Adegra 100 mg Tablet (Sildenafil Citrate) – ACI Limited

1. About Adegra (Sildenafil Citrate)

Adegra 100 mg Tablet is a brand of Sildenafil Citrate, manufactured by ACI Limited — one of Bangladesh's most trusted pharmaceutical companies. Sildenafil was the first approved oral treatment for erectile dysfunction (ED) and remains the most widely prescribed PDE5 inhibitor globally. It is also approved for the treatment of pulmonary arterial hypertension (PAH) under the brand Revatio at different dosing.

Adegra is available in three strengths — 25 mg, 50 mg, and 100 mg — allowing the prescribing physician to titrate the dose to the individual patient's response and tolerability. The 50 mg dose is typically the recommended starting dose, with adjustment to 25 mg or 100 mg based on efficacy and side effects.

2. Mechanism of Action

Sildenafil works by selectively inhibiting cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) in the smooth muscle of the corpus cavernosum of the penis. During sexual stimulation, the release of nitric oxide (NO) from the endothelium and nerve endings activates guanylate cyclase, increasing cGMP levels. Elevated cGMP causes smooth muscle relaxation and increases blood flow into the corpus cavernosum, facilitating penile erection.

By inhibiting PDE5, sildenafil prevents the breakdown of cGMP, thereby prolonging and enhancing smooth muscle relaxation and improving erectile function. Critically, sildenafil does not cause erections independently — it only enhances the natural erectile response to sexual stimulation. Without sexual arousal, sildenafil has no significant erectile effect.

In pulmonary arterial hypertension, the same PDE5 inhibition mechanism causes pulmonary vascular smooth muscle relaxation, reducing pulmonary arterial pressure and improving exercise capacity.

3. Indications

Adegra (Sildenafil Citrate) is indicated for:

• Erectile Dysfunction (ED): Treatment of male sexual dysfunction characterized by the inability to attain or maintain penile erection sufficient for satisfactory sexual performance. Suitable for ED of organic, psychogenic, or mixed etiology.
• Pulmonary Arterial Hypertension (PAH): Improvement of exercise capacity in patients with PAH (WHO Group 1), typically at 20 mg three times daily (different dosing regimen from ED use)

Sildenafil is effective across a wide range of ED patients including those with diabetes mellitus, hypertension, post-prostatectomy, spinal cord injury, and idiopathic/psychogenic ED.

4. Dosage and Administration

For Erectile Dysfunction:

• Starting dose: 50 mg taken orally approximately 1 hour before sexual activity (range: 30 minutes to 4 hours before)
• Maximum dose: 100 mg per dose; maximum once daily
• If 50 mg is too potent or causes side effects: Reduce to 25 mg
• If 50 mg is insufficient: Increase to 100 mg

Administration Tips:

• May be taken with or without food, but a high-fat meal may delay onset by up to 60 minutes
• Swallow whole with a glass of water
• Do not take more than once in 24 hours
• Avoid grapefruit juice as it may increase sildenafil blood levels
• Alcohol consumption significantly increases the risk of side effects — limit alcohol intake

Dose Adjustments:

• Elderly (≥65 years): Start with 25 mg due to reduced clearance
• Severe hepatic impairment (Child-Pugh A/B): Start with 25 mg
• Severe renal impairment (CrCl <30 mL/min): Start with 25 mg
• Concurrent use of potent CYP3A4 inhibitors (e.g., ritonavir, ketoconazole): Do not exceed 25 mg in 48 hours

5. Contraindications

Adegra (Sildenafil) must NOT be used in patients who:

• Are taking any form of organic nitrate (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate) or nitric oxide donors (e.g., amyl nitrate/"poppers") — may cause severe, potentially fatal hypotension
• Are taking riociguat (a soluble guanylate cyclase stimulator used in PAH) — risk of severe hypotension
• Have a known hypersensitivity to sildenafil or any excipient
• Have severe cardiovascular disease for whom sexual activity is inadvisable (e.g., unstable angina, recent MI within 6 months, uncontrolled heart failure, severe arrhythmias)
• Have severe hepatic impairment (Child-Pugh C)
• Have had a recent stroke or myocardial infarction within the past 6 months
• Have a history of non-arteritic anterior ischemic optic neuropathy (NAION)
• Have hypotension (resting BP <90/50 mmHg) or uncontrolled hypertension (>170/100 mmHg)

6. Warnings and Precautions

Cardiovascular Effects: Sildenafil has vasodilatory properties and can cause transient decreases in blood pressure. Use with caution in patients with anatomical deformation of the penis, predisposing to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia), and cardiac conditions. Always assess cardiac fitness for sexual activity before prescribing.

Priapism: Prolonged erections (>4 hours) and priapism (painful erections >6 hours) have been reported rarely. Seek immediate medical attention if an erection lasts more than 4 hours to prevent permanent erectile tissue damage.

Vision Changes: Cases of sudden vision loss (NAION) and sudden hearing loss have been reported. Patients with cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, coronary artery disease, smoking, age >50) are at higher risk. Discontinue immediately if sudden visual changes occur.

Diabetes and ED: ED is extremely common in men with diabetes mellitus (affects up to 70%), and sildenafil is generally effective and safe in this population. However, diabetic patients should ensure blood glucose is well-controlled, as hyperglycemia contributes to endothelial dysfunction and worsens ED.

Alpha-Blockers: Combination with alpha-blockers (e.g., prazosin, doxazosin) used for BPH or hypertension requires caution — start with the lowest sildenafil dose and take doses at different times to minimize hypotension risk.

Not for Women or Children: Adegra is for adult males only and is not indicated for use in women or children.

7. Side Effects and Adverse Reactions

Very Common (≥10%):

• Headache
• Flushing (warmth, redness of face/neck/chest)

Common (1–10%):

• Dizziness
• Nasal congestion, rhinitis
• Dyspepsia (stomach discomfort, heartburn)
• Visual disturbances: blurred vision, altered colour perception (blue-green tinge) — related to PDE6 inhibition in the retina, transient and dose-dependent
• Back pain, myalgia (at higher doses)

Uncommon/Rare (requiring prompt attention):

• Priapism (painful prolonged erection) — medical emergency if lasting >4 hours
• Hypotension — especially with concurrent nitrates or alpha-blockers
• Sudden visual loss (NAION) — discontinue and seek emergency eye care
• Sudden hearing loss or tinnitus
• Cardiovascular events (MI, angina, arrhythmia) — particularly in patients with pre-existing cardiac disease

Most common side effects are mild-to-moderate and transient, resolving within a few hours. Dose reduction typically improves tolerability.

8. Drug Interactions

Contraindicated combinations:

• Organic nitrates (nitroglycerin, ISDN, ISMN) — severe hypotension, potentially fatal
• Riociguat — severe hypotension
• Amyl nitrate ("poppers") — severe hypotension

Significant interactions (use with caution):

• Strong CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin) — increase sildenafil AUC significantly; max 25 mg/48h with ritonavir
• CYP3A4 inducers (rifampicin, carbamazepine, phenytoin) — reduce sildenafil efficacy
• Alpha-1 adrenergic blockers (doxazosin, prazosin) — additive hypotension
• Antihypertensives (amlodipine, beta-blockers, ACE inhibitors) — additional BP lowering
• Alcohol — potentiates vasodilation, increases hypotension risk and impairs sexual function
• Grapefruit juice — modest increase in sildenafil exposure via CYP3A4 inhibition

9. Pharmacokinetics

Absorption: Rapidly absorbed after oral administration. Absolute bioavailability ~41%. Tmax approximately 30–120 minutes (median 60 minutes) in fasting state. High-fat meal delays Tmax by ~60 minutes and reduces Cmax by ~29%.

Distribution: Volume of distribution ~105 L. Plasma protein binding ~96%. Does not distribute into erythrocytes. Sildenafil and its active metabolite (N-desmethylsildenafil, ~50% potency) are detectable in semen at very low concentrations — insufficient to affect partners.

Metabolism: Hepatic — primarily CYP3A4 (major) and CYP2C9 (minor). Active metabolite N-desmethylsildenafil accounts for ~20% of pharmacological activity. Both parent compound and metabolite are substrates for P-gp.

Elimination: Primarily as metabolites in feces (~80%) and urine (~13%). Terminal half-life ~3–5 hours for both sildenafil and its active metabolite. Clearance reduced in elderly and in hepatic/renal impairment.

10. Sildenafil and Diabetes Mellitus

Erectile dysfunction affects 50–70% of men with diabetes — significantly higher than the general population — due to diabetes-related damage to blood vessels (microangiopathy) and nerves (autonomic neuropathy) in the penile tissues. Sildenafil is the most extensively studied oral agent for diabetic ED and has demonstrated efficacy in multiple randomized controlled trials.

Key points for diabetic patients using Adegra:

• Sildenafil is safe and effective in most men with type 1 and type 2 diabetes
• Response rates in diabetic men (~50–60%) are somewhat lower than in non-diabetic men (~80%) due to more severe vascular and neural damage
• Good glycemic control improves overall vascular function and may enhance sildenafil's efficacy
• Diabetic men on antihypertensive therapy (common in T2DM) should be monitored for additive blood pressure lowering effects
• Diabetic autonomic neuropathy may impair the physiological sexual response, requiring adequate sexual stimulation for sildenafil to be effective

11. Efficacy Evidence

Sildenafil's efficacy in erectile dysfunction is supported by extensive clinical evidence:

• IIEF (International Index of Erectile Function) studies: ~70–80% of non-selected ED patients reported improved erections vs ~22% with placebo
• Diabetic ED: ~50–60% improvement rates in multiple large RCTs
• Post-prostatectomy ED: Demonstrated efficacy in nerve-sparing procedures
• Psychogenic ED: High response rates (~84%)
• Vascular/organic ED: ~63% improvement in ED patients with cardiovascular comorbidities
• Onset of action: Typically 30–60 minutes; effects can persist 4–6 hours

12. ACI Limited — Quality Commitment

Adegra is manufactured by ACI Limited, a leading WHO-GMP certified pharmaceutical company in Bangladesh. ACI has exported medicines to over 30 countries and maintains rigorous quality standards including:

• ISO 9001:2015 quality management certification
• WHO-GMP compliant manufacturing facilities
• Regulatory-grade bioequivalence testing
• Strict pharmaceutical-grade starting material controls

Adegra meets the same pharmacokinetic standards as innovator sildenafil, ensuring equivalent therapeutic efficacy and safety profile.

13. How to Store Adegra Tablets

• Store at room temperature below 30°C
• Keep in a cool, dry place away from direct sunlight and humidity
• Keep out of reach of children
• Do not use after the expiry date on the pack
• Keep in original blister packaging until time of use
• Do not store in bathroom cabinets (humid environment)

Frequently Asked Questions (FAQ)

Q1: How long does Adegra 100 mg take to work?

Adegra 100 mg (Sildenafil) typically begins working within 30 to 60 minutes of oral administration on an empty stomach. The maximum effect is usually seen within 1 hour. Taking the tablet after a heavy or high-fat meal may delay onset by up to 1 hour. The tablet's effect may last for 4 to 6 hours, during which time sexual stimulation will produce a response. It does not cause an automatic erection — sexual arousal is required.

Q2: Can men with diabetes safely take Adegra (Sildenafil)?

Yes — sildenafil is one of the most studied treatments for erectile dysfunction in men with diabetes and is considered safe and effective in this population. However, diabetic men should take certain precautions: (1) Inform your doctor about all medications you take, particularly nitrates or blood pressure medicines. (2) Ensure your blood pressure is well-controlled before using sildenafil. (3) Response rates may be somewhat lower than in non-diabetic men due to vascular and nerve damage, so adequate sexual stimulation is important. Always use under medical supervision.

Q3: Can I take Adegra with my heart medicines or blood pressure tablets?

Sildenafil must never be taken with nitrate medications (such as nitroglycerin patches, sprays, or tablets used for angina) — this combination can cause a dangerous and potentially fatal drop in blood pressure. Sildenafil can generally be used cautiously with antihypertensives like amlodipine or ACE inhibitors, but doses may need adjustment. Always tell your doctor about all heart and blood pressure medications before starting Adegra. Your cardiologist should assess your fitness for sexual activity if you have heart disease.

Q4: What should I do if Adegra 50 mg is not effective enough?

If the 50 mg dose does not produce satisfactory results, your doctor may increase the dose to 100 mg (the maximum dose). Take it on an empty stomach for faster onset, ensure adequate sexual stimulation, and allow enough time (at least 1 hour) after taking the tablet. If 100 mg is still insufficient, discuss alternative treatments with your urologist or andrologist — such as vacuum erection devices, penile injections (alprostadil), or specialist psychological counselling for psychogenic ED. Do not exceed 100 mg or take more than once per 24 hours.