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ABACAVIR/LAMIVUDINE 600MG/300MG FILM-COATED TABLETS

Active substance(s): ABACAVIR HYDROCHLORIDE / LAMIVUDINE

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Abacavir/Lamivudine Tablets - UK - PIL

Tell your doctor if you are taking methadone.
• ribavirin, for treating hepatitis C. Abacavir may make the
combination of ribavirin and pegylated interferon less
effective at reducing levels of hepatitis C virus in the body.
Tell your doctor if you are taking ribavirin.

Package leaflet: Information for the user

Abacavir/Lamivudine 600 mg/300 mg
film-coated tablets
abacavir/lamivudine

Read all of this leaflet carefully before you start taking this
medicine because it contains important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or
pharmacist.
- This medicine has been prescribed for you only. Do not pass
it on to others. It may harm them, even if their signs of
illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist.
This includes any possible side effects not listed in this
leaflet. See section 4.
IMPORTANT — Hypersensitivity reactions
Abacavir/Lamivudine contains abacavir (which is also an
active substance in medicines such as Trizivir, Triumeq and
Ziagen). Some people who take abacavir may develop a
hypersensitivity reaction (a serious allergic reaction), which can
be life-threatening if they continue to take abacavir containing
products.
You must carefully read all the information under
‘Hypersensitivity reactions’ in the panel in
Section 4.
The Abacavir/Lamivudine pack includes an Alert Card, to remind
you and medical staff about abacavir hypersensitivity. Keep this
card with you at all times.
What is in this leaflet
1. What Abacavir/Lamivudine is and what it is used for
2. What you need to know before you take Abacavir/Lamivudine
3. How to take Abacavir/Lamivudine
4. Possible side effects
5. How to store Abacavir/Lamivudine
6. Contents of the pack and other information

1. What Abacavir/Lamivudineis and what it is used for
Abacavir/Lamivudine is used to treat HIV (human
immunodeficiency virus) infection in adults, adolescents and
in children weighing at least 25 kg.
Abacavir/Lamivudine contains two active ingredients that are
used to treat HIV infection: abacavir and lamivudine. These belong
to a group of anti-retroviral medicines called nucleoside analogue
reverse transcriptase inhibitors (NRTIs).
Abacavir/Lamivudine does not completely cure HIV infection; it
reduces the amount of virus in your body, and keeps it at a low
level. It also increases the CD4 cell count in your blood. CD4 cells
are a type of white blood cells that are important in helping your
body to fight infection.
Not everyone responds to treatment with Abacavir/Lamivudine in
the same way. Your doctor will monitor the effectiveness of your
treatment.

2. What you need to know before you take
Abacavir/Lamivudine
Do not take Abacavir/Lamivudine:
• if you are allergic (hypersensitive) to abacavir (or any other
medicine containing abacavir - (e.g. Trizivir, Triumeq or
Ziagen), lamivudine or any of the other ingredients of this
medicine (listed in Section 6)
Carefully read all the information about hypersensitivity
reactions in Section 4.
• if you have severe liver disease
Check with your doctor if you think any of these apply to
you. Do not take Abacavir/Lamivudine.
Take special care with Abacavir/Lamivudine
Some people taking abacavir/lamivudine or other combination
treatments for HIV are more at risk of serious side effects. You
need to be aware of the extra risks:
• if you have ever had liver disease, including hepatitis B or C
(if you have hepatitis B infection, do not stop
Abacavir/Lamivudine without your doctor’s advice, as your
hepatitis may come back)
• if you are seriously overweight (especially if you are a woman)
• if you are diabetic and using insulin
• if you have a kidney problem
Talk to your doctor if any of these apply to you before using
Abacavir/Lamivudine. You may need extra check-ups, including
blood tests, while you are taking your medicine. See Section 4
for more information.
Abacavir hypersensitivity reactions
Even patients who do not have the HLA-B*5701 gene may still
develop a hypersensitivity reaction (a serious allergic reaction).
Carefully read all the information about hypersensitivity
reactions in Section 4 of this leaflet.
Risk of heart attack
It cannot be excluded that abacavir may increase the risk of
having a heart attack.
Tell your doctor if you have heart problems, if you smoke, or
have other illnesses that may increase your risk of heart disease
such as high blood pressure, or diabetes. Do not stop taking
Abacavir/Lamivudine unless your doctor advises you to do so.
Look out for important symptoms
Some people taking medicines for HIV infection develop other
conditions, which can be serious. You need to know about
important signs and symptoms to look out for while you are
taking Abacavir/Lamivudine.
Read the information ‘Other possible side effects of
combination therapy for HIV’ in Section 4 of this leaflet.
Protect other people
HIV infection is spread by sexual contact with someone who has
the infection, or by transfer of infected blood (for example, by
sharing injection needles). You can still pass on HIV when taking
this medicine, although the risk is lowered by effective
antiretroviral therapy. Discuss with your doctor the precautions
needed to avoid infecting other people.
Other medicines and Abacavir/Lamivudine
Tell your doctor or pharmacist if you are taking any other
medicines, or if you have taken any recently, including herbal
medicines or other medicines you bought without a prescription.
Remember to tell your doctor or pharmacist if you begin taking a
new medicine while you are taking Abacavir/Lamivudine.
These medicines should not be used with
Abacavir/Lamivudine:
• Emtricitabine, to treat HIV infection
• other medicinal products containing lamivudine, used to
treat HIV infection or hepatitis B infection
• high doses of trimethoprim/sulfamethoxazole, an antibiotic
• cladribine, used to treat hairy cell leukaemia
Tell your doctor if you are being treated with any of these.
Some medicines interact with Abacavir/Lamivudine
These include:
• phenytoin, for treating epilepsy.
Tell your doctor if you are taking phenytoin. Your doctor may
need to monitor you while you are taking Abacavir/Lamivudine.
• methadone, used as a heroin substitute. Abacavir
increases the rate at which methadone is removed from the
body. If you are taking methadone, you will be checked for
any withdrawal symptoms. Your methadone dose may need
to be changed.

Size : 170 x 600 mm, Colour:
Minimum Font Size 9 pt
Date: 01/06/17

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Review - 5

Pregnancy
Abacavir/Lamivudine is not recommended for use during
pregnancy. Abacavir/lamivudine and similar medicines may
cause side effects in unborn babies. If you become pregnant while
you are taking Abacavir/Lamivudine, your baby may be given
extra check-ups (including blood tests) to make sure it is
developing normally.
If you are pregnant, if you become pregnant, or if you are planning
to become pregnant:
Talk to your doctor immediately about the risks and benefits of
taking Abacavir/Lamivudine, or other medicines for treating HIV
infection, during your pregnancy.
Breast-feeding
Women who are HIV-positive must not breast-feed, because
HIV infection can be passed on to the baby in breast milk. A small
amount of the ingredients in Abacavir/Lamivudine can also pass
into your breast milk.
If you are breast-feeding, or thinking about breast-feeding:
Talk to your doctor immediately.
Driving and using machines
Abacavir/Lamivudine may cause side effects which could affect
your ability to drive or use machines.
Talk to your doctor about your ability to drive or operate
machines while taking Abacavir/Lamivudine.
Important information about some of the other ingredients of
Abacavir/Lamivudine
Abacavir/Lamivudine contains a colouring called sunset yellow
(E110), this may cause allergic reactions in some people.

3. How to take Abacavir/Lamivudine
Always take this medicine exactly as your doctor has told
you. Check with your doctor or pharmacist if you are not sure.
The recommended dose of Abacavir/Lamivudine for adults,
adolescents and children weighing 25 kg or more is one
tablet once a day.
Swallow the tablets whole, with some water. Abacavir/Lamivudine
can be taken with or without food.
Stay in regular contact with your doctor
Abacavir/Lamivudine helps to control your condition. You need to
keep taking it every day to stop your illness getting worse. You
may still develop other infections and illnesses linked to HIV
infection.
Keep in touch with your doctor, and do not stop taking
Abacavir/Lamivudine without your doctor’s advice.
If you take more Abacavir/Lamivudine than you should
If you accidentally take too much Abacavir/Lamivudine, tell your
doctor or your pharmacist, or contact your nearest hospital
emergency department for further advice.
If you forget to take Abacavir/Lamivudine
If you forget to take a dose, take it as soon as you remember.
Then continue your treatment as before. Do not take a double
dose to make up for a forgotten dose.
It is important to take Abacavir/Lamivudine regularly, because if
you take it at irregular intervals, you may be more likely to have a
hypersensitivity reaction.
If you have stopped taking Abacavir/Lamivudine
If you have stopped taking Abacavir/Lamivudine for any reason especially because you think you are having side effects, or
because you have other illness:
Talk to your doctor before you start taking it again. Your
doctor will check whether your symptoms were related to a
hypersensitivity reaction. If the doctor thinks they may have been
related, you will be told never again to take
Abacavir/Lamivudine, or any other medicine containing
abacavir (e.g. Trizivir or Ziagen). It is important that you follow
this advice.
If your doctor advises that you can start taking
Abacavir/Lamivudine again, you may be asked to take your first
doses in a place where you will have ready access to medical
care if you need it.

4. Possible side effects
Like all medicines, this medicine can cause side effects, although
not everyone gets them.
When you are being treated for HIV, it can be hard to tell whether
a symptom is a side effect of Abacavir/Lamivudine or other
medicines you are taking, or an effect of the HIV disease itself. So
it is very important to talk to your doctor about any changes
in your health.
Even patients who do not have the HLA-B*5701 gene may still
develop a hypersensitivity reaction (a serious allergic reaction),
described in this leaflet in the panel headed ‘Hypersensitivity
reactions’.
It is very important that you read and understand the
information about this serious reaction.
As well as the side effects listed below for
Abacavir/Lamivudine, other conditions can develop during
combination therapy for HIV.
It is important to read the information later in this section under
‘Other possible side effects of combination therapy for HIV’.
Hypersensitivity reactions
Abacavir/Lamivudine contains abacavir (which is also an active
substance in medicines such as Trizivir, Triumeq and Ziagen).
Abacavir can cause a serious allergic reaction known as a
hypersensitivity reaction. These hypersensitivity reactions have
been seen more frequently in people taking medicines that
contain abacavir.
Who gets these reactions?
Anyone taking Abacavir/Lamivudine could develop a hypersensitivity reaction to abacavir, which could be life threatening if they
continue to take Abacavir/Lamivudine.
You are more likely to develop this reaction if you have a gene
called HLA-B*5701 (but you can get a reaction even if you do not
have this gene). You should have been tested for this gene before
Abacavir/Lamivudine was prescribed for you. If you know you
have this gene, tell your doctor before you take Abacavir/Lamivudine.
About 3 to 4 in every 100 patients treated with abacavir in a
clinical trial who did not have the HLA-B*5701 gene developed a
hypersensitivity reaction.
What are the symptoms?
The most common symptoms are:
• fever (high temperature) and skin rash.
Other common symptoms are:
• nausea (feeling sick), vomiting (being sick), diarrhoea,
abdominal (stomach) pain, severe tiredness.
Other symptoms include:
Pains in the joints or muscles, swelling of the neck, shortness of
breath, sore throat, cough, occasional headaches, inflammation of
the eye (conjunctivitis), mouth ulcers, low blood pressure, tingling
or numbness of the hands or feet.
If you continue to take Abacavir/Lamivudine, the symptoms
will get worse, and may be life-threatening.

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Abacavir/Lamivudine Tablets - UK - PIL

When do these reactions happen?
Hypersensitivity reactions can start at any time during treatment
with Abacavir/Lamivudine, but are more likely during the first 6
weeks of treatment.
Contact your doctor immediately:
1. if you get a skin rash, OR
2. if you get symptoms from at least 2 of the following
groups:
- fever
- shortness of breath, sore throat or cough
- nausea or vomiting, diarrhoea or abdominal pain
- severe tiredness or achiness, or generally feeling ill.

Review - 5

Your body shape may change
People taking combination therapy for HIV may find that their
body shape changes, because of changes in fat distribution:
• Fat may be lost from the legs, arms or face.
• Extra fat may build up around the tummy (abdomen), or on
the breasts or internal organs.
• Fatty lumps (sometimes called buffalo hump) may appear on
the back of the neck.
It is not yet known what causes these changes, or whether they
have any long-term effects on your health. If you notice changes
in your body shape:
Tell your doctor.

Your doctor may advise you to stop taking
Abacavir/Lamivudine.

Lactic acidosis is a rare but serious side effect

If you have stopped taking Abacavir/Lamivudine.
If you have stopped taking Abacavir/Lamivudine because of a
hypersensitivity reaction, you must NEVER AGAIN take
Abacavir/Lamivudine, or any other medicine containing
abacavir (e.g. Trizivir, Triumeq or Ziagen). If you do, within
hours, your blood pressure could fall dangerously low, which
could result in death.
If you have stopped taking Abacavir/Lamivudine for any reason especially because you think you are having side effects, or
because you have other illness:
Talk to your doctor before you start again. Your doctor will
check whether your symptoms were related to a hypersensitivity
reaction. If the doctor thinks they may have been, you will then
be told never again to take Abacavir/Lamivudine, or any
other medicine containing abacavir (e.g. Trizivir, Triumeq or
Ziagen). It is important that you follow this advice.
Occasionally hypersensitivity reactions have developed in people
who start taking abacavir containing products again, but who had
only one symptom on the Alert Card before they stopped taking it.
Very rarely patients who have taken medicines containing
abacavir in the past without any symptoms of hypersensitivity
have developed a hypersensitivity reaction when they start taking
these medicines again.
If your doctor advises that you can start taking Abacavir/Lamivudine again, you may be asked to take your first doses in a place
where you will have ready access to medical care if you need it.
If you are hypersensitive to abacavir/lamivudine, return all
your unused Abacavir/Lamivudine tablets for safe disposal.
Ask your doctor or pharmacist for advice.
The Abacavir/Lamivudine pack includes an Alert Card, to remind
you and medical staff about hypersensitivity reactions. This card
contains important safety information, keep it with you at all
times.
Common side effects
These may affect up to 1 in 10 people:
• hypersensitivity reaction
• headache
• being sick (vomiting)
• feeling sick (nausea)
• diarrhoea
• stomach pains
• loss of appetite
• tiredness, lack of energy
• fever (high temperature)
• general feeling of being unwell
• difficulty in sleeping (insomnia)
• muscle pain and discomfort
• joint pain
• cough
• irritated or runny nose
• skin rash
• hair loss.

Some people taking abacavir/lamivudine, or other medicines like
it (NRTIs), develop a condition called lactic acidosis, together with
an enlarged liver.
Lactic acidosis is caused by a build-up of lactic acid in the body. It
is rare; if it happens, it usually develops after a few months of
treatment. It can be life-threatening, causing failure of internal
organs.
Lactic acidosis is more likely to develop in people who have liver
disease, or in obese (very overweight) people, especially women.
Signs of lactic acidosis include:
• feeling sick (nausea), being sick (vomiting)
• stomach pain
• generally feeling unwell
• loss of appetite, weight loss
• deep, rapid, difficult breathing
• numbness or weakness in the limbs
During your treatment, your doctor will monitor you for signs of
lactic acidosis. If you have any of the symptoms listed above or
any other symptoms that worry you:
See your doctor as soon as possible.
You may have problems with your bones
Some people taking combination therapy for HIV develop a
condition called osteonecrosis. With this condition, parts of the
bone tissue die because of reduced blood supply to the bone.
People may be more likely to get this condition:
• if they have been taking combination therapy for a long time
• if they are also taking anti-inflammatory medicines called
corticosteroids
• if they drink alcohol
• if their immune systems are very weak
• if they are overweight.
Signs of osteonecrosis include:
• stiffness in the joints
• aches and pains (especially in the hip, knee or shoulder)
• difficulty moving.
If you notice any of these symptoms:
Tell your doctor.
Other effects may show up in blood tests
Combination therapy for HIV can also cause:
• increased levels of lactic acid in the blood, which on rare
occasions can lead to lactic acidosis
• increased levels of sugar and fats (triglycerides and
cholesterol) in the blood
• resistance to insulin (so if you are diabetic, you may have to
change your insulin dose to control your blood sugar).

Uncommon side effects
These may affect up to 1 in 100 people and may show up in
blood tests:
• a low red blood cell count (anaemia) or low white blood cell
count (neutropenia)
• an increase in the level of liver enzymes
• a decrease in the number of cells involved in blood clotting
(thrombocytopenia).
Rare side effects
These may affect up to 1 in 1000 people:
• liver disorders, such as jaundice, enlarged liver or fatty liver,
inflammation (hepatitis)
• lactic acidosis (see the next section, ‘Other possible side
effects of combination therapy for HIV’)
• inflammation of the pancreas (pancreatitis)
• breakdown of muscle tissue.
Rare side effects that may show up in blood tests are:
• increase in an enzyme called amylase.
Very rare side effects
These may affect up to 1 in 10,000 people:
• numbness, tingly feelings in the skin (pins and needles)
• sensation of weakness in the limbs
• skin rash, which may form blisters and looks like small
targets (central dark spots surrounded by a paler area, with
a dark ring around the edge) (erythema multiforme)
• a widespread rash with blisters and peeling skin, particularly
around the mouth, nose, eyes and genitals
(Stevens–Johnson syndrome), and a more severe form
causing skin peeling in more than 30% of the body surface
(toxic epidermal necrolysis).
If you notice any of these symptoms contact a doctor
urgently.
Very rare side effects that may show up in blood tests are:
• a failure of the bone marrow to produce new red blood cells
(pure red cell aplasia).
If you get side effects
Tell your doctor or pharmacist if any of the side effects gets
severe or troublesome, or if you notice any side effects not listed
in this leaflet.
Other possible side effects of combination therapy for HIV
Combination therapy such as abacavir/lamivudine may cause
other conditions to develop during HIV treatment.
Symptoms of infection and inflammation
Old infections may flare up
People with advanced HIV infection (AIDS) have weak immune
systems, and are more likely to develop serious infections
(opportunistic infections). Such infections may have been “silent”
and not detected by the weak immune system before treatment
was started. After starting treatment, the immune system
becomes stronger, and may attack the infections, which can
cause symptoms of infection or inflammation. Symptoms usually
include fever, plus some of the following:
• headache
• stomach ache
• difficulty breathing
In rare cases, as the immune system becomes stronger, it
can also attack healthy body tissue (autoimmune disorders).
The symptoms of autoimmune disorders may develop many
months after you start taking medicine to treat your HIV
infection. Symptoms may include:
• palpitations (rapid or irregular heartbeat) or tremor
• hyperactivity (excessive restlessness and movement)
• weakness beginning in the hands and feet and moving
up towards the trunk of the body.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This
includes any possible side effects not listed in this leaflet. You can
also report side effects directly via the MHRA Yellow Card
Scheme, Website – www.mhra.gov.uk/yellowcard. By reporting
side effects you can help provide more information on the safety
of this medicine.

5. How to store Abacavir/Lamivudine
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on
the carton after EXP. The expiry date refers to the last day of that
month.
Store below 25°C.
Do not throw away any medicines via wastewater or household
waste. Ask your pharmacist how to throw away medicines you no
longer use. These measures will help protect the environment.

6. Contents of the pack and other information
What Abacavir/Lamivudine contains
The active substances in each Abacavir/Lamivudine film-coated
tablet are abacavir hydrochloride equivalent to 600 mg abacavir
and 300 mg of lamivudine.
The other ingredients are microcrystalline cellulose, crospovidone
(Type A), povidone (K-30), iron oxide yellow (E172) and
magnesium stearate in the core of the tablet. The tablet coating
contains hypromellose HPMC 2910 -3mPas, hypromellose HPMC
2910 -6mPas, titanium dioxide (E171), macrogol 400, polysorbate
80 and sunset yellow aluminium lake (E110).
What Abacavir/Lamivudine looks like and contents of the
pack
Abacavir/Lamivudine are orange coloured, capsule shaped,
biconvex, 20.6 mm x 9.1 film-coated tablets, engraved with“300”
on one side and “600” on other side.
Abacavir/Lamivudine are supplied in blister packs containing 30,
60 or 90 film-coated tablets, or multi blister packs containing 60
or 90 film-coated tablets.
30 film-coated tablets in bottles containing an activated carbon
sachet or an activated carbon sachet and oxygen absorber to
control the moisture in the bottle.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Amneal Pharma Europe Limited
70 Sir John Rogerson’s Quay
Dublin 2
Ireland
Manufacturer:
Lupin (Europe) Limited
Victoria Court, Bexton Road, Knutsford, Cheshire
WA16 0PF, United Kingdom
This leaflet was last revised in January 2017.

If you get any symptoms of infection and inflammation or if you
notice any of the symptoms above:
Tell your doctor immediately. Do not take other medicines for
the infection without your doctor’s advice.

Size : 170 x 600 mm, Colour:
Minimum Font Size 9 pt
Date: 01/06/17

Black,

To request a copy of this leaflet in Braille,
large print or audio format,
please call: 01371 823933

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IMPORTANT - ALERT CARD
Medicines containing Abacavir
Carry this card with you at all times
Since your medicine contains Abacavir some patients
taking it may develop a hypersensitivity reaction (serious
allergic reaction) which can be life-threatening if treatment
is continued.
CONTACT YOUR DOCTOR IMMEDIATELY
for advice on whether you should stop taking Abacavir if:
1

you get a skin rash OR

2

you get one or more symptoms from at least TWO
of the following groups:

- fever
- shortness of breath, sore throat or cough
- nausea or vomiting or diarrhoea or abdominal pain
- severe tiredness or achiness or generally feeling ill
If you have stopped taking Abacavir because of this
reaction, YOU MUST NEVER TAKE any Abacavir
containing medicine again, as within hours you may
experience a life-threatening lowering of your blood
pressure or death.
(see reverse of card)

You should immediately contact your doctor
if you think you are having a hypersensitivity
reaction to Abacavir.
Write your doctor’s details below:

Doctor: .....................................................
Tel: ............................................................
If your doctor is not available, you must
urgently seek alternative medical advice
(e.g. the emergency unit of the
nearest hospital).

ABACAVIR HYPERSENSITIVITY REACTION
Key Risk Minimisation Points:
Abacavir Hypersensitivity Reaction (HSR)
• Abacavir is associated with a risk for hypersensitivity reactions
(HSR) characterised by fever and/or rash with other symptoms
indicating multiorgan involvement.
• Symptoms usually appear within the first 6 weeks although the
reaction may occur at any time during therapy.
• Risk of abacavir HSR is higher for patients who test positive for the
HLAB* 5701 allele. However, abacavir HSRs have been reported at
a lower frequency in patients who do not carry this allele.
• Abacavir should never be initiated in patients with a positive
HLA-B*5701 status, nor in patients with a negative HLA-B*5701
status who had a suspected abacavir HSR on a previous abacavircontaining regimen.
• Abacavir must be stopped without delay, even in the absence of
the HLAB*5701 allele, if an HSR is suspected. Delay in stopping
treatment with abacavir after the onset of hypersensitivity may
result in an immediate and life-threatening reaction.
• After stopping abacavir for a suspected HSR, any product
containing abacavir must never be re-initiated.
• Restarting abacavir following a suspected HSR can result in a
return of symptoms within hours which is more severe than on
initial presentation and may include life-threatening hypotension
and death.
Abacavir rechallenge can result in a more rapid and severe
reaction, which can be fatal. Rechallenge is contraindicated

Diagnosis of Abacavir Hypersensitivity
• Symptoms usually appear within the first 6 weeks of starting
abacavir
– Median time to onset of 11 days
– However, reactions can occur at any time during therapy
• Diagnosis is complicated by
– Variable presentation with nonspecific symptoms
– Concomitant use of other antiretroviral medications
with overlapping adverse event profiles
• Symptoms improve on cessation of abacavir
Hypersenstivity Symptoms Reported with a Frequency ≥10

Fever

Rash

Nausea/
Vomiting

Malaise/
fatigue

Myalgia/
arthralgia

Headache

Diarrhoea

Pruritus

Abdominal
pain

Dyspnoea

Cough

Hetherington et al. Clin Ther. 2001;23:1603-1614.
Note: Symptomatology was evaluated from clinical trials where HLA B*5701 screening was not performed

Additional Physical and Laboratory Findings
Physical findings

Possible laboratory abnormalities

Lymphadenopathy

Haematological: lymphopaenia
and thrombocytopaenia

Mucous membrane lesions
(pharyngitis, conjunctivitis)

Chest x-ray normal or diffuse bilateral or
lobular infiltrates
Elevated liver enzymes (AST/ALT)
Increased serum creatinine and
creatinine phosphokinase

Pharmacogenetic Testing
• HLA-B*5701 allele is more common among patients who have a suspected HSR to
abacavir compared with those who do not.
• No other pharmacogenetic markers have been found that identify patients at risk of
abacavir HSR.
• Prospective pharmacogenetic screening for HLA-B*5701 can be used to identify
patients at high risk for abacavir HSR.
• HLA-B*5701 is not always present in people who have a suspected abacavir HSR
– Therefore, clinical diagnosis of suspected HSR to abacavir remains the basis for
clinical decision making
– HLA-B*5701 screening for risk of abacavir HSR should never be substituted for
appropriate clinical vigilance and patient management in individuals receiving
abacavir

Recommendations for HLA-B*5701 Screening
• Before initiating treatment with abacavir, screening for HLA-B*5701 should be
performed.
• Screening is also recommended prior to re-initiation of abacavir in patients of unknown
HLA-B*5701 status who have previously tolerated abacavir.
• HLA-B*5701 status must always be documented and explained to the patient prior to
initiating therapy.
• Results of pharmacogenetic tests for risk of abacavir HSR should never be used to
support a drug rechallenge decision after a suspected HSR
• HLA-B*5701 testing must not be used as a diagnostic test after a patient has started
treatment with abacavir

Management Of Abacavir Hypersensitivity Reaction
Counseling the Patient
• Patients must be made aware of the possibility of a hypersensitivity
reaction to Abacavir that may result in a life-threatening reaction or
death, and that the risk of a hypersensitivity reaction is increased if
they are HLA-B*5701 positive.
• Each patient should be reminded to read the Package Leaflet
included in the abacavir pack. They should be reminded of the
importance of removing the Alert Card included in the pack, and
keeping it with them at all times.
• In order to avoid restarting Abacavir, patients who have experienced
a hypersensitivity reaction should be asked to return the remaining
Abacavir product to the pharmacy
Clinical Management of Abacavir Hypersensitivity
• Regardless of HLA-B*5701 status, patients who are diagnosed with a
hypersensitivity reaction MUST discontinue Abacavir immediately.
– Abacavir must be permanently discontinued if hypersensitivity
cannot be ruled out.
• Delay in stopping treatment with abacavir after the onset of
hypersensitivity may result in an immediate and life-threatening
reaction.
• Regardless of HLA-B*5701 status, Abacavir or any medicinal product
containing abacavir, MUST NEVER be restarted in patients who have
stopped therapy due to a hypersensitivity reaction.
• Following discontinuation of abacavir, the symptoms of the reaction
should be treated according to local standard of care.

Restarting Abacavir
• Abacavir or any medicinal product containing Abacavir, MUST
NEVER be restarted in patients who have stopped therapy due
to HSR.
– Restarting Abacavir following HSR results in a prompt return of
symptoms within hours and which is usually more severe than
on initial presentation, and may include life-threatening
hypotension and death.
• If Abacavir therapy is stopped for reasons other than suspected HSR
– Screening for carriage of the HLA B*5701 allele is recommended
prior to re-initiation of Abacavir in patients of unknown
HLA-B*5701 status who have previously tolerated Abacavir.
Re-initiation of Abacavir in such patients who test positive for
the HLA-B*5701 allele is contraindicated.
– Rarely, patients who have stopped Abacavir for reasons
other than symptoms of HSR have also experienced lifethreatening reactions within hours of re- initiating Abacavir
therapy. Restarting Abacavir in such patients must be done in a
setting where medical assistance is readily available.

Further resources
• Before prescribing abacavir-containing medicines, please refer to
the respective Summary of Product Characteristics.
• Healthcare providers are asked to report any suspected adverse
reactions. Reporting forms and information can be found at
www.mhra.gov.uk/yellowcard.

Case Studies On Hypersensitivity
Case Presentation #1
A 46-year-old woman, newly diagnosed with HIV infection, initiated
therapy with abacavir, lamivudine, and efavirenz
• HLA-B*5701 status unknown
On day 8 of therapy, her physician noted a mild pruritic rash on her neck
and trunk
• The patient was afebrile, had no gastrointestinal symptoms, and felt well
• She did not have any muscle or joint aches, respiratory symptoms,
or tenderness or swelling of the lymph nodes
• She had not taken any other medications
Differential diagnoses include
• A reaction to efavirenz
• Abacavir hypersensitivity
• Immune reconstitution syndrome
Course of action
• Patient has a single mild symptom, so closely monitor for resolution or
progression before making a decision
• Review symptoms of hypersensitivity
• Instruct patient to continue all medications and immediately contact
physician if other symptoms develop
• Re-evaluate patient after 24 hours
Follow-up
• Patient continued all medications
• Rash improved over the next 4 days with no further symptoms
Conclusion
• Patient had a transient efavirenz-related rash (i.e. not a hypersensitivity
reaction)

Case Studies On Hypersensitivity
Case Presentation #1: Alternative Scenario
After noticing the rash 3 days before, the patient discontinued all
medications; the rash has since resolved
Course of action
• Permanently discontinue abacavir: Although the reaction may have
been an efavirenz rash, by stopping all drugs it is no longer possible to
differentially diagnose an abacavir hypersensitivity reaction without
exposing the patient to the risk of rechallenge
Summary
• A single symptom is not sufficient for a diagnosis of hypersensitivity
– Drug interruption after a single symptom should be avoided
- Resolution of symptom off-drug makes a differential diagnosis
impossible
– However, if abacavir is interrupted, it should not be restarted
- Resolution of symptom may represent aborted evolution of a
multisymptom hypersensitivity reaction
- Reinitiation puts the patient at risk for a rechallenge reaction
- Abacavir should be retrieved from patient to avoid the risk of
rechallenge
• Take a careful history, and review for other symptoms
• Continue to monitor the patient
• Avoid corticosteroids in case they mask the development of
additional symptoms
• Use antihistamines necessary for the patient’s comfort

Case Studies On Hypersensitivity
Case Presentation #2
29-year-old male with a history of HSV and syphilis
Newly diagnosed with HIV, low CD4 (<200 cells/mm3), and high viral load
Negative screening result for HLA-B*5701
Initiated abacavir, lamivudine, and lopinavir/r
Concomitant medications
• Valacyclovir (chronic medication) initiated before antiretroviral therapy
• Co-trimoxazole initiated with antiretrovirals
Day 8: Patient noted myalgias and low-grade fever peaking at 37.8°C
Day 9: Patient noted faint rash with low-grade fever peaking at 39°C
approximately 9 hours after morning dose
Day 10: Patient experienced same symptoms at the same time after
morning dose, but fever peaked at 38°C with fewer myalgias
Day 11: Patient was evaluated in clinic
• Temperature 37°C
• Generalised fine urticarial rash
• Asymptomatic
Course of action
• Symptoms appear to have been resolving each day despite continued
abacavir dosing over several days
• Symptom resolution and the patient’s negative HLA-B*5701 screening status
suggest another aetiology
• Continue abacavir dosing with close monitoring and discontinue cotrimoxazole
Follow-up
• Co-trimoxazole is stopped on day 11; subject is seen in the clinic on days 12 and
13, and symptoms continue to decline in severity
• Patient is given topical steroids and antihistamines for the rash
• By day 15, rash and myalgias have resolved and patient remains afebrile on
abacavir, lamivudine, and lopinavir/r
Conclusion
• Hypersensitivity to Co-trimoxazole

Case Studies On Hypersensitivity
Case Presentation #2: Alternative Scenario
Patient is seen on days 12 and 13; symptoms continue but do not
increase or decrease in severity
Patient is given topical steroids and antihistamines for the rash
By day 15, rash is resolving but myalgias continue; patient complains of
malaise
Course of action
• Permanently discontinue abacavir if no other cause of the patient’s
symptoms is identified; in this case, abacavir hypersensitivity cannot be
definitively ruled out
Summary
• Consider other causes for rash and fever when patient is taking
concurrent medications known to be associated with these
symptoms or with allergies, particularly if screening suggests a low
risk of abacavir hypersensitivity
• However, a negative HLA-B*5701 screen does not definitively rule out
the possibility of a hypersensitivity reaction
– If a diagnosis of abacavir hypersensitivity cannot be excluded,
then abacavir must be permanently discontinued, regardless of
the results of any test

Case Studies On Hypersensitivity
Case Presentation #3
• 45-year-old male initiated treatment with abacavir, lamivudine, and
boosted fosamprenavir
– HLA-B*5701 status unknown
• Day 5: Onset of vomiting
• Day 6: Onset of diarrhoea; nausea worsens with more frequent vomiting
• Day 7: Development of fever to 39°C and general weakness;
gastrointestinal symptoms continue without further increase in severity;
careful search revealed no rash
• Course of action
– Permanently discontinue abacavir
– Cumulative, multiorgan symptomatic onset indicates a high
probability of a developing abacavir hypersensitivity reaction
• Follow-up
– Within 24 hours of abacavir discontinuation, patient is afebrile and
gastrointestinal symptoms are resolving
• Conclusion
– Patient experienced abacavir hypersensitivity

Summary
• Rash is very common in abacavir hypersensitivity; however, just as
rash alone would not be sufficient for a diagnosis of a hypersensitivity
reaction, neither is the absence of rash a reason to exclude a diagnosis of
hypersensitivity in the presence of other consistent symptoms; rash may
occur late or even after discontinuation of abacavir
• Other features point towards the diagnosis of a hypersensitivity
syndrome
• Patient developed multiorgan involvement, including constitutional and
gastrointestinal symptoms
– Even in the absence of a rash, patient’s symptoms point to a possible
diagnosis of abacavir hypersensitivity
• Symptoms did not all appear at once but in a stepwise manner

+ Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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