CORICA COMBI

Corica Combi is a weekly therapy of 1 Risedronate 35 mg film-coated tablet and 6 calcium/vitamin D3 effervescent tablets. Risedronate sodium Posology The recommended dose in adults is 1 Risedronate 35 mg tablet on the first day followed on the next day by 1 calcium/vitamin D3 effervescent tablet daily for 6 days.

This 7-day sequence is then repeated each week starting with Risedronate 35 mg tablet. Method of administration The Risedronate 35 mg film-coated tablet should be taken orally on the same day each week. The absorption of risedronate sodium is affected by food, thus to ensure adequate absorption, patients should take the Risedronate 35 mg tablet  Before breakfast: At least 30 minutes before the first food, other medicinal product or drink (other than plain water) of the day.

The tablet must be swallowed whole and not sucked or chewed. To aid delivery of the tablet to the stomach the Risedronate 35 mg tablet is to be taken while in an upright position with a glass of plain water (≥120 ml). 4). 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 population Elderly No dose adjustment is necessary since bioavailability, distribution and elimination were similar in elderly (>60 years of age) compared to younger subjects.

This has also been shown in the very elderly, 75 years old and above in postmenopausal population. Renal impairment No dose adjustment is required for those patients with mild to moderate renal impairment. 2). 1). Calcium carbonate/vitamin D3 Posology Calcium/vitamin D3 effervescent tablet should be taken each day for 6 days per week starting on the day after the Risedronate 35 mg tablet is taken.

In case the Risedronate 35 mg tablet dose is missed, patients should be instructed that the Risedronate 35 mg tablet should be taken on the next day in the morning according to the dosing instructions. In this particular instance, patients should then take their calcium/vitamin D3 effervescent tablet on the following day.

Patients should be instructed that they should never take the tablet and the effervescent tablet the same day. If the calcium/vitamin D3 effervescent tablet dose is missed, the patient should be instructed to continue taking one effervescent tablet each day beginning on the day the missed dose is remembered.

Patient should be instructed that they should not take two effervescent tablets on the same day. Any remaining calcium/vitamin D3 effervescent tablet at the end of the weekly cycle should be discarded. Paediatric population Calcium/vitamin D3 is not intended for intake in children.

Method of administration The effervescent tablet is taken dissolved in a glass of water.

Summary of the safety profile Risedronate sodium 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 were mild to moderate in severity and usually did not require cessation of therapy.

Undesirable effects reported in phase III clinical studies in postmenopausal women with osteoporosis treated for up to 36 months with risedronate sodium 5mg/day (n=5020) or placebo (n=5048) and considered possibly or probably related to risedronate sodium are listed below using the following convention (incidences versus placebo are shown in brackets): very common (≥1/10); common (≥1/100; <1/10); uncommon (≥1/1,000; <1/100); rare (≥1/10,000; <1/1,000); very rare (<1/10,000).

8% vs. 0% vs. 5% vs. 3% vs. 5% vs. 0% vs. 9% vs. 9% vs. 4% vs. 2% vs. 2% vs. 1% vs. 1% vs. 1% vs. 9%) Investigations: Rare: abnormal liver function tests* * No relevant incidences from Phase III osteoporosis studies; frequency based on adverse event/laboratory/rechallenge findings in earlier clinical studies.

In a one-year, double-blind, multicentre study comparing risedronate 5 mg daily (n= 480) and risedronate sodium 35 mg weekly (n=485) in postmenopausal women with osteoporosis, the overall safety and tolerability profiles were similar.

6% vs. 2% vs. 8%).

Laboratory findings:

Early, transient, asymptomatic and mild decreases in serum calcium and phosphate levels have been observed in some patients.

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

Musculoskeletal and connective tissues disorders: Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction) (frequency rare) Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction) (frequency very rare) The following additional adverse reactions have been reported during post- marketing use (frequency unknown): Immune system disorders: anaphylactic reaction Eye disorders: iritis, uveitis Hepatobiliary disorders: serious hepatic disorders.

In most of the reported cases the patients were also treated with other products known to cause hepatic disorders. Skin and subcutaneous tissue disorders: hypersensitivity and skin reactions, including angioedema, generalised rash, urticaria and bullous skin reactions, some severe including isolated reports of Stevens-Johnson syndrome and toxic epidermal necrolysis and leukocytoclastic vasculitis.

Hair loss. Musculoskeletal and connective tissues disorders: osteonecrosis of the jaw Calcium carbonate/vitamin D3 Adverse reactions are listed below, by system organ class and frequency following convention: very common (≥1/10); common (≥1/100; <1/10); uncommon (≥1/1,000; <1/100); rare (≥1/10,000; <1/1,000); very rare (<1/10,000).

Immune system disorders Rare:

Hypersensitivity Very rare: Isolated cases of systemic allergic reactions (anaphylactic reaction, face oedema, laryngeal oedema, angioneurotic oedema) have been reported.

Metabolism and nutrition disorders Uncommon:

Hypercalcaemia and hypercalciuria.

Very rare:

Milk-alkali syndrome (frequent urge to urinate, continuing headache, continuing loss of appetite, nausea or vomiting, unusual tiredness or weakness, hypercalcaemia, alkalosis and renal impairment). 9).

Gastrointestinal disorders Rare:

Constipation, flatulence, nausea, vomiting, abdominal pain and diarrhoea.

Skin and subcutaneous disorders Rare:

Pruritus, skin rash and urticaria. 4). 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.

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5). 2). 5 standard deviations (SD)] 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). 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.

Hypocalcaemia should be treated before starting Risedronate therapy. e. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting Risedronate therapy. 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 judgment 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. In patients with mild to moderate renal impairment or a history of absorptive or renal hypercalciuria, nephrocalcinosis, kidney stone formation, or hypophosphataemia, renal function, serum and urinary calcium and phosphate should be monitored regularly.

Calcium carbonate/vitamin D3 Calcium/Vitamin D3 should be used with caution in patients with hypercalcaemia or signs of impaired renal function and the effect on calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be taken into account.

3) During long-term treatment, serum and urinary calcium levels should be followed and renal function should be monitored through measurement of serum creatinine. Monitoring is especially […]

1. 4) • Hypercalcaemia. • Hypercalciuria • Diseases and/or conditions (such as prolonged immobilization) associated with hypercalcaemia and/or hypercalciuria • Nephrolithiasis • Pregnancy and lactation. • Severe renal impairment (creatinine clearance <30ml/min).

• Hypervitaminosis D