The white, round tablet debossed with AN 351 is an oral prescription medication containing Sildenafil Citrate (20 mg base equivalent). It is the generic bioequivalent to brand-name Revatio 20 mg, commonly indicated for pulmonary arterial hypertension (PAH) and frequently prescribed off-label for erectile dysfunction (ED).
Pill Identification
Attribute – Specification
- Active Ingredient – Sildenafil Citrate, USP (20 mg sildenafil base equivalent)
- Imprint – AN 351 on one side; plain on the reverse
- Color & Shape – White to off-white, round, biconvex, film-coated tablet
- Size / Diameter – Approximately 7 mm
- Primary Manufacturer / Distributor – Amneal Pharmaceuticals
- Drug Class – Phosphodiesterase type 5 (PDE5) inhibitor
- Prescription Status – Rx-only (Non-controlled)
Mechanism of Action
Sildenafil is a potent, selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5):
- Nitric Oxide / cGMP Signaling Pathway: Under physiological conditions, endothelial cells and non-adrenergic, non-cholinergic neurons release nitric oxide activates soluble guanylyl cyclase, converting GTP to cGMP, which signals intracellular protein kinases to lower cytosolic calcium concentrations, causing vascular smooth muscle relaxation.
- PDE5 Inhibition: PDE5 is the primary enzyme responsible for the hydrolytic degradation of cGMP in the pulmonary vasculature and the corpus cavernosum of the penis. Sildenafil competitively binds to the active site of PDE5, blocking cGMP degradation and significantly extending its vasodilatory signaling.
- Targeted Hemodynamic Effects:
- In Pulmonary Arteries: Sildenafil selectively dilates the pulmonary vascular bed, reducing pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) while enhancing right-ventricular cardiac output.
- In Erectile Tissue: During sexual arousal (which triggers local release), increased cGMP levels relax the trabecular smooth muscle of the corpus cavernosum, facilitating increased arterial blood flow and venous occlusion to produce an erection.
Indications and Clinical Uses
- Pulmonary Arterial Hypertension (PAH; WHO Group 1): Indicated to improve exercise capacity and delay clinical worsening in adult patients with PAH (NYHA/WHO Functional Class II to IV).
- Erectile Dysfunction (ED): Used as an affordable alternative to 25 mg/50 mg/100 mg Viagra tablets, often prescribed as one to four 20 mg tablets taken prior to sexual activity.
- Off-Label Uses: Treatment of secondary Raynaud’s phenomenon refractory to calcium channel blockers, high-altitude pulmonary edema (HAPE) prophylaxis, and SSRI-induced sexual dysfunction.
Dosage and Administration
- Pulmonary Arterial Hypertension (Revatio Equivalent Dosing):
- Standard Adult Dosing: 20 mg orally three times daily (TID) taken approximately 4 to 6 hours apart, with or without food.
- Note: Higher daily doses (e.g., up to 80 mg TID) are generally not recommended in PAH guidelines as they do not show greater long-term hemodynamic efficacy and increase adverse event rates.
- Erectile Dysfunction (Off-Label Titration):
- Typical Adult Dosing: 20 mg to 80 mg (1 to 4 tablets) taken orally approximately 30 to 60 minutes prior to sexual activity.
- Frequency Limit: Do not take more than once within a 24-hour period.
- Impact of Food: Sildenafil may be taken with or without food; however, ingestion with a high-fat meal delays oral absorption, increasing by roughly 60 minutes and reducing by nearly 30%.
Side Effects
Common Adverse Reactions:
- Vascular / Facial: Flushing (erythema and feeling of warmth), epistaxis (nosebleeds), peripheral edema
- Central Nervous System: Headache, dizziness, insomnia, lightheadedness
- Gastrointestinal: Dyspepsia (heartburn), diarrhea, nausea, gastritis
- Respiratory: Nasal congestion, sinusitis
- Ophthalmologic: Chromatopsia (mild, transient blue/green color tinge or visual brightness due to cross-reactivity with retinal PDE6), photophobia, blurred vision
Serious Adverse Reactions:
- Profound Hypotension & Syncope: Severe blood pressure drops, particularly when combined with vasodilators or alpha-blockers.
- Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION): A rare cause of sudden, irreversible decrease or total loss of vision in one or both eyes.
- Sudden Sensorineural Hearing Loss: Abrupt decline or complete loss of hearing, sometimes accompanied by tinnitus and vertigo.
- Priapism: Prolonged erection lasting longer than 4 hours; requires emergency urological intervention to prevent permanent erectile tissue damage.
- Cardiovascular Events: Myocardial infarction, ventricular arrhythmias, and sudden cardiac death in high-risk patients.
Key Drug Interactions
- Absolute Contraindication: Nitrates and Nitric Oxide Donors
- Co-administration with organic nitrates in any formulation (e.g., nitroglycerin, isosorbide dinitrate, isosorbide mononitrate) or recreational inhalants (“poppers,” amyl nitrite/alkyl nitrite) is strictly contraindicated. The combination produces profound, life-threatening hypotension and cardiovascular collapse.
- Soluble Guanylate Cyclase (sGC) Stimulators:
- Concurrent use with riociguat is contraindicated due to severe additive hypotensive risks.
- Strong Cytochrome P450 (CYP3A4) Inhibitors:
- Sildenafil is metabolized primarily by hepatic CYP3A4 (and to a minor extent CYP2C9). Co-administration with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) significantly increases sildenafil serum levels; dosage adjustments and clinical monitoring are required.
- Alpha-Adrenergic Blockers:
- Concomitant use with alpha-blockers (e.g., tamsulosin, doxazosin) for benign prostatic hyperplasia or hypertension can cause additive, symptomatic orthostatic hypotension. Patients should be hemodynamically stable on alpha-blocker therapy before initiating a PDE5 inhibitor at the lowest possible dose.
Warnings and Precautions
- Hypotensive Risk: Sildenafil possesses systemic vasodilatory properties. Caution is required in patients with pre-existing resting hypotension , severe volume depletion, or severe left ventricular outflow obstruction (e.g., aortic stenosis).
- Cardiovascular Risk with Sexual Exertion: Physicians should assess underlying cardiovascular risk before prescribing sildenafil for erectile dysfunction, as sexual activity involves a degree of cardiac risk.
- Priapism Risk: Patients with anatomical penile deformities (such as angulation, cavernosal fibrosis, or Peyronie’s disease) or conditions predisposing to priapism (such as sickle cell anemia, multiple myeloma, or leukemia) must use sildenafil with extreme caution.
- Vision & Hearing Warning: Patients should stop taking sildenafil and seek immediate medical attention in the event of sudden visual defects or sudden hearing impairment.
- Pulmonary Veno-Occlusive Disease (PVOD): If pulmonary edema develops during sildenafil therapy for PAH, consider the possibility of underlying pulmonary veno-occlusive disease; sildenafil should be promptly discontinued if PVOD is confirmed.