Aggra 50 mg

Description

Indications
Aggra is indicated for the treatment of erectile dysfunction (ED) in men, which is characterized by the inability to achieve or sustain an erection sufficient for satisfactory sexual performance. For Aggra to be effective, sexual stimulation is necessary. It is also indicated for the treatment of pulmonary arterial hypertension.
Use as prescribed by a registered medical practitioner.

Description
Aggra is a selective and reversible inhibitor of phosphodiesterase type 5 (PDE5), which specifically targets cyclic guanosine monophosphate (cGMP). During sexual stimulation, nitric oxide is released locally. Aggra works by inhibiting PDE5, leading to increased cGMP levels in the corpus cavernosum. This process promotes smooth muscle relaxation and increased blood flow to the penile tissues, resulting in an erection. Aggra does not induce an erection without sexual stimulation.

Pharmacology
Mechanism of Action:
The process of achieving an erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual activity. NO activates the enzyme guanylate cyclase, which raises the levels of cGMP. This causes smooth muscle relaxation, allowing blood to flow into the corpus cavernosum, resulting in an erection. Sildenafil (Aggra) does not directly relax the corpus cavernosum but enhances the effect of NO by inhibiting PDE5, the enzyme responsible for degrading cGMP. Without sexual stimulation, Sildenafil has no effect on the corpus cavernosum.

Pharmacokinetics and Metabolism:
Sildenafil is quickly absorbed after oral intake, with an average bioavailability of 41% (ranging from 25% to 63%). It is primarily metabolized in the liver, mainly by cytochrome P450 3A4, producing an active metabolite with similar properties to Sildenafil. Both Sildenafil and the metabolite have a half-life of around 4 hours.

Absorption and Distribution:
Sildenafil is rapidly absorbed. Maximum plasma concentrations are typically reached within 30 to 120 minutes (mean 60 minutes) after a fasted dose. When taken with a high-fat meal, absorption is slower.

Metabolism and Excretion:
Sildenafil is cleared by hepatic enzymes. After oral or intravenous administration, the drug is predominantly excreted in the feces (around 80%) and to a lesser extent in the urine (approximately 13%).

Pharmacokinetics in Special Populations:
For elderly patients (aged 65 or older), Sildenafil clearance is reduced, resulting in 84% to 107% higher plasma AUC (area under the curve) compared to younger volunteers.

Dosage & Administration
Erectile Dysfunction:
The typical starting dose is 50 mg, taken about 1 hour before sexual activity. It can be taken anywhere between 4 hours and 30 minutes before sex. Depending on effectiveness and tolerance, the dose may be adjusted between 25 mg and 100 mg. The maximum dose is 100 mg, and it should not be taken more than once a day.

Pulmonary Arterial Hypertension:
The recommended dose for treating pulmonary arterial hypertension is 20 mg, taken three times daily, approximately 4-6 hours apart, with or without food.

Use as prescribed by a registered medical practitioner.

Interaction
Aggra is primarily metabolized by cytochrome P450 enzymes, specifically 3A4 and to a lesser extent 2C9. Inhibitors of these enzymes can increase Aggra plasma levels, while inducers can decrease them. For example, the co-administration of Cimetidine (a non-specific CYP inhibitor) can increase Aggra plasma concentrations by 56%. Strong CYP3A4 inhibitors like ketoconazole or itraconazole can lead to greater effects. Conversely, inducers like rifampin may decrease Aggra levels.

Contraindications
Aggra is contraindicated for individuals with hypersensitivity to any of its components. It should not be used in combination with nitrates due to the risk of enhanced hypotensive effects.

Side Effects
General: Facial edema, photosensitivity, chills, accidental injuries, chest pain, and abdominal discomfort.
Cardiovascular: Angina, tachycardia, hypotension, and other heart-related symptoms.
Digestive: Vomiting, dysphagia, and gastritis.
Metabolic: Thirst, edema, hyperglycemia, and gout.
Musculoskeletal: Myalgia, arthritis, and tendon rupture.
Nervous: Headache, dizziness, and visual disturbances.
Respiratory: Asthma, dyspnea, and sinusitis.
Skin: Urticaria, pruritus, and skin ulcers.
Special Senses: Vision changes, eye pain, and tinnitus.
Urogenital: Prolonged or painful erections, urinary frequency, and abnormal ejaculation.

Pregnancy & Lactation
Sildenafil is not recommended for use in women and is classified as Pregnancy Category B. There are no well-controlled studies in pregnant women, and it has shown no teratogenic effects in animal studies.

Precautions & Warnings
Before using Aggra, it is crucial to consider any underlying cardiovascular conditions, as sexual activity may exacerbate risks. Caution is advised when using Aggra in combination with alpha-blockers or other vasodilators, as this may lead to a significant drop in blood pressure.

Patients with conditions such as anatomical penis deformities, a history of priapism, or severe cardiovascular disease should consult their doctor before using Aggra.

Overdose Effects
In cases of overdose, standard supportive care should be provided. Renal dialysis is unlikely to accelerate clearance due to Aggra’s high protein binding.

Therapeutic Class
Drugs for Erectile Dysfunction.

Storage Conditions
Store in a dry place, away from light and heat. Keep out of reach of children.