Workshop 4.1: Adverse Drug Reactions
Case Scenario 1
Question
What further
background
information do
you need to
clarify the
question and
minimise the
risks when
advising the
caller?
I have just been prescribed Roaccutane and have been told that I shouldn’t
wax my legs. Will this be forever or is it only for the duration of time that I
am on it?
PERSON
MEDICINES
Who is asking?
19 year old female – about herself
Medicines (name,dose,freq)?
Roaccutane 30mg once a day.
Microgynon 30 .
New or worsening symptoms?
No symptoms.
Any allergies/medical conditions?
No allergies. Acne since mid teens.
Why asking about medicines?
Would like further explanation of
what the specialist said.
Gather the further background information BEFORE searching for information.
What information
sources would
you use?
eBNF:
Roaccutane contains isotretinoin.
Counselling Warn patient to avoid wax epilation (risk of epidermal stripping),
dermabrasion, and laser skin treatments (risk of scarring) during treatment
and for at least 6 months after stopping; patient should avoid exposure to
UV light (including sunlight) and use sunscreen and emollient (including lip
balm) preparations from the start of treatment.
Side-effects dryness of skin (with dermatitis, scaling, thinning, erythema,
pruritus), epidermal fragility (trauma may cause blistering), dryness of lips
(sometimes cheilitis), dryness of eyes (with blepharitis and conjunctivitis),
dryness of pharyngeal mucosa (with hoarseness), dryness of nasal mucosa
(with epistaxis)
Cautions exclude pregnancy before starting (perform pregnancy test 2–3
days before expected menstruation, start treatment on day 2 or 3 of
menstrual cycle)—women must practice effective contraception at least 1
month before, during, and for at least 1 month after treatment
eMC – PIL/Roaccutane:
Possible side effects
Roaccutane can have side effects, though not everybody gets them. The
effects often wear off, or stop when treatment is stopped. Your doctor can
help you deal with them.
Skin and hair problems
Very common effects (may affect more than 1 in every 10 people)
Dryness of the skin, especially of the lips and face; inflamed skin, chapped
and inflamed lips, rash, mild itching and slight peeling. Use a moisturising
cream from the start of treatment.
Skin becomes more fragile and redder than usual, especially the face.
Women who could get pregnant are only prescribed Roaccutane under strict
rules, because of the risk of birth defects (damage to the unborn baby).
Role Preparation for Nurse Advisors: Handling Medicines Calls
November 2007 v1.0
These are the rules:
You must only take Roaccutane if you have severe acne that has not got
better after any other anti-acne treatments, including antibiotics and skin
treatments.
Your doctor must have explained the risk of birth defects: you understand
why you must not get pregnant and what you need to do to prevent it.
You must have discussed contraception (birth control) with your doctor.
They will give you information on preventing pregnancy. He or she may refer
you to a specialist for contraceptive advice.
You must agree to use one or preferably two effective methods of
contraception, including condoms or a cap plus spermicide, for a month
before taking Roaccutane, during treatment and for a month afterwards.
Before you start treatment your doctor will ask you to take a pregnancy test,
which must be negative.
You must use contraception even if you do not have periods or are not
currently sexually active (unless your doctor decides this is not necessary).
You must accept the need for monthly follow up visits and more pregnancy
tests as decided by your doctor. You may have a test 5 weeks after stopping
Roaccutane. You must not get pregnant during treatment and for a month
afterwards.
Your doctor may ask you (or a guardian) to sign a form that confirms that
you have been told about the risks, and that you accept the necessary
precautions.
NetDoctor:
You should avoid exposing your skin to intense sunlight or UV light while
taking this medicine. You should use a sunscreen of at least SPF 15 when
necessary.
Isotretinoin is likely to make your skin and lips very dry, so it is
recommended that you use a moisturiser and lip balm from the start of
treatment.
You should avoid waxing any part of your body while taking isotretinoin, and
for at least six months after stopping treatment, as this could cause stripping
of the top layer of skin. Chemical dermabrasion and cutaneous laser
treatment should also be avoided during treatment with isotretinoin and for
five to six months after stopping treatment, as this could cause scarring.
Isotretinoin causes major birth defects (serious malformations of a
developing foetus) if taken during pregnancy. For this reason your doctor will
not prescribe the treatment to women who could get pregnant, unless the
following criteria are met: At least one, but preferably two (for example the
pill and condoms), effective methods of contraception must be used at all
times to prevent pregnancy. Contraception must start at least four weeks
before starting treatment, be used at all times during treatment and for at
least four weeks after stopping treatment, even if you don't have a period.
Your doctor cannot prescribe isotretinoin until you have been using effective
contraception for at least a month and have had a negative pregnancy test.
Role Preparation for Nurse Advisors: Handling Medicines Calls
November 2007 v1.0
Your doctor is only allowed to prescribe 30 days supply of isotretinoin at a
time. You will need to have a follow-up visit every month, at which you will
have to have a negative pregnancy test before a new prescription can be
issued. Five weeks after stopping treatment you should have a final
pregnancy test to make sure you have not fallen pregnant. If you think there
is a chance you could be pregnant, either during treatment, or in the first
month after stopping treatment, you must consult your doctor immediately.
What advice
would you give?
Or would you
refer?
Well-known side effect of Roaccutane related to the high dose of vitamin A.
Avoid waxing any part of the body during therapy with isotretinoin, and for up
to six months after stopping therapy, due to risk of inflammation of the skin
(dermatitis) and scarring.
Further learning points
Isotretinoin, a Vitamin A analogue, is very toxic and may only be prescribed by / under
supervision of a consultant dermatologist. It is teratogenic. Women of childbearing age must be
fully informed and practice effective contraception.
Role Preparation for Nurse Advisors: Handling Medicines Calls
November 2007 v1.0
Workshop 4.1: Adverse Drug Reactions
Case Scenario 2
Question
What further
background
information do
you need to
clarify the
question and
minimise the
risks when
advising the
caller?
My son has a rash all over his body and is feeling unwell. He has recently
started lamotrigine, could this be causing the rash?
PERSON
MEDICINES
Who is asking?
Mother about 8 years old son.
Medicines (name,dose,freq)?
Lamotrigine 5mg each day.
Sodium Valproate 200mg twice a
New or worsening symptoms?
day.
Rash – raised red bumps., not How long been on these, who
bleeding, all over him. Started prescribed them?
yesterday evening. He is hot and Lamotrigine started about 3 weeks
feels unwell.
ago by specialist as sodium valporate
not controlling the fits.
Any allergies/medical conditions?
Epilepsy.
Gather the further background information BEFORE searching for information.
What information
sources would
you use?
eBNF:
Skin reactions Serious skin reactions including Stevens-Johnson syndrome
and toxic epidermal necrolysis (rarely with fatalities) have developed
especially in children; most rashes occur in the first 8 weeks. Rash is
sometimes associated with hypersensitivity syndrome (see Side-effects,
above) and is more common in patients with history of allergy or rash from
other antiepileptic drugs. Consider withdrawal if rash or signs of
hypersensitivity syndrome develop. The CSM has advised that factors
associated with increased risk of serious skin reactions include concomitant
use of valproate, initial lamotrigine dosing higher than recommended and
more rapid dose escalation than recommended.
Counselling Warn patients to see their doctor immediately if rash or signs or
symptoms of hypersensitivity syndrome develop
eMC SPC/ Lamictal:
Undesirable effects
In double-blind, add-on clinical trials, skin rashes occurred in up to 10% of
patients taking lamotrigine and in 5% of patients taking placebo. The skin
rashes led to the withdrawal of lamotrigine treatment in 2% of patients. The
rash, usually maculopapular in appearance, generally appears within eight
weeks of starting treatment and resolves on withdrawal of lamotrigine (see
Special Warnings and Special Precautions for Use).
Rarely, serious potentially life threatening skin rashes, including Stevens
Johnson syndrome and toxic epidermal necrolysis (Lyell Syndrome) have
been reported. Although the majority recover on drug withdrawal, some
patients experience irreversible scarring and there have been rare cases of
associated death. (See Special Warnings and Special Precautions for Use)
Role Preparation for Nurse Advisors: Handling Medicines Calls
November 2007 v1.0
The approximate incidence of serious skin rashes reported as SJS in adults
and children over the age of 12 is 1 in 1000. The risk in children under the
age of 12 is higher than in adults. Available data from a number of studies
suggest that the incidence in children under the age of 12 requiring
hospitalisation due to rash ranges from 1 in 300 to 1 in 100 (see Special
Warnings and Special Precautions for Use).
In children, the initial presentation of a rash can be mistaken for an infection;
physicians should consider the possibility of a drug reaction in children that
develop symptoms of rash and fever during the first eight weeks of therapy.
Additionally the overall risk of rash appears to be strongly associated with:
High initial doses of lamotrigine and exceeding the recommended
dose escalation of lamotrigine therapy (see Posology and Method of
Administration).

Concomitant use of valproate
NetDoctor:
Adverse skin reactions have been reported with lamotrigine. These reactions
are usually mild and get better on their own, but can on rare occasions be
more serious and potentially life-threatening. The risk is higher in children
under 12 years of age and in people who are also taking the medicine
valproate. When starting treatment with lamotrigine the dose is increased
gradually to minimise the risk of developing a skin rash. For this reason it is
very important to follow the instructions you are given with this medicine,
and not to exceed the prescribed dose. If you or your child develop a rash,
fever, facial swelling or swollen glands while taking this medicine you should
consult your doctor immediately. If the doctor decides the reaction is related
to this medicine you will need to stop taking it.
What advice
would you give?
Or would you
refer?
Rash is a common side effect of lamotrigine. It is usually red and raised and
often begins within the first 8 weeks of treatment. However, it can be a more
serious side effect especially if there is also fever.
Advise that the son sees the GP immediately or is taken to A&E. Please
explain that you have phoned NHS Direct and this is what was advised. It is
important that the rash be seen by a doctor and if due to lamotrigine then
treated quickly.
Role Preparation for Nurse Advisors: Handling Medicines Calls
November 2007 v1.0
Workshop 4.1: Adverse Drug Reactions
Case Scenario 3
Question
What further
background
information do
you need to
clarify the
question and
minimise the
risks when
advising the
caller?
My husband has recently started simvastatin and has developed muscle
pain in his leg. Could it be due to this new drug?
PERSON
MEDICINES
Who is asking?
Wife about 62yr old husband.
Medicines (name, dose, freq)?
Simvastatin 10mg once daily
Aspirin 75mg once daily
New or worsening symptoms?
Muscle pain developed over last 24 How long has the patient been on
hours in lower legs and generally these prescribed medications?
feels unwell.
GP started simvastatin last week
because cholesterol level 5.7
Any allergies/medical conditions? Aspirin taken for several years.
High cholesterol
Gather the further background information BEFORE searching for information.
What information
sources would
you use?
eBNF:
Side-effects
Reversible myositis is a rare but significant side-effect of the statins (see
also CSM advice (Muscle Effects), section 2.12 and below). The statins also
cause headache, altered liver-function tests (rarely, hepatitis), paraesthesia,
and gastro-intestinal effects including abdominal pain, flatulence,
constipation, diarrhoea, nausea and vomiting. Rash and hypersensitivity
reactions (including angioedema and anaphylaxis) have been reported
rarely.
Muscle effects Myalgia, myositis, and myopathy have been reported with
the statins; if myopathy is suspected and creatine kinase is markedly
elevated (more than 5 times upper limit of normal), or muscular symptoms
are severe, treatment should be discontinued; in patients at high risk of
muscle effects, a statin should not be started if creatine kinase is elevated.
There is an increased incidence of myopathy if the statins are given at high
doses or given with a fibrate (see also CSM advice), with lipid-lowering
doses of nicotinic acid, or with immunosuppressants such as ciclosporin;
close monitoring of liver function and, if symptomatic, of creatine kinase is
required in patients receiving these drugs. Rhabdomyolysis with acute renal
impairment secondary to myoglobinuria has also been reported.
Counselling
Advise patient to report promptly unexplained muscle pain, tenderness, or
weakness.
CSM advice (muscle effects)
The CSM has advised that rhabdomyolysis associated with lipid-regulating
drugs such as the fibrates and statins appears to be rare (approx. 1 case in
every 100 000 treatment years) but may be increased in those with renal
impairment and possibly in those with hypothyroidism (see also notes
above). Concomitant treatment with drugs that increase plasma-statin
concentration increase the risk of muscle toxicity; concomitant treatment with
a fibrate and a statin may also be associated with an increased risk of
serious muscle toxicity.
Role Preparation for Nurse Advisors: Handling Medicines Calls
November 2007 v1.0
eMC SPC- Zocor:
Before the treatment All patients starting therapy with simvastatin, or whose
dose of simvastatin is being increased, should be advised of the risk of
myopathy and told to report promptly any unexplained muscle pain,
tenderness or weakness.
Whilst on treatment If muscle pain, weakness or cramps occur whilst a
patient is receiving treatment with a statin, their CK levels should be
measured. If these levels are found, in the absence of strenuous exercise, to
be significantly elevated (> 5 x ULN), treatment should be stopped. If
muscular symptoms are severe and cause daily discomfort, even if CK
levels are < 5 x ULN, treatment discontinuation may be considered. If
myopathy is suspected for any other reason, treatment should be
discontinued.
eMC PIL - Zocor
Tell your doctor quickly if you experience unexplained muscle pain,
tenderness or weakness. This is because on rare occasions, there is a risk
of muscle problems which may be serious, including muscle breakdown
which can result in kidney damage. The doctor may perform a blood test to
check the condition of your muscles before and after starting treatment.
Things to note regarding muscle effects
The risk of muscle breakdown is greater at higher doses of ‘Zocor’.
The risk of muscle breakdown is greater in certain patients. Tell your doctor
if any of the following applies to you:
kidney problems
thyroid problems
you are more than 70 years old
you have ever had muscle problems during treatment with cholesterol
lowering medicines called "statins" (such as simvastatin, atorvastatin,
pravastatin) or fibrates (such as gemfibrozil, bezafibrate).
you or close family members have a hereditary muscle disorder.
The risk of muscle problems can be greater if ‘Zocor’ is taken with certain
medicines
NetDoctor:
This medicine may occasionally have side effects on the muscles. For this
reason you should inform your doctor immediately if you experience any
unexplained muscular symptoms such as pain, tenderness, cramps or
weakness while taking this medicine. Your doctor may need to check for
side effects on the muscles by taking a blood test to measure the level of a
compound called creatine kinase (CK) in your blood. If this is the case, the
test should not be done following strenuous exercise.
What advice
would you give?
Or would you
refer?
Statins may have very rare side effects on muscles.
Advise that the husband see the GP immediately. The GP may advise that
you stop this medication and may wish to do some blood test.
Role Preparation for Nurse Advisors: Handling Medicines Calls
November 2007 v1.0