Viagra
sildenafil citrate · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE VIAGRA is indicated for the treatment of erectile dysfunction. VIAGRA is a phosphodiesterase-5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED) ( 1 )
Dosage and administration
• For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, VIAGRA may be taken anywhere from 30 minutes to 4 hours before sexual activity ( 2.1 )
• Based on effectiveness and toleration, may increase to a maximum of 100 mg or decrease to 25 mg ( 2.1 )
• Maximum recommended dosing frequency is once per day ( 2.1 ) 2.1 Dosage Information For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, VIAGRA may be taken anywhere from 30 minutes to 4 hours before sexual activity. The maximum recommended dosing frequency is once per day. Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. 2.2 Use with Food VIAGRA may be taken with or without food. 2.3 Dosage Adjustments in Specific Situations VIAGRA was shown to potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide donors such as organic nitrates or organic nitrites in any form is therefore contraindicated [ see Contraindications (4.1) , Drug Interactions (7.1) , and Clinical Pharmacology (12.2) ]. When VIAGRA is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating VIAGRA treatment and VIAGRA should be initiated at 25 mg [ see Warnings and Precautions (5.5) , Drug Interactions (7.2) , and Clinical Pharmacology (12.2) ]. 2.4 Dosage Adjustments Due to Drug Interactions Ritonavir The recommended dose for ritonavir-treated patients is 25 mg prior to sexual activity and the recommended maximum dose is 25 mg within a 48 hour period because concomitant administration increased the blood levels of sildenafil by 11-fold [ see Warnings and Precautions (5.6) , Drug Interactions (7.4) , and Clinical Pharmacology (12.3) ]. CYP3A4 Inhibitors Consider a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or saquinavir) or erythromycin. Clinical data have shown that co-administration with saquinavir or erythromycin increased plasma levels of sildenafil by about 3 fold [ see Drug Interactions (7.4) and Clinical Pharmacology (12.3) ]. 2.5 Dosage Adjustments in Special Populations Consider a starting dose of 25 mg in patients > 65 years, patients with hepatic impairment (e.g., cirrhosis), and patients with severe renal impairment (creatinine clearance <30 mL/minute) because administration of VIAGRA in these patients resulted in higher plasma levels of sildenafil [ see Use in Specific Populations (8.5 , 8.6, 8.7) and Clinical Pharmacology (12.3) ].
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS VIAGRA is supplied as blue, rounded diamond shaped film-coated tablets containing sildenafil citrate equivalent to 25 mg, 50 mg, or 100 mg of sildenafil. Tablets are debossed with “VIAGRA” on one side and “VGR 25”, “VGR 50” or “VGR 100” on the other to indicate the dosage strengths. Tablets: 25 mg, 50 mg, 100 mg ( 3 )
Contraindications
• Administration of VIAGRA to patients using nitric oxide donors, such as organic nitrates or organic nitrites in any form. VIAGRA was shown to potentiate the hypotensive effect of nitrates ( 4.1 , 7.1 , 12.2 )
• Known hypersensitivity to sildenafil or any component of tablet ( 4.2 )
• Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 4.3 ) 4.1 Nitrates Consistent with its known effects on the nitric oxide/cGMP pathway [ see Clinical Pharmacology (12.1 , 12.2) ], VIAGRA was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using nitric oxide donors such as organic nitrates or organic nitrites in any form either regularly and/or intermittently is therefore contraindicated. After patients have taken VIAGRA, it is unknown when nitrates, if necessary, can be safely administered. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [ see Dosage and Administration (2.3) , Drug Interactions (7.1) , and Clinical Pharmacology (12.2) ]. 4.2 Hypersensitivity Reactions VIAGRA is contraindicated in patients with a known hypersensitivity to sildenafil, as contained in VIAGRA and REVATIO, or any component of the tablet. Hypersensitivity reactions have been reported, including rash and urticaria [ see Adverse Reactions (6.1) ]. 4.3 Concomitant Guanylate Cyclase (GC) Stimulators Do not use VIAGRA in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including VIAGRA, may potentiate the hypotensive effects of GC stimulators.
Warnings and precautions
• Patients should not use VIAGRA if sexual activity is inadvisable due to cardiovascular status ( 5.1 )
• Patients should seek emergency treatment if an erection lasts >4 hours. Use VIAGRA with caution in patients predisposed to priapism ( 5.2 )
• Patients should stop VIAGRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of non arteritic anterior ischemic optic neuropathy (NAION). VIAGRA should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a “crowded” optic disc may also be at an increased risk of NAION. ( 5.3 )
• Patients should stop VIAGRA and seek prompt medical attention in the event of sudden decrease or loss of hearing ( 5.4 )
• Caution is advised when VIAGRA is co-administered with alpha-blockers or anti-hypertensives. Concomitant use may lead to hypotension ( 5.5 )
• Decreased blood pressure, syncope, and prolonged erection may occur at higher sildenafil exposures. In patients taking strong CYP inhibitors, such as ritonavir, sildenafil exposure is increased. Decrease in VIAGRA dosage is recommended ( 2.4 , 5.6 ) 5.1 Cardiovascular There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including VIAGRA, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. VIAGRA has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), [ see Clinical Pharmacology (12.2) ]. While this normally would be expected to be of little consequence in most patients, prior to prescribing VIAGRA, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity. Use with caution in patients with the following underlying conditions which can be particularly sensitive to the actions of vasodilators including VIAGRA – those with left ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure. There are no controlled clinical data on the safety or efficacy of VIAGRA in the following groups; if prescribed, this should be done with caution.
• Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months;
• Patients with resting hypotension (BP <90/50 mmHg) or hypertension (BP >170/110 mmHg);
• Patients with cardiac failure or coronary artery disease causing unstable angina. 5.2 Prolonged Erection and Priapism Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result. VIAGRA should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie’s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia). However, there are no controlled clinical data on the safety or efficacy of VIAGRA in patients with sickle cell or related anemias. 5.3 Effects on the Eye Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 in males aged ≥ 50. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare post-marketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [ see Adverse Reactions (6.2) ]. Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, PDE5 inhibitors, including VIAGRA, should be used with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with “crowded” optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including VIAGRA, for this uncommon condition.
Side effects
The following are discussed in more detail in other sections of the labeling:
• Cardiovascular [ see Warnings and Precautions (5.1) ]
• Prolonged Erection and Priapism [ see Warnings and Precautions (5.2) ]
• Effects on the Eye [ see Warnings and Precautions (5.3) ]
• Hearing Loss [ see Warnings and Precautions (5.4) ]
• Hypotension when Co-administered with Alpha-blockers or Anti-hypertensives [ see Warnings and Precautions (5.5) ]
• Adverse Reactions with the Concomitant Use of Ritonavir [ see Warnings and Precautions (5.6) ]
• Combination with other PDE5 Inhibitors or Other Erectile Dysfunction Therapies [ see Warnings and Precautions (5.7) ]
• Effects on Bleeding [ see Warnings and Precautions (5.8) ]
• Counseling Patients About Sexually Transmitted Diseases [ see Warnings and Precautions (5.9) ] The most common adverse reactions reported in clinical trials (≥ 2%) are headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash. Most common adverse reactions (≥ 2%) include headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness and rash ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. VIAGRA was administered to over 3700 patients (aged 19-87 years) during pre-marketing clinical trials worldwide. Over 550 patients were treated for longer than one year. In placebo-controlled clinical studies, the discontinuation rate due to adverse reactions for VIAGRA (2.5%) was not significantly different from placebo (2.3%). In fixed-dose studies, the incidence of some adverse reactions increased with dose. The type of adverse reactions in flexible-dose studies, which reflect the recommended dosage regimen, was similar to that for fixed-dose studies. At doses above the recommended dose range, adverse reactions were similar to those detailed in Table 1 below but generally were reported more frequently. Table 1. Adverse Reactions Reported by ≥2% of Patients Treated with VIAGRA and More Frequent than Placebo in Fixed-Dose Phase II/III Studies Adverse Reaction 25 mg (n=312) 50 mg (n=511) 100 mg (n=506) Placebo (n=607) Headache 16% 21% 28% 7% Flushing 10% 19% 18% 2% Dyspepsia 3% 9% 17% 2% Abnormal Vision Abnormal Vision: Mild to moderate in severity and transient, predominantly color tinge to vision, but also increased sensitivity to light, or blurred vision. 1% 2% 11% 1% Nasal Congestion 4% 4% 9% 2% Back Pain 3% 4% 4% 2% Myalgia 2% 2% 4% 1% Nausea 2% 3% 3% 1% Dizziness 3% 4% 3% 2% Rash 1% 2% 3% 1% When VIAGRA was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials of two to twenty-six weeks duration, patients took VIAGRA at least once weekly, and the following adverse reactions were reported: Table 2. Adverse Reactions Reported by ≥2% of Patients Treated with VIAGRA and More Frequent than Placebo in Flexible-Dose Phase II/III Studies Adverse Reaction VIAGRA PLACEBO N=734 N=725 Headache 16% 4% Flushing 10% 1% Dyspepsia 7% 2% Nasal Congestion 4% 2% Abnormal Vision Abnormal Vision: Mild and transient, predominantly color tinge to vision, but also increased sensitivity to light or blurred vision. In these studies, only one patient discontinued due to abnormal vision. 3% 0% Back Pain 2% 2% Dizziness 2% 1% Rash 2% 1% The following events occurred in <2% of patients in controlled clinical trials; a causal relationship to VIAGRA is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful: Body as a Whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury. Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy. Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis. Hemic and Lymphatic: anemia and leukopenia. Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia. Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis. Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia. Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased. Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis. Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes. Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia. Analysis of the safety database from controlled clinical trials showed no apparent difference in adverse reactions in patients taking VIAGRA with and without anti-hypertensive medication. This analysis was performed retrospectively, and was not powered to detect any pre-specified difference in adverse reactions.
Drug interactions
• VIAGRA can potentiate the hypotensive effects of nitrates, alpha-blockers, and anti-hypertensives ( 4.1 , 5.5 , 7.1 , 7.2 , 7.3 , 12.2 )
• With concomitant use of alpha-blockers, initiate VIAGRA at 25 mg dose ( 2.3 )
• CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase VIAGRA exposure ( 2.4 , 7.4 , 12.3 ) ▪ Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) ▪ Erythromycin or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, saquinavir): Consider a starting dose of 25 mg ( 2.4 , 7.4 ) 7.1 Nitrates Administration of VIAGRA with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Consistent with its known effects on the nitric oxide/cGMP pathway, VIAGRA was shown to potentiate the hypotensive effects of nitrates [ see Dosage and Administration (2.3) , Contraindications (4.1) , Clinical Pharmacology (12.2) ]. 7.2 Alpha-blockers Use caution when co-administering alpha-blockers with VIAGRA because of potential additive blood pressure-lowering effects. When VIAGRA is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating VIAGRA treatment and VIAGRA should be initiated at the lowest dose [ see Dosage and Administration (2.3) , Warnings and Precautions (5.5) , Clinical Pharmacology (12.2) ]. 7.3 Amlodipine When VIAGRA 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [ see Warnings and Precautions (5.5) , Clinical Pharmacology (12.2) ]. 7.4 Ritonavir and Other CYP3A4 Inhibitors Co-administration of ritonavir, a strong CYP3A4 inhibitor, greatly increased the systemic exposure of sildenafil (11-fold increase in AUC). It is therefore recommended not to exceed a maximum single dose of 25 mg of VIAGRA in a 48 hour period [ see Dosage and Administration (2.4) , Warnings and Precautions (5.6) , Clinical Pharmacology (12.3) ]. Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in 160% and 182% increases in sildenafil C max and AUC, respectively. Co-administration of saquinavir, a strong CYP3A4 inhibitor, resulted in 140% and 210% increases in sildenafil C max and AUC, respectively. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir. A starting dose of 25 mg of VIAGRA should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itraconazole) [ see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ]. 7.5 Alcohol In a drug-drug interaction study sildenafil 50 mg given with alcohol 0.5 g/kg in which mean maximum blood alcohol levels of 0.08% was achieved, sildenafil did not potentiate the hypotensive effect of alcohol in healthy volunteers [ see Clinical Pharmacology (12.2) ].
Use in specific populations
• Geriatric use: Consider a starting dose of 25 mg ( 2.5 , 8.5 )
• Severe renal impairment: Consider a starting dose of 25 mg ( 2.5 , 8.6 )
• Hepatic impairment: Consider a starting dose of 25 mg ( 2.5 , 8.7 ) 8.1 Pregnancy Risk Summary VIAGRA is not indicated for use in females. There are no data with the use of VIAGRA in pregnant women to inform any drug-associated risks for adverse developmental outcomes. Animal reproduction studies conducted with sildenafil did not show adverse developmental outcomes when administered during organogenesis in rats and rabbits at oral doses up to 16 and 32 times, respectively, the maximum recommended human dose (MRHD) of 100 mg/day on a mg/m 2 basis ( see Data ). Data Animal Data No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received oral doses up to 200 mg/kg/day during organogenesis. These doses represent, respectively, about 16 and 32 times the MRHD on a mg/m 2 basis in a 50 kg subject. In the rat pre- and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days, about 2 times the MRHD on a mg/m 2 basis in a 50 kg subject. 8.2 Lactation Risk Summary VIAGRA is not indicated for use in females. Limited data indicate that sildenafil and its active metabolite are present in human milk. There is no information on the effects on the breastfed child, or the effects on milk production. 8.4 Pediatric Use VIAGRA is not indicated for use in pediatric patients. Safety and effectiveness have not been established in pediatric patients. 8.5 Geriatric Use Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy young volunteers (18-45 years) [ see Clinical Pharmacology (12.3) ]. Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [ see Clinical Pharmacology (12.3) ]. Of the total number of subjects in clinical studies of VIAGRA, 18% were 65 years and older, while 2% were 75 years and older. No overall differences in safety or efficacy were observed between older (≥65 years of age) and younger (<65 years of age) subjects. However, since higher plasma levels may increase the incidence of adverse reactions, a starting dose of 25 mg should be considered in older subjects due to the higher systemic exposure [ see Dosage and Administration (2.5) ]. 8.6 Renal Impairment No dose adjustment is required for mild (CLcr=50-80 mL/min) and moderate (CLcr=30-49 mL/min) renal impairment. In volunteers with severe renal impairment (Clcr<30 mL/min), sildenafil clearance was reduced, resulting in higher plasma exposure of sildenafil (~2 fold), approximately doubling of C max and AUC. A starting dose of 25 mg should be considered in patients with severe renal impairment [ see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ]. 8.7 Hepatic Impairment In volunteers with hepatic impairment (Child-Pugh Class A and B), sildenafil clearance was reduced, resulting in higher plasma exposure of sildenafil (47% for C max and 85% for AUC). The pharmacokinetics of sildenafil in patients with severely impaired hepatic function (Child-Pugh Class C) have not been studied. A starting dose of 25 mg should be considered in patients with any degree of hepatic impairment [ see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ].
Pregnancy
8.1 Pregnancy Risk Summary VIAGRA is not indicated for use in females. There are no data with the use of VIAGRA in pregnant women to inform any drug-associated risks for adverse developmental outcomes. Animal reproduction studies conducted with sildenafil did not show adverse developmental outcomes when administered during organogenesis in rats and rabbits at oral doses up to 16 and 32 times, respectively, the maximum recommended human dose (MRHD) of 100 mg/day on a mg/m 2 basis ( see Data ). Data Animal Data No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received oral doses up to 200 mg/kg/day during organogenesis. These doses represent, respectively, about 16 and 32 times the MRHD on a mg/m 2 basis in a 50 kg subject. In the rat pre- and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days, about 2 times the MRHD on a mg/m 2 basis in a 50 kg subject.
Pediatric use
8.4 Pediatric Use VIAGRA is not indicated for use in pediatric patients. Safety and effectiveness have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy young volunteers (18-45 years) [ see Clinical Pharmacology (12.3) ]. Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [ see Clinical Pharmacology (12.3) ]. Of the total number of subjects in clinical studies of VIAGRA, 18% were 65 years and older, while 2% were 75 years and older. No overall differences in safety or efficacy were observed between older (≥65 years of age) and younger (<65 years of age) subjects. However, since higher plasma levels may increase the incidence of adverse reactions, a starting dose of 25 mg should be considered in older subjects due to the higher systemic exposure [ see Dosage and Administration (2.5) ].
Overdosage
In studies with healthy volunteers of single doses up to 800 mg, adverse reactions were similar to those seen at lower doses but incidence rates and severities were increased. In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine.
Description
(sildenafil citrate), an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1 H -pyrazolo[4,3- d ]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7. VIAGRA is formulated as blue, rounded diamond shaped film-coated tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: anhydrous dibasic calcium phosphate, croscarmellose sodium, FD & C Blue #2 aluminum lake, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, titanium dioxide, and triacetin. Sildenafil citrate structural formula
Mechanism of action
12.1 Mechanism of Action The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Binding Characteristics Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). Sildenafil is approximately 4,000-fold more selective for PDE5 compared to PDE3. PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision [ see Clinical Pharmacology (12.2) ]. In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle. The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro , an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo .
How supplied
(sildenafil citrate) is supplied as blue, rounded diamond shaped film-coated tablets containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil and debossed on the obverse and reverse sides as follows: 25 mg 50 mg 100 mg Obverse “VGR 25” “VGR 50” “VGR 100” Reverse “VIAGRA” “VIAGRA” “VIAGRA” Bottle of 30 NDC-58151-426-93 NDC-58151-427-93 NDC-58151-428-93 Bottle of 100 N/A NDC-58151-427-01 NDC-58151-428-01 Recommended Storage: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Nitrates Physicians should discuss with patients the contraindication of VIAGRA with regular and/or intermittent use of nitric oxide donors, such as organic nitrates or organic nitrites in any form [ see Contraindications (4.1) ]. Guanylate Cyclase (GC) Stimulators Physicians should discuss with patients the contraindication of VIAGRA with use of guanylate cyclase stimulators such as riociguat [ see Contraindications (4.3) ]. Concomitant Use with Drugs Which Lower Blood Pressure Physicians should advise patients of the potential for VIAGRA to augment the blood pressure lowering effect of alpha-blockers and anti-hypertensive medications. Concomitant administration of VIAGRA and an alpha-blocker may lead to symptomatic hypotension in some patients. Therefore, when VIAGRA is co-administered with alpha-blockers, patients should be stable on alpha-blocker therapy prior to initiating VIAGRA treatment and VIAGRA should be initiated at the lowest dose [ see Warnings and Precautions (5.5) ]. Cardiovascular Considerations Physicians should discuss with patients the potential cardiac risk of sexual activity in patients with preexisting cardiovascular risk factors. Patients who experience symptoms (e.g., angina pectoris, dizziness, nausea) upon initiation of sexual activity should be advised to refrain from further activity and should discuss the episode with their physician [ see Warnings and Precautions (5.1) ]. Sudden Loss of Vision Physicians should advise patients to stop use of all PDE5 inhibitors, including VIAGRA, and seek medical attention in the event of a sudden loss of vision in one or both eyes. 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, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. Physicians should discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye. Physicians should also discuss with patients the increased risk of NAION among the general population in patients with a “crowded” optic disc, although evidence is insufficient to support screening of prospective users of PDE5 inhibitor, including VIAGRA, for this uncommon condition [ see Warnings and Precautions (5.3) and Adverse Reactions (6.2) ]. Sudden Hearing Loss Physicians should advise patients to stop taking PDE5 inhibitors, including VIAGRA, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including VIAGRA. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [ see Warnings and Precautions (5.4) and Adverse Reactions (6.2) ]. Priapism Physicians should warn patients that prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result [ see Warnings and Precautions (5.2) ]. Avoid Use with other PDE5 Inhibitors Physicians should inform patients not to take VIAGRA with other PDE5 inhibitors including REVATIO or other pulmonary arterial hypertension (PAH) treatments containing sildenafil. Sildenafil is also marketed as REVATIO for the treatment of PAH. The safety and efficacy of VIAGRA with other PDE5 inhibitors, including REVATIO, have not been studied [ see Warnings and Precautions (5.7) ]. Sexually Transmitted Disease The use of VIAGRA offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered [ see Warnings and Precautions (5.9) ]. Distributed by: Viatris Specialty LLC Morgantown, WV 26505 U.S.A. © 2023 Viatris Inc. VIAGRA is a registered trademark of Viatris Specialty LLC, a Viatris Company. The brands listed are trademarks of their respective owners. UPJ:VGRA:R1
Label text from the FDA structured product label by Viatris Specialty LLC (revised Nov 17, 2023). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Sildenafil Citrate in 6 products
Viagra NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0069-4200 | Sildenafil Citrate 25 mg/1 Tablet, Film Coated | PFIZER LABORATORIES DIV PFIZER INC | NDA |
| 0069-4210 | Sildenafil Citrate 50 mg/1 Tablet, Film Coated | PFIZER LABORATORIES DIV PFIZER INC | NDA |
| 0069-4220 | Sildenafil Citrate 100 mg/1 Tablet, Film Coated | PFIZER LABORATORIES DIV PFIZER INC | NDA |
| 58151-426 | Sildenafil Citrate 25 mg/1 Tablet, Film Coated | Viatris Specialty LLC | NDA |
| 58151-427 | Sildenafil Citrate 50 mg/1 Tablet, Film Coated | Viatris Specialty LLC | NDA |
| 58151-428 | Sildenafil Citrate 100 mg/1 Tablet, Film Coated | Viatris Specialty LLC | NDA |
Frequently asked questions
What is Viagra used for?
1 INDICATIONS AND USAGE VIAGRA is indicated for the treatment of erectile dysfunction. VIAGRA is a phosphodiesterase-5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED) ( 1 )
What are the side effects of Viagra?
The following are discussed in more detail in other sections of the labeling: • Cardiovascular [ see Warnings and Precautions (5.1) ] • Prolonged Erection and Priapism [ see Warnings and Precautions (5.2) ] • Effects on the Eye [ see Warnings and Precautions (5.3) ] • Hearing Loss [ see Warnings and Precautions (5.4) ] • Hypotension when Co-administered with Alpha-blockers or Anti-hypertensives [… See the full label for the complete list.
Who makes Viagra?
Viagra is listed by 2 labelers in the FDA NDC directory, including PFIZER LABORATORIES DIV PFIZER INC, Viatris Specialty LLC.