Ticlid (Ticlopidine Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS:

Adverse reactions in stroke patients were relatively frequent with over 50% of patients reporting at least one. Most (30% to 40%) involved the gastrointestinal tract. Most adverse effects are mild, but 21% of patients discontinued therapy because of an adverse event, principally diarrhea, rash, nausea, vomiting, GI pain and neutropenia. Most adverse effects occur early in the course of treatment, but a new onset of adverse effects can occur after several months.

The incidence rates of adverse events listed in the following table were derived from multicenter, controlled clinical trials in stroke patients described above comparing TICLID, placebo and aspirin over study periods of up to 5.8 years. Adverse events considered by the investigator to be probably drug-related that occurred in at least 1% of patients treated with TICLID are shown in the following table:

Percent of Patients With Adverse Events in Controlled Studies (TASS and CATS)

Event	TICLID (n = 2048) Incidence	Aspirin (n = 1527) Incidence	Placebo (n = 536) Incidence
Any Events	60.0 (20.9)	53.2 (14.5)	34.3 (6.1)
Diarrhea	12.5 (6.3)	5.2 (1.8)	4.5 (1.7)
Nausea	7.0 (2.6)	6.2 (1.9)	1.7 (0.9)
Dyspepsia	7.0 (1.1)	9.0 (2.0)	0.9 (0.2)
Rash	5.1 (3.4)	1.5 (0.8)	0.6 (0.9)
GI Pain	3.7 (1.9)	5.6 (2.7)	1.3 (0.4)
Neutropenia	2.4 (1.3)	0.8 (0.1)	1.1 (0.4)
Purpura	2.2 (0.2)	1.6 (0.1)	0.0 (0.0)
Vomiting	1.9 (1.4)	1.4 (0.9)	0.9 (0.4)
Flatulence	1.5 (0.1)	1.4 (0.3)	0.0 (0.0)
Pruritus	1.3 (0.8)	0.3 (0.1)	0.0 (0.0)
Dizziness	1.1 (0.4)	0.5 (0.4)	0.0 (0.0)
Anorexia	1.0 (0.4)	0.5 (0.3)	0.0 (0.0)
Abnormal Liver Function Test	1.0 (0.7)	0.3 (0.3)	0.0 (0.0)

Incidence of discontinuation, regardless of relationship to therapy, is shown in parentheses.

Hematological:

Neutropenia/thrombocytopenia, TTP, aplastic anemia (see BOXED WARNING and WARNINGS), leukemia, agranulocytosis, eosinophilia, pancytopenia, thrombocytosis and bone-marrow depression have been reported.

Gastrointestinal:

TICLID therapy has been associated with a variety of gastrointestinal complaints including diarrhea and nausea. The majority of cases are mild, but about 13% of patients discontinued therapy because of these. They usually occur within 3 months of initiation of therapy and typically are resolved within 1 to 2 weeks without discontinuation of therapy. If the effect is severe or persistent, therapy should be discontinued. In some cases of severe or bloody diarrhea, colitis was later diagnosed.

Hemorrhagic:

TICLID has been associated with increased bleeding, spontaneous posttraumatic bleeding and perioperative bleeding including, but not limited to, gastrointestinal bleeding. It has also been associated with a number of bleeding complications such as ecchymosis, epistaxis, hematuria and conjunctival hemorrhage.

Intracerebral bleeding was rare in clinical trials in stroke patients with TICLID, with an incidence no greater than that seen with comparator agents (ticlopidine 0.5%, aspirin 0.6%, placebo 0.75%). It has also been reported postmarketing.

Rash:

Ticlopidine has been associated with a maculopapular or urticarial rash (often with pruritus). Rash usually occurs within 3 months of initiation of therapy with a mean onset time of 11 days. If drug is discontinued, recovery occurs within several days. Many rashes do not recur on drug rechallenge. There have been rare reports of severe rashes, including Stevens-Johnson syndrome, erythema multiforme and exfoliative dermatitis.

Less Frequent Adverse Reactions (Probably Related):

Clinical adverse experiences occurring in 0.5% to 1.0% of stroke patients in controlled trials include: Digestive System: GI fullness

Skin and Appendages: urticaria

Nervous System: headache

Body as a Whole: asthenia, pain

Hemostatic System: epistaxis

Special Senses: tinnitus

In addition, rarer, relatively serious and potentially fatal events associated with the use of TICLID have also been reported from postmarketing experience: Hemolytic anemia with reticulocytosis, immune thrombocytopenia, hepatitis, hepatocellular jaundice, cholestatic jaundice, hepatic necrosis, hepatic failure, peptic ulcer, renal failure, nephrotic syndrome, hyponatremia, vasculitis, sepsis, allergic reactions (including angioedema, allergic pneumonitis, and anaphylaxis), systemic lupus (positive ANA), peripheral neuropathy, serum sickness, arthropathy and myositis.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO TICLID

Possible Ticlid side effects / adverse reactions in 78 year old male

Reported by a health professional (non-physician/pharmacist) from France on 2007-02-06

Patient: 78 year old male

Reactions: Urinary Tract Infection, Sepsis, Leukopenia

Adverse event resulted in: hospitalization

Suspect drug(s):
Ticlid

Other drugs received by patient: Triatec; BI-Euglucon M; Glucobay; Pantopan; Aspirin; Cardicor

Possible Ticlid side effects / adverse reactions in 82 year old female

Reported by a consumer/non-health professional from France on 2007-02-20

Patient: 82 year old female

Reactions: Dysarthria, Confusional State, Cerebral Haemorrhage

Adverse event resulted in: hospitalization

Suspect drug(s):
Ticlid

Possible Ticlid side effects / adverse reactions in 63 year old male

Reported by a consumer/non-health professional from France on 2007-02-20

Patient: 63 year old male

Reactions: Bronchopneumonia, Neutropenia, Pyrexia, Thrombocytopenia

Adverse event resulted in: hospitalization

Suspect drug(s):
Ticlid