Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in a 160% and 182% increases in sildenafil Cmax and AUC, respectively. Co-administration of saquinavir, a strong CYP3A4 inhibitor, resulted in 140% and 210% increases in sildenafil Cmax and AUC, respectively. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir.
Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking [see Warnings and Precautions (5.3) and Patient Counseling Information (17)]. Urogenital: prolonged erection, priapism [see Warnings and Precautions (5.2) and Patient Counseling Information (17)], and hematuria. 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)].
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)]. 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)]. 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)]. 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)].
| Drug Type | Interaction Effect | Recommended Action | Risks |
|---|---|---|---|
| Nitrates | Severe hypotension | Avoid concurrent use | Potential cardiovascular collapse |
| CYP3A4 inhibitors | Increased plasma levels | Dose adjustment | Risk of increased side effects |
| Alpha-blockers | Dizziness, hypotension | Monitor closely | Additive blood pressure lowering |
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)]. VIAGRA is not indicated for use in females.
There are no data with the use of VIAGRA in pregnant women to inform any sildenafil 130mg 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/m2 basis (see 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/m2 basis in a 50 kg subject.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Viagra Generic | 200mg | 90 + 6 Pills | 170.79€ 162.66€ | |
| Viagra Generic | 150mg | 180 + 10 Pills | 236.46€ 225.20€ | |
| Viagra Generic | 50mg | 30 + 4 Pills | 54.26€ 51.68€ | |
| Kamagra Oral Jelly | 100mg | 110 + 9 Sachets | 334.87€ 318.92€ | |
| Viagra Generic | 100mg | 120 + 6 Pills | 149.50€ 142.38€ | |
| Kamagra Oral Jelly | 100mg | 90 + 8 Sachets | 303.56€ 289.10€ | |
| Kamagra Soft Tabs | 100mg | 84 + 4 Pills | 233.05€ 221.95€ | |
| Kamagra Soft Tabs | 100mg | 120 + 6 Pills | 311.78€ 296.93€ | |
| Kamagra Soft Tabs | 100mg | 32 Pills | 120.11€ 114.39€ | |
| Viagra Generic | 150mg | 270 + 10 Pills | 326.61€ 311.06€ | |
| Viagra Generic | 150mg | 20 Pills | 55.02€ 52.40€ | |
| Kamagra Polo | 100mg | 180 + 8 Pills | 446.52€ 425.26€ | |
| Viagra Generic | 25mg | 10 Pills | 25.19€ 23.99€ |
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/m2 basis in a 50 kg subject.
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. 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: 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. Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia. VIAGRA is not indicated for use in pediatric patients.
Safety and effectiveness have not been established in pediatric patients.
| Country/Region | Approval Status | Regulatory Body | Prescription Requirement | Additional Regulations |
|---|---|---|---|---|
| USA | Approved | FDA | Prescription Required | Controlled substance |
| EU | Approved | EMA | Prescription Required | Marketed under strict regulations |
| Canada | Approved | Health Canada | Prescription Required | Pharmacovigilance measures |
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)].
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. 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. The following adverse reactions have been identified during post approval use of VIAGRA.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion either due to their seriousness, reporting sildenafil cenforce frequency, lack of clear alternative causation, or a combination of these factors. Serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of VIAGRA. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of VIAGRA without sexual activity. 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.
Others were reported to have occurred hours to days after the use of VIAGRA and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors [see Warnings and Precautions (5.1) and Patient Counseling Information (17)]. Hemic and Lymphatic: vaso-occlusive crisis: In a small, prematurely terminated study of REVATIO (sildenafil) in patients with pulmonary arterial hypertension (PAH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported in patients who received sildenafil than in those randomized to placebo. The clinical relevance of this finding to men treated with VIAGRA for ED is not known. Nervous: seizure, seizure recurrence, anxiety, and transient global amnesia.
Hearing: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including VIAGRA. In some of the cases, sildenafil citrate drug medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of VIAGRA, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Warnings and Precautions (5.4) and Patient Counseling Information (17)]. Ocular: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal edema, retinal vascular disease or bleeding, and vitreous traction/detachment.