nts in group 1), 22 were able to continue treatment with THIOLA. In those withoutprior history of d-penicillamine treatment, 6% developed reactions of sufficient severity to requireTHIOLA withdrawal.
Table 1 presents adverse reactions ≥5% in either treatment group occurring in this trial.
Table 1: Adverse Reactions Occurring in One or More Patients
System Organ Class Adverse Reaction
Group 1
Previously treated
with d-penicillamine
(N = 49)
Group 2
Naïve to
d-penicillamine
(N = 17)
Blood and Lymphatic System
Disorders
anemia 1 (2%) 1 (6%)
Gastrointestinal Disorders nausea 12 (25%) 2 (12%)
emesis 5 (10%) –
diarrhea/soft stools 9 (18%) 1 (6%)
abdominal pain – 1 (6%)
oral ulcers 6 (12%) 3 (18%)
General Disorders and
Administration Site Conditions
fever 4 (8%) –
weakness 2 (4%) 2 (12%)
fatigue 7 (14%) –
peripheral (edema) 3 (6%) 1 (6%)
chest pain – 1 (6%)
Metabolism and Nutrition
Disorders
anorexia 4 (8%) –
Musculoskeletal and
Connective Tissue Disorders
arthralgia – 2 (12%)
Renal and Urinary Disorders proteinuria 5 (10%) 1 (6%)
impotence – 1 (6%)
Respiratory, Thoracic and
Mediastinal Disorders
cough – 1 (6%)
Skin and Subcutaneous Tissue
Disorders
rash 7 (14%) 2 (12%)
ecchymosis 3 (6%) –
pruritus 2 (4%) 1 (6%)
urticaria 4 (8%) –
skin wrinkling 3 (6%) 1 (6%)
Taste Disturbance
A reduction in taste perception may develop. It is believed to be the result of chelation of trace metals bytiopronin. Hypogeusia is often self-limited.
6.2 Postmarketing Experience
Adverse reactions have been reported from the literature, as well as during post-approval use of THIOLA.
Because the post-approval reactions are reported voluntarily from a population of uncertain size, it is notalways possible to reliably estimate their frequency or establish a causal relationship to THIOLA exposure.
Adverse reactions reported during the postmarketing use of THIOLA are listed by body system in Table 2.
Table 2: Adverse Reactions Reported for THIOLA Pharmacovigilance by System Organ Class and
Preferred Term
System Organ Class Preferred Term
Cardiac Disorders congestive heart failure
Ear and Labyrinth Disorder vertigo
Gastrointestinal Disorders abdominal discomfort; abdominal distension;
abdominal pain; chapped lips; diarrhea; dry
mouth; dyspepsia; eructation; flatulence;
gastrointestinal disorder; gastroesophageal
reflux disease; nausea; vomiting; jaundice;
liver transaminitis
General Disorders and Administration Site Conditions asthenia; chest pain; fatigue; malaise; pain;
peripheral swelling; pyrexia; swelling
Investigations glomerular filtration rate decreased; weight
increased
Metabolism and Nutrition Disorders decreased appetite; dehydration; hypophagia
Musculoskeletal and Connective Tissue Disorders arthralgia; back pain; flank pain; joint swelling;
limb discomfort; musculoskeletal discomfort;
myalgia; neck pain; pain in extremity
Nervous System Disorders ageusia; burning sensation; dizziness; dysgeusia;
headache; hypoesthesia
Renal and Urinary Disorders nephrotic syndrome; proteinuria; renal failure
Skin and Subcutaneous Tissue Disorders dry skin; hyperhidrosis; pemphigus foliaceus;
pruritus; rash; rash pruritic; skin irritation;
skin texture abnormal; skin wrinkling; urticaria
7 DRUG INTERACTIONS
7.1 |
