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Avanafil
Indications, Uses, Dosage, Drugs Interactions, Side effects
Avanafil
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Phosphodiesterase-5 (PDE5) inhibitors, Therapy Class:
Impotence agents, Approved Countries
India, the United States, Canada, the United Kingdom, Italy, Australia, Germany, France, Japan and Spain.
Avanafil is an impotence agents belonging to the pharmacological class of Phosphodiesterase-5 Enzyme Inhibitors (PDE5).
Avanafil is approved by the FDA for treating erectile dysfunction (the inability to keep an erection firm enough for sexual activity) in men.
Avanafil is well absorbed through the gut, taking about 31 hours for peak plasma levels ([R]-enantiomer). It binds significantly to plasma proteins (96%), undergoes liver metabolism, and is eliminated via urine and faeces.
The most common side effects of Avanafil include headache, stuffy or runny nose, flushing, sore throat, and back pain.
Avanafil is available in the form of oral tablets.
The molecule is available in India, the United States, Canada, the United Kingdom, Italy, Australia, Germany, France, Japan and Spain.
Avanafil is an impotence agent belonging to the pharmacological class of Phosphodiesterase-5 Enzyme Inhibitors (PDE5).
Avanafil prevents the breakdown of cGMP in the corpus cavernosum, which is found surrounding the penis, by inhibiting phosphodiesterase type 5 (PDE5), which is specific to cGMP. Local nitric oxide production during sexual excitement triggers the enzyme guanylate cyclase, which then produces cGMP. An erection is the consequence of increased blood flow to the penis and local smooth muscle relaxation caused by elevated levels of cGMP.
In the lack of sexual excitement or arousal, PDE5 inhibitors such as Avanafil have no impact on the person taking them since they depend on the endogenous release of nitric oxide to have their pharmacologic effect.
The data duration of Avanafil action is approximately 4 to 5 hours after administration.
The onset of Avanafil action typically occurs within 15 to 30 minutes after oral administration.
The Data of Cmax of Avanafil occurs within 30 to 45 minutes after oral administration.
The time to reach maximum concentration (Tmax) ranges from 30 to 45 minutes after ingestion.
Avanafil is available in the form of oral tablets.
Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.
As the physician recommends, take the medication orally once daily; it can be taken with or without food as directed.
Avanafil can be used for the following health conditions:
- Erectile dysfunction (impotence) in adult men by increasing blood flow to the penis during sex stimulation, which facilitates the development and maintenance of an erection.
- In some circumstances, it may also be used off-label to treat other disorders like pulmonary hypertension, where improved blood flow may be beneficial.
In Erectile dysfunction
For males with erectile dysfunction (ED), Avanafil improves erectile function and has therapeutic effects. It increases blood flow to the penile tissue, which helps to sustain and facilitate erections during intercourse. This drug acts quickly to boost sexual performance; effects usually show up 15 to 30 minutes after administration. Its effectiveness resides in its ability to maximize positive benefits while reducing reported adverse effects, providing men with a dependable and secure means of treating ED and gaining intimacy and self-assurance.
- Erectile Dysfunction (ED): To manage erectile dysfunction in men, aiding in achieving and maintaining erections during sexual activity by improving blood flow to the penis.
- Sexual Performance Enhancement: To enhance erections and the overall quality of the sexual experience by increasing blood flow to the genital area.
- Pulmonary Hypertension (Off-label): In some cases, Avanafil might be explored off-label for treating pulmonary hypertension due to its potential to improve blood flow in certain conditions affecting the pulmonary arteries.
Orally: Avanafil is typically taken orally as a single-dose tablet, and it is advised to be taken once daily with or without food and usually taken 15 to 30 minutes before anticipated sexual activity. When using Avanafil, avoid grapefruit and grapefruit juice since this may raise your risk of experiencing side effects. The dosage can be adjusted from 50 milligrams to 200 mg once daily as needed, depending on each individual's response and tolerance. Consumers must follow the recommended dosages and directions for the medication to be safe and effective.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Tablet: 50mg, 100mg, 200mg
Avanafil is available in the form of oral tablets.
Dose Adjustment in Adult Patients:
Erectile Dysfunction
100 mg PO at first, up to 15 minutes before having a sexual activity; no more than one dosage each day.
The dose can be lowered to 50 mg, taken approximately 30 minutes before sexual activity, or raised to 200 mg, taken as early as 15 minutes before sexual activity, depending on each person's efficacy and tolerance.
Use the lowest effective dose.
Dosage Modifications
When taking potent CYP3A4 inhibitors or nitrates together: Not recommended
When taking mild CYP3A4 inhibitors together, dosage should not exceed 50 mg every 24 hours.
When starting coadministration with stable alpha-blocker therapy, start at 50 mg every 24 hours.
While taking Avanafil, it is advised to Consume alcohol in moderation as too much of it might exacerbate adverse effects such as headaches, dizziness, and reductions in blood pressure. Avoid grapefruit and its juice, which may interact with Avanafil and increase its negative effects. A well-balanced diet full of fruits, whole grains, vegetables, and lean meats enhances general health and may increase the efficiency of prescription drugs. To avoid delayed onset, avoid eating large, high-fat meals before taking Avanafil. For safe and appropriate treatment, inform medical professionals about allergies, prescriptions, and preexisting health issues before using Avanafil.
The dietary restriction should be individualized as per patient requirements.
Avanafil may be contraindicated in the following conditions: -
- Anyone who has previously experienced hypersensitivity to any of the product's constituents.
- Soluble guanylate cyclase (sGC) stimulators (e.g., riociguat or vericiguat); concomitant use can cause hypotension.
- It enhances nitrate-induced hypotensive effects and is contraindicated when used alongside any form of organic nitrates.
- Patients with underlying cardiovascular disorders may be at risk for cardiovascular problems when engaging in sexual activity.
- Patients suffering from idiopathic hypertrophic subaortic stenosis or aortic stenosis, for example, should be closely observed.
- When taking moderate CYP3A4 inhibitors with Avanafil concurrently, the dose shouldn't go over 50 mg/24 hours.
- When starting therapy in conjunction with hypertension drugs such as alpha-blockers, start with 50 mg/24 hours.
- Patients with some medical issues, such as sickle cell anaemia, multiple myeloma, or leukaemia, are more susceptible to experiencing priapism.
- Alcohol consumption may raise the risk of orthostatic hypotension, elevate heart rate, and produce headaches and dizziness.
- If abrupt blindness occurs in one or both eyes, stop the treatment (may indicate non-arteritic anterior ischemic optic neuropathy).
- Safety and effectiveness have not been proven in patients with inherited retinal diseases, such as retinitis pigmentosa (usage not recommended).
- It is possible to experience sudden hearing loss; if tinnitus symptoms appear, stop therapy.
Alcohol Warning
It is unsafe to consume Avanafil with alcohol.
Breast Feeding Warning
It is not recommended for use during breastfeeding.
Pregnancy Warning
It is not recommended for use during pregnancy.
Food Warning
Avoid grapefruit and high-fat-containing meals.
The adverse reactions related to Avanafil can be categorized as:-
- Common Adverse Effects: Headache, flushing, nasal congestion, back pain, and indigestion.
- Less Common Adverse Effects: Dizziness, blurred vision, muscle pain, and changes in blood pressure.
- Rare Adverse Effects: Severe allergic reactions, prolonged or painful erections (priapism), and sudden loss of vision or hearing.
Reports from postmarketing
Cardiovascular and cerebrovascular conditions: Myocardial infarction, sudden cardiac death, cerebrovascular accident, and subarachnoid hemorrhage.
Nervous: Temporary general amnesia
Ophthalmologic: impairment of vision, vitreous detachment
Otologic: Sudden reduction or deafness
The clinically relevant drug interactions of Avanafil are briefly summarized here.
- Drug Interactions: Before taking Avanafil, inform your doctor if using HIV/AIDS, antifungals, antibiotics, antiarrhythmics, anticonvulsants, antiemetics, calcium-channel blockers, other erectile dysfunction medications, or drugs for pulmonary hypertension like riociguat.
- Drug-Food Interactions: Grapefruit juice may interact with Avanafil. Hence, refrain from consuming grapefruit juice 24 hours before taking Avanafil.
- Drug-Disease Interactions: Avoid taking Avanafil if you have a serious heart problem, uncontrolled low or high blood pressure, severe kidney or liver issues, vision loss in one eye due to insufficient blood supply, angina or chest pain during sexual activity, a recent stroke or heart attack within the past six months, or certain hereditary eye conditions like retinitis pigmentosa. Notify your doctor about priapism, bleeding disorders, active peptic ulcers, heart complications, or any physical condition affecting penis shape, such as Peyronie's disease.
The common side effects of Avanafil include:
- Headache
- Flushing: a sensation of warmth in the neck, trunk, ears, and face
- Nasal congestion (stuffy nose)
- Nasopharyngitis is an inflammation of the nasal passages and throat.
- Back pain
- Pregnancy
Pregnancy Category C (FDA): Use caution if the benefits outweigh the risks.
It is not indicated for women.
Avanafil use in pregnancy has not been studied in humans. Hence, no data suggests the danger of the medication harming development.
When total Avanafil was administered orally during organogenesis at exposures of about 8 and 6 times, respectively, the Maximum Recommended Human Dose (MRHD) of 200 mg based on AUC, no harmful developmental outcomes were seen in animal reproduction studies performed in pregnant rats and rabbits.
- Nursing Mothers
Lactating women are not advised to use Avanafil.
The effects of Avanafil and/or its metabolites on the breastfed child, the production of milk, and its presence in human or animal milk are all unknown.
- Pediatric Use
As per the FDA, safety and effectiveness in the pediatric population have not been established.
- Females and Males of Reproductive Potential
Infertility
Studies assessing the effects of Avanafil on male fertility have not been established.
Rats were shown to have reduced fertility, aberrant sperm motility and morphology, and modified oestrous cycles, according to research on animals. After a nine-week drug-free interval, the anomalous sperm results were reversible.
- Geriatric Use
The safety and efficacy of Avanafil in geriatric patients have yet to be extensively studied.
Older men (≥ 65 years old)
Dose adjustments are not required in older patients. Limited data are available in older patients aged 70 years or above.
Dose Adjustment in Kidney Impairment Patients:
Moderate to mild (CrCl < 30 mL/min): No need to modify the dosage.
Severe impairment (CrCl 15–29 mL/min): Use caution as safety and effectiveness have not been proved.
Dose Adjustment in Hepatic Impairment Patients:
Moderate to mild impairment: There is no need to modify the dosage.
Severe impairment: Use caution, as safety and effectiveness have not been proven.
Signs and Symptoms
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Avanafil.
Overconsumption of Avanafil could lead to severe headaches, dizziness, prolonged and painful erections lasting more than 4 hours (priapism), visual disturbances, and potential cardiovascular issues such as increased heart rate or lowered blood pressure.
Management
There is no specific antidote or treatment for excessive Avanafil intake, so treatment typically involves symptomatic and supportive measures. Consider gastric lavage or vomiting induction if ingestion occurred recently. Monitor vital signs, including cardiac function. Administer intravenous fluids to maintain hydration, correct electrolyte imbalances, and manage cardiovascular issues. For priapism, seek prompt healthcare intervention to prevent tissue damage. Severe overdosage complications might require hemodialysis to eliminate Avanafil and its metabolites. Avoid self-medication. Immediate medical attention and close monitoring are crucial for Avanafil overdose management.
Pharmacodynamics:
Having been shown to have an in vitro IC50 of 5.2 nM, Avanafil is a potent competitive inhibitor of phosphodiesterase 5 (PDE5). When compared with less selective PDE5 inhibitors like sildenafil and vardenafil, it is less likely to produce visual disturbances and cardiovascular adverse effects since its inhibitory effects on PDE5 are 100-fold more potent than those on PDE6 and >1000-fold more powerful than those on other PDE enzymes. Because of its rapid onset of effect, it can be taken up to 15 minutes before starting sexual activity.
Pharmacokinetics:
When taken with some hypertension medications (e.g., alpha-blockers, large doses of alcohol), PDE5 inhibitors such as Avanafil can result in considerable drug interactions. Non-arteritic anterior ischemic optic neuropathy (NAION), a rare illness that usually manifests as rapid loss of vision in one or both eyes and appears to be more common in people with a "crowded" optic disc, has also been linked to the development of PDE5 inhibitors. Individuals who exhibit any level of visual loss should stop taking all PDE5 inhibitors immediately and visit a doctor. A history of NAION or other degenerative retinal illnesses may exclude the use of avanafil therapy in some areas.
Absorption
Enzalutamide demonstrates rapid absorption from the gastrointestinal tract, achieving peak plasma concentrations within a relatively short period, typically 30 to 45 minutes after administration.
Distribution
It exhibits extensive binding to plasma proteins upon absorption, accounting for an approximate binding percentage of 99%.
Metabolism
Enzalutamide undergoes metabolic processes predominantly within the liver, catalyzed by the CYP3A4 enzyme, with a minor contribution from the CYP2C isoenzymes. This metabolic pathway yields active metabolites like M4 and inactive metabolites like M16.
Elimination
The elimination route of enzalutamide predominantly occurs via faeces, accounting for roughly 62% of excreted metabolites. Additionally, approximately 21% of metabolites are eliminated through urine.
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- Kotera J, Mochida H, Inoue H, Noto T, Fujishige K, Sasaki T, Kobayashi T, Kojima K, Yee S, Yamada Y, Kikkawa K, Omori K. Avanafil, a potent and highly selective phosphodiesterase-5 inhibitor for erectile dysfunction. J Urol. 2012 Aug;188(2):668-74. doi: 10.1016/j.juro.2012.03.115. Epub 2012 Jun 15. PMID: 22704456.
- Wang R, Burnett AL, Heller WH, Omori K, Kotera J, Kikkawa K, Yee S, Day WW, DiDonato K, Peterson CA. Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: implications for clinical safety and improved tolerability. J Sex Med. 2012 Aug;9(8):2122-9. doi: 10.1111/j.1743-6109.2012.02822.x. Epub 2012 Jul 3. PMID: 22759639.
- Katz EG, Tan RB, Rittenberg D, Hellstrom WJ. Avanafil for erectile dysfunction in elderly and younger adults: differential pharmacology and clinical utility. Ther Clin Risk Manag. 2014 Aug 27;10:701-11. doi: 10.2147/TCRM.S57610. PMID: 25210457; PMCID: PMC4155803.
- https://www.ncbi.nlm.nih.gov/books/NBK548149/
- https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202276s018lbl.pdf
- https://www.ema.europa.eu/en/medicines/human/EPAR/spedra
Dr. Chumbeni E Lotha has completed her Bachelor of Pharmacy from RIPANS, Mizoram and Doctor of Pharmacy from SGRRU,Dehradun. She can be reached at editorial@medicaldialogues.in
Dr JUHI SINGLA has completed her MBBS from Era’s Lucknow Medical college and done MD pharmacology from SGT UNIVERSITY Gurgaon. She can be contacted at editorial@medicaldialogues.in. Contact no. 011-43720751
Published on: 27 Nov 2023 6:26 AM GMT