Regadenoson
FDA Drug Information • Also known as: Lexiscan, Regadenoson
- Brand Names
- Lexiscan, Regadenoson
- Drug Class
- Adenosine Receptor Agonist [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Regadenoson is an A 2A adenosine receptor agonist that is a coronary vasodilator [ see Clinical Pharmacology ( 12.1 ) ]. Regadenoson is chemically described as adenosine, 2-[4-[(methylamino)carbonyl]-1 H -pyrazol-1-yl]. Its structural formula is: The molecular formula for regadenoson is C 15 H 18 N 8 O 5 and its molecular weight is 390.35 g/mol. Regadenoson is a sterile, nonpyrogenic solution for intravenous injection. The solution is clear and colorless. Each 1 mL in the 5 mL pre-filled syringe contains 0.08 mg regadenoson on an anhydrous basis, 10.9 mg dibasic sodium phosphate dihydrate, 5.4 mg monobasic sodium phosphate monohydrate, 150 mg propylene glycol, 1 mg edetate disodium dihydrate, and Water for Injection, with pH between 6.3 and 7.7. Structure
What Is Regadenoson Used For?
1 INDICATIONS AND USAGE Regadenoson injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress. Regadenoson is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION The recommended dose of regadenoson injection is 5 mL (0.4 mg regadenoson) administered as an intravenous injection within 10 seconds. Patients should be instructed to avoid consumption of any products containing methylxanthines, including caffeinated coffee, tea or other caffeinated beverages, caffeine-containing drug products, aminophylline and theophylline for at least 12 hours before a scheduled radionuclide MPI [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.2 )]. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer regadenoson injection if it contains particulate matter or is discolored. Administer regadenoson as an intravenous injection within 10 seconds into a peripheral vein using a 22 gauge or larger catheter or needle. Administer a 5 mL saline flush immediately after the injection of regadenoson. Administer the radionuclide myocardial perfusion imaging agent 10 to 20 seconds after the saline flush. The radionuclide may be injected directly into the same catheter as regadenoson.
The recommended dose of regadenoson is 5 mL (0.4 mg regadenoson) administered as an intravenous injection within 10 seconds; followed immediately by saline flush and radiopharmaceutical ( 2 ).Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling.
Myocardial Ischemia [ see Warnings and Precautions (5.1) ] Sinoatrial and Atrioventricular Nodal Block [ see Warnings and Precautions (5.2) ] Atrial Fibrillation/Atrial Flutter [ see Warnings and Precautions (5.3) ] Hypersensitivity, Including Anaphylaxis [ see Warnings and Precautions (5.4) ] Hypotension [ see Warnings and Precautions (5.5) ] Hypertension [ see Warnings and Precautions (5.6) ] Bronchoconstriction [ see Warnings and Precautions (5.7) ] Seizure [ see Warnings and Precautions (5.8) ] Cerebrovascular Accident (Stroke) [ see Warnings and Precautions (5.9) ] The most common (incidence ≥ 5%) adverse reactions to regadenoson are dyspnea, headache, flushing, chest discomfort, dizziness, angina pectoris, chest pain, and nausea ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. During clinical development, 1,651 patients were exposed to regadenoson, with most receiving 0.4 mg as a rapid (≤ 10 seconds) intravenous injection. Most of these patients received regadenoson in two clinical studies that enrolled patients who had no history of bronchospastic lung disease as well as no history of a cardiac conduction block of greater than first-degree AV block, except for patients with functioning artificial pacemakers. In these studies (Studies 1 and 2), 2,015 patients underwent myocardial perfusion imaging after administration of regadenoson injection (N = 1,337) or ADENOSCAN (N = 678). The population was 26 to 93 years of age (median 66 years), 70% male and primarily Caucasian (76% Caucasian, 7% African American, 9% Hispanic, 5% Asian). Table 1 shows the most frequently reported adverse reactions. Overall, any adverse reaction occurred at similar rates between the study groups (80% for the regadenoson group and 83% for the ADENOSCAN group). Aminophylline was used to treat the reactions in 3% of patients in the regadenoson group and 2% of patients in the ADENOSCAN group. Most adverse reactions began soon after dosing, and generally resolved within approximately 15 minutes, except for headache which resolved in most patients within 30 minutes. Table 1 Adverse Reactions in Studies 1 and 2 Pooled (Frequency ≥ 5%) REGADENOSON N = 1,337 ADENOSCAN N = 678 Dyspnea 28% 26% Headache 26% 17% Flushing 16% 25% Chest Discomfort 13% 18% Angina Pectoris or ST Segment Depression 12% 18% Dizziness 8% 7% Chest Pain 7% 10% Nausea 6% 6% Abdominal Discomfort 5% 2% Dysgeusia 5% 7% Feeling Hot 5% 8% ECG Abnormalities The frequency of rhythm or conduction abnormalities following regadenoson or ADENOSCAN is shown in Table 2 [ see Warnings and Precautions ( 5.2 ) ]. Table 2 Rhythm or Conduction Abnormalities 12-lead ECGs were recorded before and for up to 2 hours after dosing. in Studies 1 and 2 REGADENOSON N/N evaluable (%) ADENOSCAN N/N evaluable (%) Rhythm or conduction abnormalities includes rhythm abnormalities (PACs, PVCs, atrial fibrillation/flutter, wandering atrial pacemaker, supraventricular or ventricular arrhythmia) or conduction abnormalities, including AV block. 332/1275 (26%) 192/645 (30%) Rhythm abnormalities 260/1275 (20%) 131/645 (20%) PACs 86/1274 (7%) 57/645 (9%) PVCs 179/1274 (14%) 79/645 (12%) First-degree AV block (PR prolongation > 220 msec) 34/1209 (3%) 43/618 (7%) Second-degree AV block 1/1209 (0.1%) 9/618 (1%) AV conduction abnormalities (other than AV blocks) 1/1209 (0.1%) 0/618 (0%) Ventricular conduction abnormalities 64/1152 (6%) 31/581 (5%) Respiratory Abnormalities In a randomized, placebo-controlled trial of 999 patients...Drug Interactions
7 DRUG INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with regadenoson.
Methylxanthines, e.g., caffeine, aminophylline and theophylline, interfere with the activity of regadenoson ( 7.1 , 12.2 ). Aminophylline may be used to attenuate severe and/or persistent adverse reactions to regadenoson ( 7.1 , 10 ). Dipyridamole may increase the activity of regadenoson. When possible, withhold dipyridamole for at least two days prior to regadenoson administration ( 7.1 ). 7.1 Effects of Other Drugs on Regadenoson Methylxanthines (e.g., caffeine, aminophylline and theophylline) are non-specific adenosine receptor antagonists that interfere with the vasodilation activity of regadenoson [ see Clinical Pharmacology ( 12.2 ) and Patient Counseling Information ( 17 ) ]. Patients should avoid consumption of any products containing methylxanthines as well as any drugs containing theophylline or aminophylline for at least 12 hours before regadenoson administration. Aminophylline may be used to attenuate severe or persistent adverse reactions to regadenoson [ see Overdosage ( 10 ) ]. In clinical studies, regadenoson was administered to patients taking other cardioactive drugs (i.e., β-blockers, calcium channel blockers, ACE inhibitors, nitrates, cardiac glycosides, and angiotensin receptor blockers) without reported adverse reactions or apparent effects on efficacy. Dipyridamole may change the effects of regadenoson. When possible, withhold dipyridamole for at least two days prior to regadenoson administration. 7.2 Effect of Regadenoson on Other Drugs Regadenoson does not inhibit the metabolism of substrates for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in human liver microsomes, indicating that it is unlikely to alter the pharmacokinetics of drugs metabolized by these cytochrome P450 enzymes.Contraindications
4 CONTRAINDICATIONS Do not administer regadenoson injection to patients with:
Second- or third- degree AV block, or sinus node dysfunction unless these patients have a functioning artificial pacemaker [ see Warnings and Precautions ( 5.2 ) ]. Do not administer regadenoson to patients with: Second- or third- degree AV block, or sinus node dysfunction unless the patients have a functioning artificial pacemaker ( 4 ).Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on regadenoson use in pregnant women to inform a drug-associated risk. In animal reproduction studies, adverse developmental outcomes were observed with the administration of regadenoson to pregnant rats and rabbits during organogenesis only at doses that produced maternal toxicity (see Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data 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; maternal toxicity also occurred at these doses. Skeletal variations were increased in all treated groups. In rabbits, maternal toxicity occurred at regadenoson doses administered during organogenesis at 4 times the MRHD; however, there were no teratogenic effects in offspring at this dose. At higher doses, 12 and 20 times the MRHD, maternal toxicity occurred along with increased embryo-fetal loss and fetal malformations.
Overdosage
10 OVERDOSAGE Regadenoson overdosage may result in serious reactions [ see Warnings and Precautions ( 5 ) ]. In a study of healthy volunteers, symptoms of flushing, dizziness and increased heart rate were assessed as intolerable at regadenoson doses greater than 0.02 mg/kg. Aminophylline to Reverse Effects Methylxanthines, such as caffeine, aminophylline, and theophylline, are competitive adenosine receptor antagonists and aminophylline has been used to terminate persistent pharmacodynamic effects. Aminophylline may be administered in doses ranging from 50 mg to 250 mg by slow intravenous injection (50 mg to 100 mg over 30 to 60 seconds). Methylxanthine use is not recommended in patients who experience a seizure in association with regadenoson administration [see Warnings and Precautions ( 5.8 )].
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Regadenoson Injection is supplied as a sterile, preservative-free solution containing 0.08 mg/mL regadenoson in the following package:
Single-dose 5 mL pre-filled plastic syringes with luer-lock and fitted with an elastomeric Tip cap (NDC 60505-6288-0). Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.