Class: Phosphodiesterase Type 5 Inhibitors
VA Class: GU900
Chemical Name: 2-Hydroxy-1,2,3-propanetricarboxylate-1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d-pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methyl-piperazine
Molecular Formula: C22H30N6O4S•C6H8O7
CAS Number: 171599-83-0
Brands: Revatio, Viagra
Medically reviewed by Drugs.com. Last updated on April 1, 2019.
Introduction
Vasodilating agent; a selective phosphodiesterase (PDE) type 5 inhibitor.1 2 4 5 7 8 10 24 27 33 41 56 57 67 91 131 184 203
Uses for Sildenafil
Erectile Dysfunction (ED)
To facilitate attainment of a sexually functional erection in males with erectile dysfunction (ED, impotence).1 4 6 7 8 9 10 25 33 34 67 81 102 104 105 107 108 112 118 119 126 127 128 129 130 131 132 133 134 135 140 142 143 144 189
Most experts currently recommend that selective PDE type 5 inhibitors be offered as first-line therapy for ED unless contraindicated.189 Insufficient evidence to support the superiority of one selective PDE type 5 inhibitor over another.189
Sexual Dysfunction in Women
Has been used for the management of sexual dysfunction in women†; however, additional study needed to establish role, if any, of such therapy.28 67 79 97 150
Although sildenafil may improve physiologic response (e.g., increased blood flow to sexual organs),224 such changes have not been associated with overall improvement in sexual dysfunction in women.79 219 222 224
Also has been used in women with sexual dysfunction induced by SSRI antidepressants97 108 118 150 152 226 and in women with neurogenic sexual dysfunction (e.g., due to spinal cord injury or multiple sclerosis); however, data limited.227 228
Pulmonary Arterial Hypertension (PAH)
Symptomatic management of PAH (WHO group 1 pulmonary hypertension) to improve exercise capacity and delay clinical worsening.203 204 205 206 207 208 209 210 211 213 235
Parenteral preparation used for continued treatment in patients with PAH who are temporarily unable to take oral medication.203
Efficacy established principally in patients with NYHA/WHO functional class II–III PAH (idiopathic or associated with connective tissue diseases).203 208 235
Recommended as one of several treatment options for initial management of PAH in patients with NYHA/WHO functional class II, III, or IV symptoms who are not candidates for calcium-channel blocker therapy or in whom such therapy has failed.242 Individualize choice of therapy; consider factors such as disease severity, route of administration, potential adverse effects and costs of treatment, clinician experience, and patient preference.242 245
In patients with inadequate response to initial monotherapy, may consider combination therapy with a prostanoid or endothelin-receptor antagonist (added sequentially).242 By targeting different pathophysiologic pathways of the disease, such combination therapy may provide additive and/or synergistic benefits.243 244 246
Because increased mortality has been observed in children receiving higher (more effective) dosages of sildenafil, FDA currently does not recommend use of the drug in patients <18 years of age.203 233 (See Pediatric Use under Cautions.) Whether long-term sildenafil therapy has a beneficial effect on mortality in adults remains to be established.205 208 213 233
Sildenafil Dosage and Administration
General
ED
-
Carefully individualize dosage according to the patient’s tolerance and erectile response.1 33 67 77 81
-
Sexual stimulation is required for response to therapy.1
Administration
Administer orally or IV.203
Oral Administration
ED
Administer orally about 1 hour (range: 4 hours to 30 minutes) before sexual activity.1 60 91 127 132
Administration with a high-fat meal may delay the onset of action.1 114 115 117 131
PAH
Administer orally (as tablets or oral suspension) without regard to meals.203 208
If a dose is missed, take missed dose as soon as it is remembered, then resume regular dosing schedule; do not double dose to replace missed dose.229
Reconstitution of Oral Suspension
To reconstitute powder for oral suspension, tap bottle to release the powder.203 Add 60 mL of water to the bottle; recap and shake vigorously for at least 30 seconds.203 Add another 30 mL to bottle, recap and shake for at least 30 seconds; add a total of 90 mL of water to the bottle regardless of dose.203 The reconstituted suspension (112 mL) contains sildenafil 10 mg/mL.203
Use provided bottle adapter to fill 2-mL oral syringe (with 0.5- and 2-mL dose markings) with the reconstituted suspension.203
IV Administration
PAH
May administer by direct IV injection in patients who temporarily cannot take oral medication.203
Dosage
Available as sildenafil citrate; dosage expressed in terms of sildenafil.1 203
Adults
ED
Oral
Initially, 50 mg as a single dose no more than once daily.1 28 33 81 91 93 94 102 105 118 130 132 149 161 Depending on effectiveness and tolerance, increase dosage to a maximum of 100 mg once daily or decrease to 25 mg once daily.1 28 33 91 93 94 105 149 161
PAH
Oral
5 or 20 mg 3 times daily.203 No additional benefit with higher dosages.203
IV
2.5 or 10 mg 3 times daily by direct IV injection.203
Prescribing Limits
Adults
ED
Oral
Maximum 100 mg daily.1 60 91 114 131
PAH
Oral
Dosages up to 80 mg 3 times daily not more effective than recommended dosage of 20 mg 3 times daily.203 207 208 209
Special Populations
Hepatic Impairment
ED
Oral
Reduce initial dose to 25 mg.1 28 31 67
PAH
Oral
Mild to moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustments necessary.203
Severe hepatic impairment (Child-Pugh class C): Not studied.203
Renal Impairment
ED
Oral
Clcr <30 mL/minute: reduce initial dose to 25 mg.1 28 67 80 131
PAH
Oral
No dosage adjustment needed, even with severe impairment (Clcr <30 mL/minute).203
Geriatric Patients
ED
Reduce initial dose to 25 mg in men ≥65 years of age.1 31 67
PAH
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.203
Cautions for Sildenafil
Contraindications
-
Known hypersensitivity to sildenafil or any ingredient in the formulation.1 203
-
Concomitant use of organic nitrates or nitrites.1 29 57 67 148 154 203 Concomitant use of riociguat.247 (See Specific Drugs under Interactions.)
-
Do not use for treatment of ED in men for whom sexual activity is inadvisable because of underlying cardiovascular status.1 67 154 189
Warnings/Precautions
Warnings
Cardiovascular Effects
Serious, potentially fatal cardiovascular effects reported rarely.1 2 4 6 7 9 10 33 56 61 67 91 93 94 102 107 114 127 130 132 208
Use with caution in the treatment of ED in patients with a recent (within 6 months) MI, stroke, or life-threatening arrhythmia;1 31 101 127 144 154 155 159 in patients with resting hypotension (BP <90/50 mm Hg) or hypertension (BP >170/110 mm Hg);1 31 101 127 144 154 155 159 or in patients with cardiac failure or CAD causing unstable angina.1 31 101 127 144 154 155 159 Assess cardiovascular and cerebrovascular status (including use of organic nitrates and nitrites) prior to initiating therapy.1 28 30 31 53 64 65 67 91 93 121 154 189
Symptomatic hypotension may occur in patients receiving concomitant1 31 67 α-adrenergic blocking agents; hypotension may be severe or fatal in patients receiving an organic nitrate or nitrite concomitantly.1 28 29 31 53 57 61 67 69 148 (See Specific Drugs under Interactions.)
Consider whether patients with underlying cardiovascular disease (e.g., severe left ventricular outflow obstruction, autonomic dysfunction, resting hypotension [BP <90/50 mm Hg], fluid depletion) could be adversely affected by sildenafil’s vasodilatory activity,203 especially in combination with sexual activity.1 67 154
Use not recommended in patients with pulmonary veno-occlusive disease.203 Clinical data on use in this population are not available, and pulmonary vasodilators may worsen cardiovascular status of such patients.203 If pulmonary edema occurs during sildenafil therapy, consider the possibility of pulmonary veno-occlusive disease.203
Vaso-occlusive crisis requiring hospitalization reported in patients with pulmonary hypertension secondary to sickle cell disease who received sildenafil.1 203 Efficacy and safety of sildenafil in patients with sickle cell anemia not established.1 203
Ocular Effects
Nonarteritic anterior ischemic optic neuropathy (NAION) reported rarely in patients receiving PDE type 5 inhibitors for the treatment of ED.1 182 183 190 191 192 194 195 196 197 198 199 202 203 Potential increased risk of NAION in the second eye in patients who already have had NAION in one eye.1 182 183 196 202 203
Possible visual disturbances (e.g., blue/green vision, changes in light sensitivity), particularly at high doses.1 33 56 57 67 77 86 87 88 91 95 203 208 Possible persistent and/or serious retinal changes in older patients or with long-term use.32 87 88 95 106
Use with caution in patients with retinitis pigmentosa.1 31 32 60 155 203 Periodically monitor retinal function in patients with ocular manifestations suggestive of retinal effects and in those at risk.88 115
Otic Effects
Sudden decrease or loss of hearing reported with all PDE type 5 inhibitors, including sildenafil.1 203 214 216 217 218 Adverse otic effects (e.g., deafness, otic pain, tinnitus) observed in a few patients in controlled clinical trials.1 217 In at least 1 case, permanent, bilateral sensorineural deafness occurred.217 218
Although not clear whether such effects are directly related to PDE type 5 inhibitors or to other factors (e.g., patient’s underlying medical condition, concomitant use of other ototoxic drugs), a strong temporal relationship has been observed.1 203 214 216 217
Priapism
Possible prolonged (>4 hours) erections and priapism (painful erection >6 hours).1 31 139 146 147
May result in penile tissue damage and permanent loss of potency if priapism is not treated immediately.1 31 Use with caution in patients with conditions predisposing to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia).1 33 114 115 159 203
Interactions with Potent CYP3A4 Inhibitors
Concomitant use with potent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir) substantially increases serum sildenafil concentrations.1 203 Depending on the particular use of sildenafil (e.g., ED, PAH) and the specific CYP3A4 inhibitor, concomitant use may not be recommended or precautions (e.g., dosage adjustments) may be required.1 203 (See Specific Drugs under Interactions.)
General Precautions
Assessment of Patients with ED
Thorough medical history and physical examination recommended to diagnose ED, determine potential underlying causes, exclude potentially reversible or treatable causes, and identify appropriate treatment.1 12 28 30 31 36 57 58 65 66 70 78 82 83 94 114 115 119 144 145 160 161
Review of patient’s current drug regimens recommended to detect possible drug-induced ED.12 28 70 81 118 119 144 152 161
Hypotensive Effects
Possible hypotensive reaction in patients receiving concomitant antihypertensive therapy, in patients with CHF and a borderline low blood volume and low BP status, and in patients with left-ventricular outflow obstruction.28 31 67 (See Specific Drugs under Interactions.) Monitor BP during initiation of therapy in these patients.28 67 159
Bleeding Disorders
Use with caution in patients with bleeding disorders or active peptic ulcers.1 27 33 67 131
Incidence of epistaxis in sildenafil-treated patients is higher in those with PAH secondary to connective tissue disease (13%) than in those with primary pulmonary hypertension (3%).203
GU Precautions
Use with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie’s disease).1 33 114 115 159 203
Concomitant Therapies for ED
Safety and efficacy not established for use in combination with other treatments for ED; combined therapy is not recommended.1 155
Specific Populations
Pregnancy
Lactation
Not known whether sildenafil is distributed into milk.203 Use with caution in nursing women.203
Pediatric Use
Manufacturer states that safety and efficacy not established in children.1 203 229 Although sildenafil has been used effectively in a limited number of children† for symptomatic treatment of PAH,158 205 206 FDA currently recommends that the drug not be used for treatment of PAH in patients <18 years of age.233 248 However, FDA states that there may be situations in which the risk-benefit profile may be acceptable in individual children (e.g., when other treatment options are limited and sildenafil can be used with close monitoring).248
Increased risk of mortality observed in children receiving high dosages of sildenafil that also are the most effective dosages in this population.203 233 234 Deaths were related to disease progression in most cases.203 233
Geriatric Use
Pooled clinical trial data indicate that efficacy in men ≥65 years of age with ED is similar to that in younger men.131 157 Decreased clearance and increased plasma concentrations may increase incidence of adverse effects in geriatric patients with ED.1 60 139 (See Geriatric Patients under Dosage and Administration.)
Insufficient data from clinical trials to determine whether geriatric patients with PAH respond differently than younger adults, but other clinical experience has not identified overall differences in response relative to younger patients.203
Select dosage carefully due to greater frequency of decreased renal, hepatic, and/or cardiac function and of concomitant disease or drug therapy observed in geriatric patients.203
Hepatic Impairment
Decreased clearance.1 31 60 67 69 203 (See Hepatic Impairment under Dosage and Administration.)
Renal Impairment
Decreased clearance in patients with severe renal impairment.1 60 67 80 203 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
ED: Headache,1 4 6 7 9 10 31 33 56 91 93 104 105 107 130 132 208 flushing,1 4 7 9 33 56 67 93 105 107 130 132 dyspepsia/heartburn.1 7 10 31 33 67 91 93 102 107 132
PAH: Headache,203 208 211 dyspepsia,203 208 flushing,203 208 epistaxis,203 insomnia,203 208 exacerbated dyspnea,203 diarrhea,203 208 myalgia,203 erythema,203 208 pyrexia.203
Interactions for Sildenafil
Metabolized principally by CYP3A4 and to some extent by CYP2C9; weakly inhibits CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 in vitro.1 26 59 67 91 203
Drugs Affecting Hepatic Microsomal Enzymes
Inhibitors of CYP3A4 and CYP2C9: Potential pharmacokinetic interaction (increased plasma sildenafil concentrations).1 26 59 67 91 203 212
Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma sildenafil concentrations).1 26 59 67 91 203 212
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4:1 26 67 Potential pharmacokinetic interaction (increased substrate concentrations).203
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
α-Adrenergic blockers |
Possible potentiation of systemic vasodilation189 203 and symptomatic hypotension1 203 Doxazosin: No change or slight increase in plasma doxazosin concentrations depending on sildenafil dose203 |
In patients stable on an α-adrenergic blocker, initiate sildenafil at lowest recommended dosage for treatment of ED; in those currently receiving sildenafil, initiate α-adrenergic blocker at the lowest dosage 1 |
Alcohol |
Consider possibility that heavy alcohol ingestion could add to stress of sexual activity and risk of cardiac ischemia during coitus67 115 and that alcohol consumption also may contribute to ED12 28 58 70 82 114 115 119 |
|
Antacids |
Oral bioavailability of sildenafil unaffected by single doses of aluminum and magnesium hydroxide-containing antacid1 114 203 |
Dosage adjustments not necessary203 |
Antidepressants (e.g., SSRIs, tricyclic antidepressants) |
No effect on sildenafil pharmacokinetics1 No change in efficacy of sildenafil for treatment of ED1 |
|
Antifungals, azole (itraconazole, ketoconazole) |
Consider lower initial sildenafil dose (25 mg) for treatment of ED1 67 Concomitant use not recommended in patients receiving sildenafil for PAH203 |
|
Antihypertensive and hypotensive agents |
Potential additive hypotensive effects1 29 67 203 Amlodipine: Additional reductions in supine BP observed1 29 114 154 203 Thiazides and related diuretics, ACE inhibitors, calcium channel-blocking agents: No effect on sildenafil pharmacokinetics1 Loop and potassium-sparing diuretics, nonspecific β-adrenergic blocking agents: Increased AUC of active sildenafil metabolite (N-desmethyl sildenafil),1 but effect not expected to be clinically important1 |
Monitor BP203 |
Antipsychotics |
Efficacy of sildenafil for treatment of ED not affected by concomitant use1 60 118 |
|
Antiretroviral agents (HIV protease inhibitors) |
Decreased clearance, increased plasma concentrations of sildenafil, and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 26 59 67 84 114 136 137 139 166 167 168 169 170 171 172 173 174 175 200 201 203 230 240 |
Caution advised;84 166 167 168 169 170 171 172 173 174 175 closely monitor for adverse effects59 84 166 167 168 171 170 174 175 200 Amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, tipranavir in combination with low-dose ritonavir: Reduce initial sildenafil dose for treatment of ED to 25 mg and do not exceed a single 25-mg dose every 48 hours59 166 167 168 169 170 171 172 173 174 175 200 230 231 240 Ritonavir-boosted tipranavir in patients receiving sildenafil for PAH: Concomitant use contraindicated230 Ritonavir in patients receiving sildenafil for PAH: Concomitant use not recommended203 Saquinavir in patients receiving sildenafil for PAH: No dosage adjustments necessary203 |
Antiretroviral agents (nonnucleoside reverse transcriptase inhibitors [NNRTIs]) |
Delavirdine: Possible increased sildenafil concentrations and risk of sildenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)29 169 Etravirine: Decreased plasma sildenafil concentrations232 |
Delavirdine: Reduce initial sildenafil dose for treatment of ED to 25 mg and do not exceed a single 25-mg dose every 48 hours; monitor for adverse effects29 169 Etravirine: May administer concomitantly without dosage adjustment, but increase in sildenafil dosage may be needed based on clinical effect175 232 |
Aspirin |
No dosage adjustments necessary203 |
|
Atorvastatin |
AUC and peak plasma concentrations of either drug not substantially altered203 |
No dosage adjustments necessary203 |
β-Adrenergic blocking agents |
Possible decreased clearance of sildenafil203 |
|
Bosentan |
Decreased plasma sildenafil concentrations; increased plasma bosentan concentrations203 212 Clinical importance of pharmacokinetic interaction unclear241 |
No dosage adjustments required203 |
Cimetidine |
Consider lower initial sildenafil dose (25 mg) for treatment of ED67 No dosage adjustment necessary when used concomitantly with sildenafil for PAH203 |
|
Contraceptives, oral (ethinyl estradiol/levonorgestrel) |
AUC and peak plasma concentrations of sildenafil not substantially altered203 Pharmacokinetics of ethinyl estradiol and levonorgestrel not substantially altered203 |
No dosage adjustments necessary203 |
Epoprostenol |
Slight decrease in sildenafil exposure; not considered clinically important203 Effect on epoprostenol pharmacokinetics not known203 |
|
Heparin |
Increased bleeding time reported in animals1 |
Current evidence does not preclude concomitant heparin67 114 115 |
Inhaled nitrites (e.g., amyl or butyl nitrite) |
Possible sudden and marked BP reduction; potentially serious or even fatal26 67 92 Possible beneficial augmented cardiovascular effects in PAH204 210 211 |
Concomitant use contraindicated1 29 57 67 148 154 (see Cautions) |
Macrolides (azithromycin, erythromycin) |
Azithromycin: No pharmacokinetic interaction observed to date114 138 203 239 |
Azithromycin: No dosage adjustments necessary203 239 Erythromycin: Consider lower initial sildenafil dose (25 mg) for treatment of ED;1 239 no dosage adjustment necessary when used concomitantly with sildenafil for PAH203 |
Nitrates and nitrites (e.g., nitroglycerin, isosorbide dinitrate) |
Potentiation of vasodilatory effects (e.g., decrease in SBP of >25 mm Hg) of organic nitrates and nitrites; potentially life-threatening hypotension and/or hemodynamic compromise can result1 28 29 31 33 53 57 61 67 69 91 127 131 148 |
Concomitant use contraindicated1 29 57 67 148 154 203 (see Cautions) Some clinicians suggest that nitrates and nitrites may be given >24 hours after sildenafil, but the point at which these drugs can be given safely after sildenafil is unclear;1 29 31 67 154 avoid concomitant use unless benefits outweigh risks67 114 |
PDE inhibitors |
Nonspecific PDE inhibitors (e.g., dipyridamole, theophylline): Possible increased inotropic effects in cardiac muscle, vascular smooth muscle relaxation, and platelet-aggregation inhibition; risk of cardiotoxicity, hypotensive, or hemorrhagic event after concomitant use not known, but appears unlikely67 PDE type 5 inhibitors: Safety and efficacy of concomitant use not evaluated1 203 |
|
Rifamycins (rifabutin, rifampin) |
Possible decreased plasma sildenafil concentrations1 69 (theoretically less likely with rifabutin than rifampin103 ) |
|
Riociguat |
Possible additive hypotensive effects247 |
Concomitant use contraindicated247 |
Sodium nitroprusside |
Potentiation of vasodilatory effects (e.g., decrease in SBP of >25 mm Hg) of organic nitrates and nitrites; potentially life-threatening hypotension and/or hemodynamic compromise can result1 28 29 31 33 53 57 61 67 69 91 127 131 148 Also may potentiate the inhibitory effect of nitric oxide and sodium nitroprusside (a nitric oxide donor) on platelet aggregation1 57 67 203 |
Concomitant use contraindicated1 29 57 67 148 154 (see Cautions) Some clinicians suggest that nitrates and nitrites may be given >24 hours after sildenafil, but the point at which these drugs can be given safely after sildenafil is unclear;1 29 31 67 154 avoid concomitant use unless benefits outweigh risks67 114 |
Tolbutamide |
No dosage adjustments necessary203 |
|
Vitamin K antagonists (e.g., acenocoumarol, phenprocoumon, warfarin) |
No substantial effect on INR;1 67 114 203 however, increased bleeding (epistaxis) observed with concomitant use in patients with PAH203 Warfarin: No pharmacokinetic interaction observed1 67 114 173 |
No dosage adjustments necessary203 |
Sildenafil Pharmacokinetics
Absorption
Bioavailability
Rapidly and almost completely absorbed following oral administration;1 4 56 67 91 116 117 203 however, only about 40% of a dose reaches systemic circulation unchanged.1 4 56 67 91 114 116 131 203
Peak plasma concentration usually attained within 30–120 minutes.1 4 91 117 127 130 203
Duration
Erectile responsiveness: Approximately 2 hours.1 60 114
Onset
Erectile responsiveness: 14–20 minutes, self-recorded in the home setting.178
Food
Administration with a high-fat meal delays GI absorption;1 114 117 131 peak plasma concentrations reduced by about 30% and time to peak plasma concentration delayed by about 60 minutes.1 114 117 131
Distribution
Extent
Appears to be widely distributed in the body.1 4 67 116 131 203
Distributed to a limited extent in semen,1 67 but such concentrations are unlikely to cause any effects in sexual partners.67
Plasma Protein Binding
Approximately 96%.1 67 91 114 116 131 203
Elimination
Metabolism
Undergoes extensive metabolism in GI mucosa during absorption and on first pass through liver.91 114 116
Metabolized in the liver 116 117 131 principally by CYP3A4 and to a lesser extent by CYP2C9.1 91 131 203
Elimination Route
Excreted as metabolites in the feces (approximately 80%) and urine (approximately 13%).1 67 116 131 203
Half-life
Biphasic; terminal elimination half-life about 4 hours.1 4 67 91 116 117 127 130 131 203
Special Populations
Clearance in patients ≥65 years of age is reduced compared with that in younger adults.1 31 60 67 91 114 131 139 203
In patients with severe renal impairment (Clcr <30 mL/minute), clearance was reduced resulting in a two-fold increase in AUC and peak plasma concentrations compared with values in healthy adults.1 31 60 67 91 114 131 139 203 Pharmacokinetics not altered in mild to moderate renal impairment.1 31 131 203
Reduced clearance in patients with hepatic cirrhosis (Child-Pugh class A or B).1 31 60 114 131 203 Not studied in severe hepatic impairment (Child-Pugh class C).203
Stability
Storage
Oral
For Suspension
<30°C in original package to protect from moisture.203 After reconstitution, store at <30°C or in refrigerator (2–8°C); do not freeze.203 Discard any remaining oral suspension 60 days after reconstitution.203
Tablets
25°C (may be exposed to 15–30°C).1 203
Parenteral
Injection
25°C (may be exposed to 15–30°C).203
Actions
-
Selective inhibitor of PDEs, with a great selectivity for PDE type 5,1 2 4 5 7 8 10 24 27 33 41 56 57 67 87 88 91 131 the principal isoenzyme involved in the metabolism of cGMP to GMP in the corpora cavernosa of the penis and clitoris.1 2 4 5 33 41 42 54 57 67 91 98 131
-
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 98 127 131
-
Potentiates accumulation of cGMP only when cGMP production in the penis is increased by sexual arousal.34 91 131 No effect on erectile function in the absence of sexual stimulation.1 4 33 34 91 127 130 131 132
-
Modest peripheral vasodilation at usual dosages.1 29 31 33 53 56 67 91 203 In patients with pulmonary hypertension, induces vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilation in the systemic circulation.203 In such patients, pulmonary and systemic vascular resistance and resting arterial pressure are decreased, allowing an increase in cardiac output.203 Vasodilation and decreases in BP probably result from inhibition of PDE type 5 present in vascular smooth muscle.1 27 31 53
-
Because sildenafil can increase ocular cGMP concentrations via inhibition of PDE type 6,1 33 57 67 77 86 87 88 91 95 106 can produce transient visual abnormalities (mainly color-tinged vision, increased light perception, and blurred vision), particularly at doses >100 mg.1 33 57 67 77 86 87 88 91 95 106 107 131
Advice to Patients
-
Importance of informing clinicians if risk factors for cardiovascular disease are present prior to initiating any treatment for ED.1 28 30 31 53 64 65 67 91 93 121 154
-
Importance of informing clinician of any history of stroke, presence of low or high BP, blood diseases (e.g., sickle cell anemia, leukemia),195 or presence of retinitis pigmentosa or history of severe vision loss.1 193 195 196 198 199 203
-
Possibility of visual disturbances (e.g., blue/green vision, changes in light sensitivity), particularly at high doses,1 33 56 57 67 77 86 87 88 91 95 and of possible impairment of ability to perform tasks such as piloting a plane or operating a motor vehicle.77 115 156
-
Potential for sudden vision loss or decreased vision (i.e., nonarteritic ischemic optic neuropathy [NAION]).1 182 183 189 196 203 If NAION already has occurred in one eye, risk of NAION developing in the second eye may be increased.1 182 183 196 202 203
-
Importance of informing patients to refrain from further activity and contact their clinician if symptoms (e.g., angina pectoris, dizziness, nausea) occur upon initiation of sexual activity.1 67
-
Importance of informing patients of the potential for life-threatening hypotension and/or hemodynamic compromise with concurrent use of organic nitrates and nitrites in any form,1 28 29 31 33 53 57 61 67 69 91 127 131 148 including the recreational use of inhaled nitrites (“poppers”).26 67
-
Importance of informing patients that doses of sildenafil >25 mg should not be taken within 4 hours of administration of an α-adrenergic blocking agent.1
-
Importance of taking the drug exactly as prescribed and not exceeding recommended doses or frequency of use.106
-
Importance of seeking immediate medical attention if an erection persists longer than 4 hours or is extremely painful.1 31
-
Importance of immediately contacting a clinician if sudden loss of vision or decreased vision occurs in one or both eyes.1 182 183 193 194 195 198 199 202 203
-
Potential for transmission of sexually transmitted diseases and the possible need to use protective measures to guard against such transmission.1 26 68
-
Importance of contacting a clinician for assessment of therapeutic benefit, the need for possible dosage adjustment, and potential adverse effects.81 114 115
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 203
-
Importance of informing patients of other important precautionary information.1 203 (See Cautions.)
Preparations
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.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
For suspension |
10 mg (of sildenafil) per mL |
Revatio |
Pfizer |
Tablets, film-coated |
20 mg (of sildenafil) |
Revatio |
Pfizer |
|
25 mg (of sildenafil) |
Viagra |
Pfizer |
||
50 mg (of sildenafil) |
Viagra |
Pfizer |
||
100 mg (of sildenafil) |
Viagra |
Pfizer |
||
Parenteral |
Injection |
0.8 mg per mL (of sildenafil) |
Revatio |
Pfizer |
AHFS DI Essentials™. © Copyright 2021, Selected Revisions April 1, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. Pfizer Inc. Viagra (sildenafil citrate) prescribing information. New York, NY; 2011 Jan.
2. Anon. Sildenafil. Drugs Future. 1997; 22:138-43.
3. Bush PA, Aronson WJ, Rajfer J et al. Thel-arginine-nitric oxide-cyclic GMP pathway mediates inhibitory nonadrenergic-noncholinergic neurotransmission in the corpus cavernosum of human and rabbit. Circulation. 1993; 87(Suppl V):V-30-2.
4. Boolell M, Allen MJ, Ballard SA et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996; 8:47-52. http://www.ncbi.nlm.nih.gov/pubmed/8858389?dopt=AbstractPlus
5. Terrett NK, Bell AS, Brown D et al. Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg Med Chem Lett. 1996; 6:1819-24.
6. Boolell M, Yates PK, Wulff MB et al. Sildenafil (Viagra), a novel oral treatment with rapid onset of action for penile erectile dysfunction. Int J Impot Res. 1996; 8:147.
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