EVADAM

Pharmacodynamics

Priapism is a haemodynamic process based on smooth muscle relaxation in the corpora cavernosa and arterioles. Sexual stimulation triggers release of nitric oxide from endothelial cells and the cavernous nervous terminals in the corpora cavernosa. Nitric oxide activates guanylate cyclase, thereby increasing the synthesis of cyclic guanosine monophosphate (cGMP) destroyed by phosphodiesterase type 5 (PDE5) which promotes erectile function by increasing the amount of cGMP in the corpora cavernosa. Sildenafil acts to inhibit phosphodiesterase type 5 (PDE5).

Because nitric oxide is only released in the corpora cavernosa under sexual stimulation, the PDE5 inhibitory effect of sildenafil is not present without sexual stimulation. Evadam works to enhance the body's natural response to sexual stimulation.

Pharmacokinetics

Sildenafil is rapidly absorbed following oral administration. Maximum observed plasma concentrations are reached within 30 to 120 minutes. Sildenafil is widely distributed into body tissues. The mean steady state volume of distribution for sildenafil is 105 L.

Sildenafil and its major circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Concentrations of the metabolite are about 40% of that of sildenafil, resulting in a 20% pharmacological effect. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces and to a lesser extent in the urine.

Indications

Evadam is indicated in cases of erectile dysfunction (impotence) in adult males (the persistent or repeated inability to attain or maintain an erection sufficient for satisfactory sexual performance).

Contraindications

- Hypersensitivity to the active substance or to any of the excipients.

- Co-administration with nitrates in any form.

- Women.

- Children aged younger than 18 years.

- Patients with severe hepatic impairment.

Dosage

The recommended dose:

The recommended initial dose of Evadam is 50 mg (1 tablet) taken orally as needed approximately 30 minutes to 1 hour before anticipated sexual activity. The maximum dose frequency is once per day.

Depending on effectiveness and tolerance, the dose subsequently may be increased to a maximum recommended dose of 100 mg (2 tablets) or decreased to 25 mg. The maximum dose is 100 mg once daily.

Geriatric patients: The initial dose should be 25 mg. Then the dose may be increased depending on the body's ability to tolerance and response.

Renal impairment (creatinine clearance less than 30 ml/minute): the initial sildenafil dose should be decreased to 25 mg, since the drug’s effects may be prolonged and enhance in such patients.

Severe hepatic impairment: No recommendations.

* Patients using other medicinal products:

- The initial recommended dose of sildenafil is not more than 25 mg daily for patients receiving drugs concomitantly that are potent cytochrome P450 isoenzyme CYP3A4.  The initial recommended dose of sildenafil is not more than 25 mg every 48 hours in patients receiving any HIV protease inhibitor. 

- The initial recommended dose of sildenafil is 25 mg in patients taking an alpha-blocker.

Method of administration

Evadam is for oral use only. In all cases, follow the instructions of the physician.

Precautions

Sildenafil has systemic vasodilatory properties that may result in transient decreases in blood pressure. Patients with left ventricular outflow obstruction (such as aortic stenosis or idiopathic undiagnosed aortic valve hypertrophy) may be susceptible to the effects of vasodilators including phosphodiesterase type 5 inhibitors.

Because there are no data establishing the safety of sildenafil in the following subpopulations, the drug is not recommended in those with a recent (within 6 months) myocardial infarction, stroke, or arrhythmia; in those with cardiac failure or coronary artery disease causing angina; in those with resting hypotension (<90/50 mmHg) or hypertension (170/110 mmHg); in those with retinal degenerative diseases such as retinitis pigmentosa.

The drug should be used with caution in patients with blood clotting disorders, progressive peptic ulcer disease, and heart failure.

Stop immediately if you lose vision or hearing when taking medicine.

Tadalafil should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).

Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical assistance.

Pregnancy and lactation

Pregnancy: Although animal studies have shown that sildenafil has no effect on the fetus, there are no studies which have been performed in pregnant women.

Lactation: No studies have been performed using sildenafil in nursing women.

Effects on ability to drive and use machines

No well-controlled studies on the effects on the ability to drive and use machines have been performed. As headache, dizziness and altered vision were reported, patients should be aware of how they might be affected by sildenafil, before driving or using machines.

Undesirable effects

Sildenafil is used on 3,700 patients in global clinical studies. Side effects were reported at mild or moderate levels.

·      Common:

-          Headache, flushing and indigestion.

-          Visual disturbances such as blurred vision, photophobia, chromatopsia, cyanopsia, eye irritation, and eye pain and redness.

·      Uncommon:

-          Dizziness, insomnia, anxiety, dizziness, epistaxis, nasal congestion, fever and gastrointestinal disturbances such as diarrhea and vomiting. Priapism can occur.

-          Skin rash, erythema, hair loss, back pain or leg pain, muscle aches, edema, water retention, paresthesias and urinary tract infections.

-          Difficulty breathing, cough, rhinitis, sinusitis, bronchitis and cellulitis can occur. Sudden hearing loss has been also reported.

·   Rare:

-          Retinal hemorrhage, Non-arteritic anterior ischaemic optic neuropathy (NAION) that causes permanent blindness.

-          Anemia, leucopenia, gynaecomastia, frequent urination or urinary incontinence, bloody urine and seizures.

-          Cerebral hemorrhage and transient ischemia.

-          Palpitations, syncope, hypertension, hypotension and severe cardiovascular events including myocardial infarction, arrhythmia, tachycardia, unstable angina, sudden death from the heart.

Inform your doctor about any side effects that may occur during the treatment.

Interactions

Sildenafil metabolism is principally mediated by CYP3A4 (major route) and 2C9 (minor route). Co-administration of cytocromycin inhibitors with sildenafil can significantly increase plasma sildenafil concentrations.

In contrast, co-administration of CYP34A inhibitors, including rifampicin, phenytoin and carbamazepine with sildenafil can significantly decrease plasma sildenafil concentrations.

Overdose

In single dose up to 800 mg, adverse reactions were similar to those seen at lower doses.

In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.

Shelf-life: 36 months from the manufacturing.

Storage: Store in cool dry places, below 30⁰C, protect from direct light.

Specifications: Manufacturer’s