Naftopidil

Usage

• Naftopidil is prescribed for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the prostate gland. It is specifically indicated for the relief of dysuria (painful urination) in men with BPH.

• Pharmacological Classification: Alpha-1 adrenergic receptor antagonist (alpha-blocker).

• Mechanism of Action: Naftopidil selectively blocks alpha-1 adrenergic receptors, predominantly the alpha-1D subtype located in the prostate and bladder. This action relaxes the smooth muscles in the lower urinary tract, thus improving urine flow and reducing BPH-related symptoms. It also exhibits some affinity for 5-HT1A serotonin receptors, which can suppress bladder contractions and improve nocturia.

Alternate Names

• No widely used alternate names exist.

• Brand Names: Nafodil, Flivas, etc. (Brand names can vary regionally.)

How It Works

• Pharmacodynamics: Naftopidil relaxes the smooth muscle in the prostate and bladder neck by blocking alpha-1A adrenergic receptors, primarily the alpha-1D subtype, reducing urethral pressure and improving urine flow. Its secondary action on 5-HT1A receptors contributes to further alleviation of storage symptoms like nocturia.

• Pharmacokinetics: Naftopidil is administered orally and well-absorbed. It is metabolized primarily in the liver by CYP2C9 and CYP3A4 enzymes and excreted mainly in the bile.

• Mode of Action: Naftopidil competitively binds to alpha-1A adrenergic receptors, inhibiting the binding of norepinephrine and preventing smooth muscle contraction.

• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Alpha-1A adrenergic receptor blockade and some 5-HT1A receptor agonism.

• Elimination Pathways: Primarily hepatic metabolism via CYP2C9 and CYP3A4, followed by biliary excretion.

Dosage

Standard Dosage

Adults:

• Initial: 25 mg once daily after a meal.
• Maintenance: May be increased gradually (at 1-2 week intervals) to 50-75 mg once daily, adjusting according to symptoms. Maximum dose is 75 mg/day.

Children:

• Not recommended for use in children under 18 years of age. Safety and efficacy have not been established.

Special Cases:

• Elderly Patients: Dose adjustments may be necessary, starting with a lower dose and titrating cautiously.
• Patients with Renal Impairment: Caution is advised, especially in severe renal impairment. Dose reduction might be considered.
• Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution is advised in moderate hepatic impairment.
• Patients with Comorbid Conditions: Caution in patients with cardiovascular disease, orthostatic hypotension, or salt imbalance.

Clinical Use Cases

Naftopidil is not typically indicated for use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is for BPH/LUTS management in an outpatient setting.

Dosage Adjustments

• Adjust dosage based on individual response and tolerability.
• Consider renal and hepatic function, cardiovascular status, and concomitant medications.

Side Effects

Common Side Effects:

• Dizziness/Lightheadedness
• Orthostatic Hypotension
• Headache
• Nausea/Vomiting
• Gastrointestinal discomfort
• Nasal congestion
• Fatigue

Rare but Serious Side Effects:

• Allergic reactions (rash, itching, hives, angioedema)
• Severe hypotension
• Syncope

Long-Term Effects:

• Limited data available on long-term effects.

Adverse Drug Reactions (ADR):

• Severe allergic reactions
• Hepatic dysfunction (rare)

Contraindications

• Hypersensitivity to naftopidil
• Severe hepatic impairment
• Use in women (especially pregnant or breastfeeding)

Drug Interactions

• Other alpha-blockers (increased risk of hypotension)
• Antihypertensives (additive hypotensive effects)
• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) - may increase naftopidil levels
• CYP3A4 inducers (e.g., rifampicin, carbamazepine) - may decrease naftopidil levels
• Alcohol (may increase dizziness and drowsiness)

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Not established, contraindicated in women.

• Naftopidil is present in semen. Men should use condoms, especially if their partner is pregnant.

• Breastfeeding: Contraindicated.

Drug Profile Summary

• Mechanism of Action: Alpha-1A adrenergic receptor antagonist, especially alpha-1D subtype, relaxing smooth muscle in the prostate and bladder.
• Side Effects: Dizziness, orthostatic hypotension, headache, nausea, fatigue.
• Contraindications: Hypersensitivity, severe hepatic impairment, use in women.
• Drug Interactions: Other alpha-blockers, antihypertensives, CYP3A4 inhibitors/inducers, alcohol.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: 25-75 mg once daily.
• Monitoring Parameters: Blood pressure, liver function tests (if indicated).

Popular Combinations

• Not typically used in combination therapy for BPH. May be used with 5-alpha reductase inhibitors in some cases, though clinical benefits of the combination are not fully established.

Precautions

• Monitor blood pressure, especially at initiation and after dose adjustments.
• Evaluate hepatic and renal function in patients with existing impairments.
• Advise patients about potential for dizziness and orthostatic hypotension, especially when standing up from a lying or sitting position.
• Caution patients about operating machinery or driving.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Naftopidil?

A: The initial dose is 25 mg once daily, which can be increased to 50-75 mg/day based on individual response. The maximum dose is 75 mg per day.

Q2: What are the most common side effects?

A: Dizziness, orthostatic hypotension, headache, nausea, and fatigue.

Q3: Can Naftopidil be used in women?

A: No, Naftopidil is contraindicated in women, especially during pregnancy and breastfeeding.

Q4: How does Naftopidil work?

A: It blocks alpha-1 adrenergic receptors, relaxing the smooth muscle in the prostate and bladder, improving urine flow.

Q5: What are the serious side effects of Naftopidil?

A: Allergic reactions, severe hypotension, and syncope.

Q6: What should I do if I miss a dose?

A: Skip the missed dose and take the next dose at the regular time. Do not double the dose.

Q7: Does Naftopidil interact with other medications?

A: Yes, it can interact with other alpha-blockers, antihypertensives, CYP3A4 inhibitors/inducers, and alcohol.

Q8: Can I drink alcohol while taking Naftopidil?

A: Alcohol may exacerbate side effects like dizziness and drowsiness and should be avoided or consumed with caution.

Q9: Can Naftopidil cure BPH?

A: No, it does not cure BPH but manages the associated LUTS.

Q10: How long does it take for Naftopidil to work?

A: Patients may experience some relief within a few days, but significant improvement usually takes a few weeks.