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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Elderly
Children
Patients with Renal Impairment
Additional Dosage Information

Treatment of osteoporosis:
5mg once daily

Prevention of osteoporosis/Increase bone mass:
5mg once daily

Precautions and Warnings

Bisphosphonates have been associated with oesophagitis, gastritis, gastroduodenal ulcerations and oesophageal ulcerations. Therefore dosage instructions should be closely followed.

There is limited clinical experience in the use of risedronate in patients with oesophageal disease. Patients with a history of oesophageal disorders which delay oesophageal transit or emptying e.g. stricture or achalasia, or who are unable to stay in an upright position for at least 30 minutes after taking risedronate, should be treated with caution.

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. Instruct patients 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 treatment. Other disturbances of bone and mineral metabolism (e.g. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting risedronate therapy.

Foods, drinks (except plain water) and drugs containing polyvalent cations (such as calcium, magnesium, iron and aluminium) interfere with the absorption of risedronate and should not be taken at the same time ( see Administration ).

Treatment of osteoporosis should only be initiated in the presence of low bone mineral density (BMD T-score at hip or lumbar spine equal or less than -2.5 SD) and/or prevalent fracture.

There is limited evidence to support the efficacy of bisphosphonates in elderly women over 80 years

Supplemental calcium and vitamin D should be considered if the dietary intake is inadequate.

Patient must remain upright for at least 30 minutes after dose.

Osteonecrosis of the jaw has been reported in cancer patients taking bisphosphonate regimens often with concurrent chemotherapy and corticosteroids. These cases have mainly been associated with dental procedures such as tooth extraction and many have shown signs of local infection including osteomyelitis.

Perform dental examination with appropriate preventative procedures prior to risedronate sodium therapy in patients with risk factors (cancer chemotherapy, corticosteroids and poor oral hygiene).

Invasive dental procedures should be avoided in patients taking bisphosphonates. Advise patients to inform their dentist that they are taking bisphosphonates and should not undergo invasive dental procedures. There is no data available to suggest discontinuation of bisphosphonate treatment prior to dentistry reduces the risk of osteonecrosis of the jaw. Recovery from such procedures is likely to be prolonged.

Adequate oral hygiene should be maintained during and after treatment with bisphosphonates.

Osteonecrosis of the external auditory canal has been reported very rarely with bisphosphonates, mainly in association with long term therapy (2 years or longer). Risk factors include steroid use and chemotherapy and/or local risk factors 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 stress fractures of the proximal femoral shaft with poor healing have been reported for treatment with another bisphosphonate, alendronic acid. Limited data exists regarding a relationship for other bisphosphonates and atypical stress fractures. However, the possibility of atypical stress fractures cannot be excluded. Patients who develop atypical stress fractures should discontinue treatment and receive no further bisphosphonate treatment.

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, lactose intolerance or glucose-galactose malabsorption should not take this medicine.

CSM Warnings

The CHM recommends the following:

Atypical stress fractures of the proximal femoral shaft with poor healing have been reported rarely with long-term bisphosphonate treatment;

Patients should be re-evaluated periodically based on an assessment of the benefits and risks of the bisphosphonate treatment, especially after 5 years or more of treatment;

Patients should report any new thigh, hip or groin pain during treatment with a bisphosphonate;

Discontinuation of bisphosphonate treatment in patients suspected to have an atypical femoral fracture should be considered after an assessment of the benefits and risks of continued treatment.

Pregnancy and Lactation

Pregnancy

Contraindicated.

Animal studies have shown reproduction toxicological effects and although the significance to humans is unknown, risedronate should not be used in human pregnancy. If treatment has been discontinued before pregnancy, the very long elimination half life from bone indicates that women treated with risedronate will have detectable concentrations of the drug for a prolonged interval. If exposure occurs during gestation, detailed ultrasound examination of the foetal skeleton appears to be warranted (Briggs) although Schaeffer states that accidental use of a single dose does not justify interruption of the pregnancy or additional diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated.

It is not known whether risedronate passes into human milk. Studies in animals indicate that a small amount of risedronate sodium passes into breast milk.

However, the extremely low oral bioavailability of bisphosphonates in the non-fasting state implies that systemic levels in the nursing infant should be negligible.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Presentation

Tablets containing 5mg risedronate sodium.

Drugs List

ACTONEL 5mg tablets

risedronate sodium 5mg tablets

Therapeutic Indications

Uses

Treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures.
Treatment of established postmenopausal osteoporosis, to reduce the risks of hip fractures.

Prevention of osteoporosis in postmenopausal women with increased risk of osteoporosis.
To maintain or increase bone mass in postmenopausal women undergoing long-term (more than 3 months), systemic corticosteroid treatment at doses greater than or equal to 7.5mg/day prednisone or equivalent.

Dosage

Adults

Treatment of osteoporosis:
5mg once daily

Prevention of osteoporosis/Increase bone mass:
5mg once daily

Elderly

No dosage adjustment required.

Bioavailability, distribution and elimination have been shown to be similar in elderly patients (older than 60 years) compared to younger subjects.

There is limited evidence to support efficacy in very elderly patients aged over 80 years.

Children

Not recommended for use in children as there is insufficient clinical experience of risedronate therapy in patients under 18 years old.

The safety and efficacy of risedronate sodium is being investigated in an ongoing study of paediatric patients with osteogenesis imperfecta . Results after completion of one year randomised, double blind, placebo controlled phase do not support the use of risedronate sodium in paediatric patients with osteogenesis imperfecta due to increased number of new morphometric vertebral fractures compared to placebo.

Patients with Renal Impairment

Mild to moderate renal impairment - creatinine clearance 30ml/min or above
No dosage adjustment required

Severe renal impairment - creatinine clearance below 30ml/min
Contraindicated

The Renal Drug Handbook states that when creatinine clearance is below 30ml/min, renal clearance of risedronate is reduced by 70%. One paper suggests using a reduced dose when the glomerular filtration rate is below 30ml/min. Another paper has concluded that 50% of the suggested dose may be possible in end stage renal failure but more trials are required and osteomalacia and adynamic bone disease must be excluded first.

Additional Dosage Information

Supplemental calcium and vitamin D may be given if dietary intake is inadequate.

If a dose is missed or forgotten, a replacement dose should be taken before breakfast, between meals or in the evening (see Administration).

Administration

The tablets must be swallowed whole and not sucked or chewed.

The absorption of risedronate is affected by food and medicinal products containing polyvalent ions (for example, calcium, magnesium, iron and aluminium), thus to ensure adequate absorption patients should take the dose either at least 30 minutes before the first food, medicinal product or drink (other than water) of the day, or at least 2 hours from any food or drink at any other time of the day, and at least 30 minutes before going to bed.

To aid delivery of the tablet to the stomach, it should be taken while in the upright position with a glass of plain water (at least 120ml). Patients should not lie down for 30 minutes after taking the tablet.

Contraindications

Hypocalcaemia
Children under 18 years
Pregnancy - ( see Pregnancy)
Breastfeeding - ( see Lactation)
Severe renal impairment (creatinine clearance less than 30ml/min)
Galactosaemia