Revatio

Phosphodiesterase Inhibitors for ED
Phosphodiesterase Inhibitors for PAH

Oral Administration

May be administered without regard to meals.

Oral Liquid Formulations

Shake well for at least 10 seconds prior to each administration.
Measure dose with an oral dosing syringe or calibrated measuring device.
Concentration of the suspension is 10 mg/mL.
 
Oral suspension (e.g., Liqrev)
Storage: Store at room temperature of 20 to 25 degrees C (68 to 77 degrees F). Do not freeze. Discard any unused portion after 90 days of opening the bottle.
 
Powder for oral suspension (e.g., Revatio or generic equivalents)):
Do not mix with any other medication or additional flavoring agent.
Prior to reconstitution, tap the bottle to loosen the powder.
Reconstitute with a total of 90 mL of water added in 2 portions. Initially, add 60 mL of water to the bottle and shake vigorously for at least 30 seconds. Add the remaining 30 mL of water and shake vigorously for at least 30 seconds.
Remove the cap and press the adaptor for the oral syringe into the neck of the bottle; replace cap.
Write an expiration date of 60 days from the date of reconstitution on the bottle label.
Storage: Store below 30 degrees C (86 degrees F) or in refrigerator at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze. Discard any unused portion after 60 days.

Extemporaneous Compounding-Oral

Extemporaneous 2.5 mg/mL sildenafil oral suspension:
NOTE: Extemporaneously prepared sildenafil oral suspension is not approved by the FDA; an FDA-approved powder for oral suspension is now commercially available.
With a mortar and pestle, grind thirty 25-mg sildenafil citrate tablets to a fine powder.
In a separate container, mix 1 of the following: 1) 150 mL of Ora-Sweet with 150 mL of Ora-Plus; or 2) 150 mL of Simple Syrup, NF with 150 mL of methylcellulose 1%.
Add a small amount of the mixture to the fine powder and mix into a uniform paste. Add geometric amounts of the vehicle to the almost desired volume while mixing. Transfer to a graduated cylinder and adjust to volume while mixing.
Place in amber plastic bottles. Shake well before each use.
Storage: This suspension is stable for 91 days when stored at 4 and 25 degrees C.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Sildenafil injection is available as a ready to use solution; further dilution is not required.
Administer as an IV bolus injection.

Severe

visual impairment / Early / 1.0-11.0
myocardial infarction / Delayed / 0-2.0
cardiac arrest / Early / 0-2.0
AV block / Early / 0-2.0
ventricular tachycardia / Early / 0-2.0
intracranial bleeding / Delayed / 0-2.0
heart failure / Delayed / 0-2.0
cardiomyopathy / Delayed / 0-2.0
anaphylactoid reactions / Rapid / 0-2.0
angioedema / Rapid / 0-2.0
tendon rupture / Delayed / 0-2.0
exfoliative dermatitis / Delayed / 0-2.0
hearing loss / Delayed / 0-2.0
ocular hemorrhage / Delayed / 0-2.0
stroke / Early / Incidence not known
suicidal ideation / Delayed / Incidence not known
seizures / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known
retinal hemorrhage / Delayed / Incidence not known
non-arteritic anterior ischemic optic neuropathy / Delayed / Incidence not known
retinal edema / Delayed / Incidence not known
sickle-cell crisis / Delayed / Incidence not known

Moderate

edema / Delayed / 25.0-25.0
blurred vision / Early / 3.0-3.0
urinary incontinence / Early / 0-2.0
ejaculation dysfunction / Delayed / 0-2.0
cystitis / Delayed / 0-2.0
hematuria / Delayed / 0-2.0
angina / Early / 0-2.0
palpitations / Early / 0-2.0
hypotension / Rapid / 0-2.0
migraine / Early / 0-2.0
chest pain (unspecified) / Early / 0-2.0
orthostatic hypotension / Delayed / 0-2.0
hypoglycemia / Early / 0-2.0
peripheral edema / Delayed / 0-2.0
leukopenia / Delayed / 0-2.0
hyperuricemia / Delayed / 0-2.0
hypernatremia / Delayed / 0-2.0
hyperglycemia / Delayed / 0-2.0
gout / Delayed / 0-2.0
diabetes mellitus / Delayed / 0-2.0
anemia / Delayed / 0-2.0
ataxia / Delayed / 0-2.0
hypertonia / Delayed / 0-2.0
depression / Delayed / 0-2.0
esophagitis / Delayed / 0-2.0
glossitis / Early / 0-2.0
colitis / Delayed / 0-2.0
gastritis / Delayed / 0-2.0
dysphagia / Delayed / 0-2.0
stomatitis / Delayed / 0-2.0
myasthenia / Delayed / 0-2.0
synovitis / Delayed / 0-2.0
bone pain / Delayed / 0-2.0
contact dermatitis / Delayed / 0-2.0
skin ulcer / Delayed / 0-2.0
photophobia / Early / 0-2.0
conjunctivitis / Delayed / 0-2.0
cataracts / Delayed / 0-2.0
dyspnea / Early / 0-2.0
priapism / Early / Incidence not known
hypertension / Early / Incidence not known
euphoria / Early / Incidence not known
hallucinations / Early / Incidence not known
hostility / Early / Incidence not known
delirium / Early / Incidence not known
mania / Early / Incidence not known
confusion / Early / Incidence not known
amnesia / Delayed / Incidence not known

Mild

headache / Early / 16.0-49.0
flushing / Rapid / 9.0-19.0
dyspepsia / Early / 3.0-17.0
myalgia / Early / 2.0-14.0
back pain / Delayed / 2.0-13.0
epistaxis / Delayed / 13.0-13.0
diarrhea / Early / 9.0-12.0
nasal congestion / Early / 4.0-9.0
dizziness / Early / 2.0-4.0
nausea / Early / 2.0-3.0
rash / Early / 1.0-3.0
breast enlargement / Delayed / 0-2.0
nocturia / Early / 0-2.0
orgasm dysfunction / Delayed / 0-2.0
syncope / Early / 0-2.0
photosensitivity / Delayed / 0-2.0
chills / Rapid / 0-2.0
asthenia / Delayed / 0-2.0
abdominal pain / Early / 0-2.0
vertigo / Early / 0-2.0
drowsiness / Early / 0-2.0
hyporeflexia / Delayed / 0-2.0
tremor / Early / 0-2.0
hypoesthesia / Delayed / 0-2.0
abnormal dreams / Early / 0-2.0
paresthesias / Delayed / 0-2.0
insomnia / Early / 0-2.0
vomiting / Early / 0-2.0
gingivitis / Delayed / 0-2.0
xerostomia / Early / 0-2.0
diaphoresis / Early / 0-2.0
pruritus / Rapid / 0-2.0
urticaria / Rapid / 0-2.0
otalgia / Early / 0-2.0
tinnitus / Delayed / 0-2.0
ocular pain / Early / 0-2.0
mydriasis / Early / 0-2.0
xerophthalmia / Early / 0-2.0
sinusitis / Delayed / 0-2.0
pharyngitis / Delayed / 0-2.0
laryngitis / Delayed / 0-2.0
cough / Delayed / 0-2.0
emotional lability / Early / Incidence not known
agitation / Early / Incidence not known
anxiety / Delayed / Incidence not known
paranoia / Early / Incidence not known
irritability / Delayed / Incidence not known
ocular irritation / Rapid / Incidence not known
diplopia / Early / Incidence not known

LiQrev, Revatio, Viagra

Rx

Oral, selective phosphodiesterase type 5 (PDE5) inhibitor
Used for pulmonary arterial hypertension (PAH) and erectile dysfunction (ED)
As with other PDE5 inhibitors, contraindicated for use with nitrates because the combination can cause a sudden drop in blood pressure

For the treatment of erectile dysfunction (ED). Oral dosage (Viagra) Adults

50 mg PO as needed approximately 1 hour before anticipated sexual activity. May decrease the dose to 25 mg or increase the dose to 100 mg PO as needed approximately 1 hour before sexual activity. The dose may be taken from 30 minutes to 4 hours before sexual activity. Max: 1 dose/day and 100 mg/dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Older Adults

25 mg PO as needed approximately 1 hour before anticipated sexual activity. May increase the dose up to 100 mg PO as needed approximately 1 hour before sexual activity. The dose may be taken from 30 minutes to 4 hours before sexual activity. Max: 1 dose/day and 100 mg/dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of pulmonary hypertension. For the treatment of pulmonary hypertension to improve exercise ability and delay clinical worsening in patients with WHO Group 1 pulmonary hypertension. Oral dosage (Revatio only) Adults

20 mg PO 3 times daily. Dose may be titrated as needed based on symptoms and tolerability to a maximum of 80 mg PO 3 times daily. Although dose-response improvement in exercise ability was not observed in short-term clinical trials in adults with pulmonary hypertension, the delay in clinical worsening with long-term use of sildenafil in a clinical trial supports dosing up to a maximum of 80 mg PO 3 times daily.

Children and Adolescents weighing 45 kg or more

20 mg PO 3 times daily. A maximum dose in pediatric patients has not been identified. Based on experience in adults, the dose may be titrated as needed to a maximum of 40 mg PO 3 times daily based on symptoms and tolerability. Avoid higher dosing due to a greater risk of mortality in pediatric patients (age 1 to 17 years) treated with high dose sildenafil monotherapy.

Children and Adolescents weighing 21 to 44 kg

20 mg PO 3 times daily. Avoid higher dosing due to a greater risk of mortality in pediatric patients (age 1 to 17 years) treated with high dose sildenafil monotherapy.

Children weighing 20 kg or less

10 mg PO 3 times daily. Avoid higher dosing due to a greater risk of mortality in pediatric patients (age 1 to 17 years) treated with high dose sildenafil monotherapy.

Infants†

0.5 to 1 mg/kg/dose PO every 8 hours. Prior to the release of pediatric pulmonary hypertension guidelines, the generally accepted dose of sildenafil was 0.5 to 2 mg/kg/dose every 6 to 8 hours, with some regimens, particularly those described in earlier reports, administering doses every 4 hours; however, guidelines recommend more conservative dosing based on a greater risk of mortality in pediatric patients (age 1 to 17 years) treated with high dose sildenafil monotherapy, as seen in the STARTS-2 trial. Relevance of this data to the infant population is unclear.

Oral dosage (Liqrev only) Adults

20 mg PO three times daily.

Intravenous dosage Adults

10 mg IV 3 times daily.

For weaning of inhaled nitric oxide (iNO) in pediatric patients with pulmonary hypertension†. Oral dosage Infants and Children

0.22 to 0.5 mg/kg/dose PO as a single dose 1 hour prior to discontinuing iNO or 4 times daily. None of the 15 patients receiving a single sildenafil dose of 0.3 to 0.5 mg/kg/dose PO 1 hour prior to discontinuation of iNO experienced rebound pulmonary hypertension compared to 10 of 14 patients receiving placebo. In 7 patients receiving sildenafil 0.22 to 0.47 mg/kg/dose PO 4 times daily, mean iNO dose was significantly reduced compared to baseline within 24 hours of sildenafil initiation (12.2 vs. 29.8 ppm, p = 0.024). Guidelines recommend sildenafil use to prevent rebound pulmonary hypertension and facilitate iNO weaning in patients with evidence of increased pulmonary artery pressure upon iNO withdrawal; however, they do not provide specific dosing. Recommended maintenance dosing for pulmonary hypertension is 0.5 to 1 mg/kg/dose PO 3 times daily in persons younger than 1 year, 10 mg PO 3 times daily in persons weighing 20 kg or less, and 20 mg PO 3 times daily in persons weighing more than 20 kg.

Neonates

0.22 to 0.5 mg/kg/dose PO as a single dose 1 hour prior to discontinuing iNO or 4 times daily. None of the 15 patients receiving a single sildenafil dose of 0.3 to 0.5 mg/kg/dose PO 1 hour prior to discontinuation of iNO experienced rebound pulmonary hypertension compared to 10 of 14 patients receiving placebo. In 7 patients receiving sildenafil 0.22 to 0.47 mg/kg/dose PO 4 times daily, mean iNO dose was significantly reduced compared to baseline within 24 hours of sildenafil initiation (12.2 vs. 29.8 ppm, p = 0.024). Guidelines recommend sildenafil use to prevent rebound pulmonary hypertension and facilitate iNO weaning in patients with evidence of increased pulmonary artery pressure upon iNO withdrawal; however, they do not provide specific dosing. Recommended maintenance dosing for pulmonary hypertension is 0.5 to 1 mg/kg/dose PO 3 times daily in persons younger than 1 year, 10 mg PO 3 times daily in persons weighing 20 kg or less, and 20 mg PO 3 times daily in persons weighing more than 20 kg.

For the treatment of Raynaud's phenomenon† resistant to vasodilator therapy. Oral dosage Adults

A double-blind, placebo-controlled, crossover study evaluated sildenafil for symptomatic secondary Raynaud's phenomenon resistant to vasodilatory therapy. Patients (n = 18, 15 were female) were randomly assigned to receive placebo or sildenafil 50 mg PO twice daily for 4 weeks; a washout period of 1 week was used before crossover. The results showed that sildenafil significantly improved microcirculation and symptoms associated with Raynaud's. In patients with chronic digital ulcerations, sildenafil treatment resulted in healing of trophic lesions which reappeared or progressed when sildenafil was stopped. Ulcerations did not heal while receiving placebo. Sildenafil therapy may be an alternative therapy in patients with Raynaud's resistant to vasodilatory therapy.

For altitude sickness prophylaxis†, specifically prevention of high altitude pulmonary edema†. Oral dosage Adults

50 mg PO every 8 hours starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated as an alternative to nifedipine.  Prophylactic medications should only be considered for individuals with a prior history of high altitude pulmonary edema.

For the treatment of persistent pulmonary hypertension of the newborn† (PPHN). For adjunctive therapy for PPHN using the oral route of administration. Oral dosage Neonates

0.5 to 1 mg/kg/dose PO every 8 hours. Delay use in extremely premature infants until retinal vascularization is established. The pharmacokinetics of sildenafil are highly variable in neonates; careful dose titration and monitoring is recommended. Prior to the release of pediatric pulmonary hypertension guidelines, the generally accepted dose of sildenafil was 0.5 to 2 mg/kg/dose every 6 to 8 hours, with doses ranging up to 3 mg/kg/dose every 6 hours ; however, guidelines recommend more conservative dosing based on a greater risk of mortality in pediatric patients (age 1 to 17 years) treated with high dose sildenafil monotherapy, as seen in the STARTS-2 trial. Relevance of this data to the neonatal population is unclear.

For adjunctive therapy for PPHN using the intravenous route of administration. Continuous intravenous infusion dosage Neonates

0.4 mg/kg IV loading dose over 3 hours followed by a continuous infusion of 0.067 mg/kg/hour (1.6 mg/kg/day); this dose has been proposed based on the results of an open-label, dose-escalation study in 36 term neonates. Delay use in extremely premature infants until retinal vascularization is established.

Intermittent intravenous dosage Neonates

Very limited data are available; intermittent IV infusions have been used when oral intake was not possible in 3 neonates. An initial dosage of 0.4 to 0.5 mg/kg/dose IV every 6 hours (infused over 3 hours) was given to 2 term neonates with pulmonary hypertension secondary to congenital diaphragmatic hernia. The dose was gradually titrated up to 2 mg/kg/dose IV based on clinical response. For doses less than 1.5 mg/kg/dose IV, the infusion time was gradually decreased to over 1 hour (weaned by 1 hour every 36 to 48 hours). The third neonate (gestational age 25 weeks, postnatal age 18.6 weeks) was receiving oral sildenafil 1.67 mg/kg/dose PO every 6 hours and was converted to sildenafil 1.25 mg/kg/dose IV every 6 hours when she became "nothing-by-mouth" (NPO) status. All 3 neonates were also receiving inhaled nitric oxide at the time of sildenafil initiation. The duration of treatment ranged from 6 to 51 days, and respiratory support was able to be decreased over time in all patents.

†Indicates off-label use

Hepatic Impairment

Hepatic dosing adjustments for adults with erectile dysfunction:
Consider a starting dose of 25 mg in adults with any degree of hepatic impairment.
 
Hepatic dosing adjustments for patients with pulmonary hypertension:
No adjustment needed for adults with mild to moderate hepatic impairment (Child Pugh class A or B). The effect of severe hepatic impairment (Child Pugh class C) has not been studied. Specific guidelines for pediatric patients are not available.

Renal Impairment

Renal dosing adjustments for adults with erectile dysfunction:
CrCl 30 mL/minute or greater: No dosage adjustment is needed.
CrCl less than 30 mL/minute: Reducing starting dose to 25 mg PO.
 
Renal dosing adjustments for patients with pulmonary hypertension:
No adjustment needed for adults with renal impairment, including adults with severe renal impairment (CrCl less than 30 mL/minute). Specific guidelines for pediatric patients are not available.
 
Intermittent hemodialysis
Follow recommendations for patients with CrCl less than 30 mL/minute.

Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Adagrasib: (Major) Coadministration with adagrasib 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 adagrasib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Adagrasib is a strong CYP3A inhibitor and sildenafil is a sensitive CYP3A substrate. Coadministration of other strong CYP3A inhibitors increased the sildenafil AUC between 3- and 11-fold.
Alfuzosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alfuzosin therapy before initiating therapy with the lowest dose of sildenafil. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of alfuzosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and alfuzosin.
Aliskiren: (Moderate) Aliskiren can enhance the effects of sildenafil on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of sildenafil on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Alpha-blockers: (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. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker.
Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents. Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure.
Amiodarone: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with amiodarone is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and amiodarone is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Amlodipine: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Amlodipine; Atorvastatin: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Amlodipine; Benazepril: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Amlodipine; Celecoxib: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Amlodipine; Olmesartan: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Amlodipine; Valsartan: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of clarithromycin 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 clarithromycin. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Clarithromycin is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Apalutamide: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with apalutamide is necessary. Sildenafil is a sensitive CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Concomitant administration of strong CYP3A inducers is expected to substantially decrease plasma concentrations of sildenafil. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Aprepitant, Fosaprepitant: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministered with multi-day regimens of oral aprepitant. A dose reduction of sildenafil may be required when using for erectile dysfunction. Sildenafil is a CYP3A4 substrate and aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Atazanavir: (Major) Sildenafil is contraindicated for use with atazanavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Atazanavir; Cobicistat: (Major) Sildenafil is contraindicated for use with atazanavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold. (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin is a synthetic opiate agonist with a chemical structure similar to that of meperidine. Prolonged erections have been reported in two patients taking sildenafil with dihydrocodeine. In both cases, patients reported erections subsided immediately after orgasm when taking sildenafil alone. Although more data are needed, use caution when prescribing opiate agonists and sildenafil concomitantly.
Barbiturates: (Minor) Sildenafil is metabolized principally by the hepatic CYP3A4 and CYP2C9 isoenzymes. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of sildenafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Belzutifan: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with belzutifan is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and belzutifan is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Berotralstat: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with berotralstat is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Brigatinib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with brigatinib is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and brigatinib is a weak CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Brompheniramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Carbamazepine: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with carbamazepine is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant administration of strong CYP3A inducers is expected to substantially decrease plasma concentrations of sildenafil.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Cenobamate: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with cenobamate is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Ceritinib: (Major) Coadministration with ceritinib 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 ceritinib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Ceritinib is a strong CYP3A4 inhibitor and sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Chloramphenicol: (Major) Coadministration of chloramphenicol 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 chloramphenicol. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Chloramphenicol is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Chlorpheniramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Cimetidine: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with cimetidine is necessary. Concomitant use may increase sildenafil plasma concentrations. Cimetidine 800 mg caused a 56% increase in plasma sildenafil concentrations when coadministered with sildenafil 50 mg to healthy volunteers. Sildenafil is a CYP2C9 and CYP3A substrate and cimetidine is a nonspecific CYP inhibitor.
Ciprofloxacin: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with ciprofloxacin is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Clarithromycin: (Major) Coadministration of clarithromycin 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 clarithromycin. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Clarithromycin is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Cobicistat: (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Codeine; Phenylephrine; Promethazine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Conivaptan: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with conivaptan is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. In a drug interaction study, coadministration with a moderate CYP3A inhibitor increased the peak and overall exposure of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Crizotinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with crizotinib is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Dabrafenib: (Major) The concomitant use of dabrafenib and sildenafil may lead to decreased sildenafil concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of sildenafil efficacy. Dabrafenib is a moderate CYP3A4 inducer and sildenafil is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Danazol: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with danazol is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and danazol is a CYP3A4 inhibitor.
Darunavir: (Major) Sildenafil is contraindicated for use with darunavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Darunavir; Cobicistat: (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold. (Major) Sildenafil is contraindicated for use with darunavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold. (Major) Sildenafil is contraindicated for use with darunavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Delavirdine: (Major) Coadministration of delavirdine is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Delavirdine is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Dexamethasone: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with dexamethasone is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and dexamethasone is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Dextromethorphan; Quinidine: (Moderate) Sildenafil is metabolized principally by the hepatic isoenzymes CYP3A4 and CYP2C9. Inhibitors of these isoenzymes, such as quinidine, may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects.
Diltiazem: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with diltiazem is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Diphenhydramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Diphenoxylate; Atropine: (Moderate) Diphenoxylate/difenoxin is a synthetic opiate agonist with a chemical structure similar to that of meperidine. Prolonged erections have been reported in two patients taking sildenafil with dihydrocodeine. In both cases, patients reported erections subsided immediately after orgasm when taking sildenafil alone. Although more data are needed, use caution when prescribing opiate agonists and sildenafil concomitantly.
Doxazosin: (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. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker.
Dronedarone: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with dronedarone is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and dronedarone is a moderate CYP3A4 inhibitor.
Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. It is advisable to monitor blood pressure if the combination is necessary.
Dutasteride; Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin therapy before initiating therapy with the lowest dose of sildenafil. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of tamsulosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and tamsulosin.
Duvelisib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with duvelisib is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as sildenafil.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as sildenafil.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as sildenafil.
Elagolix: (Moderate) Monitor for reduced therapeutic effect of sildenafil if coadministered with elagolix. Concurrent use may decrease sildenafil plasma concentrations. Sildenafil is a sensitive CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer. Population pharmacokinetic analysis of data from patients in clinical trials indicated approximately 3-fold the sildenafil clearance when it was coadministered with weak CYP3A inducers.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for reduced therapeutic effect of sildenafil if coadministered with elagolix. Concurrent use may decrease sildenafil plasma concentrations. Sildenafil is a sensitive CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer. Population pharmacokinetic analysis of data from patients in clinical trials indicated approximately 3-fold the sildenafil clearance when it was coadministered with weak CYP3A inducers.
Elbasvir; Grazoprevir: (Moderate) Administering sildenafil with elbasvir; grazoprevir may result in elevated sildenafil plasma concentrations. Sildenafil is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; sildenafil is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates, such as sildenafil, can theoretically increase sildenafil exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Sildenafil is contraindicated for use with cobicistat when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Encorafenib: (Moderate) Coadministration of encorafenib with sildenafil may result in increased toxicity or decreased efficacy of sildenafil. Sildenafil is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Enzalutamide: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with enzalutamide is necessary. Sildenafil is a CYP3A4 (major) and CYP2C9 (minor) substrate. Enzalutamide is a strong CYP3A4 inducer and a moderate inducer of CYP2C9. Concomitant administration of strong CYP3A inducers is expected to substantially decrease plasma concentrations of sildenafil. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Erythromycin: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with erythromycin is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with erythromycin increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Etravirine: (Moderate) Etravirine is an inducer of CYP3A4; coadministration may result in decreased sildenafil concentrations. Dosage adjustments may be needed based on clinical efficacy.
Fedratinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fedratinib is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as sildenafil , has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of sildenafil during coadministration with fenofibric acid.
Fluconazole: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fluconazole is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Fluvoxamine: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fluvoxamine is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration of fluvoxamine increased the sildenafil AUC by 40%.
Fosamprenavir: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with fosamprenavir is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. When used for pulmonary arterial hypertension, this combination is listed as a contraindication in the fosamprenavir FDA-approved labeling. Sildenafil is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. In a drug interaction study, coadministration with a moderate CYP3A inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Glycerol Phenylbutyrate: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with glycerol phenylbutyrate is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and glycerol phenylbutyrate is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Grapefruit juice: (Moderate) Sildenafil is metabolized via the cytochrome CYP 3A4 isozyme. Grapefruit juice contains a compound that inhibits CYP3A4 in enterocytes in the GI tract. Sildenafil levels may increase; it is possible that sildenafil-induced side effects could also be increased in some individuals. One study has confirmed a potential interaction; sildenafil's AUC increased 23 percent with coadministration of grapefruit juice.
Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Hydantoins: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with phenytoin is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and phenytoin is a strong CYP3A inducer. Concomitant administration of strong CYP3A inducers is expected to substantially decrease plasma concentrations of sildenafil.
Hydralazine; Isosorbide Dinitrate, ISDN: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Idelalisib: (Major) Coadministration of idelalisib 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 idelalisib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Idelalisib is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Imatinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with imatinib is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor.
Indinavir: (Major) Sildenafil is contraindicated for use with indinavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. In a small pharmacokinetic study, the coadministration of a single dose of sildenafil (25 mg) to patients receiving indinavir (800 mg every 8 hours) resulted in markedly increased sildenafil AUC values (340% increase), as compared to historical controls. 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. Sildenafil is a sensitive CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor.
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.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. 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.
Isoniazid, INH; Rifampin: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. 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.
Isosorbide Dinitrate, ISDN: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Isosorbide Mononitrate: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
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. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Itraconazole is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; sildenafil is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates, such as sildenafil, can theoretically increase sildenafil exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Ivosidenib: (Moderate) Monitor for loss of efficacy of sildenafil during coadministration of ivosidenib; a sildenafil dose adjustment may be necessary. 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. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Ketoconazole is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of clarithromycin 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 clarithromycin. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Clarithromycin is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
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. Sildenafil is a sensitive CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
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%. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of sildenafil; monitor for potential reduction in efficacy. Sildenafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of sildenafil; monitor for potential reduction in efficacy. Sildenafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
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. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is metabolized principally by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Levoketoconazole: (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. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Ketoconazole is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
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. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Lopinavir; Ritonavir: (Major) Coadministration of ritonavir is contraindicated in patients receiving sildenafil for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. 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. Sildenafil is a sensitive CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Lumacaftor; Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; sildenafil is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates, such as sildenafil, can theoretically increase sildenafil exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of antihypertensive agents. 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. Sildenafil is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer.
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. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Mitapivat: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with mitapivat is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and mitapivat is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
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. Sildenafil is a sensitive CYP3A substrate and mobocertinib is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Monoamine oxidase inhibitors: (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.
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. 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.
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. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Nefazodone is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Nelfinavir: (Major) Sildenafil is contraindicated for use with nelfinavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
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. Sildenafil is a sensitive CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor.
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 nevirapine is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
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. Sildenafil is a sensitive CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Major) Coadministration of ritonavir is contraindicated in patients receiving sildenafil for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. 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. (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. Sildenafil is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Nitrates: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Nitroglycerin: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
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. Sildenafil is a sensitive CYP3A substrate and odevixibat is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
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. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Olutasidenib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with olutasidenib is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and olutasidenib is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Omaveloxolone: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with omaveloxolone is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and omaveloxolone is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. 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.
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. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. 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. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Pexidartinib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with pexidartinib is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Phenelzine: (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.
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. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker.
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. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker.
Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Posaconazole: (Major) Coadministration of posaconazole 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 posaconazole. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Posaconazole is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
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. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker.
Promethazine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Quinidine: (Moderate) Sildenafil is metabolized principally by the hepatic isoenzymes CYP3A4 and CYP2C9. Inhibitors of these isoenzymes, such as quinidine, may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects.
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. Sildenafil is a sensitive CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor.
Ranolazine: (Moderate) Sildenafil is metabolized principally by the hepatic CYP3A4 (major route) and 2C9 (minor route) isoenzymes. Inhibitors of these isoenzymes may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects. The manufacturer recommends dosage reduction in patients receiving potent cytochrome CYP3A4 inhibitors. Population data from patients in clinical trials did indicate a reduction in sildenafil clearance when it was coadministered with CYP3A4 inhibitors. CYP3A4 inhibitors include ranolazine.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Ribociclib: (Major) Coadministration with ribociclib 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 ribociclib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Ribociclib is a strong CYP3A4 inhibitor and sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Ribociclib; Letrozole: (Major) Coadministration with ribociclib 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 ribociclib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Ribociclib is a strong CYP3A4 inhibitor and sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Rifabutin: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. 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.
Rifampin: (Minor) Sildenafil is metabolized principally by cytochrome P450 3A4 and 2C9 enzymes. 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.
Rifapentine: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with rifapentine is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant administration of strong CYP3A4 inducers is expected to substantially decrease plasma concentrations of sildenafil. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Riociguat: (Contraindicated) Use of riociguat and sildenafil is contraindicated due to the risk of hypotension. Discontinue riociguat at least 24 hours prior to sildenafil administration and do not administer within 24 hours of sildenafil. Monitor for signs and symptoms of hypotension during transition of therapy. PDE5 inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.
Ritlecitinib: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with ritlecitinib is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. In a drug interaction study, coadministration with a moderate CYP3A inhibitor increased the AUC of sildenafil by 182%. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Ritonavir: (Major) Coadministration of ritonavir is contraindicated in patients receiving sildenafil for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. 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.
Sapropterin: (Moderate) Sapropterin acts as a cofactor in the synthesis of nitric oxide and may cause vasorelaxation. Caution should be exercised when administering sapropterin in combination with drugs that affect nitric oxide-mediated vasorelaxation such as phosphodiesterase inhibitors. When given together these agents may produce an additive reduction in blood pressure. The combination of sapropterin and a phosphodiesterase (PDE5) inhibitor did not significantly reduce blood pressure when administered concomitantly in animal studies. The additive effect of these agents has not been studied in humans.
Saquinavir: (Major) Sildenafil is contraindicated for use with saquinavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; saquinavir is a strong CYP3A4 inhibitor. Coadministration of saquinavir increased the sildenafil AUC by about 3-fold in a drug interaction study.
Silodosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin therapy before initiating therapy with the lowest dose of sildenafil. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of silodosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and silodosin.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with taurursodiol is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and taurursodiol is a weak CYP3A inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A inducers.
Sotorasib: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with sotorasib is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with St. John's Wort is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and St. John's Wort is a strong CYP3A inducer. Concomitant administration of strong CYP3A inducers is expected to substantially decrease plasma concentrations of sildenafil.
Stiripentol: (Moderate) Consider a dose adjustment of sildenafil when coadministered with stiripentol. Coadministration may alter plasma concentrations of sildenafil resulting in an increased risk of adverse reactions and/or decreased efficacy. Sildenafil is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tacrolimus: (Moderate) Consider initiating sildenafil at a low dose (25 mg) in kidney transplant recipients receiving tacrolimus. In a study of renal transplant patients, coadministration of tacrolimus with a single 50 mg dose of sildenafil resulted in an increase in the AUC, Cmax, and half-life of sildenafil. Decreases in blood pressure were also observed. No significant effect on the pharmacokinetic parameters of tacrolimus were observed.
Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin therapy before initiating therapy with the lowest dose of sildenafil. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of tamsulosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and tamsulosin.
Tazemetostat: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with tazemetostat is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Telmisartan; Amlodipine: (Moderate) Monitor for additive hypotension if amlodipine is administered concurrently with sildenafil, as both agents act independently to reduce blood pressure. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure (SBP) was 8 mmHg systolic and 7 mmHg diastolic.
Telotristat Ethyl: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with telotristat is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and telotristat is a weak CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Terazosin: (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. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker.
Tezacaftor; Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sildenafil. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; sildenafil is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates, such as sildenafil, can theoretically increase sildenafil exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Tipranavir: (Major) Sildenafil is contraindicated for use with tipranavir when used for pulmonary arterial hypertension (PAH). If used for erectile dysfunction, the dose of sildenafil should not exceed 25 mg in 48 hours with increased monitoring for adverse reactions during times of coadministration. Concurrent use is expected to substantially increase the sildenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Trandolapril; Verapamil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with verapamil is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Tranylcypromine: (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.
Tucatinib: (Major) Coadministration with tucatinib 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 tucatinib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Tucatinib is a strong CYP3A4 inhibitor and sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Vemurafenib: (Moderate) Concomitant use of vemurafenib with sildenafil may increase sildenafil exposure. In vitro studies suggest vemurafenib inhibits CYP3A and CYP2C9. Sildenafil is cleared predominantly by CYP3A (major route) and CYP2C9 (minor route). Use caution and monitor patients for potential sildenafil-related side effects.
Verapamil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with verapamil is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with a moderate CYP3A4 inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A4 inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Vericiguat: (Contraindicated) Use of vericiguat and sildenafil is contraindicated due to the risk of hypotension. Monitor for signs and symptoms of hypotension during transition of therapy. PDE5 inhibitors, including sildenafil, may potentiate the hypotensive effects of vericiguat.
Vigabatrin: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Coadministration of clarithromycin 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 clarithromycin. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Clarithromycin is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Voriconazole: (Major) Coadministration of voriconazole 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 voriconazole. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Voriconazole is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Voxelotor: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with voxelotor is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. In a drug interaction study, coadministration with a moderate CYP3A inhibitor increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Zafirlukast: (Moderate) Concomitant use of zafirlukast with sildenafil may increase sildenafil exposure. In vitro studies suggest zafirlukast inhibits CYP3A (weak) and CYP2C9 (moderate top potent). Sildenafil is cleared predominantly by CYP3A (major route) and CYP2C9 (minor route). Use caution and monitor patients for potential sildenafil-related side effects.

LiQrev Oral Susp: 1mL, 10mg
Revatio/Sildenafil/Sildenafil Citrate Intravenous Inj Sol: 0.8mg, 1mL
Revatio/Sildenafil/Sildenafil Citrate Oral Pwd F/Recon: 1mL, 10mg
Revatio/Sildenafil/Sildenafil Citrate/Viagra Oral Tab: 20mg, 25mg, 50mg, 100mg

Adults

100 mg/day PO for erectile dysfunction; 240 mg/day PO or 30 mg/day IV for pulmonary arterial hypertension.

Geriatric

100 mg/day PO for erectile dysfunction; 240 mg/day PO or 30 mg/day IV for pulmonary arterial hypertension.

Adolescents

Weight 45 kg or more: 40 mg PO 3 times daily.
Weight 21 to 44 kg: 20 mg PO 3 times daily.

Children

Weight 45 kg or more: 40 mg PO 3 times daily.
Weight 21 to 44 kg: 20 mg PO 3 times daily.
Weight 20 kg or less: 10 mg PO 3 times daily.

Infants

Safety and efficacy have not been established. Guidelines recommend 1 mg/kg/dose PO every 8 hours.

Neonates

Safety and efficacy have not been established. Guidelines recommend 1 mg/kg/dose PO every 8 hours and 0.4 mg/kg IV as a loading dose followed by a continuous infusion of 0.067 mg/kg/hour.

Sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cGMP. Cyclic guanosine monophosphate causes smooth muscle relaxation in the corpus cavernosum thereby allowing inflow of blood; the exact mechanism by which cGMP stimulates relaxation of smooth muscles has not been determined. PDE5 is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil enhances the effect of NO by inhibiting PDE5 thereby raising concentrations of cGMP in the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum and, at recommended doses, has no effect in the absence of sexual stimulation. As reported by the manufacturer, the pharmacodynamic response to sildenafil was assessed in eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction. In these studies sexual stimulation resulted in improved erections, as assessed by penile plethysmography, after sildenafil administration compared with placebo. Most studies evaluated the efficacy of sildenafil approximately 60 minutes post dose. The erectile response, as determined by penile plethysmography, generally increased with increasing sildenafil dose and plasma concentration. The time course of effect was examined in one study. The effects of sildenafil were evident for up to 4 hours, but the response was diminished compared to 2 hours.
 
In vitro studies show that sildenafil is selective for PDE5 and its effect is more potent on PDE5 than on other known phosphodiesterases. The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil can also inhibit PDE5 present in esophageal smooth muscle, lung tissue, and brain tissue. Inhibition of PDE5 in lung tissue results in relaxation of pulmonary vascular smooth muscle and subsequently pulmonary vasodilation, thereby making sildenafil an effective agent in treating pulmonary hypertension. Inhibition of PDE5 present in esophageal smooth muscle can cause a marked inhibition of esophageal motility as well as a reduction in lower esophageal sphincter (LES) tone. These effects may be beneficial in certain motor disorders involving the esophagus such as diffuse spasm, nutcracker esophagus, and hypertensive LES. However, the reduction in LES tone can worsen the symptoms of gastroesophageal reflux disease (GERD). Sildenafil is one-tenth as potent for PDE6, an enzyme found in the retina, as it is for PDE5; this lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma concentrations of the drug.

Sildenafil is administered orally or intravenously. The mean steady state volume of distribution (Vss) is 105 L, indicating widespread tissue distribution. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations. Based upon measurements of sildenafil in semen of healthy volunteers 90 minutes after dosing, less than 0.001% of the administered dose may appear in the semen of patients. Sildenafil is predominantly metabolized by hepatic cytochrome P450 (CYP) enzymes. One active metabolite with properties similar to the parent drug has been identified and is formed by N-desmethylation of sildenafil. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil and accounts for about 20% of the pharmacologic effects of sildenafil. However, the ratio of the metabolite to sildenafil is higher in patients with pulmonary arterial hypertension (PAH). The metabolite is further metabolized to inactive compounds. Sildenafil is excreted as metabolites primarily in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Both sildenafil and its active metabolite have terminal half-lives of about 4 hours. Sildenafil concentrations at 24 hours post a single 100 mg oral dose average 2 ng/mL (compared to peak plasma concentrations of approximately 440 ng/mL). While similar pharmacokinetic parameters were observed in healthy volunteers and patients with erectile dysfunction, the average steady-state concentrations were 20% to 50% higher and Cmin levels doubled in patients with PAH compared to healthy volunteers.
 
Affected cytochrome P450 isoenzymes: CYP3A4 and CYP2C9
Sildenafil is metabolized principally by the hepatic cytochrome P450 (CYP) 3A4; CYP2C9 is also involved to a lesser degree. Inhibitors of these isoenzymes may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects. Dosage reductions are recommended for patients receiving potent cytochrome CYP3A4 inhibitors.

Oral Route

Sildenafil is rapidly absorbed after oral administration, with a mean absolute bioavailability of about 41% (25% to 63%). Its pharmacokinetics are dose-proportional over the recommended dose range. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state.
 
Oral Suspension (Liqrev):
When sildenafil is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 53%; the extent of absorption (AUC) is increased by 11%.
 
Oral tablets and oral powder for suspension (Revatio, Viagra):
When sildenafil is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%.

Intravenous Route

A 10 mg IV dose is predicted to provide a pharmacological effect of sildenafil and its N-desmethyl metabolite equivalent to that of a 20 mg PO dose.

Pregnancy

Limited data do not report a clear association with the use of sildenafil and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sildenafil is used during pregnancy. No evidence of teratogenicity or embryofetal toxicity was observed in animal reproduction studies using sildenafil at doses 32- and 65-times the recommended human dose. There are risks to the mother and fetus from untreated pulmonary arterial hypertension.

Limited clinical data preclude a clear determination of the risk of sildenafil to an infant during breast-feeding. Data from a case report describe the presence of sildenafil and its active metabolite in human milk. There is insufficient information on the effects of sildenafil on the breast-fed infant and no information on the effects of sildenafil on milk production.