14 CLINICAL STUDIES
Actual doses administered were dependent
- In case of overdose, standard supportive measures should be employed.
- Symptoms of overdose are expected to be an extension of common side effects.
- Severe hypotension could occur and may require active cardiovascular support.
- Hemodialysis is not expected to accelerate clearance of sildenafil.
- The primary metabolite, N-desmethyl sildenafil, is also not significantly dialyzable.
- Management of priapism may require corporal irrigation or surgical intervention.
- There is no specific antidote for sildenafil overdose.
- If an overdose is suspected, contact a poison control center immediately.
- Provide the medical professional with the amount ingested and the time.
- Keep the patient hydrated and monitor vital signs closely.
- Ingestions in children require immediate emergency medical attention.
on body weight (see Table 5).
Frequently asked questions for Sildenafil
Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m2 basis. Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity. SUPER-1 (NCT00644605) - Sildenafil citrate monotherapy [20 mg, 40 mg, and 80 mg three times a day] A randomized, double-blind, placebo-controlled study of sildenafil citrate (SUPER-1) was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure≥25 mmHg at rest with a pulmonary capillary wedge pressure<15 mmHg). Patients were randomized to receive placebo (n=70) or sildenafil tablet 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. The study population consisted of 25% men and 75% women with a mean age of 49 years (range: 18 to 81 years) and baseline 6-minute walk distance between 100 and 450 meters (mean 343).
5.3 Effects on the Eye
Placebo-corrected mean increases in walk distance of 45 to 50 meters were observed with all doses of sildenafil citrate. These increases were significantly different from placebo, but the sildenafil citrate dose groups were not different from each other (see Figure 3), indicating no additional clinical benefit from doses higher than 20 mg three times a day. Change from Baseline in 6-Minute Walk Distance (meters) at Weeks 4, 8, and 12 in SUPER-1: Mean (95% Confidence Interval) Figure 4 displays subgroup efficacy analyses in SUPER-1 for the change from baseline in 6-Minute Walk Distance at Week 12 including baseline walk distance, disease etiology, functional class, gender, age, and hemodynamic parameters. Placebo-Corrected Change From Baseline in 6-Minute Walk Distance (meters) at Week 12 by Study Subpopulation in SUPER-1: Mean (95% Confidence Interval) Key: PAH = pulmonary arterial hypertension; CTD = connective tissue disease; PH = pulmonary hypertension; PAP = pulmonary arterial pressure; PVRI = pulmonary vascular resistance index; TID = three times daily. SUPER-2 (NCT00159887) Long-term Treatment of PAH In a long-term follow-up of patients who were treated with sildenafil (n=277), K-M estimates of survival at 1, 2, and 3 years were 94%, 88% , and 79%, respectively. Treatment Allocation by Dose and
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Body Weight in Pediatric Study
- Patient counseling points should emphasize the need for sexual stimulation.
- It is important to manage expectations; the drug may not work every time.
- Avoid high-fat meals before taking the dose for most consistent results.
- Do not take more than the prescribed dose in an attempt to improve effect.
- Report any chest pain, dizziness, or nausea during sexual activity to a doctor.
- Be aware of the signs and symptoms of priapism and seek immediate care.
- Note any visual or auditory changes and report them to a healthcare provider.
- Carry identification indicating the use of this medication.
- Inform all healthcare providers (including dentists) that you take sildenafil.
- Do not share this medication with anyone else, even if they have similar symptoms.
- Read the patient information leaflet provided with the prescription.
The proportion of patients receiving
In case of emergency/overdose
More than twice as many sildenafil citrate -treated patients 200mg sildenafil citrate (36%) as placebo-treated patients (14%) showed an improvement in at least one functional New York Heart Association (NYHA) class for PAH. Study A1481243 (NCT00323297) Sildenafil citrate Added to Bosentan Therapy - Lack of Effect on Exercise Capacity A randomized, double-blind, placebo-controlled study was conducted in 103 patients with PAH who were on bosentan therapy for a minimum of 3 months. STARTS-1 (NCT00159913) - Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension A total of 234 patients with PAH aged 1 to 17 years were treated in a randomized, double-blind, multi-center, placebo-controlled parallel group, dose-ranging study. Patients (38% male and 62% female) had body weight ≥8 kg and had idiopathic pulmonary arterial hypertension (33%), or PAH associated with congenital heart disease (systemic-to-pulmonary shunt 37%, surgical repair 30%). In this trial, 27% of patients were <7 years old. supportive medicinal products at baseline (anticoagulants,
- The future of sildenafil includes research into new therapeutic areas.
- Investigations are ongoing for its use in heart failure with preserved ejection fraction.
- Studies examine its potential benefits in Alzheimer's disease and vascular dementia.
- Its application in jet lag and sleep cycle disorders is being explored.
- Research continues for its use in various forms of female sexual dysfunction.
- Novel delivery systems, like microneedle patches, are in preclinical development.
- Combination therapies with other agents for enhanced effect are being tested.
- The search for more selective PDE5 inhibitors with fewer side effects continues.
- Genetic factors influencing drug response are an area of pharmacogenomic research.
- Sildenafil remains a valuable tool for basic research in vascular biology.
- Its story is a continuing one of scientific discovery and application.
digoxin, calcium channel blockers, diuretics
Pregnancy & Lactation
Patients were WHO Functional Class I (32%), II (51%), III (15%), or IV (0.4%). Patients were naïve for specific PAH therapy and the use of prostacyclin, prostacyclin analogues and endothelin receptor antagonists were not permitted in the study, and neither were arginine supplementation, nitrates, alpha-blockers and potent CYP450 3A4 inhibitors. The primary objective of the study was to assess the effect of Sildenafil citrate on percent change from baseline in PVO2, normalized to body weight, from baseline to week 16 as measured by the Cardiopulmonary Exercise Test (CPET) (patients who were developmentally able to perform the test, n = 115). Secondary endpoints included hemodynamic monitoring, symptom assessment, WHO Functional Class, change in background treatment, and quality of life measurements (n = 234). Patients were allocated to one of three sildenafil treatment groups (low, medium, or high) or placebo. and/or oxygen) was similar in the
- Regulatory status of sildenafil varies by country but generally requires a prescription.
- In the UK, it is a Prescription Only Medicine (POM) but can be prescribed by pharmacists.
- In some countries, it may be available in limited quantities without a prescription.
- The FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Revatio.
- The REMS is designed to inform healthcare providers about the serious risks.
- This includes the risk of use with nitrates and the potential for hearing loss.
- The medication is subject to controlled substance regulations in some regions.
- Traveling with prescription medication requires carrying it in original packaging.
- It is advisable to have a copy of the prescription or a doctor's note when traveling.
- Laws regarding the importation of prescription drugs are strict and vary.
- Always check the legal status of the medication in your destination country.
combined sildenafil treatment group (48%)
Which one should I use?
Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg doses of sildenafil, therefore the effects are not related to dose or plasma levels within this dosage range. After chronic dosing of 80 mg three times a day sildenafil to patients with systemic hypertension, the mean change from baseline in systolic and diastolic blood pressures was a decrease of 9.4 mmHg and 9.1 mmHg, respectively. An evaluation of visual function at doses up to 200 mg revealed no effects of sildenafil citrate on visual acuity, intraocular pressure, or pupillometry. Sildenafil citrate is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25 to 63%). When sildenafil tablet is taken with a high-fat meal, the rate of absorption is reduced, with a mean delay in T max of 60 minutes and a mean reduction in Cmax of 29%.
7.1 Nitrates
This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and an in vitro potency for PDE-5 approximately 50% of the parent drug. In healthy volunteers, plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil's pharmacologic effects. Both sildenafil and the active metabolite have terminal half-lives of about 4 hours. There was also a doubling of Cmin levels compared to healthy volunteers. Body weight was shown to be a good predictor of drug exposure in children. and the placebo treatment group (42%).
| Condition | Risk Factors | Recommendations |
|---|---|---|
| Use with Nitrates | Risk of severe hypotension | Avoid concurrent use |
| Severe Heart Disease | Increased cardiac stress | Consult cardiologist before use |
| Severe Liver or Kidney Impairment | Altered drug metabolism | Dose adjustment or avoid use |
| Hypotension | Blood pressure too low | Use caution, monitor blood pressure |
| Retinitis Pigmentosa | Risk of vision changes | Consult eye specialist |