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Friday, October 21, 2016

diphtheria, tetanus, acellular pertussis vaccine

Generic Name: diphtheria, tetanus, acellular pertussis vaccine (DTaP) (dif THEER ee uh, TET a nus, ay SEL yoo ler per TUS iss)

Brand names: Daptacel (DTaP), Infanrix (DTaP), Infanrix (DTaP) Preservative Free, Tripedia (DTaP), Boostrix (obsolete1)

What is diphtheria, tetanus, acellular pertussis vaccine?

Diphtheria, tetanus, and pertussis are serious diseases caused by bacteria.

Diphtheria causes a thick coating in the nose, throat, and airways. It can lead to breathing problems, paralysis, heart failure, or death.

Pertussis (whooping cough) causes coughing so severe that it interferes with eating, drinking, or breathing. These spells can last for weeks and can lead to pneumonia, seizures (convulsions), brain damage, and death.

Tetanus (lockjaw) causes painful tightening of the muscles, usually all over the body. It can lead to "locking" of the jaw so the victim cannot open the mouth or swallow. Tetanus leads to death in about 1 out of 10 cases.

Diphtheria and pertussis are spread from person to person. Tetanus enters the body through a cut or wound.

The diphtheria, tetanus acellular, and pertussis pediatric vaccine (also called DTaP) is used to help prevent these diseases in children who are ages 6 weeks to 6 years old (before the child has reached his or her 7th birthday).

This vaccine works by exposing your child to a small dose of the bacteria or a protein from the bacteria, which causes the body to develop immunity to the disease. This vaccine will not treat an active infection that has already developed in the body.

Like any vaccine, the DTaP vaccine may not provide protection from disease in every person.

What is the most important information I should know about diphtheria, tetanus, acellular pertussis vaccine?

This vaccine is given in a series of shots. The first shot is usually given when the child is 2 months old. The booster shots are then given at 4 months, 6 months, 15 months, and 18 months of age, and again between 4 and 6 years of age. Your child's booster schedule may be different from these guidelines. Follow your doctor's instructions or the schedule recommended by your local health department.

Be sure your child receives all recommended doses of this vaccine. Your child may not be fully protected against disease if he or she does not receive the full series.

Your child can still receive a vaccine if he or she has a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until the child gets better before receiving this vaccine.

Your child should not receive a booster vaccine if he or she had a life-threatening allergic reaction after the first shot.

Keep track of any and all side effects your child has after receiving this vaccine. When the child receives a booster dose, you will need to tell the doctor if the previous shot caused any side effects.

Becoming infected with diphtheria, pertussis, or tetanus is much more dangerous to your child's health than receiving this vaccine. However, like any medicine, this vaccine can cause side effects but the risk of serious side effects is extremely low.

What should I discuss with my healthcare provider before receiving this vaccine?

Your child should not receive this vaccine if he or she has ever had a life-threatening allergic reaction to any vaccine containing diphtheria, pertussis, or tetanus, or if the child has:

severe or uncontrolled epilepsy or other seizure disorder; or

if the child has received cancer chemotherapy or radiation treatment in the past 3 months.

Your child may not be able to receive this vaccine if he or she has ever received a similar vaccine that caused any of the following:

a very high fever (over 104 degrees);

a neurologic disorder or disease affecting the brain;

excessive crying for 3 hours or longer;

fainting or going into shock;

seizure (convulsions); or

Guillain-Barré syndrome (within 6 weeks after receiving a vaccine containing tetanus).

Before receiving this vaccine, tell the doctor if your child has:

a bleeding or blood clotting disorder such as hemophilia or easy bruising;

a history of seizures;

a neurologic disorder or disease affecting the brain (or if this was a reaction to a previous vaccine);

a weak immune system caused by disease, bone marrow transplant, or by using certain medicines or receiving cancer treatments; or

if the child is taking a blood thinner such as warfarin (Coumadin); or

if it has been less than 4 weeks since the child last received a DTaP vaccine.

The pediatric version of this vaccine (Daptacel, Infanrix, Tripedia) should not be given to anyone over the age of 6 years old. Another vaccine is available for use in older children and adults.

How is this vaccine given?

This vaccine is injected into a muscle. Your child will receive this injection in a doctor's office or clinic setting.

Your doctor may recommend treating fever and pain with an aspirin-free pain reliever such as acetaminophen (Tylenol) or ibuprofen (Motrin, Advil, and others) when the shot is given and for the next 24 hours. Follow the label directions or your doctor's instructions about how much of this medicine to give your child.

It is especially important to prevent fever from occurring in a child who has a seizure disorder such as epilepsy.

What happens if I miss a dose?

Contact your doctor if you will miss a booster dose or if you get behind schedule. The next dose should be given as soon as possible. There is no need to start over.

Be sure your child receives all recommended doses of this vaccine. Your child may not be fully protected if he or she does not receive the full series.

What happens if I overdose?

An overdose of this vaccine is unlikely to occur.

What should I avoid before or after receiving this vaccine?

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

Diphtheria, tetanus, acellular pertussis vaccine side effects

Your child should not receive a booster vaccine if he or she had a life-threatening allergic reaction after the first shot.

Keep track of any and all side effects your child has after receiving this vaccine. When the child receives a booster dose, you will need to tell the child's doctor if the previous shot caused any side effects.

Get emergency medical help if your child has any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if the child has a serious side effect such as:

extreme drowsiness, fainting;

fussiness, irritability, crying for an hour or longer;

seizure (black-out or convulsions); or

high fever.

Less serious side effects include:

mild fever or chills;

redness, pain, tenderness, or swelling where the shot was given;

mild fussiness or crying;

joint pain, body aches;

loss of appetite; or

mild nausea, diarrhea, or vomiting.

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 vaccine side effects to the US Department of Health and Human Services at 1-800-822-7967.

Diphtheria, tetanus, acellular pertussis vaccine Dosing Information

Usual Pediatric Dose for Diphtheria Prophylaxis:

Primary Immunization Series:

DAPTACEL (R):
6 weeks to 6 years (prior to seventh birthday): 0.5 mL IM given as a 4 dose series at 2,4, and 6 months of age, at intervals of 6 to 8 weeks and at 17 to 20 months of age. The interval between the 3rd and 4th dose should be at least 6 months.

INFANRIX (R):
6 weeks to 7 years (prior to seventh birthday): 0.5 mL IM given as a 5 dose series. The series consists of a primary immunization course of 3 doses administered at 2,4, and 6 months of age, followed by 2 booster doses, administered at 15 to 20 months of age and at 4 to 6 years of age. The recommended interval between the first three doses is 8 weeks, with a minimum interval of 4 weeks. The recommended interval between the 3rd and 4th dose is 6 to 12 months. The fifth dose is recommended before entry into kindergarten or elementary school, and is not needed if the fourth dose was given after the fourth birthday.

Tripedia (R):
6 weeks to 7 years (prior to seventh birthday): 0.5 mL IM given as a 5 dose series. The series consists of a primary immunization course of 3 doses administered at 2,4, and 6 months of age, followed by 2 booster doses, administered at 15 to 18 months of age and at 4 to 6 years of age. The recommended interval between the first three doses is 8 weeks, with a minimum interval of 4 weeks. The recommended interval between the 3rd and 4th dose is 6 to 12 months. The fifth dose is recommended before entry into kindergarten or elementary school, and is not needed if the fourth dose was given after the fourth birthday.

Booster Immunization:

BOOSTRIX (R):
10 to 18 years: 0.5 mL IM once. Five years should have elapsed between the administration of BOOSTRIX and the last dose of the recommended series of childhood DTwP and/or DTaP vaccine. Adolescents 10 to 18 years old that have completed a primary series against tetanus and who sustain wounds which are minor and uncomplicated, should receive a booster dose of a tetanus toxoid containing vaccine only if they have not received a tetanus toxoid within the preceding 10 years.

ADACEL (R):
11 to 18 years: 0.5 mL IM once. Individuals who have completed a primary series against tetanus and who sustain wounds which are minor and uncomplicated, should receive a booster dose of a tetanus toxoid containing vaccine only if they have not received a tetanus toxoid within the preceding 10 years. For tetanus prone wounds, a booster is appropriate if the patient has not received a tetanus toxoid containing preparation within the preceding 5 years.

Usual Pediatric Dose for Pertussis Prophylaxis:

Usual Pediatric Dose for Tetanus Prophylaxis:

What other drugs will affect diphtheria, tetanus, acellular pertussis vaccine?

Before receiving this vaccine, tell the doctor about all other vaccines your child has recently received.

Also tell the doctor if your child has recently received drugs or treatments that can weaken the immune system, including:

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

medications to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders, such as azathioprine (Imuran), efalizumab (Raptiva), etanercept (Enbrel), leflunomide (Arava), and others; or

medicines to treat or prevent organ transplant rejection, such as basiliximab (Simulect), cyclosporine (Sandimmune, Neoral, Gengraf), muromonab-CD3 (Orthoclone), mycophenolate mofetil (CellCept), sirolimus (Rapamune), or tacrolimus (Prograf).

This list is not complete and other drugs may interact with this vaccine. 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 diphtheria, tetanus, acellular pertussis vaccine resources

Diphtheria, tetanus, acellular pertussis vaccine Use in Pregnancy & Breastfeeding
Diphtheria, tetanus, acellular pertussis vaccine Drug Interactions
Diphtheria, tetanus, acellular pertussis vaccine Support Group
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Diphtheria Prophylaxis
Pertussis Prophylaxis
Tetanus Prophylaxis

Where can I get more information?

Your doctor or pharmacist can provide more information about this vaccine. Additional information is available from your local health department or the Centers for Disease Control and Prevention.

Dipyridamole

Class: Vasodilating Agents, Miscellaneous
VA Class: BL117
CAS Number: 58-32-2
Brands: Aggrenox, Persantine

Introduction

A non-nitrate coronary vasodilator and platelet aggregation inhibitor.¹⁰⁰ ¹⁷⁰ ¹⁷¹ ¹⁷²

Uses for Dipyridamole

Thromboembolism Associated with Prosthetic Heart Valves

Used as an adjunct to coumarin anticoagulants for the prevention of postoperative thromboembolic complications of heart valve replacement.¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁵⁶ Data are insufficient to recommend the use of dipyridamole over the combination of low-dose aspirin and warfarin in such patients.¹⁵⁶

Should not be used alone, without an oral anticoagulant, in patients with mechanical prosthetic heart valves.¹⁰¹ ¹⁰² ¹⁰⁵ ¹⁰⁸ ¹⁰⁹ ¹⁴⁰ ¹⁴¹ ¹⁴²

Transient Ischemic Attacks and Completed Thrombotic Stroke

Used in extended-release form in fixed combination with aspirin for secondary prevention of stroke in patients who have had TIAs or completed thrombotic stroke.¹⁴⁵ ¹⁴⁶ ¹⁴⁷ ¹⁴⁸ ¹⁴⁹ ¹⁵⁴ ¹⁶⁴

The American College of Chest Physicians (ACCP), American Stroke Association (ASA), and AHA consider the fixed combination of aspirin and extended-release dipyridamole an acceptable option for initial antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke and TIAs.¹⁴⁷ ¹⁴⁹ ¹⁵⁰ ¹⁵⁴ ¹⁶⁴ ¹⁸⁰ In such patients, ACCP, ASA, and AHA recommend the combination of aspirin and extended-release dipyridamole over therapy with aspirin alone and suggest therapy with clopidogrel alone over aspirin alone.¹⁵⁴ ¹⁶⁴ ¹⁸⁰

Adjunct to Thallium Myocardial Perfusion Imaging

Used IV as an adjunct to thallous (thallium) chloride Tl 201 myocardial perfusion imaging in patients unable to exercise adequately.¹⁵⁷ ¹⁵⁸ ¹⁵⁹ ¹⁶⁵

ACC and AHA recommend myocardial stress perfusion imaging with dipyridamole or adenosine or dobutamine echocardiography before or early after hospital discharge in patients with ST-segment-elevation MI who are not undergoing cardiac catheterization and who are unable to exercise.¹⁵⁷

Dipyridamole Dosage and Administration

Administration

Administer orally or IV.¹⁰⁰ ¹⁵⁸

Oral Administration

Administer conventional tablets 4 times daily.¹⁰⁰

Administer extended-release dipyridamole and aspirin fixed-combination capsules twice daily in the morning and evening without regard to food.¹⁴⁵ Swallow capsules whole without chewing.¹⁴⁵

Extended-release dipyridamole in fixed combination with aspirin is not interchangeable with the individual components of aspirin and conventional dipyridamole tablets (e.g., Persantine).¹⁴⁵

IV Administration

Dilution

Dilute injection in ≥1:2 ratio with 0.45% sodium chloride injection, 0.9% sodium chloride injection, or 5% dextrose injection to a final volume of approximately 20–50 mL.¹⁵⁸

Rate of Administration

Adjunct to thallium myocardial perfusion imaging: 0.142 mg/kg per minute for 4 minutes.¹⁵⁸

Administration Risks

Infusion of undiluted injection may cause local irritation.¹⁵⁸

Dosage

Adults

Thromboembolism Associated with Prosthetic Heart Valves

Prophylaxis

Oral

Conventional tablets: 75–100 mg 4 times daily; use in conjunction with coumarin anticoagulant therapy.¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸

Transient Ischemic Attacks and Completed Thrombotic Stroke

Secondary Prevention

Oral

Fixed combination with aspirin: 200 mg of extended-release dipyridamole and 25 mg of aspirin (1 capsule) twice daily in the morning and evening.¹⁴⁵ ¹⁵⁴

If headaches become intolerable during initial treatment, reduce dosage to 200 mg of dipyridamole and 25 mg of aspirin (1 capsule) once daily at bedtime; administer low-dose aspirin in the morning.¹⁴⁵ Resume the usual regimen (200 mg of extended-release dipyridamole and 25 mg of aspirin twice daily) as soon as possible (usually within 1 week) because no outcome data available with the reduced-dose regimen and headaches diminish during continued treatment.¹⁴⁵

Dose of aspirin in fixed-combination product may not be adequate to prevent recurrent MI or angina pectoris in patients with stroke or TIA.¹⁴⁵

If an antiplatelet effect is not desired in patients undergoing elective surgery, discontinue therapy with dipyridamole in fixed combination with aspirin 7–10 days prior to elective surgery.¹⁷⁵

Adjunct to Thallium Myocardial Perfusion Imaging

IV

Single IV dose of 0.57 mg/kg, infused at a rate of 0.142 mg/kg per minute for 4 minutes.¹⁵⁸ ¹⁶⁵ Maximum tolerated IV dose not determined; clinical experience suggests that a total dose >60 mg is not needed for any patient.¹⁵⁸

Inject thallium-201 IV ≤5 minutes following completion of the dipyridamole infusion.¹⁵⁸

Prescribing Limits

Adults

Adjunct to Thallium Myocardial Perfusion Imaging

IV

Clinical experience suggests that a total dipyridamole dose >60 mg is not needed for any patient.¹⁵⁸

Cautions for Dipyridamole

Contraindications

Known hypersensitivity to dipyridamole or any ingredient in the formulation.¹⁰⁰ ¹⁴⁵ ¹⁵⁸

Warnings/Precautions

Warnings

Cardiovascular and Cerebrovascular Effects

Serious adverse effects, including acute myocardial ischemia or MI, cardiac death, VF, symptomatic VT, stroke, transient cerebral ischemia, and seizures, reported with IV infusion.¹⁵⁸ Asystole, sinus node arrest, sinus node depression, and conduction block reported also reported with IV infusion.¹⁵⁸ Patients with abnormalities of cardiac impulse formation or conduction or severe CAD (e.g., unstable angina) may be at increased risk for these events.¹⁵⁸

Weigh the important clinical information to be gained by myocardial perfusion thallium imaging with IV dipyridamole against the risk to the patient. ¹⁵⁸ Consider the rate of false positive and false negative results of dipyridamole-assisted thallium imaging compared with coronary arteriography when choosing to use such imaging.¹⁵⁸

Monitor vital signs during and for 10–15 minutes after IV infusion; obtain an ECG using ≥1 chest lead.¹⁵⁸

Appropriate resuscitative measures should be readily available for relieving adverse effects such as severe chest pain.¹⁵⁸ If severe chest pain occurs, administer IV aminophylline in doses of 50–250 mg by slow IV injection (e.g., 50–100 mg over 30–60 seconds).¹⁵⁸ (See Specific Drugs under Interactions.) Place patients with severe hypotension in a supine position with the head tilted down, if necessary, before administration of IV aminophylline.¹⁵⁸ If the highest recommended dosage of aminophylline (250 mg) does not relieve chest pain within a few minutes, may administer sublingual nitroglycerin.¹⁵⁸ If chest pain continues despite such combination therapy, consider the possibility of MI.¹⁵⁸

If the clinical condition of the patient with an adverse event permits a 1-minute delay, may perform thallium imaging before reversal of the pharmacologic effects occurs.¹⁵⁸ ¹⁶⁵

Sensitivity Reactions

Anaphylactoid reactions and bronchospasm reported with IV dipyridamole.¹⁵⁸ Patients with a history of asthma may be at greater risk for bronchospasm.¹⁵⁸

Appropriate resuscitative measures should be readily available for relieving adverse effects such as severe bronchospasm.¹⁵⁸ ¹⁶⁵ If severe bronchospasm occurs, administer aminophylline in doses of 50–250 mg by slow IV injection (e.g., 50–100 mg over 30–60 seconds).¹⁵⁸ (See Cardiovascular and Cerebrovascular Effects under Cautions.)

General Precautions

Use of Fixed Combinations

When used in fixed combination with aspirin, consider the cautions, precautions, and contraindications associated with aspirin.¹⁴⁵

Cardiovascular Effects

Use with caution in patients with hypotension or severe CAD (e.g., unstable angina, recently sustained MI) since peripheral vasodilation may occur.¹⁰⁰ ¹⁴⁵ Dipyridamole may precipitate chest pain in patients with CAD.¹⁰⁰ ¹⁴⁵

Amount of aspirin in the commercially available fixed-combination product may not be adequate to prevent recurrent MI or angina pectoris in patients with stroke or TIA.¹⁴⁵

Hepatic Effects

Liver dysfunction (e.g., elevations of hepatic enzymes, hepatic failure) reported.¹⁰⁰ ¹⁴⁵

Specific Populations

Pregnancy

Category B: Conventional tablets and injection.¹⁰⁰ ¹⁵⁸

Category D: Fixed combination with aspirin.¹⁴⁵

Lactation

Distributed into milk.¹⁰⁰ ¹⁴⁵ ¹⁵⁸ Use caution.¹⁰⁰ ¹⁴⁵

Pediatric Use

Conventional tablets: Safety and efficacy not established in pediatric patients <12 years of age.¹⁰⁰

Fixed combination with aspirin: Safety and efficacy not established;¹⁴⁵ should not be used in pediatric patients because of aspirin component.¹⁴⁵

Injection: Safety and efficacy not established.¹⁵⁸

Common Adverse Effects

Conventional tablets: Headache,¹⁰⁰ dizziness,¹⁰⁰ GI intolerance (e.g., abdominal distress),¹⁰⁰ vomiting,¹⁰⁰ diarrhea,¹⁰⁰ flushing,¹⁰⁰ rash,¹⁰⁰ pruritus.¹⁰⁰

Injection: Chest pain/angina pectoris,¹⁵⁸ ECG changes (most commonly ST-T changes),¹⁵⁸ headache,¹⁵⁸ dizziness.¹⁵⁸

Interactions for Dipyridamole

Specific Drugs

Drug	Interaction	Comments
Adenosine	Potentiation of adenosine vasoactive effects¹⁰⁰ ¹⁶⁸ ¹⁶⁹ Increased plasma adenosine concentrations¹⁰⁰ ¹⁶⁸ ¹⁶⁹	Dosage adjustment of adenosine may be necessary¹⁰⁰ ¹⁶⁸ ¹⁶⁹
Anticholinesterase agents	Antagonizes anticholinesterase effects¹⁰⁰ ¹⁵⁸	Potential to aggravate myasthenia gravis¹⁰⁰ ¹⁵⁸
Heparin	Possible increased risk of bleeding complications¹⁶⁶ ¹⁶⁷	Use with caution and monitor closely¹⁶⁶ ¹⁶⁷
Methylxanthines (e.g., aminophylline, caffeine [e.g., coffee], theophylline	Inhibits dipyridamole vasodilatory and bronchospastic effects¹⁵⁸ ¹⁶⁵	Aminophylline used to terminate persistent adverse effects of dipyridamole¹⁵⁸ Caffeine or theophylline may lead to false-negative thallium imaging results;¹⁵⁸ some clinicians recommend withholding caffeine (e.g., coffee) for 24 hours prior to testing¹⁶⁵
Warfarin	Possible increased risk of bleeding, particularly during or after surgery; however, concomitant use does not appear to increase frequency or severity of bleeding compared with use of warfarin alone¹⁰⁰	Some clinicians recommend maintenance of PT in the lower end of the therapeutic range^a

Dipyridamole Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is variable and incomplete;¹⁰¹ ¹³⁴ ¹³⁵ ¹³⁷ ¹³⁸ ¹⁷¹ 37–66% of an oral dose (extended-release capsules containing dipyridamole in fixed combination with aspirin) may be absorbed.¹⁷¹

Following oral administration of conventional tablets, peak plasma concentrations attained in about 45–150 minutes (mean: 75 minutes).¹⁰⁰ ¹³⁴ ¹³⁵ ¹³⁶ ¹³⁸ Peak plasma dipyridamole concentrations attained in about 2 hours (range: 1–6 hours) with twice-daily dosing of extended-release capsules containing dipyridamole in fixed combination with aspirin.¹⁴⁵

Onset

Injection: Peak increase in coronary blood flow occurs 6.5 minutes after initiation of infusion.¹⁵⁸

Duration

Following IV infusion, vital signs return to baseline in approximately 30 minutes.¹⁵⁸ ¹⁶⁵

Food

Capsules containing extended-release dipyridamole in fixed combination with aspirin: High-fat meal reduces peak plasma dipyridamole concentrations and total absorption at steady state by 20–30% compared with fasting state; not clinically relevant.¹⁴⁵

Distribution

Extent

In animals, widely distributed into body tissues; small amounts cross placenta.^a

Does not cross the blood-brain barrier in animals.¹⁴⁵ ¹⁷¹

Distributed into milk.¹⁰⁰ ¹⁵⁸ ¹⁷²

Plasma Protein Binding

91–99%,¹⁰¹ ¹³⁴ ¹³⁸ ¹³⁹ ¹⁵⁸ ¹⁵⁸ ¹⁷¹ principally to α₁-acid glycoprotein (α₁-AGP) but also to albumin.¹⁵⁸ ¹⁶¹ ¹⁶²

Elimination

Metabolism

Metabolized in liver principally to monoglucuronide; small amount metabolized to diglucuronide.¹⁰⁰ ¹⁴⁵ ¹⁵⁸

Elimination Route

Metabolites eliminated principally in feces via biliary excretion¹⁰⁰ ¹⁴⁵ ¹⁵⁸ and to a much lesser extent in urine.¹⁴⁵

Half-life

Conventional tablets: Biphasic; initial half-life approximately 40–80 minutes and terminal half approximately 10–12 hours.¹⁰⁰ ¹⁰¹ ¹³⁴ ¹³⁸ ¹⁷⁵ ¹⁷⁹

Extended-release capsules containing dipyridamole in fixed combination with aspirin: 13.6 hours.¹⁴⁵

IV: Triphasic; mean half-lives of 3–12 minutes, 33–62 minutes, and 11.6–15.5 hours.¹⁵⁸

Stability

Storage

Oral

Capsules and Tablets

Conventional tablets: 25°C (may be exposed to 15–30°C).¹⁰⁰

Extended-release capsules containing dipyridamole in fixed combination with aspirin: 25°C (may be exposed to 15–30°C); protect from excessive moisture.¹⁴⁵

Parenteral

Solution for Injection

20–25°C; avoid freezing and protect from light.¹⁵⁸

Compatibility

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

Parenteral

Do not mix with other drugs in the same syringe or infusion container.¹⁵⁸

ActionsActions

Mechanism of antiplatelet effects not fully elucidated.¹⁰⁰ ¹⁰¹ ¹³⁴ ¹⁷⁰

Inhibits the uptake and metabolism of adenosine in platelets, endothelial cells and erythrocytes.¹⁰⁰ ¹⁴⁵ ¹⁷¹ Increased local concentrations of adenosine at the platelet surface stimulate platelet adenyl cyclase and increase platelet cyclic-3′,5′-adenosine monophosphate (cAMP) concentrations.¹⁰⁰ ¹⁴⁵ ¹⁷¹ Increased platelet cAMP concentrations affect platelet-activating factor, collagen, and adenosine diphosphate and inhibit mobilization of free calcium, which is involved in platelet activation.¹⁰⁰ ¹⁷⁰ ¹⁷¹ Also stimulates prostacyclin synthesis and potentiates antiplatelet effects of prostacyclin.¹⁷¹

Inhibits platelet cyclic-3′,5′-guanosine monophosphate phosphodiesterase (cGMP-PDE).¹⁰⁰ ¹⁴⁵ ¹⁷¹ ⁿ Augments increase in platelet cGMP concentrations produced by nitric oxide;¹⁰⁰ ¹⁴⁵ increased cGMP platelet concentrations inhibit platelet activation and aggregation.¹⁷¹ ⁿ

Prolongs platelet survival time in patients with prosthetic heart valves or valvular heart disease in whom platelet survival is shortened.¹⁰⁰ ^a

Mediates coronary vasodilation by inhibiting reuptake and thereby allowing accumulation of adenosine in vascular smooth muscle.¹⁵⁸ ¹⁶⁵ ⁿ

Methylxanthine derivatives (e.g., theophylline, aminophylline) block adenosine receptors on vascular smooth muscle and abolish vasodilatory effects of dipyridamole.¹⁵⁸ ¹⁶⁵ (See Specific Drugs under Interactions.)

Increases blood flow in normal coronary arteries while producing reduced blood flow in stenotic arteries (“coronary steal”).¹⁵⁸ ¹⁶⁵ Myocardial oxygen consumption and cardiac work not increased.¹⁶⁵

Myocardial uptake of thallous (thallium) chloride Tl 201 is directly proportional to coronary blood flow.¹⁵⁹ ¹⁶⁵ Less thallous chloride Tl 201 uptake¹⁵⁹ occurs in myocardium perfused by stenotic versus normal coronary arteries.¹⁵⁸ ¹⁵⁹ ¹⁶⁰ Enhances the differences in blood flow between areas served by stenotic versus normal arteries during thallium testing.¹⁵⁸ ¹⁵⁹ ¹⁶⁰ ¹⁶⁵

With IV administration, decreases BP and increases heart rate and cardiac output because of dilation of systemic resistance vessels.¹⁵⁸ ¹⁷⁰ ^a With usual oral dosages, generally no change in BP or blood flow in peripheral arteries.¹⁷⁰ ^a

Advice to Patients

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹⁰⁰ ¹⁴⁵ ¹⁵⁸

Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹⁰⁰ ¹⁴⁵ ¹⁵⁸

Importance of informing patients of other important precautionary information.¹⁰⁰ ¹⁴⁵ ¹⁵⁸ (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

Dipyridamole
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	25 mg*	Dipyridamole Tablets
			Persantine	Boehringer Ingelheim
		50 mg*	Dipyridamole Tablets
			Persantine	Boehringer Ingelheim
		75 mg*	Dipyridamole Tablets
			Persantine	Boehringer Ingelheim
Parenteral	Injection, for IV use	5 mg/mL*	Dipyridamole Injection

Dipyridamole Combinations
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules, extended-release (containing dipyridamole pellets and 25 mg immediate-release aspirin tablet)	200 mg with Aspirin 25 mg	Aggrenox	Boehringer Ingelheim

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.

Aggrenox 25-200MG 12-hr Capsules (BOEHRINGER INGELHEIM): 60/$195.99 or 180/$559.95

Dipyridamole 25MG Tablets (TEVA PHARMACEUTICALS USA): 100/$29.99 or 300/$83.97

Dipyridamole 50MG Tablets (GLENMARK PHARMACEUTICALS): 90/$54.99 or 270/$145.96

Dipyridamole 75MG Tablets (GLENMARK PHARMACEUTICALS): 100/$69.99 or 300/$189.98

Persantine 25MG Tablets (BOEHRINGER INGELHEIM): 100/$85.99 or 300/$235.98

Persantine 50MG Tablets (BOEHRINGER INGELHEIM): 100/$139.99 or 300/$399.95

Persantine 75MG Tablets (BOEHRINGER INGELHEIM): 100/$169.99 or 300/$487.97

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 February 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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119. Goldberg TH. Dipyridamole. N Engl J Med. 1987; 317:1735.

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123. Ranhosky A. Dipyridamole. N Engl J Med. 1987; 317:1734. [PubMed 3696181]

124. Jackson MR, Clagett GP. Antithrombotic therapy in peripheral arterial occlusive disease. Chest. 1998; 114(Suppl):666-82S. [PubMed 9743145]

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126. Cairns JA, Theroux P, Lewis HD et al. Antithrombotic agents in coronary artery disease. Chest. 1998; 114(Suppl):611-33S.

127. Keltz TN, Innerfield M, Gitler B et al. Dipyridamole-induced myocardial ischemia. JAMA. 1987; 257:1515-6. [IDIS 226491] [PubMed 2950248]

128. Ranhosky A. Dipyridamole-induced myocardial ischemia. JAMA. 1987; 258:203. [IDIS 231319] [PubMed 3599300]

129. Keltz TN, Gitler B, Cooper JA. Dipyridamole-induced myocardial ischemia. JAMA. 1987; 258:203-4.

130. Dalen JE, Hirsh J. Fifth ACCP consensus conference on antithrombotic therapy. Chest. 1998; 114(Suppl):439-769S.

131. The Persantine-Aspirin Reinfarction Study Research Group. Persantine and aspirin in coronary heart disease. Circulation. 1980; 62:449-61.

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136. Dresse A, Chevolet C, Delapierre D et al. Pharmacokinetics of oral dipyridamole (Persantine) and its effect on platelet adenosine uptake in man. Eur J Clin Pharmacol. 1982; 23:229-34. [IDIS 175837] [PubMed 6756935]

137. Nielsen-Kudsk F, Pedersen AK. Pharmacokinetics of dipyridamole. Acta Pharmacol Toxicol (Copenh). 1979; 44:391-9. [PubMed 474151]

138. Mahony C, Wolfram KM, Cocchetto DM et al. Dipyridamole kinetics. Clin Pharmacol Ther. 1982; 31:330-8. [IDIS 147166] [PubMed 7060316]

139. Kopitar Z, Weisenberger H. Spezifische Bindung von Dipyridamol an ein menschliches Serumprotein. Seine Isolierung, Identifizierung und Charakterisierung als α₁-saures Glycoprotein. (German; with English abstract.) Arzneim-Forsch. 1971; 21:859-62.

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141. Ribeiro PA, Al Zaibag M, Idris M et al. Antiplatelet drugs and the incidence of thromboembolic complications of the St. Jude Medical aortic prosthesis in patients with rheumatic heart disease. J Thorac Cardiovasc Surg. 1986; 91:92-8. [IDIS 210201] [PubMed 3941564]

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144. Gibbons RJ, Chatterjee K, Daley J et al. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Chronic Stable Angina). J Am Coll Cardiol. 1999; 33:2092-197. [IDIS 429504] [PubMed 10362225]

145. Boehringer Ingelheim. Aggrenox(aspirin/extended-release dipyridamole) capsules prescribing information. Ridgefield, CT; 2007 Jan 31.

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147. Albers GW, Easton JD, Sacco RL et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest. 1998; 114:(Suppl 5S):683S-98S. [IDIS 416749] [PubMed 9822071]

148. Diener HC, Cunha L, Forbes C et al. European stroke prevention study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996; 143:1-13. [PubMed 8981292]

149. Albers GW, Hart RG, Lutsep HL et al. Supplement to the guidelines for the management of transient ischemic attacks: a statement from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, American Heart Association. Stroke. 1999; 30:2502-11. [PubMed 10548693]

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158. Bedford Laboratories. Dipyridamole injection prescribing information. Bedford, OH; 2007 Dec.

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More Dipyridamole resources

Dipyridamole Side Effects (in more detail)
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Dipyridamole Support Group
0 Reviews for Dipyridamole - Add your own review/rating

Diprivan

Generic Name: propofol (PROE poe fol)

Brand Names: Diprivan

What is propofol?

Propofol slows the activity of your brain and nervous system.

Propofol is used to help you relax before and during general anesthesia for surgery or other medical procedure. Propofol is also used in critically ill patients who require a breathing tube connected to a ventilator (a machine that moves air in and out of the lungs when a person cannot breathe on their own).

Propofol may be used for other purposes not listed in this medication guide.

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

You should not receive this medication if you are allergic to propofol or to eggs, soy products, or soybeans.

Before you receive propofol, tell your doctor if you have epilepsy or other seizure disorder, high triglycerides (fats in the blood), liver disease, or kidney disease.

Your caregivers will monitor your heart function, blood pressure, and breathing while you are under the effects of propofol.

Tell your caregivers at once if you have a serious side effect such as seizure, weak or shallow breathing, fast or slow heart rate, or pain, swelling, blisters, or skin changes where the medicine was injected.

Before you receive propofol, tell your doctor about all other medications you use, especially chloral hydrate (Somnote), droperidol (Inapsine), a sedative, or a narcotic pain medication such as fentanyl (Actiq, Duragesic).

Propofol can cause severe drowsiness or dizziness, which may last for several hours. You will need someone to drive you home after your surgery or procedure. Do not drive yourself or do anything that requires you to be awake and alert for at least 24 hours after you have been treated with propofol.

What should I discuss with my health care provider before I receive propofol?

You should not receive this medication if you are allergic to propofol or to eggs, soy products, or soybeans.

If you have certain conditions, you may need a dose adjustment or special tests to safely receive this medication. Before you receive propofol, tell your doctor if you have:

epilepsy or other seizure disorder;

high triglycerides (fats in the blood);

liver disease; or

kidney disease.

FDA pregnancy category B. Propofol is not expected to be harmful to an unborn baby. However, tell your doctor if you are pregnant before you are treated with propofol. Propofol can pass into breast milk and may harm a nursing baby. Before you receive this medication, tell your doctor if you are breast-feeding a baby.

How is propofol given?

Propofol is given as an injection through a needle placed into a vein. You will receive this injection in a hospital or surgical setting.

You will relax and fall asleep very quickly after propofol is injected.

Your caregivers will monitor your heart function, blood pressure, and breathing while you are under the effects of propofol.

What happens if I miss a dose?

Since propofol is given by a healthcare professional in a controlled setting, you are not likely to miss a dose.

What happens if I overdose?

An overdose of propofol is unlikely to occur since the medication is given by a healthcare professional. Your vital signs will be closely watched while you are under anesthesia to make sure the medication is not causing any harmful effects.

What should I avoid after receiving propofol?

Propofol side effects

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

pain, swelling, blisters, or skin changes where the medicine was injected;

seizure (convulsions);

weak or shallow breathing; or

fast or slow heart rate.

Less serious side effects may include:

nausea;

cough;

slight burning or stinging around the IV needle;

mild itching or skin rash;

numbness or tingly feeling;

confusion, agitation, anxiety;

muscle pain; or

discolored urine.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect propofol?

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

chloral hydrate (Somnote);

droperidol (Inapsine);

a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Solfoton);

diazepam (Valium) or similar medicines such as alprazolam (Xanax), chlordiazepoxide (Librium), clorazepate (Tranxene), estazolam (ProSom), flurazepam (Dalmane), lorazepam (Ativan), midazolam (Versed), temazepam (Restoril), triazolam (Halcion), and others; or

a narcotic medication such as fentanyl (Actiq, Duragesic), hydrocodone (Lortab, Vicodin), hydromorphone (Dilaudid, Palladone), morphine (Kadian, MS Contin, Oramorph, and others), oxycodone (OxyContin), oxymorphone (Numorphan, Opana), and others.

This list is not complete and there may be other drugs that can interact with propofol. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Diprivan resources

Diprivan Side Effects (in more detail)
Diprivan Dosage
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Diprivan Drug Interactions
Diprivan Support Group
13 Reviews for Diprivan - Add your own review/rating

Diprivan Prescribing Information (FDA)

Diprivan Consumer Overview

Diprivan Monograph (AHFS DI)

Diprivan MedFacts Consumer Leaflet (Wolters Kluwer)

Propofol Prescribing Information (FDA)

Propofol Professional Patient Advice (Wolters Kluwer)

Compare Diprivan with other medications

Anesthesia

Where can I get more information?

Your doctor or pharmacist can provide more information about propofol.

See also: Diprivan side effects (in more detail)

Thursday, October 20, 2016

Disopyramide

Dosage Form: capsule
Disopyramide PHOSPHATE CAPSULES, USP

3127

3129

Disopyramide Description

Disopyramide Phosphate is an antiarrhythmic drug available for oral administration in capsules containing 100 mg or 150 mg of Disopyramide base, present as the phosphate. The base content of the phosphate salt is 77.6%. The structural formula of Disopyramide Phosphate is:

C21H29N3O·H3PO4 M.W. 437.47

α-[2-(diisopropylamino) ethyl]-α-phenyl-2-pyridineacetamide phosphate

Disopyramide Phosphate is freely soluble in water, and the free base (pKa 10.4) has an aqueous solubility of 1 mg/mL. The chloroform:water partition coefficient of the base is 3.1 at pH 7.2.

Disopyramide Phosphate is a racemic mixture of d- and l-isomers. This drug is not chemically related to other antiarrhythmic drugs.

Inactive Ingredients: Capsules: Hydrous Lactose, Magnesium Stearate and Sodium Starch Glycolate.

Capsule Print and Shell Constituents: D&C Red #28, D&C Red #33, D&C Yellow #10 Aluminum Lake, FD&C Blue #1 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red #40 Aluminum Lake, Gelatin, Pharmaceutical Glaze, Silicon Dioxide, Sodium Lauryl Sulfate, Synthetic Black Iron Oxide, Titanium Dioxide and additionally, may contain Propylene Glycol.

Disopyramide - Clinical Pharmacology

Mechanisms of Action

Disopyramide Phosphate is a Type 1 antiarrhythmic drug (ie, similar to procainamide and quinidine). In animal studies, Disopyramide Phosphate decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.

Electrophysiology

In man, Disopyramide Phosphate at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.

Hemodynamics

At recommended oral doses, Disopyramide Phosphate rarely produces significant alterations of blood pressure in patients without congestive heart failure (see WARNINGS). With intravenous Disopyramide Phosphate, either increases in systolic/diastolic or decreases in systolic blood pressure have been reported, depending on the infusion rate and the patient population. Intravenous Disopyramide Phosphate may cause cardiac depression with an approximate mean 10% reduction of cardiac output, which is more pronounced in patients with cardiac dysfunction.

Anticholinergic Activity

The in vitro anticholinergic activity of Disopyramide Phosphate is approximately 0.06% that of atropine; however, the usual dose for Disopyramide Phosphate is 150 mg every 6 hours compared to 0.4 to 0.6 mg for atropine (see WARNINGS and ADVERSE REACTIONS for anticholinergic side effects).

Pharmacokinetics

Following oral administration of Disopyramide Phosphate, Disopyramide phosphate is rapidly and almost completely absorbed, and peak plasma levels are usually attained within 2 hours. The usual therapeutic plasma levels of Disopyramide base are 2 to 4 mcg/mL, and at these concentrations protein binding varies from 50% to 65%. Because of concentration-dependent protein binding, it is difficult to predict the concentration of the free drug when total drug is measured.

The mean plasma half-life of Disopyramide in healthy humans is 6.7 hours (range of 4 to 10 hours). In six patients with impaired renal function (creatinine clearance less than 40 mL/min), Disopyramide half-life values were 8 to 18 hours.

After the oral administration of 200 mg of Disopyramide to 10 cardiac patients with borderline to moderate heart failure, the time to peak serum concentration of 2.3 ± 1.5 hours (mean ± SD) was increased, and the mean peak serum concentration of 4.8 ± 1.6 mcg/mL was higher than in healthy volunteers. After intravenous administration in these same patients, the mean elimination half-life was 9.7 ± 4.2 hours (range in healthy volunteers of 4.4 to 7.8 hours). In a second study of the oral administration of Disopyramide to 7 patients with heart disease, including left ventricular dysfunction, the mean plasma half-life was slightly prolonged to 7.8 ± 1.9 hours (range of 5 to 9.5 hours).

In healthy men, about 50% of a given dose of Disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite, and 10% as the other metabolites. The plasma concentration of the major metabolite is approximately one tenth that of Disopyramide. Altering the urinary pH in man does not affect the plasma half-life of Disopyramide.

Drug Interactions

Effects of other drugs on Disopyramide pharmacokinetics: In vitro metabolic studies indicated that Disopyramide is metabolized by cytochrome P450 3A4 and that inhibitors of this enzyme may result in elevation of plasma levels of Disopyramide. Although specific drug interaction studies have not been done, cases of life-threatening interactions have been reported for Disopyramide when given with clarithromycin and erythromycin.

Indications and Usage for Disopyramide

Disopyramide Phosphate is indicated for the treatment of documented ventricular arrhythmias such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening. Because of the proarrhythmic effects of Disopyramide Phosphate, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided.

Initiation of Disopyramide Phosphate treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital.

Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.

Contraindications

Disopyramide Phosphate is contraindicated in the presence of cardiogenic shock, preexisting second- or third-degree AV block (if no pacemaker is present), congenital Q-T prolongation, or known hypersensitivity to the drug.

Warnings

Mortality

In the National Heart, Lung and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-center, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had a myocardial infarction more than 6 days but less than 2 years previously, an excessive mortality or non-fatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3.0%). The average duration of treatment with encainide or flecainide in this study was 10 months.

The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain. Considering the known proarrhythmic properties of Disopyramide Phosphate and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of Disopyramide Phosphate as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.

Negative Inotropic Properties

Heart Failure/Hypotension

Disopyramide Phosphate may cause or worsen congestive heart failure or produce severe hypotension as a consequence of its negative inotropic properties. Hypotension has been observed primarily in patients with primary cardiomyopathy or inadequately compensated congestive heart failure. Disopyramide Phosphate should not be used in patients with uncompensated or marginally compensated congestive heart failure or hypotension unless the congestive heart failure or hypotension is secondary to cardiac arrhythmia. Patients with a history of heart failure may be treated with Disopyramide Phosphate, but careful attention must be given to the maintenance of cardiac function, including optimal digitalization. If hypotension occurs or congestive heart failure worsens, Disopyramide Phosphate should be discontinued and, if necessary, restarted at a lower dosage only after adequate cardiac compensation has been established.

QRS Widening

Although it is unusual, significant widening (greater than 25%) of the QRS complex may occur during Disopyramide Phosphate administration; in such cases Disopyramide Phosphate should be discontinued.

Q-T Prolongation

As with other Type 1 antiarrhythmic drugs, prolongation of the Q-T interval (corrected) and worsening of the arrhythmia, including ventricular tachycardia and ventricular fibrillation, may occur. Patients who have evidenced prolongation of the Q-T interval in response to quinidine may be at particular risk. As with other Type 1A antiarrhythmics, Disopyramide phosphate has been associated with torsade de pointes.

If a Q-T prolongation of greater than 25% is observed and if ectopy continues, the patient should be monitored closely, and consideration be given to discontinuing Disopyramide Phosphate.

Hypoglycemia

In rare instances significant lowering of blood glucose values has been reported during Disopyramide Phosphate administration. The physician should be alert to this possibility, especially in patients with congestive heart failure, chronic malnutrition, hepatic, renal or other diseases, or drugs (e.g., beta adrenoceptor blockers, alcohol) which could compromise preservation of the normal glucoregulatory mechanisms in the absence of food. In these patients, the blood glucose levels should be carefully followed.

Concomitant Antiarrhythmic Therapy

The concomitant use of Disopyramide Phosphate with other Type 1A antiarrhythmic agents (such as quinidine or procainamide), Type 1C antiarrhythmics (such as encainide, flecainide or propafenone), and/or propranolol should be reserved for patients with life-threatening arrhythmias who are demonstrably unresponsive to single-agent antiarrhythmic therapy. Such use may produce serious negative inotropic effects, or may excessively prolong conduction. This should be considered particularly in patients with any degree of cardiac decompensation or those with a prior history thereof. Patients receiving more than one antiarrhythmic drug must be carefully monitored.

Heart Block

If first-degree heart block develops in a patient receiving Disopyramide Phosphate, the dosage should be reduced. If the block persists despite reduction of dosage, continuation of the drug must depend upon weighing the benefit being obtained against the risk of higher degrees of heart block. Development of second- or third-degree AV block or unifascicular, bifascicular, or trifascicular block requires discontinuation of Disopyramide Phosphate therapy, unless the ventricular rate is adequately controlled by a temporary or implanted ventricular pacemaker.

Anticholinergic Activity

Because of its anticholinergic activity, Disopyramide phosphate should not be used in patients with glaucoma, myasthenia gravis or urinary retention unless adequate overriding measures are taken; these consist of the topical application of potent miotics (e.g., pilocarpine) for patients with glaucoma, and catheter drainage or operative relief for patients with urinary retention. Urinary retention may occur in patients of either sex as a consequence of Disopyramide Phosphate administration, but males with benign prostatic hypertrophy are at particular risk. In patients with a family history of glaucoma, intraocular pressure should be measured before initiating Disopyramide Phosphate therapy. Disopyramide phosphate should be used with special care in patients with myasthenia gravis since its anticholinergic properties could precipitate a myasthenic crisis in such patients.

Precautions

General

Atrial Tachyarrhythmias

Patients with atrial flutter or fibrillation should be digitalized prior to Disopyramide Phosphate administration to ensure that drug-induced enhancement of AV conduction does not result in an increase of ventricular rate beyond physiologically acceptable limits.

Conduction Abnormalities

Care should be taken when prescribing Disopyramide Phosphate for patients with sick sinus syndrome (bradycardia-tachycardia syndrome), Wolff-Parkinson-White syndrome (WPW), or bundle branch block. The effect of Disopyramide phosphate in these conditions is uncertain at present.

Cardiomyopathy

Patients with myocarditis or other cardiomyopathy may develop significant hypotension in response to the usual dosage of Disopyramide phosphate, probably due to cardiodepressant mechanisms. Therefore, a loading dose of Disopyramide Phosphate should not be given to such patients, and initial dosage and subsequent dosage adjustments should be made under close supervision (see DOSAGE AND ADMINISTRATION).

Renal Impairment

More than 50% of Disopyramide is excreted in the urine unchanged. Therefore Disopyramide Phosphate dosage should be reduced in patients with impaired renal function (see DOSAGE AND ADMINISTRATION). The electrocardiogram should be carefully monitored for prolongation of PR interval, evidence of QRS widening, or other signs of overdosage (see OVERDOSAGE).

Hepatic Impairment

Hepatic impairment also causes an increase in the plasma half-life of Disopyramide. Dosage should be reduced for patients with such impairment. The electrocardiogram should be carefully monitored for signs of overdosage (see OVERDOSAGE).

Patients with cardiac dysfunction have a higher potential for hepatic impairment; this should be considered when administering Disopyramide Phosphate.

Potassium Imbalance

Antiarrhythmic drugs may be ineffective in patients with hypokalemia, and their toxic effects may be enhanced in patients with hyperkalemia. Therefore, potassium abnormalities should be corrected before starting Disopyramide Phosphate therapy.

Drug Interactions

If phenytoin or other hepatic enzyme inducers are taken concurrently with Disopyramide Phosphate, lower plasma levels of Disopyramide may occur. Monitoring of Disopyramide plasma levels is recommended in such concurrent use to avoid ineffective therapy. Other antiarrhythmic drugs (e.g., quinidine, procainamide, lidocaine, propranolol) have occasionally been used concurrently with Disopyramide Phosphate. Excessive widening of the QRS complex and/or prolongation of the Q-T interval may occur in these situations (see WARNINGS). In healthy subjects, no significant drug-drug interaction was observed when Disopyramide Phosphate was coadministered with either propranolol or diazepam. Concomitant administration of Disopyramide Phosphate and quinidine resulted in slight increases in plasma Disopyramide levels and slight decreases in plasma quinidine levels. Disopyramide Phosphate does not increase serum digoxin levels.

Until data on possible interactions between verapamil and Disopyramide phosphate are obtained, Disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.

Although potent inhibitors of cytochrome P450 3A4 (e.g., ketoconazole) have not been studied clinically, in vitro studies have shown that erythromycin and oleandomycin inhibit the metabolism of Disopyramide. Cases of life-threatening interactions have been reported for Disopyramide when given with clarithromycin and erythromycin indicating that coadministration of Disopyramide with inhibitors of cytochrome P450 3A4 could result in potentially fatal interaction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Eighteen months of Disopyramide Phosphate administration to rats, at oral doses up to 400 mg/kg/day (about 30 times the usual daily human dose of 600 mg/day, assuming a patient weight of at least 50 kg), revealed no evidence of carcinogenic potential. An evaluation of mutagenic potential by Ames test was negative. Disopyramide Phosphate, at doses up to 250 mg/kg/day, did not adversely affect fertility of rats.

Pregnancy

Teratogenic Effects

Pregnancy Category C.

Disopyramide Phosphate was associated with decreased numbers of implantation sites and decreased growth and survival of pups when administered to pregnant rats at 250 mg/kg/day (20 or more times the usual daily human dose of 12 mg/kg, assuming a patient weight of at least 50 kg), a level at which weight gain and food consumption of dams were also reduced. Increased resorption rates were reported in rabbits at 60 mg/kg/day (5 or more times the usual daily human dose). Effects on implantation, pup growth, and survival were not evaluated in rabbits. There are no adequate and well-controlled studies in pregnant women. Disopyramide Phosphate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Disopyramide Phosphate has been reported to stimulate contractions of the pregnant uterus. Disopyramide has been found in human fetal blood.

Labor and Delivery

It is not known whether the use of Disopyramide Phosphate during labor or delivery has immediate or delayed adverse effects on the fetus, or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention.

Nursing Mothers

Studies in rats have shown that the concentration of Disopyramide and its metabolites is between one and three times greater in milk than it is in plasma. Following oral administration, Disopyramide has been detected in human milk at a concentration not exceeding that in plasma. Because of the potential for serious adverse reactions in nursing infants from Disopyramide Phosphate, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established (see DOSAGE AND ADMINISTRATION).

Geriatric Use

Clinical studies of Disopyramide phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Because of its anticholinergic activity, Disopyramide phosphate should not be used in patients with glaucoma, urinary retention, or benign prostatic hypertrophy (medical conditions commonly associated with the elderly) unless adequate overriding measures are taken (see WARNINGS: Anticholinergic Activity). In the event of increased anticholinergic side effects, plasma levels of Disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be reasonable, without changing the dosing interval. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS: Renal Impairment and DOSAGE AND ADMINISTRATION).

Adverse Reactions

The adverse reactions which were reported in Disopyramide Phosphate clinical trials encompass observations in 1,500 patients, including 90 patients studied for at least 4 years. The most serious adverse reactions are hypotension and congestive heart failure. The most common adverse reactions, which are dose dependent, are associated with the anticholinergic properties of the drug. These may be transitory, but may be persistent or can be severe. Urinary retention is the most serious anticholinergic effect.

The following reactions were reported in 10% to 40% of patients:

Anticholinergic: dry mouth (32%), urinary hesitancy (14%), constipation (11%)

The following reactions were reported in 3% to 9% of patients:

Anticholinergic: blurred vision, dry nose/eyes/throat

Genitourinary: urinary retention, urinary frequency and urgency

Gastrointestinal: nausea, pain/bloating/gas

General: dizziness, general fatigue/muscle weakness, headache, malaise, aches/pains

The following reactions were reported in 1% to 3% of patients:

Genitourinary: impotence

Cardiovascular: hypotension with or without congestive heart failure, increased congestive heart failure (see WARNINGS), cardiac conduction disturbances (see WARNINGS), edema/weight gain, shortness of breath, syncope, chest pain

Gastrointestinal: anorexia, diarrhea, vomiting

Dermatologic: generalized rash/dermatoses, itching

Central nervous system: nervousness

Other: hypokalemia, elevated cholesterol/triglycerides

The following reactions were reported in less than 1%:

Depression, insomnia, dysuria, numbness/tingling, elevated liver enzymes, AV block, elevated BUN, elevated creatinine, decreased hemoglobin/hematocrit

Hypoglycemia has been reported in association with Disopyramide Phosphate administration (see WARNINGS).

Infrequent occurrences of reversible cholestatic jaundice, fever, and respiratory difficulty have been reported in association with Disopyramide therapy, as have rare instances of thrombocytopenia, reversible agranulocytosis, and gynecomastia. Some cases of LE (lupus erythematosus) symptoms have been reported; most cases occurred in patients who had been switched to Disopyramide from procainamide following the development of LE symptoms. Rarely, acute psychosis has been reported following Disopyramide Phosphate therapy, with prompt return to normal mental status when therapy was stopped. The physician should be aware of these possible reactions and should discontinue Disopyramide Phosphate therapy promptly if they occur.

Overdosage

Symptoms

Deliberate or accidental overdosage of oral Disopyramide may be followed by apnea, loss of consciousness, cardiac arrhythmias, and loss of spontaneous respiration. Death has occurred following overdosage.

Toxic plasma levels of Disopyramide produce excessive widening of the QRS complex and Q-T interval, worsening of congestive heart failure, hypotension, varying kinds and degrees of conduction disturbance, bradycardia, and finally asystole. Obvious anticholinergic effects are also observed.

The approximate oral LD50 of Disopyramide phosphate is 580 and 700 mg/kg for rats and mice, respectively.

Treatment

Experience indicates that prompt and vigorous treatment of overdosage is necessary, even in the absence of symptoms. Such treatment may be lifesaving. No specific antidote for Disopyramide phosphate has been identified. Treatment should be symptomatic and may include induction of emesis or gastric lavage, administration of a cathartic followed by activated charcoal by mouth or stomach tube, intravenous administration of isoproterenol and dopamine, insertion of an intra-aortic balloon for counterpulsation, and mechanically assisted ventilation. Hemodialysis or, preferably, hemoperfusion with charcoal may be employed to lower serum concentration of the drug.

The electrocardiogram should be monitored, and supportive therapy with cardiac glycosides and diuretics should be given as required.

If progressive AV block should develop, endocardial pacing should be implemented. In case of any impaired renal function, measures to increase the glomerular filtration rate may reduce the toxicity (Disopyramide is excreted primarily by the kidney).

The anticholinergic effects can be reversed with neostigmine at the discretion of the physician.

Altering the urinary pH in humans does not affect the plasma half-life or the amount of Disopyramide excreted in the urine.

Disopyramide Dosage and Administration

The dosage of Disopyramide Phosphate must be individualized for each patient on the basis of response and tolerance. The usual adult dosage of Disopyramide Phosphate is 400 to 800 mg per day given in divided doses. The recommended dosage for most adults is 600 mg/day given in divided doses (150 mg every 6 hours). For patients whose body weight is less than 110 pounds (50 kg), the recommended dosage is 400 mg/day given in divided doses (100 mg every 6 hours). In the event of increased anticholinergic side effects, plasma levels of Disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be reasonable, without changing the dosing interval.

For patients with cardiomyopathy or possible cardiac decompensation, a loading dose, as discussed below, should not be given, and initial dosage should be limited to 100 mg every 6 to 8 hours. Subsequent dosage adjustments should be made gradually, with close monitoring for the possible development of hypotension and/or congestive heart failure (see WARNINGS).

For patients with moderate renal insufficiency (creatinine clearance greater than 40 mL/min) or hepatic insufficiency, the recommended dosage is 400 mg/day given in divided doses (100 mg every 6 hours).

For patients with severe renal insufficiency (Ccr 40 mL/min or less), the recommended dosage regimen is 100 mg at intervals shown in the table below, with or without an initial loading dose of 150 mg.

Disopyramide PHOSPHATE DOSAGE INTERVAL FOR PATIENTS WITH RENAL INSUFFICIENCY
Creatinine clearance (mL/min)	40-30	30-15	less than 15
Approximate maintenance – dosing interval	q 8 hr	q 12 hr	q 24 hr

For patients in whom rapid control of ventricular arrhythmia is essential, an initial loading dose of 300 mg of Disopyramide Phosphate (200 mg for patients whose body weight is less than 110 pounds) is recommended, followed by the appropriate maintenance dosage. Therapeutic effects are usually attained 30 minutes to 3 hours after administration of a 300-mg loading dose. If there is no response or evidence of toxicity within 6 hours of the loading dose, 200 mg of Disopyramide Phosphate every 6 hours may be prescribed instead of the usual 150 mg. If there is no response to this dosage within 48 hours, either Disopyramide Phosphate should then be discontinued or the physician should consider hospitalizing the patient for careful monitoring while subsequent Disopyramide Phosphate doses of 250 mg or 300 mg every 6 hours are given. A limited number of patients with severe refractory ventricular tachycardia have tolerated daily doses of Disopyramide Phosphate up to 1600 mg per day (400 mg every 6 hours), resulting in Disopyramide plasma levels up to 9 mcg/mL. If such treatment is warranted, it is essential that patients be hospitalized for close evaluation and continuous monitoring.

Transferring to Disopyramide Phosphate

The following dosage schedule based on theoretical considerations rather than experimental data is suggested for transferring patients with normal renal function from either quinidine sulfate or procainamide therapy (Type 1 antiarrhythmic agents) to Disopyramide Phosphate therapy:

Disopyramide Phosphate should be started using the regular maintenance schedule without a loading dose 6 to 12 hours after the last dose of quinidine sulfate or 3 to 6 hours after the last dose of procainamide.

In patients in whom withdrawal of quinidine sulfate or procainamide is likely to produce life-threatening arrhythmias, the physician should consider hospitalization of the patient.

Pediatric Dosage

Controlled clinical studies have not been conducted in pediatric patients; however, the following suggested dosage table is based on published clinical experience.

Total daily dosage should be divided and equal doses administered orally every 6 hours or at intervals according to individual patient needs. Disopyramide plasma levels and therapeutic response must be monitored closely. Patients should be hospitalized during the initial treatment period, and dose titration should start at the lower end of the ranges provided below.

SUGGESTED TOTAL DAILY DOSAGE*
* Dosage is expressed in milligrams of Disopyramide base. Since Disopyramide phosphate 100 mg capsules contain 100 mg of Disopyramide base, the pharmacist can readily prepare a 1 mg/mL to 10 mg/mL liquid suspension by adding the entire contents of Disopyramide capsules to cherry syrup. (Prepare cherry syrup as follows: cherry juice, 475 mL; sucrose 800 g; alcohol 20 mL; purified water, a sufficient quantity to make 1000 mL.) The resulting suspension, when refrigerated, is stable for one month and should be thoroughly shaken before the measurement of each dose. The suspension should be dispensed in an amber glass bottle with a child-resistant closure.
Age (years)	Disopyramide (mg/kg body weight/day)
Under 1	10 to 30
1 to 4	10 to 20
4 to 12	10 to 15
12 to 18	6 to 15

How is Disopyramide Supplied

Disopyramide Phosphate is supplied as hard gelatin capsules with a scarlet cap and blue body imprinted with “93”–“3127”, containing 100 mg of Disopyramide base present as the phosphate, in bottles of 100; with a buff cap and scarlet body imprinted with “93”–“3129”, containing 150 mg of Disopyramide base present as the phosphate, in bottles of 100.

Storage

Store at controlled room temperature, between 20° and 25°C (68° and 77°F) (see USP).

Manufactured By:

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. H 2/2004

PRINCIPAL DISPLAY PANEL

Disopyramide Phosphate Capsules 100 mg 100s Label Text

NDC 0093-3127-01

Disopyramide

PHOSPHATE

Capsules, USP

100 mg* NEW CAPSULE IMPRINT

*Each capsule contains:

Disopyramide Phosphate, equivalent to

100 mg of Disopyramide base.

Rx only

100 CAPSULES

TEVA

PRINCIPAL DISPLAY PANEL

Disopyramide Phosphate Capsules 150 mg 100s Label Text

NDC 0093-3129-01

Disopyramide

PHOSPHATE

Capsules, USP

150 mg* NEW CAPSULE IMPRINT

*Each capsule contains:

Disopyramide Phosphate, equivalent to

150 mg of Disopyramide base.

Rx only

100 CAPSULES

TEVA

Disopyramide PHOSPHATE
Disopyramide phosphate capsule

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	0093-3127
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
Disopyramide PHOSPHATE (Disopyramide)	Disopyramide	100 mg

Inactive Ingredients
Ingredient Name	Strength
MAGNESIUM STEARATE
D&C RED NO. 28
D&C RED NO. 33
D&C YELLOW NO. 10
ALUMINUM OXIDE
FD&C BLUE NO. 1
FD&C BLUE NO. 2
FD&C RED NO. 40
GELATIN
SILICON DIOXIDE
SODIUM LAURYL SULFATE
TITANIUM DIOXIDE
PROPYLENE GLYCOL

Product Characteristics
Color	BLUE, RED (scarlet)	Score	no score
Shape	CAPSULE	Size	19mm
Flavor		Imprint Code	93;3127
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	0093-3127-01	100 CAPSULE In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA070101	01/25/2011

Disopyramide PHOSPHATE
Disopyramide phosphate capsule

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	0093-3129
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
Disopyramide PHOSPHATE (Disopyramide)	Disopyramide	150 mg

Inactive Ingredients
Ingredient Name	Strength
MAGNESIUM STEARATE
D&C RED NO. 28
D&C RED NO. 33
D&C YELLOW NO. 10
ALUMINUM OXIDE
FD&C BLUE NO. 1
FD&C BLUE NO. 2
FD&C RED NO. 40
GELATIN
SILICON DIOXIDE
SODIUM LAURYL SULFATE
TITANIUM DIOXIDE
PROPYLENE GLYCOL

Product Characteristics
Color	BROWN (buff) , RED (scarlet)	Score	no score
Shape	CAPSULE	Size	19mm
Flavor		Imprint Code	93;3129
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	0093-3129-01	100 CAPSULE In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA070102	01/25/2011

Labeler - TEVA Pharmaceuticals USA Inc (118234421)

Revised: 01/2011TEVA Pharmaceuticals USA Inc

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