- risedronate sodium
POM: Prescription only medicine
This information is intended for use by health professionals
Risedronate Sodium Accord 30 mg film-coated tablets.
Method of administration
The absorption of risedronate sodium is affected by food, thus to ensure adequate absorption patients should take Risedronate Sodium Accord 30 mg film-coated tablets:
▪ Before breakfast: At least 30 minutes before the first food, other medicinal product or drink (other than plain water) of the day.
In the particular instance that before breakfast dosing is not practical, Risedronate Sodium Accord 30 mg film-coated tablets can be taken between meals or in the evening at the same time everyday, with strict adherence to the following instructions, to ensure this medicine is taken on an empty stomach:
▪ Between meals: This medicine should be taken at least 2 hours before and at least 2 hours after any food, medicinal product or drink (other than plain water).
▪ In the evening: This medicine should be taken at least 2 hours after the last food, medicinal product or drink (other than plain water) of the day. This medicine should be taken at least 30 minutes before going to bed.
If an occasional dose is missed, Risedronate Sodium Accord 30 mg film-coated tablets can be taken before breakfast, between meals, or in the evening according to the instructions above.
The tablet must be swallowed whole and not sucked or chewed. To aid delivery of the tablet to the stomach this medicine is to be taken while in an upright position with a glass of plain water (>120 ml). Patients should not lie down for 30 minutes after taking the tablet (see section 4.4).
Physicians should consider the administration of supplemental calcium and vitamin D if dietary intake is inadequate, especially as bone turnover is significantly elevated in Paget's disease.
Hypocalcaemia should be treated before starting Risedronate Sodium Accord 30 mg film-coated tablets therapy. Other disturbances of bone and mineral metabolism (e.g. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting Risedronate Sodium Accord 30 mg film-coated tablets therapy.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. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.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 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 lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicine has no or negligible influence on the ability to drive and use machines.
Nervous system disorders:Common: headache (1.8% vs. 1.4%)
Eye disorders:Uncommon: iritis*
Gastrointestinal disorders:Common: constipation (5.0% vs. 4.8%), dyspepsia (4.5% vs. 4.1%), nausea (4.3% vs. 4.0%), abdominal pain (3.5% vs. 3.3%), diarrhoea (3.0% vs. 2.7%)Uncommon: gastritis (0.9% vs. 0.7%), oesophagitis (0.9% vs. 0.9%), dysphagia (0.4% vs. 0.2%), duodenitis (0.2% vs. 0.1%), oesophageal ulcer (0.2% vs. 0.2%)Rare: glossitis (<0.1% vs. 0.1%), oesophageal stricture (<0.1% vs. 0.0%),
Musculoskeletal and connective tissues disorders:Common: musculoskeletal pain (2.1% vs. 1.9%) Very rare: Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction).
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 phase III Paget's Disease clinical trial comparing risedronate vs. etidronate (61 patients in each group), the following additional adverse experiences considered possibly or probably drug related by investigators have been reported (incidence greater in risedronate than in etidronate): arthralgia (9.8% vs. 8.2%); amblyopia, apnoea, bronchitis, colitis, corneal lesion, cramps leg, dizziness, dry eye, flu syndrome, hypocalcaemia, myasthenia, neoplasm, nocturia, oedema peripheral, pain bone, pain chest, rash, sinusitis, tinnitus, and weight decrease (all at 1.6% vs. 0.0%).Laboratory findings: Early, transient, asymptomatic and mild decreases in serum calcium and phosphate levels have been observed in some patients. The following additional adverse reactions have been reported during post-marketing use (frequency unknown):
Eye disorders:iritis, uveitisMuskuloskeletal and connective tissues disorders:osteonecrosis of the jawSkin 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, toxic epidermal necrolysis and leukocytoclastic vasculitis.hair loss.
Immune system disorders:anaphylactic reactionHepatobiliary disorders:serious hepatic disorders. In most of the reported cases the patients were also treated with other products known to cause hepatic disorders.During post-marketing experience the following reactions have been reported (frequency rare): Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction). 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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Paget's disease of the bone: In the clinical programme Risedronate Sodium Accord 30 mg film-coated tablets was studied in patients with Paget's disease. After treatment with this medicine for 2 months the following was seen:• serum alkaline phosphatase normalised in 77% of patients compared to 11% in the control group (etidronate 400 mg/day for 6 months). Significant reductions were observed in urinary hydroxyproline/creatinine and urinary deoxypyridinoline/creatinine• radiographs taken at baseline and after 6 months demonstrated a decrease in the extent of osteolytic lesions in both the appendicular and axial skeleton. No new fractures were observed. The observed response was similar in pagetic patients regardless of whether they had previously received other treatments for Paget's disease, or the severity of the disease.
53% of patients followed for 18 months after initiation of a single 2 month course of Risedronate Sodium Accord 30 mg film-coated tablets remained in biochemical remission.In a trial comparing before-breakfast dosing and dosing at other times of the day in women with postmenopausal osteoporosis, lumbar spine BMD gains were statistically higher with before-breakfast dosing.Paediatric population: The safety and efficacy of risedronate sodium has been investigated in a 3-year study (a randomized, double-blind, placebo-controlled, multicenter, parallel group study of one year duration followed by 2 years of open-label treatment) in paediatric patients aged 4 to less than 16 years with mild to moderate osteogenesis imperfecta. In this study, patients weighing 10-30 kg received risedronate 2.5 mg daily and patients weighing more than 30 kg received risedronate 5 mg daily.
After completion of its one-year randomized, double-blind, placebo-controlled phase, a statistically significant increase in lumbar spine BMD in the risedronate group versus placebo group was demonstrated; however an increased number of patients with at least 1 new morphometric (identified by x-ray) vertebral fracture was found in the risedronate group compared to placebo. During the one-year double-blind period, the percentage of patients who reported clinical fractures was 30.9% in the risedronate group and 49.0% in the placebo group. In the open-label period when all patients received risedronate (month 12 to month 36), clinical fractures were reported by 65.3% of patients initially randomized to the placebo group and by 52.9% of patients initially randomized to the risedronate group. Overall, results do not support the use of risedronate sodium in paediatric patients with mild to moderate osteogenesis imperfecta.
Absorption:Absorption after an oral dose is relatively rapid (tmax ~1 hour) and is independent of dose over the range studied (2.5 to 30 mg). Mean oral bioavailability of the tablet is 0.63% and is decreased when risedronate sodium is administered with food. Bioavailability was similar in men and women.
Distribution:The mean steady state volume of distribution is 6.3 l/kg in humans. Plasma protein binding is about 24%.
BiotransformationThere is no evidence of systemic metabolism of risedronate sodium.
Elimination:Approximately half of the absorbed dose is excreted in urine within 24 hours, and 85% of an intravenous dose is recovered in the urine after 28 days. Mean renal clearance is 105 ml/min and mean total clearance is 122 ml/min, with the difference probably attributed to clearance due to adsorption to bone. The renal clearance is not concentration dependent, and there is a linear relationship between renal clearance and creatinine clearance. Unabsorbed risedronate sodium is eliminated unchanged in faeces. After oral administration the concentration-time profile shows three elimination phases with a terminal half-life of 480 hours.
Special Populations:Elderly: No dosage adjustment is necessary.
|Tablet core:||Lactose monohydrate Cellulose microcrystallineCrospovidone Magnesium stearate.|
|Film coating:||HypromelloseMacrogol HydroxypropylcelluloseColloidal anhydrous silicaTitanium dioxide E171.|
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