Principles
The National Drug Policy makes provision for an Essential Drugs Program which is a key component in promoting rational medicines use.
The perspective adopted in the Adult Hospital Level Standard Treatment Guidelines (STGs) is that of a competent medical officer practicing in a public sector hospital. The STGs serve as a standard for practice, but do not replace sound clinical judgment. It is important to remember that the recommended treatments provided in this book are guidelines only and are based on the assumption that prescribers are competent to handle patients with the relevant conditions presenting to their facilities.
All reasonable steps have been taken to align the STGs with Department of Health guidelines that were available at the time of review. Each treatment guideline in the Adult Hospital Level STGs and Essential Medicines List (EML) has been designed as a progression in care from the current Primary Health Care (PHC) STGs and EML. A medicine is included or removed from the EML using an evidence based review of safety and effectiveness, followed by considerations of cost and other relevant practice factors. Where a referral to a tertiary facility is recommended, the relevant medicines have either been reviewed or included in the tertiary level EML, or is in the process of being reviewed. Given that the PHC STGs and EML are reviewed prior to the Adult Hospital Level STGs, there may be a period when the two STGs are not always perfectly aligned.
The dosing regimens provide the recommended doses used in usual circumstances. However, the prescribed dose should take into consideration drug-drug interactions and co-morbid states, notably renal or hepatic failure, critical illness, and morbid obesity.
It is anticipated that each Province will review the EML and prevailing tenders to compile a formulary which:
- Lists formulations and pack sizes that will facilitate care in alignment with the STGs.
- Selects the preferred member of the therapeutic class based on cost.
- Implements formulary restrictions consistent with the local environment.
- Provides information regarding the prices of medicines.
Therapeutic classes are designated in the “Medicine treatment” section of the STGs followed by an example such as, HMGCoA reductase inhibitors (statins) e.g. simvastatin. These therapeutic classes have been designated where none of the members of the class offer a significant benefit over the other registered members of the class. Always consult the local formulary to identify the example from the therapeutic class that has been approved for use in your facility.
Navigating the book
It is important that you become familiar with the contents and layout of the book in order to use the STGs effectively.
The International Classification of Diseases (ICD)-10 number has been included with the conditions to facilitate accurate recording of diagnoses. A brief description and diagnostic criteria are included to assist the medical officer to make a diagnosis. These guidelines also provide guidelines for referral of patients with more complex and uncommon conditions to tertiary facilities with the resources for further investigation and management.
The STGs are arranged into chapters according to the organ systems of the body. Conditions and medicines are cross referenced in two separate indexes of the book. In some therapeutic areas that are not easily amenable to the development of a STG, the section is limited to a list of medicines.
This edition of the Adult Hospital Level STG and EML provides additional information: a quick reference to dosing of antimicrobials for specific indications (Appendix I) and a section providing guidance on special considerations for specific medicines (Appendix II).
Furthermore, to promote transparency, in this fifth edition, revisions are accompanied by the level of evidence that is cited and hyperlinked accordingly. All evidence is graded according to the Strength Of Recommendation Taxonomy (SORT) (a patient-centered approach to grading evidence in the medical literature), described in detail on page xxxviii.
The section on Patient Education in Chronic Conditions aims to assist health workers to improve patient adherence and health, generally.
Glossary
| Term: | Description: |
|---|---|
| 16+6 gestation weeks | Second trimester:16 weeks and 6 days pregnant |
| Child Pugh score (A,B,C) | Prognostic scoring tool for chronic liver disease |
| Morbid obesity |
Obesity sufficient to prevent normal activity or physiologic function, or to cause the onset of a pathologic condition; BMI ≥ 40 kg/m 2 . |
| Renal failure | eGFR < 30 mL/minute. |
| Severe penicillin allergy |
A history of anaphylaxis, urticaria or angioedema associated with beta-lactam antimicrobials. |
| Surgical prophylaxis |
Prophylactic antibiotic therapy that reduces the risk of surgical site infection. In most instances a single antibiotic dose prior to the procedure is sufficient. Postoperative antimicrobial administration is not recommended for most surgeries as this selects for antimicrobial resistance. |
Medicines Safety
Provincial and local Pharmaceutical and Therapeutics Committees (PTCs) should develop medicines safety systems to obtain information regarding medication errors, prevalence and importance of adverse medicine events, interactions and medicines quality. These systems should not only support the regulatory pharmacovigilance plan, but should also provide pharmacoepidemiology data that will be required to inform future essential medicines decisions as well as local interventions to improve safety.
In accordance with the Medicines Control Council’s guidance on reporting adverse drug reactions in South Africa, the medical officer with the support of the PTC should report the relevant adverse reactions to the National Adverse Drug Event Monitoring Centre (NADEMC). To facilitate reporting a copy of the form and guidance on its use has been provided at the back of the book.
Feedback
Comments that aim to improve these treatment guidelines will be appreciated. The submission form and guidelines for completing the form are included in the book. Motivations will only be accepted from the Provincial PTC.
THERAPEUTIC DRUG MONITORING (TDM)
Potentially toxic medicines, medicines with narrow therapeutic indices and those with variable pharmacokinetics should be monitored regularly to optimise dosing, obtain maximum therapeutic effect, limit toxicity and assess compliance. Appendix II provides detailed information for specific medicines.
Lithium
Measure serum levels at about 12 hours after the last dose – e.g. in the morning before that day’s first dose. Levels should be less than 1 mmol/L and should be checked regularly while on therapy, with more frequent monitoring in the elderly and frail.
Aminoglycosides
Peak levels will generally be adequate if dosing is adequate (e.g. gentamicin 5 mg/kg/day in a single daily dose) and are not recommended unless the organism has a high MIC or the patient is critically ill. Trough levels taken immediately before the next dose are valuable in identifying potential toxicity before it manifests as deafness or renal impairment. Aminoglycosides are relatively contraindicated in renal impairment.
Anti-epileptics
Levels may be helpful to confirm poor adherence or to confirm a clinical suspicion of toxicity. Routine measurement in patients with well controlled seizures and no clinical evidence of toxicity, is not appropriate. Individual levels may be difficult to interpret – if in doubt, seek assistance from a clinical pharmacologist/pharmacokineticist.
PRESCRIPTION WRITING
Medicines should be prescribed only when they are necessary for treatments following clear diagnosis. Not all patients or conditions need prescriptions for medicine. In certain conditions simple advice and general and supportive measures may be more suitable.
In all cases carefully consider the expected benefit of a prescribed medication against potential risks. This is important during pregnancy where the risk to both mother and foetus must be considered.
All prescriptions should:
- be written legibly in ink by the prescriber with the full name and address of the patient, and signed with the date on the prescription form;
- specify the age and, in the case of children, weight of the patient;
- have contact details of the prescriber e.g. name and telephone number.
In all prescription writing the following should be noted:
- The name of the medicine or preparation should be written in full using the generic name.
- No abbreviations should be used due to the risk of misinterpretation. Avoid the Greek mu (ų): write mcg as an abbreviation for micrograms.
- Avoid unnecessary use of decimal points and only use where decimal points are unavoidable. A zero should be written in front of the decimal point where there is no other figure, e.g. 2 mg not 2.0 mg or 0.5 mL and not .5 mL.
- Frequency: Avoid Greek and Roman frequency abbreviations that cause considerable confusion (qid, qod, tds, tid, etc). Instead either state the frequency in terms of hours (e.g. 8 hourly) or times per day in numerals (e.g. 3x/d). È State the treatment regimen in full:
- medicine name and strength,
- dose or dosage,
- dose frequency,
- duration of treatment, e.g. amoxicillin 500 mg 8 hourly for 5 days. Note- In the case of “as required”, a minimum dose interval should be specified, e.g. every 4 hours as required.
- Most monthly outpatient scripts for chronic medication are for 28 days; check that the patient will be able to access a repeat before the 28 days are completed.
- After writing a script, check that the dose, dose units, route, frequency, and duration for each item is stated. Consider whether the number of items is too great to be practical for the patient, and check that there are no redundant items or potentially important drug interactions. Check that the script is dated and that the patient’s name and folder number are on the prescription form. Only then sign the script, and as well as signing provide some other way for the pharmacy staff to identify you if there are problems (print your name, use a stamp, or use a prescriber number from your institution’s pharmacy).
Notes on specific medicines
| ACE-inhibitor |
Angioedema is a potentially serious complication of ACE-inhibitor treatment and if it occurs it is a contraindication to continued therapy or to re-challenge |
|---|---|
|
ACE-inhibitors and ARBs |
ACE-inhibitors and ARBs can cause or exacerbate hyperkalaemia in CKD (eGFR < 60 mL/minute). Check the serum potassium before starting these medicines, and monitor serum potassium on therapy. ACE-inhibitors and ARBs are contra- indicated in pregnancy. |
| Allopurinol |
Contra-indicated in patients with eGFR < 30 mL/minute. Do not stop uric acid lowering drugs during an acute attack. |
|
Amitriptyline + citalopram |
Concomitant use of amitriptyline and citalopram may increase the risk of serotonin syndrome or neuroleptic malignant syndrome. Furthermore, there is a potential risk for QT prolongation. |
|
Anti-epileptic medicines |
Phenytoin, phenobarbitone and carbamazepine are potent enzyme inducing agents and should be used with caution with other medicines metabolised by the liver, especially warfarin, ARVs, progestin subdermal implants and oral contraceptives. |
| Benzodiazepines |
Benzodiazepines can cause respiratory depression. Monitor patients closely as benzodiazepines can exacerbate an abnormal mental state or mask important neurological signs of deterioration. Prolonged treatment with benzodiazepines often leads to tolerance and withdrawal symptoms if the medicine is discontinued abruptly. Combination therapy with more than one benzodiazepine is not indicated. |
| ß–blockers |
ß–blockers should not be used in cocaine poisoning. ß–blockers may cause bronchospasm in asthmatics. |
| Ceftriaxone |
Severe bacterial infections can mimic the features of haemorrhagic fever syndrome, and broad spectrum antibiotics, e.g. ceftriaxone, IV, 2 g daily, are indicated in every case until the diagnosis is confirmed. |
| Ciprofloxacin |
Irrational use of quinolones contributes to the emergence of XDR-TB and potential masking of active TB. |
| Clindamycin |
Clindamycin has good coverage against Gram positive organisms and anaerobes, so the addition of metronidazole is unnecessary. |
|
Folic acid + vitamin B12 |
Anemia megaloblastic: Give vitamin B12 and folic acid together until the test results are available as giving folic acid alone in patients with a B12 deficiency may precipitate a permanent neurological deficit. |
| Haloperidol |
Dosing may vary according to clinical circumstances, e.g. lower doses in the elderly or where HIV infection or HIV-related dementia is known or suspected. In the frail and elderly patient, reduce the dose by half. |
| Lithium |
Therapeutic drug monitoring is essential when using lithium. Clinical toxicity may occur even within the therapeutic range. Concomitant use of many medicines e.g. ACE-inhibitors, NSAIDs and diuretics may increase the risk of lithium toxicity. |
| Loperamide |
Contraindicated in dysentery, acute non-inflammatory diarrhoea, antibiotic-associated diarrhoea and amoebic dyssentery; as it may result in toxic megacolon |
|
Low molecular weight heparin (LMWH) |
In morbid obesity dosing of LMWH should be individualised, in discussion with a specialist. In renal failure (eGFR < 30 mL/minute), the recommended dose of LMWH is 1 mg/kg/day. Pregnant women with mechanical prosthetic valves should not receive LMWH unless antifactor Xa levels can be monitored reliably weekly. Therapeutic range is pre-dosing level 0.6 units/mL and a 4-hour peak level of 1–1.2 units/mL. |
|
Lyophilised plasma |
An alternative to fresh frozen plasma, based on limited evidence of efficacy. Does not require crossmatch prior to infusion, can be stored at room temperature and is pathogen inactivated (via a solvent detergent inactivation procedure). |
| Metformin |
Metformin should be dose adjusted in renal impairment (eGFR: 30-60 mL/minute). |
| Metronidazole |
The addition of metronidazole to amoxicillin/ clavulanic acid is unnecessary as amoxicillin/ clavulanic acid has adequate anaerobic cover. |
|
Misoprostol (for TOP) |
Misoprostol,can cause uterine rupture in women with previous Caesarean sections and those,of high parity. In these women use 200 mcg of misoprostol or alternative,methods such as extra-amniotic saline infusion without misoprostol. The dose,of misoprostol, PV, decreases with increasing gestational age because of the risk of uterine rupture. |
| Moxifloxacin |
Restricted for use in MDR-TB and in cases of severe penicillin allergy for specific indications (i.e. Hospital-acquired pneumonia, bronchiectasis, lung abscess, community acquired pneumonia, aspiration pneumonia and empyema). |
| NSAIDs |
Concomitant use of more than one NSAID has no additional clinical benefit and only increases toxicity. Chronic use of all NSAIDs is associated with varying degrees of gastrointestinal, renal and cardiovascular risks. Long-term use of NSAIDs should weigh potential benefits against these risks. |
| Oral diabetic agents |
Oral diabetic agents should not be used in type 1 diabetes and used with caution in liver and renal impairment. |
| Potassium |
Potassium will fall on insulin treatment and patients with DKA have potassium depletion even if initial potassium is normal or high. It is therefore essential to monitor and replace potassium. |
| Antivenom |
Never administer antivenom without being fully prepared to manage acute anaphylaxis. |
|
Prednisone taper |
Example of a dose reduction regimen, for an initial dose of 60 mg daily, reduce initial dose by 2/3, and continue as follows: - 40 mg/day in week 2 - 25 mg/day in week 3 - 20 mg/day in week 4 - 15 mg/day in week 5 - 10 mg /day in week 6 and - thereafter 5 mg daily for 1 week and then discontinue. Note: Weaning should be adjusted according to clinical context. If control deteriorates on weaning return to the previous effective dose. |
|
Silver sulfadiazine |
Do not use silver sulfadiazine if SJS/ TEN is thought to be due to cotrimoxazole or other sulphonamide. |
|
Sodium chloride |
Rapid correction of sodium, in hypo- natraemia, may lead to central pontine myelinolysis, which is often irreversible. Sodium should be frequently monitored and increases should be <9 mmol/L per day. |
| Spironolactone |
Monitoring of sodium, potassium and renal function is essential in patients taking spironolactone. Avoid if eGFR < 30 mL/minute. |
| SSRIs |
Adolescents with depression may have an increased risk of suicidal ideation when initiated on SSRIs. |
| Streptokinase | Do not use heparin if streptokinase is given. |
| Sulphonylureas |
Hypoglycaemia caused by a sulphonylurea can be prolonged. The patient should be hospitalised with an intravenous glucose infusion, and observed for at least 12 hours after glucose infusion has stopped. |
|
Tricyclic antidepressants |
Avoid in patients with cardiac disease and a high risk of overdose. |
| Testosterone |
Screen hypogonadal men for prostate cancer before beginning testosterone replacement. |
|
Topical retinoids |
Do not use in pregnant women. |
|
Unfractionated heparin |
Evidence indicates that PTT monitoring is not necessary with weight based dosing of unfractionated heparin. However, in patients with morbid obesity and renal failure (eGFR < 30 mL/minute) unfractionated heparin should be used with PTT monitoring to maintain the PTT at 1.5 to 2.5 times the control. PTT should be taken 4 hours after SC dose. |
| Valproate |
Do not initiate valproate during pregnancy, or if a woman intends to fall pregnant, as it is associated with a higher teratogenic potential than the other first line anti-epileptic agents. |
| Verapamil |
Never give verapamil or adenosine IV to patients with a wide QRS tachycardia as this may precipitate ventricular fibrillation. In atrial flutter, do not use verapamil as it will not convert flutter to sinus rhythm and may cause serious hypotension. |
| Warfarin |
Warfarin use requires regular INR monitoring and dose adjustment according to measured INR. See appendix II |
PENICILLIN DESENSITISATION
This has been included for information only.
Perform only in an ICU setting.
Discontinue all ß-adrenergic antagonists. Have an IV line, ECG monitor and spirometer in place. Once desensitised, treatment must not lapse as risk of subsequent allergy increases.
A history of Stevens-Johnson’s syndrome, exfoliative dermatitis, erythroderma are absolute contra-indications to desensitisation (use only as an approach to IgE sensitivity).
Oral route is preferred. 1/3 of patients develop a transient reaction during desensitisation or treatment, which is usually mild.
|
A: Reconstitute phenoxymethylpenicillin 250 mg/ 5mL |
||
|---|---|---|
| Step | Medicine mg/mL | Amount to administer (mL) |
| Strictly every 15 minutes |
B: To make 0.5 mg/mL solution: Dilute 0.5 mL of reconstituted phenoxymethylpenicillin solution in 49.5 mL water. |
|
| 1 |
0.5 mg/mL solution (1000 units/mL) |
0.1 mL |
| 2 |
0.5 mg/mL solution (1000 units/mL) |
0.2 mL |
| 3 |
0.5 mg/mL solution (1000 units/mL) |
0.4 mL |
| 4 |
0.5 mg/mL solution (1000 units/mL) |
0.8 mL |
| 5 |
0.5 mg/mL solution (1000 units/mL) |
1.6 mL |
| 6 |
0.5 mg/mL solution (1000 units/mL) |
3.2 mL |
| 7 |
0.5 mg/mL solution (1000 units/mL) |
6.4 mL |
|
C: To make 05 mg/mL solution: Dilute 1 mL of reconstituted phenoxymethylpenicillin solution in 9 mL water. |
||
| 8 |
5 mg/mL solution (10000 units/mL) |
1.2 mL |
| 9 |
5 mg/mL solution (10000 units/mL) |
2.4 mL |
| 10 |
5 mg/mL solution (10000 units/mL) |
4.8 mL |
|
D: Reconstituted phenoxymethylpenicillin 250mg/ 5mL = 50 mg/mL |
||
| 11 |
50 mg/mL (80000 units/mL) |
1.0 mL |
| 12 |
50 mg/mL (80000 units/mL) |
2.0 mL |
| 13 |
50 mg/mL (80000 units/mL) |
4.0 mL |
| 14 |
50 mg/mL (80000 units/mL) |
8.0 mL |
After step 14, observe for 30 minutes, then give 1.0 g IV. Interval between doses: 15 minutes.
Parenteral route
| Step | Medicine mg/mL | Amount to administer (mL) |
|---|---|---|
|
Strictly every 15 minutes: |
||
| 1 | 0.1 mg/mL | 0.1 mL |
| 2 | 0.1 mg/mL | 0.2 mL |
| 3 | 0.1 mg/mL | 0.4 mL |
| 4 | 0.1 mg/mL | 0.8 mL |
| 5 | 1 mg/mL | 0.16 mL |
| 6 | 1 mg/mL | 0.32 mL |
| 7 | 1 mg/mL | 0.64 mL |
| 8 | 10 mg/mL | 0.12 mL |
| 9 | 10 mg/mL | 0.24 mL |
| 10 | 10 mg/mL | 0.48 mL |
| 11 | 100 mg/mL | 0.1 mL |
| 12 | 100 mg/mL | 0.2 mL |
| 13 | 100 mg/mL | 0.4 mL |
| 14 | 100 mg/mL | 0.8 mL |
| 15 | 100 mg/mL | 0.16 mL |
| 16 | 100 mg/mL | 0.32 mL |
| 17 | 100 mg/mL | 0.64 mL |
After step 17, observe for 30 minutes, then give 1.0 g IV. Interval between doses: 15 minutes.
COTRIMOXAZOLE DESENSITISATION
Attempt desensitisation in patients with a history of cotrimoxazole intolerance, unless this was life-threatening, e.g.: Stevens-Johnson syndrome. (See Erythema Multiforme, Stevens Johnson Syndrome, Toxic Epidermal Necrolysis) . Unless the rash is severe or associated with systemic symptoms, continue treatment with careful observation for deterioration.
Desensitisation should be attempted using cotrimoxazole suspension 240 mg/5ml. Dilute the suspension appropriately and consult with your pharmacist if necessary.
NOTE
Do not administer antihistamines or steroids with this regimen.
| Time (hours) |
Cotrimoxazole dose (mL of 240mg/5mL suspension |
|---|---|
| 0 | 0.0005 |
| 1 | 0.005 |
| 2 | 0.05 |
| 3 | 0.5 |
| 4 | 5 |
| 5 |
Two single strength tablets (each tablet = 80/400 mg) followed by full dose |