Classification and severity of medication-related adverse events according to CTCAE version 4.

03 (June 14, 2010)

GRADE
SIDE EFFECT Adverse Event
1 2 3 4 5
Hepatotoxicity ALT increase >ULN - 3.0 x ULN >3.0 - 5.0 x ULN 5.0 - 20.0 x ULN >20.0 x ULN -
Bilirubin >ULN - 1.5 x ULN >1.5 - 3.0 x ULN >3.0 - 10.0 x ULN >10.0 x ULN
Hematological toxicity Anemia Hb < LLN -10 g/dL Hb <10 - 8 g/dL Hb < 8 g/dL Life-threatening Death
Platelets LLN - 75.000/mm3 <75.000–50.000/mm3 <50.000-25.000/mm3 <25.000/mm3 -
aPTT >ULN - 1.5 x ULN >1.5 - 2.5 x ULN >2.5 x ULN, - -
prolongation hemorrhage
Gastro/hepatotoxicity Nausea Loss of appetite Oral intake decreased Inadequate oral - -
Gastro intestinal without alteration without significant caloric or fluid intake
intolerance in eating habits weight loss,
dehydration or
malnutrition
Vomiting 1-2 episodes 3-5 episodes ≥ 6 episodes Life-threatening Death
(separated by 5 (separated by 5 (separated by 5
minutes) in 24 hrs. minutes) in 24 hrs. minutes) in 24 hrs.

Diarrhea Increase of < 4 Increase of 4-6 stools increase of ≥7 stools Life-threatening Death
stools per day over per day over baseline per day over baseline:
baseline incontinence
 Abdominal Pain mild pain moderate pain severe pain - -

Anaphylaxis - - Symptomatic Life-threatening Death

Hypersensitivity bronchospasm, with
or without urticarial

Pruritus Mild or localized: Intense or Intense or widespread - -

topical intervention widespread:
indicated intermittent, skin
changes from
scratching (e.g.
edema, papulation,
excoriations,
lichenification,
oozing/crusts)
Rash maculo- Macules/papules Macules/papules Macules/papules - -
papular covering <10% BSA covering 10-30% BSA covering >30% BSA
with or without with or without with or without
symptoms (e.g., symptoms (e.g., associated symptoms
pruritus, burning, pruritus, burning,
tightness) tightness)
Skin induration Mild induration, Moderate induration, Severe induration, Generalized, Death
able to move skin able to slide skin, unable to slide or associated with signs
parallel to plane unable to pinch skin pinch skin: limiting or symptoms of
(sliding) and joint movement or impaired breathing
perpendicular to orifice (e.g., mouth, or feeding
skin (pinching up) anus)
 Urticaria urticarial lession urticarial lession urticarial lession Generalized: Death
covering <10% BSA covering 10-30% BSA covering >30% BSA associated with sign
or symptoms of
impaired breathing
or feeding

*ALT: alanine transferase; ULN: upper limit of normal value; Hb: haemoglobin; BSA: body surface area
Table 6. Classification of adverse events as (partially or wholly) medication-related

Unlikely Possible Probable

Hepatotoxicity No change in ALT from 1 grade increase from baseline and Normal ALT at baseline or
baseline (HCV / HBV co-infection or > 2 grades elevation ALT
Hepatotoxic co-medication (NNRTI, and no viral hepatitis
fluconazole, anti-epileptic drugs)) and no other hepatotoxic drugs
Hypersensitivity Exposure to drug, for Co-medication, history of atopic No co-medication, no history of
(grade 1-3) which patient is known to atopic
be allergic
Anaphylactic shock > 5 days after start of < 5 days after start of treatment and < 5 days after start of treatment and
treatment recent start of concurrent medication no other medication started (e.g. co-
(e.g. co-trimoxazole or ART) trimoxazole or ART)
Hematology No change hematology 1 grade increase from baseline and no 2 grade increase from baseline and
from baseline alternative explanation (bleeding, no alternative explanation (bleeding,
medication) medication)