Persantine IV Side Effects, and Drug Interactions - Persantine

Persantine IV Side Effects, and Drug Interactions - Persantine

SIDE EFFECTS

Adverse reaction information concerning intravenous Persantine^® (dipyridamole USP) is derived from a study of 3911 patients in which intravenous Persantine^® was used as an adjunct to thallium myocardial perfusion imaging and from spontaneous reports of adverse reactions and the published literature. Serious adverse events (cardiac death, fatal and non-fatal myocardial infarction, ventricular fibrillation, asystole, sinus node arrest, symptomatic ventricular tachycardia, stroke, transient cerebral ischemia, seizures, anaphylactoid reaction, angioedema and bronchospasm) are described above (see WARNINGS). In the study of 3911 patients, the most frequent adverse reactions were: chest pain/angina pectoris (19.7%), electrocardiographic changes (most commonly ST-T changes) (15.9%), headache (12.2%), and dizziness (11.8%).

Adverse reactions occuring in greater than 1% of the patients in the study are shown in Table 1:

Less common adverse reactions occurring in 1% or less of the patients within the study included:

Cardiovascular System: Electrocardiographic abnormalities (0.8%), arrhythmia (0.6%), palpitation (0.3%), ventricular tachycardia (0.2% see WARNINGS), bradycardia (0.2%), myocardial infarction (0.1% see WARNINGS), AV block (0.1%), syncope (0.1%), orthostatic hypotension (0.1%), atrial fibrillation (0.1%), supraventricular tachycardia (0.1%), ventricular arrhythmia (0.03% see WARNINGS), heart block (0.03%), cardiomyopathy (0.03%), edema (0.03%). Central and Peripheral Nervous System: Hypothesia (0.5%), hypertonia (0.3%), nervousness/anxiety (0.2%), tremor (0.1%), abnormal coordination (0.03%), somnolence (0.03%), dysphonia (0.03%), migraine (0.03%), vertigo (0.03%).

Gastrointestinal System: Dyspepsia (1.0%), dry mouth (0.8%), abdominal pain (0.7%), flatulence (0.6%), vomiting (0.4%), eructation (0.1%), dysphagia (0.03%), tenesmus (0.03%), appetite increased (0.03%).

Respiratory System: Pharyngitis (0.3%), bronchospasm (0.2% see WARNINGS), hyperventilation (0.1%), rhinitis (0.1%), coughing (0.03%), pleural pain (0.03%).

Other: Myalgia (0.9%), back pain (0.6%), injection site reaction unspecified (0.4%), diaphoresis (0.4%), asthenia (0.3%), malaise (0.3%), arthralgia (0.3%), injection site pain (0.1%), rigor (0.1%), earache (0.1%), tinnitus (0.1%), vision abnormalities unspecified (0.1%), dysgeusia (0.1%), thirst (0.03%), depersonalization (0.03%), eye pain (0.03%), renal pain (0.03%), perineal pain (0.03%), breast pain (0.03%), intermittent claudication (0.03%), leg cramping (0.03%). In additional postmarketing experience, there have been rare reports of diarrhea, allergic reaction including urticaria, pruritus, dermatitis and rash. Mesenteric ischemia and mesenteric infarction have also been observed in association with intravenous Persantine^® (dipyridamole USP) administration.

DRUG INTERACTIONS

Oral maintenance theophylline and other xanthine derivatives such as caffeine may abolish the coronary vasodilatation induced by intravenous Persantine^® (dipyridamole USP) administration. This could lead to a false negative thallium imaging result (see Mechanism of Action). Xanthine derivatives should be avoided 24 hours before myocardial imaging with IV Persantine.

Dipyridamole has been reported to increase the plasma levels and cardiovasular effects of adenosine. Adjustment of adenosine dosage may be necessary.

Myasthenia gravis patients receiving therapy with cholinesterase inhibitors may experience worsening of their disease in the presence of dipyridamole.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 111 week oral study in mice and in a 128-142 week oral study in rats, dipyridamole USP produced no significant carcinogenic effects at doses up to 75 mg/kg (0.8 times and 1.5 times the maximum recommended daily human oral dose on a mg/m² basis in mice and rats, respectively). Mutagenicity testing with dipyridamole was negative. Reproduction studies with dipyridamole revealed no evidence of impaired fertility in rats at dosages up to 500 mg/kg, or 10 times the maximum recommended human oral dose on a mg/m² basis. A significant reduction in number of corpora lutea with consequent reduction in implantations and live fetuses was, however, observed at 1250 mg/kg (25 times the maximum recommended human oral dose on a mg/m² basis).

Pregnancy Teratogenic Effects PREGNANCY CATEGORY B

Reproduction studies have been performed in mice at doses up to 125 mg/kg, rats at doses up to 1000 mg/kg and rabbits at doses up to 40 mg/kg (1.3, 20, and 1.6 times the maximum recommended daily human oral dose on a mg/m² basis, respectively) and have revealed no evidence of harm to the fetus due to dipyridamole. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

As dipyridamole is excreted in human milk, caution should be exercised when IV Persantine^® (dipyridamole USP) ia administered to a nursing woman.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established.