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Risedronate sodium

Presentation

Tablets containing 30mg risedronate sodium.

Drugs List

  • risedronate sodium 30mg tablets
  • Therapeutic Indications

    Uses

    For the treatment of Paget's disease of bone.

    Dosage

    Adults

    The recommended daily dose is 30mg once daily for 2 months. If re-treatment is considered necessary (at least 2 months after completion of the previous course), a new treatment with the same dose and duration of therapy could be given.

    Elderly

    No dosage adjustment is necessary in elderly patients.

    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

    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.

    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 medicines containing polyvalent ions (such as 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

    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.

    Supplemental calcium and vitamin D should be considered if the dietary intake is inadequate, especially as the bone turnover is significantly elevated in Paget's disease.

    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.

    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.

    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.

    This product contains lactose. Patients with rare hereditary problems with 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, 2011) although Schaeffer (2007) 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

    Effects on Ability to Drive and Operate Machinery

    No effects are known.

    Counselling

    The tablets must be swallowed whole 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 (particularly avoid calcium containing products, also iron and mineral supplements and antacids) at any other time of the day.

    Take at least 30 minutes before going to bed. Do not take before rising.

    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).

    Stand or sit upright for at least 30 minutes after taking risedronate.

    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.

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

    Advise patients to inform their dentist that they are taking bisphosphonates and should not undergo invasive dental procedures.

    Advise patients to maintain adequate oral hygiene during and after treatment with bisphosphonates.

    Advise patient to report any ear pain, discharge or infection.

    Side Effects

    Side effects seen with all doses of risedronate are:
    Dyspepsia
    Abdominal pain
    Constipation
    Diarrhoea
    Gastritis
    Musculoskeletal pain
    Headache
    Rash
    Nausea
    Oesophagitis
    Duodenitis
    Dysphagia
    Oesophageal ulceration
    Oesophageal stricture
    Glossitis
    Iritis
    Uveitis
    Abnormal liver function tests
    Skin reactions
    Severe bullous lesions
    Angioedema
    Hypersensitivity reactions
    Osteonecrosis (primarily of the jaw)
    Stevens-Johnson syndrome
    Toxic epidermal necrosis
    Hair loss
    Anaphylactic shock
    Hepatic disorders
    Leukocytoclastic vasculitis
    Decrease in plasma calcium
    Decrease in serum phosphate
    Urticaria
    Atypical femoral fractures
    Osteonecrosis of the external auditory canal

    Additional side effects have been reported with higher doses of risedronate sodium used for treatment of Paget's disease. These include:
    Dizziness
    Influenza-like symptoms
    Weight loss
    Myasthenia
    Arthralgia
    Apnoea
    Bronchitis
    Sinusitis
    Nocturia
    Corneal lesions
    Dry eyes
    Tinnitus
    Chest pain
    Amblyopia
    Colitis
    Leg cramps
    Peripheral oedema
    Hypocalcaemia
    Neoplasm
    Bone pain

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Shelf Life and Storage

    No special requirements.

    Further Information

    Last Full Review Date: February 2012

    Reference Sources

    British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Summary of Product Characteristics: Actonel 30mg film-coated tablets. Warner Chilcott UK Ltd. Revised August 2011.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

    MHRA Drug Safety Update: Bisphosphonates: atypical stress fractures. Dated: March 2009.
    https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON041211
    Last accessed: February 3, 2012

    MHRA Drug Safety Update: Bisphosphonates-osteonecrosis of the jaw. Dated: November 2009.
    https://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087832
    Last accessed: February 3, 2012

    MHRA Drug Safety Update December 2015
    Available at: https://www.mhra.gov.uk
    Last accessed: 13 January 2016

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
    Risedronate. Last revised: January 4, 2011
    Last accessed: February 3, 2012

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