Indications

Aggra is indicated for two main conditions:

• Erectile Dysfunction (ED): This is for men who are unable to achieve or maintain an erection sufficient for satisfactory sexual performance. Sexual stimulation is necessary for Aggra to be effective.
• Pulmonary Arterial Hypertension (PAH): A type of high blood pressure that affects the arteries in the lungs and the right side of the heart.

Description

Aggra, which contains sildenafil, is a selective and reversible inhibitor of an enzyme called phosphodiesterase type 5 (PDE5). When sexual stimulation occurs, it triggers the release of nitric oxide in the penis. Aggra then works by blocking the PDE5 enzyme, which increases the levels of a substance called cGMP. This leads to the relaxation of smooth muscles and an increase in blood flow to the penis, resulting in an erection. It is important to note that Aggra does not cause an erection on its own; it requires sexual stimulation to work.

Pharmacology

Sildenafil works by enhancing the natural physiological process of an erection. During sexual stimulation, nitric oxide is released, which activates an enzyme that produces cGMP. High levels of cGMP cause the smooth muscles in the penis to relax, allowing for increased blood flow. By inhibiting PDE5, the enzyme that breaks down cGMP, sildenafil ensures that cGMP levels remain high, thereby enhancing the erection response.

Sildenafil is rapidly absorbed after oral administration, with about 41% of the dose reaching the bloodstream. The maximum concentration in the blood is typically reached within 30 to 120 minutes. The medication is primarily broken down by the liver and has a half-life of about 4 hours.

Dosage & Administration

• Erectile Dysfunction: The recommended dose is 50 mg, taken about one hour before sexual activity. This can be adjusted based on effectiveness and toleration, from a minimum of 25 mg to a maximum of 100 mg. The medication can be taken between 30 minutes and 4 hours before sexual activity, and should not be taken more than once per day.
• Special Populations: A starting dose of 25 mg should be considered for patients over 65, those with liver or severe kidney impairment, or those taking certain medications (like ketoconazole, itraconazole, or erythromycin) that can increase sildenafil levels in the blood.
• Pulmonary Arterial Hypertension: The recommended dose is 20 mg three times daily, taken approximately 4-6 hours apart, with or without food.

Interaction

Aggra is metabolized by the CYP3A4 and CYP2C9 enzymes in the liver. Inhibitors of these enzymes, such as ketoconazole, erythromycin, and some HIV protease inhibitors (saquinavir, ritonavir), can significantly increase Aggra levels in the body, which may increase both its effects and side effects. Conversely, inducers of these enzymes, like bosentan, can decrease Aggra levels. Aggra should not be taken with nitrates or nitric oxide donors due to the risk of a dangerous drop in blood pressure.

Contraindications

Aggra is contraindicated in patients who are hypersensitive to any of its components. It is also strictly contraindicated in patients who are using organic nitrates, as it can dangerously potentiate their blood pressure-lowering effects.

Side Effects

Common side effects include dizziness, headache, and fatigue.

• Cardiovascular: Serious cardiovascular events, including heart attack, stroke, and sudden cardiac death, have been reported rarely, especially in patients with pre-existing risk factors.
• Nervous: Ataxia, tremor, depression, insomnia, and in rare cases, seizures.
• Special Senses: Visual disturbances, including changes in color vision, temporary vision loss, and eye pain. Sudden hearing loss has also been reported.
• Urogenital: Prolonged erections (more than 4 hours) and priapism (painful erections lasting over 6 hours) have been reported and require immediate medical attention to prevent permanent damage.

Pregnancy & Lactation

Aggra is not indicated for use by women. It is categorized as Pregnancy Category B. Animal studies have shown no evidence of harm to the fetus.

Precautions & Warnings

A full medical assessment is needed to determine the cause of erectile dysfunction and if Aggra is the right treatment.

• Cardiovascular Risk: Patients with pre-existing cardiovascular disease should be evaluated for the risks of sexual activity, as Aggra and sexual activity can both strain the heart. It should be used with caution in patients with low blood pressure, heart failure, or specific heart conditions.
• Drug Interactions: Use caution when taking Aggra with alpha-blockers, as the combination can significantly lower blood pressure. A starting dose of 25 mg is recommended in such cases.
• Priapism: Patients with anatomical penile deformities or conditions that predispose them to priapism (like sickle cell anemia) should use Aggra with caution.
• Combinations: Do not use Aggra with other erectile dysfunction treatments.

Overdose Effects

In cases of overdose (up to 800 mg), side effects were similar to lower doses but more frequent and severe. In an overdose, supportive measures should be taken as needed. Sildenafil is highly bound to plasma proteins and is not cleared by dialysis.

Therapeutic Class

Aggra is a drug for erectile dysfunction.

Storage Conditions

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