Aggra 100 mg

Description

Indications
Aggra is used for the treatment of erectile dysfunction (ED) in men, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual activity. Sexual stimulation is required for Aggra to be effective. Additionally, Aggra is prescribed for managing pulmonary arterial hypertension (PAH).

Use this medication only as directed by a registered physician.

Description
Aggra is a selective and reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). During sexual stimulation, nitric oxide (NO) is released locally, which leads to an increase in cGMP levels in the corpus cavernosum. By inhibiting PDE5, Aggra enhances cGMP activity, facilitating smooth muscle relaxation and increased blood flow to penile tissues, resulting in an erection. It is important to note that Aggra has no effect in the absence of sexual stimulation.

Pharmacology
Mechanism of Action: The process of penile erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. This activates guanylate cyclase, increasing cGMP levels, which in turn relaxes smooth muscle and allows blood inflow. Sildenafil, the active ingredient in Aggra, does not directly relax isolated human corpus cavernosum tissue but enhances the effects of NO by inhibiting PDE5, which degrades cGMP. Consequently, sildenafil increases cGMP levels, facilitating muscle relaxation and enhanced blood flow in the corpus cavernosum. Sildenafil remains inactive in the absence of sexual stimulation.

Pharmacokinetics and Metabolism: After oral administration, sildenafil is rapidly absorbed, with a mean absolute bioavailability of 41% (ranging from 25% to 63%). It is metabolized primarily in the liver, mainly via cytochrome P450 3A4, producing an active metabolite with similar properties to sildenafil. Both sildenafil and its metabolite have an elimination half-life of approximately 4 hours.

Absorption and Distribution: Sildenafil is quickly absorbed, reaching peak plasma concentrations within 30 to 120 minutes (median: 60 minutes) after oral administration in a fasting state. A high-fat meal can delay the absorption rate.

Metabolism and Excretion: Sildenafil undergoes hepatic metabolism and is eliminated predominantly via feces (about 80% of the administered dose), with a smaller portion (approximately 13%) excreted in the urine.

Special Populations:

• Elderly patients (65 years and older): Clearance of sildenafil is reduced, leading to approximately 84% to 107% higher plasma exposure compared to younger adults.

Dosage & Administration

• Erectile Dysfunction: The standard recommended dose is 50 mg taken approximately 1 hour before sexual activity. However, it may be taken anywhere from 30 minutes to 4 hours before activity. Based on individual response and tolerance, the dose may be increased to a maximum of 100 mg or reduced to 25 mg. The maximum recommended frequency is once per day.
• Considerations for Special Populations: Plasma levels of sildenafil may be elevated in individuals over 65, those with hepatic or severe renal impairment, and those taking strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, erythromycin, or saquinavir). These patients may require an initial dose of 25 mg.
• Contraindications with Nitrates: Sildenafil enhances the hypotensive effects of nitrates; therefore, its use is contraindicated in individuals taking nitrate-containing medications.
• Use with Alpha-Blockers: Patients taking alpha-blockers should be stabilized before initiating sildenafil, which should be started at the lowest dose.
• Pulmonary Arterial Hypertension: The recommended dose is 20 mg three times a day, taken approximately 4 to 6 hours apart, with or without food.

Use this medication only as directed by a registered physician.

Drug Interactions
Aggra is primarily metabolized by the cytochrome P450 (CYP) enzymes, mainly CYP3A4 and, to a lesser extent, CYP2C9. Interactions with CYP inhibitors and inducers can alter sildenafil clearance:

• CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole, erythromycin, saquinavir): May significantly increase sildenafil plasma levels. For example, erythromycin increased sildenafil systemic exposure by 182%.
• CYP3A4 Inducers (e.g., rifampin, bosentan): Can reduce sildenafil plasma levels, leading to decreased effectiveness.
• Protease Inhibitors (e.g., ritonavir, saquinavir): Ritonavir co-administration led to an 11-fold increase in sildenafil exposure, significantly prolonging its presence in the bloodstream.
• Antacids: Single doses of magnesium hydroxide or aluminum hydroxide do not significantly affect sildenafil bioavailability.

Contraindications
Sildenafil is contraindicated in patients with known hypersensitivity to its ingredients. It should not be used in individuals taking nitrate medications due to the risk of severe hypotension.

Side Effects
Common and serious side effects may include:

• General: Facial swelling, pain, chills, and abdominal discomfort.
• Cardiovascular: Palpitations, low blood pressure, angina, arrhythmias, and in rare cases, myocardial infarction or cardiac arrest.
• Gastrointestinal: Nausea, vomiting, dry mouth, gastritis, and abnormal liver function tests.
• Hematologic: Anemia and leukopenia.
• Neurological: Dizziness, headache, tremors, insomnia, and, in rare cases, seizures.
• Respiratory: Shortness of breath, bronchitis, sinusitis, and increased cough.
• Dermatologic: Rashes, pruritus, and urticaria.
• Ophthalmologic: Vision disturbances, including temporary vision loss, photophobia, and eye pain.
• Urogenital: Prolonged erection (priapism), urinary incontinence, and breast enlargement.

Rare but serious cardiovascular events, including stroke, pulmonary hemorrhage, and sudden cardiac death, have been reported post-marketing, often in individuals with preexisting cardiovascular conditions.

Pregnancy & Lactation

• Pregnancy Category B: There are no adequate studies of sildenafil use in pregnant women. Sildenafil is not intended for use in women. Animal studies have shown no evidence of harm to fetal development.

Precautions & Warnings

• Patients should undergo a thorough medical evaluation before starting Aggra to identify underlying causes of erectile dysfunction.
• Caution is advised in patients with:
  • Cardiovascular conditions, including unstable angina or recent heart attack.
  • Severe renal or hepatic impairment.
  • Anatomical penile deformities (e.g., Peyronie’s disease).
  • Sickle cell anemia or other conditions predisposing to priapism.
• Sildenafil may potentiate the blood pressure-lowering effects of antihypertensive drugs.
• Patients with preexisting eye disorders should use sildenafil with caution.
• Priapism (painful erections lasting more than 6 hours) requires immediate medical attention to prevent permanent damage.

Overdose Effects
High doses of sildenafil (up to 800 mg) have resulted in an increased incidence of side effects, including severe headaches, dizziness, visual disturbances, and hypotension. In case of overdose, standard supportive care should be provided. Since sildenafil is highly protein-bound and not eliminated in urine, dialysis is unlikely to be effective.

Therapeutic Class
Drugs for Erectile Dysfunction

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