Common and Serious Side Effects of Sildenafil Citrate
When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving mifepristone.
| Brand Name | Manufacturer | Dose Forms | Price Range (approx.) |
|---|---|---|---|
| Viagra | Pfizer | 25 mg, 50 mg, 100 mg | $$$ |
| Sildenafil Citrate Teva | Teva Pharmaceuticals | 50 mg, 100 mg | Moderate |
| Caverta | Mankind Pharma | 50 mg, 100 mg | Affordable |
| Kamagra | Ajanta Pharma | 100 mg | Low-cost |
Sildenafil is a sensitive CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
| Drug Class | Interaction Effect | Clinical Significance |
|---|---|---|
| Nitrates | Potentiates hypotension | Absolute contraindication |
| Alpha-blockers | Increased hypotensive effect | Use with caution |
| CYP3A4 inhibitors | Increased sildenafil levels | Dose adjustment needed |
| Protease inhibitors | Elevates sildenafil exposure | Increased side effects |
Mitapivat: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with mitapivat is necessary as concurrent use may decrease sildenafil exposure. 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.
The History of Sildenafil Citrate, AKA Viagra
Sildenafil is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased sildenafil concentrations. Ketoconazole: (Major) Coadministration of ketoconazole 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 ketoconazole. Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of clarithromycin is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). Lefamulin: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with oral lefamulin is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction.
Pulmonary hypertension
Sildenafil is a sensitive CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Lenacapavir: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with lenacapavir is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. In a drug interaction study, coadministration with a moderate CYP3A inhibitor increased the AUC of sildenafil by 182%. Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of sildenafil; monitor for potential reduction in efficacy. 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.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Kamagra Polo | 100mg | 32 Pills | 125.88€ 119.89€ | |
| Kamagra Polo | 100mg | 60 + 4 Pills | 189.39€ 180.37€ | |
| Viagra Generic | 200mg | 270 + 10 Pills | 379.76€ 361.68€ | |
| Viagra Generic | 50mg | 60 + 4 Pills | 83.93€ 79.93€ | |
| Kamagra Soft Tabs | 100mg | 12 Pills | 57.55€ 54.81€ | |
| Viagra Generic | 25mg | 360 + 10 Pills | 213.68€ 203.50€ | |
| Kamagra | 100mg | 84 + 6 Pills | 264.44€ 251.85€ | |
| Kamagra Oral Jelly | 100mg | 220 + 18 Sachets | 662.24€ 630.70€ | |
| Viagra Generic | 200mg | 20 Pills | 61.69€ 58.75€ | |
| Viagra Generic | 150mg | 120 + 8 Pills | 177.58€ 169.12€ | |
| Viagra Generic | 100mg | 360 + 10 Pills | 330.21€ 314.49€ | |
| Kamagra Polo | 100mg | 180 + 8 Pills | 446.52€ 425.26€ | |
| Viagra Generic | 200mg | 360 + 10 Pills | 481.98€ 459.03€ | |
| Viagra Generic | 100mg | 10 Pills | 28.91€ 27.53€ | |
| Kamagra Oral Jelly | 100mg | 63 + 7 Sachets | 224.18€ 213.50€ | |
| Kamagra Soft Tabs | 100mg | 32 Pills | 120.11€ 114.39€ | |
| Viagra Generic | 50mg | 270 + 8 Pills | 198.48€ 189.03€ |
Mobocertinib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with mobocertinib is sildenafil pricing 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.
Dosing & Uses
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of sildenafil; monitor for potential reduction in efficacy. Letermovir: (Major) Monitor for an increase in sildenafil-related adverse reactions if coadministration with letermovir is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Concurrent use is not recommended in patients receiving sildenafil for pulmonary arterial hypertension and taking cyclosporine, because the magnitude of the interaction may be amplified. Consider a starting dose of 25 mg of sildenafil for erectile dysfunction in patients receiving letermovir with cyclosporine. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor.
How should Sildenafil Citrate Tablets be stored?
Levamlodipine: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. Levoketoconazole: (Major) Coadministration of ketoconazole is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). Lonafarnib: (Major) Coadministration with lonafarnib 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 lonafarnib. Lopinavir; Ritonavir: (Major) sildenafil products over the counter Coadministration of ritonavir is contraindicated in patients receiving sildenafil for pulmonary arterial hypertension (PAH). 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). 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).
What special dietary instructions should I follow?
Concurrent use substantially increases the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Ritonavir, a strong CYP3A4 inhibitor, increased the AUC of sildenafil, a sensitive CYP3A4 substrate, by 11-fold in a drug interaction study. Lorcaserin: (Moderate) Lorcaserin is a serotonin 2C receptor agonist, and priapism is a potential effect of 5-HT2C receptor agonism. 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.
How sildenafil is used
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). 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.
Are There Any Side Effects?
In two of the six subjects, prolonged clinical effects of sildenafil were noted for 72 hours after a single dose of sildenafil. Isavuconazonium: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with isavuconazonium is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with sildenafil. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with sildenafil. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as rifampin, will decrease plasma levels of sildenafil, however, no interaction studies have been performed.
How should I store sildenafil?
Isoniazid, INH; Rifampin: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. Itraconazole: (Major) Avoid use of sildenafil for the treatment of pulmonary hypertension during and for 2 weeks after discontinuation of itraconazole treatment. When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving itraconazole. Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. Ivosidenib: (Moderate) Monitor for loss of efficacy of sildenafil during coadministration of ivosidenib; a sildenafil dose adjustment may be necessary. Sildenafil is a sensitive CYP3A substrate and nevirapine is a weak CYP3A inducer.
- Sildenafil citrate is sometimes used off-label for other conditions.
- Off-label uses include altitude sickness and Raynaud’s phenomenon.
- Research continues into additional therapeutic effects.
- The drug’s development was led by Pfizer.
- It is often used in combination with other ED treatments.
- Patients should avoid grapefruit juice, which can affect drug levels.
- Some formulations include chewable or dissolvable tablets.
- Ongoing studies investigate its cardiovascular benefits.
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.
| Country | Legal Status | Prescription Requirement | Notes |
|---|---|---|---|
| USA | Prescription-only medication | Yes | FDA approved |
| UK | Prescription-only | Yes | MHRA regulated |
| India | Over-the-counter and prescription | Both are possible | Varies by state |
| Australia | Prescription only | Yes | TGA regulated |
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.
- Sildenafil citrate can be combined with lifestyle changes.
- Exercise and weight management improve erectile function.
- Quitting smoking enhances medication effectiveness.
- Reducing alcohol intake minimizes side effects.
- Psychological therapy may support ED treatment.
- Counseling can address underlying emotional issues.
- Regular medical check-ups are recommended.
- Patient education improves safe and effective use.