ethambutol hcl rifampicin - The KZN Pharmacy and Therapeutics by gyvwpsjkko



                                Eight Edition – January 2006
Dear Readers,

Greetings for the New Year! Here’s hoping that for 2006, KZN can show an improvement in the rational
use of medicines.

The bulletin has been dormant for some time now but work behind the scenes progresses in strength.

With the changes in the long acting calcium channel blockers from Nifedipine 30mg XL to Amlodipine
5mg, a potential saving of R5.7 million may be realised with no compromise to patient care. However, are
these calcium channel blockers (CCBs) rationally prescribed in your facility?

Embodied in rational use is efficacy, safety, quality, dosing convenience and cost. The intention is to
ensure the patient receives optimal care in respect of medicine use whilst the medicine budget is not
squandered. This Bulletin contains some data to stimulate your thoughts and action. How does your
institution fare when measured against the Essential Drug Programme?

Best wishes

Ms Mariam Cassimjee
Co-ordinator: KZN PTC
KZN Pharmaceutical Services
E-Wing, Addington Hospital
Private Bag X54318
Durban, 4000.
Telephone : 031-3327090
Fax         : 031-3681093
E-mail      :

 Articles in this issue:

 •   Medicine Consumption in KZN – cause for concern?
 •   Propanolol or Atenolol: What is the Difference?
 •   Extracts from the “Safety of medicines” (WHO PHARMACEUTICALS NEWSLETTER; No. 4,
 •   Spontaneous Reporting of Adverse Drug Reactions
                    Medicine Consumption in KZN – cause for concern?
                      (Ms Mariam Cassimjee, B Pharm, KZN Pharmaceutical Services)

Audits at some nine hospitals have shown that the usage of some medicines does not always
comply with the required standards. The following data on provincial medicine consumption can
also be used to identify areas that may need investigation and corrective action. The January
2006 ABC analysis for KwaZulu-Natal from PMSC lists the top thirty items as follows: -

 No       QTY         EXPEND         ABC                               ITEM DESCRIPTION
  1       161820   R 35,127,885.60    A    Efavirenz tablets 600mg;30''s
                                           Vaccine,combined diphtheria,pertussis,tetanus and haemophilus influenza
  2        70358   R 16,786,715.22    A
                                           type b(dtp and hib) 10 dose w/ diluent
                                           Docetaxel trihydrate for infusion eq to docetaxel anhydrous 80mg/vial;w/
  3         2882   R 12,074,139.00    A
  4       320248   R 11,332,167.63    A    Lamivudine tablets 150mg;60's
  5       516594    R 9,887,609.16    A    Amlodipine besylate tablets eq to amlodipine base 5mg;30's
                                           Salbutamol inhalation aerosol complete;100mcg/metered dose;w/ mouth
  6       808720    R 9,753,163.20    A
                                           adaptor;300 doses
  7        77681    R 9,209,859.36    A    Vaccine rabies;inactivated;human;single dose;w/ diluent;1's
                                           Insulin injection human;biosynth.;yeast deriv.;soluble 30%;isoph.
  8       344355    R 8,824,188.65    A
                                           Ethambutol HCl,rifampicin,isoniazid + pyrazinam.tabs patient ready
  9       133170    R 8,086,157.13    A
                                           pack;275mg,150mg,75mg and 400mg;80's

  10      193943    R 7,743,482.97    A    Rifampicin and isoniazid tablets patient ready pack;300mg and 150mg;40's

  11      273820    R 7,514,694.44    A    Phenytoin sodium capsules patient ready pack;100mg;84's
  12     1148400    R 6,373,620.00    A    Medroxyprogesterone acetate injection long-acting 150mg;1ml
  13       28076    R 6,337,314.72    A    Erythromycin stearate tablets film coated;250mg;500's
  14       19948    R 6,244,122.96    A    Efavirenz capsules 200mg;90's
                                           Test strips & color chart,glucose in blood semi-quantitative;visual comparison
  15      101732    R 6,103,920.00    A
                                           or accuchek meters;80-110mg/dl;50's
                                           Ethambutol hcl.,rifampicin,isoniazid + pyrazinam.tabs patient ready
  16       75922    R 6,051,742.62    A
                                           pack;275mg,150mg,75mg and 400mg;100's
  17     1451908    R 5,530,574.99    A    Amoxycillin trihydrate capsules patient ready pack;500mg;15's
  18      508730    R 5,498,595.92    A    Cefuroxime sodium for injection sterile;750mg
                                           Co-trimoxazole tablets patient ready pack;sulphamethoxazole 400mg and
  19     1128384    R 5,172,262.43    A
                                           trimethoprim 80mg;56's

  20      102762    R 4,920,243.29    A    Rifampicin and isoniazid tablets patient ready pack;300mg and 150mg;40's

  21      228382    R 4,847,832.46    A    Vaccine measles;live;atten.virus;m/dose;10 dose;w/diluent 1's
  22     1905740    R 4,649,243.30    A    Enalapril maleate tablets 10mg;28's
  23        3904    R 4,441,658.88    A    Terizidone capsules 250mg;100's
  24      499037    R 4,436,438.93    A    Flucloxacillin capsules patient ready pack;250mg;20's
  25      182859    R 4,417,873.44    A    Stavudine capsules 40mg;60's
  26      559386    R 4,279,582.59    A    Albendazole suspension 100mg/5ml;20ml
  27       19793    R 4,179,094.02    A    Sulphasalazine tablets enteric coated;500mg;100's
                                           Insulin human isophane suspension inject.;biosynthetic;yeast
  28      162520    R 3,965,488.00    A
                                           deriv.;prefil.disp.syr.;100iu/ml;(p/phane penset);3ml
  29      285640    R 3,927,314.76    A    Vaccine poliomyelitis;oral trivalent;10 dose
  30       32388    R 3,913,177.07    A    Nalidixic acid tablets 500mg;100's

Whilst an ABC analysis is based on figures from actual supply data for a certain period of time,
extrapolating these figures to an annual usage gives a fair indication of consumption. High

expenditure on vaccines is expected and ARVs are used in a controlled manner in dedicated
sites. What can be deduced from the other medicines listed above?
The 6th item on the analysis is salbutamol inhaler, a 300 dose unit. The EDP STGs state clearly
that this preparation should be used as a “reliever” in asthma.1 Very few patients should be
treated with inhaled salbutamol alone, and then only for symptomatic relief. The “controller” (also
sometimes termed “preventer”) medicines, budesonide or beclomethasone, are the mainstay of
treatment in asthma.2 These preparations should be used on a continual basis, twice daily. What
is the practice in your facility? Do all asthma prescriptions conform to the STGs? This perhaps
warrants a check. A sample of prescriptions can be made and the following checked: -

•     The diagnosis on the patient’s folder (to give a clear indication for use).
•     Whether the STGs are being followed and if not, for what reason.
•     The frequency of dispensing of the inhaler, which will give an indication of usage and whether
      a check on technique or use is necessary.

The 5th item on the ABC analysis is amlodipine besylate, whereas the 22nd is enalapril maleate.
Should amlodipine feature so high up in the ABC analysis? Partly the reason lies in the difference
in price (see the table below for the cost per tablet/dose). Almost 4 times as many packs of
enalapril were issued by PMSC compared to amlodipine. Long-acting calcium channel blockers
are not recommended as first- or even second-line choices in the step-care of hypertension.3,4
The only exception, as noted in the KZN STGs (and those produced by the Hypertension Society
of SA), is in the management of isolated systolic hypertension. In such cases, a CCB may be
combined with a thiazide. In most cases, therefore, amlodipine should be used as add-on in the
fourth step of treatment. An audit of a sample of prescriptions within your institution would give a
fair indication how hypertension is being managed. The following details would have to be
determined: -

•     The diagnosis on the patient’s file (to identify cases of isolated systolic hypertension as well
      as any concomitant conditions that may affect the choice of add-on agents).
•     The antihypertensive agents being prescribed, and how the prescription matches the EDP
      STGs or any possible reasons for deviating from that approach.

Presently the costs per tablet of the hypertensive agents are: -

    Amlodipine 5mg                                                 R0.64
    Atenolol 50mg                                                  R0.08
    Atenolol 100mg                                                 R0.13
    Enalapril 5mg                                                  R0.08
    Enalapril 10mg                                                 R0.09
    Hydrochlorothiazide 25mg                                       R0.06
    Maximum dose of Hydrochlorothiazide 12,5mg (as
    recommended for hypertension on the EDP STGs)5

Sulphasalazine 500mg tablets (at number 27 on the ABC analysis) cost R2.11 per tablet. Almost
20 000 packs of 100 were issued by PMSC. This agent is included in the EDP STG for the
treatment of ulcerative colitis, Crohn’s disease and as a disease modifying anti-rheumatic
medication.6 It is listed as a prescriber level 3 item (for specialist only). The high usage in KZN
may well warrant scrutiny of all prescriptions to ensure correct usage.

You be the judge of fair use at your facility.

    It is worth calling for an ABC analysis for your facility and using a sampling technique to
    determine compliance to the EDP STGs. Taking matters up with your Drug and Therapeutics
    Committee will enable changes. Let us strive for optimal care of the patient with conservation of
    the pharmaceutical budget as intended by the EDP.
    1. Essential Drug Programme South Africa; Primary Health Care Standard Treatment
         Guidelines and Essential Drug List; 2003 Edition; Pages 195 & 196
    2. Essential Drug Programme South Africa; Primary Health Care Standard Treatment idelines
         and Essential Drug List; 2003 Edition; Pages 195 & 196
    3. Essential Drug Programme South Africa; Primary Health Care Standard Treatment
         Guidelines and Essential Drug List; 2003 Edition; Page 75
    4. Essential Drug Programme South Africa; Hospital Level Standard Treatment Guidelines and
         Essential Drug List; 1998 Edition; Page 73
    5. Essential Drug Programme South Africa; Primary Health Care Standard Treatment
         Guidelines and Essential Drug List; 2003 Edition; Page 75
    6. Essential Drug Programme South Africa; Hospital Level Standard Treatment Guidelines and
         Essential Drug List; 1998 Edition; Pages 1, 5 & 242

                    Propanolol or Atenolol: What is the Difference?
                         (Ms Mariam Cassimjee, B Pharm, KZN Pharmaceutical Services)

   Should propanolol be prescribed for hypertension? This question was prompted by the discovery of
   two prescriptions for propanolol, prescribed instead of atenolol, at a district hospital in KZN.

   Two aspects need to be examined:
       • Propanolol has a shorter duration of action necessitating frequent daily dosing (as much as
          4 times a day, unless supplied as a sustained release formulation), whereas atenolol is
          longer acting (allowing once or twice daily dosing);
       • Propanolol is non-selective, whereas atenolol is cardioselective.
   On the EDP STGs, propanolol is recommended for the short-term management of supraventricular
   tachycardia, followed by atenolol for maintenance. It is not recommended for hypertension.1

   In general, it is believed that convenience of dosing lends itself to better patient adherence. The
   choice of a longer-acting agent for the management of a chronic condition is therefore justified.
   Although beta-blockers should never be used in asthmatics and should be used with caution, if at
   all, in diabetics, it has been stated that atenolol is associated with a “reduced risk of bronchospasm,
   hypoglycaemia and peripheral vasoconstriction when daily dosage is in the lower range because of
   cardioselectivity” (USPDI, 14th Edition, Page 559).

   These are among the factors that have directed the development of the EDP STGs. They are worth
   applying in practice.

   References: -
   1. Essential Drug Programme South Africa; Hospital Level Standard Treatment Guidelines and
      Essential Drug List; 1998 Edition; Page 47
   2. USPDI, 14th Edition, Page 559.

                                       Extracts from “Safety of medicines”
                      WHO PHARMACEUTICALS NEWSLETTER; No. 4, 2004
Reports of diabetes

Australia. Australia's Adverse Drug Reactions Advisory Committee (ADRAC) has received reports of
hyperglycaemia associated with four of the atypical antipsychotics: clozapine, olanzapine, quetiapine and
risperidone (for details see Table 1). In the ADRAC reports, the median age at diabetes onset for olanzapine was
42 years (range 30–56) and for clozapine was 38 years (17–70). Median time to onset of diabetes was 13 months
(range 2 days to 4 years) for olanzapine and 25 months (20 days to 8 years) for clozapine.

Of the 19 reports of diabetes with olanzapine, olanzapine was the sole suspected agent in 17, and of the 52 reports
with clozapine, clozapine was the sole suspected agent in 49. In some of the reports received by ADRAC, recovery
followed withdrawal of the antipsychotic but in others, continuing antidiabetic treatment was required.

 Table 1. Antipsychotic-associated diabetes
                                              Clozapine         Olanzapine        Risperidone          Quetiapine
 Diabetes                                        52                  19                  3                   3
 Impaired glucose metabolism                     55                  13                  4                   2
 Weight increase                                 51                  66                 17                   1
 Total reports                               2826                   922                 510                   144
Reference: Australian Adverse Drug Reactions Bulletin Vol. 23, No. 3, June 2004. Available on the Internet at

ADR update from Finland
Finland. Finland's National Agency for Medicines has reviewed common antipsychotic-associated reactions
reported to its adverse drug reaction (ADR) registry, and found that the atypical antipsychotics "do not appear to be
without adverse effects". During the 30-year period covered by Finland's ADR registry, a total of 974 antipsychotic-
associated ADRs have been reported, 564 of which have been received since 1994. Clozapine was the suspected
drug in 484 reports, with adverse events including leucopenia, granulocytopenia and agranulocytosis, often with
infectious signs, and was the suspected drug in 22 fatalities (see Table 2 for other antipsychotics). Since 1994, as
use of the newer atypical antipsychotics has replaced use of conventional antipsychotics, the majority of reports,
even after clozapine (n = 306), involved these newer agents (risperidone [n = 65], olanzapine [45] and quetiapine
[36]) and, even with the increasing use of these newer agents, there were still reports of serious adverse events
(see Table 2).

 Table 2. Antipsychotic-associated ADRs                   Table 3. Serious events since 1994
 over 30·years
 Antipsychotic            Number of reports                               Event                        Number of
 Chlorpromazine                          75                                     Heart disorders             44
 Risperidone                             71                                   Blood dyscrasias              32
 Olanzapine                              52               Milk secretion/ hyperprolactinaemia               29
 Haloperidol                             43                                      Liver disorders            28
 Thioridazine                            39                                             Oedema              11
 Quetiapine                              38                           Extrapyramidal symptoms               10
                                                                                       Seizures              8
                                                                             Tardive dyskinesia              7
                                                                                        Death 2             27
Reference: TABU: Drug Information from the National Agency for Medicines, Finland, 2: 50-52, 2004.

                         Spontaneous Reporting of Adverse Drug Reactions
                            (KZN Pharmacovigilance Task Team – 2005)

Over the last decades, a number of studies have noted that illness and death due to medicine is one of
the major health problems. However, is this true for KZN?

In the USA, where practice standards are deemed to be better than in South Africa, it has been
estimated that adverse drug reactions (ADRs) are the 4th to 6th largest cause of death, resulting in
several thousands of patients dying each year, and many more suffering from ADRs.1

In the USA: -
• 6.7% of patients experience serious ADR in the in-patient setting or are admitted as a result of an
     ADR.1, 2
• 10% of all hospital admissions are due to ADRs.3

In Germany: -
• The treatment of ADRs was estimated to have cost $588m/year in 1997, with 30.7% of admissions
    preventable (admissions resulted in a median length of stay of 8.7 days).4

In addition to the sufferings of the patients, the treatment of ADRs imposes a high financial burden on
healthcare. Some countries spend 15-20% of their hospital budget dealing with drug complications.3

More recent data from the United Kingdom have shown that ADRs are responsible for 6.5% of hospital
admissions, accounting for 4% of hospital bed capacity.5 The overall fatality was 0.15% and 70% of the
ADRs were avoidable. The estimated annual cost to the UK NHS was $847 million.

The importance of pharmacovigilance is best detailed in the specific aims the World Health
Organization set for the WHO Collaborating Centre for International Drug Monitoring, which are: -

•   “to improve patient care and safety in relation to the use of medicines and all medical and
    paramedical interventions,
•   to improve public health and safety in relation to the use of medicines,
•   to contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging
    their safe, rational and more effective (including cost-effective) use, and
•   to promote understanding, education and clinical training in pharmacovigilance and its effective
    communication to the public.”

The WHO has further widened ‘pharmacovigilance’ to include: -

•   substandard medicines
•   medication errors
•   lack of efficacy reports
•   use of medicines for indications that are not approved and for which there is inadequate scientific
•   case reports of acute and chronic poisoning
•   assessment of drug-related mortality
•   abuse and misuse of medicines
•   adverse interactions of medicines with chemicals, other medicines, and food.

Reporting of these ADRs is a problem internationally. The occurrence of ADRs is influenced by the
types of drugs used, the awareness of the problem by the health workers, as well as the population. In
addition, ADRs may be confused with the disease process for which they are meant to treat e.g.
diarrhoea seen in children with HIV, may occur as a result of ARVs used to treat AIDS. Locally, in South
Africa, there is little co-coordinated effort in place for reporting across the provinces.

Figure 1 highlights the problem at hand in South Africa, with very little direct reporting for a population
of 44 million. There is need for more health workers to become aware of ADRs and of the significance
of direct reporting of these events. Direct reporting in SA has been estimated to be < 100 p.a.

                   Annual ADR Reporting Rate: South Africa
       Number of Reports
                                                                                                Not indicated
         300                                                                                    Manufacturer
         200                                                                                    Direct
           1987 1990 1993 1996 1999 2002

Figure 1: Slide presentation by Dr Ushma Mehta to the KZN Pharmacovigilance Committee – 18
November 2004.

On 7 September 2004, Dr Manto Tshabalala-Msimang, in her speech on the occasion of opening the
National Pharmacovigilance Centre at MEDUNSA, listed the specific aims of the comprehensive
antiretroviral pharmacovigilance programme as: -

•    to determine the burden of drug-related morbidity and mortality in patients with HIV and AIDS,
     particularly associated with ARV use, and develop measures to minimize this negative impact;
•    to provide training and information to health personnel and patients on the safe use of
     antiretrovirals and other medicines commonly used amongst people with HIV and AIDS;
•    to develop systems to assess the risks and benefits of treatments commonly used in patients with
     HIV, STI and TB;
•    to identify, assess and communicate any new safety concerns associated with the use of
     antiretrovirals and other HIV medicines;
•    to support regulatory and public health decision-making through an efficient surveillance system
     that monitor quality, benefits and risk or harm associated with ARVs and other medicines currently
     used in the health sector;
•    to minimise the impact of misleading or unproven associations between adverse events and ARV
•    to detect, assess, and respond to safety concerns related to complementary and traditional
     medicines used in HIV-infected patients;
•    to establish an early warning system for resistance to antimicrobials commonly used in HIV,
     including, but not limited to, antiretrovirals; and
•    to respond to claims of efficacy of untested products and treatment modalities.

Meeting these goals is going to be a mammoth task. A visit to KZN’s intranet site will give you some
information to get started -

References: -
1. Lazarou J et al. Incidence of Adverse Drug Reactions in Hospitalized Patients. A Meta-analysis of
     Prospective Studies. JAMA 1998; 279:1200-1205.
2. Wiffen P et al. Adverse drug reactions in hospital patients. A systemic review of prospective and
     retrospective studies. Bandolier Extra 2002; June: 1–15.
3. EU Medicine and Drug Safety (
4. Goettler M, Schneeweiss S, Hasford J. Adverse Drug Reaction Monitoring - Cost and benefits
     considerations part II: cost and preventability of adverse drug reactions leading to hospital
     admission. Pharmacopeidemiol Drug Safety 1997; 6 (suppl. 3):S79-S90.
5. Pirmohamed M et al. Adverse drug reactions as cause of admission to hospital: prospective
     analysis of 18 820 patients. BMJ 2004; 329:15-19.


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