Histatrol

Generic Name: histamine (Intradermal route)

HIS-ta-meen

Commonly used brand name(s)

In the U.S.

• Histatrol

Available Dosage Forms:

• Solution


• Injectable

Therapeutic Class: Diagnostic Agent

Uses For Histatrol

Histamine is used to help diagnose problems or disease of the stomach. This test determines how much acid your stomach produces.

How the stomach test is done: Before this medicine is given, the stomach contents are emptied through a tube. Then the dose of histamine, which is based on body weight, is injected under the skin. Five minutes later, the stomach contents are emptied and tested for acidity. This procedure may be repeated several times. An antihistamine medicine may be given before the histamine is injected to prevent a possible unwanted effect.

Histamine is to be used only under the supervision of a doctor.

Before Using Histatrol

In deciding to use a diagnostic test, any risks of the test must be weighed against the good it will do. This is a decision you and your doctor will make. Also, other things may affect test results. For this test, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

There is no specific information comparing the use of histamine in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of histamine in the elderly with use in other age groups.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this diagnostic test. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart disease or


• High blood pressure (severe) or


• Low blood pressure or


• Lung disease (especially asthma)—May make these conditions worse.

• Kidney disease (severe)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Pheochromocytoma—Histamine may cause serious damage to the brain and blood vessels.

Proper Use of Histatrol

A nurse or other trained health professional will give you this medicine in a hospital. This medicine is given through a needle placed under the skin.

Precautions While Using Histatrol

Do not swallow saliva during the test. The saliva may affect the results of the test.

Histatrol Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

• Dizziness


• fainting


• fast or pounding heartbeat


• headache (continuing or severe)


• lightheadedness


• nervousness

Less common or rare

• Bluish coloration of face


• blurred vision


• chest discomfort or pain


• convulsions (seizures)


• decrease in blood pressure (sudden)


• diarrhea (severe)


• difficulty with breathing


• flushing or redness of the face


• nausea and vomiting (severe)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Abdominal spasms or cramps


• diarrhea


• metallic taste


• nausea or vomiting


• stomach pain


• swelling or redness at the place of injection

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Histatrol resources

• Histatrol Drug Interactions
• Histatrol Support Group
• 0 Reviews · Be the first to review/rate this drug

• Histamine Phosphate Prescribing Information (FDA)

Disopyramide Phosphate

Class: Class Ia Antiarrhythmics
VA Class: CV300
CAS Number: 22059-60-5
Brands: Norpace, Norpace CR

• Mortality


• 
  

  Excessive mortality or nonfatal cardiac arrest rate (7.7%) in encainide- or flecainide-treated patients with asymptomatic non-life-threatening ventricular arrhythmias (with MI history >6 days but <2 years) in NHLBI’s long-term CAST study relative to placebo.^a (See Mortality under Cautions.)

  
  


• 
  

  Applicability of CAST findings to other populations (e.g., those without recent MI) uncertain.^a

  
  


• 
  

  Because of disopyramide’s proarrhythmic properties and lack of evidence of improved survival for any antiarrhythmic drug, reserve disopyramide for life-threatening ventricular arrhythmias.^a

  
  

Introduction

Antiarrhythmic agent (class IA).^b

Uses for Disopyramide Phosphate

Precise role in antiarrhythmic therapy has not been established.^b Some experts recommend that disopyramide should be reserved for use as an alternative drug when lidocaine, quinidine, or procainamide is ineffective or adverse effects of these drugs are intolerable.^b

Limited information is available on combination therapy with other antiarrhythmic drugs such as lidocaine, quinidine, or procainamide to treat or prevent serious, refractory arrhythmias.^b

Ventricular Arrhythmias

Suppression and prevention of recurrent life-threatening ventricular arrhythmias (e.g., sustained VT).¹¹² (See Boxed Warning.)

Because of the disopyramide’s arrhythmogenic potential and lack of evidence for improved survival for class I antiarrhythmic agents,^a use for less severe arrhythmias is not recommended.^a

Avoid treatment of asymptomatic VPCs.^a

Atrial Arrhythmias

IV disopyramide (not commercially available in the US) has been used to convert atrial fibrillation, atrial flutter, and paroxysmal atrial tachycardia† to normal sinus rhythm when electrical cardioversion is not indicated or is ineffective.^{b 127} Also used to prevent recurrence after conversion by other methods†.^b

Other antiarrhythmic drugs (e.g., amiodarone, dofetilide, flecainide, ibutilide, propafenone) are preferred^{128 129} in patients with no left ventricular dysfunction.¹²⁷

Adequate anticoagulation may be necessary before administration of disopyramide for conversion of atrial fibrillation to normal sinus rhythm, (atrial fibrillation is≥48 hours).^{127 128}

Disopyramide Phosphate Dosage and Administration

General

• 
  

  Adjust dosage carefully according to individual requirements and response and the general condition and cardiovascular status of the patient.^b

  
  


• 
  

  Initiate disopyramide therapy only in a hospital setting.¹¹²

  
  


• 
  

  ECG monitoring of cardiac function and determination of plasma concentrations are recommended, especially when given to patients with an increased risk of adverse reactions (e.g., those with severe heart disease, hypertension, hepatic or renal disease).^{a b}

  
  

Administration

Administer orally.^b

Oral Administration

Conventional capsules: Administer orally every 6 hours or at intervals according to individual requirements.^b

Extended-release capsules: Administer orally every 12 hours.^a

For rapid control of ventricular arrhythmias, conventional capsules should be used; do not use extended-release capsules.^b

Dosage

Available as disopyramide phosphate; dosage expressed in terms of disopyramide.^b

Reduce dosage in patients with moderate or severe renal insufficiency, hepatic insufficiency, cardiomyopathy, possible cardiac decompensation, AMI, and in patients weighing <50 kg.^b

Pediatric Patients

Ventricular Arrhythmias

Oral

Optimum pediatric dosage has not been established; however, dosage recommendations have been made based on clinical experience.^b

Initiate dose titration at the lower end of the recommended ranges; monitor plasma drug concentrations and therapeutic response carefully.^b

For children unable to swallow the capsules, a suspension may be extemporaneously prepared by mixing the contents of disopyramide phosphate conventional capsules in cherry syrup to produce suspensions that contain 1–10 mg of disopyramide per mL.^b The extended-release capsules should not be used for the preparation of an extemporaneous suspension.^b

Give total daily dose in equally divided doses every 6 hours or at intervals according to individual requirements.^b

Total Daily Pediatric Dosage Based on Age and Weight

Age	Total Daily Pediatric Dosage
<1 year of age	10–30 mg/kg
1–4 years of age	10–20 mg/kg
4–12 years of age	10–15 mg/kg
12–18 years of age	6–15 mg/kg

Adults

Ventricular Arrhythmias

Oral (Conventional Capsules)

Usual dosage: 400–800 mg daily, given in divided doses.¹¹²

Adults weighing ≥50 kg: Usually 150 mg every 6 hours.^{a b}

Adults weighing <50 kg: Usually 100 mg every 6 hours.^{a b}

Oral (Extended-release Capsules)

Usual dosage: 400–800 mg daily, given in divided doses.¹¹²

Adults weighing ≥50 kg: Usually 300 mg every 12 hours.^{a b}

Adults weighing <50 kg: Usually 200 mg every 12 hours.^{a b}

Rapid Control

Oral (Conventional Capsules)

Adults weighing ≥50 kg: Initially, 300 mg followed by 150 mg every 6 hours.^b

Adults weighing <50 kg: Initially, 200 mg followed by 150 mg every 6 hours.^b

If there is no therapeutic response and if no toxic effects occur within 6 hours after the initial 300-mg dose, 200-mg doses may be given every 6 hours.^b If there is no response to this dosage in 48 hours, discontinue disopyramide and initiate alternative therapy.^b

Alternatively, the patient may be hospitalized, closely evaluated, and continuously monitored while the dosage is increased to 250 or 300 mg every 6 hours.^b

Severe Refractory VT

Oral (Conventional Capsules)

Up to 400 mg every 6 hours may be required (resulting in plasma disopyramide concentrations up to 9 mcg/mL).^a

Patients should be hospitalized, closely evaluated, and continuously monitored.^a

Rapid Control In Patients with Cardiomyopathy or Possible Cardiac Decompensation

Oral (Conventional Capsules)

Do not administer an initial loading dose.^b

Do not exceed an initial dosage of 100 mg every 6 hours.^b

Carefully adjust dosage in these patients while closely monitoring for hypotension and/or CHF.^b (See CHF and Hypotension under Cautions.)

Switching from Another Class I Antiarrhythmic Agent

Oral (Conventional Capsules or Extended-release Capsules)

Administer the usual dosage of disopyramide (without an initial loading dose) 6–12 hours after the last dose of quinidine sulfate or 3–6 hours after the last dose of procainamide.^b

If withdrawal of quinidine or procainamide is likely to produce life-threatening arrhythmias, hospitalize and closely monitor patient.^b

Switching from Conventional to Extended-release Capsules

Oral (Extended-release)

Initiate usual maintenance schedule (e.g., 300 mg every 12 hours) of extended-release capsules 6 hours after the last dose of the conventional capsules.^b

Dosage Modification for Toxicity

If increased anticholinergic adverse effects occur, monitor plasma concentrations of disopyramide and adjust dosage accordingly.^a Dosage may be reduced by one-third and the same dosing interval maintained (e.g., 600 mg daily reduced to 400 mg daily).^a

Prescribing Limits

Adults

Ventricular Arrhythmias

Patients with Cardiomyopathy or Possible Cardiac Decompensation

Oral (Conventional Capsules)

Maximum initial dosage: 100 mg every 6 hours.^b

Special Populations

Hepatic Impairment

Oral

Usual dosage: 100 mg every 6 hours as conventional capsules or 200 mg every 12 hours as extended-release capsules.^b

Renal Impairment

Oral

Do not use extended-release capsules in patients with a Cl_cr ≤40 mL/minute.^b

Patients with moderately impaired renal function (Cl_cr >40 mL/minute): Usually, 100 mg every 6 hours as conventional capsules or 200 mg every 12 hours as extended-release capsules.^b

In patients with severely impaired renal function (Cl_cr ≤40 mL/minute), the usual dosage of conventional capsules is 100 mg (with or without an initial 150-mg dose) given at the following approximate intervals depending on the patient’s Cl_cr:^b

Clcr (mL/minute)	Dosage Interval
30–40	every 8 h
15–30	every 12 h
<15	every 24 h

Geriatric Patients

Select dosage with caution (generally starting at the low end of the dosing range) because of age-related decreases in hepatic, renal, and/or cardiac function, and concomitant disease and drug therapy.^a

If adverse anticholinergic effects occur, monitor plasma disopyramide concentrations and adjust dosage as needed.^a (See Dosage Modification for Toxicity under Dosage and Administration.)

Cautions for Disopyramide Phosphate

Contraindications

• 
  

  Preexisting 2nd or 3rd degree AV block (if an artificial pacemaker has not been inserted).^b

  
  


• 
  

  Cardiogenic shock.^b

  
  


• 
  

  Known hypersensitivity to disopyramide.^b

  
  

Warnings/Precautions

Warnings

Mortality

In CAST study, excessive rate of mortality and nonfatal cardiac arrest reported in patients with asymptomatic, non-life-threatening ventricular arrhythmias and recent MI (>6 days but <2 years previously) who were receiving encainide or flecainide compared with placebo.^a

Because of disopyramide’s arrhythmogenic potential and the lack of evidence for improved survival for class I antiarrhythmic agents,^{112 116 117 118} use disopyramide only for life-threatening arrhythmias.¹¹² Use in less severe arrhythmias currently is not recommended, and treatment of asymptomatic VPCs should be avoided.¹¹²

Initiate therapy only in a hospital setting.¹¹²

CHF and Hypotension

May cause or worsen CHF or produce severe hypotension.^a Hypotension occurs more commonly in patients with primary cardiomyopathy or inadequately compensated CHF.^a

Do not use in patients with uncompensated or marginally compensated CHF or hypotension unless the CHF or hypotension is secondary to cardiac arrhythmia.^a In patients with a history of heart failure, cardiac function must be carefully maintained, including optimal digitalization.^a

If hypotension occurs or CHF worsens, discontinue disopyramide and, if necessary, resume therapy at a lower dosage only after establishing adequate cardiac compensation.^a

Increased risk of severe hypotension in patients with myocarditis or other cardiomyopathy.^b Do not administer a loading dose to such patients; select initial dosage and make subsequent dosage adjustments under close supervision.^b (See Patients with Cardiomyopathy or Possible Cardiac Decompensation under Dosage and Administration.)

Arrhythmogenic Effects

Possible worsening of existing arrhythmias or occurrence of new arrhythmias, including VT and VF associated with prolonged QT interval.^{a b} Increased risk of such effects if used concomitantly with other drugs (i.e., quinidine) that prolong the QT interval.^{a b}

Atypical VT (torsades de pointes) and cardiac arrest have occurred rarely.^{128 a b}

If a QT prolongation >25% occurs and if ectopy continues, monitor patient closely.^a Consider discontinuance of disopyramide.^a

Rarely, clinically important widening (>25%) of the QRS complex has occurred;^a in such cases discontinue disopyramide.^{128 a}

Hypoglycemia

Hypoglycemia reported rarely.^{a b}

Monitor blood glucose concentrations closely in patients with compromised glucoregulatory mechanisms in the absence of food (e.g., patients with CHF, chronic malnutrition, hepatic or renal disease, those using alcohol or receiving certain drugs [e.g., β-adrenergic blockers]).^b

Concurrent Use with Other Antiarrhythmics

Reserve combined use for serious arrhythmias unresponsive to monotherapy; monitor closely.^a

Heart Block

Reduce dosage if first-degree AV heart block occurs.^b If the block persists, weigh the benefit of therapy against the potential risk of higher degrees of AV block.^b

If second- or third-degree AV block or unifascicular, bifascicular, or trifascicular block occurs, discontinue disopyramide therapy, unless the ventricular rate is adequately controlled by an artificial pacemaker.^b

Anticholinergic Effects

Possible anticholinergic effects; do not use in patients with glaucoma, myasthenia gravis, or urinary retention without instituting adequate overriding measures (e.g., pilocarpine ophthalmic drops for glaucoma, catheter drainage or operative relief for urinary retention).^a

Possible increased risk of urinary retention in males with benign prostatic hypertrophy.^a

Measure intraocular pressure before initiating therapy in patients with a family history of glaucoma.^a

May precipitate myasthenic crisis; use with caution in patients with myasthenia gravis.^a

Use with caution in geriatric patients. (See Geriatric Use under Cautions.)^a

General Precautions

Atrial Tachyarrhythmias

Possible enhanced AV conduction; patients with atrial flutter or fibrillation should be digitalized prior to administration.^b

Conduction Abnormalities

Use with caution in patients with sick sinus syndrome (including bradycardia-tachycardia syndrome), Wolff-Parkinson-White syndrome, or bundle-branch block, since effects of the drug in these conditions are unpredictable.^b

Potassium Imbalance

Correct abnormalities in serum potassium concentration before initiating therapy.^a

May be ineffective in patients with hypokalemia and toxic effects may be enhanced in patients with hyperkalemia.^a

Specific Populations

Pregnancy

Category C.^a

Lactation

Distributed into milk.¹¹² Discontinue nursing or the drug.¹¹²

Pediatric Use

Safety and efficacy not established.^a However, disopyramide has been used in children.^{a b} (See Pediatric Patients under Dosage and Administration.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^a

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.^a (See Geriatric Patients under Dosage and Administration.)

Substantially eliminated by kidneys; assess renal function periodically and adjust dosage accordingly.^a (See Renal Impairment under Dosage and Administration.)

Possible anticholinergic effects; not generally recommended for use in patients with glaucoma, urinary retention, or benign prostatic hypertrophy unless adequate overriding measures are taken.^a (See Anticholinergic Effects under Warnings.)

Hepatic Impairment

Increased plasma half-life; dosage adjustment recommended.^a (See Hepatic Impairment under Dosage and Administration.)

Patients with cardiac dysfunction are more likely to have comorbid hepatic impairment.^a

Carefully monitor ECG for prolongation of PR interval, evidence of QRS widening, or other signs of toxicity.^a

Renal Impairment

Increased plasma half-life; dosage adjustments necessary based on degree of renal impairment.^a (See Renal Impairment under Dosage and Administration.)

Carefully monitor ECG for prolongation of PR interval, evidence of QRS widening, or other signs of toxicity.^a

Not recommended for use in patients with severe renal insufficiency (Cl_cr ≤40 mL/min).^a

Common Adverse Effects

Anticholinergic effects (e.g., dry mouth, urinary hesitancy, constipation, blurred vision, dry nose/eyes/throat), urinary frequency/urgency, urinary retention, nausea, pain/bloating/gas, dizziness, general fatigue/muscle weakness, headache, malaise, aches/pains.^{a b}

Interactions for Disopyramide Phosphate

Appears to be metabolized principally by CYP3A4.^a

Drugs Affecting Hepatic Microsomal Enzymes

Inducers of hepatic microsomal enzymes: Potential pharmacokinetic interaction (decreased plasma disopyramide concentrations).^{a b} When used concomitantly, closely monitor serum disopyramide concentrations to avoid subtherapeutic concentrations.^b

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma disopyramide concentrations).^a

Specific Drugs

Drug	Interaction	Comments
Antiarrhythmic agents (e.g., quinidine, procainamide, lidocaine, encainide, flecainide, propafenone, propranolol)	Possible additive or antagonistic cardiac effects; toxic effects may be additiveb Potential for severe negative inotropic effects or enhanced conduction prolongation, especially in cardiac decompensationa Concomitant use with quinidine may result in slight increases in plasma disopyramide concentrations and slight decreases in plasma quinidine concentrations112	Reserve concomitant use for the management of life-threatening arrhythmias unresponsive to monotherapy; monitor closelyb a
Anticholinergic agents	Possible additive effectsb
Diazepam	No interaction noted in healthy individualsa
Digoxin	Concomitant use does not appear to increase serum digoxin concentrations112
Macrolide antibiotics (e.g., erythromycin, clarithromycin)	Increased plasma disopyramide concentrations and increased risk of serious toxicity (e.g., prolongation of the QT-interval, widening of the QRS complex, polymorphic ventricular tachycardia, ventricular fibrillation)112 115 126 a b	Close monitoring recommended112 a
Phenytoin	Potential for increased metabolism of disopyramideb	Monitor serum disopyramide concentrations closely to avoid subtherapeutic concentrationsb
Verapamil	Potential for additive negative inotropic effectsb	Concomitant use not recommended b Discontinue disopyramide 48 hours prior to initiating verapamil therapy; do not reinstitute disopyramide until 24 hours after verapamil has been discontinuedb

Disopyramide Phosphate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed (60–83%) after oral administration.^b

Bioavailability of disopyramide from the extended-release and conventional capsules appears similar.^a

Peak plasma concentrations attained in 2–2.5 or 4.9 hours after oral administration of conventional or extended-release capsules, respectively.^{a b}

Onset

Onset of action usually is within 0.5–3 hours after oral administration of a single 300-mg dose (conventional capsules).^a

Duration

Antiarrhythmic effect persists 1.5–8.5 hours after oral administration of conventional capsules.^b

Plasma Concentrations

Plasma disopyramide concentrations of approximately 2–4 mcg/mL generally required to suppress ventricular arrhythmias; concentrations up to 9 mcg/mL have been required in a limited number of patients with severe refractory VT.^{a b}

Plasma concentrations >9 mcg/mL associated with toxic effects.^b

Distribution

Extent

Distributed throughout the extracellular body water; not extensively bound to tissues.^b

Equally distributed between plasma and erythrocytes.^b

Disopyramide crosses the placenta and is distributed into milk.^{a b}

Plasma Protein Binding

Approximately 50–65%; decreases as the concentration of disopyramide and its metabolites increase.^b

Special Populations

In patients with renal insufficiency, the volume of distribution is slightly decreased.^b

Patients with AMI (without CHF) may have lower peak plasma concentrations and smaller volumes of distribution compared with healthy individuals.^b

Elimination

Metabolism

Metabolized in the liver to an N-monodealkylated metabolite and other unidentified metabolites.^b

Plasma concentration of the N-monodealkylated metabolite is approximately 10% of the concentration of disopyramide.^b

The N-monodealkylated metabolite has less antiarrhythmic activity but greater anticholinergic activity than does disopyramide.^b

CYP3A4 involved in metabolism.^a

Elimination Route

After oral administration, 50% of an oral dose excreted in urine as unchanged drug, 20% as the N-monodealkylated metabolite, and about 10% as unidentified metabolites; about 10% is excreted in feces as unchanged drug and metabolites.^{a b}

Urinary pH apparently does not affect the rate of renal excretion.^b

Half-life

Conventional capsules: Elimination half-life 4–10 hours.^a

Extended-release capsules: Elimination half-life 6.9–16.4 hours.^a

Special Populations

Plasma half-life prolonged in patients with hepatic or renal insufficiency.^b

In patients with Cl_cr <40 mL/minute, plasma half-life ranged from 8–18 hours.^b

Disopyramide is removed by hemodialysis.^b

In patients with heart disease, including left ventricular dysfunction, the mean plasma half-life was slightly prolonged to 7.8 hours (range: 5–9.5 hours).^a

Stability

Storage

Oral

Capsules (Conventional and Extended-release)

25°C (may be exposed to 15–30°C).^a

Suspension

Oral suspensions of disopyramide phosphate prepared extemporaneously from conventional capsules of the drug and cherry syrup at concentrations ranging from 1–10 mg/mL reportedly are stable for 1 month when stored at 2–8°C.^b

Dispense in amber glass bottles.^b

ActionsActions

• 
  

  A class I (membrane-stabilizing) antiarrhythmic agent with actions similar to those of procainamide and quinidine.^b

  
  


• 
  

  Regarded as a myocardial depressant because it decreases myocardial excitability and conduction velocity, and may depress myocardial contractility.^b

  
  


• 
  

  Possesses anticholinergic properties, which may modify the direct myocardial effects of the drug.^b

  
  


• 
  

  Exact mechanism of antiarrhythmic action has not been established; is believed to combine with fast sodium channels in their inactive state and thereby inhibit recovery after repolarization in a time- and voltage-dependent manner that is associated with subsequent dissociation of the drug from the sodium channels.^b

  
  


• 
  

  Exhibits electrophysiologic effects characteristic of class IA antiarrhythmic agents (i.e., exhibits intermediate rates of attachment and dissociation transmembrane sodium channels).^b

  
  


• 
  

  Suppresses automaticity in the His-Purkinje system.^b

  
  


• 
  

  Decreases the automaticity of ectopic atrial and ventricular pacemakers, shortens or does not change the sinus node recovery time, and decreases conduction velocity in the atria and ventricles.^b

  
  


• 
  

  Has little effect on conduction velocity through the AV node or the His-Purkinje system, but accessory pathway conduction velocity is decreased.^b

  
  


• 
  

  Generally prolongs the effective refractory period (ERP) of the atria and the ventricles.^b

  
  


• 
  

  Usually has little effect on the ERP of the AV node or the His-Purkinje system; however, the effect on the AV node is unpredictable in patients with preexisting conduction disturbances.^b

  
  


• 
  

  Generally causes little or no prolongation of the PR interval or the QRS complex, but the QT interval or QT interval corrected for rate (QT_c) may be prolonged.^b

  
  


• 
  

  Generally has little effect on resting sinus rate and has a direct negative inotropic effect on the heart.^b

  
  


• 
  

  Usually decreases cardiac output 10–15% in patients without compromised myocardial function.^b

  
  


• 
  

  It has not been established whether disopyramide has local anesthetic properties.^b

  
  

Advice to Patients

• 
  

  Potential for toxicity (e.g., cardiovascular, anticholinergic).^a

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^a

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.^a

  
  


• 
  

  Importance of informing patients of other important precautionary information.^a (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

Disopyramide Phosphate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	100 mg (of disopyramide)*	Disopyramide Phosphate Capsules	Sandoz, Teva, Watson
			Norpace	Searle
		150 mg (of disopyramide)*	Disopyramide Phosphate Capsules	Sandoz, Teva, Watson
			Norpace	Searle
	Capsules, extended-release	100 mg (of disopyramide)*	Disopyramide Phosphate Extended-Release Capsules	Ethex
			Norpace CR	Searle
		150 mg (of disopyramide)*	Disopyramide Phosphate Extended-release Capsules	Ethex
			Norpace CR	Searle

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.

Disopyramide Phosphate 100MG Capsules (WATSON LABS): 90/$46.99 or 270/$119.98

Disopyramide Phosphate 150MG Capsules (WATSON LABS): 30/$28.79 or 90/$60.42

Norpace 100MG Capsules (PFIZER U.S.): 90/$149.99 or 270/$430.98

Norpace 150MG Capsules (PFIZER U.S.): 30/$59.99 or 90/$155.97

Norpace CR 100MG 12-hr Capsules (PFIZER U.S.): 60/$114.99 or 180/$321.97

Norpace CR 150MG 12-hr Capsules (PFIZER U.S.): 60/$140.99 or 180/$402.98

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 April 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

51. Meinertz T, Langer KH, Kasper W et al. Disopyramide-induced intrahepatic cholestasis. Lancet. 1977; 2:828-9. [IDIS 76520] [PubMed 71640]

52. Riccioni N, Bozzi L, Susini N et al. Disopyramide-induced intrahepatic cholestasis. Lancet. 1977; 2:1362-3. [IDIS 77286] [PubMed 74773]

100. Haworth E, Burroughs AK. Disopyramide and warfarin interaction. Br Med J. 1977; 2:866-7. [PubMed 922330]

101. Ryll C, Davis LJ. Warfarin-disopyramide interaction? Drug Intell Clin Pharm. 1979; 13:260.

102. Sylven C, Anderson P. Evidence that disopyramide does not interact with warfarin. BMJ. 1983; 286:1181. [IDIS 169731] [PubMed 6404381]

103. Mangini RJ, ed. Drug interaction facts. St. Louis: JB Lippincott Co; 1984(Jul):41.

104. Moore AR. Disopyramide and warfarin. Br Med J. 1977; 29:1158.

105. Edmonds ME, Hayler AM, Holt DW. Untitled. (A case of intra-hepatic cholestasis after disopyramide therapy.) Eur J Clin Pharmacol. 1980; 18:285-6. Letter. (IDIS 124932)

106. Bakris GL, Cross PD, Hammarsten JE. Disopyramide-associated liver dysfunction. Mayo Clin Proc. 1983; 58:265-7. [IDIS 169726] [PubMed 6834895]

107. Craxi A, Gatto G, Maringhini A et al. Disopyramide and cholestasis. Ann Intern Med. 1980; 93(1 Part 1):150-1. [IDIS 122061] [PubMed 7396302]

108. Doody PT. Disopyramide hepatotoxicity and disseminated intravascular coagulation. South Med J. 1982; 75:496-7. [IDIS 150092] [PubMed 7071649]

109. Scheinman SJ, Poll DS, Wolfson S. Acute cardiac failure and hepatic ischemia induced by disopyramide phosphate. Yale J Biol Med. 1980; 53:361-6. [PubMed 7222741]

110. Antonelli D, Koltun B, Barzilay J. Acute hepatotoxic effect of disopyramide. Chest. 1984; 86:274. [IDIS 188645] [PubMed 6744970]

111. Tonkin AM, Joel SE, Reynolds JL. Unusual hepatocellular and cardiovascular complications of disopyramide. Chest. 1980; 77:125. [IDIS 109081] [PubMed 7351137]

112. Searle. Norpace and Norpace CR (disopyramide phosphate) prescribing information. Chicago, IL; 1997 Apr 4.

113. Epstein A, Barland P. The diagnostic value of antihistone antibodies in drug-induced lupus erythematosus. Arthritis Rheum. 1985; 28:158-62. [IDIS 196264] [PubMed 3882094]

114. Wanner WR, Irvin WS. Disopyramide and antinuclear antibodies. Am Heart J. 1981; 101:687-9. [IDIS 131129] [PubMed 6971570]

115. Ragosta M, Weihl AC, Rosenfeld LE. Potentially fatal interaction between erythromycin and disopyramide. Am J Med. 1989; 86:465-6. [IDIS 253377] [PubMed 2467560]

116. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction: an overview of results from randomized controlled trials. JAMA. 1993; 270:1589-95. [IDIS 320343] [PubMed 8371471]

117. Pratt CM, Moye L. The Cardiac Arrhythmia Suppression Trial: implications for antiarrhythmic drug development. J Clin Pharmacol. 1990; 30:967-74. [IDIS 274583] [PubMed 2122983]

118. Hine LK, Laird NM, Hewitt P et al. Meta-analysis of empirical long-term antiarrhythmic therapy after myocardial infarction. JAMA. 1989; 262:3037-40. [IDIS 260965] [PubMed 2509746]

119. The Cardiac Arrhythmia Suppression Trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989; 321:406-12. [IDIS 257848] [PubMed 2473403]

120. Ruskin JN. The Cardiac Arrhythmia Suppression Trial (CAST). N Engl J Med. 1989; 321:386-8. [IDIS 257833] [PubMed 2501683]

121. Vlay SC. Lessons from the past and reflections on the Cardiac Arrhythmia Suppression Trial. Am J Cardiol. 1990; 65:112-3. [PubMed 1688480]

122. Pratt CM, Brater DC, Harrell FE Jr et al. Clinical and regulatory implications of the Cardiac Arrhythmia Suppression Trial. Am J Cardiol. 1990; 65:103-5. [PubMed 1688479]

123. Morganroth J, Bigger JT Jr, Anderson JL. Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available. Am J Cardiol. 1990; 65:40-8. [PubMed 1688481]

124. Pratt C, Ward DE, Camm AJ. Lessons from the cardiac arrhythmia suppression trial. BMJ. 1989; 299:805-6. [IDIS 259519] [PubMed 2510839]

125. Coyle JD, Schaal SF. An interim perspective on the removal of encainide and flecainide from the Cardiac Arrhythmia Suppression Trial. DICP. 1989; 23:478-9. [IDIS 254807] [PubMed 2500783]

126. Paar D, Terjung B, Sauerbruch T. Life-threatening interaction between clarithromycin and disopyramide. Lancet. 1997; 349:326-7. [IDIS 380134] [PubMed 9024381]

127. American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: advanced cardiovascular life support. Circulation. 2000; 102(Suppl I):I86-171.

128. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I):IV1-211.

129. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Circulation. 2006; 114:e257-354. [PubMed 16908781]

a. Searle. Norpace and Norpace CR (disopyramide phosphate) prescribing information. Chicago, IL; 2001 Sept.

b. AHFS drug information 2007. McEvoy GK, ed. Disopyramide Phosphate. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1584-7.

More Disopyramide Phosphate resources

• Disopyramide Phosphate Side Effects (in more detail)
• Disopyramide Phosphate Use in Pregnancy & Breastfeeding
• Drug Images
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• Disopyramide Phosphate Support Group
• 4 Reviews for Disopyramide Phosphate - Add your own review/rating

• Disopyramide Prescribing Information (FDA)


• disopyramide Concise Consumer Information (Cerner Multum)


• disopyramide Advanced Consumer (Micromedex) - Includes Dosage Information


• Disopyramide MedFacts Consumer Leaflet (Wolters Kluwer)


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• Norpace CR Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Disopyramide Phosphate with other medications

• Arrhythmia

pennyroyal

Generic Name: pennyroyal (PEH nee roy al)

Brand Names:

What is pennyroyal?

The use of pennyroyal in cultural and traditional settings may differ from concepts accepted by current Western medicine. When considering the use of herbal supplements, consultation with a primary health care professional is advisable. Additionally, consultation with a practitioner trained in the uses of herbal/health supplements may be beneficial, and coordination of treatment among all health care providers involved may be advantageous.

Pennyroyal is also known as Mentha pulegium, pulegium, American pennyroyal, run-by-the-ground, lurk-in-the-ditch, pudding grass, piliolerial, mosquito plant, squaw balm, and squawmint tickweed.

Pennyroyal has been used for digestive disorders, liver and gallbladder disorders, gout, colds, increased urination, as an insect repellant, to induce menstruation, and topically for skin diseases.

Since the use of pennyroyal oil has been associated with serious, even fatal, liver and kidney damage, oral or topical use of pennyroyal oil is generally not recommended.

Pennyroyal has not been evaluated by the FDA for safety, effectiveness, or purity. All potential risks and/or advantages of pennyroyal may not be known. Additionally, there are no regulated manufacturing standards in place for these compounds. There have been instances where herbal/health supplements have been sold which were contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.

Pennyroyal may also have uses other than those listed in this product guide.

What is the most important information I should know about pennyroyal?

Since the use of pennyroyal oil has been associated with serious, even fatal, liver and kidney damage, oral or topical use of pennyroyal oil is generally not recommended.

Pennyroyal oil has been associated with cases of severe liver and kidney damage. Notify your doctor immediately if you develop nausea, vomiting, abdominal pain, unusual fatigue, loss of appetite, yellow skin or eyes, itching, dark urine, clay colored stools, or little or no urine. These symptoms may be early signs of liver or kidney damage.

Do not take pennyroyal without first talking to your doctor if you are pregnant or could become pregnant. In large doses, pennyroyal has been reported to cause abortion. Fatalities have resulted from the doses of oil required to exert an abortifacient effect.

Pennyroyal has not been evaluated by the FDA for safety, effectiveness, or purity. All potential risks and/or advantages of pennyroyal may not be known. Additionally, there are no regulated manufacturing standards in place for these compounds. There have been instances where herbal/health supplements have been sold which were contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.

What should I discuss with my healthcare provider before taking pennyroyal?

Before taking pennyroyal, talk to your doctor, pharmacist, or health care professional if you have allergies (especially to plants), have any medical condition, or if you take other medicines or other herbal/health supplements. Pennyroyal may not be recommended in some situations.

Do not take pennyroyal without first talking to your doctor if you are pregnant or could become pregnant. In large doses, pennyroyal has been reported to cause abortion. Fatalities have resulted from the doses of oil required to exert an abortifacient effect. Do not take pennyroyal without first talking to your doctor if you are breast-feeding a baby. It is also not known whether pennyroyal will harm a nursing infant. There is no information available regarding the use of pennyroyal by children. Do not give any herbal/health supplement to a child without first talking to the child's doctor.

How should I take pennyroyal?

The use of pennyroyal in cultural and traditional settings may differ from concepts accepted by current Western medicine. When considering the use of herbal supplements, consultation with a primary health care professional is advisable. Additionally, consultation with a practitioner trained in the uses of herbal/health supplements may be beneficial, and coordination of treatment among all health care providers involved may be advantageous.

Since the use of pennyroyal oil has been associated with serious, even fatal, liver and kidney damage, oral or topical use of pennyroyal oil is generally not recommended.

If you choose to take pennyroyal, use it as directed on the package or as directed by your doctor, pharmacist, or other health care provider.

Standardized extracts and tinctures of herbal/health supplements may provide a more reliable dose of the product.

To ensure the correct dose, measure the liquid forms of pennyroyal with a dropper or a dose-measuring spoon or cup.

Some forms of pennyroyal can be brewed to form a tea for drinking.

Do not use different formulations (e.g., liquids, teas, and others) of pennyroyal at the same time, unless specifically directed to do so by a health care professional. Using different formulations together increases the risk of an overdose of pennyroyal.

Store pennyroyal as directed on the package. In general, pennyroyal should be protected from light.

What happens if I miss a dose?

Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra pennyroyal 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.

Symptoms of a pennyroyal overdose have included abdominal pain, nausea, vomiting, diarrhea, lethargy, agitation, delirium, seizures, fever, increased blood pressure and pulse rate, rash, paralysis, liver damage, kidney damage, unconsciousness, and death.

What should I avoid while taking pennyroyal?

Follow your healthcare provider's instructions about any restrictions on food, beverages, or activity.

Pennyroyal side effects

Although rare, allergic reactions to pennyroyal may occur. Stop taking pennyroyal and seek emergency medical attention if you experience symptoms of a serious allergic reaction including difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives.

Pennyroyal oil has been associated with cases of severe liver and kidney damage. Notify your doctor immediately if you develop nausea, vomiting, abdominal pain, unusual fatigue, loss of appetite, yellow skin or eyes, itching, dark urine, clay colored stools, or little or no urine. These symptoms may be early signs of liver or kidney damage.

Stop taking pennyroyal and call your healthcare provider at once if you have a serious side effect such as:

• 
  

  abdominal pain, nausea, vomiting, diarrhea;

  
  


• 
  

  lethargy, paralysis, and unconsciousness;

  
  


• 
  

  agitation and delirium;

  
  


• 
  

  seizures;

  
  


• 
  

  fever;

  
  


• 
  

  increased blood pressure and pulse rate; and

  
  


• 
  

  rash.

  
  

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 pennyroyal?

Interactions between pennyroyal and other prescription or over-the-counter medicines or herbal/health supplements have not been reported. Talk to your doctor, pharmacist, or health care professional before taking pennyroyal if you are taking any other medicines or supplements.

More pennyroyal resources

• Pennyroyal Drug Interactions
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• Pennyroyal Natural MedFacts for Professionals (Wolters Kluwer)


• Pennyroyal Natural MedFacts for Consumers (Wolters Kluwer)

Compare pennyroyal with other medications

• Gout
• Herbal Supplementation
• Indigestion
• Overactive Bladder
• Premenstrual Dysphoric Disorder
• Skin Rash

Where can I get more information?

• Consult with a licensed healthcare professional before using any herbal/health supplement. Whether you are treated by a medical doctor or a practitioner trained in the use of natural medicines/supplements, make sure all your healthcare providers know about all of your medical conditions and treatments.

Minims Proxymetacaine and Fluorescein

Minims*

Proxymetacaine & Fluorescein

Proxymetacaine Hydrochloride

BP 0.5% w/v and Fluorescein Sodium BP 0.25% w/v

About Minims Proxymetacaine & Fluorescein

The name of this medicine is Minims Proxymetacaine & Fluorescein. Each Minims unit contains proxymetacaine hydrochloride in a concentration of 0.5% w/v and fluorescein sodium in a concentration of 0.25% w/v. The solution also contains purified water, providone K30, sodium hydroxide and hydrochlorid acid. Each Minims unit is a sterile, single-use container which holds approximately 0.5ml of solution. Each carton contains 20 Minims units. Proxymetacaine is a local anaesthetic which temporarily numbs the surface of the eye. Fluorescein temporarily colours your eyes orange or green and helps your doctor or eye specialist to examine them.

Who makes Minims Proxymetacaine & Fluorescein ?

Minims Proxymetacaine & Fluorescein is manufactured by

Laboratoire Chauvin S.A. ZI Ripotier,

07200/Aubenas,

France

The Marketing Authorisations for Minims Proxymetacaine & Fluorescein (PL 0033/0152) is held by

Chauvin Pharmaceuticals Ltd.

106 London Road,

Kingston-Upon-Thames

KT2 6TN

England

What is Minims Proxymetacaine & Fluorescein?

Minims Proxymetacaine & Fluorescein is used to numb and stain the surface of the eye, for a short time only, to allow a variety of procedures to be performed. Most often, Minims Proxymetacaine & Fluorescein is used to allow your doctor or eye specialist to measure the pressure inside your eye or to perform minor operations such as the removal of foreign bodies. This product is not intended for use as a long term treatment for painful eye conditions.

Before using Minims Proxymetacaine & Fluorescein

Are you allergic to any of the substances mentioned in the section "About Minims Proxymetacaine & Fluorescein"?

Do you suffer from heart disease?

Do you have an over-active thyroid gland?

If the answer to any of these questions is yes, you should tell your doctor or eye specialist before using this product.

If you are pregnant (or think you might be) or if you are breast feeding, you should tell your doctor or eye specialist before Minims Proxymetacaine & Fluorescein is used. You may still receive this eye drop but it is possible that an alternative may be used.

Minims Proxymetacaine & Fluorescein may cause mild stinging when the drops are first added. You sight may also become blurred for a short time. Make sure that you do not drive or operate machinery until your sight has returned to normal.

Minims Proxymetacaine & Fluorescein is not intended for long term use. Frequent use of local anaesthetic in the eye over long periods of time may affect your eyesight.

This product should not be used in premature babies.

Using Minims Proxymetacaine & Fluorescein

The doctor or eye specialist will put the drops in for you. One or two drops will be instilled into your eye immediately before the procedure. You may be asked to press on the inner corners of your eyes for a minute to stop the solution draining into your nose and throat, through the tear ducts.

Your eye will remain numb for up to 30 minutes. It is important not to rub your eye and to keep it free of dust during the time your eye is numb.

Your doctor or eye specialist will make sure that your eye is properly protected.

If too much stain has been put in to your eye it may be washed away using a sterile saline solution.

The Minims unit should be thrown away after a single use, even if some solution remains.

It is very unlikely that you will suffer an overdose from Minims.

Proxymetacaine & Fluorescein, but if you suddenly feel unwell after receiving the drops, tell your doctort or eye specialist.

After using Minims Proxymetacaine & Fluorescein

Minims Proxymetacaine & Fluorescein may cause allergic reaction wich have occasionally occured. These can affect the cornea (the clear membrane covering the front of the eye) and the iris. Your doctor or eye specialist will be able to tell you if an allergic reaction occurs. Other possible side effects which are very rare, include redness and irriatation of the eye, swelling around the eye, rarely difficulty in breathing and symptoms of shock and itchy skin rash with raised eye blotches.

Tell your doctor or eye specialist if you suffer from any unwanted effects after using Minims Proxymetacaine & Fluoresceinthat are not mentioned in this leaflet.

Storing Minims Proxymetacaine & Fluorescein

• The expiry date is printed on each Minims unit overwrap and on the carton label. Do not use it after this date.


• Minims Proxymetacaine & Fluorescein should be stored in a refrigerator at 2-8°C and prevented from freezing.


• If necessary, the product may be stored at temperatures not exceeding 25°C for up to 1 month only, in which case a label bearing the relevant expiry date will be affixed to the carton label.

This leaflet applies to Minims Proxymetacaine & Fluorescein only, but it does not contain all the information that is known about it. If you have any questions or are not sure about anything, ask a doctor, eye specialist or pharmacist.

* Trade Mark

Date of Preparation: January 1999.

Date of Partial Revision: August 2005.

Chauvin Pharmaceuticals Ltd

106 London Road

Kingston-Upon-Thames

KT2 6TN

England

Tel:020 8781 2900

Fax:020 8781 2901

Art.76439 0504107/4

Pancreaze

pancrelipase

Dosage Form: capsule
FULL PRESCRIBING INFORMATION

Indications and Usage for Pancreaze

Pancreaze (pancrelipase) is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions.

Pancreaze Dosage and Administration

Dosage

Pancreaze is not interchangeable with other pancrelipase products.

Pancreaze is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of Pancreaze should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet (see Limitations on Dosing below).

Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences.1, 2, 3 Pancreaze should be administered in a manner consistent with the recommendations of the Conferences provided in the following paragraphs. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.

Infants (up to 12 months)

Infants may be given 2,000 to 4,000 lipase units per 120 mL of formula or per breast-feeding. Do not mix Pancreaze capsule contents directly into formula or breast milk prior to administration [see Dosage and Administration (2.2)].

Children Older than 12 Months and Younger than 4 Years

Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal for children less than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Children 4 Years and Older and Adults

Enzyme dosing should begin with 500 lipase units/kg of body weight per meal for those older than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Usually, half of the prescribed Pancreaze dose for an individualized full meal should be given with each snack. The total daily dose should reflect approximately three meals plus two or three snacks per day.

Enzyme doses expressed as lipase units/kg of body weight per meal should be decreased in older patients because they weigh more but tend to ingest less fat per kilogram of body weight.

Limitations on Dosing

Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines.1, 2, 3

If symptoms and signs of steatorrhea persist, the dosage may be increased by a healthcare professional. Patients should be instructed not to increase the dosage on their own. There is great inter-individual variation in response to enzymes; thus, a range of doses is recommended. Changes in dosage may require an adjustment period of several days. If doses are to exceed 2,500 lipase units/kg of body weight per meal, further investigation is warranted.

Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Doses greater than 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures, indicative of fibrosing colonopathy, in children with cystic fibrosis less than 12 years of age [see Warnings and Precautions (5.1)]. Patients currently receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.

Administration

Pancreaze should always be taken as prescribed by a healthcare professional.

Infants (up to 12 months)

Pancreaze should be administered to infants immediately prior to each feeding, using a dosage of 2,000 to 4,000 lipase units per 120 mL of formula or per breast-feeding. Contents of the capsule may be sprinkled on small amounts of acidic soft food with a pH of 4.5 or less (e.g., applesauce) and given to the infant within 15 minutes. Contents of the capsule may also be administered directly to the mouth. Administration should be followed by breast milk or formula. Contents of the capsule should not be mixed directly into formula or breast milk as this may diminish efficacy. Care should be taken to ensure that Pancreaze is not crushed or chewed or retained in the mouth, to avoid irritation of the oral mucosa.

Children and Adults

Pancreaze should be taken during meals or snacks, with sufficient fluid. Pancreaze capsules and capsule contents should not be crushed or chewed. Capsules should be swallowed whole.

For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled on small amounts of acidic soft food with a pH of 4.5 or less (e.g., applesauce). The Pancreaze-soft food mixture should be swallowed immediately without crushing or chewing, and followed with water or juice to ensure complete ingestion. Care should be taken to ensure that no drug is retained in the mouth.

Dosage Forms and Strengths

The active ingredient in Pancreaze evaluated in clinical trials is lipase. Pancreaze is dosed by lipase units.

Pancreaze is available in 4 color coded capsule strengths.

Other active ingredients include protease and amylase. Each Pancreaze capsule strength contains the specified amounts of lipase, protease, and amylase as follows:

• 4,200 USP units of lipase; 10,000 USP units of protease; 17,500 USP units of amylase capsules have a yellow opaque body and clear cap, printed with "McNEIL" and "MT 4"


• 10,500 USP units of lipase; 25,000 USP units of protease; 43,750 USP units of amylase capsules have a pink opaque body and clear cap, printed with "McNEIL" and "MT 10"


• 16,800 USP units of lipase; 40,000 USP units of protease; 70,000 USP units of amylase capsules have a salmon opaque body and clear cap, printed with "McNEIL" and "MT 16"


• 21,000 USP units of lipase; 37,000 USP units of protease; 61,000 USP units of amylase capsules have a white opaque body and cap, printed with "McNEIL" and "MT 20"

Contraindications

None.

Warnings and Precautions

Fibrosing Colonopathy

Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.4,5 Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures in children less than 12 years of age.1 Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs.1 It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day [see Dosage and Administration (2.1)].

Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.

Potential for Irritation to Oral Mucosa

Care should be taken to ensure that no drug is retained in the mouth. Pancreaze should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss or enzyme activity [see Dosage and Administration (2.2) and Patient Counseling Information (17)]. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled to a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce. The Pancreaze-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.

Potential for Risk of Hyperuricemia

Caution should be exercised when prescribing Pancreaze to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.

Potential Viral Exposure from the Product Source

Pancreaze is sourced from pancreatic tissue from swine used for food consumption. Although the risk that Pancreaze will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.

Allergic Reactions

Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase). The risks and benefits of continued Pancreaze treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.

Adverse Reactions

The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions [see Warnings and Precautions (5)]

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 the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The short-term safety of Pancreaze was assessed in two clinical trials conducted in 57 patients with exocrine pancreatic insufficiency (EPI) due to CF. Study 1 was conducted in 40 patients, ages 8 years to 57 years; Study 2 was conducted in 17 patients, ages 6 to 30 months. In Study 1, Pancreaze was administered in a dose of approximately 6,300 lipase units per kilogram per day for lengths of treatment ranging from 8 to 26 days; in Study 2, Pancreaze was administered in four treatment arms (doses of 1,375, 2,875, 4,735, and 5,938 lipase units per kilogram per day) for lengths of treatment ranging from 6 to 11 days. The population was nearly evenly distributed in gender, and approximately 96% of patients were Caucasian.

Study 1 was a randomized, double-blind, placebo-controlled, study of 40 patients, ages 8 to 57 years, with EPI due to CF. In this study, patients received Pancreaze at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) for 14 days, followed by randomization to Pancreaze or matching placebo for 7 days of treatment. The mean exposure to Pancreaze during this study, including titration period and randomized withdrawal period, was 18 days.

The incidence of adverse events (regardless of causality) was higher during placebo treatment (60%) than during Pancreaze treatment (40%). The most common adverse events reported during the study were gastrointestinal complaints, which were reported more commonly during placebo treatment (55%) than during Pancreaze treatment (30%). The type and incidence of adverse events were similar in children (8 to 11 years), adolescents (12 to 17 years), and adults (greater than 18 years).

Table 1 enumerates treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 10%) treated with either Pancreaze or placebo in Study 1. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology.

Table 1: Treatment-Emergent Adverse Events Occurring in at least 2 Patients (greater than or equal to 10%) in Either Treatment Group of the Placebo-Controlled, Clinical Study of Pancreaze

MedDRA Primary System Organ Class Preferred Term	Pancreaze (N=20) n (%)	Placebo (N=20) n (%)
Gastrointestinal Disorders
Abdominal pain	2 (10%)	3 (15%)
Abdominal pain upper	1 (5%)	3 (15%)
Flatulence	1 (5%)	3 (15%)
Diarrhea	0 (0%)	4 (20%)
Abnormal feces	0 (0%)	3 (15%)
General Disorders And Administration Site Conditions
Fatigue	0 (0%)	2 (10%)

Study 2 was a randomized, investigator-blinded, dose-ranging study of 17 patients, ages 6 to 30 months, with EPI due to CF. All patients were transitioned from their usual PEP treatment to Pancreaze at 375 lipase units per kilogram body weight per meal for a 6 day run-in period. Patients were then randomized to receive Pancreaze at one of four doses (375, 750, 1,125, and 1,500 lipase units per kilogram body weight per meal) for 5 days. Adverse events were collected on patient diary entries and at each study visit.

The most commonly reported adverse events were gastrointestinal, including diarrhea and vomiting, and were similar in type and frequency across treatment arms and to those reported in the double-blind, placebo-controlled trial (Study 1).

Postmarketing Experience

Post-marketing data for Pancreaze has been available since 1988. The safety data is similar to that described below.

Delayed- and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, and skin disorders including pruritus, urticaria and rash. In general, these products have a well defined and favorable risk-benefit profile in exocrine pancreatic insufficiency.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Drug Interactions

No drug interactions have been identified. No formal interaction studies have been conducted.

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic effects

Pregnancy Category C: Animal reproduction studies have not been conducted with pancrelipase. It is not known whether pancrelipase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pancreaze should be given to a pregnant woman only if clearly needed. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a pregnant woman with exocrine pancreatic insufficiency. Adequate caloric intake during pregnancy is important for normal maternal weight gain and fetal growth. Reduced maternal weight gain and malnutrition can be associated with adverse pregnancy outcomes.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Pancreaze is administered to a nursing woman. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a nursing mother with exocrine pancreatic insufficiency.

Pediatric Use

The short-term safety and effectiveness of Pancreaze were assessed in two clinical studies in pediatric patients with EPI due to CF; one study included patients ages 6 to 30 months, and the other included patients ages 8 years to 17 years.

Study 1 was a randomized, double-blind, placebo-controlled study in 40 patients, 14 of whom were pediatric patients, including 7 children aged 8 to 11 years, and 7 adolescents aged 12 to 17 years. The safety and efficacy in pediatric patients in this study were similar to adult patients [see Adverse Reactions (6.1) and Clinical Studies (14)].

Study 2 was a randomized, investigator-blinded, dose-ranging study in 17 pediatric patients aged 6 to 30 months. When patient regimen was switched from their usual PEP regimen to Pancreaze, patients showed similar control of their fat malabsorption [see Adverse Reactions (6.1) and Clinical Studies (14)].

The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase consisting of the same active ingredient (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis has been described in the medical literature and through clinical experience.

Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences [see Dosage and Administration (2.1)]. Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age [see Warnings and Precautions (5.1)].

Overdosage

In Study 1, a 10 year-old patient was administered a Pancreaze dose of 12,399 lipase units per kilogram per day for the duration of the open-label and randomized withdrawal periods. The patient experienced mild abdominal pain throughout both study periods. Abnormal chemistry data at the end of the study included mild elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum phosphate. Abnormal hematology data at the end of the study included mild elevations of hematocrit. No abnormalities from analyses of urinalysis or uric acid were noted.

Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)]. High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia, and should be used with caution in patients with a history of hyperuricemia, gout, or renal impairment [see Warnings and Precautions (5.3)].

Pancreaze Description

Pancreaze is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains multiple enzyme classes, including porcine-derived lipases, proteases, and amylases.

Each capsule for oral administration contains enteric-coated microtablets that are each approximately 2 mm in diameter.

The active ingredient evaluated in clinical trials is lipase. Pancreaze is dosed by lipase units. Other active ingredients include protease and amylase.

Inactive ingredients in Pancreaze include cellulose, colloidal anhydrous silica, crospovidone, magnesium stearate, methacrylic acid ethyl acrylate copolymer, montan glycol wax, simethicone emulsion, talc and triethyl citrate.

Pancreaze is available in four color coded strengths. Each Pancreaze capsule strength contains the specified amounts of lipase, protease, and amylase as follows:

4,200 USP units of lipase; 10,000 USP units of protease; 17,500 USP units of amylase. The hard gelatin capsules have a yellow opaque body and clear cap imprinted with "McNEIL" and "MT 4". The capsule shell contains gelatin, titanium dioxide, sodium lauryl sulfate, sorbitan monolaurate, iron oxide, and gelatin capsule imprint ink.

10,500 USP units of lipase; 25,000 USP units of protease; 43,750 USP units of amylase. The hard gelatin capsules have a pink opaque body and clear cap imprinted with "McNEIL" and "MT 10". The capsule shell contains gelatin, titanium dioxide, sodium lauryl sulfate, sorbitan monolaurate, iron oxide, and gelatin capsule imprint ink.

16,800 USP units of lipase; 40,000 units of protease; 70,000 USP units of amylase. The hard gelatin capsules have a salmon opaque body and clear cap imprinted with "McNEIL" and "MT 16". The capsule shell contains gelatin, titanium dioxide, sodium lauryl sulfate, sorbitan monolaurate, iron oxide, and gelatin capsule imprint ink.

21,000 USP units of lipase; 37,000 units of protease; 61,000 USP units of amylase. The hard gelatin capsules have a white opaque body and cap imprinted with "McNEIL" and "MT 20". The capsule shell contains gelatin, titanium dioxide, sodium lauryl sulfate, sorbitan monolaurate, and gelatin capsule imprint ink.

Pancreaze - Clinical Pharmacology

Mechanism of Action

The pancreatic enzymes in Pancreaze catalyze the hydrolysis of fats to monoglyceride, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

Pharmacokinetics

The pancreatic enzymes in Pancreaze are enteric-coated to minimize destruction or inactivation in gastric acid. Pancreaze is expected to release most of the enzymes in vivo at pH greater than 5.5. Pancreatic enzymes are not absorbed from the gastrointestinal tract in appreciable amounts.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed with pancrelipase.

Clinical Studies

The short-term safety and efficacy of Pancreaze were evaluated in two studies conducted in 57 patients with exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF).

Study 1 was a randomized, double-blind, placebo-controlled study of 40 patients, ages 8 to 57 years, with EPI due to CF. In this study, patients received Pancreaze at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) for 14 days (open label period) followed by randomization to Pancreaze or matching placebo for 7 days of treatment (double-blind withdrawal period). Only patients with coefficient of fat absorption (CFA) ≥80% in the open label period were randomized to the double-blind withdrawal period. The mean dose during the controlled treatment period was 6,400 lipase units per kilogram per day. All patients consumed a high-fat diet (greater than or equal to 100 grams of fat per day) during the treatment period.

The primary efficacy endpoint was the change in CFA from the open label period to the end of the double-blind withdrawal period. The CFA was determined by a 72-hour stool collection period during both treatment periods, when both fat excretion and fat ingestion were measured (Table 2).

Table 2. Change in CFA in Study 1 (Open Label Period to End of Double-Blind Withdrawal Period)

	Pancreaze n=20	Placebo n=20
* Minimum of 72 hours from start of open label period. † Double-blind withdrawal period ranged from 4 to 7 days. ‡ p<0.001
CFA [%]
Open Label Period* (Mean, SD)	88 (5)	91 (5)
End of Double-Blind Withdrawal Period† (Mean, SD)	87 (8)	56 (25)
Change in CFA‡ [%]
Open Label Period to End of Double-Blind Withdrawal Period (Mean, SD)	-2 (6)	-34 (23)
Treatment Difference Point Estimate (95% CI)	33 (25, 40)

At the end of the double-blind withdrawal period, the mean change in CFA from the open label period to the end of the double-blind withdrawal period was -2% with Pancreaze treatment compared to -34% with placebo treatment. There were similar responses to Pancreaze by age and gender.

Study 2 was a randomized, investigator-blinded, dose-ranging study of 17 patients, ages 6 months to 30 months (mean 18 months) with EPI due to CF. The final analysis population was limited to 16 patients; 1 patient was excluded due to withdrawal of consent. All patients were transitioned from their usual PEP treatment to Pancreaze at 375 lipase units per kilogram body weight per meal for a 6 day run-in period. Patients were then randomized to receive Pancreaze at one of four doses (375, 750, 1,125, and 1,500 lipase units per kilogram body weight per meal) for 5 days. The CFA was measured at the end of the run-in period and at the end of the randomized period (Table 3).

Table 3. Change in CFA in Study 2 (End of Run-in Period to End of Study)

	375 units lipase/kg/meal n=4	750 units lipase/kg/meal n=4	1,125 units lipase/kg/meal n=4	1,500 units lipase/kg/meal n=4
* End of Run-in Period; † End of Study
CFA (%)
Day 6* (Mean, SD)	93 (2)	90 (5)	81 (11)	93 (3)
Day 11† (Mean, SD)	92 (3)	91 (4)	80 (13)	91 (2)
Change in CFA (%)
Day 6 to Day 11 (Mean, SD)	-2 (3)	1 (3)	-1 (3)	-2 (3)

Overall, patients showed similar CFA at the end of the run-in period (mean Pancreaze dose of 1,600 lipase units per kilogram body weight per day) as at the end of the study across the four treatment arms.

REFERENCES

1. Borowitz DS, Grand RJ, Durie PR, et al. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Journal of Pediatrics. 1995; 127: 681–684.


2. Borowitz DS, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. Journal of Pediatric Gastroenterology Nutrition. 2002 Sep; 35: 246–259.


3. Stallings VA, Start LJ, Robinson KA, et al. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. Journal of the American Dietetic Association. 2008; 108: 832–839.


4. Smyth RL, Ashby D, O'Hea U, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-control study. Lancet. 1995; 346: 1247–1251.


5. FitzSimmons SC, Burkhart GA, Borowitz DS, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. New England Journal of Medicine. 1997; 336: 1283–1289.

How Supplied/Storage and Handling

Pancreaze (pancrelipase) Delayed-Release Capsules

4,200 USP units of lipase; 10,000 USP units of protease; 17,500 USP units of amylase.

Pancreaze (pancrelipase) is supplied as hard gelatin capsules with a yellow opaque body and clear cap imprinted with "McNEIL" and "MT 4" and packaged in bottles of 100–(NDC 50458-341-60).

Pancreaze (pancrelipase) Delayed-Release Capsules

10,500 USP units of lipase; 25,000 USP units of protease; 43,750 USP units of amylase.

Pancreaze (pancrelipase) is supplied as hard gelatin capsules with a pink opaque body and clear cap imprinted with "McNEIL" and "MT 10" and packaged in bottles of 100–(NDC 50458-342-60).

Pancreaze (pancrelipase) Delayed-Release Capsules

16,800 USP units of lipase; 40,000 USP units of protease; 70,000 USP units of amylase.

Pancreaze (pancrelipase) is supplied as hard gelatin capsules with a salmon opaque body and clear cap imprinted with "McNEIL" and "MT 16" and packaged in bottles of 100–(NDC 50458-343-60).

Pancreaze (pancrelipase) Delayed-Release Capsules

21,000 USP units of lipase; 37,000 USP units of protease; 61,000 USP units of amylase.

Pancreaze (pancrelipase) is supplied as hard gelatin capsules with a white opaque body and cap imprinted with "McNEIL" and "MT 20" and packaged in bottles of 100–(NDC 50458-346-60).

Storage and Handling

Avoid heat. Pancreaze hard gelatin capsules should be stored in a dry place in the original container. After opening, KEEP THE CONTAINER TIGHTLY CLOSED between uses to PROTECT FROM MOISTURE. Do not store above 25°C (77°F).

The Pancreaze 4200 USP Units of lipase bottle contains a desiccant packet. DO NOT eat or throw away the packet (desiccant) in your medicine bottle. This packet will protect your medicine from moisture.

Keep out of reach of children.

DO NOT CRUSH Pancreaze delayed-release capsules or the capsule contents.

Patient Counseling Information

See Medication Guide

Dosing and Administration

• Instruct patients and caregivers that Pancreaze should only be taken as directed by their healthcare professional. Patients should be advised that the total daily dose should not exceed 10,000 lipase units/kg body weight/day unless clinically indicated. This needs to be especially emphasized for patients eating multiple snacks and meals per day. Patients should be informed that if a dose is missed, the next dose should be taken with the next meal or snack as directed. Doses should not be doubled [see Dosage and Administration (2)].


• Instruct patients and caregivers that Pancreaze should always be taken with food. Patients should be advised that Pancreaze delayed-release capsules and the capsule contents must not be crushed or chewed as doing so could cause early release of enzymes and/or loss of enzymatic activity. Patients should swallow the intact capsules with adequate amounts of liquid at mealtimes. If necessary, the capsules contents can also be sprinkled on soft acidic foods. [see Dosage and Administration (2)].


• Instruct patients to notify their healthcare professional if they are pregnant or are thinking of becoming pregnant during treatment with Pancreaze [see Use in Specific Populations (8.1)].


• Instruct patients to notify their healthcare professional if they are breast feeding or are thinking of breast feeding during treatment with Pancreaze [see Use in Specific Populations (8.3)].

Fibrosing Colonopathy

Advise patients and caregivers to follow dosing instructions carefully, as doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal (10,000 lipase units/kg of body weight/day) have been associated with colonic strictures in children below the age of 12 years [see Dosage and Administration (2)].

Allergic Reactions

Advise patients and caregivers to contact their healthcare professional immediately if allergic reactions to Pancreaze develop [see Warnings and Precautions (5.5)].

Manufactured by:

Nordmark Arzneimittel GmbH & Co. KG

25436 Uetersen, Germany.

Manufactured for:

McNeil Pediatrics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

Titusville, NJ 08560.

©Ortho-McNeil-Janssen Pharmaceuticals, Inc. 2010

MEDICATION GUIDE

Pancreaze (pan-kre-aze)

(pancrelipase)

Delayed-Release Capsules

Read this Medication Guide before you start taking Pancreaze and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment.

What is the most important information I should know about Pancreaze?

• Pancreaze may increase your chance of having a rare bowel disorder called fibrosing colonopathy. This condition is serious and may require surgery. The risk of having this condition may be reduced by following the dosing instructions that your doctor gave you. Call your doctor right away if you have any unusual or severe:
  
  • stomach area (abdominal) pain
  
  
  • bloating
  
  
  • trouble passing stool (having bowel movements)
  
  
  • nausea, vomiting, or diarrhea
  
  

Take Pancreaze exactly as prescribed by your doctor. Do not take more or less Pancreaze than directed by your doctor.

What is Pancreaze?

Pancreaze is a prescription medicine used to treat people who cannot digest food normally because their pancreas does not make enough enzymes due to cystic fibrosis or other conditions. Pancreaze may help your body use fats, proteins, and sugars from food.

Pancreaze contains a mixture of digestive enzymes including lipases, proteases, and amylases from pig pancreas.

Pancreaze is safe and effective in children when taken as prescribed by your doctor.

What should I tell my doctor before taking Pancreaze?

Before taking Pancreaze, tell your doctor about all your medical conditions, including if you:

• are allergic to pork (pig) products.


• have a history of blockage of your intestines, or scarring or thickening of your bowel wall (fibrosing colonopathy)


• have gout, kidney disease, or high blood uric acid (hyperuricemia)


• have trouble swallowing capsules


• have any other medical condition


• are pregnant or plan to become pregnant. It is not known if Pancreaze will harm your unborn baby.


• are breast-feeding or plan to breast-feed. It is not known if Pancreaze passes into your breast milk. You and your doctor should decide if you will take Pancreaze or breast-feed.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, or herbal supplements.

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.

How should I take Pancreaze?

Take Pancreaze exactly as your doctor tells you.

• Do not take more capsules in a day than the number your doctor tells you to take (total daily dose).


• Always take Pancreaze with a meal or snack and plenty of fluid. If you eat a lot of meals or snacks in a day, be careful not to go over your total daily dose.


• Your doctor may change your dose based on the amount of fatty foods you eat or based on your weight.


• Do not crush or chew the Pancreaze capsules or their contents, and do not hold the capsule or contents in your mouth. Crushing, chewing or holding the Pancreaze Capsules in your mouth may cause irritation in your mouth or change the way Pancreaze works in your body.

Giving Pancreaze to infants (children up to 12 months):

1. Give Pancreaze right before each feeding of formula or breast milk.


2. Do not mix Pancreaze capsule contents directly into formula or breast milk.


3. Open the capsules and sprinkle the contents directly into your infant's mouth or mix the contents in a small amount of soft food such as applesauce. These foods should be the kind found in baby food jars that you buy at the store, or other food recommended by your doctor.


4. If you sprinkle the Pancreaze on food, give the Pancreaze and food mixture to your child right away. Do not store Pancreaze that is mixed with food.


5. Give your child enough liquid to completely swallow the Pancreaze contents or the Pancreaze and food mixture.


6. Look into your child's mouth to make sure that all of the medicine has been swallowed.

Giving Pancreaze to children and adults

1. Swallow Pancreaze capsules whole and take them with enough liquid to swallow them right away.


2. If you have trouble swallowing capsules, open the capsules and sprinkle the contents on a small amount of acidic food such as applesauce. Ask your doctor about other foods you can mix with Pancreaze.


3. If you sprinkle Pancreaze on food, swallow it right after you mix it and drink plenty of water or juice to make sure the medicine is swallowed completely. Do not store Pancreaze that is mixed with food.


4. If you forget to take Pancreaze, call your healthcare provider or wait until your next meal and take your usual number of capsules. Take your next dose at your usual time. Do not make up for missed doses.

What are the possible side effects of Pancreaze?

Pancreaze may cause serious side effects, including:

• See "What is the most important information I should know about Pancreaze?"


• Irritation of the inside of your mouth. This can happen if Pancreaze is not swallowed completely.


• Increase in blood uric acid levels. This may cause worsening of swollen, painful joints (gout) caused by an increase in your blood uric acid levels


• Allergic reactions including trouble with breathing, skin rashes, or swollen lips.

Call your doctor right away if you have any of these symptoms.

The most common side effects of Pancreaze include:

• Pain in your stomach (abdominal area)


• Gas

Other Possible Side Effects

Pancreaze and other pancreatic enzyme products are made from the pancreas of pigs, the same pigs people eat as pork. These pigs may carry viruses. Although it has never been reported, it may be possible for a person to get a viral infection from taking pancreatic enzyme products that come from pigs.

Tell your doctor if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of Pancreaze. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to McNeil Pediatrics at 1-800-526-7736.

How do I store Pancreaze?

• Store Pancreaze at room temperature below 77°F (25°C). Avoid heat.


• Keep Pancreaze in a dry place and in the original container.


• After opening the bottle, keep it closed tightly between uses.


• The Pancreaze 4200 USP Units of lipase bottle contains a desiccant packet. DO NOT eat or throw away the packet (desiccant) in your medicine bottle. This packet will protect your medicine from moisture.


• Store Pancreaze in a dry place.

Keep Pancreaze and all medicines out of reach of children.

General information about Pancreaze

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pancreaze for a condition for which it was not prescribed. Do not give Pancreaze to other people to take, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Pancreaze. If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about Pancreaze that is written for healthcare providers.

For more information go to www.RXFORSAFETY.com or call 1-800-526-7736 (Monday - Friday 9am to 5pm EST).

What are the ingredients in Pancreaze?

Active Ingredient: lipase, protease, amylase

Inactive Ingredients: cellulose, colloidal anhydrous silica, crospovidone, magnesium stearate, methacrylic acid ethyl acrylate copolymer, montan glycol wax, simethicone emulsion, talc and triethyl citrate. The capsule shell contains gelatin, titanium dioxide, sodium lauryl sulfate, sorbitan monolaurate, and gelatin capsule imprint ink. Pancreaze 4,200, 10,500, and 16,800 USP Units of lipase also contain iron oxide.

Manufactured by:

Nordmark Arzneimittel GmbH & Co. KG

25436 Uetersen, Germany.

Manufactured for:

McNeil Pediatrics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

Titusville, NJ 08560.

Revised: April 2010

©Ortho-McNeil-Janssen Pharmaceuticals, Inc. 2010

PRINCIPAL DISPLAY PANEL - 4,200 Unit Bottle Label

NDC 50458-341-60

Pancreaze™

(pancrelipase)

Delayed-Release Capsules

Each capsule contains:

Lipase 4,200 USP Units

Amylase 17,500 USP Units

Protease 10,000 USP Units

DOSE BY LIPASE UNITS

Attention Pharmacist: Dispense

the accompanying Medication

Guide to each patient.

100 capsules

PRINCIPAL DISPLAY PANEL - 4,200 Unit Capsule Carton

NDC 50458-341-60

Pancreaze™

(pancrelipase)

Delayed-Release Capsules

Each capsule contains:

Lipase 4,200 USP Units

Amylase 17,500 USP Units

Protease 10,000 USP Units

DOSE BY LIPASE UNITS

Each capsule contains enteric

coated pancrelipase microtablets.

Attention Pharmacist:

Dispense the accompanying

Medication Guide to each

patient.

Rx only.

100 capsules

Pancreaze  pancrelipase  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 50458-341 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PANCRELIPASE (PANCRELIPASE LIPASE) PANCRELIPASE LIPASE 4200 [USP'U]