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Council for Medical Schemes Therapeutic Algorithms for the Chronic Disease List Conditions December 2002 First Draft 1 This first daft of the Therapeutic Algorithms for the Chronic Disease List Conditions was developed by Bettina Taylor with the support of Medscheme Integrated Care Division. The document is provided as an Appendix to the following report: The Costing of the Proposed Chronic Disease List Benefits in South African Medical Schemes in 2001 By Professor Heather McLeod, Professor Alan Rothberg, Leslie Pels, Sean Eekhout, Deus Bazira Mubangizi and Dr Therese Fish December 2002 Centre for Actuarial Research (CARE) A Research Unit of the University of Cape Town Centre for Actuarial Research University of Cape Town Private Bag Rondebosch 7701 SOUTH AFRICA Medscheme Integrated Care Division Private Bag X124 Bryanston 2021 SOUTH AFRICA Telephone: +27 (0)21 650 2475 Fax: +27 (0)21 689 7580 E-mail: [email protected] E-mail for Professor McLeod: [email protected] Telephone: +27 (0)11 510 2000 Fax: +27 (0)11 463 5195 E-mail for Bettina Taylor: [email protected] E-mail for Professor Rothberg: [email protected] 2 Introduction to the First Draft The Regulations dated 4 November 2002 that introduced the Chronic Disease List state: Treatment: Diagnosis, medical management and medication, to the extent that this is provided for by way of a therapeutic algorithm for the specified condition, published by the Minister by notice in the Gazette. It is the intention that these therapeutic algorithms be discussed with stakeholders and published in the course of 2003 for implementation on 1 January 2004. The Standard Treatment Guidelines and Essential Drugs List published by the Department of Health in 1998 forms the basis of this document. All guidelines relevant to the diseases included in the CDL conditions have been collated without any change to the content of information. Editorial changes have focused on layout and consolidation of information. The clinical staff of Medscheme Integrated Care identified a number of problem areas and have suggested the following solutions: Some of the clinical information is outdated e.g. ACE-inhibitors have become the standard of care in patients with congestive cardiac failure. It is important that all guidelines are revised by a team of experts from a clinical perspective. Certain key diseases are not adequately covered in the Standard Treatment Guidelines. Of particular concern is the lack of information pertaining to the treatment of hyperlipidaemia and multiple sclerosis. These diseases should be addressed as a matter of urgency. Although the guidelines focus on maintenance management of chronic diseases, some do refer to acute intermittent therapies that may be indicated for the respective diseases. It is important that the final CDL document clearly states which acute/intermittent therapies are expected to be covered. The administrative complexities and financial risks that may arise from including some of these must be carefully considered in the final decision-making process. It is suggested that a task team be appointed to be responsible for documenting and maintaining the treatment algorithms for the CDL conditions. Ideally this team should work closely with the Standard Treatment Guidelines and the EDL committee. The task team should have representation from private funders, relevant clinical disciplines and the public sector. Actuarial and pricing expertise should be sought once initial clarity has been achieved in order to estimate the price of the algorithms. This may result in an iterative process of refining the algorithms and sufficient time needs to be allocated to this possibility. A project manager should be identified to ensure that the process moves forward in time for schemes to incorporate the benefits in their pricing in August 2003, in order to ensure a smooth introduction of benefits from 1 January 2004. Preliminary recommendations for a package of tests, equipment and visits in respect of each CDL condition were costed in the report and the spreadsheet is provided separately. 3 Table of Contents Introduction to the First Draft............................................................................................. 3 Table of Contents ..................................................................................................................4 1. Cardiovascular Disease ................................................................................................ 6 1.1. Hypertension ....................................................................................................... 6 1.1.1. Paediatrics ....................................................................................................... 6 1.1.2. Adults .............................................................................................................. 7 1.2. Hyperlipidaemia ................................................................................................ 10 1.3. Coronary Artery Disease................................................................................... 11 1.4. Cardiac Failure / Cardiomyopathy .................................................................... 12 1.4.1. Paediatrics ..................................................................................................... 12 1.4.2. Adults ............................................................................................................ 12 1.5. Dysrhythmias .................................................................................................... 15 2. Respiratory Disease ....................................................................................................16 2.1. Asthma .............................................................................................................. 16 2.1.1. Paediatrics ..................................................................................................... 16 2.1.2. Adults ............................................................................................................ 17 2.2. Chronic Obstructive Pulmonary Disease .......................................................... 19 2.3. Bronchiectasis ................................................................................................... 20 2.3.1. Paediatrics ..................................................................................................... 20 2.3.2. Adults ............................................................................................................ 21 3. Endocrine Disease .......................................................................................................22 3.1. Diabetes Mellitus Type 1 .................................................................................. 22 3.1.1. Paediatrics ..................................................................................................... 22 3.1.2. Adults ............................................................................................................ 23 3.2. Diabetes Mellitus Type 2 .................................................................................. 24 3.3. Hypothyroidism ................................................................................................ 25 3.3.1. Paediatrics ..................................................................................................... 25 3.3.2. Adults ............................................................................................................ 25 3.4. Addison’s Disease ............................................................................................. 26 4. CNS Disease .................................................................................................................27 4.1. Epilepsy............................................................................................................. 27 4.1.1. Paediatrics ..................................................................................................... 27 4.1.2. Adults ............................................................................................................ 27 4.2. Parkinson’s Disease .......................................................................................... 29 4.3. Multiple Sclerosis ............................................................................................. 30 5. Psychiatric Disease ......................................................................................................31 5.1. Bipolar Mood Disorder ..................................................................................... 31 5.2. Schizophrenia .................................................................................................... 32 6. Musculoskeletal Disease ............................................................................................. 33 4 6.1. Rheumatoid Arthritis ........................................................................................ 33 7. Immunological Disease ............................................................................................... 35 7.1. Systemic Lupus Erythematosus ........................................................................ 35 8. Gastro-Intestinal Disease ........................................................................................... 36 8.1. Crohn’s Disease ................................................................................................ 36 8.1.1. Paediatrics ..................................................................................................... 36 8.1.2. Adults ............................................................................................................ 36 8.2. Ulcerative Colitis .............................................................................................. 38 8.2.1. Paediatrics ..................................................................................................... 38 8.2.2. Adults ............................................................................................................ 38 9. Renal Disease ...............................................................................................................40 9.1. Chronic Renal Disease ...................................................................................... 40 9.2. Chronic Renal Failure ....................................................................................... 40 9.2.1. Paediatrics ..................................................................................................... 40 9.2.2. Adults ............................................................................................................ 41 9.3. Nephrotic Syndrome ......................................................................................... 42 9.3.1. Paediatrics ..................................................................................................... 42 9.3.2. Adults ............................................................................................................ 43 9.4. Pyelonephritis and Obstructive/ Reflux Nephropathy ...................................... 44 9.4.1. Paediatrics ..................................................................................................... 44 9.5. Renal Calculi ..................................................................................................... 45 10. Haematological Disease .............................................................................................. 46 10.1. Haemophilia A and B........................................................................................ 46 11. Opthalmological Disease ............................................................................................ 47 11.1. Glaucoma .......................................................................................................... 47 5 1. Cardiovascular Disease 1.1. Hypertension 1.1.1. Paediatrics Definition Elevation of systemic blood pressure beyond the 95th blood pressure centile for age on at least three different occasions at weekly to monthly intervals (excluding acute hypertensive states). Diagnostic criteria The blood pressure values in the table can be regarded as the upper limit of normal (95th centile). All blood values in excess should be treated. Hypertension may be asymptomatic or symptomatic. If symptomatic, it usually presents with the clinical features of the underlying disease or the target organ system involved, e.g. hypertensive encephalopathy, pulmonary oedema or renal disease. Blood pressure values for age – upper limit of normal Age <12 hours 1 week 6 wks-6 yrs 8yrs 9yrs 10yrs 12yrs Systolic 80 100 115 120 125 130 135 Diastolic 50 70 82 84 86 88 14yrs 140 90 Referral criteria Confirmed hypertension in any child – to determine the underlying cause (if necessary) and to initiate treatment. Hypertension not responding satisfactorily to treatment. Treatment objectives Maintain blood pressure at or slightly below the 95th centile for age. (Blood pressure should not be decreased by more than 25% in the acute phase). Determine and treat any underlying cause of hypertension. Non-drug treatment Weight reduction when appropriate. Salt restriction. Aerobic exercise. Identify and treat the underlying cause. 6 Drug treatment Essential hypertension Treat stepwise, beginning with a diuretic. Hydrochlorothiazide, oral, 0.5-1mg/kg as a single dose. Max. 12.5mg per day. The subsequent steps correspond to those used in cases of secondary hypertension. Secondary hypertension If fluid load is contributory, furosemide, oral, 1-5mg/kg/24 hours in 2-4 divided doses (together with potassium supplementation, as needed). Otherwise, omit the diuretic. Step 1 - Beta-blockers Propranolol, oral, 1-8mg/kg/24 hours in 3 divided doses, OR Atenolol, oral, 1-2mg/kg/24 hours as a single dose or in 2 divided doses. Beta-blockers contraindicated in asthmatic patients. Step 2 – Vasodilators Hydralazine, oral, 1-5mg/kg/24 hours in 3-4 divided doses, OR Prazosin, oral, 0.1-0.5mg/kg/24 hours in 2 divided doses; max. 20mg per day. Prazosin should be initiated by paediatrician. Use half the calculated dose for the first 35 days to reduce orthostatic hypotension. Step 3 - ACE-inhibitors Captopril, oral, 1-6mg/kg/24 hours in 3 divided doses; neonates 0.03-2mg/kg/24 hours, OR Enalapril, oral, 0.2-1mg/kg/24 hours in 2 divided doses. Creatinine clearance must be >30-50mL/minute and renal artery stenosis must be excluded. Captopril should be initiated by a paediatrician. Step 4 - Calcium channel blockers Nifedipine, oral, 0.2-1mg/kg/24 hours in 3-4 divided doses (6-8 hourly). 1.1.2. Adults Aim is to reduce blood pressure to <140/90mmHg, and to less than 160/95 in the elderly with no co-morbidity. Patients with diabetic renal disease should have their BP reduced to < 130/80. Refer if the patient is compliant with therapy and the blood pressure is refractory while on drugs from three different classes, one of which being a diuretic all cases where secondary hypertension is suspected 7 Drug treatment Diuretics Hydrochlorothiazide, oral, 12.5mg daily. In patients with fluid retention, increase to 25mg daily. If unresponsive to latter or if creatinine > 150mol/l, furosemide, oral, 40160mg daily. First line therapy for all patients (except during pregnancy, where diuretics in general are contra-indicated, and high dose diuretics should not be used). Centrally-acting agents Reserpine, oral, 0.1mg daily. Continued from primary care as additional therapy. (For hypertension in pregnancy, methyldopa, oral, 250mg twice daily, increase to maximum dose of 500mg tds) Beta-blockers Atenolol, oral, 50mg daily, can be increased to 100mg daily in patients with insufficient beta blockade. In addition to hydrochlorothiazide may be beneficial in the following conditions: angina/ after myocardial infarction tachydysrhythmias pregnancy. ACE-inhibitors e.g. Perindopril, oral, 4mg daily or ramipril 2.5mg – 10mg daily Use if target blood pressure is not achieved with the above-listed medications. Also for: heart failure left ventricular hypertrophy after myocardial infarction (remodelling prevented) diabetes with micro-albuminuria. In renal failure, use ACE-inhibitor only if serum K+ < 5mmol/l. Alpha blockers e.g. Prazosin, oral, 1-5mg 2-3 times daily, max. dose 20mg daily. Start with low dose, titrate upwards. A first dose hypotensive effect can occur. Consider use for chronic renal failure, heart failure, prostatic hypertrophy and hypertension in pregnancy. This is a third-line anti-hypertensive drug. Calcium channel blockers e.g. Verapamil, oral, 40-80mg 3 times daily, OR Verapamil sustained release, oral, 120-360mg one or twice daily, OR Nifedipine long- acting, oral, 30-90mg daily, OR Amlodipine, oral 2.5mg daily, initially, and up to a maximum of 10mg once daily (dose should only be increased after 10-14 days) Nifedipine, oral, 5mg, for short term, emergency use only. 8 Benefits in: angina pectoris peripheral vascular disease in elderly patients systolic hypertension These drugs are metabolically neutral. Arteriolar vasodilators (For hypertension in pregnancy, hydralazine, oral, 25mg tds, increase to 50mg qid) (For hypertension in pregnancy, aspirin, soluble, oral, 75mg daily may be used). Preliminary comments: The adult section is an edited consolidation of three chapters of the SA Treatment Guidelines and Essential Drugs List (Hypertension, Malignant Hypertension, Hypertension in Pregnancy). The cheapest available agent within a therapeutic group should form the benchmark agent for PMBs, irrespective of whether this agent has been listed as the specific example in the above guideline. For example, perindopril and ramipril are listed as examples of ACEinhibitors in the current treatment guide, yet an alternative ACE-inhibitor may be the most cost-effective agent available in the private sector. The latter rather than the former should thus form the benchmark for PMB reimbursement in the private sector. This principle should apply to all conditions. 9 1.2. Hyperlipidaemia Principles of drug treatment Based on adequate non-drug measures being the cornerstone of treatment initially, and subsequent to drug inclusion. Accurate determination and characterisation of lipid abnormalities. The role of associated risk factors, including lifestyle, race, gender and age. Treatment of underlying and causative secondary conditions. The place of drugs in primary and secondary prevention. The rational use of drugs for associated conditions. The rational use of hypolipidaemic drugs – efficacy, proven effects, cost, side effects, additional benefits and comparisons. Classes of drugs to be used singly or in combination. Therapeutic profiles of all drugs – lipid disorders and for underlying conditions. Preliminary comments This is one of the three most expensive chronic conditions to treat, if one considers chronic medication expenditure. Not only is this section covered very poorly in the Standard Treatment Guidelines, but it also appears that no associated drugs are listed on the Essential Drugs Lists. Before PMBs for chronic medication are implemented, it is imperative that an explicit “minimum care” guideline is collated for use of lipidlowering drugs. The international trend is for higher doses of such drugs being recommended for increasing target populations, a “best practice” trend that could financially cripple health systems. PMBs should probably only mandate reimbursement of lipid-lowering drugs for patients with familial hyperlipidaemia and for those with established atherosclerotic disease and abnormal lipid levels. 10 1.3. Coronary Artery Disease Aim of therapy is To identify and aggressively modify risk factors such as smoking, hyperlipidaemia, diabetes mellitus, hypertension, obesity, coagulation risk and menopause. Pain relief Detection and treatment of atherosclerotic progression and complications Drug treatment For specific prophylaxis: Nitrates short acting ,e.g. glyceryl trinitrate, sublingual, 0.5mg, at first indication or before known situation. Repeat if necessary after 5 minutes. OR Isosorbide dinitrate, sublingual, 5mg when necessary, and repeated at 5 minutes’ intervals if required. If nitrates are no longer effective, this may be due to deterioration of the coronary artery disease, an unrecognized trigger, or improper storage of the drug. For long-term prevention of angina: Nitrates, long acting e.g. isosorbide mononitrate, oral, 10-20mg twice daily OR Isosorbide dinitrate, oral, 40mg, twice daily, at 8:00 and 14:00 hours. Adjust to optimal dosage, this also depends on product. Beta blockers e.g. atenolol, oral, 50-100mg daily (titrate to resting heart rate of approximately 60 beats per minute) PLUS Aspirin soluble, oral, 75-150mg daily. (long-term prophylaxis for thrombosis) Calcium channel blocker e.g. verapamil, oral, 120-360mg daily, in 4 divided doses OR Diltiazem, oral, 180-360mg daily in 2 divided doses (where verapamil is inappropriate). Caution: contraindicated in-patients with established or borderline cardiac failure and inpatients with intracardiac conduction disturbances. Use if verapamil is inappropriate. Preliminary comments Hormone supplementation is no longer regarded as risk modifying therapy in postmenopausal females, and should as such not form part of PMBs for coronary artery disease. Anti-obesity drugs are expensive with insufficient long-term clinical outcomes data. They should thus not be regarded as reimbursable under the PMBs. Obesity management should focus on diet and exercise. 11 1.4. Cardiac Failure / Cardiomyopathy 1.4.1. Paediatrics Drug treatment: Combination drug therapy is usually indicated, e.g. digoxin AND a diuretic, with or without an ACE inhibitor. Digoxin, oral, 0.01 mg/kg/dose 8 hourly for 3 doses, and then maintenance, oral, 0.01 mg/kg/24 hours in 2 divided doses, for as long as needed to control the cardiac failure. Digoxin is contraindicated in bradycardia, heart block, cardiac tamponade or hypertrophic cardiomyopathy. Monitor digoxin blood levels and ECG. Diuretics Furosemide, oral, 1-3mg/kg/24 hours as a single dose, or in 4 divided oral doses with or without spironolactone (aldosterone antagonist), oral, 2-4mg/kg/24 hours in 2 divided doses. Continue diuretic therapy as long as needed to control heart failure. Side-effects – hypokalemia, hypochloraemic alkalosis (may increase digitalis toxicity). Monitor blood potassium levels. Potassium supplements may be necessary if furosemide is used without an aldosterone antagonist. Afterload reduction - ACE inhibitor or vasodilator Captopril, oral, initially 0.5mg/kg/24 hours in 3 divided doses (8 hourly) for 24 – 48 hours. Increase every 24-48 hours by 0.5 mg/kg/24 hours until maintenance dose of 3-5 mg/kg/24hours is reached. Continue as long as needed to control the cardiac failure or consider in persistent heart failure where other measures have failed; only after consultation with a pediatrician or pediatric cardiologist. Monitor blood potassium levels and stop potassium supplements while patient is on an ACE inhibitor. Captopril is not registered for pediatric use. 1.4.2. Adults Non-drug treatment Limited physical activity Lifestyle modification, including attention to dietary factors such as salt restriction, limited alcohol use and correction of vitamin deficiencies Avoidance of medication having a negative effect on cardiac output, or myocardial conductivity, eg. beta blockers Anticipation and treatment of complications Drug treatment Diuretics 12 Furosemide 40mg – 120mg per day in divided doses (ceiling in dose according to renal function and for maintenance, or when oral thiazide resistance occurs or ceiling of effect is reached; the dose must be titrated to response) OR Hydrochlorothiazide, oral 50mg – 100mg per day. Dosage may be reduced or even stopped if dry body weight is regained. Indicated for mild to moderate fluid retention as initial treatment and after successful diuresis with furosemide, and renal function being normal. MAY BE COMBINED WITH Spironolactone, oral, 25mg – 400mg once or twice daily. Indicated to retain potassium; contra-indicated in combination with ACE-inhibitors; do not give additional potassium. Potassium chloride tablets, not enteric coated, oral,40 – 120mg mmol/day in divided doses. Use with high-dose furosemide only. Can be discontinued in most patients after 34 weeks. Avoid in renal failure. If potassium blood level > 3 mmol/l, simply monitor blood levels closely. Digoxin, usual dose: oral, 0.125mg daily. May be increased to 0.25mg daily. Dosages should be reduced in the elderly and in patients with renal impairment. Use for systolic or pump failure with a dilated heart, especially in atrial fibrillation. Not recommended in concentric hypertrophy and after acute myocardial infarction. ACE-inhibitors Eg. perindopril, oral, 4mg daily. These drugs to be used when adequate control is not achieved with other therapy. Anticoagulants Warfarin, oral, 5mg daily. Not routinely recommended, usage is controversial, is useful in atrial fibrillation after embolic events and in severly dilated hearts. Monitor progress with INR to keep within therapeutic range. Antiarrhythmics Refer to dysrhythmia section. Not for asymptomatic ventricular arrhythmias. Always exclude electrolyte abnormalities and drug toxicity first. Beta blocker Eg. carvedilol, oral, start with the lowest possible dose (6.25mg – 12.5mg) once daily. Titrate upwards depending on response. Maximum dose 50mg daily. To be prescribed by a cardiologist only. 13 Preliminary comments The cardiac failure syndrome and cardiomyopathy chapters in the Standard Treatment Guide have been consolidated into one section, as they contain the same information in both chapters, i.e. they are duplications of each other. Vitamin supplementation should only form part of PMBs where vitamin deficiency has been proven as a cause for cardiomyopathy (eg. RBC transketolase activity and response to thiamine in patients with suspected beri-beri) 14 1.5. Dysrhythmias Supraventricular tachyarrythmia Drug treatment Beta blockers Short-acting e.g. propranolol, oral, 10-40mg 6 hourly for short periods, to slow down the heartrate. Should be followed by long-acting, eg. atenolol, oral, 50mg – 100mg for maintenance to slow down ventricular response. Contraindicated in heart failure, asthma, and chronic airway disease. Alternative: verapamil, sotalol or digoxin as decided by the cardiologist. Verapamil, oral, 40-120 mg 8 hourly for maintenance. To slow down ventricular response. Not to be given together with beta blockers. Contra-indicated in WPW syndrome and other wide complex tachycardia, OR Digoxin, oral, initial dose: 0.25-0.5mg. A higher loading dose may be given. Maintenance dose: 0.125-0.25mg daily. Useful if there is heart failure. Contraindicated in WPW syndrome. Half-life is doubled by verapamil. Dosages must be adjusted in the elderly and patients with renal impairment. Warfarin, oral, 5mg daily, adjusted to therapeutic range, depending on the INR. (given long-term). Prophylaxis in chronic atrial fibrillation. Amiodarone, oral, 200mg daily in patients with recurrent post-myocardial infarction ventricular tachycardia. Also, for prophylaxis of paroxysmal atrial fibrillation or other SVT. To be prescribed by a cardiologist only. Serious long-term side effects and long half-life are major disadvantages. 15 2. Respiratory Disease 2.1. Asthma 2.1.1. Paediatrics Assessment of severity of asthma Criteria Mild Frequency of Not more than once attacks of cough a month and/or wheeze Night time cough None and/or wheeze Prior admission to None hospital for asthma PEFR (%age of predicted value of patient’s best) > 80 Moderate Not more than once a week Severe More than once a week or continuous Infrequent (<once a week) One previous admission Frequent 60 - 80 >one previous admission or admission to ICU < 60 Non-drug treatment Environmental control -Avoid exposure to cigarette smoke and triggers such as preservatives (eg. sulphites, benzoates) and certain pets (eg. cats). Take measures against house dust mite, if identified as a trigger, eg. plastic mattress covers, removal of bedroom carpets, washing of blankets in hot water (>70 degrees C), etc. Drug treatment Mild Asthma Bronchodilator on a “when needed” basis to relieve symptoms. Use a short-acting beta2 agonist (inhalation therapy preferred.) Salbutamol, oral, 015mg/kg/dose 4 times daily, OR Salbutamol MDI, 100 micrograms 3-4 times daily, until symptoms are relieved; spacer devices are recommended Moderate Asthma Regular anti-inflammatory treatment with low-dose inhaled steroids (<400 micrograms/day); the lowest possible effective dose of steroids should be used. Doses < 400micrograms/day are associated with minimal side-effects. Efficacy and safety of inhaled steroids are increased by the use of spacer devices. Beclometasone, 100 micrograms inhaled 2-4 times daily, according to response. OR In children > 6yrs of age Budesonide, 200 –400 micrograms/24 hours in 2-4 divided doses. 16 PLUS Bronchodilator on a “when needed” basis to relieve symptoms: Salbutamol, oral or inhaled, dosages as above. Severe Asthma Regular anti-inflammatory treatment with inhaled steroid: Beclomethasone or budesonide – doses as above. PLUS Regular Bronchodilator: Salbutamol, oral or inhaled, dosages as above. Maintenance treatment with daily or alternate day oral steroids is indicated only in those patients not controlled by high-dose inhaled steroids used on a regular basis. Other drugs used occasionally: Theophylline: Theophylline anhydrous, oral - titrate dose for optimal response. Initial doses: 12 - < 15kg, 100mg 12 hourly; max. 300mg/day 15 - < 20kg, 100mg 12 hourly, max. 400mg/day 20 - < 30kg, 150mg 12 hourly, max. 600mg/day 30 - < 40kg, 200mg 12 hourly, max. 800mg/day 40 - < 50kg, 200mg 12 hourly, max. 900mg/day Theophyllines are used where beta2agonists or anti-inflammatory therapy (steroids and inhaled cromoglycate) are not available, or if patient is non-responsive to other treatment modalities. Rectal use is contra-indicated in children. Avoid short-acting preparations. Monitor theophylline blood levels. Ipratropium bromide, by inhalation, >6yrs, 40 micrograms 3-4 times daily 3-6 yrs, 20 micrograms 3 times daily. Used as an adjunct to beta2agonists. It is especially useful in small children in whom coughing and wheezing are major symptoms. Not registered for use in children < 3yrs. 2.1.2. Adults Drug treatment Maintenance therapy Beta-2 stimulants, e.g. salbutamol or fenoterol, MDI, 100-200 micrograms, 4-6 hourly as necessary OR Salbutamol, nebulised, 2.5-5 mg undiluted given over 3 minutes, repeat 4-6 hourly OR Fenoterol, nebulised, 1.25-2.5 mg undiluted given over 3 minutes, repeat 4-6 hourly. AND/OR Ipratropium bromide, MDI, 40-120 micrograms 6-8 hourly (to be prescribed by a specialist only) 17 PLUS, if required Budesonide, inhaled, 200 micrograms twice daily, if no peak flow or other lung function test assessment available. Higher doses should be based on lung function test and evidence of clinically meaningful response. Dosages of more than 800 micrograms per day are reserved for pulmonologist only, and should not normally be used, as higher dosages cause significant metabolic effects. All inhaled steroids should be administered via a spacer. Indications for use include the following: more than one episode of cough and / or per week Severe attacks even if infrequent, especially if hospitalisations were needed. Nighttime cough and / or wheeze, especially if more than once per week. PEFR less than 80% predicted. PLUS, if required; Prednisone, oral, 5-10mg/day, or 15mg on alternate days. Doses of 20-40 mg daily for 7 days may be needed for short term exacerbation’s in patients not responding to the above. Theophylline slow release, oral, initial 400 mg/day in 2-3 divided doses 8-12 hourly, followed by increments of 150-200 mg/day every third day until a max. dose of 14 mg/kg/day, or a max. of 900 mg/day, has been achieved. Higher doses of theophylline should be guided by blood level monitoring. The elderly are more susceptible to theophylline toxicity and theophylline dosages need to be reduced by about 30%. Combinations of xanthine deriatives with ephedrine-like substances and sedatives have no place in the treatment of asthma. Intercurrent bacterial infections Antimicrobials may be used for 7-10 days e.g. doxycycline, oral, 100 mg twice daily OR amoxicillin, oral, 500 mg 8 hourly OR trimethoprim/sulfamethoxazole 80/400 mg, oral, 1 tablet twice daily. Preliminary comments The use of antimicrobials should not fall within the ambit of PMBs for asthma. These agents are cheap and are only used intermittently for the treatment of acute bacterial infections. Having to guarantee payment for such agents would add administrative complexities (and thus costs) that cannot be justified within the current benefit design architecture. It is thus recommended that they are excluded from PMBs for the moment. The need for nebulised bronchodilators as part of asthma maintenance therapy should be reviewed. Medscheme’s experience is that this form of drug administration is used inappropriately in the private sector, and it is recommended that nebulised bronchodilators do not fall within the ambit of PMBs. 18 2.2. Chronic Obstructive Pulmonary Disease Drug treatment Beta-2-stimulants, E.g. salbutamol, or fenoterol, MDI, 200 micrograms, 4-6 hourly as needed OR Salbutamol, nebulised, 2.5-5mg undiluted given over 3 minutes, repeated 4-6 hourly OR Fenoterol, nebulised, 1.25-2.5mg undiluted given over 3 minutes, repeat 4-6 hourly. AND/OR Ipratropium bromide MDI with spacer, 40-120 micrograms 6-8 hourly as needed. Theophylline slow release, oral, initially at 400mg/day in 2-3 divided dosages (8-12 hourly). Serum levels should be done after 4-5 days and doses adjusted accordingly. The elderly are more susceptible to theophylline toxicity and theophylline dosages need to be reduced by about 30%. Do not exceed 900mg/day. Trials of corticosteroids (unless contraindicated): Prednisone, oral, 20mg daily for 28 days, after which lung function testing needs to be repeated. If no significant improvement in lung function values, the prednisone should be stopped. Maintenance dose of corticosteroids can often be tapered down to a dose of 510mg daily, or 10-15mg on alternate days. This forms part of a diagnostic assessment by responsiveness to therapy, except in acute bronchospasm. A patient with COAD should be in a stable phase if prednisone is used for this diagnostic assessment. Annual vaccination during the autumn months against epidemic influenza varieties. Preliminary comments Only chronic ongoing medicines should form part of the requirements for PMBs for chronic medication. Thus, at this point in time, influenza vaccinations should be excluded. This recommendation is based on administrative considerations. Preauthorisation of acute medicines is administratively tedious and potentially labourintensive, and inclusion of such should only be considered at a later stage (when the operational systems for chronic medicine PMB administration and implementation have been established). The Medscheme experience is that nebulisers are used frequently and inappropriately in patients with COAD. If they are to form part of PMBs, very clear guidelines should be established outlining the clinical setting where they should be funded. 19 2.3. Bronchiectasis It is important to identify and treat the underlying disorder. 2.3.1. Paediatrics Drug treatment Appropriate antibiotic therapy is required for acute lung infections or acute exacerbation of a chronic infection. Initiate treatment with the following antibiotics, and reassess when results of culture and sensitivity tests become available, or if response to treatment is unsatisfactory. Gentamicin, IV, 2.5 mg/kg 8 hourly for at least 14 days PLUS Ampicillin, IV, <20kg, 50-100 mg/kg/ 24hours in 4 divided doses; > 20 kg, 250-500 mg 6 hourly, for at least 14 days PLUS Cloxacillin, IV, <2 yrs, 62.5 –125 mg 6 hourly for 14 days, >2yrs. 125-500 mg 6 hourly for at least 14 days PLUS Metronidazole, oral, 7.5 mg/kg 8 hourly for at least 14 days IV antibiotics may be changed to oral antibiotics when the patient shows signs of improvement. Amoxicillin, oral, < 20kg, 20-40 mg/kg/24 hours in 3 divided doses, 20 kg, 125-250 mg 8 hourly, for 14 days PLUS Flucloxacillin, oral <2 yrs, 62.5 –125 mg 6 hourly for 14 days, >2yrs, 250-500 mg 6 hourly for 14 days PLUS Metronidazole, oral, 7.5 mg/kg 8 hourly for 14 days These oral and IV antibiotic regimens do not apply to children with Cystic fibrosis. In the presence of bronchoconstriction, bronchodilators may be of some benefit. Salbutamol nebuliser solution (5mg/mL), 1 ml mixed with an equal volume of 0.9 % sodium chloride solution, nebulised 4 hourly. Do not continue salbutamol nebulisation if there is no beneficial response. Influenza vaccine is recommended annually. For patients with cystic fibrosis, yearly Haemophilus influenzae vaccinations are also suggested. 20 2.3.2. Adults Empiric antibiotic therapy in patients with bronchiectasis needs to be prolonged and may often be up to three weeks, depending on the extent of the bronchiectasis and the organisms suspected. In patients otherwise stable and with mild bronchiectasis: Amoxicillin, oral, 500 mg 8 hourly, for 14 days OR Trimethoprim/sulfamethoxazole 80/400mg, oral, 2 tablets twice daily for 14 days OR Doxycycline, oral, 100mg twice daily for 2 weeks. More severely ill patients may need hospitalization and initiation of antibiotic therapy IV. Suggested therapy includes: Ampicillin, IV, 1g 6 hourly plus PLUS Gentamicin, IV, at a loading dose of 3-5 mg/kg, and maintenance dose of 1.5mg/kg 8 hourly according to response. IV therapy in these patients should be changed to oral therapy only after clinical improvement. Subsequent antibiotic therapy should be based on results of sputum investigations. Oral and inhaled bronchodilators may be used as for asthma or chronic bronchitis. N.B. Cardiac failure must be treated along conventional lines. Diuretics should be used cautiously. Preliminary comments Comments as per COPD. Further, although bronchiectasis is a chronic condition, only bronchodilator therapy may be necessary on an ongoing basis. Antibiotics are used intermittently, and should thus not be regarded as chronic medication per se. The practicality of including antibiotics within PMBs at this early stage should thus be considered carefully. Should antibiotics be included, it is imperative that the recommendations are reviewed, as antibiotic policies are dynamic (with changing sensitivity patterns). Also, the adult and paediatric guidelines should be brought in line (e.g. with regards to influenza vaccination, should the latter be included in the final PMBs) 21 3. Endocrine Disease 3.1. Diabetes Mellitus Type 1 3.1.1. Paediatrics Drug treatment insulin therapy Total daily dose: 0.6-1.5 units/kg/24 hours. The total daily dose is divided so that 2/3 is given in the morning and 1/3 in the evening, or 20% before each meal and 40% at night. Short-acting insulin is injected 15-30 minutes before a meal. Insulin doses are adjusted to keep blood glucose at 6-8mmol/L. When adjusting the insulin dose, do not increase or decrease by more than 2 units at a time. The most suitable areas for insulin injection are: the upper, outer area of the arms; the front and side of the thigh; the upper, outer surface of the buttocks, and the abdomen (except the area close to the navel). Establish a pattern for injecting, i.e. horizontally or vertically. Vary the site of injection according to this pattern. When the area has been fully covered move to another area. Patients doing strenuous exercise should not inject into their legs. Insulin regimens Regimen 1: Breakfast – intermediate/long-acting (2/3 dose) + short-acting insulin (1/3 dose) = 2/3 of total daily dose Supper – intermediate/long-acting (2/3 of dose) + short-acting insulin (1/3 of dose) = 1/3 of daily dose. Regimen 2: Breakfast – short-acting insulin (1/3 of dose) + intermediate/long-acting (2/3 of dose) = 2/3 of total daily dose Supper – short-acting insulin (1/3 of dose) and at night (+/- 22H00) intermediate/longacting (2/3 of dose) = 1/3 of daily dose Regimen 3: Breakfast – short-acting insulin – 20% of total daily dose Lunch - short-acting insulin – 20% of total daily dose Supper - short-acting insulin – 20% of total daily dose At night (+/- 22H00) - intermediate/long-acting - 40% of total daily dose. For hypoglycaemia, ivi dextrose/ glucagon therapy should be considered in the following circumstances: Unsatisfactory response to oral carbohydrate Inability to take oral carbohydrate 22 Signs of disorientation, stupor, convulsions, coma Glucagon, imi, sc, ivi, children <30kg, 0.5mg; children > 30kg, 1mg 3.1.2. Adults Drug treatment Insulin: Very rapid acting - onset of action 10min, peak action 1 hour, duration of action 3 hours; injections daily, immediately prior to meals. Short-acting - onset of action 30min, peak action 2-5 hours, duration of action 5-8 hours, injections daily, 30 min prior to meals. Intermediate-acting - onset of action 1-3 hours, peak action 6-12 hours, duration of action 16-24 hours, injections once to twice daily. Biphasic mixtures e.g. 30/70 - onset of action 30 min, peak action 2-12 hours, duration of action 16-24 hours, injections once to twice daily. Glucagon, imi, 1mg at once, where necessary for hypoglycaemia. Preliminary comments The minimum standard of care reimbursable without financial limits should be insulin vials (as opposed to eg. pensets). Should there be limited use of latter at State facilities, then strict clinical guidelines for such use must be established. Glucagon is acute therapy administered on a “as needed” basis, and for reasons mentioned previously should not form part of PMBs at this stage. 23 3.2. Diabetes Mellitus Type 2 Dietary therapy and weight loss is the corner stone of treatment of patients with type 2 diabetes. Drug Treatment Use if glycaemic targets are not reached after lifestyle modification for 3 months or newly diagnosed patients with very high blood glucose levels (15-20mmol/L) who are not dehydrated or in keto-acidosis. One drug initially, but combine with metformin or insulin if targets are not achieved. Sulphonylureas (hypoglycaemia can be a problem) E.g. Tolbutamide, oral, 250mg 2-3 times daily, up to 1500 mg/day OR Glipizide, oral, 2.5mg once to twice daily, up to 30mg/day OR Gliclazide, oral, 40mg once to twice daily, up to 320mg/day OR Glibenclamide, oral, 2.5mg once to twice daily, up to 15mg/day AND/OR Biguanides (useful in obese patients): Metformin, oral 500 or 850mg 1-3 times daily, total max. daily dose 3000mg OR Insulin As per insulin protocols outlined under type 1 diabetes mellitus 24 3.3. Hypothyroidism 3.3.1. Paediatrics Drug treatment Levothyroxine sodium, oral, 75-100 micrograms/m2 once daily Neonates and infants, 10-15 micrograms/kg as a single daily dose The dose of levothyroxine per kg day decreases with increase in age. Dosage must be adjusted to blood levels of T4 and TSH. 3.3.2. Adults Drug treatment For acute, recent hypothyroidism, levothyroxine, oral, 100 micrograms daily. Check TSH, FT4, (FT3) after 2-3 months. For long-standing hypothyroidism, levothyroxine, oral, 50 micrograms daily If there is a risk of ischaemic heart disease, start at 25 micrograms daily and increase by 25 micrograms every 4 weeks. TSH levels may take several months to stabilise. Check FT4 TSH annually. Hypothyroidism in pregnancy – on treatment: Levythyoxine, oral, 50 micrograms daily and titrate to desired effect. About 60% of hypothyroid pregnant women need an increase in thyroxine therapy in the second and third trimesters. Check TSH monthly and increase thyroxine doses to keep serum TSH levels low normal. After delivery, revert to pre-conception doses. 25 3.4. Addison’s Disease Maintenance Treatment Fludrocortisone, oral, 0.05-0.15 mg daily PLUS Hydrocortisone, IV, 20-40 mg daily OR Prednisone, oral, 5-7.5 mg in the morning. DIABETES INSIPIDUS Non-drug treatment Rehydration Drug treatment Desmopressin nasal solution, 10-40micrograms once to twice daily Larger doses can lead to water overload and hyponatraemia. 26 4. CNS Disease 4.1. Epilepsy 4.1.1. Paediatrics Drug treatment Monotherapy is preferred, but combination therapy may be necessary. Drug Seizure type Tonic Partial Absence Phenobarbital + + Sodium valproate + + + Carbamazepine + + Ethosuximide + Phenobarbital, oral, 3-5mg/kg/24 hours as single dose at night. Phenobarbital is not recommended as maintenance therapy for children older than 1 yr. due to undesirable side effects such as sedation, behaviour disturbances, hyperkinesia and dependence. Sodium valproate, oral, 20-50mg/kg/24 hours in 2 or 3 divided doses. Carbamazepine, oral, 15-20mg/kg/24hours in 2 to 3 divided doses. Carbamazepine should be initiated slowly over a period of 2-3 weeks. Idiosyncratic reactions, such as Stevens-Johnson syndrome, may occur. Ethosuximide, oral, 20-35mg/kg/24 in 3 divided doses or as a single dose at night (maintenance dosage). Initially, 3-6 yrs, 250mg as a single daily dose; >6 yrs, 500mg as a single daily dose, adjusted according to plasma levels and clinical response. Ethosuximide is indicated in absence seizures not responding to valproate. Lamotrigine is given as add-on therapy for drug-resistant paediatric epileptic syndromes, such as Lennox-Gastaut syndrome. A paediatric neurologist should initiate this drug. Routine daily prophylaxis is no longer recommended for patients with febrile seizures. However, for children with recurrent complex febrile seizures, prophylactic treatment can be considered. 4.1.2. Adults Drug treatment For tonic clonic, partial focal, partial complex seizures with and without secondary generalisation: 27 The aim is to use monotherapy i.e. a single anti-convulsant, until the seizures are controlled or intolerable side effects occur. Therapy should not be initiated after 1 attack only and only if evidence of epilepsy has been established. Phenytoin, oral, 5mg/kg/day, in single or divided doses. The usual maintenance dosage is 200-300 mg/day AND/OR Carbamazepine, oral, 600-1 800mg/day in 2 divided doses AND/OR Phenobarbitone, oral, 60-180mg/day in divided doses Monitor plasma levels for efficacy and toxicity. Anti-convulsants may make oral contraceptives ineffective. For idiopathic seizures with absence, tonic clonic or myoclonic seizures: Sodium valproate, oral, average dose 500mg twice daily, max. 2 500mg/day. Dosages should be increased gradually over 6 weeks. To be prescribed by a specialist only. For typical absences only Ethosuximide, oral, average dose 250-500mg 3 times daily. Not indicated for other seizures. To be prescribed by a specialist only. For myoclonic jerks Clonazepam, oral, 0.5-2mg 3 times a daily. Used as “add on” therapy. Preliminary comments The need for lamotrigine in adult patients should be reviewed. This drug is currently listed in the paediatric section only. 28 4.2. Parkinson’s Disease Drug treatment Early disease: Anticholinergics, Set therapeutic targets so that the patients are not overtreated. E.g. benzhexol, oral, 1-2mg daily, start with lowest dose, titrate upwards, max. dose 15mg/day in 3-4 divided doses OR Orphenadrine, oral, 50-100mg 3-4 times daily, start at lowest dose and titrate upwards. Parkinsonism, not drug induced: Levodopa/benserazide, 100/25mg 3 times daily, increase weekly by 100/25mg until desired response is achieved. Best for bradykinesia, rigidity and postural disturbance. OR Levodopa/carbidopa, 200/50mg, 3 times daily, increase by 100/25mg daily or every alternate day until desired effect is achieved. To be prescribed by a neurologist only. Levodopa complications: Bromocriptine, oral, 1.25mg daily for 1 week, increase according to response to 2.5mg/day for week two, 2.5mg twice daily for third week, then 2.5mg 3 times daily. Dopamine agonists may be used at secondary level after consultation with neurologist. 29 4.3. Multiple Sclerosis Not listed Preliminary comments Although this is a low frequency disease, chronic medication for multiple sclerosis can be very expensive. Interferons registered for use in this condition amount to > R100 000 per annum, despite having dubious long-term efficacy. These drugs reduce acute exarcerbations by 1/3 and delay progression of disability by some months. However, long-term disability does not appear to be influenced positively. It is thus imperative that drugs to be covered for multiple sclerosis are clearly defined. Medscheme suggests that interferons do NOT form part of PMBs for MS, but that corticosteroids, antidepressants, muscle relaxants and urinary antispasmodics are included. 30 5. Psychiatric Disease 5.1. Bipolar Mood Disorder Drug treatment Treatment with lithium salt or carbamazepine is effective, but usually after the manic episode has been controlled with an antipsychotic (haloperidol). Maintenance therapy Lithium, oral, 20mg/kg/day in divided doses, range: 500 –1 200mg/day, keep plasma levels at 0.4 – 0.8mmol/L Lithium dosage is determined by monitoring the blood level of the drug. The therapeutic blood level is usually higher than the prophylactic blood level. Therapeutic blood levels of lithium should be maintained for 4-6 months, whereas prophylactic blood levels can be maintained life-long. Lithium’s toxic blood levels and therapeutic drug levels do not differ greatly, and patients should therefore be closely monitored OR Carbamazepine, oral, 200 – 600 mg 2-3 times daily OR Sodium valproate, oral, 200-500 mg 3 times daily as a mood stabilizer Major depressive episodes Tricyclic antidepressants (TCA’s) (not for patients with cardiac conduction disturbances or high suicide risk; as lethal in overdose; start with lower than therapeutic doses and titrate up to therapeutic doses within about 7 days) Eg. amitriptyline, oral, 75mg – 150mg/day, titrate up to 300mg/day OR Imipramine, oral, 75 - 150mg/day Selective serotonin re-uptake inhibitors (SSRI’s) (for patients with contra-indications to TCA’s; to be prescribed by a psychiatrist only) Eg. fluoxetine, oral, 20 – 40mg daily Treat for at least 6 months. 31 5.2. Schizophrenia Schizoaffective and mood disorder as well as substance abuse or general medical conditions must be excluded. Drug treatment Stabilisation phase (before progressing to long-term therapy) Haloperidol, oral, 1-15 mg/day OR Chlopromazine, oral, 75-300mg/day in divided doses Maintenance Fluphenazine decanoate, IM 12.5-100mg every 3-4 weeks as chronic therapy OR Flupentixol decanoate, IM, 20-60mg every 2-4 weeks as chronic therapy Extrapyramidal side-effects Biperiden, slow IV or IM, 2mg, repeated every 30 minutes if necessary up to a max. of 4 doses daily. Higher doses of up to 5mg have been used. Preliminary comments Emergency therapy has not been listed above, as it is assumed that this would not form part of PMBs for chronic medication. Parenteral administration of biperiden, as listed in the Standard Treatment Guideline, should also be excluded from chronic medication PMBs. 32 6. Musculoskeletal Disease 6.1. Rheumatoid Arthritis During acute flare-ups, affected joints should be rested and day and/or night splints should be used. Drug treatment Pain alleviation Paracetamol, oral, 500-1000mg 6 hourly, when needed OR Paracetamol/codeine phosphate (500/10 mg) oral, 1-2 tablets 6 hourly (for more severe pain) Non steroidal anti-inflammatory agents (NSAID’s) – use for active inflammation with pain Eg. indometacin, oral, 25-50mg 3 times daily OR Ibuprofen, oral, 400-800mg 3 times daily Indometacin rectal, 100mg at night, as part of the total daily dose of NSAID, may be needed in some patients with severe nocturnal pain. The anti-inflammatory action of the NSAIDs may take 2-4 weeks to become evident. Reduced NSAID dosages have to be used in the elderly and in patients with impaired renal function. Concomitant use of more than one NSAID only increases toxicity, and has no additional benefit. Cimetidine oral, 200mg twice daily, may be considered for those at risk for gastrointestinal side effects of the NSAID’s (the elderly, previous gastrointestinal bleeding or ulcer) Disease-modifying anti-rheumatic medication (DMARD’s) - Patients not responding to NSAIDs and non-pharmacological therapy within 4-6 weeks, should seek specialist advice for consideration of therapy with disease-modifying anti-rheumatic medication (DMARD). Chloroquine sulphate, oral, 150-300mg (as base) daily AND/OR Sulfasalazine, oral, 1000mg twice daily AND/OR Methotrexate, oral, 7.5mg weekly; patients on methotrexate should be placed on supplementary folic acid, oral, 5mg daily AND/OR Azathioprine, oral, 50-150mg/day Doses of most of these are gradually titrated to a maintenance dose. DMARDs must be used only if adequate monitoring for toxicity is regularly performed. This applies particularly to retinal toxicity caused by chloroquine and to methotrexate (bone marrow, liver etc.) Oral corticosteroids 33 Prednisone, oral, 40-60mg/day for 2-4 weeks; review periodically and possibly taper down or use for longer duration at doses of 5-10mg/day. May be used at higher doses for short periods. Intra-articular corticosteroids (may be needed in selected cases; to be prescribed by a rheumatologist only) Methylprednisolone acetate, 20-80mg OR Betamethasone, 0.75-6.0mg, depending on joint size 34 7. Immunological Disease 7.1. Systemic Lupus Erythematosus Avoidance of sunlight exposure and avoidance of medications implicated in triggering or causing deterioration of SLE. Sun protective barriers may be implicated. Drug treatment Corticosteroids Prednisone, 1-2mg/kg/day initially, tapered to the lowest maintenance doses after a response has been obtained. The usual maintenance dose is +/- 10mg/day. Immunosuppressive therapy (for patients not responding, immunosuppressive therapy may be given on a referral basis) Azathioprine, oral, 25-50mg 3 times daily OR Cyclophosphamide, oral, 200mg/day For skin and joint involvement Chloroquine sulphate, oral, 150-300mg (base) /day Use should be controlled by regular opthamological examination. Severe Raynaud’s phenomenon Nifedipine, oral, 5-10mg 3 times daily Dose titrated to a safe level, which does not produce hypotension. Severe headache or depression Amitriptyline, oral, 25-75mg daily Hypercoagulable states Aspirin, soluble, oral, 150mg daily AND/OR Warfarin, oral, 2.5mg daily or less frequently Prophylaxis to supplement conservative measures. Hormonal contraceptive therapy May be indicated for women in their fertile years, as flare-up of lupus is associated with hormone changes and pregnancy. Preliminary comments Sun-protective barrier creams should not be part of PMBs, unless also provided as minimum standard of care by State hospitals. Hormone contraceptive therapy available at State facilities should be defined. 35 8. Gastro-Intestinal Disease 8.1. Crohn’s Disease 8.1.1. Paediatrics Non-drug treatment Enteral nutrition to achieve optimal growth. Total parental nutrition may be used in patients with severe IBD. Crohn’s disease remission can be induced by semi-elemental feeds for 6-8 weeks. Drug treatment Prednisone, oral, 1-2mg/kg/24 hours until improvement is evident. Taper over 2 weeks to stop PLUS Sulfasalazine (if colon involvement is present). Dosage as for ulcerative colitis PLUS Metronidazole, oral, 7.5mg/kg 8 hourly for peri-anal disease Duration of treatment should be individualized. 8.1.2. Adults Low residue foods in patients with strictures is recommended. Total parental nutrition may be needed for management of strictures or obstruction. Drug treatment Diarrhoea Loperamide, oral, 2-4mg 4 times daily as required for diarrhoea (max. 16mg/day) OR Codeine phosphate, oral, 30-60mg 3 times daily may often relieve the diarrhoea. Specific treatment Really only effective in acute active disease Mild cases Sulfasalazine, oral, 500mg twice daily, up to 1500mg 3 times daily. However, 1-2g 4-6 times daily may be given for acute attacks for 3 weeks. 5-amino-salicylic acid preparations (e.g. olsalazine, mesalazine) should be used only in patients intolerant to sulfasalazine. These patients should be referred for initiation of treatment with these drugs. Severe disease ADD prednisone, oral, 20-40mg daily, tapered to lowest possible maintenance dose OR 36 Prednisolone sodium phosphate retention enemas 20mg/100mL twice daily (to be prescribed by a gastroenterologist only) Very severe disease May require above therapy PLUS Azathioprine, oral, 1-2mg/kg daily OR Methotrexate, oral, 7.5mg weekly Both azathioprine and methotrexate to be prescribed by a gastroenterologist only. Perianal disease Metronidazole, oral, 400mg twice daily Correct vitamin and mineral deficiencies. Preliminary comments Should enteral feeds form part of PMB requirements, details of formulations available at State facilities and guidelines for their use must be defined. This also applies to the correction of vitamin and mineral deficiencies. 37 8.2. Ulcerative Colitis 8.2.1. Paediatrics Non-drug treatment Enteral nutrition to achieve optimal growth. Total parental nutrition may be used in patients with severe IBD. Drug treatment Sulfasalazine, oral, 50mg/kg/24 hours in 3 divided doses until improvement is evident, then maintenance therapy to decrease frequency of relapses, 25mg/kg/24 hours in 3 divided doses PLUS Hydrocortisone, rectal, 50mg daily for 1 week OR Prednisone, oral, 1-2mg/kg/24 hours in 3 divided doses or as a single morning dose for 3-4 weeks, tapered to stop, under cover of maintenance sulfasalazine (25mg/kg/24 hours in 3 divided doses) Immunosuppressives After repeated (2-3) attempts to taper steroids have failed, ADD: Azathioprine, oral, 2 mg/kg/24 hours in 2 divided doses (to be initiated by a specialist only) Severe disease Methylprednisolone, IV, 2mg/kg/24 hours for 3 days Criteria: more than 6 bloody stools daily, abdominal pain, fever, anaemia, hypoalbuminaemia 8.2.2. Adults Correct electrolyte, haematinic and nutritional deficiencies. Milk avoidance may benefit some patients. Drug treatment Mild cases Loperamide, oral,2-4mg after each loose stool (max. 16mg/day) PLUS Sulfasalazine, oral, 500mg twice daily, up to 1500mg 3 times daily. However, 1-2g 4-6 times daily may be given for acute attacks for 3 weeks. 5-amino-salicylic acid preparations (e.g. olsalazine, mesalazine) should be used only in patients intolerant to sulfasalazine. These patients should be referred for initiation of treatment with these drugs. 38 Severe disease ADD prednisone, oral, 20-40mg daily, tapered to lowest possible maintenance dose OR Prednisolone sodium phosphate retention enemas 20mg/100mL twice daily (to be prescribed by a gastroenterologist only) Very severe disease May require above therapy PLUS Azathioprine, oral, 1-2mg/kg daily OR Methotrexate Both azathioprine and methotrexate to be prescribed by a gastroenterologist only. Preliminary comments Should enteral feeds form part of PMB requirements, details of formulations available at State facilities and guidelines for their use must be defined. This also applies to the correction of vitamin and mineral deficiencies. 39 9. Renal Disease 9.1. Chronic Renal Disease See Chronic Renal Failure; Nephrotic Syndrome; Pyelonephritis and Obstructive/ Reflux Nephropathy; and Renal Calculi. 9.2. Chronic Renal Failure Determine and treat the underlying cause of the chronic renal failure. Monitor fluid intake and output, blood pressure, daily weight. 9.2.1. Paediatrics Drug treatment Patients with chronic renal failure usually require the following: Aluminium hydroxide suspension, 300 mg/ml 5-10 ml as required for rapid reduction of high phosphate levels, in short term. Calcium carbonate, 2-4 tablets chewed 3 times daily. (1 tablet is equivalent to 0.168g elemental calcium.) Calcium carbonate taken with meals as a phosphate binder, or between meals as a calcium supplement (where serum phosphate is not raised). To increase serum calcium and to offset renal osteodystrophy Alfacalcidol, oral, initially 0.25 micrograms twice weekly, increased to 1 microgram per 24 hours in 2 divided doses. Should be started before serum phosphate reaches the upper limit of normal (maintain at the lower limit of normal) and when the glomerular filtration rate has fallen to 20 – 30 ml/minute. Limited to use by pediatricians. Correction of metabolic acidosis Citric acid-sodium bicarbonate combinations, oral, <6yrs. 2g 2-3 times daily, 6-12yrs. 4g 2-3 times daily, >12 yrs. 4-8g 2-3 times daily Should be given if serum CO2 <16mmmol/L. Anaemia Epoetin Alfa, SC, 25-100 micrograms/kg once weekly in 2-3 divided doses. To be used by designated specialists or paediatric nephrologists only. Hypertension Refer to hypertension section. 40 9.2.2. Adults Drug treatment Uraemia – effects and complications Renal replacement therapies, according to protocols in specialised centres. National guidelines should be consulted. Hypertension Refer to hypertension section. To lower phosphate levels Calcium carbonate, oral, 500-1500mg/day in divided doses. Preferred to aluminium hydroxide. Anaemia – chronic Treatment of anaemia must focus on halting progression or reversal of renal disease/failure. Anaemia has many causes and mechanisms. Definitive treatments e.g. transplant or dialysis often improves the condition. It is important to identify factors likely to aggravate the condition. Epoetin alfa (erythropoietin) to be prescribed by a specialist only (on a named patient basis). Hyperparathyroidism Calcitriol, oral, 0.25-1 microgram 4 times daily. To be prescribed by specialist only. Acidosis Sodium bicarbonate, oral, 300-600 mg 3 times daily. Caution - sodium load. Long-term, non-urgent need for potassium removal Sodium polystyrene sulfonate, oral, 20-40 g with 100mL sorbitol 20% 4-6 times daily or rectally 50-75g mixed with 50-100mL sorbitol 70% plus water. Retain for 2 hours and repeat every 4 hours. Rectal administration is less effective. Fluid overload Furosemide, oral Pruritus, neurological symptoms: According to symptoms. Where NEPHRITIS is the cause of the chronic renal failure, prednisone, oral, 1-2 mg/kg/day (average 40 – 60mg) should be prescribed for steroidresponsive disease (eg. SLE and other auto-allergic disease) by a nephrologist; this dose should be tapered to an optimal maintenance dose. 41 9.3. Nephrotic Syndrome Monitor daily fluid intake and output; restrict sodium while oedema is present and advise normal to high protein diet. 9.3.1. Paediatrics Drug treatment: Mild to moderate oedema Spironolatone, oral, 3-5mg/kg/24 hours in 2-3 doses AND/OR Hydrochlorothiazide, oral, 1-2mg/kg/24 hours in 2 divided doses OR Furosemide, oral, 1-5mg/kg/24 hours in 2-3 divided doses or as a single dose. Great care must be taken not to give diuretics to a volume-depleted child. Severe oedema: (Albumin 20% IV, 0.5-1g/kg/24 hours administered over 12-24 hours, followed by Furosemide, IV, 1-2mg/kg as a single dose) OR Furosemide, oral, 1-2mg/kg 4 hourly plus PLUS Metolazone, oral, 0.2 - 0.4mg/kg/24 hours in 2 divided doses. Careful monitoring of electrolyte levels and renal function is mandatory. Intravascular volume must be adequate before diuretic therapy. To be prescribed by paediatric nephrologist or designated specialist only. Thrombotic complications To reduce thrombotic complications during periods of oedema aspirin soluble, oral, 75-150mg daily. Urine protein loss Patients not responding to other measures Captopril, oral, 1-5mg/kg/24 hours in 2-3 divided doses can have a useful limiting effect on protein loss in the urine. Fluid status and renal function must be monitored closely as the use of captopril in a volume-depleted patient can aggravate renal function impairment. Stop captopril if diarrhoea or vomiting occurs. To be prescribed by paediatric nephrologist or designated specialist only. Prophylaxis for pneumococcal infections Phenoxymethylpenicillin, oral, 125-250 mg twice daily during periods of oedema. For all nephrotic patients in remission Pneumococcal vaccine, IM, children >2 yrs, 0.5mL (single dose). Specific drug therapy Where minimal change disease is proven or highly probable - 42 Prednisone, oral, 60mg/m2/24 hours or 2 mg/kg/24 hours as a single morning dose (max. 60mg per 24 hours) for 4-6 weeks. Then the same dose on alternate days for another 4 weeks tapered over the following 2 weeks and stopped. Steroid supplementation should be given during periods of severe illness or surgery for up to 12 months following a course of steroids lasting 14 days or more. Various regimens may be used. Relapses Each relapse that occurs more than 30 days after discontinuation of treatment is treated similarly to the initial episode, except that the daily steroid dose is changed to alternate days as soon as the urine has been protein-free for 3-5 days. (It does not have to be continued for 4-6 weeks.) Patients who relapse within 30 days after withdrawing alternate-day steroids should be maintained on an alternate-day regimen and the dose tapered to the minimum effective level. Steroid toxicity and frequent relapses Where steroid toxicity (i.e. Cushingoid facies, hypertension, growth failure, cataracts) and frequent relapses occur: Cyclophosphamide therapy, oral or IV, should be considered by paediatric nephrologist or designated specialist only. Steroid resistance: Patients who do not respond to daily dose steroids within 4-6 weeks are designated steroid-resistant. They may respond to cyclophosphamide, intravenous pulse methylprednisolone, or ciclosporin, depending on the histological diagnosis. Steroid-resistant patients should undergo renal biopsy and be treated and followed up at a level 3-health facility by a paediatric nephrologist or other designated specialist. 9.3.2. Adults Drug treatment Prednisone, oral, 1-2mg/kg/day (average: 40 – 60mg) Hypertension ACE-inhibitor as first-line therapy Oedema Cautious diuretic use Eg. Furosemide, oral, 20 – 40mg daily initially Prevention or treatment of thrombotic complications Following heparin, Warfarin, oral, 5mg/day. Control with INR to keep in therapeutic range. 43 9.4. Pyelonephritis and Obstructive/ Reflux Nephropathy 9.4.1. Paediatrics Avoid irritant soaps and bubble baths. Prevent constipation. Determine and correct the underlying anatomical and/or functional abnormalities. Ensure adequate intake of fluids to irrigate bladder and to dilute high bacterial concentrations. Perineal hygiene. Regular complete emptying of the bladder and/or double voiding (i.e. making an additional attempt at voiding after the initial flow of urine has ceased). Prophylaxis: Trimethoprim/sulfamethoxazole combination preparation, oral, 6 weeks-5months, 20/100mg at night, If continent: 6 months-5yrs, 40/200mg at night, 6-12yrs, 80/400mg at night Otherwise: 6 weeks-5yrs, 20/100mg twice daily, 6 months –5yrs, 40/200mg twice daily, 6-12yrs, 80/400mg twice daily. OR Nitrofurantoin, oral, 1-2mg/kg at night if continent, otherwise 1-2mg/kg twice daily. Reduce if impaired renal function. Prophylaxis is required when recurrent infections or relapses occur, and where there is structural and/or functional abnormality of the urinary tract, which cannot be corrected. Urine cultures should be repeated at least every 3 months while on Prophylaxis and every 3 months for a year after cessation of treatment 44 9.5. Renal Calculi Fluid intake 2.5 – 3.5l/day, especially in warm climates. Lifestyle changes to minimise “ash” and calculus formation. Drug treatment For hypocitraturia Potassium citrate mixture BP, oral, 10-15ml, well diluted with water, 3 times daily for 10 days; repeat as necessary. For uric acid stones (not necessarily gout): Potassium citrate mixture BP, oral PLUS Allopurinol, oral, 300mg daily For mild metabolic hypercalciuria (absorptive type) Hydrochlorothiazide, oral, 50mg daily for 1 month. Can be repeated. Preliminary comments Erythropoietin is expensive and clear consensus guidelines should be collated, defining the drug’s place in treatment. The specific therapies for pruritus and neurological symptoms in chronic renal failure need to be defined, if to be covered under PMBs. For nephrotic syndrome, the need for thrombotic prophylaxis in children must be defined. Guidelines for the use of warfarin should also be more explicit. For recurrent pyelonephritis in children, acute antibiotic regimens have not been listed, as it is anticipated that only chronic prophylactic antibiotic therapy may require coverage under PMBs. It appears that for hypocitraturia, long-term treatment to prevent recurrence of renal calculi is not recommended. It should thus be excluded from this PMB section. 45 10. Haematological Disease 10.1. Haemophilia A and B Non-drug treatment Apply ice packs, bed rest and rest of affected joint/limb; no weight bearing; splints in acute phase (no circumferential casting); rehabilitation exercises. If immunization is indicated, press on injection site for at least 5 minutes after injection. Great caution must be exercised when taking blood specimen. Drug treatment Factor V111 deficiency with no inhibitor present Factor V111, 1 unit/kg intravenously raises Factor V111 level by 2%. Minor bleeds 15-25 units/kg; major bleeds 40 units/kg. Give 12 hourly until pain free and full movement of joint/limb restored. if inhibitor present: refer to haemophiliac centre or specialist health facility Factor V111 half-life = 8-12 hours. Factor IX deficiency with no inhibitor present Factor IX, 1 unit/kg intravenously raises Factor IX level by 1.5%. Minor bleeds 15-20 units/kg; major bleeds 40 units/kg. Give daily until patient is pain free and has full movement of the joint/limb. Factor IX half-life = 16-24 hours. Pain control Analgesics at appropriate dosages. Aspirin is contraindicated. Mucous membrane bleeds Tranexamic acid, IV or oral, 25mg/kg/dose 6 hourly Contraindicated in haematuria, factor IX deficiency, and with prothrombin complex concentrate. Desmopressin, IV, 03 micrograms/kg in at least 30mL 0.9% sodium chloride over 30 minutes Used only in established responders of mild factor V111 deficiency. Avoid IM injections. Preliminary comments No drugs should be listed under PMBs for chronic medication. The above treatments are all reimbursable under the hospital PMBs. 46 11. Opthalmological Disease 11.1. Glaucoma Drug treatment Sympathomimetics E.g. adrenaline drops, 1-2% once (effect is to reduce intra-ocular pressure, but is less effective than pilocarpine or timolol) OR Parasympathomimetics E.g. Pilocarpine drops 1%-2%, every 4-8 hours adjusted to response (to be prescribed by an ophthalmologist only) OR Pilocarpine gel, 4%, 10-15mm once daily at bedtime (to be prescribed by an ophthalmologist only) OR Beta-blocker E.g. Timolol eye drops, 0.25%, 1 drop twice daily, increase to 0.5% solution once daily (to be prescribed by an ophthalmologist only) AND/OR Carbonic anhydrase inhibitor E.g. Acetazolamide, oral, 250mg 1-4 times daily (to be added to beta-blocker depending on intra-ocular pressure; usually used along with potassium chloride to prevent hpokalaemia) Preliminary comments Adrenaline eye drops no longer appear to be available in SA. Short-term use of hyperosmotic agents has not been listed specifically, as its use is probably covered under the hospital PMBs. 47