Adenocor

How old is patient? < 1 1-5 6-15 16-29 30-45 46-60 > 60

Adenocor uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Adenocor reviews

1 INDICATIONS AND USAGE

Adenocor Injection, USP is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately.

Adenocor Injection, USP, a pharmacologic stress agent, is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately (1)

2 DOSAGE AND ADMINISTRATION

The recommended Adenocor injection dose is 0.14 mg/kg/min infused over six minutes (total dose of 0.84 mg/kg) (Table 1).

• Administer Adenocor injection only as a continuous peripheral intravenous infusion
• Inject Thallium-201 at the midpoint of the Adenocor injection infusion (i.e., after the first three minutes of Adenocor injection)
• Thallium-201 is physically compatible with Adenocor injection and may be injected directly into the Adenocor injection infusion set
• Inject Thallium-201 as close to the venous access as possible to prevent an inadvertent increase in the dose of Adenocor injection (the contents of the intravenous tubing) being administered

Visually inspect Adenocor injection for particulate matter and discoloration prior to administration. Do not administer Adenocor injection if it contains particulate matter or is discolored.

There are no data on the safety or efficacy of alternative Adenocor injection infusion protocols. The safety and efficacy of Adenocor injection administered by the intracoronary route have not been established.

Patient Weight (kilograms)	Infusion Rate (mL per minute over 6 minutes for total dose of 0.84 mg/kg)
45	2.1
50	2.3
55	2.6
60	2.8
65	3
70	3.3
75	3.5
80	3.8
85	4
90	4.2

The nomogram displayed in Table 1 was derived from the following general formula:

Recommended dose is 0.14 mg/kg/min infused over six minutes as a continuous peripheral intravenous infusion (total dose of 0.84 mg/kg) (2)

formula

3 DOSAGE FORMS AND STRENGTHS

Adenocor Injection, USP is supplied as 20 mL and 30 mL single-dose vials containing a sterile, nonpyrogenic, clear solution of Adenocor 3 mg per mL.

Adenocor Injection, USP: 3 mg per mL in single-dose vials (3)

4 CONTRAINDICATIONS

Adenocor is contraindicated in patients with:

• Second- or third-degree AV block (except in patients with a functioning artificial pacemaker)
• Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker)
• Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)
• Known hypersensitivity to Adenocor

• Second- or third-degree AV block (except in patients with a functioning artificial pacemaker) (4)
• Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker) (4)
• Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma) (4)
• Known hypersensitivity to Adenocor (4)

5 WARNINGS AND PRECAUTIONS

• Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction. Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia. Appropriate resuscitative measures should be available
• Sinoatrial (SA) and Atrioventricular (AV) Nodal Block. First-, second-or third-degree AV block, or sinus bradycardia can occur. Discontinue Adenocor if patient develops persistent or symptomatic high-grade AV block (5.2)
• Bronchoconstriction. Can induce dyspnea, bronchoconstriction, and respiratory compromise, especially in patients with obstructive pulmonary disease. Discontinue Adenocor if patient develops severe respiratory difficulties (5.3)
• Hypotension. Significant hypotension can occur. Discontinue Adenocor if patient develops persistent or symptomatic hypotension (5.4)
• Cerebrovascular Accidents. Hemorrhagic and ischemic cerebrovascular accidents have occurred (5.5)
• Seizures. New onset or recurrence of convulsive seizures have occurred. Use of methylxanthines (e.g., caffeine, aminophylline and theophylline) is not recommended in patients who experience a seizures in association with Adenocor (5.6)
• Hypersensitivity. Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Have personnel and resuscitative equipment immediately available (5.7)
• Atrial Fibrillation. Reported in patients with or without a history of atrial fibrillation (5.8)
• Hypertension. Clinically significant increases in systolic and diastolic pressure have been observed (5.9)

5.1 Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction

Fatal and nonfatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and myocardial infarction have occurred following Adenocor infusion. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example, unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to Adenocor. Appropriate resuscitative measures should be available .

5.2 Sinoatrial and Atrioventricular Nodal Block

Adenocor exerts a direct depressant effect on the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. In clinical trials, approximately 6% of patients developed AV block following Adenocor administration .

Use Adenocor with caution in patients with pre-existing first-degree AV block or bundle branch block. Do not use in patients with high-grade AV block or sinus node dysfunction (except in patients with a functioning artificial pacemaker). Discontinue Adenocor in any patient who develops persistent or symptomatic high-grade AV block.

5.3 Bronchoconstriction

Adenocor administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Adenocor should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis). Do not use in patients with bronchoconstriction or bronchospasm (e.g., asthma). Discontinue Adenocor in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to Adenocor administration .

5.4 Hypotension

Adenocor is a potent peripheral vasodilator and can induce significant hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency. Discontinue Adenocor in any patient who develops persistent or symptomatic hypotension.

5.5 Cerebrovascular Accident

Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of Adenocor including hypotension or hypertension can be associated with these adverse reactions .

5.6 Seizures

New-onset or recurrence of convulsive seizures has occurred following Adenocor. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with Adenocor. Methylxanthine use is not recommended in patients who experience seizures in association with Adenocor administration .

5.7 Hypersensitivity, Including Anaphylaxis

Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Symptomatic treatment may be required. Have personnel and appropriate treatment available. Resuscitative measures may be necessary if symptoms progress .

5.8 Atrial Fibrillation

Adenocor can cause atrial fibrillation in patients with or without a history of atrial fibrillation. Atrial fibrillation typically began 1.5 to 3 minutes after initiation of Adenocor, lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm .

5.9 Hypertension

Adenocor can induce clinically significant increases in systolic and diastolic blood pressure. Most increases resolved spontaneously within several minutes, but in some cases, hypertension lasted for several hours .

6 ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the prescribing information:

• Fatal Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction
• Sinoatrial and Atrioventricular Nodal Block
• Bronchoconstriction
• Hypotension
• Cerebrovascular Accident
• Seizures
• Hypersensitivity
• Atrial fibrillation
• Hypertension

Most common adverse reactions (incidence ≥ 10%) are: flushing; chest discomfort; shortness of breath; headache; throat, neck or jaw discomfort; gastrointestinal discomfort; and dizziness (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 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.

The following adverse reactions, with an incidence of at least 1%, were reported with Adenocor among 1,421 patients in clinical trials. 11% of the adverse reactions occurred several hours after Adenocor administration. 8% of the adverse reactions began with Adenocor infusion and persisted for up to 24 hours.

The most common (incidence ≥ 10%) adverse reactions to Adenocor are flushing, chest discomfort, shortness of breath, headache, throat, neck or jaw discomfort, gastrointestinal discomfort, and dizziness (Table 2).

Adverse Reactions	Adenocor N=1,421
Flushing	44%
Chest discomfort	40%
Dyspnea	28%
Headache	18%
Throat, neck or jaw discomfort	15%
Gastrointestinal discomfort	13%
Lightheadedness/dizziness	12%
Upper extremity discomfort	4%
ST segment depression	3%
First-degree AV block	3%
Second-degree AV block	3%
Paresthesia	2%
Hypotension	2%
Nervousness	2%
Arrhythmias	1%

Adverse reactions to Adenocor of any severity reported in less than 1% of patients include:

Body as a Whole:	back discomfort, lower extremity discomfort, weakness
Cardiovascular System:	myocardial infarction, ventricular arrhythmia, third-degree AV block, bradycardia, palpitation, sinus exit block, sinus pause, T-wave changes, hypertension (systolic blood pressure > 200 mm Hg)
Respiratory System:	cough
Central Nervous System:	drowsiness, emotional instability, tremors
Genital/Urinary System:	Vaginal pressure, urgency
Special Senses:	blurred vision, dry mouth, ear discomfort, metallic taste, nasal congestion, scotomas, tongue discomfort

6.2 Post-Marketing Experience

The following adverse reactions have been reported from marketing experience with Adenocor. Because these reactions are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders:	cardiac arrest, atrial fibrillation, cardiac failure, myocardial infarction, tachycardia, ventricular arrhythmia
Gastrointestinal Disorders:	nausea and vomiting
General Disorders and Administration Site Conditions:	chest pain, injection site reaction, infusion site pain
Immune System Disorders:	hypersensitivity
Nervous System Disorders:	cerebrovascular accident including intracranial hemorrhage, seizure activity including tonic-clonic (grand mal) seizures, loss of consciousness
Respiratory, Thoracic and Mediastinal Disorders:	bronchospasm, respiratory arrest, throat tightness

7 DRUG INTERACTIONS

• Methylxanthines interfere with the activity of Adenocor
• Nucleoside transport inhibitors such as dipyridamole can increase the activity of Adenocor (7.1)

7.1 Effects of Other Drugs on Adenocor

• The vasoactive effects of Adenocor are inhibited by Adenocor receptor antagonists, (such as methylxanthines (e.g., caffeine, aminophylline, and theophylline). The safety and efficacy of Adenocor in the presence of these agents has not been systematically evaluated .
• The vasoactive effects of Adenocor are potentiated by nucleoside transport inhibitors such as dipyridamole. The safety and efficacy of Adenocor in the presence of dipyridamole has not been systematically evaluated.
• Whenever possible, drugs that might inhibit or augment the effects of Adenocor should be withheld for at least five half-lives prior to the use of Adenocor.

7.2 Effects of Adenocor on Other Drugs

Adenocor injection has been given with other cardioactive drugs (such as beta adrenergic blocking agents, cardiac glycosides, and calcium channel blockers) without apparent adverse interactions, but its effectiveness with these agents has not been systematically evaluated. Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, Adenocor should be used with caution in the presence of these agents .

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Adenocor; nor have studies been performed in pregnant women. Because it is not known whether Adenocor can cause fetal harm when administered to pregnant women, Adenocor should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Adenocor is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Adenocor in nursing infants, the decision to interrupt nursing after administration of Adenocor or not to administer Adenocor, should take into account the importance of the drug to the mother.

8.4 Pediatric Use

The safety and effectiveness of Adenocor in patients less than 18 years of age have not been established.

8.5 Geriatric Use

Clinical studies with Adenocor did not include sufficient numbers of subjects aged younger than 65 years to determine whether they respond differently. Other reported experience has not revealed clinically relevant differences of the response of elderly in comparison to younger patients.

10 OVERDOSAGE

The half-life of Adenocor is less than 10 seconds and adverse reactions of Adenocor usually resolve quickly when the infusion is discontinued, although delayed or persistent reactions have been observed. Methylxanthines, such as caffeine, aminophylline, and theophylline, are competitive Adenocor receptor antagonists and theophylline has been used to terminate persistent adverse reactions. In clinical trials, theophylline (50 to 125 mg slow intravenous injection) was used to attenuate Adenocor adverse reactions in approximately 2% of patients. Methylxanthine use is not recommended in patients who experience seizures in association with Adenocor .

11 DESCRIPTION

Adenocor is an endogenous nucleoside and is chemically described as 6-amino-9-beta-D-ribofuranosyl-9-H-purine. Adenocor has the following structural formula:

The molecular formula for Adenocor is C₁₀H₁₃N₅O₄ and its molecular weight is 267.24.

Adenocor is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH of the solution.

Each Adenocor Injection, USP vial contains a sterile, non-pyrogenic solution of Adenocor 3 mg/mL and sodium chloride 9 mg/mL in water for injection, with pH between 4.5 and 7.5.

Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Adenocor causes cardiac vasodilation which increases cardiac blood flow. Adenocor is thought to exert its pharmacological effects through activation of purine receptors. Although the exact mechanism by which Adenocor receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A₂ receptors in smooth muscle cells. Adenocor may also lessen vascular tone by modulating sympathetic neurotransmission. The intracellular uptake of Adenocor is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, Adenocor is rapidly phosphorylated by Adenocor kinase to Adenocor monophosphate, or deaminated by Adenocor deaminase to inosine. These intracellular metabolites of Adenocor are not vasoactive.

Myocardial uptake of thallium-201 is directly proportional to coronary blood flow. Since Adenocor significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, Adenocor causes relatively less thallium-201 uptake in vascular territories supplied by stenotic coronary arteries i.e., a greater difference is seen after Adenocor between areas served by normal and areas served by stenotic vessels than is seen prior to Adenocor.

12.2 Pharmacodynamics

Hemodynamic Effects

Adenocor produces a direct negative chronotropic, dromotropic and inotropic effect on the heart, presumably due to A₁-receptor agonism, and produces peripheral vasodilation, presumably due to A₂-receptor agonism. The net effect of Adenocor in humans is typically a mild to moderate reduction in systolic, diastolic and mean arterial blood pressure associated with a reflex increase in heart rate. Rarely, significant hypotension and tachycardia have been observed .

12.3 Pharmacokinetics

Distribution

Intravenously administered Adenocor distributes from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical.

Metabolism

Intracellular Adenocor is metabolized either via phosphorylation to Adenocor monophosphate by Adenocor kinase, or via deamination to inosine by Adenocor deaminase in the cytosol. Since Adenocor kinase has a lower K_m and V_max than Adenocor deaminase, deamination plays a significant role only when cytosolic Adenocor saturates the phosphorylation pathway. Inosine formed by deamination of Adenocor can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Adenocor monophosphate formed by phosphorylation of Adenocor is incorporated into the high-energy phosphate pool.

Elimination

While extracellular Adenocor is primarily cleared from plasma by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of Adenocor deaminase.

Specific Populations

Renal Impairment

As Adenocor does not require renal function for its activation or inactivation, renal impairment would not be expected to alter its effectiveness or tolerability.

Hepatic Impairment

As Adenocor does not require hepatic function for its activation or inactivation, hepatic impairment would not be expected to alter its effectiveness or tolerability.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals have not been performed to evaluate adenosine's carcinogenic potential or potential effects on fertility. Adenocor was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.

Adenocor, however, like other nucleosides at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety of chromosomal alterations.

14 CLINICAL STUDIES

In two crossover comparative studies involving 319 subjects who could exercise (including 106 healthy volunteers and 213 patients with known or suspected coronary disease), Adenocor and exercise thallium images were compared by blinded observers. The images were concordant for the presence of perfusion defects in 85.5% of cases by global analysis (patient by patient) and up to 93% of cases based on vascular territories.

In the two studies, 193 patients also had recent coronary arteriography for comparison (healthy volunteers were not catheterized). The sensitivity for detecting angiographically significant disease (≥ 50% reduction in the luminal diameter of at least one major vessel) was 64% for Adenocor and 64% for exercise testing. The specificity was 54% for Adenocor and 65% for exercise testing. The 95% confidence limits for Adenocor sensitivity were 56% to 78% and for specificity were 37% to 71%.

Intracoronary Doppler flow catheter studies have demonstrated that a dose of intravenous Adenocor of 0.14 mg/kg/min produces maximum coronary hyperemia (relative to intracoronary papaverine) in approximately 95% of cases within two to three minutes of the onset of the infusion. Coronary blood flow velocity returns to basal levels within one to two minutes of discontinuing the Adenocor infusion.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Adenocor Injection, USP is supplied as 20 mL and 30 mL single-dose vials of sterile, nonpyrogenic solution in normal saline as follows:

NDC	Adenocor Injection, USP	Package Factor
25021-307-20	60 mg per 20 mL Single-Dose Vial	1 vial per carton
25021-307-21	60 mg per 20 mL Single-Dose Vial	10 vials per carton
25021-307-30	90 mg per 30 mL Single-Dose Vial	1 vial per carton
25021-307-31	90 mg per 30 mL Single-Dose Vial	10 vials per carton

16.2 Storage and Handling

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F).

Do not refrigerate as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.

Discard unused portion.

Sterile, Nonpyrogenic, Preservative-free.

The container closure is not made with natural rubber latex.

17 PATIENT COUNSELING INFORMATION

• Advise patients that they may be at increased risk of fatal and nonfatal heart attacks, abnormal heart rhythms, cardiac arrest, heart block, significant increase or decrease in blood pressure, bronchoconstriction, hypersensitivity reactions, seizures, or cerebrovascular accidents with the use of Adenocor .
• Advise patients with COPD or asthma to discuss their respiratory history with their clinician before scheduling a myocardial perfusion imaging study with Adenocor .
• Methylxanthines have the potential to impact the effects of Adenocor. Instruct patients to avoid consumption of any products containing methylxanthines, including caffeinated coffee, tea or other caffeinated beverages, caffeine-containing drug products, aminophylline, and theophylline prior to the myocardial perfusion imaging study. Question patients about a history of seizures .

SAGENT

Mfd. for SAGENT Pharmaceuticals

Schaumburg, IL 60195 (USA)

Made in India

©2014 Sagent Pharmaceuticals, Inc.

Revised: September 2014

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label

NDC 25021-307-20

Rx only

Adenocor Injection, USP

60 mg per 20 mL (3 mg per mL)

For Intravenous Infusion Only

20 mL Single-Dose Vial

Adenocor pharmaceutical active ingredients containing related brand and generic drugs:

• Adenosine

Adenocor available forms, composition, doses:

• Injectable; Injection; Adenosine 3 mg / ml

Adenocor destination | category:

• Human:
• Cardiac drugs
• Class IV antiarrythmics

Adenocor Anatomical Therapeutic Chemical codes:

• C01EB10 - Adenosine

Adenocor pharmaceutical companies:

• DKSH
• Sanofi-Aventis
• Torrent Pharmaceuticals
• Zuellig Pharma

References

1. Dailymed."ADENOSINE INJECTION, SOLUTION [SAGENT PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. Dailymed."ADENOSINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
3. "adenosine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Adenocor?

Depending on the reaction of the Adenocor after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Adenocor not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Adenocor addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

Review

sdrugs.com conducted a study on Adenocor, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Adenocor consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology