Included as part of the PRECAUTIONS section

Myocardial Ischemia

Fatal cardiac arrest, life threatening ventricular arrhythmias, and myocardial infarction may result from the ischemia induced by pharmacologic stress agents. Cardiac resuscitation equipment and trained staff should be available before administering Lexiscan. If serious reactions to Lexiscan occur, consider the use of aminophylline, an adenosine antagonist, to shorten the duration of increased coronary blood flow induced by Lexiscan [see OVERDOSAGE].

Sinoatrial and Atrioventricular Nodal Block

Adenosine receptor agonists including Lexiscan can depress the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. In clinical trials first degree AV block (PR prolongation > 220 msec) developed in 3% of patients within 2 hours of Lexiscan administration; transient second degree AV block with one dropped beat was observed in one patient receiving Lexiscan. All episodes of AV block were asymptomatic and did not require intervention.

Hypotension

Adenosine receptor agonists including Lexiscan induce arterial vasodilation and hypotension. Decreased systolic blood pressure ( > 35 mm Hg) was observed in 7% of patients and decreased diastolic blood pressure ( > 25 mm Hg) was observed in 4% of patients within 45 min of Lexiscan administration. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, left main coronary artery stenosis, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency.

Bronchoconstriction

Adenosine receptor agonists may cause bronchoconstriction and respiratory compromise. For patients with known or suspected bronchoconstrictive disease, chronic obstructive pulmonary disease (COPD) or asthma, appropriate bronchodilator therapy and resuscitative measures should be available prior to Lexiscan administration [see OVERDOSAGE and Patient Counseling Information].

The incidence of bronchoconstriction (FEV1 reduction > 15% from baseline) was assessed in two clinical studies. In a randomized, controlled study of 49 patients with moderate to severe COPD, the rate of bronchoconstriction was 12% and 6%, for the Lexiscan and placebo groups, respectively. In a randomized, controlled study of 48 patients with mild to moderate asthma who had previously been shown to have bronchoconstrictive reactions to adenosine monophosphate, the rate of bronchoconstriction was the same (4%) for both the Lexiscan and placebo groups. In both studies, dyspnea was reported as an adverse reaction in the Lexiscan group (61% for patients with COPD; 34% for patients with asthma) while no subjects in the placebo group experienced dyspnea.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Regadenoson was negative in the Ames bacterial mutation assay, chromosomal aberration assay in Chinese hamster ovary (CHO) cells, and mouse bone marrow micronucleus assay.

Long-term animal studies have not been conducted to evaluate Lexiscan's carcinogenic potential or potential effects on fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate well-controlled studies with Lexiscan in pregnant women. Lexiscan should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus.

Reproductive studies in rats showed that regadenoson doses 10 and 20 times the maximum recommended human dose (MRHD) based on body surface area, caused reduced fetal body weights and significant ossification delays in fore- and hind limb phalanges and metatarsals; however, maternal toxicity also occurred at these doses. Skeletal variations were increased in all treated groups. In rabbits, there were no teratogenic effects in offspring at regadenoson doses 4 times the MRHD, although signs of maternal toxicity occurred at this dose. At regadenoson doses equivalent to 12 and 20 times the MRHD, maternal toxicity occurred along with increased embryo-fetal loss and fetal malformations. It is not clear whether malformations that occurred at maternally toxic doses of regadenoson in both animal species were due to fetal drug effects or only to the maternal toxic effects.

Because animals received repeated doses of regadenoson, their exposure was significantly higher than that achieved with the standard single dose administered to humans [see Animal Toxicology and Pharmacology].

Nursing Mothers

It is not known whether Lexiscan is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Lexiscan in nursing infants, the decision to interrupt nursing after administration of Lexiscan or not to administer Lexiscan, should take into account the importance of the drug to the mother. Based on the pharmacokinetics of Lexiscan, it should be cleared 10 hours after administration. Therefore, nursing women may consider interrupting nursing for 10 hours after administration.

Pediatric Use

Safety and effectiveness in pediatric patients ( < 18 years of age) have not been established.

Geriatric Use

Of the 1,337 patients receiving Lexiscan in Studies 1 and 2, 56% were 65 years of age and over and 24% were 75 years of age and over. Older patients ( ≥ 75 years of age) had a similar adverse event profile compared to younger patients ( < 65 years of age), but had a higher incidence of hypotension (2% vs. < 1%).

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