Generic Name

α1‑adrenergic receptor antagonist

Mechanism

• Targeting α1‑adrenergic receptors
• *Qalsody* binds competitively to α1‑adrenergic receptors primarily located on the smooth muscle of the prostate, bladder neck, and urethra.
• This selective blockade reduces smooth‑muscle tone, thereby decreasing prostatic urethral resistance and improving urine flow.
• Pharmacodynamic profile
• The drug’s affinity is highest for the α1A subtype, which predominates in the prostate, and to a lesser extent for α1B and α1D subtypes.

Pharmacokinetics

• Absorption
• Rapid oral absorption; peak plasma concentration (Cmax) reached ~1.5 h after dosing.
• Food delays absorption slightly but does not significantly reduce bioavailability.
• Distribution
• Protein binding: ~60 %, mainly to albumin.
• Volume of distribution: ~35 L.
• Metabolism
• Primary hepatic metabolism via CYP3A4; minor pathways involve conjugation.
• Excretion
• Renal elimination constitutes ~70 % of the dose.
• Half‑life (t½): 4‑8 h (average ~6 h).
• Dosage adjustments
• No dose reduction required for mild to moderate renal impairment.
• Caution in severe hepatic impairment due to reduced clearance.

Indications

• Benign prostatic hyperplasia (BPH)
• Treatment of LUTS—e.g., weak stream, hesitancy, incomplete emptying, and urinary frequency.
• Open‑label studies have shown significant improvement in IPSS (International Prostate Symptom Score) and maximum urinary flow rate (Qmax).

Contraindications

• Contraindicated
• Hypersensitivity to alfuzosin or any excipients.
• Severe aortic stenosis *(hemodynamic instability)*.
• Warnings
• Orthostatic hypotension: particularly in the first weeks of therapy or with dose escalation.
• Drug interactions
• *CYP3A4 inhibitors* (ketoconazole, clarithromycin) increase plasma concentrations.
• *Cardiac drugs* (digoxin, amiodarone) may potentiate hypotensive effects.
• Pregnancy: Category C; use only if benefits outweigh risks.

Dosing

• Initial dose: 10 mg orally once daily (morning), either with or without food.
• Maintenance: 15 mg once daily if adequate symptom control is not achieved at the 10 mg dose.
• Administration considerations
• Take at the same time each day to minimize peaks and troughs.
• Avoid concurrent use of high‑dose antihypertensives to reduce additive hypotension.

Adverse Effects

• Common (≤10 %)
• Dizziness / light‑headedness
• Orthostatic hypotension
• Headache
• Flushing (redness, warmth)
• Palpitations (often benign)
• Nasal congestion
• Serious (≤1 %)
• Severe orthostatic hypotension → syncope or falls
• Hypotensive crisis (systolic BP < 90 mmHg)
• Severe allergic reactions (rash, pruritus, anaphylaxis)

Monitoring

• Blood pressure & heart rate
• Baseline and after 4‑8 h post‑dose to detect orthostatic changes.
• Renal & hepatic panels
• At baseline and every 4–6 weeks if renal dysfunction is present.
• Serum digoxin levels (if concomitant therapy)
• Adjust dose as clinically indicated.
• Symptom assessment
• IPSS and Qmax at 4 weeks, then periodically.

Clinical Pearls

• Titrate cautiously: Begin at 10 mg; if symptoms persist after 4 weeks, increase to 15 mg. A gradual titration mitigates orthostatic hypotension.
• Day‑time dosing: Administer in the morning; this aligns peak plasma levels with daytime activity, reducing nocturia and nighttime hypotension.
• Synergistic therapy: Combining Qalsody with a 5α‑reductase inhibitor (e.g., finasteride) can address both dynamic obstruction (via α1 blockade) and static obstruction (by shrinking prostate volume).
• Patient education: Advise patients to rise slowly from sitting or lying positions and to monitor their pulse and BP daily, especially after dose adjustments or when adding new medications.
• Food interaction nuance: A high‑fat meal slightly delays absorption (~30 min); however, the overall bioavailability remains unchanged, so no dose change is needed.
• Adverse effect management: For patients experiencing flushing or headache, *assume* a mild vasodilatory effect; these symptoms typically resolve within 2–3 weeks. If persistent, consider dose reduction or alternative α‑blocker.

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• Keywords: Qalsody, alfuzosin, alpha‑1 receptor antagonist, BPH, LUTS, pharmacokinetics, dosing, adverse effects, orthostatic hypotension, clinical pearls.