Tegopen

Generic Name: cloxacillin (klox a SILL in)

Brand Names: Cloxapen, Tegopen

What is Tegopen (cloxacillin)?

Cloxacillin is an antibiotic in the class of drugs called penicillins. It fights bacteria in your body.

Cloxacillin is used to treat many different types of infections caused by staphylococcus bacteria ("staph" infections).

Cloxacillin may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Tegopen (cloxacillin)?

Take all of the cloxacillin that has been prescribed for you even if you begin to feel better. Your symptoms may begin to improve before the infection is completely treated. Do not break, chew, open, or crush the capsules. Swallow them whole. Cloxacillin may decrease the effectiveness of birth control pills. Use a second method of birth control while taking cloxacillin to protect against pregnancy.

Who should not take Tegopen (cloxacillin)?

If you have ever had an allergic reaction to another penicillin or to a cephalosporin, do not take cloxacillin unless your doctor is aware of your allergy and monitors your therapy.

Before taking this medication, tell your doctor if you have kidney disease, stomach or intestinal disease, or infectious mononucleosis. You may not be able to take cloxacillin because of an increased risk of side effects.

If you are a diabetic, some glucose urine tests may give false positive results while you are taking cloxacillin.

Cloxacillin is in the FDA pregnancy category B. This means that it is unlikely to harm an unborn baby. Do not, however, take cloxacillin without first talking to your doctor if you are pregnant. It is not known whether cloxacillin passes into breast milk. Do not take this medication without first talking to your doctor if you are breast-feeding a baby.

How should I take Tegopen (cloxacillin)?

Take cloxacillin exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water. Take cloxacillin on an empty stomach 1 hour before or 2 hours after meals.

Do not drink juice or carbonated beverages (soda) with your dose of cloxacillin. These beverages will decrease the effectiveness of the drug.

Cloxacillin should be taken at evenly spaced intervals throughout the day and night to keep the level in your blood high enough to treat the infection.

Do not crush, chew, or open the capsules. Swallow them whole. Shake the suspension well before measuring a dose. To ensure that you get a correct dose, measure the liquid form of cloxacillin with a dose-measuring spoon or cup, not a regular tablespoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one. Take all of the cloxacillin that has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated. Store the capsules at room temperature and store the suspension in the refrigerator for longer use. The suspension is good for 14 days if it is stored in the refrigerator. Throw away any unused liquid after this amount of time.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the dose you missed and take only your next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.

If you have only missed one dose, you can take the rest of your scheduled doses for the day at evenly spaced intervals.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of an cloxacillin overdose include muscle spasms or weakness, pain or twitching, pain in the fingers or toes, loss of feeling in the fingers or toes, seizures, confusion, coma, and agitation.

What should I avoid while taking Tegopen (cloxacillin)?

Alcohol may irritate your stomach if taken with cloxacillin, so use it with moderation.

Tegopen (cloxacillin) side effects

If you experience any of the following serious side effects, stop taking cloxacillin and seek emergency medical attention:

• 
  

  an allergic reaction (shortness of breath; closing of your throat; hives; swelling of your lips, face, or tongue; rash; or fainting);

  
  


• 
  

  seizures;

  
  


• 
  

  severe watery diarrhea and abdominal cramps; or

  
  


• 
  

  unusual bleeding or bruising.

  
  

Other, less serious side effects maybe more likely to occur. Continue to take cloxacillin and talk to your doctor if you experience

• 
  

  mild nausea, vomiting, diarrhea, or abdominal pain;

  
  


• 
  

  white patches on the tongue (thrush/yeast infection);

  
  


• 
  

  itching or discharge of the vagina (vaginal yeast infection); or

  
  


• 
  

  black, "hairy" tongue or sore mouth or tongue.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Tegopen (cloxacillin)?

Some drugs may decrease the effects of cloxacillin and prevent it from properly treating your infection. Before taking cloxacillin, tell your doctor if you are taking any of the following drugs:

• 
  

  cholestyramine (Questran) or colestipol (Colestid); or

  
  


• 
  

  another antibiotic (for the same or for a different infection) such as erythromycin (Ery-Tab, E-Mycin, E.E.S., others), tetracycline (Sumycin, others), minocycline (Minocin), doxycycline (Doryx, Vibramycin, others), or any other.

  
  

Cloxacillin may decrease the effectiveness of birth control pills. Use a second method of birth control while taking cloxacillin to protect against pregnancy.

Cloxacillin increases the effects of methotrexate, and you may need a dose adjustment during therapy with cloxacillin.

Cloxacillin also increases the side effects of allopurinol (Zyloprim) and may cause a rash.

Probenecid (Benemid) increases the effects of cloxacillin. These drugs may be used together for this purpose; however, be sure your doctor is aware if you are taking probenecid. You may need a lower dose of cloxacillin.

Drugs other than those listed here may also interact with cloxacillin. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More Tegopen resources

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

• Cloxapen Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Tegopen with other medications

• Bladder Infection
• Pneumonia
• Skin and Structure Infection
• Upper Respiratory Tract Infection

Where can I get more information?

• Your pharmacist has additional information about cloxacillin written for health professionals that you may read.

What does my medication look like?

Cloxacillin is available generically and with a prescription in 250 and 500 mg capsules and in a suspension formulation of 120 mg per 5 mL (1 teaspoon). Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

See also: Tegopen side effects (in more detail)

Nabumetone

Class: Other Nonsteroidal Anti-inflammatory Agents
Chemical Name: 4-(6-Methoxy-2-naphthyl)-2-butanone
Molecular Formula: C₁₅H₁₆O₂
CAS Number: 42924-53-8

• Cardiovascular Risk


• 
  

  Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).¹ Risk may increase with duration of use.¹ Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.¹ (See Cardiovascular Effects under Cautions.)

  
  


• 
  

  Contraindicated for the treatment of pain in the setting of CABG surgery.¹

  
  

• GI Risk


• 
  

  Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).¹ Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.¹ Geriatric individuals are at greater risk for serious GI events.¹ (See GI Effects under Cautions.)

  
  

Introduction

Prototypical NSAIA;¹ prodrug with little pharmacologic activity until oxidized in the liver to form an active metabolite that is structurally similar to naproxen.^{1 2 3}

Uses for Nabumetone

Consider potential benefits and risks of nabumetone therapy as well as alternative therapies before initiating therapy with the drug.¹ Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.¹

Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.¹

Nabumetone Dosage and Administration

General

• 
  

  Consider potential benefits and risks of nabumetone therapy as well as alternative therapies before initiating therapy with the drug.¹

  
  

Administration

Oral Administration

Administer orally once or twice daily without regard to meals.¹

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.¹ Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.¹

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

Initially, 1 g once daily.¹ May increase dosage to 1.5–2 g daily, given as a single daily dose or 2 divided doses.¹

Patients weighing <50 kg may be less likely to need dosages >1 g daily.¹

Prescribing Limits

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

Maximum 2 g daily.¹

Special Populations

Renal Impairment

Dosage adjustment not necessary in patients with mild renal impairment (Cl_cr >50 mL/minute).¹

In patients with moderate renal impairment (Cl_cr 30–49 mL/minute), initiate at ≤750 mg daily (maximum initial dosage is 750 mg daily).¹ Monitor renal function; may increase dosage to 1.5 g daily.¹

In patients with severe renal impairment (Cl_cr <30 mL/minute), initiate at ≤500 mg daily (maximum inital dosage is 500 mg daily).¹ Monitor renal function; may increase dosage to 1 g daily.¹

Cautions for Nabumetone

Contraindications

• 
  

  Known hypersensitivity to nabumetone or any ingredient in the formulation.¹

  
  


• 
  

  History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.^{1 2}

  
  


• 
  

  Treatment of perioperative pain in the setting of CABG surgery.¹

  
  

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with an increased risk of serious adverse cardiovascular thrombotic events in certain situations.¹ Several prototypical NSAIAs also have been associated with an increased risk of cardiovascular events.^{4 5 6} Current data insufficient to assess risk associated with nabumetone.^{4 5 6}

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dosage for the shortest duration necessary.¹

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).^a

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.¹ (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.¹ Use with caution in patients with hypertension; monitor BP.¹ Impaired response to certain diuretics may occur.¹ (See Specific Drugs under Interactions.)

Fluid retention and edema reported.¹ Caution in patients with fluid retention or heart failure.¹

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.¹

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol; alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole) or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.¹

Potential for overt renal decompensation.¹ Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in patients with volume depletion, in geriatric patients, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.^{1 c} (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.¹

Immediate medical intervention and discontinuance for anaphylaxis.¹

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.¹

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.¹ Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).¹

Photosensitivity Reactions

Photosensitivity reactions possible.¹

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.¹

Elevations of serum ALT or AST reported.¹

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.¹ Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.¹

Hematologic Effects

Anemia reported rarely.¹ Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.¹

May inhibit platelet aggregation and prolong bleeding time.¹

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.¹

May mask certain signs of infection.¹

Obtain CBC and chemistry profile periodically during long-term use.¹

Specific Populations

Pregnancy

Category C.¹ Avoid use in third trimester because of possible premature closure of the ductus arteriosus.¹

Lactation

Active metabolite is distributed into milk in rats; not known whether nabumetone or its metabolites are distributed into milk in humans.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children.¹

Geriatric Use

Caution advised.¹ Safety and efficacy profiles similar to those in younger adults.¹ However, fatal adverse GI effects reported more frequently in geriatric patients than in younger adults.¹

Hepatic Impairment

Caution advised in patients with severe hepatic impairment, since formation of the active metabolite depends on biotransformation in the liver.¹

Renal Impairment

Use with caution in patients with renal disease.¹ Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.¹

Dosage adjustments necessary in patients with moderate or severe renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Oxidized and conjugated metabolites that are excreted in urine may accumulate in patients with renal failure, potentially resulting in adverse effects.¹

Common Adverse Effects

Abdominal pain, constipation, diarrhea, dizziness, dyspepsia, edema, flatulence, headache, nausea, positive stool guaiac test, pruritus, rash, tinnitus.¹

Interactions for Nabumetone

Protein-bound Drugs

Could be displaced from binding sites by, or could displace from binding sites, other protein-bound drugs.¹

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Reduced BP response to ACE inhibitor1 Possible deterioration of renal function in individuals with renal impairmentc	Monitor BP1
Angiotensin II receptor antagonists	Reduced BP response to angiotensin II receptor antagonistc Possible deterioration of renal function in individuals with renal impairmentc	Monitor BPc
Antacids (aluminum-containing)	No effect on 6-methoxy-2-naphthylacetic acid (6MNA) bioavailability1
Aspirin	Increased risk of GI ulceration and other complications1 No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs1	Manufacturer states that concomitant use not recommended1
Diuretics (furosemide, thiazides)	Reduced natriuretic effects possible1	Monitor for diuretic efficacy and renal failure1
Lithium	Increased plasma lithium concentrations1	Monitor for lithium toxicity1
Methotrexate	Possible toxicity associated with increased plasma methotrexate concentrations1	Caution advised1
Warfarin	Possibility of bleeding complications1	Caution advised1

Nabumetone Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.¹ Rapidly biotransformed to active metabolite, 6MNA; peak plasma concentration of 6MNA usually attained within 2.5–4 hours.¹ Approximately 35% of a 1-g dose is metabolized to 6MNA.¹ Unchanged nabumetone is not detected in plasma.¹

Food

Food increases rate of nabumetone absorption; increases rate but not extent of metabolism to 6MNA.¹

Special Populations

In geriatric patients, steady-state plasma 6MNA concentrations are higher than in younger individuals.¹

Distribution

Plasma Protein Binding

6MNA: >99%.¹

Elimination

Metabolism

6MNA is extensively metabolized in the liver to inactive metabolites; 6MNA does not appear to undergo enterohepatic recirculation.¹

Elimination Route

Excreted mainly in urine as metabolites of 6MNA and metabolites of nabumetone.¹

Half-life

6MNA: about 23–30 hours.¹

Special Populations

In patients with moderate renal impairment (Cl_cr 30–49 mL/minute) and severe renal impairment (Cl_cr <30 mL/minute), elimination half-life of 6MNA increased.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

ActionsActions

• 
  

  Inhibits cyclooxygenase-1 (COX-1) and COX-2.¹

  
  


• 
  

  Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.¹

  
  

Advice to Patients

• 
  

  Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.¹

  
  


• 
  

  Risk of serious cardiovascular events with long-term use.¹

  
  


• 
  

  Risk of GI bleeding and ulceration.¹

  
  


• 
  

  Risk of serious skin reactions.¹ Risk of anaphylactoid and other sensitivity reactions.¹

  
  


• 
  

  Risk of hepatotoxicity.¹

  
  


• 
  

  Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.¹

  
  


• 
  

  Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.¹

  
  


• 
  

  Importance of discontinuing nabumetone and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.¹ Importance of seeking immediate medical attention if an anaphylactic reaction occurs.¹

  
  


• 
  

  Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Importance of avoiding nabumetone in late pregnancy (third trimester).¹

  
  


• 
  

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

  
  


• 
  

  Importance of informing 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

Nabumetone

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	500 mg*	Nabumetone Tablets	Par, Sandoz, Teva
		750 mg*	Nabumetone Tablets	Par, Sandoz, Teva

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.

Nabumetone 500MG Tablets (SANDOZ): 60/$39.99 or 180/$109.98

Nabumetone 750MG Tablets (SANDOZ): 60/$65.99 or 180/$180.98

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. GlaxoSmithKline. Relafen (nabumetone) tablets prescribing information. Research Triangle Park, NC; 2006 Feb.

2. Dahl SL. Nabumetone: a “nonacidic” nonsteroidal antiinflammatory drug. Ann Pharmacother. 1993; 27:456-63. [IDIS 313113] [PubMed 8477124]

3. Friedel HA, Langtry HD, Buckley MM. Nabumetone: a reappraisal of its pharmacology and therapeutic use in rheumatic diseases. Drugs. 1993; 45:131-56. [PubMed 7680981]

4. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44. [PubMed 16968831]

5. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5. [PubMed 16740558]

6. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6. [PubMed 16968830]

a. Food and Drug Administration. Analysis and recommendations for Agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6. From FDA web site ().

c. Merck & Co., Inc. Dolobid (diflunisal) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

More Nabumetone resources

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

• Nabumetone Prescribing Information (FDA)


• Nabumetone MedFacts Consumer Leaflet (Wolters Kluwer)


• Nabumetone Professional Patient Advice (Wolters Kluwer)


• nabumetone Advanced Consumer (Micromedex) - Includes Dosage Information


• Relafen Consumer Overview


• Relafen Prescribing Information (FDA)

Compare Nabumetone with other medications

• Back Pain
• Frozen Shoulder
• Muscle Pain
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Kerafoam Foam

Pronunciation: ue-REE-a
Generic Name: Urea
Brand Name: Kerafoam

Kerafoam Foam is used for:

Treating dry, rough, scaly skin caused by certain conditions (eg, dermatitis, psoriasis, eczema, cracked skin, calluses). It may also be used for certain other skin or nail conditions as determined by your doctor.

Kerafoam Foam is a debriding agent. It works by helping the breakdown of dead skin, which helps to loosen and shed hard and scaly skin. It also softens and moisturizes the skin.

Do NOT use Kerafoam Foam if:

• you are allergic to any ingredient in Kerafoam Foam

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

Before using Kerafoam Foam:

Some medical conditions may interact with Kerafoam Foam. 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 the affected area is broken or severely irritated

Some MEDICINES MAY INTERACT with Kerafoam Foam. Because little, if any, of Kerafoam Foam is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Kerafoam Foam 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 Kerafoam Foam:

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

• Wash your hands immediately before and after using Kerafoam Foam unless your hands are part of the treated area.


• Prime the container before the first use. To do this, point the container away from yourself and others. Hold it upright. Press down on the actuator for 3 to 5 seconds, or until foam begins to appear.


• Shake well before each use.


• To use Kerafoam Foam, hold the container upright. Apply Kerafoam Foam to the affected skin as directed by your doctor. Rub in gently until the medicine is completely absorbed.


• After you use Kerafoam Foam, wipe any excess foam off of the container.


• If you miss a dose of Kerafoam Foam and you are using it regularly, use 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 use 2 doses at once.

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

Important safety information:

• Kerafoam Foam is for external use only. Do not get it in your eyes, nose, mouth, or on your lips. If you get Kerafoam Foam in your eyes, rinse them right away with cool water.


• Do not apply to broken or severely irritated skin.


• Do not use more than the recommended dose or use for longer than prescribed without checking with your doctor.


• Do not use Kerafoam Foam for other skin conditions at a later time.


• PREGNANCY and BREAST-FEEDING: It is not known if Kerafoam Foam can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Kerafoam Foam while you are pregnant. It is not known if Kerafoam Foam is found in breast milk. If you are or will be breast-feeding while you use Kerafoam Foam, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Kerafoam Foam:

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:

Mild, temporary burning, itching, irritation, or stinging.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); redness; severe or persistent burning or irritation.

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: Kerafoam 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 ( http://www.aapcc.org), or emergency room immediately.

Proper storage of Kerafoam Foam:

Store Kerafoam Foam at room temperature, between 59 and 77 degrees F (15 and 25 degrees C). Avoid temperatures above 120 degrees F (49 degrees C). Do not freeze. Store upright away from heat and direct sunlight. Do not puncture, break, or burn the canister even if it appears to be empty. Keep Kerafoam Foam out of the reach of children and away from pets.

General information:

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


• Kerafoam Foam 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 Kerafoam Foam. 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 Kerafoam resources

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

Compare Kerafoam with other medications

• Dermatological Disorders
• Dry Skin
• Pityriasis rubra pilaris

Trivaris Intravitreal ophthalmic

Generic Name: triamcinolone (ophthalmic) (trye am SIN oh lone off THAL mik)

Brand Names: Triesence, Trivaris Intravitreal

What is Trivaris Intravitreal (triamcinolone (ophthalmic))?

Triamcinolone is a steroid. It prevents the release of substances in the body that cause inflammation.

Triamcinolone ophthalmic (for the eyes) is injected into the eye to treat inflammation caused by disease or injury. Triamcinolone ophthalmic is usually given after steroid eye drops have been used without successful treatment of symptoms.

Triamcinolone ophthalmic is also used during a certain type of eye surgery.

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

What is the most important information I should know about Trivaris Intravitreal (triamcinolone (ophthalmic))?

You should not receive this medication if you are allergic to triamcinolone, or if you have a fungal infection anywhere in your body. Do not use triamcinolone if you are pregnant. It could harm the unborn baby.

Before receiving triamcinolone ophthalmic, tell your doctor if you have any type of bacterial, fungal, or viral infection (including tuberculosis). Also tell your doctor if you have cataracts or glaucoma, herpes infection of your eye, diabetes, high blood pressure, congestive heart failure, a thyroid disorder, myasthenia gravis, a stomach or intestinal disorder, or a history of recent heart attack.

Before you receive any vaccine, talk with the doctor who is treating you with triamcinolone ophthalmic. Some vaccines may not work as well or could cause harmful side effects during treatment with steroid medicine.

Steroids can lower the blood cells that help your body fight infections. Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles.

There are many other drugs that can interact with triamcinolone. Tell your doctor about all medications you use. Keep a list of all your medicines and show it to any healthcare provider who treats you.

What should I discuss with my health care provider before receiving Trivaris Intravitreal (triamcinolone (ophthalmic))?

You should not receive this medication if you are allergic to triamcinolone, or if you have a fungal infection anywhere in your body.

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

• 
  

  herpes infection of your eye;

  
  


• 
  

  eye conditions such as cataract or glaucoma;

  
  


• 
  

  diabetes;

  
  


• 
  

  high blood pressure, congestive heart failure;

  
  


• 
  

  any type of bacterial, fungal, or viral infection (including tuberculosis);

  
  


• 
  

  a thyroid disorder;

  
  


• 
  

  a muscle disorder such as myasthenia gravis;

  
  


• 
  

  diverticulitis, stomach or intestinal ulcer, or recent stomach surgery; or

  
  


• 
  

  if you have recently had a heart attack.

  
  

FDA pregnancy category D. Do not receive triamcinolone if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. Triamcinolone can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

This medication can decrease bone formation which could lead to osteoporosis, especially with long-term use. Talk with your doctor about your specific risk of bone loss while receiving triamcinolone ophthalmic.

Steroids can affect growth in children. Talk with your doctor if you think your child is not growing at a normal rate while using this medication.

How is triamcinolone ophthalmic given?

Triamcinolone ophthalmic is given as an injection into your eye. Your doctor will use a medicine to numb your eye before giving you the injection. You will receive this injection in your doctor's office or other clinic setting.

For at least 30 minutes after your injection, your eyes will be checked periodically to make sure the injection has not caused any side effects.

Long-term use of steroids can cause harmful effects on the eyes, such as glaucoma or cataracts. If you receive triamcinolone ophthalmic for longer than 6 weeks, your doctor may want you to have regular eye exams.

Steroids can lower the blood cells that help your body fight infections. This can make it easier for you to get sick from being around others who are ill, or from bacteria in a skin wound. Steroids can also slow the healing of skin wounds. Use caution to prevent illness, infection, or injury.

Your doctor may instruct you to limit your salt intake while you are receiving triamcinolone ophthalmic. You may also need to take potassium supplements. Follow your doctor's instructions.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using triamcinolone.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your injection.

What happens if I overdose?

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

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while receiving Trivaris Intravitreal (triamcinolone (ophthalmic))?

Do not receive a smallpox vaccine or any other "live" vaccine if you are being treated long-term with triamcinolone ophthalmic. Some vaccines may not work as well during treatment with steroid medicine at certain doses. Some vaccines may even cause dangerous side effects when used during steroid treatment. Before you receive any vaccine, talk with the doctor who is treating you with triamcinolone ophthalmic.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroids.

Trivaris Intravitreal (triamcinolone (ophthalmic)) 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:

• 
  

  problems with your vision, pain behind your eyes, or seeing halos around lights;

  
  


• 
  

  eye swelling, redness, severe discomfort, crusting or drainage (may be signs of infection);

  
  


• 
  

  large red or purple spots on your skin;

  
  


• 
  

  fast or slow heart rate;

  
  


• 
  

  feeling short of breath, swelling in your hands or feet;

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, uneven heartbeats, seizure);

  
  


• 
  

  severe dizziness or nausea;

  
  


• 
  

  severe depression, changes in mood or behavior, seizures (convulsions); or

  
  


• 
  

  severe pain in your upper stomach.

  
  

Less serious side effects may include:

• 
  

  mild eye discomfort;

  
  


• 
  

  headaches, back aches, weakness;

  
  


• 
  

  bloating, appetite changes, weight gain;

  
  


• 
  

  changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist), roundness in your face;

  
  


• 
  

  increased acne or facial hair;

  
  


• 
  

  menstrual problems (in women), impotence or loss of interest in sex (in men);

  
  


• 
  

  dry skin, thinning skin, changes in skin color;

  
  


• 
  

  bruising, sweating more than usual; or

  
  


• 
  

  any wound that will not heal.

  
  

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 Trivaris Intravitreal (triamcinolone (ophthalmic))?

Many drugs can interact with triamcinolone. Below is just a partial list. Tell your doctor if you are using:

• 
  

  amphotericin B (Fungizone, AmBisome, Abelcet);

  
  


• 
  

  birth control pills or hormone replacement therapy;

  
  


• 
  

  a blood thinner such as warfarin (Coumadin);

  
  


• 
  

  cholestyramine (Prevalite, Questran);

  
  


• 
  

  cyclosporine (Neoral, Gengraf, Sandimmune);

  
  


• 
  

  digoxin (digitalis, Lanoxin);

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  insulin or an oral diabetes medication;

  
  


• 
  

  isoniazid (for treating tuberculosis);

  
  


• 
  

  rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), or rifapentine (Priftin);

  
  


• 
  

  an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), or telithromycin (Ketek);

  
  


• 
  

  an antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend);

  
  


• 
  

  aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), etodolac (Lodine), indomethacin (Indocin), piroxicam (Feldene), and others;

  
  


• 
  

  heart or blood pressure medication such as diltiazem (Cartia, Cardizem), quinidine (Quin-G), or verapamil (Calan, Covera, Isoptin, Verelan);

  
  


• 
  

  HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), fosamprenavir (Lexiva), indinavir (Crixivan), nevirapine (Viramune), saquinavir (Invirase, Fortovase), ritonavir (Norvir, Kaletra), and others;

  
  


• 
  

  medications to treat dementia, such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), tacrine (Cognex); or

  
  


• 
  

  seizure medication such as carbamazepine (Carbatrol, Tegretol), phenobarbital (Solfoton), phenytoin (Dilantin), and others.

  
  

This list is not complete and there are many other drugs that can interact with triamcinolone. 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. Keep a list of all your medicines and show it to any healthcare provider who treats you.

More Trivaris Intravitreal resources

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

Compare Trivaris Intravitreal with other medications

• Temporal Arteritis
• Uveitis

Where can I get more information?

• Your doctor can provide more information about triamcinolone ophthalmic.

See also: Trivaris Intravitreal side effects (in more detail)

Totect

Generic Name: dexrazoxane (Intravenous route)

dex-ray-ZOX-ane

Commonly used brand name(s)

In the U.S.

• Totect


• Zinecard

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Cardioprotective Agent

Uses For Totect

Dexrazoxane is used to help prevent or lessen a toxic effect to your heart that is caused by certain medicines that are used to treat cancer.

Dexrazoxane is also used to treat tissue damage caused by the leakage of certain medicines that are used to treat cancer .

This medicine is available only with your doctor's prescription.

Before Using Totect

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of dexrazoxane in the pediatric population. Safety and efficacy have not been established .

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of dexrazoxane in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require an adjustment of dosage in patients receiving dexrazoxane .

Interactions with Medicines

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

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Blood disorder or bleeding problem (e.g., leukopenia, neutropenia, or thrombocytopenia)—May make this condition worse .

• Kidney disease—The effects may be increased because of slower removal of the medicine from the body .

Proper Use of dexrazoxane

This section provides information on the proper use of a number of products that contain dexrazoxane. It may not be specific to Totect. Please read with care.

A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed into one of your veins .

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Precautions While Using Totect

Using this medicine while you are pregnant can harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor right away .

Dexrazoxane can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.


• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin.


• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.


• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.


• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.


• Avoid situations where bruising or injury could occur .

Totect Side Effects

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

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

More common

• Bluish color


• changes in skin color


• chest pain


• cold hands and feet


• cough or hoarseness


• difficult or labored breathing


• fever or chills


• lower back or side pain


• pain, redness, or swelling in arm or leg


• painful or difficult urination


• pale skin


• shortness of breath


• sneezing


• sore throat


• swelling of hands, ankles, feet, or lower legs


• tenderness


• tightness in chest


• troubled breathing


• unusual bleeding or bruising


• unusual tiredness or weakness


• wheezing

Less common

• Black, tarry stools


• chest discomfort


• fast, irregular, or pounding heartbeat


• pain at place of injection


• ulcers, sores, or white spots in mouth

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

More common

• Diarrhea


• difficulty having a bowel movement (stool)


• discouragement


• dizziness


• feeling sad or empty


• hair loss, thinning of hair


• headache


• irritability


• lack or loss of appetite


• loss of interest or pleasure


• muscle pain, spasms, cramps, or stiffness


• nausea


• stomach pain


• trouble concentrating


• trouble sleeping


• vomiting


• weight loss

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

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

See also: Totect side effects (in more detail)

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

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

More Totect resources

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

• Totect Consumer Overview


• Totect Prescribing Information (FDA)


• Dexrazoxane Prescribing Information (FDA)


• Dexrazoxane Professional Patient Advice (Wolters Kluwer)


• Dexrazoxane MedFacts Consumer Leaflet (Wolters Kluwer)


• Dexrazoxane Hydrochloride Monograph (AHFS DI)


• Zinecard Prescribing Information (FDA)

Compare Totect with other medications

• Extravasation

Tamsulosin

Dosage Form: capsule
FULL PRESCRIBING INFORMATION

Indications and Usage for Tamsulosin

Tamsulosin hydrochloride capsules are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) [see Clinical Studies (14)]. Tamsulosin hydrochloride capsules are not indicated for the treatment of hypertension.

Tamsulosin Dosage and Administration

Tamsulosin hydrochloride capsules 0.4 mg once daily is recommended as the dose for the treatment of the signs and symptoms of BPH. It should be administered approximately one-half hour following the same meal each day.

For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing, the dose of Tamsulosin hydrochloride capsules can be increased to 0.8 mg once daily. Tamsulosin hydrochloride capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [see Warnings and Precautions (5.2)].

If Tamsulosin hydrochloride capsules administration is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose, therapy should be started again with the 0.4 mg once-daily dose.

Dosage Forms and Strengths

Capsule: 0.4 mg, hard-shell gelatin capsule with a blue opaque cap and a blue opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over 2500 in black ink on both the cap and the body.

Contraindications

Tamsulosin hydrochloride capsules are contraindicated in patients known to be hypersensitive to Tamsulosin hydrochloride or any component of Tamsulosin hydrochloride capsules. Reactions have included skin rash, urticaria, pruritus, angioedema and respiratory symptoms [see Adverse Reactions (6.2)].

Warnings and Precautions

Orthostasis

The signs and symptoms of orthostasis (postural hypotension, dizziness and vertigo) were detected more frequently in Tamsulosin hydrochloride capsule-treated patients than in placebo recipients. As with other alpha adrenergic blocking agents there is a potential risk of syncope [see Adverse Reactions (6.1)]. Patients beginning treatment with Tamsulosin hydrochloride capsules should be cautioned to avoid situations where injury could result should syncope occur [see Patient Counseling Information (17.1)].

Drug Interactions

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6. Tamsulosin hydrochloride capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Tamsulosin hydrochloride capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin), in combination with strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, in patients known to be CYP2D6 poor metabolizers particularly at a dose higher than 0.4 mg (e.g., 0.8 mg) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Tamsulosin hydrochloride capsules should be used with caution in combination with cimetidine, particularly at a dose higher than 0.4 mg (e.g., 0.8 mg) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Tamsulosin hydrochloride capsules should not be used in combination with other alpha adrenergic blocking agents [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

Caution is advised when alpha adrenergic blocking agents including Tamsulosin hydrochloride capsules are coadministered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].

Caution should be exercised with concomitant administration of warfarin and Tamsulosin hydrochloride capsules [see Drug Interactions (7.4) and Clinical Pharmacology (12.3)].

Priapism

Rarely (probably less than 1 in 50,000 patients), Tamsulosin, like other alpha1 antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients must be advised about the seriousness of the condition [see Patient Counseling Information (17.2)].

Screening for Prostate Cancer

Prostate cancer and BPH frequently coexist; therefore, patients should be screened for the presence of prostate cancer prior to treatment with Tamsulosin hydrochloride capsules and at regular intervals afterwards [see Patient Counseling Information (17.3)].

Intraoperative Floppy Iris Syndrome

 Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha1 blockers, including Tamsulosin hydrochloride capsules [see Adverse Reactions (6.2)].

Most reports were in patients taking the alpha1 blocker when IFIS occurred, but in some cases, the alpha1 blocker had been stopped prior to surgery. In most of these cases, the alpha1 blocker had been stopped recently prior to surgery (2 to 14 days), but in a few cases, IFIS was reported after the patient had been off the alpha1 blocker for a longer period (5 weeks to 9 months). IFIS is a variant of small pupil syndrome and is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs and potential prolapse of the iris toward the phacoemulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.

 IFIS may increase the risk of eye complications during and after the operation. The benefit of stopping alpha1 blocker therapy prior to cataract surgery has not been established. The initiation of therapy with Tamsulosin in patients for whom cataract surgery is scheduled is not recommended.

Sulfa Allergy

In patients with sulfa allergy, allergic reaction to Tamsulosin hydrochloride capsules has been rarely reported. If a patient reports a serious or life threatening sulfa allergy, caution is warranted when administering Tamsulosin hydrochloride capsules.

Adverse Reactions

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The incidence of treatment-emergent adverse events has been ascertained from six short-term U.S. and European placebo-controlled clinical trials in which daily doses of 0.1 to 0.8 mg Tamsulosin hydrochloride capsules were used. These studies evaluated safety in 1,783 patients treated with Tamsulosin hydrochloride capsules and 798 patients administered placebo. Table 1 summarizes the treatment-emergent adverse events that occurred in ≥ 2% of patients receiving either Tamsulosin hydrochloride capsules 0.4 mg or 0.8 mg and at an incidence numerically higher than that in the placebo group during two 13-week U.S. trials (US92-03A and US93-01) conducted in 1,487 men.

Table 1: Treatment Emergent* Adverse Events Occurring in ≥ 2% of Tamsulosin Hydrochloride Capsules or Placebo Patients in Two U.S. Short-Term Placebo-Controlled Clinical Studies

* A treatment-emergent adverse event was defined as any event satisfying one of the following criteria: The adverse event occurred for the first time after initial dosing with double-blind study medication. The adverse event was present prior to or at the time of initial dosing with double-blind study medication and subsequently increased in severity during double-blind treatment; or The adverse event was present prior to or at the time of initial dosing with double-blind study medication, disappeared completely, and then reappeared during double-blind treatment. † Coding preferred terms also include cold, common cold, head cold, flu, and flu-like symptoms. ‡ Coding preferred terms also include nasal congestion, stuffy nose, runny nose, sinus congestion, and hay fever.
Body System/ Adverse Event	Tamsulosin Hydrochloride Capsules Groups		Placebo
	0.4 mg n = 502	0.8 mg n = 492	n = 493
Body As Whole
Headache	97 (19.3%)	104 (21.1%)	99 (20.1%)
Infection†	45 (9%)	53 (10.8%)	37 (7.5%)
Asthenia	39 (7.8%)	42 (8.5%)	27 (5.5%)
Back Pain	35 (7%)	41 (8.3%)	27 (5.5%)
Chest Pain	20 (4%)	20 (4.1%)	18 (3.7%)
Nervous System
Dizziness	75 (14.9%)	84 (17.1%)	50 (10.1%)
Somnolence	15 (3%)	21 (4.3%)	8 (1.6%)
Insomnia	12 (2.4%)	7 (1.4%)	3 (0.6%)
Libido Decreased	5 (1%)	10 (2%)	6 (1.2%)
Respiratory System
Rhinitis‡	66 (13.1%)	88 (17.9%)	41 (8.3%)
Pharyngitis	29 (5.8%)	25 (5.1%)	23 (4.7%)
Cough Increased	17 (3.4%)	22 (4.5%)	12 (2.4%)
Sinusitis	11 (2.2%)	18 (3.7%)	8 (1.6%)
Digestive System
Diarrhea	31 (6.2%)	21 (4.3%)	22 (4.5%)
Nausea	13 (2.6%)	19 (3.9%)	16 (3.2%)
Tooth Disorder	6 (1.2%)	10 (2%)	7 (1.4%)
Urogenital System
Abnormal Ejaculation	42 (8.4%)	89 (18.1%)	1 (0.2%)
Special Senses
Blurred Vision	1 (0.2%)	10 (2%)	2 (0.4%)

Signs and Symptoms of Orthostasis

In the two U.S. studies, symptomatic postural hypotension was reported by 0.2% of patients (1 of 502) in the 0.4 mg group, 0.4% of patients (2 of 492) in the 0.8 mg group, and by no patients in the placebo group. Syncope was reported by 0.2% of patients (1 of 502) in the 0.4 mg group, 0.4% of patients (2 of 492) in the 0.8 mg group and 0.6% of patients (3 of 493) in the placebo group. Dizziness was reported by 15% of patients (75 of 502) in the 0.4 mg group, 17% of patients (84 of 492) in the 0.8 mg group, and 10% of patients (50 of 493) in the placebo group. Vertigo was reported by 0.6% of patients (3 of 502) in the 0.4 mg group, 1% of patients (5 of 492) in the 0.8 mg group and by 0.6% of patients (3 of 493) in the placebo group.

Multiple testing for orthostatic hypotension was conducted in a number of studies. Such a test was considered positive if it met one or more of the following criteria: (1) a decrease in systolic blood pressure of ≥ 20 mmHg upon standing from the supine position during the orthostatic tests; (2) a decrease in diastolic blood pressure ≥ 10 mmHg upon standing, with the standing diastolic blood pressure < 65 mmHg during the orthostatic test; (3) an increase in pulse rate of ≥ 20 bpm upon standing with a standing pulse rate ≥ 100 bpm during the orthostatic test; and (4) the presence of clinical symptoms (faintness, lightheadedness/lightheaded, dizziness, spinning sensation, vertigo, or postural hypotension) upon standing during the orthostatic test.

Following the first dose of double-blind medication in Study 1, a positive orthostatic test result at 4 hours post-dose was observed in 7% of patients (37 of 498) who received Tamsulosin hydrochloride capsules 0.4 mg once daily and in 3% of the patients (8 of 253) who received placebo. At 8 hours post-dose, a positive orthostatic test result was observed for 6% of the patients (31 of 498) who received Tamsulosin hydrochloride capsules 0.4 mg once daily and 4% (9 of 250) who received placebo (Note: patients in the 0.8 mg group received 0.4 mg once daily for the first week of Study 1).

In Studies 1 and 2, at least one positive orthostatic test result was observed during the course of these studies for 81 of the 502 patients (16%) in the Tamsulosin hydrochloride capsules 0.4 mg once-daily group, 92 of the 491 patients (19%) in the Tamsulosin hydrochloride capsules 0.8 mg once-daily group, and 54 of the 493 patients (11%) in the placebo group.

Because orthostasis was detected more frequently in Tamsulosin hydrochloride capsule-treated patients than in placebo recipients, there is a potential risk of syncope [see Warnings and Precautions (5.1)].

Abnormal Ejaculation

Abnormal ejaculation includes ejaculation failure, ejaculation disorder, retrograde ejaculation and ejaculation decrease. As shown in Table 1, abnormal ejaculation was associated with Tamsulosin hydrochloride capsules administration and was dose related in the U.S. studies. Withdrawal from these clinical studies of Tamsulosin hydrochloride capsules because of abnormal ejaculation was also dose-dependent with 8 of 492 patients (1.6%) in the 0.8 mg group and no patients in the 0.4 mg or placebo groups discontinuing treatment due to abnormal ejaculation.

Laboratory Tests

No laboratory test interactions with Tamsulosin hydrochloride capsules are known. Treatment with Tamsulosin hydrochloride capsules for up to 12 months had no significant effect on prostate-specific antigen (PSA).

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Tamsulosin hydrochloride capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Tamsulosin hydrochloride capsules.

Allergic-type reactions such as skin rash, urticaria, pruritus, angioedema and respiratory symptoms have been reported with positive rechallenge in some cases. Priapism has been reported rarely. Infrequent reports of dyspnea, palpitations, hypotension, atrial fibrillation, arrhythmia, tachycardia, skin desquamation including reports of Stevens-Johnson Syndrome, constipation and vomiting have been received during the post-marketing period.

During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha1 blocker therapy [see Warnings and Precautions (5.5)].

Drug Interactions

Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6.

Concomitant treatment with ketoconazole (a strong inhibitor of CYP3A4) resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 2.2 and 2.8, respectively [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of Tamsulosin hydrochloride have not been evaluated [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Concomitant treatment with paroxetine (a strong inhibitor of CYP2D6) resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 1.3 and 1.6, respectively [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in Tamsulosin exposure exists when Tamsulosin hydrochloride capsules 0.4 mg is coadministered with strong CYP3A4 inhibitors in CYP2D6 PMs, Tamsulosin hydrochloride 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of Tamsulosin hydrochloride have not been evaluated [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

The effects of coadministration of both a CYP3A4 and a CYP2D6 inhibitor with Tamsulosin hydrochloride capsules have not been evaluated. However, there is a potential for significant increase in Tamsulosin exposure when Tamsulosin hydrochloride capsules 0.4 mg is coadministered with a combination of both CYP3A4 and CYP2D6 inhibitors [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Cimetidine

Treatment with cimetidine resulted in a significant decrease (26%) in the clearance of Tamsulosin hydrochloride, which resulted in a moderate increase in Tamsulosin hydrochloride AUC (44%) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Other Alpha Adrenergic Blocking Agents

The pharmacokinetic and pharmacodynamic interactions between Tamsulosin hydrochloride capsules and other alpha adrenergic blocking agents have not been determined; however, interactions between Tamsulosin hydrochloride capsules and other alpha adrenergic blocking agents may be expected [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

PDE5 Inhibitors

Caution is advised when alpha adrenergic blocking agents including Tamsulosin hydrochloride are coadministered with PDE5 inhibitors. Alpha adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Warfarin

A definitive drug-drug interaction study between Tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitro and in vivo studies are inconclusive. Caution should be exercised with concomitant administration of warfarin and Tamsulosin hydrochloride capsules [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Nifedipine, Atenolol, Enalapril

Dosage adjustments are not necessary when Tamsulosin hydrochloride capsules are administered concomitantly with nifedipine, atenolol, or enalapril [see Clinical Pharmacology (12.3)].

Digoxin and Theophylline

Dosage adjustments are not necessary when a Tamsulosin hydrochloride capsule is administered concomitantly with digoxin or theophylline [see Clinical Pharmacology (12.3)].

Furosemide

Tamsulosin hydrochloride capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in Tamsulosin hydrochloride Cmax and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the Tamsulosin hydrochloride capsules dosage [see Clinical Pharmacology (12.3)].

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects. Pregnancy Category B

Administration of Tamsulosin hydrochloride to pregnant female rats at dose levels up to approximately 50 times the human therapeutic AUC exposure (300 mg/kg/day) revealed no evidence of harm to the fetus. Administration of Tamsulosin hydrochloride to pregnant rabbits at dose levels up to 50 mg/kg/day produced no evidence of fetal harm. Tamsulosin hydrochloride capsules are not indicated for use in women.

Nursing Mothers

Tamsulosin hydrochloride capsules are not indicated for use in women.

Pediatric Use

Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations.

A description of the data from pediatric studies of Tamsulosin hydrochloride capsules is contained in the approved labeling for Boehringer Ingelheim’s Flomax® capsules. However, due to Boehringer Ingelheim’s marketing exclusivity rights, a description of these pediatric studies is not contained in the approved labeling for this Tamsulosin hydrochloride capsules.

Geriatric Use

Of the total number of subjects (1,783) in clinical studies of Tamsulosin, 36% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and the other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)].

Renal Impairment

Patients with renal impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosing. However, patients with end-stage renal disease (CLcr < 10 mL/min/1.73 m2) have not been studied [see Clinical Pharmacology (12.3)].

Hepatic Impairment

Patients with moderate hepatic impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosage. Tamsulosin hydrochloride has not been studied in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

Overdosage

Should overdosage of Tamsulosin hydrochloride capsules lead to hypotension [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)], support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, then administration of intravenous fluids should be considered. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that Tamsulosin hydrochloride is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit.

Tamsulosin Description

Tamsulosin hydrochloride is an antagonist of alpha1A adrenoceptors in the prostate.

Tamsulosin hydrochloride is (-)-(R)-5-[2-[[2-(o-Ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Tamsulosin hydrochloride, USP is a white to off-white powder that melts with decomposition at approximately 230°C. It is sparingly soluble in water and methanol, slightly soluble in glacial acetic acid and ethanol, and practically insoluble in ether.

The molecular formula of Tamsulosin hydrochloride is C20H28N2O5S • HCl. The molecular weight of Tamsulosin hydrochloride is 444.97. Its structural formula is:

Each Tamsulosin hydrochloride capsule, USP for oral administration contains Tamsulosin hydrochloride 0.4 mg, and the following inactive ingredients: calcium stearate, D&C Red No. 28, FD&C Blue No. 1, gelatin, methacrylic acid copolymer, microcrystalline cellulose, polysorbate 80, sodium hydroxide, sodium lauryl sulfate, talc, titanium dioxide and triethyl citrate.

The imprinting ink contains the following: black iron oxide, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, propylene glycol and shellac glaze.

Meets Dissolution Test 5.

Tamsulosin - Clinical Pharmacology

Mechanism of Action

The symptoms associated with benign prostatic hyperplasia (BPH) are related to bladder outlet obstruction, which is comprised of two underlying components: static and dynamic. The static component is related to an increase in prostate size caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma. However, the severity of BPH symptoms and the degree of urethral obstruction do not correlate well with the size of the prostate. The dynamic component is a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1 adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.

Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in the human prostate. At least three discrete alpha1 adrenoceptor subtypes have been identified: alpha1A, alpha1B, and alpha1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha1 receptors in the human prostate are of the alpha1A subtype.

Tamsulosin hydrochloride capsules are not intended for use as an antihypertensive drug.

Pharmacodynamics

Urologic pharmacodynamic effects have been evaluated in neurologically impaired pediatric patients and in adults with BPH [see Use in Specific Populations (8.4) and Clinical Studies (14)].

Pharmacokinetics

The pharmacokinetics of Tamsulosin hydrochloride have been evaluated in adult healthy volunteers and patients with BPH after single and/or multiple administration with doses ranging from 0.1 mg to 1 mg.

Absorption

Absorption of Tamsulosin hydrochloride from Tamsulosin hydrochloride capsules 0.4 mg is essentially complete (> 90%) following oral administration under fasting conditions. Tamsulosin hydrochloride exhibits linear kinetics following single and multiple dosing, with achievement of steady-state concentrations by the fifth day of once-a-day dosing.

Effect of Food

The time to maximum concentration (Tmax) is reached by 4 to 5 hours under fasting conditions and by 6 to 7 hours when Tamsulosin hydrochloride capsules are administered with food. Taking Tamsulosin hydrochloride capsules under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak concentrations (Cmax) compared to fed conditions (Figure 1).

Figure 1: Mean Plasma Tamsulosin Hydrochloride Concentrations Following Single-Dose Administration of Tamsulosin Hydrochloride Capsules 0.4 mg Under Fasted and Fed Conditions (n = 8)

The effects of food on the pharmacokinetics of Tamsulosin hydrochloride are consistent regardless of whether a Tamsulosin hydrochloride capsule is taken with a light breakfast or a high-fat breakfast (Table 2).

Table 2: Mean (± S.D.) Pharmacokinetic Parameters Following Tamsulosin Hydrochloride Capsules 0.4 mg Once Daily or 0.8 mg Once Daily with a Light Breakfast, High-Fat Breakfast or Fasted

Pharmacokinetic Parameter	0.4 mg QD to healthy volunteers; n = 23 (age range 18 to 32 years)		0.8 mg QD to healthy volunteers; n = 22 (age range 55 to 75 years)
	Light Breakfast	Fasted	Light Breakfast	High-Fat Breakfast	Fasted
Cmin (ng/mL)	4 ± 2.6	3.8 ± 2.5	12.3 ± 6.7	13.5 ± 7.6	13.3 ± 13.3
Cmax (ng/mL)	10.1 ± 4.8	17.1 ± 17.1	29.8 ± 10.3	29.1 ± 11	41.6 ± 15.6
Cmax/Cmin Ratio	3.1 ± 1	5.3 ± 2.2	2.7 ± 0.7	2.5 ± 0.8	3.6 ± 1.1
Tmax (hours)	6	4	7	6.6	5
T1/2 (hours)	-	-	-	-	14.9 ± 3.9
AUCτ (ng•hr/mL)	151 ± 81.5	199 ± 94.1	440 ± 195	449 ± 217	557 ± 257
Cmin = observed minimum concentration Cmax = observed maximum Tamsulosin hydrochloride plasma concentration Tmax = median time-to-maximum concentration T1/2 = observed half-life AUCτ = area under the Tamsulosin hydrochloride plasma time curve over the dosing interval

Distribution

The mean steady-state apparent volume of distribution of Tamsulosin hydrochloride after intravenous administration to ten healthy male adults was 16 L, which is suggestive of distribution into extracellular fluids in the body.

Tamsulosin hydrochloride is extensively bound to human plasma proteins (94% to 99%), primarily alpha1 acid glycoprotein (AAG), with linear binding over a wide concentration range (20 to 600 ng/mL). The results of two-way in vitro studies indicate that the binding of Tamsulosin hydrochloride to human plasma proteins is not affected by amitriptyline, diclofenac, glyburide, simvastatin plus simvastatin-hydroxy acid metabolite, warfarin, diazepam, propranolol, trichlormethiazide, or chlormadinone. Likewise, Tamsulosin hydrochloride had no effect on the extent of binding of these drugs.

Metabolism

There is no enantiomeric bioconversion from Tamsulosin hydrochloride [R(-) isomer] to the S(+) isomer in humans. Tamsulosin hydrochloride is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged. However, the pharmacokinetic profile of the metabolites in humans has not been established. Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6 as well as via some minor participation of other CYP isoenzymes. Inhibition of hepatic drug-metabolizing enzymes may lead to increased exposure to Tamsulosin [see Warnings and Precautions (5.2) and Drug Interactions (7.1)]. The metabolites of Tamsulosin hydrochloride undergo extensive conjugation to glucuronide or sulfate prior to renal excretion.

Incubations with human liver microsomes showed no evidence of clinically significant metabolic interactions between Tamsulosin hydrochloride and amitriptyline, albuterol (beta agonist), glyburide (glibenclamide) and finasteride (5alpha-reductase inhibitor for treatment of BPH). However, results of the in vitro testing of the Tamsulosin hydrochloride interaction with diclofenac and warfarin were equivocal.

Excretion

On administration of the radiolabeled dose of Tamsulosin hydrochloride to four healthy volunteers, 97% of the administered radioactivity was recovered, with urine (76%) representing the primary route of excretion compared to feces (21%) over 168 hours.

Following intravenous or oral administration of an immediate-release formulation, the elimination half-life of Tamsulosin hydrochloride in plasma ranged from 5 to 7 hours. Because of absorption rate-controlled pharmacokinetics with Tamsulosin hydrochloride capsules, the apparent half-life of Tamsulosin hydrochloride is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the target population.

Tamsulosin hydrochloride undergoes restrictive clearance in humans, with a relatively low systemic clearance (2.88 L/h).

Specific Populations

Pediatric Use

Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations [see Use in Specific Populations (8.4)].

Geriatric (Age) Use

Cross-study comparison of Tamsulosin hydrochloride capsules overall exposure (AUC) and half-life indicates that the pharmacokinetic disposition of Tamsulosin hydrochloride may be slightly prolonged in geriatric males compared to young, healthy male volunteers. Intrinsic clearance is independent of Tamsulosin hydrochloride binding to AAG, but diminishes with age, resulting in a 40% overall higher exposure (AUC) in subjects of age 55 to 75 years compared to subjects of age 20 to 32 years [see Use in Specific Populations (8.5)].

Renal Impairment

The pharmacokinetics of Tamsulosin hydrochloride have been compared in six subjects with mild-moderate (30 ≤ CLcr < 70 mL/min/1.73 m2) or moderate-severe (10 ≤ CLcr < 30 mL/min/1.73 m2) renal impairment and six normal subjects (CLcr > 90 mL/min/1.73 m2). While a change in the overall plasma concentration of Tamsulosin hydrochloride was observed as the result of altered binding to AAG, the unbound (active) concentration of Tamsulosin hydrochloride, as well as the intrinsic clearance, remained relatively constant. Therefore, patients with renal impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosing. However, patients with end-stage renal disease (CLcr < 10 mL/min/1.73 m2) have not been studied [see Use in Specific Populations (8.6)].

Hepatic Impairment

The pharmacokinetics of Tamsulosin hydrochloride have been compared in eight subjects with moderate hepatic impairment (Child-Pugh’s classification: Grades A and B) and eight normal subjects. While a change in the overall plasma concentration of Tamsulosin hydrochloride was observed as the result of altered binding to AAG, the unbound (active) concentration of Tamsulosin hydrochloride does not change significantly, with only a modest (32%) change in intrinsic clearance of unbound Tamsulosin hydrochloride. Therefore, patients with moderate hepatic impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosage. Tamsulosin hydrochloride has not been studied in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].

Drug Interactions

Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

The effects of ketoconazole (a strong inhibitor of CYP3A4) at 400 mg once daily for 5 days on the pharmacokinetics of a single Tamsulosin hydrochloride capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 2.2 and 2.8, respectively [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of Tamsulosin hydrochloride have not been evaluated [see Warnings and Precautions (5.2) and Drug Interactions (7.1)].

The effects of paroxetine (a strong inhibitor of CYP2D6) at 20 mg once daily for 9 days on the pharmacokinetics of a single Tamsulosin hydrochloride capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with paroxetine resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 1.3 and 1.6, respectively [see Warnings and Precautions (5.2) and Drug Interactions (7.1)]. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). A fraction of the population (about 7% of Caucasians and 2% of African Americans) are CYP2D6 PMs. Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in Tamsulosin exposure exists when Tamsulosin hydrochloride 0.4 mg capsules