
Nitrates: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated.
| Form | Strengths | Route of Administration | Notes |
|---|---|---|---|
| Tablets | 25 mg, 50 mg, 100 mg | Oral | Most common form |
| Sublingual Tablets | 25 mg, 50 mg | Sublingual | Faster absorption |
| Extended-release Capsules | 100 mg | Oral | Less common |
| Oral Suspension | Customizable doses | Oral | Experimental/clinical use |
Nitroglycerin: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Nitroprusside: (Contraindicated) Concomitant use of nitroprusside and sildenafil is contraindicated due to the risk of additive hypotension.
If the patient has taken sildenafil, at least 24 hours must elapse before nitroprusside administration is considered; monitor hemodynamics closely. In addition, sildenafil may potentiate the nitric oxide-mediated platelet anti-aggregatory effect of nitroprusside. Odevixibat: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with odevixibat is necessary as concurrent use may decrease sildenafil exposure.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Olutasidenib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with olutasidenib is necessary as concurrent use may decrease sildenafil exposure. Omaveloxolone: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with omaveloxolone is necessary as concurrent use may decrease sildenafil exposure.
It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as rifabutin, will decrease plasma levels of sildenafil, however, no interaction studies have been performed.
Mitotane: (Major) Use caution if mitotane and sildenafil are used concomitantly, and monitor for decreased efficacy of sildenafil and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and sildenafil is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of sildenafil. Population pharmacokinetic analysis of data from patients in clinical trials indicated approximately 3-fold the sildenafil clearance when it was co-administered with mild CYP3A inducers. Mobocertinib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with mobocertinib is necessary as concurrent use may decrease sildenafil exposure. Monoamine oxidase inhibitors: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with sildenafil.
Nebivolol: (Moderate) Monitor closely for decreased efficacy of either drug if sildenafil is coadministered with nebivolol. The AUC of sildenafil was decreased by 21% when coadministered with nebivolol. A similar decrease in the concentration of d-nebivolol (less than 20% in the AUC) was also observed with coadministration of sildenafil. Nebivolol; Valsartan: (Moderate) Monitor closely for decreased efficacy of either drug if sildenafil is coadministered with nebivolol. Nefazodone: (Major) Coadministration of nefazodone is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). Oritavancin: (Moderate) Coadministration of oritavancin and sildenafil may result in increases or decreases in sildenafil exposure and may increase side effects or decrease efficacy of sildenafil. Sildenafil is primarily metabolized by CYP3A4, but is also metabolized by CYP2C9. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C9.
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If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy. Coadministration of pazopanib and sildenafil, a CYP3A4 substrate, may cause an increase in systemic concentrations of sildenafil. Use caution when administering these drugs concomitantly. Perindopril; Amlodipine: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Pexidartinib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with pexidartinib is necessary as concurrent use may decrease sildenafil exposure.
Because there is little experience with the combination of lorcaserin and medications indicated for erectile dysfunction (e.g., phosphodiesterase inhibitors), combined use should be approached with caution. Lorlatinib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with lorlatinib is necessary as concurrent use may decrease sildenafil exposure. Lumacaftor; Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Mavacamten: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with mavacamten is necessary as concurrent use may decrease sildenafil exposure. Mifepristone: (Major) Coadministration with mifepristone is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving mifepristone. Sildenafil is a sensitive CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Mitapivat: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with mitapivat is necessary as concurrent use may decrease sildenafil exposure. Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with sildenafil. Phenoxybenzamine: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of sildenafil. Phentolamine: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of sildenafil. Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Posaconazole: (Major) Coadministration of posaconazole is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH).
Nicardipine: (Moderate) Nicardipine is an inhibitor of CYP3A4 isoenzymes. Co-administration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates, such as sildenafil. Nifedipine: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response. For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.
Nilotinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with nilotinib is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Nirmatrelvir; Ritonavir: (Major) Coadministration of ritonavir is contraindicated in patients receiving sildenafil for pulmonary arterial hypertension (PAH). (Major) Concomitant use of ritonavir-boosted nirmatrelvir and sildenafil, when used for pulmonary arterial hypertension (PAH), is contraindicated; consider an alternative COVID-19 therapy. Consider withholding sildenafil, when used for erectile dysfunction, during concomitant receipt of ritonavir-boosted nirmatrelvir. Coadministration may increase sildenafil exposure resulting in increased toxicity. When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving posaconazole.
When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving nefazodone. Nelfinavir: (Major) Sildenafil is contraindicated for use with nelfinavir when used for pulmonary arterial hypertension (PAH). Sildenafil is a sensitive CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. Nesiritide, BNP: (Major) No formal drug interaction trials have been conducted with nesiritide. Sildenafil use within 24 hours was an exclusion criteria for nesiritide treatment during clinical trials.
Although not identified during clinical trials, the potential for symptomatic hypotension may be significantly increased when coadministering nesiritide with sildenafil. Sildenafil should be avoided within 24 hours before or after nesiritide use. Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with netupitant; palonosetron is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Nevirapine: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with nevirapine is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and sildenafil oral strips nevirapine is a weak CYP3A inducer. Prazosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of sildenafil. Promethazine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. Quinidine: (Moderate) Sildenafil is metabolized principally by the hepatic isoenzymes CYP3A4 and CYP2C9.
| Property | Description | Value | Notes |
|---|---|---|---|
| Molecular Formula | - | C22H30N6O4S | Chemical composition |
| Molecular Weight | - | 474.6 g/mol | Molar mass |
| Melting Point | - | 195-198°C | Crystalline form |
| Solubility in Water | - | Slightly soluble | At room temperature |
| pH of Aqueous Solution | - | 3.5 - 4.0 | Depends on concentration |
Quinine: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with quinine is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction.