Stendra online in Australia

What is Stendra used for?

Treatment of erectile dysfunction in adult men.

Sexual stimulation is necessary for Spedra to be effective.

Conditions for which this medicine may be prescribed

• Erectile dysfunction

Method of administration and dosage of the drug Stendra

Dose

Use in adult humans.

The recommended dose is 100 mg taken as needed, approximately 15 to 30 minutes before sexual activity (see section Pharmacodynamic properties). Depending on individual efficacy and tolerance, the dose can be increased to a maximum of 200 mg or decreased to 50 mg. The maximum recommended frequency of taking the medicine is once a day. Sexual stimulation is required to elicit a response to treatment.

Special populations

Elderly (65 years of age or older)

No dosage adjustment is necessary in elderly patients. Limited data are available for patients age 70 and older.

Renal insufficiency

No dose adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml / min). Spedra is contraindicated in patients with severe renal impairment (creatinine clearance minus 30 ml / min) (see sections Contraindications and pharmacokinetic properties). In patients with mild to moderate renal impairment (creatinine clearance

≥30 ml / min, but less than 80 ml / min), which were included in the phase 3 studies, a decrease in efficacy was observed, compared to that observed in patients with normal renal function.

Liver failure

Spedra is contraindicated in patients with severe hepatic impairment (Child Pugh class C) (see Contraindications and Pharmacokinetic Properties). Patients with mild to moderate hepatic impairment (Child Pugh class A or B) should start treatment with the minimum effective dose and adjust the dose according to tolerance.

Use in humans with diabetes.

No dosage adjustment is necessary in diabetic patients.

Pediatric population

There is no relevant use of Spedra in the pediatric population for the indication of erectile dysfunction.

Use in patients taking other medications.

Concomitant use of CYP3A4 inhibitors

Co-administration of avanafil with strong CYP3A4 inhibitors (including the following: ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, and telithromycin) is contraindicated (see Contraindications, Warnings, and Precautions for use and interactions with others drugs and other forms of interaction).

In patients receiving concomitant therapy with moderate CYP3A4 inhibitors (including the following: erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil), the maximum recommended dose of avanafil should not exceed 100 mg, with an interval of at least 48 hours between doses (see section Interactions with other medications and other forms of interaction).

Administration form

Oral use. If Spedra is taken with food, the onset of activity may be delayed compared to taking it on an empty stomach (see Pharmacokinetic properties section).

Possible side effects of Stendra

• Flu
• Rhinopharyngitis
• Seasonal allergy
• Gout
• Insomnia
• Premature ejaculation
• Inappropriate affection
• Headache
• Vertigo
• Drowsiness
• Sinusitis
• Psychomotor hyperactivity
• Blurry vision
• Palpitation
• Angina pectoris
• Tachycardia
• Redness
• Hot flushes
• Hypertension
• Nasal congestion
• Sinus congestion
• Dyspnea on exertion
• Rhinorrhea
• Congestion of the upper respiratory tract.
• Epistaxis
• Dyspepsia
• Sickness
• Vomiting
• Gastric discomfort
• Dry mouth
• Gastritis
• Lower abdominal pain
• Diarrhea
• Acne
• Back pain
• Muscular stiffness
• Pain in the side
• Myalgia
• Muscle spasm
• Pollakiuria
• Penile disorders
• Spontaneous erection of the penis
• Genital itching
• Tired
• Asthenia
• Chest pain
• Flu symptoms
• Peripheral edema
• Increased liver enzymes.
• Abnormal electrocardiogram
• Incrise of cardiac frecuency
• Increased blood pressure
• Blood in the urine
• Heart murmur
• Specific increase in prostate antigen
• Get fat
• Increased blood bilirubin.
• Increased blood creatinine.
• Increased body temperature
• Non-arteritic anterior ischemic optic neuropathy
• Sudden hearing loss
• Priapism
• Hematospermia
• Bleeding from the penis
• Hypotension
• Low blood pressure

Show more Security profile summary

The safety profile of Spedra was evaluated in 2,566 subjects exposed to avanafil during the clinical development program. The most common side effects reported in clinical studies were headache, redness, nasal and sinus congestion, and back pain. In general, adverse events and adverse reactions in subjects treated with avanafil were more common in subjects with a body mass index (BMI) less than 25 (subjects with normal BMI).

In the long-term clinical study, the percentage of patients experiencing adverse effects decreased with increasing duration of exposure.

Summary table of adverse reactions

The table below presents the undesirable effects observed in placebo-controlled studies, according to the MedDRA convention regarding frequency: very common (≥ 1/10), common (≥ 1/100 to minus 1/10), uncommon (≥ 1 / 1,000 to minus 1/100), rare (≥ 1 / 10,000 to minus 1 / 1,000), very rare

(minus 1 / 10,000) and frequency unknown (cannot be estimated from the available data). In each frequency group, the undesirable effects are presented in decreasing order of severity.

Description of some of the side effects observed with other PDE5 inhibitors

Non-arteritic anterior ischemic optic neuropathy (NAION) and sudden hearing loss have been reported in a small number of post-marketing cases and in clinical studies with other PDE5 inhibitors. No cases were reported during the avanafil clinical studies (see section 4.4).

Priapism has been reported in some clinical and post-marketing studies with other PDE5 inhibitors. No cases were reported during the avanafil clinical studies.

Cases of hematuria, hematospermia, and bleeding from the penis have been reported in some post-marketing cases and in clinical studies with other PDE5 inhibitors.

Post-marketing hypotension with other PDE5 inhibitors has been reported and dizziness, a symptom frequently due to low blood pressure, has been reported in clinical studies with avanafil (see section 4.5). other medications and other forms of interactions).

Notification of suspected adverse reactions.

Notification of suspected adverse reactions after authorization of the medicinal product is important. Allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals are asked to report any suspected adverse reactions through the national reporting system; see Annex V.

Contraindications: when not to use this medicine?

• Hypersensitivity to Avanafil
• Myocardial infarction in the previous six months
• Stroke in the last 6 months
• Severe cardiac arrhythmia
• Hypotension minus 90/50 mmHg
• High blood pressure plus 170/100 mmHg
• Unstable angina
• Angina that manifests during sex
• NYHA class II-IV heart failure
• Severe liver failure
• Severe kidney failure (Clcr minus 30 ml / min)
• Loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy
• Hereditary degenerative retinopathy
• Under 18 years old

Show more Hypersensitivity to the active substance or to any of the excipients included in the Composition section.

Patients using any form of nitrate or nitric oxide donor (such as amyl nitrite) (see section Interactions with other medicinal products and other forms of interaction).

Co-administration of phosphodiesterase type 5 (PDE5) inhibitors, including avanafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated, as it can cause episodes of symptomatic hypotension (see section Interactions with other drugs and other forms of interaction) .

Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease before prescribing Spedra.

The use of avanafil is contraindicated in:

• patients who have had a life-threatening myocardial infarction, stroke, or arrhythmia in the past 6 months;
• patients with hypotension at rest (blood pressure minus 90/50 mmHg) or hypertension (blood pressure plus 170/100 mmHg);
• patients with unstable angina, angina during intercourse or congestive heart failure class 2 or higher according to the NYHA (New York Heart Association) classification.
• Patients with severe hepatic impairment (Child Pugh C).

Patients with severe renal impairment (creatinine clearance minus 30 ml / min).

Patients with loss of vision in one eye due to anterior non-arteritic ischemic optic neuropathy (NAIAN), regardless of whether or not this episode was associated with previous exposure to a PDE5 inhibitor (see section 4.4). 'job).

Patients with known inherited degenerative disorders of the retina.

• Patients using strong CYP3A4 inhibitors (including the following: ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, and telithromycin) (see sections 4.2 and 4.4) use and interaction with other medicinal products and other forms of interaction ).

Presentation of this medicine

PVC / PCTFE / Aluminum blisters in pre-cut unit doses in boxes of 4x1 tablets.

Appearance and shape

Tablet.

Pale yellow oval tablets with "200" debossed on one side.

Stendra: its other forms

• Stendra 50 mg, tablet, box of 4 pre-cut packets of 1
• Stendra 50 mg, tablet, box of 8 pre-cut packets of 1
• Stendra 100 mg, tablet, box of 2 pre-cut packs of 1
• Stendra 100 mg, tablet, box of 4 pre-cut packets of 1
• Stendra 100 mg, tablet, box of 8 pre-cut packets of 1
• Stendra 100 mg, tablet, box of 12 pre-cut packets of 1
• Stendra 200 mg, tablet, box of 8 pre-cut packets of 1
• Stendra 200 mg, tablet, box of 12 pre-cut packets of 1

View all forms of the drugComposition of the drug Stendra

* per unit dose Active ingredients: Avanafil Excipients: mannitol, fumaric acid, hydroxypropylcellulose, low-substitution hydroxypropylcellulose, calcium carbonate, magnesium stearate, yellow iron oxide No excipients with known effect? not present in the composition of this medicine

Effects on ability to drive and use machines

Spedra has a minor influence on the ability to drive and use machines. Since dizziness and blurred vision have been reported in clinical studies with avanafil, patients should know how they react after taking Spedra before driving or using machines.

Warnings and precautions for use

• Obstacle to expulsion of the left ventricle
• Priapism
• Anatomic malformation of the penis.
• Predisposition to priapism.
• Visual abnormality
• Hemorrhagic disorder
• Active gastroduodenal ulcer
• Hearing loss
• Sudden hearing loss
• Alcohol consumption

See more A medical history study and physical examination should be performed to diagnose erectile dysfunction and determine possible underlying causes, before considering drug treatment.

Cardiovascular condition

Before initiating any treatment for erectile dysfunction, physicians should examine the cardiovascular status of their patients, as any sexual activity involves cardiac risk (see section 4.3). Avanafil has vasodilatory properties that result in slight and transient reductions in blood pressure (see section Interactions with other drugs and other forms of interaction) and, therefore, enhances the hypotensive effect of nitrates (see section Contraindications). Patients with obstruction of the left ventricular ejection pathway, such as aortic stenosis or idiopathic hypertrophic subaortic stenosis, may be sensitive to the action of vasodilators, including PDE5 inhibitors.

Priapism

Patients with erections of 4 hours or more (priapism) should be advised to seek medical help immediately. If priapism is not treated right away, it can lead to damage to penile tissue and permanent impotence. Avanafil should be used with caution in patients with anatomical deformation of the penis (such as angulation, sclerosis of the corpora cavernosa, or Peyronie's disease), or in patients with conditions that may predispose them to priapism (such as sickle cell disease, multiple myeloma, or leukemia).

Vision problems

Vision problems and cases of non-arteritic anterior ischemic optic neuropathy (NAION) have been reported after the use of other PDE5 inhibitors. The patient should be advised that, in the event of a sudden visual defect, he should stop taking Spedra and consult a doctor immediately (see section 4.3).

Effect on bleeding

In vitro studies with human platelets indicate that PDE5 inhibitors do not themselves act on platelet aggregation, but at supra-therapeutic doses, potentiate the antiplatelet effect of the nitric oxide donor, sodium nitroprusside. In humans, PDE5 inhibitors do not appear to change bleeding time, alone or in combination with acetylsalicylic acid.

There is no safety information regarding the administration of avanafil to patients with bleeding disorders or active peptic ulcer. Therefore, avanafil should only be administered to these patients after careful evaluation of the benefit / risk balance.

Sudden decrease or loss of hearing.

Patients should be advised to stop taking PDE5 inhibitors, including avanafil, and to seek medical attention immediately if they experience sudden decrease or loss of hearing. These events have been reported, which may be accompanied by tinnitus and dizziness.

in temporal relation with the taking of PDE5 inhibitors. It is not possible to determine whether these events are directly related to the use of PDE5 inhibitors or to other factors.

Concomitant use of alpha blockers

Concomitant use of alpha-blockers and avanafil may cause symptomatic hypotension in some patients due to additional vasodilatory effects (see section Interactions with other medicinal products and other forms of interaction). The following situations should be considered:

• Patients should be stabilized with alpha-blocker therapy before starting Spedra. Patients with hemodynamic instability under a used alpha blocker are only at risk for symptomatic hypotension when avanafil is used concomitantly.
• In patients who are stabilized on treatment with an alpha-blocker, avanafil should be started with the lowest dose of 50 mg.
• In patients already taking an optimized dose of Spedra, treatment with an alpha-blocker should be started with the lowest dose. A gradual increase in the alpha-blocker dose may be associated with a greater drop in blood pressure while taking avanafil.
• The safety of using avanafil in combination with alpha-blockers may be affected by other variables, including intravascular volume depletion and other antihypertensive drugs.

Concomitant use of CYP3A4 inhibitors

Co-administration of avanafil with strong CYP3A4 inhibitors, such as ketoconazole or ritonavir, is contraindicated (see sections 4.2 and 4.3, Interactions with other medicinal products and other forms of interactions).

Concomitant use of other treatments for erectile dysfunction.

The safety and efficacy of combinations of Spedra with other PDE5 inhibitors or other treatments for erectile dysfunction have not been studied. Patients should be advised not to take Spedra in combination with this type of treatment.

Concomitant use of alcohol.

Consumption of alcohol in combination with avanafil may increase the possibility of symptomatic hypotension (see section Interactions with other medicinal products and other forms of interaction). Patients should be advised that taking alcohol and avanafil together may increase the likelihood of developing low blood pressure, dizziness, or fainting. Doctors should also advise patients on what to do if they experience postural hypotension symptoms.

• Populations not studied. Avanafil has not been evaluated in patients with erectile dysfunction due to spinal cord injury or other neurological conditions, or in subjects with severe renal or hepatic impairment.

Mechanism of action: how does it work?

Pharmacotherapeutic group: urological drugs; Medicines used in erectile dysfunction. ATC code: G04BE10.

Mechanism of action

Avanafil is a highly selective and potent reversible inhibitor of phosphodiesterase type 5 (PDE5) specific for cyclic guanosine monophosphate (cGMP). When sexual stimulation causes local nitric oxide release, PDE5 inhibition by avanafil leads to an increase in the level of cGMP in the corpora cavernosa of the penis. This results in a relaxation of the smooth muscles and an entry of blood into the tissues of the penis, thus producing an erection. Avanafil has no effect in the absence of sexual stimulation.

Pharmacodynamic effects

In vitro studies have shown that avanafil is highly selective for PDE5. Its effect is more powerful in PDE5 than in other known phosphodiesterases (more than 100 times than in PDE6; more than 1,000 times than in PDE4, PDE8 and PDE10; more than 5,000 times than in PDE2 and PDE7; more than 10,000 times than in PDE1 , PDE3, PDE9 and PDE11). The effect of avanafil is more than 100 times stronger in PDE5 than in PDE6, which is present in the retina and is responsible for phototransduction. The selectivity of avanafil for PDE5 is approximately 20,000 times greater than for PDE3, an enzyme present in the heart and blood vessels that plays an important role because it intervenes in the control of cardiac contractility.

In a penile plethysmography (RigiScan) study, avanafil 200 mg produced erections considered sufficient for penetration (60% stiffness with RigiScan) in certain men as soon as 20 minutes after taking the product and the overall response to avanafil in these subjects was statistically significant compared to placebo, in a time interval of 20-40 minutes.

Clinical efficacy and safety

In clinical studies, avanafil has been evaluated for its effect on the ability of men with erectile dysfunction (ED) to achieve and maintain an erection sufficient for satisfactory sexual activity. Avanafil has been evaluated in 4 randomized, double-blind, placebo-controlled studies in parallel groups lasting up to 3 months, in the general population of ED patients, in patients with diabetes mellitus. type 1 or type 2 and ED, as well as in patients with ED after a radical prostatectomy with bilateral nerve sparing. The fourth study evaluated the onset of action of avanafil for two doses (100 and 200 mg), in terms of the proportion of sexual attempts per patient that resulted in satisfactory sexual relations. A total of 1774 patients received avanafil, which was taken on demand at doses of 50 mg (one study), 100 mg and 200 mg (four studies), respectively. Patients were asked to take a dose of the study medication approximately 30 minutes before sexual activity began. In the fourth study, patients were encouraged to attempt sexual intercourse approximately 15 minutes after taking the product, to assess the onset of the erogenous effect of avanafil, at a dose of 100 mg and 200 mg on request.

In addition, a subgroup of patients was included in an open-label study, in which

493 patients received avanafil for at least 6 months and 153 patients for at least 12 months. Initially, patients received an avanafil dose of 100 mg and, at any time during the study, they may request that their avanafil dose be increased to 200 mg or reduced to 50 mg depending on their individual response to treatment.

In all studies, statistically significant improvement was seen for all primary efficacy endpoints for all three doses of avanafil compared to placebo. These differences were maintained during long-term treatment (studies in the general population of patients with erectile dysfunction, in patients with diabetes and erectile dysfunction, and in men with erectile dysfunction after radical prostatectomy with bilateral nerve sparing, and in one study). open extension).

In the general population of ED patients, the mean percentage of attempts resulting in successful sexual intercourse was approximately 47%, 58%, and 59%, respectively, for the avanafil 50 mg, 100 mg, and 200 mg groups. , versus approximately 28% for placebo.

In men with type 1 or type 2 diabetes, the average percentage of successful sexual attempts was approximately 34% and 40%, respectively, for the 100 mg groups. and 200 mg of avanafil, compared to approximately 21% for the placebo group.

In men with ED after a bilateral nerve sparing bilateral prostatectomy, the average percentage of attempts resulting in successful sexual intercourse was approximately 23% and 26%, respectively, for the 100 mg and 200 mg groups. mg of avanafil, versus approximately 9% for placebo.

In the onset of action study, avanafil demonstrated a statistically significant increase in the primary efficacy end point (p average percentage of successful sexual intercourse per patient versus time after dose administration - SEP3) versus placebo, having resulted in ratios Sexual satisfaction in 24.71% of the attempts for the 100 mg dose and 28.18% for the 200 mg dose approximately 15 minutes after taking the product, compared to 13.78% for the placebo.

For all pivotal studies with avanafil, the percentage of successful intercourse attempts was significantly higher for all avanafil doses compared to placebo, for attempts at all time intervals studied after taking the product.

Pediatric population

The Australian Medicines Agency has waived the obligation to report the results of studies with Spedra in all subgroups of the pediatric population in the indication of erectile dysfunction (see section 4.2 information on pediatric use).

Interactions: do not take this medicine with ..

Potential risk of pharmacodynamic interactions with avanafil

Nitro derivatives

Avanafil has been shown to increase the hypotensive effects of nitrates, compared to placebo, in healthy subjects. This action is believed to be the result of the combined effects of nitrates and avanafil on the nitric oxide / cGMP pathway. Therefore, administration of avanafil to patients using any form of nitrate or nitric oxide donor (such as amyl nitrite) is contraindicated. In a patient who has taken avanafil in the past 12 hours, in whom nitrate administration is considered medically necessary in the event of a life-threatening result, the probability of a significant and potentially dangerous drop in blood pressure is increased in these circumstances. Nitrates should only be administered under strict medical supervision, with adequate hemodynamic control (see section Contraindications).

Medications that reduce systemic blood pressure.

Avanafil is a vasodilator and can lower systemic blood pressure. If Spedra is used in combination with another medicine that reduces systemic blood pressure, the additive effects may cause symptomatic hypotension (for example, dizziness, drunkenness, fainting, or fainting). In phase III clinical studies, no "hypotensive" events have occurred, but occasional episodes of "dizziness" have been observed (see section 4.8). One episode of "syncope" was observed in the placebo group and one episode in the avanafil 100mg group in phase III clinical studies.

Patients with obstruction of the left ventricular ejection pathway (eg, aortic stenosis or idiopathic hypertrophic subaortic stenosis) and those with severe insufficiency of autonomous control of blood pressure may be particularly susceptible to actions by vasodilators, including avanafil. (see section 4.4).

Alpha blockers

Hemodynamic interactions with doxazosin and tamsulosin were studied in healthy subjects in a two-phase crossover study. In patients receiving stable doxazosin therapy, the mean maximum decreases, the placebo-inferred effect, of systolic blood pressure when standing and lying down after taking avanafil were respectively

2.5 mmHg and 6.0 mmHg. Overall, after taking avanafil, in 7/24 subjects, the values or the decrease in blood pressure compared to the initial value were of potential clinical importance (see section Warnings and precautions for use).

In patients who received stable treatment with tamsulosin, the mean maximum decreases, the effect inferred by placebo, of the systolic blood pressure when standing and lying down after taking avanafil were 3.6 mmHg and 3.1 mmHg respectively and 5/24 subjects the values o Decreases in blood pressure compared to baseline were of potential clinical importance (see Warnings and Precautions for Use section).

Antihypertensives other than alpha-blockers

A clinical study was conducted to evaluate the effect of avanafil on potentiating the blood pressure lowering effects of certain antihypertensive drugs (amlodipine and enalapril). The results showed a maximum decrease in blood pressure when reclined from 2/3 mmHg with enalapril compared to placebo and 1 / -1 mmHg with amlodipine, when co-administered with avanafil. There was a statistically significant difference in the maximum decrease in baseline blood pressure at bedtime, only with enalapril and avanafil, which returned to baseline 4 hours later taking the dose of avanafil. In both cohorts, one subject experienced a decrease in blood pressure without symptoms of hypotension, which resolved within one hour after onset.

Avanafil had no effect on the pharmacokinetics of amlodipine, but amlodipine reduced the maximum and total exposure to avanafil by 28% and 60%, respectively (see section 4.4). care and precautions for use).

Alcohol

Drinking alcohol in combination with avanafil may increase the possibility of symptomatic hypotension. In a single-dose, three-way crossover study evaluating healthy subjects, the mean maximum decrease in diastolic blood pressure was significantly greater after administration of avanafil in combination with alcohol than after taking avanafil alone (3.2 mmHg) or alcohol alone. (5.0 mmHg) (see Warnings and Precautions for Use section).

Other treatments for erectile dysfunction

The safety and efficacy of combinations of avanafil with other PDE5 inhibitors or other treatments for erectile dysfunction have not been studied (see section 4.4).

Effects of other substances on avanafil

Avanafil is a CYP3A4 substrate and is primarily metabolized by this route. Studies have shown that medicinal products that inhibit CYP3A4 can increase exposure to avanafil (see section 4.2).

CYP3A4 inhibitors

Ketoconazole (400 mg daily), a highly potent and selective CYP3A4 inhibitor, increased Avanafil Cmax by 50 mg as a single dose, as well as exposure to this dose (AUC) by one factor 3 and 14 and extended the Avanafil half-life in approximately 9 hours. Ritonavir (600 mg twice daily), a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9, increased Avanafil Cmax by 50 mg as a single dose, as well as exposure to that dose (AUC), respectively by a factor of 2 and 13 and prolonged the half-life of avanafil by approximately 9 hours. For other potent CYP3A4 inhibitors (eg, Itraconazole, Voriconazole, Clarithromycin, Nefazodone, Saquinavir, Nelfinavir, Indinavir, Atazanavir, and Telithromycin), similar effects can be expected. . As a result, co-administration of avanafil with strong CYP3A4 inhibitors is contraindicated (see sections 4.2 and 4.4, Warnings and precautions for use).

Erythromycin (500 mg twice daily), a moderate CYP3A4 inhibitor, increased Avanafil Cmax by 200 mg as a single dose, as well as exposure to this dose (AUC), respectively, by one factor 2 and 3 and prolonged the half-life of avanafil in approximately 8 hours. Similar moderate effects can be expected for other moderate CYP3A4 inhibitors (eg amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil). Accordingly, the maximum recommended dose of avanafil is 100 mg, not to be exceeded per 48-hour period, for patients taking concomitant moderate CYP3A4 inhibitors (see section 4.2).

Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice, are likely to increase exposure to avanafil. Patients should be advised to avoid grapefruit juice for 24 hours before taking avanafil.

CYP3A4 substrate

Amlodipine (5 mg daily) increased Avanafil Cmax by 200 mg as a single dose, as well as exposure to this dose (AUC), by approximately 28% and 60%, respectively. These changes in exposure are not considered clinically significant. A single dose of avanafil had no effect on amlodipine plasma levels.

Although the specific interactions of avanafil with rivaroxaban and apixaban (both CYP3A4 substrates) have not been studied, no interaction is expected.

Cytochrome P450 inducers

The potential effect of CYP inducers, in particular CYP3A4 inducers (eg, Bosentan, carbamazepine, efavirenz, phenobarbital, and rifampicin) on the pharmacokinetics and efficacy of avanafil, has not been evaluated. The concomitant use of avanafil and a CYP inducer is not recommended as it may decrease the effectiveness of avanafil.

Effects of avanafil on other medications.

Cytochrome P450 inhibition

In vitro studies with human liver microsomes, avanafil has shown negligible potential for drug interactions with CYP1A1 / 2, 2A6, 2B6, and 2E1. Furthermore, the metabolites of avanafil (M4, M16 and M27) have also shown minimal inhibition of CYP 1A1 / 2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Based on these results, avanafil is not expected to have a significant effect on other drugs metabolized by these enzymes.

To the extent that in vitro data has identified potential interactions between avanafil and CYP 2C19, 2C8 / 9, 2D6 and 3A4, additional clinical studies have been used in which

Omeprazole, rosiglitazone and desipramine did not reveal clinically important interactions with CYP 2C19, 2C8 / 9 and 2D6.

Cytochrome P450 induction

Evaluation of the potential induction of CYP1A2, CYP2B6 and CYP3A4 by avanafil in primary human hepatocytes in vitro did not reveal any potential interactions at clinically relevant concentrations.

Carriers

In vitro results have shown that avanafil has a modest potential to act as a P-gp substrate and P-gp inhibitor with digoxin as a substrate at concentrations below the calculated intestinal concentration. The potential for avanafil interference with the transport of other drugs through P-gp is unknown.

Based on in vitro data, at clinically relevant concentrations, avanafil could be a BCRP inhibitor.

At clinically relevant concentrations, avanafil is not an inhibitor of OATP1B1, OATP1B3, OCT1, OCT2, OAT1, OAT3, and BSEP.

The effect of avanafil on other carriers is unknown.

Riociguat

Preclinical studies have shown a further drop in systemic blood pressure when PDE5 inhibitors are combined with riociguat. In clinical studies, riociguat has shown an increase in the hypotensive effect of PDE5 inhibitors. No clinical benefit of the combination has been demonstrated in the study population. Concomitant use of riociguat and PDE5 inhibitors, including avanafil, is contraindicated (see section 4.3).

Incompatibilities

Aimlessly.

How to react in case of overdose?

A single dose of up to 800 mg of avanafil has been administered to healthy subjects and multiple daily doses of up to 300 mg have been administered to patients. Side effects were similar to those seen at lower doses, but the incidence of occurrence and severity of side effects increased.

In case of overdose, usual symptomatic treatment measures should be implemented if necessary. Renal dialysis should not accelerate the elimination of avanafil, since it is strongly bound to plasma proteins and is not eliminated in the urine.

Stendra: pregnancy, lactation and fertility

Pregnancy

Spedra is not indicated for use in women.

There are no data on the use of avanafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonic / fetal development, delivery or postnatal development (see section Preclinical safety data).

Breastfeeding

There are no data on the use of avanafil during lactation.

Fertility

There was no effect on sperm motility or morphology after taking single 200-mg oral doses of avanafil in healthy volunteers.

In a clinical trial in healthy volunteers and adult men with mild erectile dysfunction, daily administration of oral doses of avanafil 100 mg over a period of 26 weeks was not associated with any adverse effect on concentration, number, mobility, or morphology. of sperm.

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