Risendros^® (Tablets) Instructions for Use

Marketing Authorization Holder

Sanofi Russia JSC (Russia)

Manufactured By

Zentiva, k.s. (Czech Republic)

ATC Code

M05BA07 (Risedronic acid)

Active Substance

Risedronic acid (Rec.INN registered by WHO)

Dosage Form

Risendros®

Film-coated tablets, 35 mg: 2, 4, 8, or 12 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets orange in color, round, biconvex.

Excipients: microcrystalline cellulose – 230.5 mg, crospovidone – 8.0 mg, magnesium stearate – 1.5 mg.

Film coating composition: hypromellose 2910/5 – 5.57 mg, talc – 2.388 mg, macrogol 6000 – 0.82 mg, titanium dioxide – 1.1 mg, iron oxide red (E172) – 0.02 mg, iron oxide yellow (E172) – 0.102 mg.

2 pcs. – blisters (1) – cardboard packs.
4 pcs. – blisters (1) – cardboard packs.
4 pcs. – blisters (2) – cardboard packs.
4 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Bone resorption inhibitor for osteoporosis

Pharmacotherapeutic Group

Bone resorption inhibitor – bisphosphonate

Pharmacological Action

Inhibitor of bone resorption. Belongs to the group of bisphosphonates, regulates phosphorus-calcium metabolism, reduces bone resorption, stimulates osteogenesis.

Risedronic acid binds to hydroxyapatite at the cellular level and suppresses osteoclast function, reducing bone resorption. The time to reach the maximum therapeutic effect is 3-6 months, the duration of the therapeutic action is 12 months.

Pharmacokinetics

Absorption

Absorption of the drug after oral administration is relatively rapid, occurring in approximately 1 hour. The average bioavailability of the drug is 0.63%, which decreases when taken with food.

Distribution and Metabolism

Plasma protein binding – 24%. V_d – 6.3 L/kg. There are no data confirming systemic metabolism of risedronic acid.

Elimination

Approximately half of the absorbed dose is excreted by the kidneys within 24 hours. The mean renal clearance is 105 mL/min and the mean total clearance is 122 mL/min. Renal clearance is independent of drug concentration; there is a linear relationship between renal clearance and creatinine clearance.

Unabsorbed Risedronic acid is excreted through the intestine unchanged.

Indications

• Treatment of established postmenopausal osteoporosis;
• Treatment of osteoporosis in men at high risk of fractures.

ICD codes

Dosage Regimen

The drug is taken orally. The tablet should be swallowed whole, without chewing, and washed down with plain water (>120 mL). It is preferable to take the drug while in an upright position. After taking the tablet, the patient should not lie down for 30 minutes.

The drug must be taken on the same day of the week. The absorption of risedronic acid depends on food intake, so Risendros^® should be taken at least 30 minutes before the first meal, other medication, or drink (other than water).

For adults, the drug is prescribed at a dose of 35 mg once a week.

If a dose is missed, it should be taken on the day the patient remembers. Then, return to taking one tablet once a week on the usual day. Do not take 2 tablets on the same day.

During treatment, adherence to an adequate diet with sufficient calcium and vitamin D is recommended. If necessary, additional calcium and vitamin D supplements may be prescribed.

The optimal duration of osteoporosis treatment with bisphosphonates has not been established. The need for continued therapy should be determined individually for each patient based on an assessment of the benefit-risk ratio of using Risendros^®, especially after 5 or more years of use.

In elderly patients, dose adjustment of the drug is not required, as the bioavailability, distribution, and elimination parameters in this group of patients (over 60 years of age) do not significantly differ from those in young patients. Similar parameters have been recorded in very elderly patients (75 years of age and older).

In patients with mild to moderate renal impairment (CrCl >30 mL/min), no dose or dosage regimen adjustment is required. In patients with severe renal impairment (CrCl <30 mL/min), the use of the drug is contraindicated.

In children and adolescents under 18 years of age, the use of the drug is contraindicated due to insufficient data on its efficacy and safety.

Adverse Reactions

Most of the adverse effects observed in clinical trials were mild to moderate in severity and generally did not require discontinuation of therapy.

Adverse events are listed below with the following conventional grouping: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%), rare (≥0.01% and <0.1%), very rare (<0.01%), frequency not known (cannot be estimated from the available data).

From the digestive system common – constipation, dyspepsia, nausea, abdominal pain, diarrhea; uncommon – gastritis, esophagitis, dysphagia, duodenitis, esophageal ulcer; rare – glossitis, esophageal stricture; frequency not known – severe liver dysfunction (in most reported cases, patients were also taking other drugs that could cause liver dysfunction).

From the nervous system common – headache; rare – dizziness, asthenia, increased fatigue.

From the musculoskeletal system common – musculoskeletal pain; rare – calf muscle cramps; very rare – osteonecrosis of the jaw (following tooth extraction or oral inflammation).

From the sensory organs uncommon – iritis (scleral hyperemia, eye pain); rare – amblyopia, blurred vision, dryness of the eye mucosa, tinnitus.

From the skin and subcutaneous tissues frequency not known – leukocytoclastic vasculitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Allergic reactions frequency not known – angioedema, urticaria, anaphylactic reaction.

Other infections (including urinary tract infections), increased blood pressure; frequency not known – hair loss, slight decrease in serum calcium and phosphate concentrations.

Contraindications

• Hypocalcemia;
• Severe renal impairment (CrCl <30 mL/min);
• Pregnancy;
• Lactation (breastfeeding);
• Childhood and adolescence under 18 years;
• Hypersensitivity to the components of the drug.

With caution

• In erosive and ulcerative lesions of the gastrointestinal mucosa (including history), in patients with a history of impaired esophageal function (such as stricture or achalasia);
• If it is impossible to remain in an upright position for at least 30 minutes after taking the tablet.

Use in Pregnancy and Lactation

There are insufficient data on the use of risedronate sodium in pregnant women. Experimental studies in animals have shown reproductive toxicity. The potential risk to humans is unknown.

In experimental studies in animals, it was noted that a small amount of risedronate sodium is excreted in breast milk.

Risedronate sodium should not be used during pregnancy and lactation.

Use in Renal Impairment

In patients with mild to moderate renal impairment (CrCl >30 mL/min), no dose or dosage regimen adjustment is required. In patients with severe renal impairment (CrCl <30 mL/min), the use of the drug is contraindicated.

Pediatric Use

In children and adolescents under 18 years of age, the use of the drug is contraindicated due to insufficient data on its efficacy and safety.

Geriatric Use

In elderly patients, dose adjustment of the drug is not required, as the bioavailability, distribution, and elimination parameters in this group of patients (over 60 years of age) do not significantly differ from those in young patients. Similar parameters have been recorded in very elderly patients (75 years of age and older).

Data on the efficacy of bisphosphonates, including risedronate, in elderly women (>80 years) are limited.

Special Precautions

Before starting therapy with the drug, it is necessary to correct hypocalcemia, as well as other pathologies affecting bone and mineral metabolism (for example, impaired parathyroid function, vitamin D deficiency). With insufficient dietary intake of calcium and vitamin D, their additional intake is necessary.

The efficacy of bisphosphonates in the treatment of postmenopausal osteoporosis has been proven in patients with low bone mineral density and/or previous fractures. Old age or the presence of clinical risk factors for fractures alone are not sufficient criteria for starting osteoporosis treatment with bisphosphonates.

Data on the efficacy of bisphosphonates, including risedronate, in elderly women (>80 years) are limited.

The use of bisphosphonates is associated with the occurrence of esophagitis, gastritis, esophageal ulcers, and gastroduodenal ulcers. Therefore, the drug Risendros^® should be used with caution

• In patients who have a history of impaired esophageal function that slows esophageal transit or emptying (e.g., esophageal stricture or achalasia);
• In patients who cannot remain in an upright position for at least 30 minutes after taking the tablet;
• In patients with active or recent diseases of the esophagus or upper gastrointestinal tract (including an established diagnosis of Barrett’s esophagus).

Patients should be warned about the need to strictly follow the dosing instructions for Risendros^® and to be alert to any signs or symptoms related to the esophagus. Patients should be instructed to seek prompt medical attention if they develop symptoms of esophageal irritation, such as dysphagia, pain on swallowing, retrosternal pain, or new/worsening heartburn.

Cases of osteonecrosis of the jaw following tooth extraction and/or local infection (including osteomyelitis) have been reported in cancer patients. Before starting treatment with bisphosphonates, patients with concomitant risk factors (e.g., cancer, chemotherapy, radiation therapy, corticosteroid therapy, poor oral hygiene) should undergo a dental examination with appropriate therapeutic dental treatment. During treatment, such patients should, if possible, avoid invasive dental procedures.

Food, beverages (other than plain water) and medications containing polyvalent cations (such as calcium, magnesium, iron, and aluminum) interfere with the absorption of bisphosphonates, so they should not be taken simultaneously with the drug Risendros^®.

Atypical subtrochanteric and diaphyseal femoral fractures have been reported during therapy with bisphosphonates, mainly in patients receiving long-term treatment for osteoporosis. These fractures occurred with minimal or no trauma. When examining a patient with suspected atypical femoral fracture, discontinuation of bisphosphonate therapy should be considered based on an individual assessment of the benefit-risk ratio.

During treatment with bisphosphonates, the patient should be advised to report any pain in the thigh, hip, or groin. Any patient presenting with such symptoms should be evaluated for an atypical femoral fracture.

Effect on ability to drive vehicles and operate machinery

No adverse effects of Risendros^® on the ability to drive vehicles and engage in activities requiring concentration and speed of psychomotor reactions have been reported. However, the drug may in rare cases cause dizziness, asthenia, and increased fatigue, so caution should be exercised when driving vehicles and operating machinery.

Overdose

Symptoms (potentially possible): hypocalcemia.

Treatment: intake of milk, administration of antacids containing magnesium, calcium, or aluminum. In case of significant overdose, gastric lavage is recommended to remove the unabsorbed drug.

Drug Interactions

Medicinal products containing polyvalent cations, such as calcium, magnesium, iron, and aluminum, may reduce the absorption of the drug.

There are no clinically significant interactions with NSAIDs (including acetylsalicylic acid), H₂-histamine receptor blockers, proton pump inhibitors, antacid medications, slow calcium channel blockers, beta-blockers, thiazide diuretics, glucocorticosteroids, anticoagulants, anticonvulsants, cardiac glycosides.

The drug is compatible with HRT drugs.

Storage Conditions

The drug does not require special storage conditions. It should be stored out of the reach of children.

Shelf Life

Shelf life – 2 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.