type 5-mediated hydrolysis of cGMP. [1][2][4][5][7][8][10][33][41][42][127][131] During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpora cavernosa.
Drugs Affecting Gastric Acidity
[1][2][4][56][67][91][131] By selectively inhibiting PDE type 5, sildenafil causes accumulation of cGMP in various tissues. [1][2][4][5][31][33][34][41][42][56][57][67][91][131] Because sildenafil potentiates the accumulation of cGMP rather than stimulating its production, the drug is effective only when cGMP production in the penis is increased by sexual arousal. [34][91][131] Sildenafil at recommended doses has no effect on erectile function in the absence of sexual stimulation. [1][4][33][34][91][127][130][131][132] Sildenafil also exhibits some activity against other PDE isoenzymes. [1][4][5][31][44][57][67][87][88] In vitro, sildenafil is about 10 times more active against PDE type 5 than against PDE type 6, greater than 70-80 times more active against PDE type 5 than against PDE type 1, greater than 1000 times more active against PDE type 5 than against PDE types 2 and 4, and 4000 times more active against PDE type 5 than against PDE type 3. [1]Advise patients to seek immediate medical attention for a sudden loss of vision in one or both eyes while taking sildenafil. [1] Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including possible permanent loss of vision.
| Side Effect | Severity | Common Occurrence | Advice |
|---|---|---|---|
| Headache | Mild | Common | Hydrate, OTC pain relief |
| Flushing | Mild | Common | Cool environment |
| Nasal Congestion | Mild | Fairly common | Decongestants |
| Dizziness | Mild | Uncommon | Sit/lie down momentarily |
[1]Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking sildenafil.
- Sildenafil is a popular choice for men seeking non-invasive ED therapy.
- It's important to have realistic expectations about sildenafil's effects.
- The medication does not increase libido but improves blood flow.
- Patients should limit alcohol consumption when using sildenafil.
- It is recommended to consult a doctor if ED persists despite medication.
- Sildenafil can be used as part of a comprehensive ED treatment plan.
- The medication should be taken approximately an hour before planned activity.
- Some patients experience no side effects at prescribed doses.
- Always confirm that sildenafil is stored properly to maintain efficacy.
- Report any unusual symptoms, such as chest pain or vision loss, immediately.
[1] These events may be accompanied by tinnitus and dizziness. [1]Advise patients to seek prompt medical attention for an erection that lasts more than 4 hours. [1] If it is not treated right away, priapism can permanently damage the penis. [1]Inform patients taking sildenafil for erectile dysfunction that the drug offers no protection against sexually transmitted diseases and patients should use necessary protective measures to guard against such diseases, including the human immunodeficiency virus (HIV).
| Condition | Ideal Range | Additional Notes |
|---|---|---|
| Temperature | 15°C to 30°C | Avoid extreme heat or cold |
| Humidity | Low humidity | Keep in dry place |
| Light | Keep away from direct sunlight | Protect from light |
| Packaging | Original packaging, airtight | Prevent moisture exposure |
[1]Instruct the patient to seek medical attention immediately if they take too much sildenafil. [1]Inform patients of the risk of symptomatic low blood pressure (e.g., dizziness, lightheadedness, fainting). [1] Monitor blood pressure when administering sildenafil in combination with blood pressure lowering drugs (e.g., α-adrenergic blocking agents). [1]Advise patients to take sildenafil with or without food 1 hour or, if needed, 30 minutes to 4 hours before sexual activity. [1] Inform patients that taking sildenafil with a high-fat meal may cause delayed onset.
When oral medications might not be safe
[1] Advise patients taking Viagra® not to take Revatio® or other PDE type 5 inhibitors. [1]Advise patients of the potential for sildenafil to augment the blood pressure lowering effect of α-adrenergic blocking agents (e.g., doxazosin) and anti-hypertensive medications (e.g., amlodipine) and concomitant administration may lead to symptomatic hypotension in some patients. [1]Inform patients taking sildenafil for erectile dysfunction and with potential for cardiac risk of sexual activity (e.g., patients with preexisting cardiovascular risk factors) to refrain from further activity and seek medical attention immediately if they experience symptoms (e.g., chest pain, dizziness, nausea) upon initiation of sexual activity. [1]Advise patients to seek immediate medical attention for a sudden loss of vision in one or both eyes while taking sildenafil. [1] Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including possible permanent loss of vision.
How is this drug best given?
[1]Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking sildenafil. [1] These events may be accompanied by tinnitus and dizziness. [1]Advise patients to seek prompt medical attention for an erection that lasts more than 4 hours. [1] If it is not treated right away, priapism can permanently damage the penis. [1]Inform patients taking sildenafil for erectile dysfunction that the drug offers no protection against sexually transmitted diseases and patients should use necessary protective measures to guard against such diseases, including the human immunodeficiency virus (HIV). [1]Advise patient to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. [1]Inform patients of other important precautionary information. Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
- Sildenafil has been shown to aid men with diabetes-related ED.
- The drug may also reduce blood pressure temporarily.
- Some men may not respond to sildenafil due to various health factors.
- It is recommended to take sildenafil on an empty stomach for faster effects.
- Overdose symptoms include dizziness, fainting, and pain in the chest.
- Sildenafil should not be used with other erectile dysfunction medications simultaneously.
- Patients should inform their doctor if they experience prolonged erections.
- Certain medical conditions require cautious use of sildenafil.
- The medication can sometimes cause changes in color perception.
- Always check the expiration date before using sildenafil pills.
