Spedra

Uses

Spedra is a phosphodiesterase 5 (PDE5) inhibitor used for the treatment of erectile dysfunction

Spedra is also used to associated treatment for these conditions: Erectile Dysfunction

How Spedra works

Spedra inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for the degradation of cGMP in the corpus cavernosum located around the penis. Sexual arousal results in the local release of nitric oxide, which in turn stimulates the enzyme guanylate cyclase to produce cGMP. Elevated levels of cGMP result in local smooth muscle relaxation and increased blood flow to the penis (i.e. an erection).

As PDE5 inhibitors like avanafil require the endogenous release of nitric oxide in order to exert their pharmacologic effect, they have no effect on the user in the absence of sexual stimulation/arousal.

Dosage

Spedra dosage

For most patients, the starting dose is 100 mg taken approximately 30 minutes before sexual activity, on an as needed basis.Spedra may be taken with or without food. Take Spedra no more than once a day.

The dose may be increased to 200 mg or decreased to 50 mg based on efficacy and/or tolerability. Use the lowest dose that provides benefit.

Do not use Spedra with strong CYP3A4 inhibitors. If taking a moderate CYP3A4 inhibitor, the dose should be no more than 50 mg in a 24-hour period. In patients on stable alpha-blocker therapy, the recommended starting dose of Spedra is 50 mg.

Side Effects

Most common adverse reactions (greater than or equal to 2%) include headache, flushing, nasal congestion, nasopharyngitis, and back pain

Toxicity

Experience with avanafil overdose is limited. Single doses of up to 800mg and repeat doses of up to 300mg have been administered - these patients experienced adverse effects similar to those seen at therapeutic doses but with increased incidence and severity. Patients experiencing an overdosage of avanafil should be treated with standard symptomatic and supportive measures. Dialysis is unlikely to be of benefit in cases of overdose as avanafil is highly protein-bound in plasma.

Precaution

Patients should not use Spedra if sexual activity is inadvisable due to cardiovascular status or any other reason.

Use of Spedra with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than 3 units) may lead to hypotension.

Patients should seek emergency treatment if an erection lasts greater than 4 hours.

Patients should stop Spedra and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non Arteritic Ischemic Optic Neuropathy (NAION). Discuss with patients the increased risk of NAION in patients with a history of NAION.

Patients should stop taking Spedra and seek prompt medical attention in the event of sudden decrease or loss of hearing.

Interaction

Spedra can potentiate the hypotensive effect of nitrates, alphablockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase Spedra exposure.

Food Interaction

• Avoid excessive or chronic alcohol consumption. Substantial alcohol consumption (e.g. >3 units) in combination with avanafil may increase the risk of hypotension.
• Take with or without food. High-fat meals slow absorption, but not to a clinically significant extent.

[Moderate] GENERALLY AVOID: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors are used with alcohol, as both are mild systemic vasodilators.

In clinical pharmacology studies, more subjects administered alcohol at a dose of 0.7 g

There were reports of postural dizziness, and orthostatic hypotension was observed in some.

When tadalafil 20 mg was administered with alcohol at a lower dose of 0.6 g

Neither tadalafil nor alcohol affected the plasma concentrations of the other.

Administration of avanafil 200 mg with alcohol at a dose of 0.5 g

The plasma concentrations of alcohol were not affected.

Sildenafil 50 mg and vardenafil 20 mg reportedly did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08% and in healthy volunteers administered alcohol at a dose of 0.5 g

Alcohol and vardenafil plasma levels were not altered when dosed simultaneously.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of avanafil, which is primarily metabolized by CYP450 3A4.

However, the interaction has not been studied.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients taking avanafil should avoid consuming large amounts of alcohol, which may increase the potential for orthostatic signs and symptoms including increase in heart rate, decrease in standing blood pressure, dizziness, and headache.

It may also be appropriate to avoid consuming large amounts of grapefruit juice.

Some authorities advise that grapefruit juice should be avoided within 24 hours prior to taking avanafil.

Spedra Drug Interaction

Major: vardenafil, sildenafilModerate: arginine, metoprolol, metoprololUnknown: 5-hydroxytryptophan, charcoal, umeclidinium / vilanterol, anastrozole, aspirin, ipratropium, amoxicillin / clavulanate, rosuvastatin, sodium iodide, acetaminophen, tiotropium, cyanocobalamin, ascorbic acid, cholecalciferol, menaquinone

Spedra Disease Interaction

Major: cardiovascular disease, renal dysfunctionModerate: priapism, alcoholism, hearing loss, liver disease, retinitis pigmentosa, seizure disorders

Volume of Distribution

The apparent volume of distribution of avanafil is 47 to 83 L.

Elimination Route

Spedra is rapidly absorbed following oral administration (T_max of 30-45 minutes) and appears to have low to moderate oral bioavailability, though formal studies have not been conducted. Administration with a meal results in a mean delay in T_max of 1.12 to 1.25 hours, a 39% mean reduction in C_max, and a negligible effect on AUC.

Half Life

Studies have demonstrated variability in the terminal elimination half-life of avanafil, with estimates ranging between 5 - 17 hours.

Elimination Route

Following oral administration, avanafil is extensively metabolized. Approximately 62% of a given dose is excreted as metabolites in the feces and approximately 21% as metabolites in the urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. Spedra is not indicated for use in women. There are no adequate and well-controlled studies of Spedra in pregnant women.

Contraindication

Administration of Spedra to patients using any form of organic nitrate is contraindicated. Hypersensitivity to any component of the Spedra tablet

Special Warning

Pediatric Use: STENDRA is not indicated for use in pediatric patients. Safety and efficacy in patients below the age of 18 years has not been established.

Geriatric Use: Of the total number of subjects in clinical studies of avanafil, approximately 23% were 65 and over. No overall differences in efficacy and safety were observed between subjects over 65 years of age compared to younger subjects; therefore no dose adjustment is warranted based on age alone. However, a greater sensitivity to medication in some older individuals should be considered.

Renal & hepatic impairment patients: Do not use in patients with severe renal & hepatic impairment

Acute Overdose

Single doses up to 800 mg have been given to healthy subjects, and multiple doses up to 300 mg have been given to patients. In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance because avanafil is highly bound to plasma proteins and is not significantly eliminated in the urine.

Storage Condition

Store at 20-25°C

Innovators Monograph

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