Trust Guideline for the Administration of Bisphosphonate Therapy (Pamidronate or Zoledronic Acid) in Children

Transcription

1 Trust Guideline for the Administration of Bisphosphonate Therapy For Use in: By: For: Division responsible for document: Key words: Name of document author: Job title of document author: Name of document author s Line Manager: Job title of author s Line Manager: Supported by: Assessed and approved by the: Jenny Lind Children s Department Registered Paediatric Nurses and Medical Staff Children with primary or secondary osteoporosis & osteogenesis imperfecta Women and Children s Division Bisphosphonate therapy, Zoledronic Acid, Disodium Pamidronate Infusion Catherine Tranter, Dr Nandu Thalange, Rosalind Howe Paediatric Rheumatology Specialist Nurse, Consultant Paediatrician, Paediatric Pharmacist David Booth Chief of Division Dr Chris Upton, Clinical Director Clinical Guidelines Assessment Panel Date of approval: 07/03/2017 Ratified by or reported as approved to (if applicable): To be reviewed before: 07/03/2020 To be reviewed by: Authors Reference and / or Trust Docs ID No: 1350 Version No: Description of changes: No clinical changes Compliance links: None If Yes - does the strategy/policy deviate from the recommendations of N/A NICE? If so why? If approved by committee or Governance Lead Chair s Action; tick here Clinical Standards Group and Effectiveness Sub- Board This guideline has been approved by the Trust's Clinical Guidelines Assessment Panel as an aid to the diagnosis and management of relevant patients and clinical circumstances. Not every patient or situation fits neatly into a standard guideline scenario and the guideline must be interpreted and applied in practice in the light of prevailing clinical circumstances, the diagnostic and treatment options available and the professional judgement, knowledge and expertise of relevant clinicians. It is advised that the rationale for any departure from relevant guidance should be documented in the patient's case notes. The Trust's guidelines are made publicly available as part of the collective endeavour to continuously improve the quality of healthcare through sharing medical experience and knowledge. The Trust accepts no responsibility for any misunderstanding or misapplication of this document. Available via Trust Docs Version: 3 Trust Docs ID: 1350 Page 1 of 6

2 Objective/s To ensure the safe administration and monitoring of bisphosphonate therapy by qualified nursing staff. Rationale For safe administration of bisphosphonate therapy in children. Broad recommendations Background Bisphosphonates increase bone mineral density by binding strongly to hydroxyapatite crystals in bone, interfering with bone remodelling by slowing the rate of growth and dissolution, thereby reducing the rate of bone turnover, with a resulting increase in bone mass. Through these actions, bisphosphonates restore vertebral shape, alleviate bone pain and improve mobility and may have an anti-inflammatory effect. Bisphosphonates seem to be well tolerated in children. In adults there is a risk of osteonecrosis of the jaw, with risk factors including malignancy, smoking, dental disease. All children should maintain good oral hygiene and have routine dental check-ups. If used in a young person with cancer, a dental check should occur PRIOR to treatment. Indications for use Primary structural defects in type I collagen and other structural bone proteins (e.g.osteogenesis imperfecta). Fibrous dysplasia of bone (e.g. McCune-Albright syndrome). Bone abnormalities resulting from systemic disease or the effects of systemic treatment (e.g. steroid treatment of chronic disease or immobilization). Bone matrix abnormalities (e.g. osteoporosis pseudoglioma syndrome). Conditions with a primary defect in bone mineralization (e.g. idiopathic juvenile osteoporosis). Malignancy associated hypercalcaemia. Reflex Sympathetic Dystrophy (or Localised Idiopathic Pain Syndrome). Patient exclusion criteria Pregnancy. Hypersensitivity to bisphosphonates (or any of excipients). Infants under 2 years of age (require a different treatment regime). Available via Trust Docs Version: 3 Trust Docs ID: 1350 Page 2 of 6

3 Treatment Considerations Decision to start Bisphosphonate therapy will be taken by the patient s lead consultant after counselling of patient and parents. Patients commencing bisphosphonate therapy should have an adequate calcium intake, and routine vitamin D supplementation. For patients known to be vitamin D deficient, colecalciferol 300,000 units may be administered by IM injection to reduce the risk of post-treatment hypocalcaemia, prior to commencing the bisphosphonate therapy. The choice of bisphosphonate therapy will be determined by the patient s lead consultant. Appropriate information should be provided to the family and patient. Sexually active teenage girls must use contraception while undergoing active treatment, and for 6 months after treatment cessation, as the risks to unborn children are unknown. Only nurses who are intravenously trained should administer treatment. Drug Interactions Avoid concurrent use with other bisphosphonates. Investigations The following blood tests should be done prior to the bisphosphonate infusion: o o FBC, Urea & electrolytes, Liver function tests, Bone profile (Calcium, phosphate and alkaline phosphatase), magnesium & parathyroid hormone, prior to each infusion. 25-hydroxy-Vitamin D (annually). For patients on steroid therapy: o Random glucose, HbA1c. Urine sample (ideally the second void urine) to be sent for bone turnover markers (Urine NTX). Other blood tests as clinically indicated. In patients with vitamin D deficiency, an abrupt fall in serum calcium may occur after the infusion. If the patient has any unusual neuromuscular symptoms, particularly after the first infusion, then the calcium should be checked (see also side-effects). It is usually appropriate to monitor bone mineral density by DEXA scanning. A baseline DEXA scan should normally be performed prior to initiation of therapy, and then after 12 months, to verify that treatment is effective. Thereafter, the scans may be reduced to 2-3 yearly. Prescription Available via Trust Docs Version: 3 Trust Docs ID: 1350 Page 3 of 6

4 The drug should be prescribed on the drug infusion section of the drug chart. The dose and duration of the infusion must be specified. For the patients FIRST TREATMENT please prescribe regular Ibuprofen and paracetamol to ameliorate the flu-like side effects (for the 3 days of pamidronate or single day of zoledronic acid). Zoledronic Acid Zoledronic acid, 0.05mg/kg, max 5mg, is given by intravenous infusion over 30 minutes. It is usually given every 6 months, but in some circumstances, can be given 4 monthly. After the infusion is complete, administer a 30ml flush over 5-10 minutes. Administration zoledronic acid comes as a 4mg in 5mL concentrate. Withdraw 5mL and make up to 100mL with sodium chloride 0.9%. Infuse the required volume over 30 minutes. Disodium Pamidronate Pamidronate, 3mg/kg/course (maximum 180mg/course), is given over two (1.5mg/kg/day, max 90mg), or three days, (1mg/kg/day, max 60mg), as determined by the requesting consultant. For the first treatment course, the duration of infusion should be 4 hours, but thereafter may be reduced to 2-4 hours. The time interval between the doses can vary between hours for convenience of patients. After the infusion is complete, administer a 30ml flush over 5-10 minutes. Treatment is repeated every three months, for the first year of therapy, but may be reduced thereafter, depending on clinical response. Dose Size of infusion bag Diluent Rate FIRST INFUSION Rate (if patient tolerated first infusion) Up to 5mg 28ml NaCl 0.9% 7 ml/hour 14 ml/hour 5-9mg 50ml NaCl 0.9% 15 ml/hour 30 ml/hour 10-18mg 100ml NaCl 0.9% 30 ml/hour 60 ml/hour 19-45mg 250ml NaCl 0.9% 70 ml/hour 140 ml/hour 46-90mg 500ml NaCl 0.9% 140 ml/hour 280 ml/hour Administration Disodium pamidronate is available in 30mg, 60mg or 90mg vials, some brands are supplied as a dry powder others as a concentrate solution. Dry powder forms of disodium pamidronate need to be initially reconstituted with water for injection as per Available via Trust Docs Version: 3 Trust Docs ID: 1350 Page 4 of 6

5 package instruction. Both forms must be further diluted with sodium chloride 0.9% as per table 1 above. The concentration of disodium pamidronate in the final IV solution should be no greater than 12 mg /100 ml Monitoring/Observations Height & weight. Blood pressure. Baseline CEWS and blood pressure, with follow-up observations as clinically indicated. Side effects of Bisphosphonate Therapy Side effects are particularly common with the first infusion. Approximately half of the children undergoing their first infusion may experience temporary 'flu-like' symptoms' but side effects become much less marked over time. Adverse effects include: Flu like illness, fever, musculoskeletal aches and pains, and vomiting. Patients should be advised to give regular Paracetamol and/or ibuprofen 4-6 hourly (unless contraindicated). Bisphosphonates may cause hypocalcaemia. Regular vitamin D supplementation is advisable for all patients receiving bisphosphonate therapy. Calcium intake should be optimised prior to initiating therapy, and an adequate calcium intake should be maintained throughout time on treatment. Acute hypocalcaemia (muscle cramps, numbness, stiffness and tingling of hands and feet, with positive Chvostek or Trousseau sign), may require treatment with calcium gluconate. It may be avoided by optimising vitamin D and calcium intake prior to therapy. Frequency of Side-effects Frequent: Fever and influenza-like symptoms sometimes accompanied by malaise, rigor, fatigue and flushes. (> 10%) Biochemical: Hypocalcaemia, Hypophosphataemia. Occasional: Reactions at the infusion site: pain, redness, swelling, induration, phlebitis, thrombophlebitis. (>1 10%) Musculoskeletal: bone pain, arthralgia, myalgia. Blood: lymphopenia. Rare: Blood: Anaemia, leucopenia. (> 0.001%) Cardiovascular: Hypo/hypertension. Skin: Rash, pruitis. Isolated cases: Blood: Thombocytopenia. (< 0.001%) Biochemical: Abnormal liver function tests, increase in serum creatinine and urea. Available via Trust Docs Version: 3 Trust Docs ID: 1350 Page 5 of 6

6 After Treatment Ensure follow-up arrangements are in place with the relevant clinician. Arrange the subsequent bisphosphonate infusion, as specified by the referring consultant. Clinical audit standards Use of routine vitamin D supplementation Appropriate laboratory monitoring Clinical effectiveness, determined by DEXA Administration as per clinical guideline. The audit results will be shared with colleagues in the Jenny Lind Children s Department, including formal presentation at departmental governance meetings. Summary of development and consultation process undertaken before registration and dissemination This guideline has been written by the Kit Tranter, Nandu Thalange & Kate Armon. It has been circulated for comment in the Paediatric Directorate and Pharmacy. This version has been endorsed by the Clinical Guidelines Assessment Panel. Distribution list/ dissemination method CDW, CAU, Buxton, Pharmacy Services, Trust Intranet. References 1. Ooi HL, Briody J, Biggin A, Cowell CT, Munns CF. Intravenous zoledronic Acid given every 6 months in childhood osteoporosis. Horm Res Paediatr. 2013;80(3): Simm PJ, Johannesen J, Briody J, McQuade M, Hsu B, Bridge C, Little DG, Cowell CT, Munns CF. Zoledronic acid improves bone mineral density, reduces bone turnover and improves skeletal architecture over 2 years of treatment in children with secondary osteoporosis. Bone Nov;49(5): Sbrocchi AM, Rauch F, Jacob P, McCormick A, McMillan HJ, Matzinger MA, Ward LM. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int Nov;23(11): Bachrach LK, Ward LM. Clinical review 1: Bisphosphonate use in childhood osteoporosis. Available via Trust Docs Version: 3 Trust Docs ID: 1350 Page 6 of 6