Ranoprost

I N S T R U C T I O N for medical use of the medicinal product RANOPROST (RANOPROST)

Composition:

Active substance: tamsulosine;

1 capsule contains tamsulosine hydrochloride 0.4 mg;

Excipients: microcrystalline cellulose, magnesium stearate, methacrylate copolymer dispersion (dispersion of methacrylic acid-ethyl acrylate copolymer (1:1) (30%), sodium hydroxide, triacetin, talc, titanium dioxide (E 171).

Pharmaceutical form. Capsules.

Main physicochemical properties:

hard gelatin capsules with brown cap and orange body, size "2", marked with "R" on the cap and "TSN 400" on the body in black edible ink; the capsules contain white or almost white granular material.

Pharmacotherapeutic group.

Agents used in benign prostatic hyperplasia. α1-adrenergic receptor antagonists.

ATC code G04C A02.

Pharmacological Properties.

Pharmacodynamics.

Ranoprost selectively and competitively blocks postsynaptic α1-adrenoceptors, particularly α1A and α1D subtypes, located in the smooth muscle of the prostate gland, bladder neck, and prostatic urethra. This leads to reduced smooth muscle tone in the prostate, bladder neck, and prostatic urethra, resulting in improved urinary flow.

Concurrently, symptoms of obstruction and irritation associated with benign prostatic hyperplasia are alleviated (difficulty initiating urination, weakened urinary stream, post-void dribbling, sensation of incomplete bladder emptying, frequent urination, nocturia, urinary urgency).

The ability of α1A-adrenoceptor blockers to reduce arterial blood pressure is related to decreased peripheral resistance. Ranoprost at a daily dose of 0.4 mg does not cause clinically significant reduction in systemic arterial pressure (BP), both in patients with arterial hypertension and in patients with normal baseline BP.

Pharmacokinetics.

Absorption. Ranoprost is well absorbed from the gastrointestinal tract, with bioavailability nearly 100%. Absorption of tamsulosin is somewhat slower when taken after food intake. Consistent absorption is achieved when the patient takes Ranoprost at the same time each day after meals. The pharmacokinetics of tamsulosin are linear.

After a single dose administered following food intake, peak plasma concentration of tamsulosin is reached approximately 6 hours later. Steady-state concentration is achieved by day 5 of daily dosing. The maximum plasma concentration at steady state is approximately two-thirds higher than that achieved after a single dose.

Distribution. Plasma protein binding is 99%. The volume of distribution is low—up to 0.2 L/kg.

Metabolism. Tamsulosin hydrochloride does not undergo a first-pass effect and is slowly metabolized in the liver, forming pharmacologically active metabolites that retain high selectivity for α1-adrenoceptors. The majority of the active substance circulates in the bloodstream unchanged.

Elimination. Tamsulosin hydrochloride is excreted via the kidneys; 4–6% of the dose is excreted unchanged. The elimination half-life of tamsulosin is 19 hours after a single dose and 15 hours at steady state, respectively.

Clinical characteristics.

Indications.

Treatment of functional disorders of the lower urinary tract due to benign prostatic hyperplasia.

Contraindications.

Hypersensitivity reactions, including Quincke's angioedema, to tamsulosin hydrochloride or to any of the excipients; orthostatic hypotension; severe hepatic impairment.

Interaction with other medicinal products and other forms of interaction.

Interactions have been studied only in adults.

No drug interactions were observed when tamsulosin hydrochloride was administered concomitantly with atenolol, enalapril, nifedipine, or theophylline. Concomitant administration with cimetidine increases, while with furosemide decreases, the plasma concentration of tamsulosin; however, since these levels remain within the normal range, no special dose adjustment of tamsulosin is required.

In in vitro studies, diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin, and warfarin do not affect the free fraction of tamsulosin in human plasma. Similarly, tamsulosin does not alter the levels of free fractions of diazepam, propranolol, trichlormethiazide, and chlormadinone in human plasma.

However, diclofenac and warfarin may increase the elimination rate of tamsulosin.

Concomitant administration of tamsulosin hydrochloride with strong CYP3A4 inhibitors may lead to increased effects of tamsulosin hydrochloride. Concomitant use with ketoconazole (a known potent CYP3A4 inhibitor) resulted in increases in Cmax and AUC by up to 2.2 and 2.8 times, respectively.

Concomitant administration of tamsulosin hydrochloride and paroxetine (a potent CYP2D6 inhibitor) leads to increases in Cmax and AUC by up to 1.3 and 1.6 times, respectively, but this is not considered clinically significant.

Tamsulosin hydrochloride should not be prescribed in combination with strong CYP3A4 inhibitors in patients who are poor metabolizers of CYP2D6.

Tamsulosin hydrochloride should be used with caution when combined with strong and moderate CYP3A4 inhibitors.

Concomitant administration with other α1-adrenoblockers may enhance the hypotensive effect.

Special precautions for use

Intraoperative floppy iris syndrome (IFIS) has been reported in some patients undergoing cataract or glaucoma surgery while taking or having taken tamsulosin. This condition, characterized by iris flaccidity, is associated with α1-receptor blockade. Therefore, tamsulosin is not recommended for patients scheduled to undergo cataract or glaucoma surgery.

It is generally recommended to discontinue tamsulosin treatment 1–2 weeks prior to cataract or glaucoma surgery. However, the optimal timing and necessity of discontinuation have not yet been definitively established.

Ophthalmic surgeons should be informed if a patient is currently or has previously been treated with tamsulosin in order to anticipate and manage potential complications related to iris instability during surgery.

As with other α1-adrenoblockers, use of Ranoprost Kassul may in individual cases lead to a reduction in blood pressure, which may occasionally result in loss of consciousness. If early signs of orthostatic hypotension (e.g., dizziness, weakness) occur, the patient should immediately lie down and remain in a horizontal position until symptoms resolve.

Prior to initiating treatment with Ranoprost, a medical evaluation should be performed to rule out other underlying conditions that may cause symptoms similar to benign prostatic hyperplasia. A digital rectal examination of the prostate should be conducted before starting treatment, and if necessary, a prostate-specific antigen (PSA) test should be performed before treatment initiation and at regular intervals during therapy.

Ranoprost should be used with particular caution in patients with severe renal impairment (creatinine clearance <10 mL/min), as clinical studies with Ranoprost in this patient population have not been conducted.

Tamsulosin hydrochloride should not be co-administered with strong inhibitors of CYP3A4 in patients who are also poor metabolizers of CYP2D6.

Tamsulosin hydrochloride should be used with caution when co-administered with strong or moderate inhibitors of CYP3A4 (see section Interaction with other medicinal products and other forms of interaction).

Use during pregnancy or breastfeeding

This medicinal product is intended for use in men only.

Fertility

During short- and long-term clinical trials with tamsulosin, ejaculation disorders were observed. Cases of ejaculation disorder, retrograde ejaculation, and impaired ejaculation have been reported in the post-marketing period.

Ability to influence reaction rate when driving or operating machinery

Studies on the effect of the drug on the ability to drive or operate machinery have not been conducted. However, patients should be warned about the potential occurrence of dizziness.

Dosage and Administration.

For adults, take 1 capsule once daily at the same time after a meal (after breakfast). Swallow the capsule whole, without chewing, with a glass of water.

The duration of treatment is determined individually.

Renal impairment does not require dose adjustment.

Patients with mild to moderate hepatic impairment also do not require dose reduction.

Children.

The drug is not intended for use in children.

Safety and efficacy of tamsulosin in children have not been evaluated.

Overdose.

Overdose of tamsulosin hydrochloride may potentially cause severe hypotensive effects. Severe hypotension has been reported at various levels of overdose.

Treatment.

In case of a sharp drop in blood pressure due to overdose, supportive therapy should be administered to restore normal cardiovascular function (e.g., the patient should be placed in a supine position). If this measure is ineffective, infusion therapy and administration of vasopressor agents should be initiated. Renal function should be monitored, and general supportive therapy should be provided. Due to the high degree of protein binding of tamsulosin, hemodialysis is unlikely to be effective.

To prevent further absorption of the drug, induced vomiting may be considered. In cases of significant overdose, gastric lavage with activated charcoal and low-osmotic laxatives such as sodium sulfate should be administered.

Adverse reactions.

Central nervous system: dizziness, headache, fainting.

Eye disorders: blurred vision*, visual disturbances*.

Cardiovascular system: palpitations, postural hypotension.

Respiratory system: rhinitis, epistaxis*.

Gastrointestinal disorders: constipation, diarrhea, nausea, vomiting.

Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, angioneurotic edema, Stevens-Johnson syndrome, erythema multiforme*, exfoliative dermatitis*.

Reproductive system: ejaculation disorders, including retrograde ejaculation and ejaculation failure.

General disorders: asthenia.

*- reported during the post-marketing period.

During post-marketing surveillance, cases of intraoperative iris instability (intraoperative floppy iris syndrome) during cataract and glaucoma surgery have been reported in patients receiving tamsulosin (see section "Special precautions").

Post-marketing experience: in addition to the above-mentioned adverse reactions, cases of atrial fibrillation, arrhythmia, tachycardia, and dyspnea have been reported. Since these cases were reported spontaneously, the frequency of reporting and the role of tamsulosin in these cases cannot be reliably established.

Shelf life.

2 years.

Storage conditions.

Store in a dry place, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

10 capsules in a blister; 3 blisters in a cardboard pack.

Prescription category. Prescription only.

Manufacturer.

San Pharmaceutical Industries Limited / Sun Pharmaceutical Industries Limited.

Manufacturer's address and location of business activity.

Industrial Area 3, Dewas - 455001, India / Industrial Area 3, Dewas, 455001, India.