Download Appendix K

Council for Medical Schemes
Therapeutic Algorithms for the
Chronic Disease List Conditions
December 2002
First Draft
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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]
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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 Some of the clinical information is outdated e.g. ACE-inhibitors have become the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.
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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
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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
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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.
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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
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Drug treatment
Diuretics
Hydrochlorothiazide, oral, 12.5mg daily. In patients with fluid retention, increase to
25mg daily. If unresponsive to latter or if creatinine > 150mol/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.
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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.
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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.
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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.
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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
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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.
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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)
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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.
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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.
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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)
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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.
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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 -
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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.
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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
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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.
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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.
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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.
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