RISEDRONATE SODIUM

Posology The recommended dose in adults is one Risedronate Sodium 35mg gastro-resistant tabletsorally once a week. The tablet should be taken on the same day each week. The optimal duration of bisphosphonate treatment for osteoporosis has not been established.

The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of risedronate on an individual patient basis, particularly after 5 or more years of use. Special populations Elderly Of the patients receiving risedronate 35 mg gastro-resistant tablets in postmenopausal osteoporosis studies, 59% were 65 and over, while 13 % were 75 and over.

No overall differences in safety and effectiveness were observed between these patients and younger patients. Patients with renal impairment No dosage adjustment is required for those patients with mild to moderate renal impairment.

2). 1). Method of administration Risedronate Sodium 35mg gastro-resistant tabletsshould be taken orally in the morning immediately after breakfast. 2). The tablet must be swallowed whole and not sucked or chewed. To aid delivery of the tablet to the stomach, it is to be taken while in an upright position with a glass of plain water (≥120 ml).

4). Supplemental calcium and vitamin D should be considered if the dietary intake is inadequate. Patients should be instructed that if a dose is missed, it should be taken on the day that the tablet is remembered. Patients should then return to taking one tablet once a week on the day the tablet is normally taken.

Two tablets should not be taken on the same day.

Summary of the safety profile The most commonly reported side effects with risedronate tablets are gastrointestinal disorders including abdominal pain, diarrhoea, dyspepsia, nausea, constipation; musculoskeletal pain and headache. Tabulated list of adverse reactions from clinical studies Risedronate sodium has been studied in phase III clinical studies involving more than 15,000 patients.

The majority of undesirable effects observed in clinical studies was mild to moderate in severity and usually did not require cessation of therapy. Adverse experiences reported in phase III clinical studies in postmenopausal women with osteoporosis and considered possibly or probably related to risedronate sodium are listed below using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table 1 MedDRA System Organ Class Common Uncommon Rare Infections and infestations Influenza Blood and lymphatic system disorders Leukopenia, neutropenia Immune system disorders Hypersensitivity Endocrine disorders Hyperparathyroidism secondary Metabolism and nutrition disorders Hypercalcaemia Psychiatric disorders Depression Nervous system disorders Headache Dizziness, paresthesia, hypoaestesia Eye disorders Iritis*, ocular hyperaemia, conjunctivitis, vision blurred Ear and labyrinth disorders Vertigo Vascular disorders Hot flush, hypotension Respiratory, thoracic and mediastinal disorders Cough Gastrointestinal disorders Abdominal pain including abdominal pain upper and abdominal pain lower, constipation, dyspepsia, nausea, diarrhoea, vomiting Gastritis, Helicobacter gastritis, oesophagitis, dysphagia, duodenitis, oesophageal ulcer, abdominal discomfort, abdominal distension, erosive esophagitis, gastritis erosive, haematochezia, hyperchlorhydria, eructation, flatulence, gastritis atrophic, gastroesophageal reflux disease, gingivitis, haemorrhoids, hiatus hernia, melaena, abdominal tenderness, aphtous stomatitis, colitis, dry mouth, faecal incontinence, gastric mucosal hypertrophy, gastrointestinal inflammation, gastrointestinal pain, hypoaesthesia oral, lip swelling, odynophagia, swollen tongue Oesophageal stricture, glossitis Hepatobiliary disorders Abnormal liver function tests* Skin and subcutaneous tissue disorders Erythema, Henoch- Schonlein purpura, urticarial, dermatitis allergic, pruritus, rash Musculoskeletal and connective tissues disorders Musculoskeletal pain Arthralgia, back pain, muscle spasm, myalgia, pain in extremity, bone pain, muscle fatigue, muscular weakness, neck pain, pain in jaw Renal and Urinary disorders Nephrolithiasis Reproductive system and breast disorders Ovarian cyst General disorders and Asthenia, chills, administration site conditions fatigue, influenza like illness, chest discomfort, chest pain, face oedema, oedema, oedema peripheral, pain, pyrexia Investigations Blood calcium andphosphate decreased, heart rate irregular, urine analysis abnormal, transaminases increased blood alkaline phosphatase increased, blood parathyroid hormone increased, occult blood, platelet count decreased * No relevant incidences from Phase III osteoporosis studies; frequency based on adverse event/laboratory/rechallenge findings in earlier clinical studies.

Description of selected adverse events Gastrointestinal disorders In the Phase III study, comparing risedronate 35 mg gastro-resistant tablets and risedronate sodium 5 mg daily (immediate-release) more patients that used NSAID/aspirin reported upper gastrointestinal treatment-emergent adverse events than non-users.

4% in the NSAID/aspirin non-users in the 5 mg immediate-release before-breakfast group A higher incidence of upper abdominal pain was seen when risedronate 35 mg gastro-resistant tablets were taken in a fasted state 30 minutes before breakfast.

6% in the 5 mg immediate-release group.

During post marketing experience the following reactions have been reported Rare:

Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).

Very rare:

Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction). Frequency not known (cannot be estimated from available data) Eye disorders Iritis, uveitis, orbital inflammation Musculoskeletal and connective tissues disorders Osteonecrosis of the jaw Skin and subcutaneous tissue disorders Hypersensitivity and skin reactions, including angioedema, and bullous skin reactions, some severe including isolated reports of Stevens Johnson syndrome, toxic epidermal necrolysis and leukocytoclastic vasculitis.

Hair loss Immune system disorders Anaphylactic reaction Hepatobiliary disorders Serious hepatic disorders. In most of the reported cases the patients were also treated with other products known to cause hepatic disorders. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

5). 2). Efficacy of bisphosphonates in the treatment of osteoporosis is related to the presence of low bone mineral density and/or prevalent fracture. High age or clinical risk factors for fracture alone are not sufficient reasons to initiate treatment of osteoporosis with a bisphosphonate.

1). Hypocalcaemia should be treated before starting risedronate therapy. e. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting risedronate therapy. Upper gastrointestinal adverse reactions Bisphosphonates have been associated with oesophagitis, gastritis, oesophageal ulcerations and gastroduodenal ulcerations.

g. stricture or achalasia. - In patients who are unable to stay in the upright position for at least 30 minutes after taking the tablet. - If risedronate is given to patients with active or recent oesophageal or upper gastrointestinal problems (including known Barrett’s oesophagus).

Prescribers should emphasise to patients the importance of paying attention to the dosing instructions and be alert to any signs and symptoms of possible oesophageal reaction. The patients should be instructed to seek timely medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing, retrosternal pain or new/worsened heartburn.

Osteonecrosis of the jaw Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates.

Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates. g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw.

Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit /risk assessment. Osteonecrosis of the external auditory canal Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy.

Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

Atypical fractures of the femur Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare.

These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture.

Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture. This medicinal product contains less than 1 mmol sodium (23 mg) per gastro-resistant tablet, that is to say essentially ‘sodium-free’.

1. 4). Pregnancy and lactation. Severe renal impairment (creatinine clearance <30 ml/min).