Drug Side Effects, Toxicities,
and Interactions
Key Questions
1. What are side effects and toxicities of
ART?
2. Why do we need to know the side effects
and toxicities of ART?
3. What is the management of toxicities and
side effects?
4. How do we prevent the occurrence of
side effects and toxicities?
Definitions
• Side effects:
– This refers to unwanted but natural and anticipated consequences of
taking a particular medication.
– Such effects result from action on normal or healthy cells, tissues or
organ systems other than the one for which the drug was prescribed
– Eg lactic acidosis due to blockage of enzyime in mitochondria, hair loss
in anticancer drugs
Adverse effect:
– Adverse reactions are rare and unforeseen bodily responses to a drug.
Eg allergic reaction (NVP rash).
Toxicity:
– This refers to the systemic effects of a drug that are related to the
overall level of the medication in the bloodstream.
– Drug toxicitymay occur with overdosage of a medication, accumulation
of the drug in the body over time or the inability of the patients body to
eliminate the drug.
Why is it important to identify
toxicity effects of ARVs?
Toxicity can decrease adherence,
counselling is extremely important
Disfiguring e.g after Steven Johnson
Syndrome, Lipodystrophy
Death
Side Effects and Toxicities of ARVs
Please review the two charts in your
Participant’s Guide:
1. Common Side Effects of ARV Drugs
(in the back of your Guide)
2. Toxicities and Side Effects of Drugs by Class
(in Module IV: Side Effects Session)
Case Study Practice
Let’s work in four groups to practice
identifying and managing real cases of side
effects, drug interactions and toxicities of
ARVs.
Scenario 1
Nabatanzi is a 7 month old girl who was started on
triommune baby tablets 6 days ago.
Her grandmother returns today to see you because
Nabatanzi has developed an itchy rash on her neck and
back last evening.
She is worried that it appears to be spreading even other
parts of her body.
She has no fever, and the rash has not formed any
blisters. Her neighbour, who also has a child with HIV, has
told her the rash is a sign that the drugs make the child
sicker and asked her to stop them. She is confused.
Photo courtesy of Dr Israel Kalyesubula
Scenario 1
Which drug do you think caused the rash?
Nevirapine
What would you tell the grandmother?
Reassure her that while the reaction may be
bothersome, it does not require change of therapy.
Remind her to continue monitoring the child and to
report immediately if the rash gets worse and
develops blistering.
Mild NVP rash
Nevirapine is the commonest ARV causing skin rash as a side
effect.
The rash usually appears in the first 6 weeks of starting treatment
To prevent nevirapine associated rash, NVP is initially given at half
the full dose for the first two weeks as the health worker monitors for
skin rash and signs of acute liver toxicity such as yellow eyes,
abdominal pain, vomiting and lethargy
Reassure the child and caregiver that while the reaction may be
bothersome, it does not require change of therapy.
Give symptomatic treatment.
mother should continue monitoring the child and to report
immediately if the rash gets worse and develops blistering
Scenario 2
Mbabazi is a 5 year old child who has been on
Combivir, and Nevirapine for 10 days now.
His concerned mother brings him to see you
because he has developed peeling and
ulceration of his skin and mucous membranes.
His mother says his condition began as a rash
all over the body and has steadily gotten worse
over the last 2 days.
She denies he has been burned.
Scenario 2
• Which drug do you think is responsible for
this clinical picture?
Nevirapine
• How would you manage the child?
Immediately discontinue all ARV drugs, manage
the child as for burns
Ensure the child has adequate hydration & nutrition
Keep in a sterile environment, cover with antibiotics,
and give pain killers.
Monitor the child’s vital sign closely
Steven Johnson Syndrome
This is a severe hypersensitivity reaction affecting the skin and the
mucous membranes
Can be caused by any drug. NVP is the most common ARV causing
SJS, but can also be caused cotrimoxazole
Immediately discontinue all ARV drugs, manage the child as for
burns.
Ensure the child has adequate hydration and nutrition.
Keep in a sterile environment, cover with antibiotics, and give pain
killers.
Monitor the child’s vital sign closely.
Refer patient or consult with a doctor about re-introducing ARV
drugs using modified regimen when the patient has stabilized.
Scenario 3
Acayo is a 4 year old child who has been on combivir
and EFV for 4 months now.
She has been brought in for a routine monitoring visit.
You notice that she tires easily, when she runs around
your office. You also notice that her hands and conjuctiva
are pale.
On reviewing her labs, her baseline Hb was10mg/dl. You
request for a repeat Hb, a differential count and a blood
slide to rule out malaria.
The Hb returns as 6.3mg/dl, the blood slide is negative,
and the differential count showed a normal white cell
distribution.
Scenario 3
What drug is responsible for this clinical
picture?
Zidovudine
How would you manage this patient?
Get her admitted and assessed for blood transfusion,
supplement with haematinics
Stop AZT and substitute with either Abacavir, Tenofovir
or Stavudine
AZT induced Anaemia
Zidovudine can cause severe anaemia as a side effect.
Make sure the anaemia is not caused by malaria or other
infectious causes
Subsitute zidovudine with stavudine or tenofovir drugs.
Always consult with a colleague before making the drug
substitution
Give folic acid or transfuse if signs of failure are present.
Signs of failure include palpitation, fast heart beat and
swollen feet.
Scenario 4
Karamagi, an 8 year old boy, has been taking his
antiretroviral drugs for 3 weeks now.
His older brother, Kato, 14 years, sleeps in the
same room with him and has noted that:
– Karamagi wakes up at night screaming
– Describes strange dreams.
– Is depressed, keeps to himself and restless and
irritable.
Kato is also on ARVs
– And has developed a buffalo hump, gaunt
appearance, breast tissue enlargement, tingling
sensation in the feet
Which common side effects can you
identify for both boys?
The side effects mentioned include:
Bizarre dreams/nightmares
Buffalo hump
(lipodystrophy)
Depression
Breast (lipodystrophy)
Irritable
Poor concentration in class
Potato on a matchstick
appearance (lipodystrophy)
Gaunt appearance
(lipoatrophy)
Tingling sensation
(peripheral neuropathy)
Scenario 4
• Which ARV in Karamagi’s regimen could be
responsible for what is being observed?
Efavirenz
• Should Karamagi’s offending drug be substituted
now?
No, do not substitute it now, watch him closely and if
the side effects do not disappear over the next 2
weeks or they are getting worse, substitute EFV for
NVP
Scenario 4
• Which ARV in Kato’s regimen could be
responsible for what is being observed?
Stavudine
• Should Kato’s drug be switched?
Yes, switch to Zidovudine or Abacavir
Drug Interactions
NVP and antiTB drugs (Rifampicin):
Rifampicin reduces the serum levels of NVP to near
sub therapeutic levels.
Avoid using NVP and Rifampicin together, or
increase the dose of NVP
PI and antiTB drugs:
Rifampicin reduces the serum levels of PI to near
sub therapeutic levels.
Avoid using them together
Never use AZT and d4T together.
They antagonize each other
Drug Toxicities
NVP and cotrimoxazole are important causes of hepatitis. Other
ARV drugs can cause it as well.
ALT above X5 upper range is a sign of significant damage
ALT > 2x UNL: should not be given nevirapine at baseline.
d4T + ddI should be avoided in PLHIV with abnormal LFTs (raised
ALT, AST or bilirubin).
Among the NNRTs Efavirenz is the best tolerated
If available: Transaminases (ALT) at baseline, after 2 weeks, four
weeks, and two months on Nevirapine.
Every six months if no problem.
Preventing hepatitis
ALT > 2x UNL: should not be given nevirapine
at baseline.
d4T + ddI should be avoided in PLHA with
abnormal LFTs (raised ALT, AST or bilirubin).
Among the NNRTs Efavirenz is the best
tolerated
If available: Transaminases (ALT) at baseline,
after 2 weeks, four weeks, and two months on
Nevirapine.
Every six months if no problem.
Management of hepatitis
Stop all drugs if transaminases are more than 5
times upper limit of normal
Hepatotoxic drugs should be discontinued at
lower levels of LFT abnormalities if there are
clinical symptoms of hepatitis.
Raised ALT or AST occurs in 5-15% of people
taking NNRTIs, but is symptomatic in less than
1%.