Saizen

Generic Name: somatropin (soe ma TROE pin)

Brand Names: Genotropin, Genotropin Miniquick, Humatrope, Norditropin, Norditropin Cartridge, Norditropin FlexPro Pen, Norditropin Nordiflex Pen, Nutropin, Nutropin AQ, Omnitrope, Saizen, Serostim, Tev-tropin, Zorbtive

What is Saizen (somatropin)?

Somatropin is a form of human growth hormone. Human growth hormone is important in the body for the growth of bones and muscles.

Somatropin is used to treat growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth, and other causes. Somatropin is also used to prevent severe weight loss in people with AIDS, or to treat short bowel syndrome.

Somatropin may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Saizen (somatropin)?

Before you receive somatropin, tell your doctor about all your past and present medical conditions, especially allergies, trauma, surgery, diabetes, cancer, breathing problems, liver or kidney disease, scoliosis, high blood pressure, pancreas disorder, underactive thyroid, or a brain tumor.

Also tell your doctor about all other medications you use, especially steroids or diabetes medications. Your dosages of these medicines may need to be changed when you start using somatropin. Do not stop using a steroid suddenly or change any of your medication doses without your doctor's advice.

If you have Prader-Willi syndrome and are using somatropin, call your doctor promptly if you develop signs of lung or breathing problems such as shortness of breath, coughing, or new or increased snoring.

Call your doctor at once if you have sudden and severe pain in your upper stomach with nausea and vomiting, fast heartbeat, increased thirst or urination, weight loss, or vision changes and sudden, severe pain behind your eyes.

What should I discuss with my healthcare provider before using Saizen (somatropin)?

Before you receive somatropin, tell your doctor if you have ever had an allergic reaction to a growth hormone medicine, or to drug preservatives such as benzyl alcohol, metacresol or glycerin. You should not use this medication if you are allergic to somatropin, or if you have:

• 
  

  diabetic retinopathy (a serious eye condition caused by diabetes);

  
  


• 
  

  cancer; or

  
  


• 
  

  Prader-Willi syndrome and are also overweight or have sleep apnea or severe respiratory (lung) problems.

  
  

You should also not use somatropin if you have a serious medical condition after having:

• 
  

  open heart surgery or stomach surgery;

  
  


• 
  

  trauma or other medical emergency; or

  
  


• 
  

  breathing problems (such as lung failure).

  
  

To make sure you can safely take somatropin, tell your doctor if you have any of these other conditions:

• 
  

  liver disease;

  
  


• 
  

  kidney disease (or if you are on dialysis);

  
  


• 
  

  diabetes;

  
  


• 
  

  a pituitary gland disorder;

  
  


• 
  

  scoliosis;

  
  


• 
  

  high blood pressure (hypertension);

  
  


• 
  

  a pancreas disorder (especially in children);

  
  


• 
  

  a history of cancer;

  
  


• 
  

  carpal tunnel syndrome;

  
  


• 
  

  underactive thyroid; or

  
  


• 
  

  a brain tumor or lesion.

  
  

FDA pregnancy category B. Some brands of somatropin are not expected to harm an unborn baby, including Genotropin, Omnitrope, Saizen, Serostim, and Zorbtive. FDA pregnancy category C. It is not known whether certain other brands of somatropin will harm an unborn baby, including Humatrope, Norditropin, Nutropin, and Tev-tropin. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether somatropin passes into breast milk or if it could harm a nursing baby. Do not use somatropin without telling your doctor if you are breast-feeding a baby.

How should I use Saizen (somatropin)?

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your dose and brand of somatropin, and how often you give it will depend on what you are being treated for. Follow the directions on your prescription label.

Somatropin is injected into a muscle or under the skin. You may be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

Use a different place on your body each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row. Do not inject this medicine into skin or muscle that is red, sore, infected, or injured.

Do not shake the medication bottle or you may ruin the medicine. When mixing somatropin with a diluent (liquid), use a gentle swirling motion. Do not use the medication if it has changed colors or has particles in it. Call your doctor for a new prescription.

Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

To be sure this medication is helping your condition and not causing harm, your blood and growth progress will need to be tested often. Your eyes may also need to be checked. Visit your doctor regularly.

If you are being treated for short bowel syndrome, follow the diet plan created for you by your doctor or nutrition counselor to help control your condition. Somatropin is not a cure for short bowel syndrome.

If you use a form of somatropin that comes in a cartridge for use with an injection pen, use only the pen injection system provided with the somatropin brand you use.

How you store this medicine will depend on what brand you are using and what diluent you are mixing somatropin with. After mixing somatropin, you may need to use it right away or you may be able to store it for later use. Read and carefully follow the instructions provided with your medicine about proper storage of somatropin before and after it has been mixed. Ask your pharmacist if you have any questions about proper storage of your medication.

Throw away any somatropin left over after the expiration date on the label has passed.

What happens if I miss a dose?

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

Call your doctor if you miss more than 3 doses in a row.

What happens if I overdose?

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

Overdose can cause tremors or shaking, cold sweats, increased hunger, headache, drowsiness, weakness, dizziness, fast heartbeat, and nausea. Long-term overdose may cause excessive growth.

What should I avoid while using Saizen (somatropin)?

If you use Zorbtive to treat short bowel syndrome, avoid drinking fruit juices or soda beverages. Follow the instructions of your doctor or nutrition counselor about what types of liquids you should drink while using Zorbtive.

Avoid drinking alcohol if you have short bowel syndrome. Alcohol can irritate your stomach and could make your condition worse.

Saizen (somatropin) side effects

If you have Prader-Willi syndrome, call your doctor promptly if you develop signs of lung or breathing problems such as shortness of breath, coughing, or new or increased snoring. Rare cases of serious breathing problems have occurred in patients with Prader-Willi syndrome who use somatropin.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

• 
  

  severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

  
  


• 
  

  increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss;

  
  


• 
  

  sudden and severe pain behind your eyes, vision changes;

  
  


• 
  

  swelling in your head, face, hands, or feet; or

  
  


• 
  

  numbness or tingling in your wrist, hand, or fingers.

  
  

Less serious side effects may include:

• 
  

  headache, feeling tired;

  
  


• 
  

  redness, soreness, swelling, rash, itching, pain, or bruising where the medicine was injected;

  
  


• 
  

  pain in your arms or legs, joint stiffness or pain;

  
  


• 
  

  muscle pain; or

  
  


• 
  

  cold symptoms such as stuffy nose, sneezing, sore throat.

  
  

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

What other drugs will affect Saizen (somatropin)?

Before using somatropin, tell your doctor if you use insulin or take oral (by mouth) medicine to treat diabetes. Somatropin may affect blood sugar levels and you may need to adjust your dose of the diabetes medication. Do not change the dose of your diabetes medication without your doctor's advice.

Tell your doctor if you use any type of steroid medicine such as cortisone, dexamethasone, methylprednisolone, prednisone, and others. Steroids can make somatropin less effective and your doses may need to be adjusted. Do not stop using a steroid suddenly. Follow your doctor's instructions.

Tell your doctor about all other medications you use, especially cyclosporine (Gengraf, Neoral, Sandimmune), seizure medication, birth control pills, anabolic steroids, or hormone replacement medications for men or women.

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

More Saizen resources

• Saizen Side Effects (in more detail)
• Saizen Use in Pregnancy & Breastfeeding
• Saizen Drug Interactions
• Saizen Support Group
• 1 Review for Saizen - Add your own review/rating

• Saizen MedFacts Consumer Leaflet (Wolters Kluwer)


• Saizen Prescribing Information (FDA)


• Saizen Subcutaneous, Injection Advanced Consumer (Micromedex) - Includes Dosage Information


• Somatropin Professional Patient Advice (Wolters Kluwer)


• Genotropin Prescribing Information (FDA)


• Genotropin Advanced Consumer (Micromedex) - Includes Dosage Information


• Genotropin MedFacts Consumer Leaflet (Wolters Kluwer)


• Humatrope Cartridge MedFacts Consumer Leaflet (Wolters Kluwer)


• Humatrope Prescribing Information (FDA)


• Norditropin MedFacts Consumer Leaflet (Wolters Kluwer)


• Norditropin Prescribing Information (FDA)


• Nutropin MedFacts Consumer Leaflet (Wolters Kluwer)


• Nutropin Prescribing Information (FDA)


• Nutropin AQ MedFacts Consumer Leaflet (Wolters Kluwer)


• Nutropin AQ Prescribing Information (FDA)


• Nutropin Depot Prescribing Information (FDA)


• Omnitrope Prescribing Information (FDA)


• Omnitrope MedFacts Consumer Leaflet (Wolters Kluwer)


• Omnitrope Consumer Overview


• Serostim Prescribing Information (FDA)


• Serostim MedFacts Consumer Leaflet (Wolters Kluwer)


• Tev-Tropin Prescribing Information (FDA)


• Tev-Tropin MedFacts Consumer Leaflet (Wolters Kluwer)


• Zorbtive Prescribing Information (FDA)


• Zorbtive Consumer Overview


• Zorbtive MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Saizen with other medications

• Adult Human Growth Hormone Deficiency
• Pediatric Growth Hormone Deficiency
• Short Stature for Age

Where can I get more information?

• Your pharmacist can provide more information about somatropin.

See also: Saizen side effects (in more detail)

Seb-Prev

sulfacetamide sodium gel

Dosage Form: gel
Seb-Prev™ GEL (SODIUM SULFACETAMIDE 10%)

Seb-Prev Gel

(Sodium Sulfacetamide 10%)

Rx Only

FOR DERMATOLOGIC USE ONLY

NOT FOR OPHTHALMIC USE

Seb-Prev Description

Each gram of Seb-Prev™ Gel contains 100 mg of Sulfacetamide Sodium USP in a vehicle consisting of edetate disodium, glycerin, methylparaben, propylene glycol, purified water, sodium thiosulfate, and xanthan gum.

Sulfacetamide sodium is C8H9N2NaO3S•H2O with a molecular weight of 254.24. Chemically, it is Acetamide N-[(4-aminophenyl)sulfonyl]-, monosodium salt, monohydrate, with the following structural formula:

Sulfacetamide sodium is an odorless, white, crystalline powder with a bitter taste. It is freely soluble in water, sparingly soluble in alcohol, while practically insoluble in benzene, in chloroform, and in ether.

Seb-Prev - Clinical Pharmacology

Sulfacetamide sodium exerts a bacteriostatic effect against sulfonamide sensitive Gram-positive and Gram-negative microorganisms commonly isolated from secondary cutaneous pyogenic infections. It acts by restricting the synthesis of folic acid required by bacteria for growth, by its competition with para-aminobenzoic acid. There are no clinical data available on the degree and rate of systemic absorption of Seb-Prev™ Gel when applied to the skin or scalp. However, significant absorption of sulfacetamide sodium through the skin has been reported.

The following in vitro data are available but their clinical significance is unknown. Organisms which show susceptibility to sulfacetamide sodium are: Streptococci, Staphylococci, E. coli, Klebsiella pneumoniae, Pseudomonas pyocyanea, Salmonella species, Proteus vulgaris, Nocardia and Actinomyces.

Indications and Usage for Seb-Prev

Seb-Prev™ Gel is intended for topical application in the following scaling dermatoses: seborrheic dermatitis and seborrhea sicca (dandruff). It also is indicated for the treatment of secondary bacterial infections of the skin due to organisms susceptible to sulfonamides.

Contraindications

Seb-Prev™ Gel is contraindicated in persons with known or suspected hypersensitivity to sulfonamides or to any of the ingredients of the product.

Warnings

Sulfonamides are known to cause Stevens-Johnson syndrome in hypersensitive individuals. Stevens-Johnson syndrome also has been reported following the use of sulfacetamide sodium topically. Cases of drug-induced systemic lupus erythematosus from topical sulfacetamide also have been reported. In one of these cases, there was a fatal outcome.

Precautions

General

Nonsusceptible organisms, including fungi, may proliferate with the use of this preparation. Hypersensitivity reactions may recur when a sulfonamide is readministered, irrespective of the route of administration, and cross hypersensitivity between different sulfonamides may occur. If Seb-Prev™ Gel produces signs of hypersensitivity or other untoward reactions, discontinue use of the preparation. Systemic absorption of topical sulfonamides is greater following application to large, infected, abraded, denuded, or severely burned areas. Under these circumstances, potentially any of the adverse effects produced by the systemic administration of these agents could occur and appropriate observations and laboratory determinations should be performed.

Information For Patients

Patients should discontinue Seb-Prev™ Gel if the condition becomes worse, or if a rash develops in the area being treated or elsewhere. Seb-Prev™ Gel also should be discontinued promptly and the physician notified if any arthritis, fever, or sores in the mouth develop. For external use only. Avoid contact with eyes and mucous membranes. Keep this and all medications out of reach of children. In case of accidental ingestion, call a physician or poison control center immediately (see OVERDOSAGE).

Drug Interactions

Seb-Prev™ Gel is incompatible with silver preparations.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies for carcinogenic potential have not been performed on Seb-Prev™ Gel to date. Studies on reproduction and fertility also have not been performed. One author detected chromosomal nondisjunction in the yeast, Saccharomyces cerevisiae, following application of sulfacetamide sodium. The significance of this finding to the topical use of sulfacetamide sodium in the human is unknown.

Pregnancy

Teratogenic effects

Pregnancy Category C

Animal reproduction studies have not been conducted with Seb-Prev™ Gel. It also is not known whether Seb-Prev™ Gel can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Seb-Prev™ Gel should be given to a pregnant woman only if clearly needed.

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 Seb-Prev™ Gel is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children under the age of 12 years have not been established.

Adverse Reactions

Reports of irritation and hypersensitivity to sulfacetamide sodium are uncommon. The following adverse reactions, reported after administration of sterile ophthalmic sulfacetamide sodium, are noteworthy: instances of Stevens-Johnson syndrome and instances of local hypersensitivity which progressed to a syndrome resembling systemic lupus erythematosus; in one case a fatal outcome has been reported (see WARNINGS).

Overdosage

The oral LD50 of sulfacetamide in mice is 16.5 g/kg. The LD50 for topical administration of sulfacetamide has not been determined. Oral overdosage may cause nausea and vomiting. Large oral overdosage may cause hematuria, crystalluria, and renal shutdown due to the precipitation of sulfa crystals in the renal tubules and the urinary tract. In the event of overdosage, call a physician or poison control center; emergency treatment should be started immediately.

Treatment: The patient should be induced to vomit, even if emesis has occurred spontaneously. Pharmacologic vomiting by the administration of ipecac syrup is a preferred method. However, vomiting should not be induced in patients with impaired consciousness. The action of ipecac is facilitated by physical activity and by the administration of eight to twelve fluid ounces of water. If emesis does not occur within 15 minutes, the dose of ipecac should be repeated. Precautions against aspiration must be taken, especially in infants and children. Following emesis, any drug remaining in the stomach may be absorbed by activated charcoal administered as a slurry with water. If vomiting is unsuccessful or contraindicated, gastric lavage should

be performed. Isotonic and one-half isotonic saline are the lavage solutions of choice. Saline cathartics, such as milk of magnesia, draw water into the bowel by osmosis and, therefore, may be valuable for their action in rapid dilution of bowel content. After emergency treatment, the patient should continue to be medically monitored.

Observe kidney function for up to 1 week and have the patient ingest copious amounts of fluid during this period. Mannitol infusions may be helpful at the first sign of oliguria. Alkalinization of the urine by ingestion of bicarbonate is very helpful in preventing crystallization of sulfa drug in the kidney.

Seb-Prev Dosage and Administration

Seborrheic dermatitis including seborrhea sicca: Apply to affected areas twice daily (morning and evening), or as directed by your physician. Avoid contact with eyes or mucous membranes. Repeat application as described for eight to ten days.

As the condition subsides, the interval between applications may be lengthened. Applications once or twice weekly or every other week may prevent recurrence. Should the condition recur after stopping therapy, the application of Seb-Prev™ Gel should be reinitiated as at the beginning of treatment.

Secondary cutaneous bacterial infections: Apply to affected areas twice daily for eight to ten days.

How is Seb-Prev Supplied

Seb-Prev™ Gel is available as follows:

30 g tube (NDC 45802-960-94)

60 g tube (NDC 45802-960-96)

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Do not freeze.

Occasionally, a slight yellowish discoloration may occur when an excessive amount of the product is used and comes in contact with white fabrics. This discoloration is readily removed by ordinary laundering without bleaches.

MANUFACTURED BY

STIEFEL LABORATORIES, INC.

CORAL GABLES, FL 33134

DISTRIBUTED BY

PERRIGO®

ALLEGAN, MI 49010

Rev. 10/07

81084

: 5P600 RC J1

Principal Display Panel - 30 g Carton

Seb-Prev™ Gel

(Sodium Sulfacetamide 10%)

For Dermatologic Use Only. Not for Ophthalmic Use.

Rx Only

Seb-Prev(tm) Gel - 30 g Carton

Principal Display Panel - 30 g Tube

Seb-Prev™ Gel

(Sodium Sulfacetamide 10%)

For Dermatologic Use Only. Not for Ophthalmic Use.

Rx Only

Seb-Prev(tm) Gel - 30 g Tube

Principal Display Panel - 60 g Carton

Seb-Prev™ Gel

(Sodium Sulfacetamide 10%)

For Dermatologic Use Only. Not for Ophthalmic Use.

Rx Only

Seb-Prev(tm) Gel - 60 g Carton

Principal Display Panel - 60 g Tube

Seb-Prev™ Gel

(Sodium Sulfacetamide 10%)

For Dermatologic Use Only. Not for Ophthalmic Use.

Rx Only

Seb-Prev(tm) Gel - 60 g Tube

PERRIGO SEB PREV  sodium sulfacetamide  gel

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 45802-960 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SULFACETAMIDE SODIUM (SULFACETAMIDE) SULFACETAMIDE SODIUM 100 mg  in 1 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color YELLOW (clear to pale yellow) Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 45802-960-94 1 TUBE In 1 CARTON contains a TUBE 1 30 g In 1 TUBE This package is contained within the CARTON (45802-960-94) 2 45802-960-96 1 TUBE In 1 CARTON contains a TUBE 2 60 g In 1 TUBE This package is contained within the CARTON (45802-960-96)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Unapproved drug other		08/19/2008

Labeler - Perrigo New York Inc (078846912)

Revised: 08/2010Perrigo New York Inc

More Seb-Prev resources

• Seb-Prev Side Effects (in more detail)
• Seb-Prev Use in Pregnancy & Breastfeeding
• Seb-Prev Support Group
• 0 Reviews for Seb-Prev - Add your own review/rating

• Seb-Prev Concise Consumer Information (Cerner Multum)


• Seb-Prev Lotion MedFacts Consumer Leaflet (Wolters Kluwer)


• Klaron Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• Mexar Wash MedFacts Consumer Leaflet (Wolters Kluwer)


• Ovace Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Ovace Plus Shampoo MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Seb-Prev with other medications

• Seborrheic Dermatitis
• Secondary Cutaneous Bacterial Infections

Tambocor

Generic Name: Flecainide Acetate
Class: Class Ic Antiarrhythmics
VA Class: CV300
Chemical Name: N-(2-Piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide monoacetate
Molecular Formula: C₁₇H₂₀F₆N₂O₃•C₂H₄O₂
CAS Number: 54143-56-5

Introduction

Local anesthetic-type class IC antiarrhythmic agent.^{1 2 3 4 5 6 7 146 147 165 247}

Uses for Tambocor

Ventricular Arrhythmias

Suppression and prevention of recurrent life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia).^{1 2 3 4 5 24 52 53 77 89 90 91 92 110 125 161 162 165 166 175 176 177 178 179} (See Mortality under Cautions.)

Supraventricular Tachyarrhythmias

Prevention of paroxysmal supraventricular tachyarrhythmias (PSVT), including AV nodal reentrant tachycardia and AV reentrant tachycardia (Wolff-Parkinson-White syndrome); other symptomatic, including disabling, supraventricular tachycardias of unspecified mechanisms; and symptomatic, disabling supraventricular arrhythmias (paroxysmal atrial fibrillation/flutter [PAF]) in patients without structural heart disease.^{1 35 110 115 140 192 193 194 197 198 199 200 201 206 218 247}

Used in the conversion of recent-onset (≤48 hours duration) atrial fibrillation to normal sinus rhythm.²⁴⁷

Has been used for out-of-hospital self-administration (“pill-in-the-pocket” approach) as a single oral loading dose to terminate recent-onset PAF† in carefully selected adults with mild or no heart disease.^{243 244 224 228 242} May result in reduced hospitalizations and emergency room visits.^{243 244 224 228 242}

Tambocor Dosage and Administration

General

• 
  

  Monitor plasma flecainide concentrations when feasible, especially in patients with severe hepatic¹ or renal impairment, severe CHF,^{1 43 165} or life-threatening ventricular arrhythmias.¹³⁶ Maintain trough plasma flecainide concentrations at <0.7–1 mcg/mL.^{1 2 59 70 78 104 165} (See Plasma Concentrations under Pharmacokinetics.)

  
  


• 
  

  Clinical and ECG monitoring (e.g., Holter monitoring) is recommended during therapy.^{1 89 165}

  
  

Administration

Oral Administration

Administer orally in 2 equally divided doses daily at 12-hour intervals.^{1 2 165}

If arrhythmias are not adequately controlled or drug is not well tolerated with twice-daily dosing, may give in 3 divided doses daily at 8-hour intervals.^{1 2 59 89 146 150 165}

Dosage

Available as flecainide acetate; dosage expressed in terms of flecainide.¹

Adjust dosage carefully according to individual requirements and response, patient tolerance, and the general condition and cardiovascular status of the patient.^{1 2 3 89 165}

To minimize effects on cardiac conduction, use lowest possible effective dosage.^{1 2 165}

Consider dosage reduction if PR interval increases to ≥300 ms,^{1 2 165} QRS duration increases to ≥180 ms,^{1 2 165} QT_c interval increases substantially,^{46 50 89} and/or new bundle-branch block develops.^{89 1 2 89 165}

If 2nd or 3rd degree AV block or bifascicular block occurs, discontinue therapy unless a temporary or implanted artificial ventricular pacemaker is in place to ensure adequate ventricular rate.^{1 2 89 165}

Oral loading doses generally not used since arrhythmogenicity and CHF may occur.^{1 165} However, single oral loading doses (e.g., 200–300 mg) have been used with apparent safety for conversion of recent-onset atrial fibrillation to normal sinus rhythm† in individuals with mild or no structural heart disease.^{224 228 233 235 236 240 241 242 243 244}

Adults

Ventricular Arrhythmias

Oral

Initially, 100 mg every 12 hours.^{1 2 165} Increase dosage in increments of 50 mg twice daily every 4 days until optimum response is obtained or maximum dosage of 400 mg daily is reached.^{1 2 165}

Dosages >300 mg daily generally not required.^{1 2 165}

Supraventricular Arrhythmias

Oral

Initially, 50 mg every 12 hours.^{1 192 193 200} Increase dosage in increments of 50 mg twice daily every 4 days until optimum response is obtained or maximum dosage of 300 mg daily is reached.¹

Self-administration for Conversion of Paroxysmal Atrial Fibrillation†

Oral

Patients ≥70 kg: 300 mg as a single oral loading dose 5 minutes after onset of palpitations.^{224 242}

Patients <70 kg: 200 mg as a single oral loading dose 5 minutes after onset of palpitations.^{224 242}

Remain in sitting or supine position until resolution of palpitations or for ≥4 hours after dose.^{224 242} Seek medical advice if palpitations do not resolve within 6–8 hours, if previously unexperienced symptoms (e.g., dyspnea, presyncope, syncope) occur, or if marked increase in heart rate occurs.²²⁴

Do not take more than one dose during a 24-hour period.²²⁴

Prescribing Limits

Adults

Ventricular Arrhythmias

Oral

Maximum 400 mg daily.^{1 2 165}

Supraventricular Arrhythmias

Oral

Maximum 300 mg daily for treatment of PSVT.¹

Self-administration for Conversion of Paroxysmal Atrial Fibrillation†

Oral

Maximum 300 mg as single oral dose in 24-hour period for adults ≥70 kg.^{224 242 224}

Maximum 200 mg as single oral dose in 24-hour period for adults <70 kg.^{224 242}

Special Populations

Hepatic Impairment

Reduce dosage as necessary.^{1 3 165} Longer intervals (>4 days) between dosage adjustments are required.^{1 2 165} Monitor plasma concentrations closely to guide dosage adjustments.^{1 3 165}

Renal Impairment

In patients with Cl_cr ≤35 mL/minute, initial dosage of 100 mg once daily or 50 mg twice daily is recommended.¹ Longer intervals (>4 days) between dosage adjustments are required.^{1 2 165} Monitor plasma concentrations closely to guide dosage adjustments.^{1 2 165}

Cautions for Tambocor

Contraindications

• 
  

  Preexisting 2nd or 3rd degree AV block, bifascicular block (right bundle branch block associated with left hemiblock),^{1 2 89 165} or trifascicular block,⁸⁹ unless pacemaker is in place.

  
  


• 
  

  Cardiogenic shock.^{1 2 165}

  
  


• 
  

  Known hypersensitivity to flecainide.^{1 2 165}

  
  

Warnings/Precautions

Warnings

Mortality

Excessive rate of mortality or nonfatal cardiac arrest reported in patients with asymptomatic or mildly symptomatic non-life-threatening ventricular arrhythmias and recent MI (>6 days but <2 years previously) (CAST study).^{161 163 174 175 176 177 181 182 190 191}

Limit use of flecainide in patients with ventricular arrhythmias to those with life-threatening arrhythmias;^{161 163 165 170 176 177 178 181} use in patients with less severe ventricular arrhythmias, even when symptomatic, is not recommended.^{161 163 165 170 176 177 178}

Do not use in patients with recent MI.¹

Patients with Chronic Atrial Fibrillation

Not adequately studied in patients with chronic atrial fibrillation; possible VT or VF or paradoxical increase in ventricular rate.^{1 207 208 209} Use in these patients is not recommended.^{1 207 208 209}

Arrhythmogenic Effects

Potential for new and/or more severe or potentially fatal arrhythmias (principally ventricular tachyarrhythmias but also increased VPCs or supraventricular arrhythmias).^{1 2 27 43 44 45 46 47 48 49 50 51 52 151 159 165} Risk appears to be related to dosage and underlying cardiac disease.^{1 2 27 151}

Clinical and ECG evaluations are essential prior to and during therapy.^{1 2 89} Follow recommended dosage schedule closely.^{1 2 27 165} Monitor plasma drug concentrations and avoid concentrations >1 mcg/mL.²⁷ If possible, avoid concomitant use of other antiarrhythmic agents.^{27 43 44}

Initiation of Therapy

Initiate flecainide therapy in hospital setting with ECG monitoring for patients with sustained VT, regardless or their cardiac status.^{1 2 89 151 165}

Consider initiating flecainide in hospital setting for other patients with underlying structural heart disease^{1 89 151 165} (particularly those with serious disease)^{89 136 151} and for patients transferring from therapy with another antiarrhythmic agent in whom discontinuance of the current antiarrhythmic agent is likely to result in life-threatening arrhythmias.^{1 165}

Discontinuance of Therapy

Withdraw flecainide therapy from patients with sustained ventricular arrhythmias in hospital setting under continuous ECG monitoring; ^{164 172 182} consider hospitalization when withdrawing therapy from patients with nonsustained arrhythmias.¹⁷²

CHF

Potential for new or worsened CHF, particularly in patients with cardiomyopathy, preexisting severe CHF (NYHA class III or IV), or ejection fraction <30%.¹

If CHF or myocardial dysfunction develops, dosage reduction may be necessary.²

Use with caution in patients with a history of CHF or myocardial dysfunction,^{1 2 89 146 151 154 165} particularly those with advanced failure or dysfunction.^{1 2 19 27 62 63 89 91 146} Carefully monitor such patients; do not exceed recommended initial dosage.^{1 2 165} Monitor plasma flecainide concentrations and adjust dosage to maintain trough concentrations <0.7–1 mcg/mL.^{1 2 165} If progressive CHF occurs despite reduction of flecainide dosage and/or optimum management with other therapy, discontinue flecainide.^{1 2 154 165}

Effects on Cardiac Conduction

To minimize effects on cardiac conduction, use lowest possible effective dosage.^{1 2 165}

Consider dosage reduction if PR interval increases to ≥300 ms,^{1 2 165} QRS duration increases to ≥180 ms,^{1 2 165} QT_c interval increases substantially,^{46 50 89} and/or new bundle-branch block develops⁸⁹ .^{1 2 89 165}

If 2nd or 3rd degree AV block or bifascicular block occurs, discontinue flecainide unless a temporary or implanted artificial ventricular pacemaker is in place to ensure adequate ventricular rate.^{1 2 89 165}

Atypical ventricular tachycardia-like (torsades de pointes-like) arrhythmia reported rarely.^{1 165}

Patients with Sinus Node Dysfunction

Potential for sinus bradycardia, pause, or arrest in patients with sick sinus syndrome (including bradycardia-tachycardia syndrome); use with extreme caution, if at all,¹³⁶ in such patients.^{1 2 90 151 165}

Initiate therapy in hospital setting for patients with sinus node dysfunction.^{1 2}

Changes in Endocardial Pacing Threshold

Potential for increased endocardial pacing threshold and suppression of ventricular escape rhythms.^{32 38 39}

Use with caution in patients with permanent artificial pacemakers or temporary pacing electrodes;^{1 2 32 38 39 165} do not administer to patients with existing poor thresholds or nonprogrammable artificial pacemakers unless suitable pacing rescue is available.^{1 2 165}

In patients with pacemakers, determine pacing threshold before and 1 week after initiating therapy and at regular intervals thereafter.^{1 2 165}

Potassium Imbalance

Correct any preexisting potassium imbalance before initiating flecainide.^{1 165}

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk.^{1 165} Discontinue nursing or the drug.^{1 165}

Pediatric Use

Safety and efficacy not established in children.^{1 165} Limited data suggest that flecainide may be useful for management of refractory paroxysmal reentrant supraventricular tachycardias in pediatric patients.¹²⁷

Possible proarrhythmic effects.¹ Has been associated with cardiac arrest and sudden death in pediatric patients with structural heart disease.¹

Use should be supervised directly by a cardiologist experienced in the treatment of arrhythmias in children.¹ Initiate therapy in hospital setting equipped with ECG monitoring.¹

Hepatic Impairment

Elimination may be markedly prolonged; use only if benefits clearly outweigh risks.^{1 165} Monitor plasma concentrations and reduce dosage as necessary.^{1 3 165}

Renal Impairment

Elimination may be impaired; use with caution.^{1 2 70 165} Monitor plasma concentrations and reduce dosage as necessary.^{1 165}

Common Adverse Effects

Dizziness, visual disturbances,^{1 2 3 4 5 30 58 59 76 77 78 94 95 96 97 98 101 102 103 104 124 150 165} dyspnea,¹ headache,^{1 2 30 94 95 97 98 102 103 104 165} nausea,^{1 94 95 97} fatigue,^{1 2 124 165} palpitation,^{1 2 165} chest pain.^{1 2 165}

Interactions for Tambocor

CYP2D6 involved in metabolism.^{1 245}

Antiarrhythmic Agents

Potential for increased risk of arrhythmogenic effects;^{27 43 91 126} additive, synergistic, or antagonistic cardiac effects; or additive adverse effects.^{108 112 131 136}

Avoid concomitant use with other antiarrhythmic agents if possible;^{27 43 44} reserve concomitant use for carefully selected and managed patients with severe refractory arrhythmias.^{77 92 108 110 111 112 122}

Diuretics

No apparent interaction when used concomitantly with diuretics in clinical trials.¹

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Possible increase in plasma flecainide concentrations, particularly in extensive metabolizers.^{1 245}

CYP2D6 inducers: Potential pharmacokinetic interaction; increased rate of flecainide elimination.¹

Protein-bound Drugs

Pharmacokinetic interaction unlikely.¹

Specific Drugs and Foods

Drug or Food	Interaction	Comments
Acidifying agents (e.g., ammonium chloride)	Urinary excretion of flecainide increased and elimination half-life decreased in presence of very acidic urine 80 85	Flecainide dosage adjustment may be necessary70
Alkalinizing agents (e.g., high-dose antacids, carbonic anhydrase inhibitors, sodium bicarbonate)	Urinary excretion of flecainide decreased and elimination half-life increased in presence of very alkaline urine 80 85	Flecainide dosage adjustment may be necessary70
Amiodarone	Increased plasma flecainide concentrations1	Reduce flecainide dosage by 30–50%1 131 142 156 157 165 monitor patient closely;1 142 165 monitor plasma flecainide concentrations adjust flecainide dosage as necessary1 142 165
Antacids	No effect on rate or extent of flecainide absorption1 2 70 72
β-adrenergic blocking agents	Potential for additive negative inotropic effects.1 2 165 Increased plasma concentrations of flecainide and propranolol.1 133 165
Carbamazepine	Possible increased rate of flecainide elimination1
Cimetidine	Possible reduction in nonrenal and renal clearance of flecainide135 Possible increased flecainide elimination half-life and increased plasma flecainide concentrations 1	Possible flecainide dosage reduction; further study needed.135
Clozapine	Possible increased plasma flecainide concentrations1 246	Use with caution and monitor closely, especially patients with extensive-metabolizer phenotype1 246 Adjust flecainide and/or clozapine dosage as necessary1 246
Digoxin	Possible increased plasma digoxin concentrations1 132 133 134 165	Monitor for signs of digoxin toxicity133 134
Disopyramide	Potential for negative inotropic effects1	Use concomitantly only if potential benefits outweigh risk1
Milk	Possible reduction of flecainide absorption in infants1	Consider reducing flecainide dosage when milk is removed from infant’s diet1
Phenytoin	Possible increased rate of flecainide elimination1
Phenobarbital	Possible increased rate of flecainide elimination1
Quinidine	Possible increased plasma flecainide concentrations1 245	Use with caution and monitor closely, especially patients with extensive-metabolizer phenotype1 245 Adjust flecainide and/or quinidine dosage as necessary1 245
Verapamil	Potential for negative inotropic effects1	Use concomitantly only if potential benefits outweigh risk1 2 165

Tambocor Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed following oral administration,^{1 2 70 71 72 73 165} with peak plasma concentrations generally reached within 2–3 hours.^{1 2 56 70 71 72 73 165} Absolute bioavailability is approximately 85–90%.^{2 70}

No substantial first-pass metabolism.^{1 2 70 71 165}

Food

Food may slightly decrease rate^{2 70} but does not affect extent of absorption.^{1 2 70 72 165}

Plasma Concentrations

Trough plasma concentrations are 0.2–1 mcg/mL in most patients successfully treated with flecainide.^{1 59 77 92 165 189}

Increased risk of adverse cardiac effects (e.g., conduction defects, bradycardia) at plasma concentrations >0.7–1 mcg/mL;^{1 2 70 78 165} possible increased arrhythmogenicity at concentrations >1 mcg/mL.^{27 45 50 78}

Distribution

Extent

Rapidly and apparently widely distributed following IV administration.^{70 71 79}

Appears to be distributed into milk.^{1 165}

Plasma Protein Binding

About 40–50%.^{1 2 70 81 82 83 165}

Elimination

Metabolism

Extensively metabolized, probably in the liver, to 2 major metabolites and at least 3 unidentified minor metabolites;^{1 70 73 165} unlikely that major metabolites contribute substantially to therapeutic or toxic effects.^{1 2 70 86}

CYP2D6 involved in metabolism.^{1 245}

Elimination Route

Excreted almost completely in urine as unchanged drug and metabolites.^{1 2 70 73 165}

Plasma clearance is decreased when urine pH ≥8.¹

Half-life

Biphasic; terminal elimination half-life is about 11.5–16 hours.^{56 70 72 80}

Special Populations

In patients with VPCs,^{1 2 30 58 59 70 75 76 165} CHF,^{2 56 70} or renal^{1 2 70 165} or hepatic¹ impairment, plasma clearance is decreased.

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.^{1 165}

ActionsActions

• 
  

  Membrane-stabilizing antiarrhythmic agent; exhibits local anesthetic effects.^{1 2 3 4 5 6 12 13 14 165}

  
  


• 
  

  Principal effect on cardiac tissue appears to be concentration-dependent inhibition of transmembrane influx of extracellular sodium ions via fast sodium channels.^{6 11 12 13 14 15 16 17}

  
  


• 
  

  Combines with fast sodium channels within the myocardium and inhibits rapid sodium influx, which decreases the maximal rate of depolarization of phase 0 of the action potential.^{6 11 12 13 14 15 16 17}

  
  


• 
  

  Combines with fast sodium channels in their inactive state^{12 13 17} and inhibits recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels.^{12 13 17}

  
  


• 
  

  Exhibits electrophysiologic effects characteristic of class IC antiarrhythmic agents, which slowly attach to and dissociate from transmembrane sodium channels.^{1 2 3 4 5 12 13 14 20 165}

  
  


• 
  

  Produces dose-related decrease in intracardiac conduction throughout the heart, with the most marked effect on conduction within the His-Purkinje system.^{1 2 3 4 5 22 24 165}

  
  


• 
  

  Produces dose-related increases in PR, QRS, AH, and, to a lesser degree, QT intervals.^{1 2 3 22 23 24 25 27 30 52 53 58 59 76 89 94 102 104 165}

  
  


• 
  

  May increase atrial effective refractory period (ERP) ^{22 23 24 26 31 36 77 145} and ventricular ERP.^{23 24 25 36 52 53 77 92}

  
  


• 
  

  Exhibits a mild to moderate negative inotropic effect.^{1 2 10 18 19 60 61 62 63 64 65 66 67 68 165}

  
  

Advice to Patients

• 
  

  Importance of not altering therapy without first consulting clinician.^{162 164 172}

  
  


• 
  

  Advise patients who self-administer loading dose for conversion of paroxysmal atrial fibrillation to remain in a supine or sitting position until resolution of palpitations or for a period of at least 4 hours following the dose.^{224 242} Importance of informing clinician if palpitations do not resolve within 6–8 hours, previously unexperienced symptoms (e.g., dyspnea, presyncope, syncope) occur, or a marked increase in heart rate develops.²²⁴

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (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

Flecainide Acetate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	50 mg*	Flecainide Acetate Tablets
			Tambocor	3M
		100 mg*	Flecainide Acetate Tablets
			Tambocor (scored)	3M
		150 mg*	Flecainide Acetate Tablets
			Tambocor (scored)	3M

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.

Flecainide Acetate 100MG Tablets (MYLAN): 60/$83.98 or 180/$232.95

Flecainide Acetate 150MG Tablets (MYLAN): 60/$114.98 or 180/$319.93

Flecainide Acetate 50MG Tablets (ROXANE): 60/$57.99 or 180/$155.97

Tambocor 100MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$229.98 or 180/$659.99

Tambocor 150MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$310 or 180/$886.02

Tambocor 50MG Tablets (GRACEWAY PHARMACEUTICALS): 60/$145.98 or 180/$421.98

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, in

Thiabendazole

Pronunciation: thye-a-BEN-da-zole
Generic Name: Thiabendazole
Brand Name: Mintezol

Thiabendazole is used for:

Treating worm infections. It may also be used for other conditions as determined by your doctor.

Thiabendazole is an anthelmintic. The exact way Thiabendazole works is unknown. It is thought to work by blocking egg and larva production. It may also block a certain enzyme needed by the parasite.

Do NOT use Thiabendazole if:

• you are allergic to any ingredient in Thiabendazole

Contact your doctor or health care provider right away if any of these apply to you.

Before using Thiabendazole:

Some medical conditions may interact with Thiabendazole. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have liver or kidney problems


• if you have anemia or improper nutrition or you are dehydrated

Some MEDICINES MAY INTERACT with Thiabendazole. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Xanthine derivatives (eg, theophylline) because side effects, including risk of nausea, vomiting, heart problems, or seizures, may be increased by Thiabendazole

This may not be a complete list of all interactions that may occur. Ask your health care provider if Thiabendazole may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Thiabendazole:

Use Thiabendazole as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Thiabendazole after meals.


• Chew thoroughly before swallowing.


• To clear up your infection completely, continue using Thiabendazole for the full course of treatment even if you feel better in a few days.


• If you miss a dose of Thiabendazole, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Thiabendazole.

Important safety information:

• Thiabendazole may cause drowsiness, dizziness, blurred vision, or lightheadedness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Thiabendazole. Using Thiabendazole alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Strict hygiene is essential to prevent reinfection. To prevent getting this infection again, disinfect toilet facilities daily and change and wash underwear, bed linens, towels, and pajamas daily.


• Pinworm infections are easily spread to others. If one family member has a pinworm infection, all family members in close contact with the patient should be treated. This decreases the chance of spreading the infection.


• Do not use Thiabendazole to prevent worm infestations.


• Thiabendazole may cause high blood sugar (eg, thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, fruity breath odor). If these symptoms occur, tell your doctor immediately.


• LAB TESTS, including liver function tests, may be performed to monitor your progress. Be sure to keep all doctor and lab appointments.


• Use Thiabendazole with caution in the ELDERLY because they may be more sensitive to its effects.


• Use Thiabendazole with extreme caution in CHILDREN younger than 4 years of age or who weigh less than 30 pounds (13.6 kg). Safety and effectiveness in these age and weight groups have not been established.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Thiabendazole during pregnancy. It is unknown if Thiabendazole is excreted in breast milk. Do not breast-feed while taking Thiabendazole.

Possible side effects of Thiabendazole:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Appetite loss; bad urine odor; diarrhea; dizziness; drowsiness; dry eyes; giddiness; headache; indigestion; irritability; nausea; sensation of floating; stomach upset or pain; tiredness; vomiting; weakness; worms in mouth or nose.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in urine; blurred vision; change in vision; chills; collapse; confusion; dark urine; depression; enlarged lymph nodes; flushing; hoarseness; increased thirst or urination; loss of coordination; numbness; red, swollen, or blistered skin; ringing in the ears; seizures; severe stomach pain; sore throat or fever; strange feeling in your eyes; uncontrolled urination; vision tinged yellow; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Thiabendazole side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include changes in vision or personality; mental/mood changes.

Proper storage of Thiabendazole:

Store Thiabendazole at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Thiabendazole out of the reach of children and away from pets.

General information:

• If you have any questions about Thiabendazole, please talk with your doctor, pharmacist, or other health care provider.


• Thiabendazole is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Thiabendazole. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Thiabendazole resources

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

• Thiabendazole Professional Patient Advice (Wolters Kluwer)


• thiabendazole Concise Consumer Information (Cerner Multum)


• thiabendazole Advanced Consumer (Micromedex) - Includes Dosage Information


• Mintezol Prescribing Information (FDA)

Compare Thiabendazole with other medications

• Angiostrongylosis
• Ascariasis
• Capillariasis
• Cutaneous Larva Migrans
• Dracunculiasis
• Hookworm Infection, Necator or Ancylostoma
• Strongyloidiasis
• Trichinosis
• Trichostrongylosis
• Visceral Larva Migrans, Toxicariasis
• Whipworm Infection

Tasmar

tolcapone

Dosage Form: tablet, film coated
Tasmar®

(tolcapone)

TABLETS

Before prescribing Tasmar, the physician should be thoroughly familiar with the details of this prescribing information.

Tasmar SHOULD NOT BE USED BY PATIENTS UNTIL THERE HAS BEEN A COMPLETE DISCUSSION OF THE RISKS AND THE PATIENT HAS PROVIDED WRITTEN ACKNOWLEDGEMENT THAT THE RISKS HAVE BEEN EXPLAINED (SEE PATIENT ACKNOWLEDGEMENT OF RISKS SECTION).

Warning

Because of the risk of potentially fatal, acute fulminant liver failure, Tasmar (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies (see INDICATIONS and DOSAGE AND ADMINISTRATION sections).

Because of the risk of liver injury and because Tasmar, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from Tasmar.

Tasmar therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis).

Patients who develop evidence of hepatocellular injury while on Tasmar and are withdrawn from the drug for any reason may be at increased risk for liver injury if Tasmar is reintroduced. Accordingly, such patients should not ordinarily be considered for retreatment.

Cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported in postmarketing use. As of May 2005, 3 cases of fatal fulminant hepatic failure have been reported from more than 40,000 patient years of worldwide use. This incidence may be 10- to 100-fold higher than the background incidence in the general population. Underreporting of cases may lead to significant underestimation of the increased risk associated with the use of Tasmar. All 3 cases were reported within the first six months of initiation of treatment with Tasmar. Analysis of the laboratory monitoring data in over 3,400 Tasmar-treated patients participating in clinical trials indicated that increases in SGPT/ALT or SGOT/AST, when present, generally occurred within the first 6 months of treatment with Tasmar.

A prescriber who elects to use Tasmar in face of the increased risk of liver injury is strongly advised to monitor patients for evidence of emergent liver injury. Patients should be advised of the need for self-monitoring for both the classical signs of liver disease (eg, clay colored stools, jaundice) and the nonspecific ones (eg, fatigue, loss of appetite, lethargy).

Although a program of periodic laboratory monitoring for evidence of hepatocellular injury is recommended, it is not clear that periodic monitoring of liver enzymes will prevent the occurrence of fulminant liver failure. However, it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended.

Before starting treatment with Tasmar, the physician should conduct appropriate tests to exclude the presence of liver disease. In patients determined to be appropriate candidates for treatment with Tasmar, serum glutamic-pyruvic transaminase (SGPT/ALT) and serum glutamic-oxaloacetic transaminase (SGOT/AST) levels should be determined at baseline and periodically (i.e. every 2 to 4 weeks) for the first 6 months of therapy. After the first six months, periodic monitoring is recommended at intervals deemed clinically relevant. Although more frequent monitoring increases the chances of early detection, the precise schedule for monitoring is a matter of clinical judgement. If the dose is increased to 200 mg tid (see DOSAGE AND ADMINISTRATION section), liver enzyme monitoring should take place before increasing the dose and then be conducted every 2 to 4 weeks for the following 6 months of therapy. After six months, periodic monitoring is recommended at intervals deemed clinically relevant.

Tasmar should be discontinued if SGPT/ALT or SGOT/AST levels exceed 2 times the upper limit of normal or if clinical signs and symptoms suggest the onset of hepatic dysfunction (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, and right upper quadrant tenderness).

Tasmar Description

Tasmar® is available as tablets containing 100 mg or 200 mg tolcapone.

Tolcapone, an inhibitor of catechol-O-methyltransferase (COMT), is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa therapy. It is a yellow, odorless, non-hygroscopic, crystalline compound with a relative molecular mass of 273.25. The chemical name of tolcapone is 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone. Its empirical formula is C14H11NO5 and its structural formula is:

Inactive ingredients: Core: lactose monohydrate, microcrystalline cellulose, dibasic calcium phosphate anhydrous, povidone K-30, sodium starch glycolate, talc and magnesium stearate. Film coating: hydroxypropyl methylcellulose, titanium dioxide, talc, ethylcellulose, triacetin and sodium lauryl sulfate, with the following dye systems: 100 mg — yellow and red iron oxide; 200 mg — red iron oxide.

Tasmar - Clinical Pharmacology

Mechanism of Action

Tolcapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT).

In mammals, COMT is distributed throughout various organs. The highest activities are in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing the metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.

The precise mechanism of action of tolcapone is unknown, but it is believed to be related to its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. Tolcapone enters the CNS to a minimal extent, but has been shown to inhibit central COMT activity in animals.

Pharmacodynamics

COMT Activity in Erythrocytes

Studies in healthy volunteers have shown that tolcapone reversibly inhibits human erythrocyte catechol-O-methyltransferase (COMT) activity after oral administration. The inhibition is closely related to plasma tolcapone concentrations. With a 200-mg single dose of tolcapone, maximum inhibition of erythrocyte COMT activity is on average greater than 80%. During multiple dosing with tolcapone (200 mg tid), erythrocyte COMT inhibition at trough tolcapone blood concentrations is 30% to 45%.

Effect on the Pharmacokinetics of Levodopa and its Metabolites

When tolcapone is administered together with levodopa/carbidopa, it increases the relative bioavailability (AUC) of levodopa by approximately twofold. This is due to a decrease in levodopa clearance resulting in a prolongation of the terminal elimination half-life of levodopa (from approximately 2 hours to 3.5 hours). In general, the average peak levodopa plasma concentration (Cmax) and the time of its occurrence (Tmax) are unaffected. The onset of effect occurs after the first administration and is maintained during long-term treatment. Studies in healthy volunteers and Parkinson's disease patients have confirmed that the maximal effect occurs with 100 mg to 200 mg tolcapone. Plasma levels of 3-OMD are markedly and dose-dependently decreased by tolcapone when given with levodopa/carbidopa.

Population pharmacokinetic analyses in patients with Parkinson's disease have shown the same effects of tolcapone on levodopa plasma concentrations that occur in healthy volunteers.

Pharmacokinetics of Tolcapone

Tolcapone pharmacokinetics are linear over the dose range of 50 mg to 400 mg, independent of levodopa/carbidopa coadministration. The elimination half-life of tolcapone is 2 to 3 hours and there is no significant accumulation. With tid dosing of 100 mg or 200 mg, Cmax is approximately 3 µg/mL and 6 µg/mL, respectively.

Absorption

Tolcapone is rapidly absorbed, with a Tmax of approximately 2 hours. The absolute bioavailability following oral administration is about 65%. Food given within 1 hour before and 2 hours after dosing of tolcapone decreases the relative bioavailability by 10% to 20% (see DOSAGE AND ADMINISTRATION).

Distribution

The steady-state volume of distribution of tolcapone is small (9 L). Tolcapone does not distribute widely into tissues due to its high plasma protein binding. The plasma protein binding of tolcapone is >99.9% over the concentration range of 0.32 to 210 µg/mL. In vitro experiments have shown that tolcapone binds mainly to serum albumin.

Metabolism and Elimination

Tolcapone is almost completely metabolized prior to excretion, with only a very small amount (0.5% of dose) found unchanged in urine. The main metabolic pathway of tolcapone is glucuronidation; the glucuronide conjugate is inactive. In addition, the compound is methylated by COMT to 3-O-methyl-tolcapone. Tolcapone is metabolized to a primary alcohol (hydroxylation of the methyl group), which is subsequently oxidized to the carboxylic acid. In vitro experiments suggest that the oxidation may be catalyzed by cytochrome P450 3A4 and P450 2A6. The reduction to an amine and subsequent N-acetylation occur to a minor extent. After oral administration of a 14C-labeled dose of tolcapone, 60% of labeled material is excreted in urine and 40% in feces. Tolcapone is a low-extraction-ratio drug (extraction ratio = 0.15) with a moderate systemic clearance of about 7 L/h.

Special Populations

Tolcapone pharmacokinetics are independent of sex, age, body weight, and race (Japanese, Black and Caucasian). Polymorphic metabolism is unlikely based on the metabolic pathways involved.

Hepatic Impairment

A study in patients with hepatic impairment has shown that moderate non-cirrhotic liver disease had no impact on the pharmacokinetics of tolcapone. In patients with moderate cirrhotic liver disease (Child-Pugh Class B), however, clearance and volume of distribution of unbound tolcapone was reduced by almost 50%. This reduction may increase the average concentration of unbound drug by twofold (see DOSAGE AND ADMINISTRATION). Tasmar therapy should not be initiated if the patient exhibits clinical evidence of active liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal (see BOXED WARNING).

Renal Impairment

The pharmacokinetics of tolcapone have not been investigated in a specific renal impairment study. However, the relationship of renal function and tolcapone pharmacokinetics has been investigated using population pharmacokinetics during clinical trials. The data of more than 400 patients have confirmed that over a wide range of creatinine clearance values (30 mL/min to 130 mL/min) the pharmacokinetics of tolcapone are unaffected by renal function. This could be explained by the fact that only a negligible amount of unchanged tolcapone (0.5%) is excreted in the urine. The glucuronide conjugate of tolcapone is mainly excreted in the urine but is also excreted in the bile. Accumulation of this stable and inactive metabolite should not present a risk in renally impaired patients with creatinine clearance above 25 mL/min (see DOSAGE AND ADMINISTRATION). Given the very high protein binding of tolcapone, no significant removal of the drug by hemodialysis would be expected.

Drug Interactions

See PRECAUTIONS: Drug Interactions.

Clinical Studies

The effectiveness of Tasmar as an adjunct to levodopa in the treatment of Parkinson's disease was established in three multicenter randomized controlled trials of 13 to 26 weeks' duration, supported by four 6-week trials whose results were consistent with those of the longer trials. In two of the longer trials, tolcapone was evaluated in patients whose Parkinson's disease was characterized by deterioration in their response to levodopa at the end of a dosing interval (so-called fluctuating patients with wearing-off phenomena). In the remaining trial, tolcapone was evaluated in patients whose response to levodopa was relatively stable (so-called non-fluctuators).

Fluctuating Patients

In two 3-month trials, patients with documented episodes of wearing-off phenomena, despite optimum levodopa therapy, were randomized to receive placebo, tolcapone 100 mg tid or 200 mg tid. The formal double-blind portion of the trial was 3 months long, and the primary outcome was a comparison between treatments in the change from baseline in the amount of time spent "On" (a period of relatively good functioning) and "Off" (a period of relatively poor functioning). Patients recorded periodically, throughout the duration of the trial, the time spent in each of these states.

In addition to the primary outcome, patients were also assessed using sub-parts of the Unified Parkinson's Disease Rating Scale (UPDRS), a frequently used multi-item rating scale intended to evaluate mentation (Part I), activities of daily living (Part II), motor function (Part III), complications of therapy (Part IV), and disease staging (Parts V and VI); an Investigator's Global Assessment of Change (IGA), a subjective scale designed to assess global functioning in 5 areas of Parkinson's disease; the Sickness Impact Profile (SIP), a multi-item scale in 12 domains designed to assess the patient's functioning in multiple areas; and the change in daily levodopa/carbidopa dose.

In one of the studies, 202 patients were randomized in 11 centers in the United States and Canada. In this trial, all patients were receiving concomitant levodopa and carbidopa. In the second trial, 177 patients were randomized in 24 centers in Europe. In this trial, all patients were receiving concomitant levodopa and benserazide.

The following tables display the results of these 2 trials:

Table 1. US/Canadian Fluctuator Study

* Compared to placebo. † Hours "Off" or "On" are based on the percent of waking day "Off" or "On",assuming a 16-hour waking day.
Primary Measure
	Baseline (hrs)	Change from Baseline at Month 3 (hrs)	p-value*
Hours of Wake Time "Off " †
Placebo	6.2	-1.2	—
100 mg tid	6.4	-2.0	0.169
200 mg tid	5.9	-3.0	<0.001
Hours of Wake Time "On" †
Placebo	8.7	1.4	—
100 mg tid	8.1	2.0	0.267
200 mg tid	9.1	2.9	0.008
Secondary Measures
	Baseline	Change from Baseline
		at Month 3	p-value*
Levodopa Total Daily Dose (mg)
Placebo	948	16	—
100 mg tid	788	-166	<0.001
200 mg tid	865	-207	<0.001
Global (overall) % Improved
Placebo	—	42	—
100 mg tid	—	71	<0.001
200 mg tid	—	91	<0.001
UPDRS Motor
Placebo	19.5	-0.4	—
100 mg tid	17.6	-1.9	0.217
200 mg tid	20.6	-2.0	0.210
UPDRS ADL
Placebo	7.5	-0.3	—
100 mg tid	7.7	-0.8	0.487
200 mg tid	8.3	0.2	0.412
SIP (total)
Placebo	14.7	-2.2	—
100 mg tid	14.9	-0.4	0.210
200 mg tid	17.6	-0.3	0.216

Table 2. European Fluctuator Study

Effects on "Off" time and levodopa dose did not differ by age or sex.
* Compared to placebo. † Hours "Off" or "On" are based on the percent of waking day "Off" or "On", assuming a 16-hour waking day.
Primary Measure
	Baseline (hrs)	Change from Baseline at Month 3 (hrs)	p-value*
Hours of Wake Time "Off " †
Placebo	6.1	-0.7	—
100 mg tid	6.5	-2.0	0.008
200 mg tid	6.0	-1.6	0.081
Hours of Wake Time "On" †
Placebo	8.5	-0.1	—
100 mg tid	8.1	1.7	0.003
200 mg tid	8.4	1.7	0.003
Secondary Measures
	Baseline	Change from Baseline
		at Month 3	p-value*
Levodopa Total Daily Dose (mg)
Placebo	660	-29	—
100 mg tid	667	-109	0.025
200 mg tid	675	-122	0.010
Global (overall) % Improved
Placebo	—	37	—
100 mg tid	—	70	0.003
200 mg tid	—	78	<0.001
UPDRS Motor
Placebo	24.0	-2.1	—
100 mg tid	22.4	-4.2	0.163
200 mg tid	22.4	-6.5	0.004
UPDRS ADL
Placebo	7.9	-0.5	—
100 mg tid	7.5	-0.9	0.408
200 mg tid	7.7	-1.3	0.097
SIP (total)
Placebo	21.6	-0.9	—
100 mg tid	16.6	-1.9	0.419
200 mg tid	18.4	-4.2	0.011

Non-fluctuating Patients

In this study, 298 patients with idiopathic Parkinson's disease on stable doses of levodopa/carbidopa who were not experiencing wearing-off phenomena were randomized to placebo, tolcapone 100 mg tid, or tolcapone 200 mg tid for 6 months at 20 centers in the United States and Canada. The primary measure of effectiveness was the Activities of Daily Living portion (Subscale II) of the UPDRS. In addition, the change in daily levodopa dose, other subscales of the UPDRS, and the SIP were assessed as secondary measures. The results are displayed in the following table:

Table 3. US/Canadian Non-fluctuator Study

Effects on Activities of Daily Living did not differ by age or sex.
* Compared to placebo.
Primary Measure
	Baseline	Change from Baseline
		at Month 6	p-value*
UPDRS ADL
Placebo	8.5	0.1	—
100 mg tid	7.5	-1.4	<0.001
200 mg tid	7.9	-1.6	<0.001
Secondary Measures
	Baseline	Change from Baseline
		at Month 6	p-value*
Levodopa Total Daily Dose (mg)
Placebo	364	47	—
100 mg tid	370	-21	<0.001
200 mg tid	381	-32	<0.001
UPDRS Motor
Placebo	19.7	0.1	—
100 mg tid	17.3	-2.0	0.018
200 mg tid	16.0	-2.3	0.008
SIP (total)
Placebo	6.9	0.4	—
100 mg tid	7.3	-0.9	0.044
200 mg tid	7.3	-0.7	0.078
Percent of Patients who
Developed Fluctuations
Placebo	—	26	—
100 mg tid	—	19	0.297
200 mg tid	—	14	0.047

INDICATIONS

Tasmar is indicated as an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson's disease. Because of the risk of potentially fatal, acute fulminant liver failure, Tasmar (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies. Because of the risk of liver injury and because Tasmar, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from Tasmar.

The effectiveness of Tasmar was demonstrated in randomized controlled trials in patients receiving concomitant levodopa therapy with carbidopa or another aromatic amino acid decarboxylase inhibitor who experienced end of dose wearing-off phenomena as well as in patients who did not experience such phenomena (see CLINICAL PHARMACOLOGY: Clinical Studies).

Contraindications

Tasmar tablets are contraindicated in patients with liver disease, in patients who were withdrawn from Tasmar because of evidence of Tasmar-induced hepatocellular injury or who have demonstrated hypersensitivity to the drug or its ingredients.

Tasmar is also contraindicated in patients with a history of nontraumatic rhabdomyolysis or hyperpyrexia and confusion possibly related to medication (see PRECAUTIONS: Events Reported With Dopaminergic Therapy).

Warnings

(SEE BOXED WARNING) Because of the risk of potentially fatal, acute fulminant liver failure, Tasmar (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies (see INDICATIONS and DOSAGE AND ADMINISTRATION sections).

Because of the risk of liver injury and because Tasmar, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from Tasmar.

Tasmar therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis).

Patients who develop evidence of hepatocellular injury while on Tasmar and are withdrawn from the drug for any reason may be at increased risk for liver injury if Tasmar is reintroduced. Accordingly, such patients should not ordinarily be considered for retreatment.

In controlled Phase 3 trials, increases to more than 3 times the upper limit of normal in ALT or AST occurred in approximately 1% of patients at 100 mg tid and 3% of patients at 200 mg tid. Females were more likely than males to have an increase in liver enzymes (approximately 5% vs 2%). Approximately one third of patients with elevated enzymes had diarrhea. Increases to more than 8 times the upper limit of normal in liver enzymes occurred in 0.3% at 100 mg tid and 0.7% at 200 mg tid. Elevated enzymes led to discontinuation in 0.3% and 1.7% of patients treated with 100 mg tid and 200 mg tid, respectively. Elevations usually occurred within 6 weeks to 6 months of starting treatment. In about half the cases with elevated liver enzymes, enzyme levels returned to baseline values within 1 to 3 months while patients continued Tasmar treatment. When treatment was discontinued, enzymes generally declined within 2 to 3 weeks but in some cases took as long as 1 to 2 months to return to normal.

Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. It is theoretically possible, therefore, that the combination of Tasmar and a non-selective MAO inhibitor (eg, phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism. For this reason, patients should ordinarily not be treated concomitantly with Tasmar and a non-selective MAO inhibitor.

Tolcapone can be taken concomitantly with a selective MAO-B inhibitor (eg, selegiline).

Precautions

Hypotension/Syncope

Dopaminergic therapy in Parkinson's disease patients has been associated with orthostatic hypotension. Tolcapone enhances levodopa bioavailability and, therefore, may increase the occurrence of orthostatic hypotension. In Tasmar clinical trials, orthostatic hypotension was documented at least once in 8%, 14% and 13% of the patients treated with placebo, 100 mg and 200 mg Tasmar tid, respectively. A total of 2%, 5% and 4% of the patients treated with placebo, 100 mg and 200 mg Tasmar tid, respectively, reported orthostatic symptoms at some time during their treatment and also had at least one episode of orthostatic hypotension documented (however, the episode of orthostatic symptoms itself was invariably not accompanied by vital sign measurements). Patients with orthostasis at baseline were more likely than patients without symptoms to have orthostatic hypotension during the study, irrespective of treatment group. In addition, the effect was greater in tolcapone-treated patients than in placebo-treated patients. Baseline treatment with dopamine agonists or selegiline did not appear to increase the likelihood of experiencing orthostatic hypotension when treated with Tasmar. Approximately 0.7% of the patients treated with Tasmar (5% of patients who were documented to ha