xtended-release TRENTAL tablets, immediate-release TRENTAL capsules, or the corresponding placebos. The incidence of adverse reactions was higher in the capsule studies (where dose related increases were seen in digestive and nervous system side effects) than in the tablet studies. Studies with the capsule include domestic experience, whereas studies with the extended-release tablets were conducted outside the U.S.
The table indicates that in the tablet studies few patients discontinued because of adverse effects.
INCIDENCE (%) OF SIDE EFFECTS Extended-Release Tablets Immediate-Release Capsules
Commercially Available Used only for Controlled Clinical Trials
TRENTAL Placebo TRENTAL Placebo
(Numbers of Patients at Risk) (321) (128) (177) (138)
Discontinued for Side Effect 3.1 0 9.6 7.2
CARDIOVASCULAR SYSTEM
Angina/Chest Pain 0.3 - 1.1 2.2
Arrhythmia/Palpitation - - 1.7 0.7
Flushing - - 2.3 0.7
DIGESTIVE SYSTEM
Abdominal Discomfort - - 4.0 1.4
Belching/Flatus/Bloating 0.6 - 9.0 3.6
Diarrhea - - 3.4 2.9
Dyspepsia 2.8 4.7 9.6 2.9
Nausea 2.2 0.8 28.8 8.7
Vomiting 1.2 - 4.5 0.7
NERVOUS SYSTEM
Agitation/Nervousness - - 1.7 0.7
Dizziness 1.9 3.1 11.9 4.3
Drowsiness - - 1.1 5.8
Headache 1.2 1.6 6.2 5.8
Insomnia - - 2.3 2.2
Tremor 0.3 0.8 - -
Blurred Vision - - 2.3 1.4
TRENTAL has been marketed in Europe and elsewhere since 1972. In addition to the above symptoms, the following have been reported spontaneously since marketing or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain:
Cardiovascular - dyspnea, edema, hypotension.
Digestive - anorexia, cholecystitis, constipation, dry mouth/thirst.
Nervous - anxiety, confusion, depression, seizures, aseptic meningitis.
Respiratory - epistaxis, flu-like symptoms, laryngitis, nasal congestion.
Skin and Appendages - brittle fingernails, pruritus, rash, urticaria, angioedema.
Special Senses - blurred vision, conjunctivitis, earache, scotoma.
Miscellaneous - bad taste, excessive salivation, leukopenia, malaise, sore throat/swollen neck glands, weight change.
A few rare events have been reported spontaneously worldwide since marketing in 1972. Although they occurred under circumstances in which a causal relationship with pentoxifylline could not be established, they are listed to serve as information for physicians. Cardiovascular — angina, arrhythmia, tachycardia, anaphylactoid reactions. Digestive — hepatitis, jaundice, increased liver enzymes; and Hemic and Lymphatic — decreased serum fibrinogen, pancytopenia, aplastic anemia, leukemia, purpura, thrombocytopenia.
OVERDOSAGE
Overdosage with TRENTAL has been reported in pediatric patients and adults. Symptoms appear to be dose related. A report from a poison control center on 44 patients taking overdoses of enteric-coated pentoxifylline tablets noted that symptoms usually occurred 4–5 hours after ingestion and lasted about 12 hours. The highest amount ingested was 80 mg/kg; flushing, hypotension, convulsions, somnolence, loss of consciousness, fever, and agitation occurred. All patients recovered. In addition to symptomatic treatment and gastric lavage, special attention must be given to supporting respiration, maintaining system
