Atenolol

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
CAS Number: 29122-68-7
Brands: Tenoretic, Tenormin

Introduction

β₁-Selective adrenergic blocking agent.^{111 118 120 274 c}

Uses for Atenolol

Hypertension

Management of hypertension; used alone or in combination with other classes of antihypertensive agents.^{100 108 109 110 111 128 152 153 154 155 156 157 158 159 170 171 172 173}

One of several preferred initial therapies in hypertensive patients with ischemic heart disease,^{170 223} heart failure,^{220 231 246 252} or diabetes mellitus.²¹⁴

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.²³¹

Angina

Management of chronic stable angina pectoris.^{111 112}

A component of the standard therapeutic measures in the management of unstable angina or non-ST-segment elevation/non-Q-wave MI†.^{223 224 274}

AMI

Secondary prevention following AMI to reduce the risk of cardiovascular mortality.^{111 113 120 122 123 124 132 169 274}

Supraventricular Tachyarrhythmias

β-Adrenergic blocking agents, including atenolol, are one of several preferred antiarrhythmic agents for the treatment of stable, narrow-complex supraventricular tachycardias (e.g., paroxysmal supraventricular tachycardia† [reentry supraventricular tachycardia], ectopic† or multifocal atrial tachycardia†, junctional tachycardia†) if the rhythm is not controlled by vagal maneuvers or adenosine in patients with preserved left ventricular function and for rate control in atrial fibrillation or flutter† in patients with preserved left ventricular function.²⁷⁴

Ventricular Tachyarrhythmias

Reducing the incidence of ventricular fibrillation† associated with myocardial ischemia or infarction.^{169 211 274}

Treatment of sustained polymorphic ventricular tachycardia† following AMI.^{169 211}

CHF

Bisoprolol, carvedilol, and extended-release metoprolol have been shown to be effective in reducing the risk of death in patients with chronic heart failure; however, these positive findings should not be considered indicative of β-adrenergic blocking agent class effect.²⁶¹

Vascular Headache

Prophylaxis of migraine headache†.²²⁸

Atenolol is not recommended for the treatment of a migraine attack that has already started.²²⁸

Alcohol Withdrawal

Management of acute alcohol withdrawal† in conjunction with a benzodiazepine.^{101 229}

Atenolol should not be used as monotherapy for acute alcohol withdrawal†.^{229 230}

Atenolol Dosage and Administration

General

• 
  

  Individualize dosage according to patient response.¹¹¹

  
  


• 
  

  β₁-Adrenergic blocking selectivity diminishes as dosage is increased.^{111 120}

  
  


• 
  

  If long-term therapy is discontinued, reduce dosage gradually over a period of about 2 weeks.^{111 120}

  
  

Administration

Administer orally or by slow IV injection.^c

Oral Administration

Once-daily dosing usually is sufficient in the management of hypertension.^c

IV Administration

Monitor heart rate, BP, and ECG during IV therapy.¹²⁰

Dilution

May be administered undiluted by slow IV injection or diluted in dextrose injection, sodium chloride injection, or dextrose and sodium chloride injection prior to administration.¹²⁰

For solution and drug compatibility information, see Compatibility under Stability.

Rate of Administration

Administer at a rate of 1 mg/minute.¹²⁰

Dosage

Pediatric Patients

Hypertension†

Oral

Some experts recommend an initial dosage of 0.5–1 mg/kg daily given as a single dose or in 2 divided doses.²⁵⁸ Increase dosage as necessary up to a maximum dosage of 2 mg/kg (up to 100 mg) daily given as a single dose or in 2 divided doses.²⁵⁸

Adults

Hypertension

Monotherapy

Oral

Initially, 25–50 mg once daily.^{214 215} Full hypotensive response may require 2 weeks.^c

If necessary, increase to 100 mg once daily.²¹⁴ Some patients may have improved BP control with twice-daily dosing.¹⁷⁰

Combination Therapy.

Oral

Atenolol in fixed combination with chlorthalidone: initially, 50 mg of atenolol and 25 mg of chlorthalidone once daily.¹¹⁸ If response is not optimal, 100 mg of atenolol and 25 mg of chlorthalidone once daily.¹¹⁸

Initial use of fixed-combination preparations is not recommended; adjust by administering each drug separately, then use the fixed combination if the optimum maintenance dosage corresponds to the ratio of drugs in the combination preparation.^{118 c} Administer separately for subsequent dosage adjustment.^c

May add another antihypertensive agent when necessary (gradually using half of the usual initial dosage to avoid an excessive decrease in BP).¹¹⁸

Angina

Oral

Initially, 50 mg once daily.¹¹¹

If optimum response is not achieved within 1 week, increase to 100 mg once daily.¹¹¹

Some patients may require 200 mg once daily for optimum effect.¹¹¹

AMI

Early Treatment

IV

Initially, 2.5–5 mg over 2–5 minutes.^{113 120 169}

If initial dose is tolerated, ¹¹³ then 2.5–5 mg every 2–10 minutes to a total of 10 mg over 10–15 minutes.^{113 120 169}

Oral (following IV dosage)

If the total IV dose is tolerated, administer 50 mg orally 10 minutes later, then 50 mg orally 12 hours later.^{111 113 120 169}

Continue 100 mg daily (as a single daily dose or in 2 equally divided doses) for 6–9 days (or until a contraindication [e.g., bradycardia or hypotension requiring treatment] develops or the patient is discharged).^{111 113 120 124 169}

If necessary, may reduce to 50 mg daily.^{111 113}

Oral alternative dosage

May eliminate IV doses and administer orally when safety of IV use is questionable and oral therapy is not contraindicated.^{111 120}

Administer 100 mg once daily or in 2 equally divided doses for at least 7 days^{111 120}

Late Treatment

Oral

If not initiated acutely (see AMI: Early Treatment, under Dosage and Administration), initiate long-term therapy within a few days of an AMI.¹⁶⁹

Optimum duration remains to be clearly established,^{111 120} but studies suggest optimum benefit with at least 1–3 years of therapy after infarction (if not contraindicated).^{111 113 120 122 132 134}

Indefinite continuation of therapy (unless contraindicated) has been recommended.^{169 173}

Supraventricular Tachyarrhythmias†

Paroxysmal Supraventricular Tachycardia†, Junctional Tachycardia†, Ectopic Tachycardia†, Multifocal Atrial Tachycardia†)

IV

5 mg by slow IV infusion over 5 minutes has been used.²⁷⁴ If arrhythmia persists 10 minutes after first dose and the first dose was well tolerated, give a second 5-mg dose over 5 minutes.²⁷⁴

Atrial Fibrillation†

IV

Slow IV infusion: 2.5–5 mg over 2–5 minutes as necessary to control rate, up to 10 mg over a 10- to 15-minute period.^{169 211}

Alternatively, 5 mg by slow IV infusion over 5 minutes has been used.²⁷⁴ If arrhythmia persists 10 minutes after first dose and the first dose was well tolerated, give a second 5-mg dose over 5 minutes.²⁷⁴

Monitor heart rate, BP, and ECG; discontinue when efficacy is achieved, SBP declines to <100 mm Hg, or heart rate slows to <50 bpm.¹⁶⁹

Vascular Headache†

Prevention of Common Migraine†

Oral

Dosage has not been established; in clinical studies 100 mg daily was usual effective dosage.²²⁸

Prescribing Limits

Pediatric Patients

Hypertension†

Oral

Maximum 2 mg/kg (up to 100 mg) daily.²⁵⁸

Adults

Hypertension

Monotherapy

Oral

Increasing beyond 100 mg daily usually does not result in further improvement in blood pressure control.^{111 c}

AMI

Early Treatment

IV

Maximum 10 mg over 10–15 minutes.^{113 120 169}

Supraventricular Tachyarrhythmias†

Atrial Fibrillation†

IV

Maximum 10 mg over a 10- to 15-minute period.^{169 211}

Special Populations

Hepatic Impairment

Minimal hepatic metabolism; no dosage adjustment recommended.^{111 120}

Renal Impairment

Hypertension

Oral

Modify doses and/or frequency of administration in response to the degree of renal impairment.^c

Initial dose of 25 mg daily may be necessary.¹¹¹

Measure BP just prior to the dose to ensure persistence of adequate BP reduction.¹¹¹

Cl_cr 15–35 mL/minute per 1.73 m²

Maximum 50 daily.¹¹¹

Cl_cr<15 mL/minute per 1.73 m²

Maximum 25 mg daily or 50 mg every other day.^{111 120}

Hemodialysis

May administer 25 or 50 mg after each dialysis.¹¹¹

Marked reductions in BP may occur; give under careful supervision.¹¹¹

Geriatric Patients

Hypertension

Oral

Modification of dosage may be necessary because of age-related decreases in renal function.¹¹¹

Initially, 25 mg daily may be necessary.¹¹¹

Measure BP just prior to a dose to ensure persistence of adequate BP reduction.¹¹¹

Bronchospastic Disease

Oral

Initially, 50 mg daily and use lowest possible dosage.¹¹¹ If dosage must be increased, consider administering in 2 divided doses daily to decrease peak blood levels.¹¹¹ A β₂-adrenergic agonist bronchodilator should be available.¹¹¹ (See Bronchospastic Disease under Cautions.)

Cautions for Atenolol

Contraindications

• 
  

  Patients with sinus bradycardia,^{111 118 120 220} AV block greater than first degree,^{111 118 120 220 274} cardiogenic shock,^{111 118 120 220} overt or decompensated cardiac failure. Patients with AMI not promptly and effectively controlled by 80 mg IV furosemide or equivalent therapy.^{111 118 120 220}

  
  


• 
  

  Do not use in patients with untreated pheochromocytoma.^{111 118 120}

  
  


• 
  

  Hypersensitivity to atenolol or any ingredient in the formulation.^{111 118 120 220}

  
  

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation of CHF; possible decreased exercise tolerance in patients with left ventricular dysfunction.

Initiate therapy and subsequent dosage adjustments in patients with CHF under close medical supervision. Prior to initiation of the drug, stabilize patient on other therapy (e.g., ACE inhibitor, diuretic, and/or cardiac glycoside). Symptomatic improvement may not be evident for 2–3 months after initiating therapy.

Avoid use in patients with decompensated CHF; use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with ACE inhibitors, cardiac glycosides, and/or diuretics); use with extreme caution in patients with substantial cardiomegaly.

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending cardiac failure occur; if cardiac failure continues, discontinue therapy, gradually if possible.

History of Anaphylactic Reactions

Possible increased reactivity to a variety of allergens; patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.^{111 118 120}

Calcium-channel Blocking Agents

Concomitant use may cause bradycardia, heart block, increased left ventricular and diastolic blood pressure, particularly in patients with preexisting conduction abnormalities or left ventricular dysfunction.^{111 120} (See Specific Drugs under Interactions.)

Bronchospastic Disease

Possible bronchoconstriction, especially at dosages >100 mg daily.^c Cautious use recommended in patients with bronchospastic disease (patients who do not respond to or cannot tolerate other hypotensive agents).^{111 120}

Initiate therapy with 50 mg daily and use lowest possible dosage; β₁-selectivity is not absolute.^{111 120} Twice-daily dosing and concomitant use of a β₂-adrenergic agonist bronchodilator may minimize risk of bronchospasm.^{111 120 c}

If bronchospasm occurs, reduce dosage or discontinue atenolol (gradually if possible) and administer supportive treatment.^{111 120 c}

Anesthesia and Major Surgery

Possible increased risks associated with general anesthesia.¹¹¹ (See Anesthetics, General [Myocardial Depressant] under Interactions.)

Withdrawal of β-adrenergic blocking agent prior to surgery is not recommended in most patients.¹¹¹

Correct vagal dominance (if any) with atropine (1–2 mg IV).¹¹¹

Atenolol effects can be reversed by cautious administration of β-agonists (e.g., dobutamine, isoproterenol).^{111 120}

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia, particularly tachycardia.^{111 120}

β₁-Selective atenolol does not potentiate insulin-induced hypoglycemia or delay recovery of blood glucose to normal levels.^{111 120}

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.^{111 120}

Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.^{111 120}

General Precautions

Peripheral Arterial Circulatory Disorders

May be aggravated.^{111 118 120}

Other Precautions

Atenolol shares the toxic potentials of β-adrenergic blocking agents; observe usual precautions of these agents.^c

When used in fixed combination with chlorthalidone, consider the cautions, precautions, and contraindications associated with thiazide diuretics.^{115 116 117 118}

Specific Populations

Pregnancy

Category D.^{111 118 120}

Lactation

Distributed into milk;^{103 107 111 118 120 125 129} caution if used in nursing women.^{111 118 120 151}

Pediatric Use

Safety and efficacy remain to be fully established in children;^{111 118 120} however, some experts have recommended dosages for hypertension based on current limited clinical experience.²⁵⁸

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults; however, use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.^{111 118 120}

Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary.¹¹¹ Evaluation of geriatric patients with hypertension or MI should always include assessment of renal function.^{111 120} (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Decreased clearance; use with caution and adjust dosage based on degree of renal impairment.^{111 120} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Tiredness,^{111 120} hypotension,^{111 120} heart failure,^{111 120} bradycardia,^{111 113 120 124} ventricular tachycardia,^{111 120} dizziness,^{111 120} cold extremities,^{111 120} depression,^{111 120} supraventricular tachycardia (atrial fibrillation or flutter),^{111 120} bundle branch block and major axis deviation,^{111 120} fatigue,^{111 120} dyspnea.^{111 120}

Interactions for Atenolol

Specific Drugs

Drug	Interaction	Comments
β-Adrenergic blocking agents	Potential additive effect111 120	Adjust initial and subsequent atenolol dosage downward based on clinical findings (e.g., blood pressure, heart rate)111 120
Anesthetics, general (myocardial depressant)	Increased risk of hypotension and heart failurec	Use with caution111 (see Anesthesia and Major Surgery under Cautions)
Calcium-channel blockers (e.g., verapamil, diltiazem)	Additive hypotensive effect; may be used to therapeutic advantagec Potential for bradycardia and heart block, increase in left ventricular end diastolic pressure111 120	Adjust dosage carefullyc Patients with preexisting conduction abnormalities or left ventricular dysfunction particularly susceptible111 120
Catecholamine-depleting drugs (e.g., reserpine)	Potential for additive effects (increased hypotension and marked bradycardia)111 120	Monitor closely for symptoms (e.g., vertigo, syncope, postural hypotension)111 120
Clonidine	May exacerbate rebound hypertension following discontinuance of clonidine111 120	Discontinue atenolol therapy several days before clonidine discontinuance.111 120 If replacing clonidine, delay initiation of atenolol for several days after stopping clonidine111 120
Hydralazine	Additive hypotensive effect; may be used to therapeutic advantagec	Adjust dosage carefullyc
Methyldopa	Additive or potentiated hypotensive effect; may be used to therapeutic advantagec	Adjust dosage carefully when used concurrentlyc
NSAIAs (e.g., indomethacin, aspirin)	Potential for decreased atenolol antihypertensive effect111 118 120	Studies indicate no clinically important interaction; concomitant administration appears safe and effective111 118 120

Atenolol Pharmacokinetics

Absorption

Bioavailability

50–60% following oral administration.^c

Onset

1 hour following oral administration.^{111 120} Within 5 minutes following IV administration.^{111 120}

Duration

At least 24 hours following oral administration (antihypertensive and β-adrenergic blocking effects).^{111 120} About 12 hours following IV administration (effect on heart rate).¹²⁰

Special Populations

In geriatric patients, plasma concentrations are increased.^{111 118 120}

Distribution

Extent

Well distributed into most tissues and fluids except brain and CSF.^c

Readily crosses the placenta, has been detected in cord blood.^{102 111 118 120}

Distributed into milk in concentrations higher than those in serum.^{103 107 111 118 120 125 129 131}

Plasma Protein Binding

Approximately 6–16%.^{111 118 120}

Elimination

Metabolism

Little or no hepatic metabolism.^c

Elimination Route

40–50% excreted unchanged in urine following oral administration;^c remainder in feces, principally as unabsorbed drug.^c

Half-life

6–7 hours.^c

Special Populations

In patients with Cl_cr 15–35 mL/minute per 1.73 m², plasma half-life is increased to 16–27 hours; in progressive renal impairment plasma half-life is >27 hours.^c

In geriatric patients, total clearance is decreased by about 50%, plasma half-life is prolonged.^{111 118 120}

Hemodialysis: 1–12% removed.^c

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 20–25°.¹¹¹

Tablets (Atenolol and Chlorthalidone)

Tight, light-resistant containers at 20–25°.¹¹¹

Parenteral

Injection

20–25°.¹²⁰

Protect from light.¹²⁰

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Manufacturer states that dilutions in dextrose injection, sodium chloride injection, or sodium chloride and dextrose injection are stable for 48 hours if not used immediately.¹²⁰

Drug Compatibility

Y-Site CompatibilityHID

Compatible
Meperidine HCl
Meropenem
Morphine sulfate
Incompatible
Amphotericin B cholesteryl sulfate complex

ActionsActions

• 
  

  Inhibits response to adrenergic stimuli by competitively blocking β₁-adrenergic receptors within the myocardium.^c Blocks β₂-adrenergic receptors within bronchial and vascular smooth muscle only in high doses (e.g., >100 mg daily).^c

  
  


• 
  

  Decreases resting and exercise-stimulated heart rate and reflex orthostatic tachycardia by about 25–35%.^c Slows AV nodal conduction.^c

  
  


• 
  

  No intrinsic sympathomimetic activity and little or no membrane-stabilizing effect on the heart.^c

  
  


• 
  

  Reduces BP by decreasing cardiac output, suppressing renin release, and/or decreasing sympathetic outflow from the CNS.^c

  
  


• 
  

  In patients with angina pectoris, blocks catecholamine-induced increases in heart rate, myocardial contractility, and BP, resulting in decreased myocardial oxygen consumption.^{111 120 c}

  
  


• 
  

  Possibly increases oxygen requirements in patients with heart failure due to increased left ventricular fiber length and end diastolic pressure.¹¹¹

  
  


• 
  

  Increases airway resistance (at doses >100 mg) in patients with asthma and/or COPD.^c

  
  


• 
  

  Produces little or no changes in serum insulin concentrations, time to recovery from insulin-induced hypoglycemia, or free fatty acid response to hypoglycemia.^c

  
  

Advice to Patients

• 
  

  Importance of taking medication exactly as prescribed.^c

  
  


• 
  

  Importance of not interrupting or discontinuing therapy without consulting clinician.^c

  
  


• 
  

  If a dose is missed, importance of patient taking only the next scheduled dose (i.e., the next dose should not be doubled).^c

  
  


• 
  

  Importance of advising patients with coronary artery disease to temporarily limit their physical activity when discontinuing therapy.^{111 118 120}

  
  


• 
  

  Importance of immediately informing clinician at the first sign or symptom of impending cardiac failure (e.g., weight gain, increased shortness of breath) or if any difficulty in breathing occurs.^c

  
  


• 
  

  Importance of patients undergoing major surgery informing anesthesiologist or dentist they are receiving the drug.^c

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.^c

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{111 118 120}

  
  


• 
  

  Importance of clinician informing women who are or plan to become pregnant of risk to fetus.^{111 118 120}

  
  


• 
  

  Importance of informing patient of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atenolol

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	25 mg*	Atenolol Tablets
			Tenormin	AstraZeneca
		50 mg*	Atenolol Tablets
			Tenormin (scored)	AstraZeneca
		100 mg*	Atenolol Tablets
			Tenormin	AstraZeneca
Parenteral	Injection, for IV use	0.5 mg/mL	Tenormin I.V.	AstraZeneca

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atenolol Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	50 mg with Chlorthalidone 25 mg*	Atenolol and Chlorthalidone Tablets
			Tenoretic (scored)	AstraZeneca
		100 mg with Chlorthalidone 25 mg*	Atenolol and Chlorthalidone Tablets
			Tenoretic	AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Atenolol 100MG Tablets (SANDOZ): 90/$19.99 or 180/$39.98

Atenolol 25MG Tablets (SANDOZ): 90/$14.99 or 180/$23.98

Atenolol 50MG Tablets (SANDOZ): 90/$17.99 or 180/$27.97

Atenolol-Chlorthalidone 100-25MG Tablets (MYLAN): 90/$30.99 or 180/$59.97

Atenolol-Chlorthalidone 50-25MG Tablets (MYLAN): 30/$13.99 or 90/$32.97

Tenoretic 100 100-25MG Tablets (ASTRAZENECA): 30/$86.99 or 90/$240.98

Tenoretic 50 50-25MG Tablets (ASTRAZENECA): 30/$61.99 or 90/$170.96

Tenormin 100MG Tablets (ASTRAZENECA): 30/$82.98 or 90/$227.13

Tenormin 25MG Tablets (ASTRAZENECA): 30/$61.15 or 90/$159.4

Tenormin 50MG Tablets (ASTRAZENECA): 30/$61.14 or 90/$163.78

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions September 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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122. Yusuf S, Wittes J, Friedman L. Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction. JAMA. 1988; 260:2088-93. [IDIS 246179] [PubMed 2901501]

123. ISIS-1 (First International Study of Infarct Survival) Collaborative Group. Mechanisms for the early mortality reduction produced by beta-blockade started early in acute myocardial infarction: ISIS-1. Lancet. 1988; 1:921-3. [PubMed 2895838]

124. Yusuf S, Sleight P, Rossi P et al. Reduction in infarct size, arrhythmias and chest pain by early intravenous beta blockade in suspected acute myocardial infarction. Circulation. 1983; 67(6 Part 2):I-32-41. [IDIS 171441] [PubMed 6851037]

125. Schimmel MS, Eidelman AJ, Wilschanski MA et al. Toxic effects of atenolol consumed during breast feeding. J Pediatr. 1989; 114:476-8. [IDIS 251776] [PubMed 2921694]

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127. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988; 2:349-60. [PubMed 2899772]

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129. Atkinson H, Begg EJ. Concentrations of beta-blocking drugs in human milk. J Pediatr. 1990; 116:156. [IDIS 262800] [PubMed 1967306]

130. Koren G. Concentrations of beta-blocking drugs in human milk. J Pediatr. 1990; 116:156.

131. Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk: clinical pharmacokinetic considerations. Clin Pharmacokinet. 1988; 14:217-40. [IDIS 241547] [PubMed 3292101]

132. American College of Cardiology and American Heart Association. ACC/AHA guidelines for the early management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Early Management of Patients with Acute Myocardial Infarction). Circulation. 1990; 82:664-707. [IDIS 269868] [PubMed 2197021]

133. Buck ML, Wiest D, Gillette PC et al. Pharmacokinetics and pharmacodynamics of atenolol in children. Clin Pharmacol Ther. 1989; 46:629-33. [IDIS 261662] [PubMed 2598566]

134. Goldman L, Sia STB, Cook EF et al. Costs and effectiveness of routine therapy with long-term beta-adrenergic antagonists after acute myocardial infarction. N Engl J Med. 1988; 319:152-7. [IDIS 243813] [PubMed 2898733]

135

Allergenic Extract, Bluefish

Allergenic Extract

Warning

Diagnostic and therapeutic allergenic extracts are intended to be administered by a physician who is an allergy specialist and experienced in allergenic diagnostic testing and immunotherapy and the emergency care of anaphylaxis.

This product should not be injected intravenously. Deep subcutaneous routes have been safe. Sensitive patients may experience severe anaphylactic reactions resulting in respiratory obstruction, shock, coma and/or death. (See Adverse Reactions)

Serious adverse reactions should be reported to Nelco Laboratories immediately and a report filed to: MedWatch, The FDA Medical Product Problem Reporting Program, at 5600 Fishers Lane, Rockville, Md. 20852-9787, call 1-800-FDA-1088.

Extreme caution should be taken when using allergenic extracts for patients who are taking beta-blocker medications. In the event of a serious adverse reaction associated with the use of allergenic extracts, patients receiving beta-blockers may not be responsive to epinephrine or inhaled brochodialators.(1)(See Precautions)

Allergenic extracts should be used with caution for patients with unstable or steroid-dependent asthma or underlying cardiovascular disease. (See Contraindications)

Allergenic Extract, Bluefish Description

Allergenic extracts are sterile solutions consisting of the extractable components from various biological sources including pollens, inhalants, molds, animal epidermals and insects. Aqueous extracts are prepared using cocas fluid containing NaCl 0.5%, NaHCO3 0.0275%, WFI, preservative 0.4% Phenol. Glycerinated allergenic extracts are prepared with cocas fluid and glycerin to produce a 50% (v/v) allergenic extract. Allergenic Extracts are supplied as concentrations designated as protein nitrogen units (PNU) or weight/volume (w/v) ratio. Standardized extracts are designated in Bioequivalent Allergy Units (BAU) or Allergy Units (AU). (See product insert for standardized extracts)

For diagnostic purposes, allergenic extracts are to be administered by prick-puncture or intradermal routes. Allergenic extracts are administered subcutaneously for immunotherapy injections.

Allergenic Extract, Bluefish - Clinical Pharmacology

The pharmacological action of allergenic extracts used diagnostically is based on the liberation of histamine and other substances when the allergen reacts with IgE antibodies attached to the mast cells. When allergenic extracts are used for immunotherapy, the effect is an increase in immunoglobulin G (IgG) and an increased T suppresser lymphocyte which interferes with the allergic response.(2) With repeated administration of allergenic extracts changes develop in regards to IgG and IgE production and mediator-releasing cells. The histamine release response is reduced in some patients.

Indications and Usage for Allergenic Extract, Bluefish

Allergenic extracts are indicated for use in diagnostic testing and as part of a treatment regime for allergic disease, as established by allergy history and skin test reactivity.

Allergenic extracts are indicated for the treatment of allergen specific allergic disease for use as hyposensitization or immunotherapy when avoidance of specific allergens can not be attained. The use of allergenic extracts for therapeutic purpose has been established by well-controlled clinical studies. Allergenic extracts may be used as adjunctive therapy along with pharmacotherapy which includes antihistamines, corticosteroids, and cromoglycate, and avoidance measures. Allergenic extracts for therapeutic use should be given using only the allergen selection to which the patient is allergic, has a history of exposure and are likely to be exposed to again.

Contraindications

Allergenic extracts should not be used if the patient has asthma, cardiovascular disease, emphysema, diabetes, bleeding diathesis or pregnancy, unless a specific diagnosis of type 1 allergic disease is made based on skin testing and the benefits of treatment outweigh the risks of an adverse reaction during testing or treatment. Allergenic extracts are not indicated for use in patients who are not clinically allergic or who are not skin reactive to an allergen. Allergenic extracts should be discontinued or the concentration of potency substantially reduced in patients who experience unacceptable adverse reactions.

Warnings

DO NOT INJECT INTRAVENOUSLY.

Epinephrine 1:1000 should be available.

Concentrated extracts must be diluted with sterile diluent prior to first use on a patient for treatment or intradermal testing. All concentrates of glycerinated allergenic extracts have the ability to cause serious local and systemic reactions including death in sensitive patients. Sensitive patients may experience severe anaphylactic reactions resulting in respiratory obstruction, shock, coma and /or death.(4)(See Adverse Reactions) An allergenic extract should be temporarily withheld from patients or the dose of the extract adjusted downward if any of the following conditions exist: (1) Severe symptoms of rhinitis and/or asthma (2) Infections or flu accompanied by fever and (3) Exposure to excessive amounts of clinically relevant allergen prior to a scheduled injection. When switching patients to a new lot of the same extract the initial dose should be reduced 3/4 so that 25% of previous dose is administered.

Precautions

GENERAL: Epinephrine 1:1000 should be available as well as personnel trained in administering emergency treatment. Allergenic Extracts are not intended for intravenous injections. For safe and effective use of allergenic extracts, sterile diluents, sterile vials, sterile syringes should be used and aseptic precautions observed when making a dilution and/or administering the allergenic extract injection. A sterile tuberculin syringe graduated in 0.1 ml units to measure each dose for the prescribed dilution should be used. To reduce the risk of an occurrence of adverse reactions, begin with a careful personal history plus a physical exam. Confirm your findings with scratch or intradermal skin testing.

Standardized extracts are those labeled in AU/ml units or BAU/ml units. Standardized extracts are not interchangeable with extracts previously labeled as wt/vol or PNU/ml. Before administering a standardized extract, read the accompanying insert contained with standardized extracts.

Information for Patients: All concentrates of allergenic extracts have the ability to cause serious local and systemic reactions including death in sensitive patients. Patients should be informed of this risk prior to skin testing and immunotherapy. Patients should be instructed to recognize adverse reaction symptoms that may occur and to report all adverse reactions to a physician. Patients should be instructed to remain in the office for 30 minutes during testing using allergenic extracts and at least 30 minutes after therapeutic injections using allergenic extracts.

DRUG INTERACTIONS: Some drugs may affect the reactivity of the skin; patients should be instructed to avoid medications, particularly antihistamines and sympathomimetic drugs, for at least 24 hours prior to skin testing. Antihistamines and Hydroxyzine can significantly inhibit the immediate skin test reactions as they tend to neutralize or antagonize the action of histamine.(3) This effect has been primarily documented when testing was performed within 1 to 2 hours after drug ingestion. Partial inhibition of the skin test reaction had been observed for longer periods. Epinephrine injection inhibits the immediate skin test reactions for several hours. Patients on delayed absorption antihistamine tablets should be free of such medication for 48 hours before testing. Patients using Astemizole (Hismanal) may experience prolonged suppression and should be free from such medication for up to 6 to 8 weeks prior to testing. Refer to package insert from an applicable long acting antihistamine manufacturer for additional information.

Extreme caution should be taken when using allergenic extracts on patients who are taking beta-blockers. Patients on non-selective beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.

Carcinogenesis, mutagenesis, impairment of fertility:

Long term studies in animals have not been conducted with allergenic extracts to determine their potential carcinogenicity, mutagenicity or impairment of fertility.

Pregnancy: Category C: Animal reproduction studies have not been conducted with Allergenic Extracts. It is not known whether allergenic extracts can cause fetal harm when administered to pregnant women or can affect reproduction capacity. Allergenic extracts should be given to pregnant women only if clearly needed.

Nursing Mothers: It is not known whether this drug appears in human milk. Because many drugs are detected in human milk, caution should be exercised when Allergenic Extracts are administered to a nursing woman. There are no current studies on extract components in human milk, or their effect on the nursing infant.

Pediatric Use: Allergenic extracts have been used in children over two years of age.(5)

Adverse Reactions

Adverse systemic reactions usually occur within minutes and consist primarily of allergic symptoms such as: generalized skin erythema, urticaria, pruritus, angioedema, rhinitis, wheezing, laryngeal edema, itching of nose and throat, breathlessness, dyspnea, coughing, hypotension and marked perspiration. Less commonly, nausea, emesis, abdominal cramps, diarrhea and uterine contractions may occur. Severe reactions may cause anaphylaxis or shock and loss of consciousness and rarely death.

The treatment of systemic allergic reactions is dependent upon the system complex. Antihistamines may offer relief of recurrent urticaria, associated skin reactions and gastrointestinal symptoms. Corticosteroids may provide benefit if symptoms are prolonged or recurrent. (See Overdose section)

Local Reactions consisting of erythema, itching, swelling tenderness and sometimes pain may occur at the injection site. These reactions may appear within a few minutes to hours and persist for several days. Local cold applications and oral antihistamines may be effective treatment. For marked and prolonged local reactions the use of antihistamines or anti-inflammatory medications may be dictated. Serious adverse reactions should be reported to Nelco Laboratories immediately and a report can be filed to: MedWatch, The FDA Medical Product Problem Reporting Program, at 5600 Fishers Lane, Rockville, MD 20852-9787, call 1-800-FDA-1088.

Overdosage

Overdose can cause both local and systemic reactions. An overdose may be prevented by careful observation and questioning of the patient about the previous injection.

If systemic or anaphylactic reaction, does occur, apply a tourniquet above the site of injection and inject intramuscularly or subcutaneously 0.3 to 0.5ml of 1:1000 Epinephrine Hydrochloride into the opposite arm. The dose may be repeated in 5-10 minutes if necessary. Loosen the tourniquet at least every 10 minutes. The Epinephrine Hydrochloride 1:1000 dose for infants to 2 years is 0.05 to 0.1 ml, for children 2 to 6 years it is 0.15 ml, for children 6-12 years it is 0.2 ml.

Patients unresponsive to Epinephrine may be treated with Theophylline. Studies on asthmatic subjects reveal that plasma concentrations of Theophylline of 5 to 20 µg/ml are associated with therapeutic effects. Toxicity is particularly apparent at concentrations greater than 20 µg/ml. A loading dose of Aminophylline of 5.8 mg/kg intravenously followed by 0.9 mg/kg per hour results in plasma concentrations of approximately 10 µg/ml for patients not previously receiving theophylline. (Mitenko and Ogilive, Nicholoson and Chick,1973)

Other beta-adrenergic drugs such as Isoproterenol, Isoetharine, or Albuterol may be used by inhalation. The usual dose to relieve broncho-constriction in asthma is 0.5 ml of the 0.5% solution for Isoproterenol HCl. The Albuterol inhaler delivers approximately 90 mcg of Albuterol from the mouthpiece. The usual dosage for adults and children would be two inhalations repeated every 4-6 hours. Isoetharine supplied in the Bronkometer unit delivers approximately 340 mcg Isoetharine. The average dose is one to two inhalations. Respiratory obstruction not responding to parenteral or inhaled bronchodilators may require oxygen, intubation and the use of life support systems.

Allergenic Extract, Bluefish Dosage and Administration

General Precautions

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permits.

The dosage of allergenic extracts is dependent upon the purpose of the administration. Allergenic extracts can be administered for diagnostic use or for therapeutic use.

When allergenic extracts are administered for diagnostic use, the dosage is dependent upon the method used. Two methods commonly used are scratch testing and intradermal testing. Both types of tests result in a wheal and flare response at the site of the test which usually develops rapidly and may be read in 20-30 minutes.

Diagnostic Use: Scratch Testing Method

Scratch testing is considered a simple and safe method although less sensitive than the intradermal test. Scratch testing can be used to determine the degree of sensitivity to a suspected allergen before using the intradermal test. This combination lessens the severity of response to an allergen which can occur in a very sensitive patient.

The most satisfactory testing site is the patient's back or volar surface of the arms from the axilla to 2.5 or 5cm above the wrist, skipping the anti-cubital space. If using the back as a testing site, the most satisfactory area are from the posterior axillary fold to 2.5 cm from the spinal column, and from the top of the scapula to the lower rib margins.

Allergenic extracts for diagnostic use are to be administered in the following manner: To scratch surface of skin, use a circular scarifier. Do not draw blood. Tests sites should be 4 cm apart to allow for wheal and flare reaction. 1-30 scratch tests may be done at a time. A separate sterile scratch instrument is to be used on each patient to prevent transmission of homologous serum hepatitis or other infectious agents from one patient to another.

The recommended usual dosage for Scratch testing is one drop of allergen applied to each scratch site. Do not let dropper touch skin. Always apply a control scratch with each test set. Sterile Diluent (for a negative control) is used in exactly the same way as an active test extract. Histamine may be used as a positive control. Scratch or prick test sites should be examined at 15 and 30 minutes. To prevent excessive absorption, wipe off antigens producing large reactions as soon as the wheal appears. Record the size of the reaction.

Interpretation of Scratch Test

Skin tests are graded in terms of the wheal and erythema response noted at 10 to 20 minutes. Wheal and erythema size may be recorded by actual measurement as compared with positive and negative controls. A positive reaction consists of an area of erythema surrounding the scarification that is larger than the control site. For uniformity in reporting reactions, the following system is recommended. (6)

REACTION	SYMBOL	CRITERIA
Negative	-	No wheal. Erythema absent or very slight (not more than 1 mm diameter).
One Plus	+	Wheal absent or very slight erythema present (not more than 3 mm diameter).
Two Plus	++	Wheal not more than 3mm or erythema not more than 5mm diameter.
Three Plus	+++	Wheal between 3mm and 5mm diameter, with erythema. Possible pseudopodia and itching.
Four Plus	++++	A larger reaction with itching and pain.

Diagnostic Use: Intradermal Skin Testing Method

Do not perform intradermal test with allergens which have evoked a 2+ or greater response to a Scratch test. Clean test area with alcohol, place sites 5 cm apart using separate sterile tuberculin syringe and a 25 gauge needle for each allergen. Insert needle tip, bevel up, into intracutaneous space. Avoid injecting into blood vessel, pull back gently on syringe plunger, if blood enters syringe change position of needle. The recommended dosage and range for intradermal testing is 0.05 ml of not more than 100 pnu/ml or 1:1000 w/v (only if puncture test is negative) of allergenic extract. Inject slowly until a small bleb is raised. It is important to make each bleb the same size.

Interpretation of Intradermal Test:

The patient's reaction is graded on the basis of size of wheal and flare as compared to control. Use 0.05 ml sterile diluent as a negative control to give accurate interpretation. The tests may be accurately interpreted only when the saline control site has shown a negative response. Observe patient for at least 30 minutes. Tests can be read in 15-20 minutes. Edema, erythema and presence of pseudopods, pain and itching may be observed in 4 plus reactions. For uniformity in reporting reactions the following system is recommended. (6)

REACTION	SYMBOL	CRITERIA
Negative	-	No increase in size of bleb since injection. No erythema.
One Plus	+	An increase in size of bleb to a wheal not more than 5mm diameter, with associated erythema.
Two Plus	++	Wheal between 5mm and 8mm diameter with erythema.
Three Plus	+++	Wheal between 8mm and 12mm diameter with erythema and possible pseudopodia and itching or pain.
Four Plus	++++	Any larger reaction with itch and pain, and possible diffuse blush of the skin surrounding the reaction area.

Therapeutic Use: Recommended dosage & range

Check the listed ingredients to verify that it matches the prescription ordered. When using a prescription set, verify the patient's name and the ingredients listed with the prescription order. Assess the patient's physical and emotional status prior to giving as injection. Do not give injections to patients who are in acute distress. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dosage of allergenic extracts is a highly individualized matter and varies according to the degree of sensitivity of the patient, his clinical response and tolerance to the extract administered during the early phases of an injection regimen. The dosage must be reduced when transferring a patient from non-standardized or modified extract to standardized extract. Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of immunotherapy as well as during maintenance therapy. After therapeutic injections patients should be observed for at least 20 minutes for reaction symptoms.

SUGGESTED DOSAGE SCHEDULE

The following schedule may act as a guide. This schedule has not been proven to be safe or effective. Sensitive patients may begin with smaller doses of weaker solutions and the dosage increments can be less.

STRENGTH	DOSE	VOLUME
Vial #1	1	0.05
1:100,000 w/v	2	0.10
10 pnu/ml	3	0.15
1 AU/ml	4	0.20
1 BAU/ml	5	0.30
	6	0.40
	7	0.50
Vial #2	8	0.05
1:10,000 w/v	9	0.10
100 pnu/ml	10	0.15
10 AU/ml	11	0.20
10 BAU/ml	12	0.30
	13	0.40
	14	0.50
Vial #3	15	0.05
1:1,000 w/v	16	0.10
1,000 pnu/ml	17	0.15
100 AU/ml	18	0.20
100 BAU/ml	19	0.30
	20	0.40
	21	0.50
Vial #4	22	0.05
1:100 w/v	23	0.07
10,000 pnu/ml	24	0.10
1,000 AU/ml	25	0.15
1,000 BAU/ml	26	0.20
	27	0.25
Maintenance Refill	28	0.25
1:100 w/v	29	0.25
10,000 pnu/ml	30	0.25
1,000 AU/ml	31	0.25
1,000 BAU/ml	32	0.25
subsequent doses	33	0.25

Preparation Instructions:

All dilutions may be made using sterile buffered diluent. The calculation may be based on the following ratio:

Volume desired x Concentration desired = Volume needed x Concentration available.

Example 1: If a 1:10 w/v extract is available and it is desired to use a 1:1,000 w/v extract substitute as follows:

Vd x Cd = Vn x Ca

10ml x 0.001 = Vn x 0.1

0.1 ml = Vn

Using a sterile technique, remove 0.10 ml of extract from the 1:10 vial and place it into a vial containing 9.90 ml of sterile diluent. The resulting ratio will be a 10 ml vial of 1:1,000 w/v.

Example 2: If a 10,000 pnu/ml extract is available and it is desired to use a 100 pnu/ml extract substitute as follows:

10ml x 100 = Vn x 10,000

0.1 ml = Vn

Using a sterile technique, remove 0.10 ml of extract from the 10,000 pnu/ml vial and place it into a vial containing 9.90 ml of sterile diluent. The resulting concentration will be a 10 ml vial of 100 pnu/ml.

Example 3: If a 10,000 AU/ml or BAU/ml extract is available and it is desired to use a 100 AU/ml or BAU/ml extract substitute as follows: Vd x Cd = Vn x Ca

10ml x 100 = Vn x 10,000

0.1 ml = Vn

Using a sterile technique, remove 0.10 ml of extract from the 10,000 AU/ml or BAU/ml vial and place it into a vial containing 9.90 ml of sterile diluent. The resulting concentration will be 10ml vial of 100 AU/ml or BAU/ml.

Intervals between doses: The optimal interval between doses of allergenic extract has not been definitely established. The amount of allergenic extract is increased at each injection by not more than 50%-100% of the previous amount and the next increment is governed by the response to the last injection. There are three generally accepted methods of pollen hyposensitizing therapy.

1. PRESEASONAL

Treatment starts each year 6 to 8 weeks before onset of seasonal symptoms. Maximal dose reached just before symptoms are expected. Injections discontinued during and following season until next year.

2. CO-SEASONAL

Patient is first treated during season with symptoms. Low initial doses are employed to prevent worsening of condition. This is followed by an intensive schedule of therapy (i.e. injections given 2 to 3 times per week). Fewer Allergists are resorting to this Co-seasonal therapy because of the availability of more effective, symptomatic medications that allow the patient to go through a season relatively symptom free.

3. PERENNIAL

Initially this is the same as pre seasonal. The allergen is administered twice weekly or weekly for about 20 injections to achieve the maximum tolerated dose. Then, maintenance therapy may be administered once a week or less frequently.

Duration of Treatment: The usual duration of treatment has not been established. A period of two or three years of injection therapy constitutes an average minimum course of treatment.

How is Allergenic Extract, Bluefish Supplied

Allergenic extracts are supplied with units listed as: Weight/volume (W/V), Protein Nitrogen Units (PNU/ml), Allergy Units (AU/ml) or Bioequivalent Allergy Units (BAU/ml).

Sizes:

Diagnostic Scratch: 5 ml dropper application vials

Diagnostic Intradermal: 5 ml or 10 ml vials.

Therapeutic Allergens: 5 ml, 10 ml, 50 ml multiple dose vials.

STORAGE

The expiration date of allergen extracts is listed on the container label. Store extracts upon arrival at 2° to 8°C and keep them in this range during office use.

WARRANTY:We warrant that this product was prepared and tested according to the standards of the FDA and is true to label. Because of biological differences in individuals and because allergenic extracts are manufactured to be potent and because we have no control over the conditions of use, we cannot and do not warrant either a good effect or against an ill effect following use.

REFERENCES

1 Jacobs, Robert L., Geoffrey W.Rake,Jr., et.al. Potentiated Anaphylaxis in Patients with Drug-induced Beta-adrenergic Blockade. J.Allergy & Clin. Immunol., 68(2): 125-127. August 1981.

2 Ishizaka,K.: Cellular Events in the IgE Antibody Response. Adv. in Immuno. 23:50-75, 1976.

3. Lockey, R.F., Bukantz, S.C., Allergen Immunotherapy. New York,NY: Marcel Dekker Inc., 1991.

4. Reid,M.J., Lockey,R.F., Turkeltaub,P.C., Platts-Mills,T.A.E., Survey of fatalities from skin testing and immunotherapy 1985-1989. Journal of Allergy Clin. Immunol. 92 (1): 6-15, July 1993.

5. Murray, A.B., Ferguson, A., Morrison, B., The frequency and severity of cat allergy vs dog allergy in atopic children. J. Allergy Clin. Immunolo: 72, 145-9, 1983.

6. Lockey, R.F., Bukantz, S.C., Allergen Immunotherapy. New York,NY: Marcel Dekker Inc., 1991.

CONTAINER LABELING

BLUEFISH  bluefish  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 36987-1193 Route of Administration INTRADERMAL, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BLUEFISH (BLUEFISH) BLUEFISH 0.1 g  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE   SODIUM BICARBONATE   WATER   PHENOL   GLYCERIN

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 36987-1193-1 5 mL In 1 VIAL, MULTI-DOSE None 2 36987-1193-2 10 mL In 1 VIAL, MULTI-DOSE None 3 36987-1193-3 30 mL In 1 VIAL, MULTI-DOSE None 4 36987-1193-4 50 mL In 1 VIAL, MULTI-DOSE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA102192	08/29/1972

Labeler - Nelco Laboratories, Inc. (054980867)

Registrant - Nelco Laboratories, Inc. (054980867)

Establishment
Name	Address	ID/FEI	Operations
Nelco Laboratories, Inc.		054980867	manufacture

Revised: 12/2009Nelco Laboratories, Inc.

Foltabs 800

Dosage Form: tablet
Foltabs 800 Tablets

Foltabs 800 Description

Foltabs™ 800 is a scored green round multivitamin tablet. The tablet is debossed with “ML” on the scored side

and plain on the other.

Each tablet contains:

Vitamin B6 (Pyridoxine HCl) ................................................................. 10 mg

Folic Acid ...............................................................................................800 μg

Cyanocobalamin .....................................................................................115 μg

INACTIVE INGREDIENTS: Dicalcium Phosphate Dihydrate, Microcrystalline Cellulose, Stearic Acid, Silicon Dioxide, Croscarmellose Sodium, Magnesium Stearate, Polydextrose, Hypromellose, Polyethylene Glycol, Titanium Dioxide, D&C Yellow #10, Triacetin, FD&C Blue #1, FD&C Yellow #6

Indications and Usage for Foltabs 800

Foltabs™ 800 is a multivitamin prescription supplement indicated for the use in improving the nutritional status of patients as prescribed by their physician.

Contraindications

This product is contraindicated in patients with a known hypersensitivity to any of the ingredients.

Warnings

Folic acid alone is improper therapy in the treatment of pernicious anemia and other

megaloblastic anemias where vitamin B12 is deficient.

KEEP OUT OF THE REACH OF CHILDREN. In case of accidental overdose, call a doctor or poison control center immediately.

Precautions

General

NOTICE: Contact with moisture can produce surface discoloration or erosion of

the tablet.

Folic acid in doses above 0.1 mg may obscure pernicious anemia in that hematologic remission can occur while neurological manifestations progress.

Adverse Reactions

Allergic sensitization has been reported following both oral and parenteral administration of folic acid.

Foltabs 800 Dosage and Administration

One tablet daily or as directed by a physician.

How is Foltabs 800 Supplied

FOLCAPS Tablet is a round, green-coated bisected tablet debossed 'ML' on one side and plain on the other side.

Bottles of 60 tablets ................................. NDC 68308-325-60

DISPENSE IN A TIGHT, LIGHT RESISTANT CONTAINER AS DEFINED BY THE

USP/NF WITH A CHILD RESISTANT CLOSURE. Store at controlled room

temperature 20°-25°C (68°-77°F). Excursions permitted to 15°-30°C

(59°-86°F). [See current USP].

Manufactured for:

Midlothian Laboratories

Montgomery, AL 36117

www.midlothianlabs.com

Rev. 12/09

CONTAINER LABEL

Immediate Container Label

Foltabs 800  vitamins tablets  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68308-325 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PYRIDOXINE HYDROCHLORIDE (PYRIDOXINE) PYRIDOXINE HYDROCHLORIDE 115 mg FOLIC ACID (FOLIC ACID) FOLIC ACID 800 ug CYANOCOBALAMIN (CYANOCOBALAMIN) CYANOCOBALAMIN 115 ug

Inactive Ingredients Ingredient Name Strength DIBASIC CALCIUM PHOSPHATE DIHYDRATE 160 mg

Product Characteristics Color GREEN Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code ML Contains

Packaging # NDC Package Description Multilevel Packaging 1 68308-325-10 60 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Unapproved drug other		01/01/2009

Labeler - Midlothian Laboratories (142122824)

Revised: 11/2009Midlothian Laboratories

Amturnide

Generic Name: aliskiren, amlodipine, and hydrochlorothiazide (AL is KYE ren, am LOE de peen, HYE droe klor oh THYE a zide)

Brand Names: Amturnide

What is aliskiren, amlodipine, and hydrochlorothiazide?

Aliskiren is an anti-hypertensive (blood pressure lowering) medication. It works by decreasing substances in the body that narrow blood vessels and raise blood pressure.

Amlodipine is in a group of drugs called calcium channel blockers. Amlodipine relaxes (widens) blood vessels and improves blood flow.

Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

The combination of aliskiren, amlodipine, and hydrochlorothiazide is used to treat high blood pressure (hypertension).

Aliskiren, amlodipine, and hydrochlorothiazide is usually given after other blood pressure medications have been tried without successful treatment of symptoms.

Aliskiren, amlodipine, and hydrochlorothiazide may also be used for purposes not listed in this medication guide.

What is the most important information I should know about aliskiren, amlodipine, and hydrochlorothiazide?

Do not use this medication if you are pregnant. It could harm the unborn baby. Stop using this medication and tell your doctor right away if you become pregnant. You should not take this medication if you are allergic to aliskiren (Tekturna, Tekamlo), amlodipine (Norvasc, Caduet, Exforge, Lotrel, Tribenzor, Twynsta), hydrochlorothiazide (HCTZ, HydroDiuril, Hyzaar, Vaseretic, Zestoretic, and many others), or sulfa drugs (Bactrim, Septra, Sulfatrim, SMX-TMP, and others). You should not take aliskiren, amlodipine, and hydrochlorothiazide if you have severe kidney disease or are unable to urinate, or if you are also taking itraconazole (Sporanox) or cyclosporine (Gengraf, Neoral, Sandimmune).

Before you take aliskiren, amlodipine, and hydrochlorothiazide, tell your doctor if you have kidney or liver disease, glaucoma, lupus, asthma, congestive heart failure, angina (chest pain), coronary artery disease, an electrolyte imbalance (such as low potassium or magnesium), a penicillin allergy, if you are on a low-salt diet, or if you have ever had an allergic reaction to a blood pressure medication.

Your chest pain may become worse when you first start taking the medicine or when your dose is increased. Call your doctor if your chest pain is severe or ongoing. Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

What should I discuss with my healthcare provider before taking aliskiren, amlodipine, and hydrochlorothiazide?

You should not take this medication if you are allergic to aliskiren (Tekturna, Tekamlo), amlodipine (Norvasc, Caduet, Exforge, Lotrel, Tribenzor, Twynsta), hydrochlorothiazide (HCTZ, HydroDiuril, Hyzaar, Vaseretic, Zestoretic, and many others), or sulfa drugs (Bactrim, Septra, Sulfatrim, SMX-TMP, and others). You should not take aliskiren, amlodipine, and hydrochlorothiazide if you have severe kidney disease or are unable to urinate, or if you are also taking itraconazole (Sporanox) or cyclosporine (Gengraf, Neoral, Sandimmune).

To make sure you can safely take aliskiren, amlodipine, and hydrochlorothiazide, tell your doctor if you have any of these other conditions:

• 
  

  kidney disease (or if you are on dialysis);

  
  


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  liver disease;

  
  


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  congestive heart failure;

  
  


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  angina (chest pain);

  
  


• 
  

  glaucoma;

  
  


• 
  

  systemic lupus erythematosus (SLE);

  
  


• 
  

  asthma;

  
  


• 
  

  coronary artery disease (hardened arteries);

  
  


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  an electrolyte imbalance (such as low levels of potassium or magnesium in your blood);

  
  


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  if you are allergic to penicillin;

  
  


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  if you are on a low-salt diet; or

  
  


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  if you have ever had an allergic reaction to a blood pressure medication.

  
  

FDA pregnancy category D. Do not use aliskiren, amlodipine, and hydrochlorothiazide if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. This medication can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking aliskiren, amlodipine, and hydrochlorothiazide. It is not known whether this medication passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking aliskiren, amlodipine, and hydrochlorothiazide.

How should I take aliskiren, amlodipine, and hydrochlorothiazide?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.

Your chest pain may become worse when you first start taking the medicine or when your dose is increased. Call your doctor if your chest pain is severe or ongoing.

Aliskiren, amlodipine, and hydrochlorothiazide may be taken with or without food, but take it the same way each time.

While using aliskiren, amlodipine, and hydrochlorothiazide, you may need blood tests at your doctor's office. Your blood pressure will need to be checked often. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using aliskiren, amlodipine, and hydrochlorothiazide.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking aliskiren, amlodipine, and hydrochlorothiazide. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life. Store in the original container at room temperature, away from moisture and heat.

See also: Amturnide dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include rapid heartbeats, severe dizziness, warmth or tingly feeling, and fainting.

What should I avoid while taking aliskiren, amlodipine, and hydrochlorothiazide?

Do not use potassium supplements or salt substitutes while you are taking aliskiren, amlodipine, and hydrochlorothiazide, unless your doctor has told you to. Drinking alcohol can further lower your blood pressure and may increase certain side effects of aliskiren, amlodipine, and hydrochlorothiazide.

Avoid taking with foods that are high in fat, which can make it harder for your body to absorb aliskiren, amlodipine, and hydrochlorothiazide.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Aliskiren, amlodipine, and hydrochlorothiazide side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using aliskiren, amlodipine, and hydrochlorothiazide and call your doctor at once if you have a serious side effect such as:

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  swelling in your hands, ankles, or feet;

  
  


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  feeling like you might pass out;

  
  


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  vision problems, eye pain, or seeing halos around lights;

  
  


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  low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling);

  
  


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  high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling); or

  
  


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  chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling.

  
  

Less serious side effects may include:

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  headache;

  
  


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  dizziness; or

  
  


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  stuffy nose, sore throat.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect aliskiren, amlodipine, and hydrochlorothiazide?

Tell your doctor about all other heart or blood pressure medications you are taking.

Before using aliskiren, amlodipine, and hydrochlorothiazide, tell your doctor if you regularly use other medicines that can lower blood pressure (such as sedatives, narcotic pain medicine, sleeping pills, and medicine for seizures or anxiety). They can add to the blood pressure lowering effects of aliskiren, amlodipine, and hydrochlorothiazide.

Tell your doctor about all other medicines you use, especially:

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  atorvastatin (Lipitor, Caduet);

  
  


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  cholestyramine (Questran) or colestipol (Colestid);

  
  


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  furosemide (Lasix);

  
  


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  irbesartan (Avapro);

  
  


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  lithium (Eskalith, Lithobid);

  
  


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  quinidine (Quin-G);

  
  


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  simvastatin (Zocor, Simcor, Vytorin, Juvisync);

  
  


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  tacrolimus (Prograf);

  
  


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  verapamil (Calan, Covera, Isoptin, Verelan);

  
  


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  insulin or oral diabetes medication;

  
  


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  an oral, nasal, inhaled, or injectable steroid medicine;

  
  


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  any other diuretic (water pill);

  
  


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  antifungal medication such as fluconazole (Diflucan), ketoconazole (Nizoral), miconazole (Oravig), or voriconazole (Vfend);

  
  


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  HIV or AIDS medications such as nelfinavir (Viracept), ritonavir (Norvir, Kaletra), or saquinavir (Invirase); or

  
  


• 
  

  non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others.

  
  

This list is not complete and other drugs may interact with aliskiren, amlodipine, and hydrochlorothiazide. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Amturnide resources

• Amturnide Side Effects (in more detail)
• Amturnide Dosage
• Amturnide Use in Pregnancy & Breastfeeding
• Drug Images
• Amturnide Drug Interactions
• Amturnide Support Group
• 0 Reviews for Amturnide - Add your own review/rating

• Amturnide Prescribing Information (FDA)


• Amturnide Advanced Consumer (Micromedex) - Includes Dosage Information


• Amturnide MedFacts Consumer Leaflet (Wolters Kluwer)


• Amturnide Consumer Overview

Compare Amturnide with other medications

• High Blood Pressure

Where can I get more information?

• Your pharmacist can provide more information about aliskiren, amlodipine, and hydrochlorothiazide.

See also: Amturnide side effects (in more detail)