- Avanafil is indicative for treatment of erectile dysfunction any origin. Its effect is observed only under the influence of sexual stimulation.
- Dapoxetine is very helpful in case of premature ejaculation. Besides, it improves emotional condition of a man considerably.
Avanafil effect is based on the capacity of this substance to block quickly and efficiently a special enzyme located in membranes of penis cavernous bodies, specific phosphodiesterase type 5. This leads to growth of concentrations of cyclic guanosinediphosphate in unstriated muscles of cavernous bodies and enhancement of vasodilatory impact of nitrogen oxide produced from nerve endings of penis in response to sexual arousal. This synergism promotes the development of mighty and steady erection under the influence of sexual stimulation. After the intake, avanafil is fast absorbed in gastro-intestinal tract by 99% connecting with plasma proteins and reaching maximal plasma concentrations after 30-40 minutes after the intake.
A man’s age taking avanafil-based medications (such as Stendra, Avana-50, Avana-100, or Avana-200) doesn’t have any impact on content of active substance in blood plasma and its metabolism. Food intake doesn’t influence the quality of active substance absorption but may slow down the absorption rate considerably.
Metabolism of medicinal products containing avanafil occurs with participation of hepatic enzymes. Inactive metabolites of the medication are cleared with feces (around 60%) and urine (around 20%), as well as with semen (around 2%).
Mild and moderate hepatic impairments haven’t considerably influenced pharmacokinetics and pharmacodynamics of avanafil and do not require correction of its dose. In case of severe disorders of hepatic or renal functions, pharmacokinetics and pharmacodynamics of avanafil was not studied.
Diabetes of 1 and 2 type hasn’t changed the indicators pharmacokinetic and pharmacodynamic features of medications containing avanafil and hasn’t required the dosage correction. Avanafil-based medications haven’t influenced adversely semen quality and its fertility which has been proved by clinical trials with participation of healthy volunteers.
Dapoxetine mechanism of action in case of premature ejaculation is connected with slowing down of serotonin reuptake by neurons with subsequent enhancement of neurotransmitter impact on pre- and post-synaptic receptors. Ejaculation process is generally regulated by sympatic nervous system. Postganglionic sympatic nerve filaments innervate seminal vesicles, seminal duct, prostatic gland, urethra muscles, and neck of the urinary bladder causing their coordinated constriction for achievement of ejaculation. Dapoxetine influences ejaculation reflex increasing latent period and decreasing reflectory impulsation of ganglia motoneurons of perineum. Stimulus causing ejaculation is generated in cerebro-spinal reflectory center which is controlled by cerebrum via brain stem including preoptic and paraventricular.
Dapoxetine is quickly absorbed, and its maximal concentration in blood plasma is achieved in 1-2 hours after its intake. Fat food acceptance decreases maximal concentration of dapoxetine (by 10%) and increases area under the concentration-time curve and the time of achievement of maximal concentration in blood plasma (by 12%). Nevertheless, the degree of dapoxetine absorption is not changed. The changes are not clinically significant. Thus, dapoxetine may be used regardless of food acceptance. More than 99% of dapoxetine get connected with plasma proteins.
According to clinical trials, dapoxetine is metabolized by many enzymes of liver and kidneys, especially CYP2D6, CYP3A4 and flavin-containing monooxygenase of kidneys. Dapoxetine is fast cleared which is proved by low concentration of substance in blood plasma (less than 5% from maximum) in 24 hours after dosage intake.
In case of daily intake the accumulation of substance in organism is minimal. In case of peroral intake, elimination half-life is around 19 hours. One-time administration of dapoxetine in the dose of 60mg hasn’t exposed any significant difference in pharmacokinetics indicators of cound elderly men and men at earlier age.
Application of Avanafil- and Dapoxetine-Based Medications
Initial dosage of the medication is 100mg. If necessary, it may be decreased up to 50mg or enhanced up to 200mg. Maximal daily dose is 200mg. It is prohibited to exceed it. Avanafil-containing medicines are recommended being taken with water 15-20 minutes after its intake and lasts up to 6 hours.
Simultaneous intake with food may slow down avanafil absorption rate in gastro-intestinal tract and delay the occurrence of medicine’s effect. Avanafil-containing medicines should not be combined with intake of grapefruit or grapefruit juice, since it may cause avanafil overdose.
Dapoxetine-based medications are represented by tableted form designed for peroral intake. Tablets should be swallowed with at least a glass of water. Dapoxetine should be taken regardless of food acceptance. Recommended initial dose for all men is 30mg. This dosage is taken 1-3 hours before expected sexual intercourse. In case of insufficient effect and good tolerability of 30-mg dose, it may be increased to 60mg. Maximally recommended frequency of usage is once per 24 hours.
A doctor prescribing dapoxetine for premature ejaculation therapy must estimate all risks and benefits of the medication intake after the first four weeks of treatment or after the intake of six doses and has to determine the risk-benefit ratio in order to decide the worthwhileness of further treatment with dapoxetine.
Contraindications to Avanafil and Dapoxetine Administration
Avanafil- and dapoxetine-containing drugs are not to be administered in the following cases:
- Allergy to main substances and their intolerability;
- Combined intake with nitrates-containing medications and nitrogen oxide donors;
- Unstable angina in case angina attacks are caused by sexual activity;
- Severe myocardium dysfunctions;
- Severe, life-threatening heart beat arrhythmia;
- Acute myocardium infraction and apoplectic attach within the last six months before medications intake;
- Severe arterial hypotension and hypertension;
- Acute hepatic and renal impairments;
- Hereditary diseases of eye retina accompanying with its degeneration and vision loss of one eye due to anterior ischaemic optic neuropathy of optic nerve;
- Priapism and penis deformation;
- Co-administration with ketoconazole, itraconazole, ritonavir, telithromycin.
- Simultaneous intake with monoamine oxidase inhibitors and within 14 days of termination of their administration. And monoamine oxidase inhibitors are prohibited to be taken within seven days after avanafil- and dapoxetine-containing medications;
- Patients under 18 years of age.
Dapoxetine is also not to be combined with selective serotonin reuptake inhibitors, thioridazine, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants and other medications having serotoninergic impact. Also, dapoxetine is not to be combined with CYP3A4 inhibitors.
Side-effects after avanafil intake in recommended doses are met very seldom and disappear right after avanafil impact termination. Among them are:
- Short-term facial erythema;
- Sickliness and headache connected with vasodilatory action of the medication;
- Blurred vision and color perception impairment;
- Swelling of nasal passage and difficult nasal breathing;
- Myodynia and dorsalgia;
- Allergic reactions on avanafil and other medications’ auxiliary agents.
- Insomnia, fatigue, anxiety, restlessness, unusual dreams;
- Depression, euphoria condition, mood swings, overwrought angst;
- Indifference, sleep disorder, nightmares, low libido, loss of libido, anorgasmia;
- Impaired concentration, fainting, postural vertigo, taste distortion;
- Lethargy, blurred vision, arterial blood pressure drop, pains in an eye, ear buzzing
- Sinus bradycardia, tachycardia, systolic hypertension, stuffiness in nose, yawning, nausea;
- Vomit, diarrhea, uncleared bowels, stomachache, dyspepsia, bloat, abdominal swelling, dryness in mouth, itch, cold sweat;
- Erectile dysfunction, absence of ejaculation, orgasm failure, anorgasmia in men, paresthesia of male sexual organs;
- Irritancy, feeling of heat, intoxication feeling.
Overdose of Avanafil- and Dapoxetine-Containing Drugs
In case all recommended doses and recommendations for medications intake are observed, the overdose doesn’t occur. In case the dosage is surpassed, the enhancement of side-effects is observed. Therapy is symptomatic, since due to high connectivity of avanafil and dapoxetine with plasma proteins, hemodialysis doesn’t take any therapeutic effect.
In case your attending doctor prescribed you to take dapoxetine or avanafil regularly, and you missed the dose of one of these medications, resume taking them as soon as you noticed this. Anyway, if it is the time for your next dose of one of these drugs, exclude the missed dosage and return to your regular schedule of medications intake. Do not double the dosage unless otherwise provided directly.