Dalfaz^® SR (Tablets) Instructions for Use

Marketing Authorization Holder

Sanofi Winthrop Industrie (France)

ATC Code

G04CA01 (Alfuzosin)

Active Substance

Alfuzosin (Rec.INN registered by WHO)

Dosage Form

Dalfaz® SR

Extended-release tablets 10 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Extended-release tablets round, biconvex, three-layer (one white layer between two yellow layers of different color intensity); inclusions are allowed.

Composition of the first layer of the tablet hypromellose, hydrogenated castor oil, ethylcellulose 20, iron oxide yellow (E172), colloidal hydrated silicon dioxide, magnesium stearate.

Composition of the second layer of the tablet alfuzosin hydrochloride, mannitol, hypromellose, microcrystalline cellulose, povidone, colloidal hydrated silicon dioxide, magnesium stearate.

Composition of the third layer of the tablet hypromellose, hydrogenated castor oil, povidone, iron oxide yellow (E172), colloidal hydrated silicon dioxide, magnesium stearate.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Drug used for urination disorders associated with benign prostatic hyperplasia. Alpha₁-adrenergic blocker

Pharmacotherapeutic Group

Alpha1-adrenergic blocker

Pharmacological Action

An alpha₁-adrenergic blocker, a quinazoline derivative. It selectively acts on postsynaptic α₁-adrenergic receptors. In vitro studies have shown the selectivity of alfuzosin’s action on α₁-adrenergic receptors located in the prostate gland, in the area of the bladder neck and in the prostatic part of the urethra.

As a result of a direct effect on the smooth muscle of the prostate tissue, it reduces the resistance to urine outflow.

Alfuzosin improves urination parameters by reducing urethral tone and bladder outflow resistance, and facilitates bladder emptying.

In placebo-controlled studies of alfuzosin in patients with benign prostatic hyperplasia, a significant increase in the maximum urine flow rate (Q_max) was detected, averaging 30% in patients with Q_max ≤15 ml/s. This improvement was noted after the first dose of the drug. A significant decrease in urine flow resistance and an increase in the volume of urine excreted also occurred; a significant decrease in residual urine volume was observed.

Pharmacokinetics

Absorption and Distribution

When taking Dalfaz^® SR, due to the characteristics of the dosage form that provides prolonged release of alfuzosin hydrochloride, the average bioavailability in middle-aged healthy volunteers is 104.4% compared to the immediate-release form (when taken at 2.5 mg twice a day).

C_max is reached 9 hours after taking the drug compared to 1 hour for the immediate-release form. Plasma protein binding is about 90%.

Metabolism and Excretion

Alfuzosin undergoes significant metabolism in the liver, only 11% of the administered dose is excreted unchanged in the urine; most of the inactive metabolites (75-90%) are excreted in the feces.

T_1/2 is 9.1 hours.

Pharmacokinetics in Special Clinical Cases

In elderly patients, pharmacokinetic parameters (C_max and AUC) do not increase.

In patients with renal impairment, C_max and AUC are moderately increased (which is not clinically significant and does not require a change in the dosage regimen), while T_1/2 does not change.

The pharmacokinetic profile of the drug does not change in patients with chronic heart failure.

Indications

• Treatment of functional symptoms of benign prostatic hyperplasia;
• As an adjuvant for catheter use in acute urinary retention associated with benign prostatic hyperplasia.

ICD codes

Dosage Regimen

The drug is taken orally, after meals.

For treatment of functional symptoms of benign prostatic hyperplasia the recommended dose is 1 tab. (10 mg) once a day.

As an adjuvant for catheter use in acute urinary retention associated with benign prostatic hyperplasia, the recommended dose is 1 tab. (10 mg) once a day, starting from the first day of catheterization. The drug is used for 3-4 days, i.e., 2-3 days during catheter use and 1 day after its removal.

Tablets should be swallowed whole.

Adverse Reactions

From the digestive system nausea, epigastric pain, diarrhea, dry mouth.

From the CNS headache, dizziness, weakness, drowsiness, asthenic syndrome, fainting, syncope.

From the cardiovascular system tachycardia, orthostatic hypotension, in patients with coronary artery disease – exacerbation of angina symptoms.

Allergic reactions: rarely – skin rash, itching.

Other edema, skin hyperemia.

Contraindications

• Orthostatic hypotension;
• Severe liver dysfunction;
• Severe renal failure (creatinine clearance < 30 ml/min);
• Intestinal obstruction (due to the content of castor oil in the drug);
• Hypersensitivity to alfuzosin and/or other components of the drug.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

Use in Renal Impairment

In patients with renal impairment, C_max and AUC are moderately increased, without a noticeable increase in T_1/2 (these changes are not clinically significant and do not require a change in the dosage regimen).

The drug is contraindicated in severe renal failure (creatinine clearance < 30 ml/min).

Special Precautions

In some cases, especially in patients receiving antihypertensive therapy, within a few hours after taking the drug (as with other α₁-adrenergic blockers), postural hypotension may develop with or without symptoms (dizziness, fatigue, increased sweating). In such situations, the patient should lie down until the symptoms completely disappear. These reactions are usually temporary, occur at the beginning of treatment and usually do not affect the continuation of therapy. The patient should be warned about the possibility of such reactions.

Patients with coronary insufficiency should not be prescribed Dalfaz^® SR as monotherapy. Treatment of coronary insufficiency must be continued. If angina attacks persist or their course worsens, the drug should be discontinued.

Patients should be warned that the tablets should be swallowed whole. Breaking the tablet may lead to inappropriate release and absorption of the active substance and, accordingly, to adverse reactions that may develop rapidly.

Effect on the ability to drive vehicles and operate machinery

Side effects such as dizziness, visual disturbances and asthenia may occur mainly at the beginning of treatment. This should be taken into account when driving vehicles and operating machinery.

Overdose

Symptoms arterial hypotension.

Treatment hospitalization is indicated, the patient should be in a lying position. Treatment of arterial hypotension is carried out (administration of vasoconstrictors, solutions and high-molecular-weight substances; measures aimed at increasing the circulating blood volume). Dialysis is ineffective due to the high degree of binding of alfuzosin to plasma proteins.

Drug Interactions

Not recommended combinations

With other α₁-adrenergic blockers (prazosin, urapidil, minoxidil): increased hypotensive effect, risk of severe postural hypotension.

Combinations to be considered

With antihypertensive drugs: increased hypotensive effect and risk of postural hypotension (additive effect).

With inhibitors of the CYP3A4 system (ketoconazole, itraconazole, ritonavir): increased concentration of alfuzosin in the blood.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.