Case Study 7:
Medication Review

February 2000

Scenario
Mrs Beverly March is a 72- year-old who has well controlled hypertension and
no other risk factors for cardiovascular disease. She suffers from reflux
oesophagitis and occasionally requires pain relief for knee pain.
Her current medications are:
atenolol 50mg mane
ranitidine 150mg bd

enalapril 10mg mane

piroxicam 20mg prn for knee pain

On questioning and discussing her medications you learn that she is also
taking a multivitamin and sometimes uses ibuprofen which she buys from the
pharmacy. In addition she sometimes forgets her antihypertensive
medications. Mrs March weighs 65kg.

Inside
Results

page 3

Expert Commentary
Dr Charles Ovadia
Grant Kardachi

page 9
page 11

References

page 14

Case Study Results

One thousand two hundred and eighty-eight responses to this case have been received.
A sample of one hundred responses have been aggregated and compiled for feedback.
Question 1
Do you identify any of the following (please specify):
Drug-Drug Interaction

83% of respondents identified a drug-drug interaction. These responses are

summarised in the table below.
Interaction
Enalapril and NSAIDs
Piroxicam and ibuprofen
Atenolol and NSAIDs
Atenolol and enalapril
Antihypertensives and NSAIDs
Unspecified

Percentage of
Respondents *
34
30
13
4
1
22

* respondents may have indicated more than one response

Drug-Disease Interaction

Drug-disease interaction was considered by 92% of respondents. The responses are

shown in table below.
Interaction
Reflux oesophagitis and NSAIDs
Hypertension and NSAIDs
Unspecified

Percentage of
Respondents *
64
23
26

* respondents may have indicated more than one response

Contraindication For One (Or More) Of The Drugs

Of the 70% of respondents who indicated that Mrs March had a contraindication for
one (or more) of the drugs, 50% of respondents identified NSAIDs and 20% did not
specify the drug(s) involved. 25% of respondents stated that NSAIDs should have
been avoided in Mrs March because of her reflux oesophagitis while 5% considered
contraindicated because of both reflux and hypertension.

Evidence Of An Adverse Drug Event, Side Effect Of A Drug

Of the 54% of respondents who reported that Mrs March had a side effect associated
with the use of a drug(s), 37% attributed her reflux oesophagitis symptoms to
NSAIDs use while 17% did not specify a particular association.

Concordance Problem

59% of respondents identified concordance problems and of those 14% reported noncompliance with antihypertensive medications. 11% of respondents thought Mrs
March was self-medicating with over-the-counter ibuprofen without the knowledge of
her doctor and hence duplication of NSAID use for knee pain. It was noted from a
few responses that the term concordance was not fully understood compared to the
better-known term compliance.

Need for Investigations

61% of respondents would undertake further investigations.

Investigation
Endoscopy
Creatinine/renal function
Urea & electrolytes
X-ray of the knee
Full blood count (incl. RBC)
Iron studies
Lipid profile
H. pylori screening
Liver function tests
Blood sugar levels
Blood pressure monitoring
Thyroid function tests
Unspecified
* respondents may have indicated more than one response

Percentage of
Respondents *

24
16
15
9
6
3
3
3
2
2
2
1
11

Question 2
What other health professional would you involve in this medication
review?
89% of the respondents stated they would call on the services of other health
professional(s).
Health Professional

Percentage of
Respondents *
79
34
20
10
9
5
5
2
11

Pharmacist
Physiotherapist
Community nurse
Specialist
Gastroenterologist
Dietician
Social worker
Rheumatologist
None
* respondents may have indicated more than one response

Question 3
What reference sources would you use (if any):
Most respondents would use references for further information.
Referral Source

MIMS (hard
copy/electronic version)
Medical Director
(incl. A-Z dex)
Therapeutic Guidelines
series
Australian Medicines
Handbook
From the pharmacist
Australian Prescription
Products Guide
Current Therapeutics
Australian Prescriber
Medical journals
Pharmaceutical
representatives
Other

Percentage of Respondents*
Appropriate
doses
42

Drug
Appropriate
interactions indications

New
medicines

50

32

28

20

21

12

3
2

4
2

2
2

3
2

2
1
1
0

3
1
0
0

2
2
1
0

5
0
4
5

*respondents may have indicated more than one response

Question 4
What action would you take?
All respondents would take action and review Mrs Marchs therapy.
Add a medication

38% of respondents stated that they would add a medication. The list below outlines
the agents selected.
Medication
Paracetamol
Proton pump inhibitors
Celecoxib
Glucosamine
Aspirin EC 100mg
Indapamide
Liniment

Percentage of
Respondents *
33
2
2
1
1
1
1

* respondents may have indicated more than one response

Cease a medication

84% of respondents would cease a medication(s). Various responses are detailed

below.
Medication
NSAIDs
Piroxicam only
Ibuprofen only
Atenolol only
One of the antihypertensives
Enalapril only
Piroxicam & enalapril
Piroxicam & ranitidine
Unspecified

Percentage of
Respondents *
38
16
14
6
3
1
1
1
16

* respondents may have indicated more than one response

Increase dose

9% of respondents would increase the dose of a medication(s).

Medication
Enalapril
One of the antihypertensives
Atenolol
Unspecified
* respondents may have indicated more than one response

Percentage of
Respondents *
5
2
1
1

Reduce Dose

11% of respondents would consider lowering the dose of a medication(s).

Medication
Piroxicam
Antihypertensives (one or both)
Atenolol after ceasing NSAIDs
Enalapril
Ranitidine after ceasing NSAIDs

Percentage of
Respondents *
6
2
1
1
1

* respondents may have indicated more than one response

Substitute An Alternative Medication

66% of respondents would substitute with an alternative medication and the table
below outlines the choices selected.
Substitute
Paracetamol for NSAIDs
Unspecified agent for NSAIDs
Celecoxib for piroxicam and/or ibuprofen
Omeprazole for ranitidine
Long acting ACE inhibitor for enalapril
Low dose thiazides for atenolol
Long acting agent(s) for current antihypertensives
Thiazides for enalapril
Unspecified agent(s) for current antihypertensives
Diuretics for both antihypertensives
Paracetamol and/or celecoxib for NSAIDs
Less ulcerogenic NSAIDs for piroxicam
Unspecified agent for ranitidine
Physiotherapy for NSAIDs
Unspecified

Percentage
respondents*
30
12
9
5
3
2
2
1
1
1
1
1
1
1
10

* respondents may have indicated more than one response

Discuss Medication Regimen With Patient

93% of respondents would discuss the medication regimen with Mrs March.

Discuss Side Effects With Patient

94% of respondents considered counselling Mrs March about the side effects of the
medications she is currently taking.

Other Actions

32% of respondents would take other actions summarised below.

Warn against concurrent use of piroxicam and ibuprofen
Encourage the use of paracetamol instead of NSAIDs
Consider the use of celecoxib
Investigate the severity of knee pain and symptoms of reflux oesophagitis
Encourage non-pharmacological management for knee pain e.g. physiotherapy with
or without hydrotherapy, liniment
Exercise regimen
Diet and salt restriction
If oesphagitis present change from ranitidine to proton pump inhibitor
May not require ranitidine after stopping NSAIDs
Investigate the compliance problem
Investigate memory impairment
Discuss importance of compliance
Recommend compliance enhancing devices e.g. Webster pack, Dosette
Investigate the requirement for multivitamins
Encourage compliance and consider monotherapy for hypertension
Stop all antihypertensives and monitor blood pressure (BP). If BP rises restart one of
her antihypertensives or start on low dose thiazides
Stop all NSAIDs and monitor BP. The effectiveness of ACE inhibitor increases in the
absence of NSAIDs

Expert Commentary
Dr Charles Ovadia
GP Project Manager for the Divisions National Consortium for the
Quality Use of Medicine in General Practice (DiNCQUM GP) project,
Polypharmacy in the Elderly
Central Sydney Division of General Practice
The case of Mrs Beverley March looks simple for a medication review as she has only
a few diseases and approximately six drugs. But the principles we learn in handling
her medication review are as valid as when dealing with patients who have ten or
more medications. We know that the older the patient, the more medications they are
on, the more likely they are to have an adverse event and the greater the possibility of
admission to hospital.
Question 1
Do you identify any of the following?
Certainly she has problems of drug-drug interaction and drug-disease interaction.
5 We know that NSAIDs cause problems with hypertension by causing an increase
in blood pressure; and also cause problems in the treatment of hypertension by
decreasing the efficacy of antihypertensives. There is the added risk of electrolyte
disturbance such as hyperkalaemia with ACE inhibitors.
5 NSAIDs are also implicated in upper GI symptoms and in worsening of
symptoms in patients with reflux disease. NSAIDs in older patients in particular
are a leading cause of hospitalisation and certainly cause deaths due to GI bleed
and perforation. The use of ranitidine (Zantac, Rani, DBL Ranitidine,
Ranoxyl, Ranihexal) in Mrs March does not offer an additional benefit against
NSAIDs induced ulcers, however, the risk can be reduced by concomitant
therapy with omeprazole (Losec, Acimax ,Maxor) or double-dosage
famotidine (Pepcidine, Amfamox)1 .
The problem of taking two NSAIDs worsens the prospect of interaction.
So certainly, we would think that Mrs March, who only occasionally requires pain
relief for her knee, would do well to have her NSAIDs withdrawn for the sake of her
hypertension and reflux.
I understand concordance to be an agreement that is reached between the patient and
the doctor, about the management of a disease and use of medication for that disease
in a manner that is suitable for that patient.
There is no urgent indication for investigation at this time.

Question 2
What other health professional would you involve in this medication
review?
Certainly if she had a regular pharmacist, and I would encourage her to have one, it
would be worthwhile to discuss Mrs Marshs problems with her permission.
Physiotherapy, muscular strengthening exercises, heat packs, are all useful to help
reduce the need for analgesia.
Question 3
What reference sources would you use?
All the sources mentioned are useful and I agree that MIMS and Medical Director are
most used, but the Australian Medicines Handbook and Therapeutic Guidelines series
are increasing in reputation.
One of the most useful sources of information to show patients is in fact Consumer
Medicine Information (CMI) because they are written in simpler language and are
more accessible to the patients.
The CMI for piroxicam (Mobilis, Feldene, Candyl, Pirohexal, Rosig) states to
tell your doctor if you have heartburn, indigestion, high blood pressure, taking other
NSAIDs, taking medicines to treat high blood pressure.

Question 4
What action would you take?
Certainly it would be worth a trial to cease the NSAIDs and institute the use of
paracetamol up to 4g per day when necessary for her occasional pain. This then could
be followed by a decrease in her other medication such as the enalapril (Renitec,
Amprace) or ranitidine.
As she has uncomplicated hypertension, there is not a clear indication for an ACE
inhibitor; but there is proven long term benefits with beta-blockers and low dose
thiazides. ACE inhibitors are indicated when there are complications such as diabetes,
renal damage with hypertension or decreased left ventricular function.
Currently there is an Australia wide GP trial underway to test the value of ACE
inhibitors versus thiazide called the ANBP2 trial which will provide information in
the next 2-3 years.
The fact that she occasionally forgets her medication may be an innocent event in
itself; or it may be a clue that Mrs March needs help in organising a schedule e.g.
before meals or after breakfast or a dated pack or Dosette or Webster pack, or even a
first clue to loss of cognitive function and she may require further examination e.g. by
Mini Mental.

So by careful discussion with the patient and of course explaining all side effects as
GPs always do, we would achieve an optimal outcome.

Grant Kardachi
Community Pharmacist (accredited for Medication Management Review)
Novar Gardens Pharmacy, Novar Gardens, South Australia
President, Pharmaceutical Society of Australia (South Australia Branch)
Question 1
Do you identify any of the following:
Drug - Drug Interaction

The majority of respondents identified a drug to drug interaction in the case, however,
only 34% specified the most clinically important interaction between enalapril and the
NSAIDs. There is a significant potential for NSAIDs to reduce the efficacy of
enalapril as an antihypertensive. In addition, both NSAIDs and ACE inhibitors can
independently, and by different mechanisms, produce an acute functional decline in
glomerular filtration rate in susceptible patients (e.g. patients with renal impairment,
heart failure, dehydration etc). When these are combined the risk of acute renal
impairment is substantially increased 2. The combination can also, independent of any
renal function decline, increase the propensity to hyperkalaemia.
Atenolol (Noten, Tenormin, Tenlol, Anselol, Atehexal, Tensig, SBPA
Atenolol, DBL Atenolol) and NSAIDS was also identified as a potential problem.
Although Mrs March is stated to have well-controlled BP, the use of NSAIDs may
reduce impair control and additional monitoring is warranted. This applies to control
with any antihypertensives and is not specific to beta-blockers. NSAIDs may inhibit
renal prostaglandin synthesis, allowing unopposed pressor systems to produce
hypertension2.
Atenolol and enalapril was identified as a drug-drug interaction by some respondents.
The combination is logical and will provide additive BP lowering if required.
A number of respondents specified an interaction between piroxicam and ibuprofen
(Brufen, Rafen). I agree that this combination is illogical, but apart from the
potential for increased NSAIDs side effect there wont be an interaction. However, the
issue of over the counter medication is an important factor.

Mrs March may be unaware that the ibuprofen that she buys for pain relief is also
an NSAIDs. I would hope that she would be appropriately counselled in the pharmacy
to identify the concurrent use of two NSAIDs. Mrs March needs to understand that
she has two NSAIDs and a rational treatment plan explained to her. Ibuprofen, with
lower risk of serious gastrointestinal adverse effects and its shorter half-life is the
preferred drug in the elderly.
Drug- Disease Interaction

A major connection was correctly identified as NSAIDs and reflux oesophagitis. Less
obvious to the respondents, but equally clinically problematic, is the adverse
interaction of NSAIDs with hypertension as discussed previously.
Contraindication For One (Or More) Of The Drugs

The majority of respondents cited NSAIDs as a contraindication. This is probably

correct although it may well depend on her prn usage i.e. if used for several days at
a time only, NSAIDs may give some relief when symptoms are severe and may not
adversely effect the reflux oesophagitis. Of the NSAIDs, piroxicam is very long
acting and generally not the best choice in the elderly. A less potent, shorter acting
agent such as ibuprofen may be a better choice for this type of prn use.
Concordance/compliance has been mentioned. Concordance is just another term for
compliance. The essential point I would like to make here is that many pharmacies
now prepare weekly medications for patients at risk of drug misadventure. Lack of
patient compliance is still one of the major reasons for hospitalisation. Improving
compliance can result in substantial saving to the health care system. General
practitioners can discuss with their local pharmacist, the services that they are able to
provide in this area. We often forget that simple issues can make an enormous
difference.
Question 2
What other health professional would you involve in this medication
review?
Obviously I think it is appropriate and particularly encouraging that 79% stated they
would call on the service of a pharmacist for help in this review. Physiotherapy rated
second with 34% and I think that we should always keep in mind nonpharmacological treatments where necessary for symptomatic relief.

Question 3
What reference sources would you use?
It is noted that MIMS and Medical Director were the two major resources used for
information. I find material from the Australian Medicines Handbook 2000
particularly useful independent reference as well as Drug Interaction Facts3 which is
available as hard copy and electronic version. The main features of Drug Interactions
Facts are the listings of drug or drug classes, which may interact, and the significance
of these which include onset, severity and documentation including evaluation based
on supporting biomedical literature.

Question 4
What action would you take?
Paracetamol was the drug of choice for those who wanted to add a medication. I
would agree with this and I think the emphasis needs to be on regular paracetamol
dosing where appropriate and not just when required. I would suggest this as first line
treatment instead of NSAIDs, particularly in patients with hypertension, heart failure
or renal impairment.
Those who wished to cease a medication focused on NSAIDs. Some chose piroxicam
only and an equal number ibuprofen only and a larger number chose to cease both. As
mentioned above, I think the best choice is paracetamol alone initially. For many
patients it can prove an effective treatment. If necessary, then a short acting NSAID
can be introduced for short periods of time when required. If paracetamol is effective
and NSAIDs can be ceased, then an improvement in reflux symptoms may make it
possible to trial a withdrawal of ranitidine.
Over 90% said they would discuss the medication regimen with Mrs March and
include discussion concerning side effects. This is appropriate considering the
availability of NSAIDs over the counter in pharmacies and the frequency of
gastrointestinal side effects.
A range of other actions was mentioned by the respondents. Some highlighted nonpharmacological treatments e.g. physiotherapy, exercise regimens and liniments. It is
important to always consider such support treatments, which can make the patient feel
more comfortable. None of the 100 respondents sampled mentioned the antiinflammatory gels now available. Some patients respond well to them and they may
be particularly useful when the problem is localised to a particular joint or small area
of discomfort. This treatment may suffice and there would be no need for oral
therapy.

References
1. Writing Group. Therapeutic Guidelines: Gastrointestinal 2nd edition. North
Melbourne: Therapeutic Guidelines Limited; 1998.
2. Australian Medicines Handbook 2000. Adelaide: Australian Medicines
Handbook P/L; 2000.
3. Tatro DS, ed. Drug Interaction Facts. St. Louis: Facts and Comparisons;
1999.