Aggra 50 mg

Description

Indications
Aggra is prescribed for the treatment of erectile dysfunction in men, which is characterized by the inability to achieve or maintain an erection sufficient for satisfying sexual performance. For optimal effectiveness, sexual stimulation is necessary. In addition, Aggra is indicated for the treatment of pulmonary arterial hypertension.
Use as directed by a registered healthcare professional.

Description
Aggra is a selective and reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). When sexual stimulation triggers the release of nitric oxide in the body, Aggra inhibits PDE5, leading to increased levels of cGMP in the corpus cavernosum. This action relaxes smooth muscles and allows increased blood flow into the penile tissues, resulting in an erection. Aggra will not produce an erection in the absence of sexual stimulation.

Pharmacology
Mechanism of Action:
The mechanism of penile erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual arousal. NO activates the enzyme guanylate cyclase, which increases the levels of cGMP, causing smooth muscle relaxation and the influx of blood into the corpus cavernosum. Sildenafil, the active ingredient in Aggra, does not directly relax the smooth muscle of the corpus cavernosum but enhances the effects of NO by inhibiting PDE5. This enzyme typically degrades cGMP, so by inhibiting PDE5, Sildenafil promotes higher levels of cGMP, leading to smooth muscle relaxation and increased blood flow during sexual activity.

Pharmacokinetics and Metabolism:
Sildenafil is quickly absorbed after oral administration, with an average bioavailability of 41%. It is metabolized primarily in the liver by the cytochrome P450 3A4 enzyme system. Sildenafil and its active metabolite have a half-life of approximately 4 hours. When taken with high-fat meals, the absorption rate is slower.

Absorption and Distribution:
Sildenafil reaches peak plasma concentrations within 30 to 120 minutes when taken on an empty stomach. After meals, particularly those high in fat, absorption is slower.

Metabolism and Excretion:
The drug is primarily metabolized in the liver and excreted as metabolites, mainly in the feces (around 80%) and to a lesser extent in the urine (about 13%).

Pharmacokinetics in Special Populations:
In elderly patients (65 years and older), Sildenafil clearance is reduced, leading to higher plasma concentrations compared to younger individuals.

Dosage & Administration

• Erectile dysfunction:
  The usual starting dose is 50 mg, taken approximately 1 hour before sexual activity. It may be taken anywhere from 4 hours to 30 minutes before sexual activity. Depending on efficacy and tolerance, the dose can be adjusted to 100 mg (maximum) or decreased to 25 mg. The maximum recommended frequency is once per day.

  For patients with certain conditions (e.g., over 65 years of age, liver or kidney impairment, or taking potent CYP3A4 inhibitors), starting with a lower dose (25 mg) is recommended to avoid higher plasma levels, which could increase both effectiveness and the risk of side effects.

• Pulmonary arterial hypertension:
  The recommended dosage is 20 mg, three times daily, taken approximately 4-6 hours apart, with or without food.

Important note:
Aggra should not be used by patients who are concurrently using nitrates in any form, as it can cause significant hypotension. In patients on alpha-blocker therapy, Sildenafil should be started at a lower dose.

Interactions
Aggra is primarily metabolized by CYP3A4, so drugs that inhibit this enzyme (e.g., ketoconazole, erythromycin) may increase the plasma concentration of Sildenafil. Conversely, CYP3A4 inducers (e.g., rifampin) may reduce its effectiveness. Concomitant use with certain other medications, such as HIV protease inhibitors (e.g., ritonavir), can significantly increase Sildenafil exposure, potentially leading to side effects. Careful monitoring and dose adjustments are recommended when using Aggra alongside other medications.

Contraindications
Aggra should not be used by individuals who are hypersensitive to any of its ingredients. It is also contraindicated for patients using nitrates, as the combination can result in dangerously low blood pressure.

Side Effects
Common side effects of Aggra include headaches, facial flushing, dizziness, nasal congestion, and indigestion. In rare cases, severe cardiovascular or cerebrovascular events, such as heart attacks and strokes, have been reported, particularly in patients with pre-existing cardiovascular conditions. Other potential side effects include:

• Cardiovascular: Angina, tachycardia, hypotension, arrhythmias.
• Nervous system: Headaches, dizziness, visual disturbances, and in rare instances, seizures or loss of consciousness.
• Urogenital: Priapism (prolonged erections), painful erections, and changes in ejaculation.

Pregnancy & Lactation
Aggra is not intended for use in women, and there is insufficient data regarding its safety during pregnancy. In animal studies, Sildenafil showed no teratogenic effects. However, its use in pregnant women is not recommended.

Precautions & Warnings
Before using Aggra, a thorough medical evaluation should be done, particularly in patients with a history of cardiovascular disease, as sexual activity may increase the risk of heart-related events. Special caution is required in patients with anatomical penile abnormalities, bleeding disorders, or a history of priapism.

Aggra may interact with medications that lower blood pressure, and it should be used with caution in patients taking antihypertensive drugs or alpha-blockers. Additionally, it should not be combined with other erectile dysfunction treatments or nitrate-based medications.

Overdose Effects
In cases of overdose, the symptoms may be more severe than those seen at lower doses. Standard supportive measures should be taken, as renal dialysis is unlikely to accelerate the clearance of Sildenafil due to its high plasma protein binding.

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

Therapeutic Class
Erectile Dysfunction Medications