Label: VARDENAFIL HYDROCHLORIDE tablet
]Ritonavir (600 mg b.i.d.) co-administered with vardenafil hydrochloride tablets 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13 fold increase in vardenafil C max. The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a HIV protease inhibitor and a highly strong CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half-life of vardenafil to 26 hours. Consequently, it is recommended not to exceed a single 2.5 mg vardenafil hydrochloride tablets dose in a 72-hour period when used in combination with ritonavir.
Brand names
]Ritonavir (600 mg b.i.d.) co-administered with vardenafil hydrochloride tablets 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13 fold increase in vardenafil C max. The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a HIV protease inhibitor and a highly strong CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half-life of vardenafil to 26 hours. Consequently, it is recommended not to exceed a single 2.5 mg vardenafil hydrochloride tablets dose in a 72-hour period when used in combination with ritonavir. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).] .Cobicistat with vardenafil hydrochloride tablets can result in increased plasma concentrations, therefore it is recommended that a single 2.5 mg dose of vardenafil hydrochloride tablets should not be exceeded in a 72-hour period.
InChI key
[See Dosage and Administration (2.4) and Warnings and Precautions (5).] .Moderate CYP3A4 inhibitorsErythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in C max when co administered with vardenafil hydrochloride tablets 5 mg in healthy volunteers. It is recommended not to exceed a single 5 mg dose of vardenafil hydrochloride tablets in a 24-hour period when used in combination with erythromycin. ]Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure.Other Drug InteractionsNo pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters.Cimetidine (400 mg b.i.d.) had no effect on vardenafil bioavailability (AUC) and maximum concentration (C max) of vardenafil when co-administered with 20 mg vardenafil hydrochloride tablets in healthy volunteers.7.3 Effects of Vardenafil on Other DrugsIn vitro studiesVardenafil and its metabolites had no effect on CYP1A2, 2A6, and 2E1 (Ki >100 micromolar). Weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4) were found, but Ki values were in excess of plasma concentrations achieved following dosing. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).] .Cobicistat with vardenafil hydrochloride tablets can result in increased plasma concentrations, therefore it is recommended that a single 2.5 mg dose of vardenafil hydrochloride tablets should not be exceeded in a 72-hour period. [See Dosage and Administration (2.4) and Warnings and Precautions (5).] .Moderate CYP3A4 inhibitorsErythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in C max when co administered with vardenafil hydrochloride tablets 5 mg in healthy volunteers. It is recommended not to exceed a single 5 mg dose of vardenafil hydrochloride tablets in a 24-hour period when used in combination with erythromycin. ]Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure.Other Drug InteractionsNo pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters.Cimetidine (400 mg b.i.d.) had no effect on vardenafil bioavailability (AUC) and maximum concentration (C max) of vardenafil when co-administered with 20 mg vardenafil hydrochloride tablets in healthy volunteers.7.3 Effects of Vardenafil on Other DrugsIn vitro studiesVardenafil and its metabolites had no effect on CYP1A2, 2A6, and 2E1 (Ki >100 micromolar). Weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4) were found, but Ki values were in excess of plasma concentrations achieved following dosing.
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The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 C max values after an 80 mg vardenafil dose.In vitro data suggest that vardenafil has the potential to inhibit P-glycoprotein (P-gp) at therapeutic doses.
5.7 Congenital or Acquired QT Prolongation
Adverse Reactions
While concomitant use of vardenafil hydrochloride tablets did not significantly increase plasma concentrations of digoxin, a P-gp substrate, the effect on plasma concentrations of P-gp substrates that are more sensitive than digoxin (e.g. dabigatran) is not known.In vivo studiesNifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil hydrochloride tablets when taken in combination. In these patients whose hypertension was controlled with nifedipine, vardenafil hydrochloride tablets 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo.Ritonavir and Indinavir: Upon concomitant administration of 5 mg of vardenafil hydrochloride tablets with 600 mg BID ritonavir, the C max and AUC of ritonavir were reduced by approximately 20%. Upon administration of 10 mg of vardenafil hydrochloride tablets with 800 mg TID indinavir, the C max and AUC of indinavir were reduced by 40% and 30%, respectively. Nitrates: Concomitant use of vardenafil hydrochloride tablets and nitrates and nitric oxide donors is contraindicated. Potentiation of the vidalista 20mg uk hypotensive effects of nitrates for patients with ischemic heart disease has not been evaluated, and concomitant use of vardenafil hydrochloride tablets and nitrates is contraindicated [see Contraindications (4.1) and Clinical Pharmacology (12.2).
| Parameter | Value | Notes |
|---|---|---|
| Absorption Time | 30-60 minutes | After oral intake |
| Peak Plasma | 60 minutes | Approximate peak |
| Half-life | 4-5 hours | Duration of effect |
| Bioavailability | ~15% | Oral bioavailability |
[See Dosage and Administration (2.4), Warnings and Precautions (5.6), and Clinical Pharmacology (12.2).] Antihypertensives: Vardenafil hydrochloride tablets may add to the blood pressure lowering effects of antihypertensive agents. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1.
Drug Label Information
Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in C max when co administered with vardenafil hydrochloride tablets 5 mg in healthy volunteers. [See Dosage and Administration (2.4) and Warnings and Precautions (5).] Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure. No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters. The most potent inhibitory activity fildena 200 mg was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 C max values after an 80 mg vardenafil dose.
Pharmacological Class
In vitro data suggest that vardenafil has the potential to inhibit P-glycoprotein (P-gp) at therapeutic doses. Nifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. In these patients whose hypertension was controlled with nifedipine, vardenafil hydrochloride tablets 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo. 8 USE IN SPECIFIC POPULATIONS 8.1 PregnancyRisk SummaryVardenafil hydrochloride tablets are not indicated for use in females.There are no data with the use of vardenafil hydrochloride tablets in pregnant women to inform any drug-associated risks. In animal reproduction studies conducted in pregnant rats and rabbits, no adverse developmental outcomes were observed with oral administration of vardenafil during organogenesis at exposures for unbound vardenafil and its major metabolite at approximately 100 and 29 times, respectively, the maximum recommended human dose (MRHD) of 20 mg based on AUC (see Data).DataAnimal DataNo evidence of specific potential for teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits that received vardenafil at up to 18 mg/kg/day during organogenesis. Alcohol: Vardenafil hydrochloride tablets (20 mg) did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers when administered with alcohol (0.5 g/kg body weight, approximately 40 mL of absolute alcohol in a 70 kg person).
What is the Competitive Landscape for Vardenafil Hydrochloride?
Alcohol: Vardenafil hydrochloride tablets (20 mg) did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers when administered with alcohol (0.5 g/kg body weight, approximately 40 mL of absolute alcohol in a 70 kg person). Alcohol and vardenafil plasma levels were not altered when dosed simultaneously. Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)] . Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil AUC and a 4-fold increase in maximum concentration (C max) when co-administered with vardenafil hydrochloride tablets (5 mg) in healthy volunteers.
Other Interactions
[See Dosage and Administration (2.4) and Warnings and Precautions (5).] Indinavir (800 mg t.i.d.) co-administered with vardenafil hydrochloride tablets 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil C max and a 2-fold increase in vardenafil half-life. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).] Ritonavir (600 mg b.i.d.) co-administered with vardenafil hydrochloride tablets 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13 fold increase in vardenafil C max. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).]. Cobicistat with vardenafil hydrochloride tablets can result in increased plasma concentrations, therefore it is recommended that a single 2.5 mg dose of vardenafil hydrochloride tablets should not be exceeded in a 72-hour period. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]. Alcohol and vardenafil plasma levels were not altered when dosed simultaneously. Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)] .
5.13 Risks in Patients with Phenylketonuria
Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil AUC and a 4-fold increase in maximum concentration (C max) when co-administered with vardenafil hydrochloride tablets (5 mg) in healthy volunteers. [See Dosage and Administration (2.4) and Warnings and Precautions (5).] Indinavir (800 mg t.i.d.) co-administered with vardenafil hydrochloride tablets 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil C max and a 2-fold increase in vardenafil half-life. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).] Ritonavir (600 mg b.i.d.) co-administered with vardenafil hydrochloride tablets 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13 fold increase in vardenafil C max. [See Dosage and Administration (2.4) and Warnings and Precautions (5.2).]. Cobicistat with vardenafil hydrochloride tablets can result in increased plasma concentrations, therefore it is recommended that a single 2.5 mg dose of vardenafil hydrochloride tablets should not be exceeded in a 72-hour period. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]. Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in C max when co administered with vardenafil hydrochloride tablets 5 mg in healthy volunteers. [See Dosage and Administration (2.4) and Warnings and Precautions (5).] Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure. No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine.
Other Comments
The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 C max values after an 80 mg vardenafil dose.In vitro data suggest that vardenafil has the potential to inhibit P-glycoprotein (P-gp) at therapeutic doses. While concomitant use of vardenafil hydrochloride tablets did not significantly increase plasma concentrations of digoxin, a P-gp substrate, the effect on plasma concentrations of P-gp substrates that are more sensitive than digoxin (e.g. dabigatran) is not known.In vivo studiesNifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil hydrochloride tablets when taken in combination. In these patients whose hypertension was controlled with nifedipine, vardenafil hydrochloride tablets 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo.Ritonavir and Indinavir: Upon concomitant administration of 5 mg of vardenafil hydrochloride tablets with 600 mg BID ritonavir, the C max and AUC of ritonavir were reduced by approximately 20%.
How is vardenafil supplied (dosage forms)?
Upon administration of 10 mg of vardenafil hydrochloride tablets with 800 mg TID indinavir, the C max and AUC of indinavir were reduced by 40% and 30%, respectively. Nitrates: Concomitant use of vardenafil hydrochloride tablets and nitrates and nitric oxide donors is contraindicated. Potentiation of the vidalista 20mg uk hypotensive effects of nitrates for patients with ischemic heart disease has not been evaluated, and concomitant use of vardenafil hydrochloride tablets and nitrates is contraindicated [see Contraindications (4.1) and Clinical Pharmacology (12.2). [See Dosage and Administration (2.4), Warnings and Precautions (5.6), and Clinical Pharmacology (12.2).] Antihypertensives: Vardenafil hydrochloride tablets may add to the blood pressure lowering effects of antihypertensive agents. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters.
| Condition | Risk | Advice |
|---|---|---|
| Nitrate use | Severe hypotension | Avoid use in patients taking nitrates |
| Severe hepatic impairment | Increased drug levels | Use with caution or avoid |
| Hypotension | Worsening of blood pressure | Monitor blood pressure regularly |
| Retinitis pigmentosa | Possible vision risks | Consult ophthalmologist |
The most potent inhibitory activity fildena 200 mg was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 C max values after an 80 mg vardenafil dose.
- Vardenafil 10mg is one of the options for treating ED, alongside others like sildenafil.
- The pill should be taken as directed; do not split or crush it.
- It should not be taken by those with hypersensitivity to its components.
- Consult your healthcare provider before starting vardenafil if unsure about safety.
- The medication may improve quality of life and intimate relationships.
- Regular medical evaluation is important to ensure safe medication use.
- Not all men respond to vardenafil; some may require alternative treatments.
- Side effects like dizziness can impair your ability to operate machinery.
- Avoid using vardenafil if you are taking medications that contain nitrates.
- Always keep track of your medication usage and report adverse effects.
In vitro data suggest that vardenafil has the potential to inhibit P-glycoprotein (P-gp) at therapeutic doses.
| Drug Class | Interaction Type | Effect | Recommendation |
|---|---|---|---|
| Nitrates | Additive hypotension | Risk of severe low blood pressure | Do not combine |
| CYP3A4 inhibitors | Increased Vardenafil levels | Potential side effects | Adjust dosage if necessary |
| Alpha-blockers | Enhanced hypotensive effect | Dizziness, fainting | Use with caution |
| Alpha-adrenergic agents | Blood pressure changes | Fluctuations in BP | Monitor blood pressure closely |
Nifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or C max of nifedipine, a drug that is metabolized via CYP3A4.
Where can I get more information?
This dose is approximately 100 fold (rat) and 29 fold (rabbit) greater than the AUC values for unbound vardenafil and its major metabolite in humans given the MRHD of 20 mg.In the rat pre-and postnatal development study, the NOAEL (no observed adverse effect level) for maternal toxicity was 8 mg/kg/day. Retarded physical development of pups in the absence of maternal effects was observed following maternal exposure to 1 and 8 mg/kg possibly due to vasodilatation and/or secretion of the drug into milk. The number of living pups born to rats exposed pre- and postnatally was reduced at 60 mg/kg/day. Based on the results of the pre- and postnatal study, the developmental NOAEL is less than 1 mg/kg/day. Based on plasma exposures in the rat developmental toxicity study, 1 mg/kg/day in the pregnant rat is estimated to produce total AUC values for unbound vardenafil and its major metabolite comparable to the human AUC at the MRHD of 20 mg.8.2 LactationRisk SummaryVardenafil hydrochloride tablets are not indicated for use in females.There is no information on the presence of vardenafil and its major metabolite in human milk, the effects on breastfed infant, or the effects on milk production.
Related treatment guides
Vardenafil is present in rat milk of lactating rats (see Data).DataVardenafil was secreted into the milk of lactating rats at concentrations approximately 10-fold greater than found in the plasma. In these patients whose hypertension was controlled with nifedipine, vardenafil hydrochloride tablets 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo. 8 USE IN SPECIFIC POPULATIONS 8.1 PregnancyRisk SummaryVardenafil hydrochloride tablets are not indicated for use in females.There are no data with the use of vardenafil hydrochloride tablets in pregnant women to inform any drug-associated risks. In animal reproduction studies conducted in pregnant rats and rabbits, no adverse developmental outcomes were observed with oral administration of vardenafil during organogenesis at exposures for unbound vardenafil and its major metabolite at approximately 100 and 29 times, respectively, the maximum recommended human dose (MRHD) of 20 mg based on AUC (see Data).DataAnimal DataNo evidence of specific potential for teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits that received vardenafil at up to 18 mg/kg/day during organogenesis.
- Vardenafil HCl 10mg can be an effective treatment when used responsibly.
- Always follow the prescribed dosing schedule for safety and efficacy.
- The medication may need to be adjusted based on individual response.
- Use with caution if you have a history of cardiovascular disease.
- Discuss all current medications with your doctor to avoid interactions.
- Vardenafil is not recommended for use by women or children.
- Be aware of possible side effects and seek medical help when needed.
- Alcohol and fatty foods can interfere with the drug’s performance.
- Proper sexual stimulation is required for the drug to work effectively.
- Regular follow-up with your healthcare provider is encouraged.
This dose is approximately 100 fold (rat) and 29 fold (rabbit) greater than the AUC values for unbound vardenafil and its major metabolite in humans given the MRHD of 20 mg.In the rat pre-and postnatal development study, the NOAEL (no observed adverse effect level) for maternal toxicity was 8 mg/kg/day.
- Vardenafil 10mg is available by prescription only, ensure your doctor’s approval.
- It is intended for use in adult men diagnosed with erectile dysfunction.
- Be cautious with dosing if you have kidney or liver problems.
- Remember that sexual activity carries health risks for some men.
- Report any adverse effects, especially chest pain or prolonged erections.
- It’s important to discuss your complete medical history before use.
- The medication does not protect against sexually transmitted infections.
- Do not share your medication with others to prevent misuse.
- Use vardenafil only as directed to avoid potential health hazards.
- Pharmacist or doctor can clarify any questions about proper use.
Retarded physical development of pups in the absence of maternal effects was observed following maternal exposure to 1 and 8 mg/kg possibly due to vasodilatation and/or secretion of the drug into milk. The number of living pups born to rats exposed pre- and postnatally was reduced at 60 mg/kg/day. Based on the results of the pre- and postnatal study, the developmental NOAEL is less than 1 mg/kg/day. Based on plasma exposures in the rat developmental toxicity study, 1 mg/kg/day in the pregnant rat is estimated to produce total AUC values for unbound vardenafil and its major metabolite comparable to the human AUC at the MRHD of 20 mg.8.2 LactationRisk SummaryVardenafil hydrochloride tablets are not indicated for use in females.There is no information on the presence of vardenafil and its major metabolite in human milk, the effects on breastfed infant, or the effects on milk production. Vardenafil is present in rat milk of lactating rats (see Data).DataVardenafil was secreted into the milk of lactating rats at concentrations approximately 10-fold greater than found in the plasma.