13 NONCLINICAL TOXICOLOGY
Alcohol Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%. 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/m 2basis. SUPER-1 (NCT00644605) -Sildenafil monotherapy [20 mg, 40 mg, and 80 mg three times a day] A randomized, double-blind, placebo-controlled study of sildenafil (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 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. 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.
| Condition | Details | Remarks |
|---|---|---|
| Temperature | Store between 15°C to 30°C | Protect from excessive heat |
| Light Exposure | Keep in a dark place or in opaque container | Protect from light |
| Humidity | Avoid high humidity environments | Prevent product degradation |
| Shelf Life | Typically 2 years from manufacturing date | Check expiry date before use |
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. Each bottle contains white to off-white crystalline powders containing 1.57 g of sildenafil citrate USP (equivalent to 1.12 g sildenafil).
- Manufacturing of sildenafil syrup requires specialized equipment.
- The syrup form must undergo stability testing before release.
- Some formulations may include sweeteners to improve taste.
- Off-label compounding can carry legal and safety risks.
- Clinicians should carefully consider risks before prescribing syrup.
Recommended storage for sildenafil for oral suspension: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature] in the original package in order to protect from moisture. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 This Patient Information has been approved by the U.S. Food and Drug Administration. Sildenafil for Oral Suspension (sil den' a fil) Read this Instructions for Use before you start taking sildenafil for oral suspension and each time you get a refill. Supplies you will need to take or give a dose of sildenafil oral suspension (See Figure A): 1 bottle of sildenafil for oral suspension with pre-inserted bottle adaptor 1 oral dosing syringe (provided in the carton) Shake the bottle of sildenafil for oral suspension for 10 seconds before each use.
Proper Use
This Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 SILDENAFIL- sildenafil powder, for suspension Lupin Pharmaceuticals, Inc. Pediatric use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil) tablets.
Pregnancy Categories
Do not mix with any other medication or additional flavoring agent White to light yellow colored granular powder containing 1.57 g of sildenafil citrate (equivalent to 1.12 g of sildenafil) in a bottle intended for reconstitution. Most, patients had underlying anatomic or vascular risk factors for developing NAION, including low cup to disc ratio ("crowded disc"). It is not possible to determine whether these reported events are related directly to the use of sildenafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors. Inform patients taking sildenafil for oral suspension not to take VIAGRA or other PDE5 inhibitors. In a 12-week, placebo-controlled clinical study and an open-label extension study (SUPER-1) in 277 sildenafil-treated adults with PAH (WHO Group I) [see Clinical Studies (14)], the adverse reactions that were reported by at least 10% of sildenafil-treated patients in any dosing group,and were more frequent in sildenafil-treated patients than in placebo-treated patients are shown in Table 1.
How is sildenafil supplied (dosage forms)?
In a placebo-controlled fixed dose titration study (PACES-1) of sildenafil (starting with recommended dose of 20 mg and increased to 40 mg and then 80 mg all three times a day) as an adjunct to intravenous epoprostenol in patients with PAH, no new safety issues were identified except for edema, which occurred in 25% of subjects in the combined sildenafil + epoprostenol group compared with 13% of subjects in the epoprostenol group [see Clinical Studies (14)]. In a rat pre-and postnatal development study, the no-observed-adverse-effect dose was 30 mg/kg/day (equivalent to 5-times the RHD on a mg/m2 basis). The safety and efficacy of Sildenafil have been established in pediatric patients younger than 1 year of age. Clinical studies of sildenafil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients. Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white or almost white, slightly hygroscopic, crystalline powder and a molecular weight of 666.7. (See Figure E) If your dose of sildenafil for oral suspension is 1 mL (10 mg), measure 0.5 mL two times for a total of 1 mL of sildenafil for oral suspension. (See Figure G) If you are giving sildenafil for oral suspension, make sure they are in an upright position before giving the medicine. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured for: Camber Pharmaceuticals, Inc.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Kamagra Oral Jelly | 100mg | 63 + 7 Sachets | 224.18€ 213.50€ | |
| Kamagra Polo | 100mg | 180 + 8 Pills | 446.52€ 425.26€ | |
| Viagra Generic | 50mg | 120 + 6 Pills | 129.64€ 123.47€ | |
| Viagra Generic | 25mg | 360 + 10 Pills | 213.68€ 203.50€ | |
| Viagra Generic | 25mg | 90 + 6 Pills | 105.03€ 100.03€ | |
| Viagra Generic | 150mg | 30 + 2 Pills | 72.32€ 68.88€ | |
| Viagra Generic | 50mg | 10 Pills | 26.87€ 25.59€ | |
| Viagra Generic | 50mg | 30 + 4 Pills | 54.26€ 51.68€ | |
| Kamagra Polo | 100mg | 60 + 4 Pills | 189.39€ 180.37€ | |
| Kamagra | 100mg | 84 + 6 Pills | 264.44€ 251.85€ | |
| Kamagra Soft Tabs | 100mg | 272 + 12 Pills | 593.42€ 565.16€ | |
| Viagra Generic | 100mg | 180 + 8 Pills | 199.37€ 189.88€ |
Piscataway, NJ 08854 SILDENAFIL- sildenafil powder, for suspension Lupin Pharmaceuticals, Inc. Pediatric use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil) tablets. Do not mix with any other medication or additional flavoring agent White to light yellow colored granular powder containing 1.57 g of sildenafil citrate (equivalent to 1.12 g of sildenafil) in a bottle intended for reconstitution. Most, patients had underlying anatomic or vascular risk factors for developing NAION, including low cup to disc ratio ("crowded disc"). It is not possible to determine whether these reported events are related directly to the use of sildenafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors. Inform patients taking sildenafil for oral suspension not to take VIAGRA or other PDE5 inhibitors. In a 12-week, placebo-controlled clinical study and an open-label extension study (SUPER-1) in 277 sildenafil-treated adults with PAH (WHO Group I) [see Clinical Studies (14)], the adverse reactions that were reported by at least 10% of sildenafil-treated patients in any dosing group,and were more frequent in sildenafil-treated patients than in placebo-treated patients are shown in Table 1. In a placebo-controlled fixed dose titration study (PACES-1) of sildenafil (starting with recommended dose of 20 mg and increased to 40 mg and then 80 mg all three times a day) as an adjunct to intravenous epoprostenol in patients with PAH, no new safety issues were identified except for edema, which occurred in 25% of subjects in the combined sildenafil + epoprostenol group compared with 13% of subjects in the epoprostenol group [see Clinical Studies (14)]. In a rat pre-and postnatal development study, the no-observed-adverse-effect dose was 30 mg/kg/day (equivalent to 5-times the RHD on a mg/m2 basis). The safety and efficacy of Sildenafil have been established in pediatric patients younger than 1 year of age. Clinical studies of sildenafil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger patients.
12.1 Mechanism of Action
Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white or almost white, slightly hygroscopic, crystalline powder and a molecular weight of 666.7. Sildenafil for Oral Suspension: Sildenafil for oral suspension is supplied as white to light yellow colored granular powder containing 1.57 g of sildenafil citrate (equivalent to1.12 g sildenafil) in an amber glass bottle intended for reconstitution. After chronic dosing of 80 mg three times a day to patients with PAH, no clinically relevant effects on electrocardiogram (ECG).
| Region | Estimated Market Size (2023) | Growth Rate | Key Players | Typical Uses Scope |
|---|---|---|---|---|
| North America | $150 million | 5% annually | Pfizer, Cipla, Teva | ED, pulmonary hypertension |
| Europe | $100 million | 4.5% annually | Bayer, Sun Pharma | Pulmonary hypertension, off-label uses |
| Asia-Pacific | $200 million | 7% annually | Cipla, Aurobindo, Zydus | Broader use, pediatric cases |
| Rest of World | $50 million | 3.5% annually | Various local manufacturers | Growing awareness and approval |
SUPER-1 (NCT00644605) - Sildenafil monotherapy [20 mg, 40 mg, and 80 mg three times a day] A randomized, double-blind, placebo-controlled study of Sildenafil (SUPER-1)was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure ≥ 25 mmHg at sildenafil citrate drug rest with a pulmonary capillary wedge pressure <15 mmHg). Patients were randomized to receive placebo (n=70) or Sildenafil 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. The improvement in walk distance was apparent after 4 Week of treatment and was maintained at week 8 and week 12.
16. How is Sildenafil Oral Suspension supplied
Alcohol Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%. 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/m 2basis. SUPER-1 (NCT00644605) -Sildenafil monotherapy [20 mg, 40 mg, and 80 mg three times a day] A randomized, double-blind, placebo-controlled study of sildenafil (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 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. 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.
Drug Interactions
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. Each bottle contains white to off-white crystalline powders containing 1.57 g of sildenafil citrate USP (equivalent to 1.12 g sildenafil). Recommended storage for sildenafil for oral suspension: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature] in the original package in order to protect from moisture. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 This Patient Information has been approved by the U.S.
Before taking sildenafil,
Food and Drug Administration. Sildenafil for Oral Suspension (sil den' a fil) Read this Instructions for Use before you start taking sildenafil for oral suspension and each time you get a refill. Supplies you will need to take or give a dose of sildenafil oral suspension (See Figure A): 1 bottle of sildenafil for oral suspension with pre-inserted bottle adaptor 1 oral dosing syringe (provided in the carton) Shake the bottle of sildenafil for oral suspension for 10 seconds before each use. (See Figure E) If your dose of sildenafil for oral suspension is 1 mL (10 mg), measure 0.5 mL two times for a total of 1 mL of sildenafil for oral suspension. (See Figure G) If you are giving sildenafil for oral suspension, make sure they are in an upright position before giving the medicine. PACES-1 (NCT00159861) - Sildenafil Co-administered with Epoprostenol A randomized, double-blind, placebo controlled study (PACES-1) was conducted in 267 patients with PAH who were taking stable doses of intravenous epoprostenol. Table 4 displays the number of patients with clinical worsening events in (PACES-1). Kaplan- Meier plot of time to clinical worsening is presented in Figure 5. Patients were randomized to placebo or sildenafil (20 mg three times a day) in combination with bosentan (62.5 to 125 mg twice a day).The primary efficacy endpoint was the change from baseline at Week 12 in 6-minute walk distance (6MWD). Each bottle contains white to light yellow colored granular powder containing 1.57 g of sildenafil citrate (equivalent to 1.12 g sildenafil).
- Contraindications include hypersensitivity to sildenafil.
- Patients with heart conditions should consult a cardiologist before use.
- Sildenafil’s safety profile is well-studied in adults.
- The syrup should not be used with children without medical advice.
- Proper disposal of unused syrup is important to avoid misuse.
Store below 30°C (86°F) or in refrigerator at 2° to 8°C (36° to 46°F). The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products. Sildenafil (Sil-DEN-a-fil) for Oral Suspension What is the most important information I should know about sildenafil for oral suspension? Nitroglycerin in any form including tablets, patches, sprays, and ointments Street drugs called "poppers" (amyl nitrate, butyl nitrate or nitrite) Riociguat ,a medicine that treats pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Ask your healthcare provider or pharmacist if you are not sure if you are taking a nitrate or a guanylate cyclase stimulator medicine. See "What are the possible side effects of Sildenafil for oral suspension?" Before taking sildenafil for oral suspension, tell your healthcare provider about all of your medical conditions, including if you: have bleeding problems or a stomach (peptic) ulcer.
Consumer Information Use and Disclaimer
Nitroglycerin in any form including tablets, patches, sprays, and ointments Street drugs called "poppers" (amyl nitrate, butyl nitrate or nitrite) Riociguat ,a medicine that treats pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Ask your healthcare provider or pharmacist if you are not sure if you are taking a nitrate or a guanylate cyclase stimulator medicine. See "What are the possible side effects of Sildenafil for oral suspension?" Before taking sildenafil for oral suspension, tell your healthcare provider about all of your medical conditions, including if you: have bleeding problems or a stomach (peptic) ulcer. have an eye problem called retinitis pigmentosa have ever had sudden loss of vision in one or both eyes, including an eye problem called non-arteritic anterior have ever had hearing problems such as ringing in the ears, dizziness, or loss of hearing have a deformed penis shape or Peyronie's disease have any blood cell problems such as sickle cell anemia are pregnant or plan to become pregnant. Sildenafil for oral suspension passes into your breast milk.
What should I tell my healthcare provider before taking sildenafil?
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Sildenafil for oral suspension and certain other medicines may affect each other and can cause side effects Especially tell your healthcare provider if you take: See "What is the most important information I should know aboutsildenafil for oral suspension?" Do nottake VIAGRA or other PDE-5 inhibitors during treatment with sildenafil for oral suspension. Keep a list of your or your child's medicines and show it to your healthcare provider and pharmacist when you get a new medicine. Your healthcare provider may change your dose of sildenafil for oral suspension as needed. Sildenafil may be prescribed to you as sildenafil oral suspension.
Warnings and Precautions
Take your prescribed dose of sildenafil for oral suspension 3 times a day. See the detailed Instructions for Use that comes with sildenafil for oral suspension for information on how to take or give sildenafil oral suspension.Sildenafil oral suspension will be mixed for you by your pharmacist. If you take too much sildenafil for oral suspension, call your healthcare provider or go to the nearest hospital emergencyroom right away. Sildenafil for oral suspension may cause serious side effects, including: See "What is the most important information I should know about sildenafil for oral suspension?" Decreased blood pressure.Sildenafil for oral suspension may cause low blood pressure that last for a short time. have an eye problem called retinitis pigmentosa have ever had sudden loss of vision in one or both eyes, including an eye problem called non-arteritic anterior have ever had hearing problems such as ringing in the ears, dizziness, or loss of hearing have a deformed penis shape or Peyronie's disease have any blood cell problems such as sickle cell anemia are pregnant or plan to become pregnant. Sildenafil for oral suspension passes into your breast milk. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Sildenafil for oral suspension and certain other medicines may affect each other and can cause side effects Especially tell your healthcare provider if you take: See "What is the most important information I should know aboutsildenafil for oral suspension?" Do nottake VIAGRA or other PDE-5 inhibitors during treatment with sildenafil for oral suspension. Keep a list of your or your child's medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
2.3 Reconstitution of the Powder for Oral Suspension
Sildenafil for Oral Suspension: Sildenafil for oral suspension is supplied as white to light yellow colored granular powder containing 1.57 g of sildenafil citrate (equivalent to1.12 g sildenafil) in an amber glass bottle intended for reconstitution. After chronic dosing of 80 mg three times a day to patients with PAH, no clinically relevant effects on electrocardiogram (ECG). SUPER-1 (NCT00644605) - Sildenafil monotherapy [20 mg, 40 mg, and 80 mg three times a day] A randomized, double-blind, placebo-controlled study of Sildenafil (SUPER-1)was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure ≥ 25 mmHg at sildenafil citrate drug rest with a pulmonary capillary wedge pressure <15 mmHg). Patients were randomized to receive placebo (n=70) or Sildenafil 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. The improvement in walk distance was apparent after 4 Week of treatment and was maintained at week 8 and week 12.
5.3 Epistaxis
PACES-1 (NCT00159861) - Sildenafil Co-administered with Epoprostenol A randomized, double-blind, placebo controlled study (PACES-1) was conducted in 267 patients with PAH who were taking stable doses of intravenous epoprostenol. Table 4 displays the number of patients with clinical worsening events in (PACES-1). Kaplan- Meier plot of time to clinical worsening is presented in Figure 5. Patients were randomized to placebo or sildenafil (20 mg three times a day) in combination with bosentan (62.5 to 125 mg twice a day).The primary efficacy endpoint was the change from baseline at Week 12 in 6-minute walk distance (6MWD). Each bottle contains white to light yellow colored granular powder containing 1.57 g of sildenafil citrate (equivalent to 1.12 g sildenafil).
Dosage Modifications
Store below 30°C (86°F) or in refrigerator at 2° to 8°C (36° to 46°F). The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products. Sildenafil (Sil-DEN-a-fil) for Oral Suspension What is the most important information I should know about sildenafil for oral suspension? Your healthcare provider may change your dose of sildenafil for oral suspension as needed. Sildenafil may be prescribed to you as sildenafil oral suspension. Take your prescribed dose of sildenafil for oral suspension 3 times a day. See the detailed Instructions for Use that comes with sildenafil for oral suspension for information on how to take or give sildenafil oral suspension.Sildenafil oral suspension will be mixed for you by your pharmacist. If you take too much sildenafil for oral suspension, call your healthcare provider or go to the nearest hospital emergencyroom right away. Sildenafil for oral suspension may cause serious side effects, including: See "What is the most important information I should know about sildenafil for oral suspension?" Decreased blood pressure.Sildenafil for oral suspension may cause low blood pressure that last for a short time.