cilostazol

sye-LOE-sta-zol

Commonly used brand name(s)

In the U.S.

• Pletal

Available Dosage Forms:

• Tablet

Therapeutic Class: Platelet Aggregation Inhibitor

Pharmacologic Class: Phosphodiesterase Inhibitor

Uses For cilostazol

Cilostazol improves the flow of blood through blood vessels. It is used to reduce leg pain caused by poor circulation (intermittent claudication). Cilostazol makes it possible to walk farther before having to rest because of leg pain.

Cilostazol works by keeping blood from clotting and by dilating or relaxing the blood vessels.

Cilostazol is available only with your doctor's prescription.

Before Using cilostazol

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 cilostazol, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to cilostazol 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

Studies on cilostazol have been done only in adult patients, and there is no specific information comparing the use of cilostazol in children with use in other age groups.

Geriatric

cilostazol has been tested in a limited number of patients and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

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

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking cilostazol, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using cilostazol with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab


• Alteplase, Recombinant


• Aspirin


• Bromfenac


• Celecoxib


• Citalopram


• Clopidogrel


• Dabigatran Etexilate


• Desirudin


• Desvenlafaxine


• Diclofenac


• Diflunisal


• Dipyridamole


• Duloxetine


• Eptifibatide


• Escitalopram


• Etodolac


• Fluoxetine


• Flurbiprofen


• Fluvoxamine


• Ginkgo


• Ibuprofen


• Ibuprofen Lysine


• Indomethacin


• Ketoprofen


• Ketorolac


• Magnesium Salicylate


• Mefenamic Acid


• Meloxicam


• Milnacipran


• Nabumetone


• Naproxen


• Nefazodone


• Nepafenac


• Oxaprozin


• Paroxetine


• Piroxicam


• Prasugrel


• Rivaroxaban


• Salsalate


• Sertraline


• Sulfinpyrazone


• Sulindac


• Ticlopidine


• Tirofiban


• Tolmetin


• Venlafaxine

Using cilostazol with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Clarithromycin


• Diltiazem


• Erythromycin


• Ketoconazole


• Omeprazole

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using cilostazol with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use cilostazol, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

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

• Active bleeding (including peptic ulcers and intracranial bleeding [e.g., bleeding on the brain]) or


• Blood or blood clotting disorders or


• Congestive heart failure—cilostazol should not be used.

• Kidney disease or


• Liver disease—Special caution should be used.

• Thrombocytopenia (low platelet count in the blood)—Caution should be used.

Proper Use of cilostazol

To help you remember to take your medicine, try to get into the habit of taking it at the same time each day.

Dosing

The dose of cilostazol 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 cilostazol. 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.

• For oral dosage form (tablets):
  
  • For treatment of peripheral vascular disease (circulation problems):
    
    • Adults—100 milligrams (mg) two times a day, taken at least one half hour before or two hours after breakfast and dinner. In patients who take certain other medicines at the same time as cilostazol, the dose may be 50 mg two times a day.
    
    
    • Children—Use and dose must be determined by a doctor.
    
    
  
  

Missed Dose

If you miss a dose of cilostazol, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using cilostazol

It may take several weeks for cilostazol to work. If you feel that cilostazol is not working, do not stop taking it on your own. Instead, check with your doctor.

Smoking tobacco products, such as cigarettes, may worsen your condition since nicotine may further narrow blood vessels and may also affect how cilostazol works. Therefore, it is best to avoid smoking.

You should not take cilostazol with grapefruit juice. You may, however, take it with other citrus juices.

cilostazol 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

• Fast or irregular heartbeat


• fever

Less common

• Abnormal bleeding


• bloody or black tarry stools


• bruises and/or red spots on the skin


• fainting


• nausea, heartburn, and/or indigestion (severe or continuing)


• nosebleeds


• stiff neck


• stomach pain, cramping, or burning (severe)


• swelling of the tongue


• vomiting of blood or material that looks like coffee grounds

Incidence not known

• Abdominal or stomach pain


• area rash


• bleeding gums


• bleeding tendency


• blistering, peeling, loosening of skin


• blood in urine or stools


• blurred vision


• chest pain


• chills


• clay-colored stools


• confusion


• cough or hoarseness


• coughing up blood


• dark urine


• diarrhea


• difficult breathing


• drowsiness


• fever with or without chills


• general feeling of tiredness or weakness


• headache, sudden and severe


• inability to speak


• irregular heartbeat


• itching of eyes


• itching of skin


• joint or muscle pain


• lab results that show problems with the liver


• light-colored stools


• loss of appetite


• loss of consciousness


• lower back or side pain


• nausea and vomiting


• painful or difficult urination


• pinpoint red spots on skin


• red, irritated eyes


• red skin lesions, often with a purple center


• seizures


• shortness of breath


• skin rash


• slurred speech


• sores, ulcers, or white spots on lips or in mouth


• stomach pain


• swollen glands


• temporary blindness


• unpleasant breath odor


• unusual bleeding or bruising


• unusual tiredness or weakness


• weakness in arm and/or leg on one side of the body, sudden and severe


• weakness of part of body


• wheezing


• yellow eyes or skin

Symptoms of overdose

• Diarrhea


• dizziness or lightheadedness when getting up from a lying or sitting position


• fast or irregular heartbeat


• headache (severe)

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

More commonLess common

• Bone pain


• burning feeling in throat or chest


• difficulty in swallowing


• hives


• pain or stiffness in joints


• ringing or buzzing in ears


• swelling of face, fingers, and/or lower legs

Incidence not known

• Bruising


• hot flushes


• pain

• Back pain


• dizziness


• gas


• headache


• increased cough


• pain or stiffness in muscles


• pounding heartbeat


• runny or stuffy nose


• sore throat


• swelling of arms or legs

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: cilostazol 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 cilostazol resources

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

• cilostazol Concise Consumer Information (Cerner Multum)


• Cilostazol Prescribing Information (FDA)


• Cilostazol Monograph (AHFS DI)


• Cilostazol Professional Patient Advice (Wolters Kluwer)


• Cilostazol MedFacts Consumer Leaflet (Wolters Kluwer)


• Pletal Prescribing Information (FDA)

Compare cilostazol with other medications

• Intermittent Claudication

Anakinra

Class: Disease-modifying Antirheumatic Agents
Chemical Name: N2-l-methionyl-interleukin 1 receptor antagonist (human isoform × reduced)
Molecular Formula: C₇₅₉H₁₁₈₆N₂₀₈O₂₃₂S₁₀
CAS Number: 143090-92-0
Brands: Kineret

Introduction

Recombinant human interleukin-1 (IL-1) receptor antagonist; biologic response modifier and disease-modifying antirheumatic drug (DMARD).^{1 11}

Uses for Anakinra

Rheumatoid Arthritis in Adults

Used alone or in combination with DMARDs other than tumor necrosis factor (TNF) blocking agents (e.g., adalimumab, etanercept, infliximab) for the management of signs and symptoms of rheumatoid arthritis and to inhibit progression of structural damage associated with the disease in adults with moderately to severely active disease who have had an inadequate response to therapy with one or more DMARDs.^{1 3 4 5 12 13} (See Interactions.)

Anakinra Dosage and Administration

General

• 
  

  Monitor neutrophil counts prior to and during anakinra therapy.^{1 12} (See Neutropenia under Cautions.)

  
  

Administration

Sub-Q Administration

Administer sub-Q at approximately the same time each day.¹

Administer sub-Q injections into the thighs, abdomen, upper arms, or buttocks.¹⁷ Rotate injection sites.¹⁷ Do not make injections into areas where the skin is tender, bruised, red, or hard; into scars or stretch marks; or close to a vein.¹⁷

Allow anakinra prefilled syringe to reach room temperature (about 60–90 minutes) prior to administration.¹⁷ Do not remove the needle cover until the prefilled syringe has reached room temperature.¹⁷

Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug.¹

Dosage

Adults

Rheumatoid Arthritis

Sub-Q

100 mg (entire contents [0.67 mL] of one prefilled syringe) daily.¹

Prescribing Limits

Adults

Rheumatoid Arthritis

Sub-Q

Dosages >100 mg daily do not appear to provide additional benefit.¹

Special Populations

Renal Impairment

Rheumatoid Arthritis

Sub-Q

Consider decreasing dosage to 100 mg every other day in patients with severe renal insufficiency or end-stage renal disease (Cl_cr <30 mL/minute, as estimated from S_cr).^{1 15} (See the Special Populations sections under Pharmacokinetics and under Cautions.)

Cautions for Anakinra

Contraindications

• 
  

  Known hypersensitivity to Escherichia coli-derived proteins, anakinra, or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Infectious Complications

Increased incidence of serious infections reported.^{1 9 12} (See Infection under Cautions.) Do not initiate anakinra therapy in patients with active infections.¹ Discontinue the drug in patients who develop a serious infection.¹ Safety and efficacy have not been evaluated in immunosuppressed patients or patients with chronic infections.¹

Interactions

Concomitant use of TNF blocking agents (e.g., adalimumab, etanercept, infliximab) not recommended.¹ Increased incidence of serious infections and lack of additional clinical benefit with combined anakinra and etanercept therapy.¹

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and anaphylactoid reactions reported rarely.^{1 11}

If a severe hypersensitivity reaction occurs, discontinue anakinra immediately and institute appropriate interventions as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, IV fluids, antihistamines, maintenance of BP).¹

Latex Sensitivity

The needle cover of the prefilled syringe contains dry natural rubber (latex); individuals sensitive to latex should not handle the needle cover.¹

Major Toxicities

Infection

The incidence of infection, including serious infections, is increased in patients receiving anakinra.¹ Infections of bacterial origin (e.g., cellulitis, pneumonia, bone and joint) most common.¹ Opportunistic infections (fungal, mycobacterial, bacterial, viral) reported rarely.¹ Patients with asthma may be at a higher risk for developing serious infections.¹

Risk of serious infection and neutropenia increased in patients receiving concomitant anakinra and etanercept compared with etanercept alone.^{1 5}

Hematologic Effects

Small reductions reported in WBC, ANC, and platelet counts; small increases in eosinophil counts reported.^{1 13}

General Precautions

Immunologic Effects

Effect of anakinra in patients with active and/or chronic infections or on the subsequent development of malignancy not fully elucidated.¹

Anti-anakinra antibodies reported after therapy; not associated with increased adverse events.¹ Effect of neutralizing antibodies on clinical response not fully elucidated.^{1 3 11 13}

Do not administer live-virus vaccines to patients receiving anakinra.¹ (See Vaccines under Interactions.)

Neutropenia

Neutropenia (ANC < 1000/mm²) and/or reduced neutrophil counts reported.¹ Monitor ANC before therapy is initiated, monthly for 3 months, and then every 3 months for a period up to 1 year during anakinra therapy.^{1 12}

Malignancies and Lymphoproliferative Disorders

Increased incidence of lymphoma compared with general population reported in patients with rheumatoid arthritis receiving anakinra.¹ However, patients with rheumatoid arthritis, especially those with highly active disease, may be at increased risk of lymphoma.¹ Role of human interleukin-1 receptor antagonist (IL-1Ra)-induced immunosuppression in the development of malignancies is unknown.¹

Increased incidence of malignancies involving the breast and respiratory and digestive systems has been reported.¹ Increased incidence of melanoma also reported; clinical importance unknown.¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Not known whether anakinra is distributed into milk.¹ Caution if used in nursing women.¹

Pediatric Use

Evaluated in a limited number of children 2–17 years of age with polyarticular course juvenile rheumatoid arthritis†; efficacy not established (insufficient numbers of children have been enrolled in trials).¹ Adverse effects observed in children similar to those in adults.¹ Use of anakinra in pediatric patients is not recommended.¹ The currently available prefilled syringes are not designed to deliver pediatric doses accurately.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Geriatric patients may be at increased risk of serious infection; use with caution.¹

Geriatric patients may be at increased risk of toxic reactions due to impaired renal function; use with caution.¹ (See Renal Impairment under Cautions.)

Hepatic Impairment

Not studied in patients with severe hepatic impairment.¹

Renal Impairment

Risk of toxic reactions increased; consider dosage reduction.¹ (See Renal Impairment under Dosage and Administration.)

Elimination reduced in patients with renal insufficiency.¹ (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Injection-site reaction,^{1 3 5 9 10 12 13} infections (principally bacterial origin),^{1 3 11 13} headache,^{1 13} nausea,¹ neutropenia,¹ diarrhea,¹ influenza-like symptoms,^{1 11} abdominal pain.^{1 13}

Interactions for Anakinra

Used concomitantly with methotrexate, sulfasalazine, hydroxychloroquine, gold, penicillamine, leflunomide, and/or azathioprine in clinical studies;^{1 3 13} specific drug interactions not evaluated in humans.^{1 11}

Vaccines

Live virus vaccines should not be administered to patients receiving anakinra.¹ Information is not available regarding whether anakinra would affect the rate of secondary transmission of vaccine virus following administration of a live virus vaccine or regarding any other effect of vaccination on patients receiving the drug.¹

Information not available regarding effects of vaccination with inactivated vaccine.¹

Specific Drugs

Drug	Interaction	Comments
Abatacept		Concomitant use not recommended; clinical experience insufficient to establish safety and efficacy16
Methotrexate	Pharmacokinetic interaction unlikely;1 no alterations in clearance or toxicologic profile of anakinra or methotrexate with concomitant administration in rats1
Tetanus toxoid	Immunologic response preserved in 1 study1
TNF blocking agents (e.g., adalimumab, etanercept, infliximab)	Increased incidence of adverse effects (serious infections, neutropenia) and no added clinical benefit reported with combined anakinra and etanercept therapy compared with etanercept alone1 14	Concomitant use not recommended1 14

Anakinra Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is 95% after sub-Q administration; peak plasma concentrations attained within 3–7 hours.¹

Distribution

Extent

Not known whether anakinra crosses the placenta or is distributed into milk.¹

Elimination

Metabolism

Metabolic fate of anakinra not fully elucidated; no unexpected accumulation after daily sub-Q dosing for up to 24 weeks.^{1 15}

Elimination Route

Excreted principally in urine.^{1 15}

Half-life

Terminal half-life averages 4–6 hours.¹

Special Populations

In patients with renal impairment, plasma clearance was reduced by 16–75% depending on Cl_cr.^{1 15} Less than 2.5% of dose removed by hemodialysis or CAPD.¹ (See Renal Impairment under Dosage and Administration.)

Gender and age (adjusted for Cl_cr and body weight) do not have substantial effect on mean plasma clearance.¹

Pharmacokinetics not studied in patients with hepatic impairment.¹

Stability

Storage

Parenteral

Injection

2–8°C; do not freeze or shake.¹ Protect from light.¹

ActionsActions

• 
  

  A biosynthetic (recombinant DNA origin) form of human interleukin-1 (IL-1) receptor antagonist (IL-1Ra).

  
  


• 
  

  A biologic response modifier that blocks the biologic activity of endogenous IL-1.^{1 3 4 5 9 10 12 11}

  
  


• 
  

  Competitively inhibits binding of IL-1 to the interleukin-1 type I receptor (IL-1RI) expressed in many tissues and organs.^{1 10} Decreases inflammation and cartilage degradation associated with rheumatoid arthritis.^{1 2 5 10 12}

  
  

Advice to Patients

• 
  

  Importance of providing patient a copy of manufacturer’s patient information.¹

  
  


• 
  

  Importance of patient informing clinician about existing or recurrent infections prior to initiating therapy.^{1 17}

  
  


• 
  

  Importance of instructing patient and/or caregiver regarding proper dosage and administration of anakinra, including the use of aseptic technique and safe disposal of needles and syringes, in patients whose clinician has determined that the drug can safely and effectively be self-administered in the patient’s home by the patient, family member, or other responsible individual.¹

  
  


• 
  

  Importance of advising patient and/or caregiver about recognition and reporting of adverse effects of anakinra (e.g., sensitivity reactions, infection).¹

  
  


• 
  

  Importance of informing clinician if allergy to latex exists.¹¹

  
  


• 
  

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

Anakinra (Recombinant DNA Origin)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use	100 mg/0.67 mL	Kineret (preservative-free; available in prefilled disposable syringes)	Amgen

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.

Kineret 100MG/0.67ML Solution (BIOVITRUM AB): 4/$406.6 or 18/$1599.06

Disclaimer

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

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

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

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

References

1. Amgen Inc. Kineret (anakinra) injection prescribing information. Thousand Oaks, CA; 2006 Dec 15.

2. Schiff MH. Role of interleukin 1 and interleukin 1 receptor antagonist in the mediation of rheumatoid arthritis. Ann Rheum Dis. 2000; 59(Suppl 1):i103-8. [IDIS 455654] [PubMed 11053099]

3. Bresnihan B, Alvaro-Gracia JM, Cobby M, et al., Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum1998; 41:2196-204.

4. Jiang Y, Genant HK, Watt I, et al.A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum 2000; 43:1001-9. [PubMed 10817552]

5. Anon. Anakinra (kineret) for rheumatoid arthritis. Med Lett Drugs Ther. 2002; 44:18-9.

6. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatology Association 1987: revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315-24. [PubMed 3358796]

7. Hochberg MC, Chang RW, Dwosh I et al. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992; 35:498-502. [PubMed 1575785]

8. Felson DT, Anderson JJ, Boers M et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995; 38:727-35. [PubMed 7779114]

9. Bresnihan B.The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoid arthritis. Semin Arthritis Rheum. 2001; 30(Suppl 2):17-20. [PubMed 11357167]

10. Bresnihan B. The prospect of treating rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. BioDrugs. 2001; 15:87-97. [PubMed 11437678]

11. Amgen Inc,Thousand Oaks, CA: Personal communication.

12. Calabrese LH. Anakinra treatment of patients with rheumatoid arthritis. Ann Pharmacother. 2002; 36:1204-9. [IDIS 485217] [PubMed 12086555]

13. Cohen S, Hurd E, Cush J, Schiff M et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002; 46:614-24. [PubMed 11920396]

14. Spencer-Green G. Dear healthcare professional letter: Important Drug Warning. Abbott Park, IL: Abbott Laboratories; 2004 Nov.

15. Yang BB, Baughman S, Sullivan JT. Pharmacokinetics of anakinra in subjects with different levels of renal function. Clin Pharmacol Ther. 2003; 74:85-94. [PubMed 12844139]

16. Bristol-Myers Squibb. Orencia (abatacept) prescribing information. Princeton, NJ; 2005 Dec.

17. Amgen Inc. Kineret (anakinra) patient information. Thousand Oaks, CA; 2006 Dec 15.

More Anakinra resources

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

• Anakinra MedFacts Consumer Leaflet (Wolters Kluwer)


• Anakinra Professional Patient Advice (Wolters Kluwer)


• anakinra Subcutaneous Advanced Consumer (Micromedex) - Includes Dosage Information


• Kineret Prescribing Information (FDA)


• Kineret Consumer Overview

Compare Anakinra with other medications

• Rheumatoid Arthritis
• Schnitzler Syndrome
• Still's Disease

guaifenesin and phenylephrine

Generic Name: guaifenesin and phenylephrine (gwye FEN e sin and FEN il EFF rin)

Brand names: Aldex G, Aquatab D, Crantex, D-Phen 1000, D-Tab, Deconex, Deconsal II, Deconsal Pediatric, Despec, Donatussin Drops, Duomax, Duraphen 1000, Duraphen II, Duratuss, Dynex LA, ExeTuss, Extendryl G, Fenesin PE IR, Genexa LA, Gentex LA, Gilphex TR, Guaiphen-D 1200, Guaiphen-D 600, Guaiphen-PD, Guiadex PD, Guiatex PE, J-Max, Liquibid D-R, Liquibid-D, Liquibid-PD, Lusonex, Maxiphen, Medent-PE, MontePhen, Mucinex Children's Cold, Mucus Relief Sinus, Mydex, Nariz, Nasex, Nescon-PD, Nexphen PD, Norel EX, PE-Guai, Pendex, Prolex D, Refenesen PE, Reluri, Rescon-GG, Respa-PE, Robitussin Head & Chest Congestion, Simuc, Simuc-GP, Sina-12X, Sinupan, SINUvent PE, Sitrex PD, Sudafed PE Non-Drying Sinus, Sudex, Triaminic Chest & Nasal Congestion, Visonex, Wellbid-D, Xedec, Xedec II, Xpect-PE, Zotex GPX, ...show all 109 brand names.Efasin, Amidal, Chemdal, Quindal, Endal, Entex LA, Entex (obsolete formulation), Crantex LA Capsules, Amitex LA, Entex ER, Crantex ER, Liquibid-D 1200, Phenavent LA, Phenavent D, Guaifed Caps, Guaifed PD, Phenavent, Tussbid, Phenavent PED, Prolex PD, Aldex, Crantex LA Tablets, Duratuss GP, Sitrex, Wellbid-D 1200, Nasex-G, Guaifen PE, Ambi 40/1000, Triaminic Chest & Nasal Congestion, Duratuss PE, Nazarin, Robitussin Head & Chest Congestion, Zyrphen, ExeTuss-GP, Deconex IR, Quintex, Medent-PEI, Liquibid PD-R, Zoden Drops, Entex LQ, Tussi-Pres PE, Supress-PE, Lusair, Reese Onetab Congestion & Cough

What is guaifenesin and phenylephrine?

There are many brands and forms of guaifenesin and phenylephrine available and not all brands are listed on this leaflet.

Guaifenesin is an expectorant. It helps loosen congestion in your chest and throat, making it easier to cough out through your mouth.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of guaifenesin and phenylephrine is used to treat stuffy nose and sinus congestion, and to reduce chest congestion caused by the common cold or flu.

Guaifenesin and phenylephrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about guaifenesin and phenylephrine?

There are many brands and forms of guaifenesin and phenylephrine available and not all brands are listed on this leaflet.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Ask a doctor or pharmacist before using any other cough, cold, or allergy medicine. Guaifenesin and phenylephrine are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains guaifenesin or phenylephrine.

What should I discuss with my healthcare provider before taking guaifenesin and phenylephrine?

You should not use this medication if you are allergic to guaifenesin or phenylephrine, or to other decongestants, diet pills, stimulants, or ADHD medications. Do not use guaifenesin and phenylephrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. Serious, life threatening side effects can occur if you use guaifenesin and phenylephrine before the MAO inhibitor has cleared from your body.

Ask a doctor or pharmacist if it is safe for you to take this medication if you have:

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  heart disease or high blood pressure;

  
  


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  diabetes;

  
  


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  circulation problems;

  
  


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  glaucoma;

  
  


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  overactive thyroid; or

  
  


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  enlarged prostate or problems with urination.

  
  

It is not known if this medication may be harmful to an unborn baby. Do not use this medication without your doctor's advice if you are pregnant. This medication passes into breast milk and could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take guaifenesin and phenylephrine?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving cough or cold medicine to a child. Death can occur from the misuse of cough or cold medicine in very young children.

Measure the liquid form of this medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time. Take guaifenesin and phenylephrine with food if it upsets your stomach. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash. Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cough or cold medicine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

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

Overdose symptoms may include nausea, vomiting, numbness or tingly feeling, dizziness, and feeling restless or nervous.

What should I avoid while taking guaifenesin and phenylephrine?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of guaifenesin and phenylephrine. Ask a doctor or pharmacist before using any other cough, cold, or allergy medicine. Guaifenesin and phenylephrine are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains guaifenesin or phenylephrine.

Avoid taking this medication with diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Guaifenesin and phenylephrine side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

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  fast, pounding, or uneven heartbeat;

  
  


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  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


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  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms;

  
  


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

  
  


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  nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

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  vomiting, upset stomach;

  
  


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  warmth, tingling, or redness under your skin;

  
  


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  feeling excited or restless (especially in children);

  
  


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  sleep problems (insomnia);

  
  


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  skin rash or itching;

  
  


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  headache; or

  
  


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  dizziness.

  
  

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.

Guaifenesin and phenylephrine Dosing Information

Usual Adult Dose for Cough and Nasal Congestion:

Tablets:
Guaifenesin 550 mg- phenylephrine 8.5 mg: 1 tablet orally every 6 to 8 hours, not to exceed 4 tablets a day.
Guaifenesin 380 mg- phenylephrine 10 mg: 1 tablet orally every 4 hours, not to exceed 6 tablets a day.
Guaifenesin 200 mg- phenylephrine 5 mg: 2 tablets orally every 4 hours, not to exceed 12 tablets a day.

Liquid:
Guaifenesin 75 mg- phenylephrine 7.5 mg/5 mL: 10 mL orally every 4 to 6 hours, up to 40 mL a day.
Guaifenesin 100 mg- phenylephrine 5 mg/5 mL or guaifenesin 200 mg- phenylephrine 7.5 mg/5 mL: 10 mL orally every 4 to 6 hours, up to 40 mL a day.
Guaifenesin 100 mg- phenylephrine 7.5 mg/5 mL: 5 to 10 mL orally every 4 to 6 hours, up to 40 mL a day.
Guaifenesin 200 mg- phenylephrine 5 mg/5 mL: 5 to 10 mL orally every 4 to 6 hours, up to 60 mL a day.
Guaifenesin 100 mg- phenylephrine 10 mg/5 mL: 5 mL orally every 4 to 6 hours, up to 40 mL a day.

Tablets, extended-release:
Guaifenesin 275 mg- phenylephrine 25 mg: 1 to 2 tablets orally every 12 hours, up to 4 tablets a day.
Guaifenesin 600 mg- phenylephrine 18 mg, or guaifenesin 300 mg- phenylephrine 20 mg, or guaifenesin 600 mg- phenylephrine 15 mg, or guaifenesin 315 mg- phenylephrine 20 mg: 2 tablets orally every 12 hours.
Guaifenesin 600 mg- phenylephrine 10 mg or guaifenesin 600 mg- phenylephrine 25 mg: 1 to 2 tablets orally every 12 hours.
Guaifenesin 600 mg- phenylephrine 20 mg: 1 to 2 tablets orally every 12 hours, up to 2 tablets a day.
Guaifenesin 600 mg- phenylephrine 30 mg, or guaifenesin 600 mg- phenylephrine 40 mg, or guaifenesin 650 mg- phenylephrine 40 mg: 1 tablet orally every 12 hours.
Guaifenesin 650 mg- phenylephrine 23.75 mg, or guaifenesin 650 mg- phenylephrine 25 mg: 1 tablet orally every 12 hours not to exceed 2 tablets a day.
Guaifenesin 800 mg- phenylephrine 20 mg: 1 tablet orally every 8 hours not to exceed 3 tablets a day.
Guaifenesin 800 mg- phenylephrine 30 mg, or guaifenesin 800 mg- phenylephrine 40 mg, or guaifenesin 835 mg- phenylephrine 25 mg, or guaifenesin 835 mg- phenylephrine 30 mg or guaifenesin 900 mg- phenylephrine 25 mg, or guaifenesin 900 mg- phenylephrine 30 mg, or guaifenesin 1000 mg- phenylephrine 30 mg, or guaifenesin 1000 mg- phenylephrine 40 mg, or guaifenesin 1050 mg- phenylephrine 30 mg, or guaifenesin 1200 mg- phenylephrine 25 mg, or guaifenesin 1100 mg- phenylephrine 30 mg, or guaifenesin 1200 mg- phenylephrine 20 mg, or guaifenesin 1200 mg- phenylephrine 30 mg, or guaifenesin 1200 mg- phenylephrine 35 mg: 1 tablet orally every 12 hours not to exceed 2 tablets a day.
Guaifenesin 600 mg- phenylephrine 12.5 mg: 1 to 2 tablets orally every 12 hours or 1 tablet every 8 hours not to exceed 4 tablets a day.

Capsule, extended-release:
Guaifenesin 200 mg- phenylephrine 7.5 mg, or guaifenesin 300 mg- phenylephrine 10 mg: 1 to 2 capsules orally every 12 hours.
Guaifenesin 375 mg- phenylephrine 20 mg: 1 to 2 capsules orally every 12 hours, up to 3 capsules a day.
Guaifenesin 400 mg- phenylephrine 15 mg: 1 capsule orally every 12 hours.

Usual Pediatric Dose for Cough and Nasal Congestion:

guaifenesin-phenylephrine 20 mg- 1.5 mg/ mL:
2 years to 5 years: 1 mL orally every 4 to 6 hours as needed. Do not exceed 4 doses in 24 hours.
6 years to 12 years: 2 mL orally every 4 to 6 hours as needed. Do not exceed 4 doses in 24 hours.

guaifenesin 100 mg- phenylephrine 5 mg/5 mL or guaifenesin 200 mg- phenylephrine 7.5 mg/5 mL or guaifenesin 75 mg - phenylephrine 7.5 mg/5 mL:
2 years to 6 years: 2.5 mL orally every 4 to 6 hours, up to 4 doses/day.
6 years to 11 years: 5 mL orally every 4 to 6 hours, up to 4 doses/day.

guaifenesin 50 mg- phenylephrine 2.5 mg/5 mL or guaifenesin 100 mg- phenylephrine 2.5 mg/5 mL:
2 years to 5 years: 5 mL orally every 4 hours, up to 6 doses a day.
6 years to 11 years: 10 mL orally every 4 hours, up to 6 doses a day.

guaifenesin 200 mg- phenylephrine 5 mg/5 mL:
2 years to 5 years: 2.5 mL orally every 4 hours, up to 6 doses a day.
6 years to 11 years: 5 mL orally every 4 hours, up to 6 doses a day.

Guaifenesin 100 mg- phenylephrine 10 mg/5 mL:
2 years to 5 years: 1.25 mL orally every 4 to 6 hours, up to 8 doses a day.
6 years to 11 years: 2.5 mL orally every 4 to 6 hours, up to 8 doses a day.

6 years to 11 years:
Guaifenesin 550 mg- phenylephrine 8.5 mg: 1/2 tablet orally every 6 to 8 hours, not to exceed 2 tablets a day.

Tablets, extended-release:
Guaifenesin 600 mg- phenylephrine 10 mg or guaifenesin 600 mg- phenylephrine 25 mg: 1/2 to 1 tablet orally every 12 hours.
Guaifenesin 600 mg- phenylephrine 18 mg or guaifenesin 600 mg- phenylephrine 15 mg: 2 tablets orally every 12 hours.
Guaifenesin 650 mg- phenylephrine 40 mg: 1/2 tablet orally every 12 hours.
Guaifenesin 800 mg- phenylephrine 20 mg: 1/2 tablet orally every 8 hours not to exceed 1.5 tablets a day.
Guaifenesin 900 mg- phenylephrine 30 mg, or guaifenesin 650 mg- phenylephrine 23.75 mg: 1/2 tablet orally every 12 hours not to exceed 2 tablets a day.
Guaifenesin 800 mg- phenylephrine 40 mg, or guaifenesin 315 mg- phenylephrine 15 mg: 1 tablet orally every 12 hours not to exceed 2 tablets a day.
Guaifenesin 800 mg- phenylephrine 30 mg, or guaifenesin 650 mg- phenylephrine 25 mg, or guaifenesin 835 mg- phenylephrine 25 mg, or guaifenesin 835 mg- phenylephrine 30 mg, or guaifenesin 900 mg- phenylephrine 25 mg, or guaifenesin 1000 mg - phenylephrine 30 mg, or guaifenesin 1000 mg- phenylephrine 40 mg, or guaifenesin 1050 mg- phenylephrine 30 mg, or guaifenesin 1100 mg- phenylephrine 30 mg, guaifenesin 1200 mg- phenylephrine 20 mg, or guaifenesin 1200 mg- phenylephrine 30 mg: 1/2 tablet orally every 12 hours not to exceed 1 tablet a day.

12 yrs and older:
Guaifenesin 100 mg- phenylephrine 5 mg/5 mL: 10 mL orally every 4 to 6 hours, up to 4 doses a day.
Guaifenesin 550 mg- phenylephrine 8.5 mg: 1 tablet orally every 6 to 8 hours, not to exceed 4 tablets a day.
Guaifenesin 380 mg- phenylephrine 10 mg: 1 tablet orally every 4 hours, not to exceed 6 tablets a day.
Guaifenesin 200 mg- phenylephrine 5 mg: 2 tablets orally every 4 hours, not to exceed 12 tablets a day.
Guaifenesin 100 mg- phenylephrine 10 mg/5 mL: 5 mL orally every 4 to 6 hours, up to 8 doses a day.

Tablets, extended-release:
Guaifenesin 800 mg- phenylephrine 20 mg: 1 tablet every 8 hours not to exceed 3 tablets a day.
Guaifenesin 275 mg- phenylephrine 25 mg or guaifenesin 600 mg- phenylephrine 15 mg: 1 tablet orally every 12 hours.
Guaifenesin 600 mg- phenylephrine 10 mg or guaifenesin 600 mg- phenylephrine 25 mg: 1 to 2 tablets orally every 12 hours.
Guaifenesin 600 mg- phenylephrine 18 mg, or guaifenesin 315 mg- phenylephrine 20 mg: 2 tablets orally every 12 hours.
Guaifenesin 600 mg- phenylephrine 40 mg: 1 tablet orally every 12 hours.
Guaifenesin 650 mg- phenylephrine 23.75 mg, or guaifenesin 650 mg- phenylephrine 25 mg, or guaifenesin 800 mg- phenylephrine 30 mg, or guaifenesin 800 mg- phenylephrine 40 mg, or guaifenesin 835 mg- phenylephrine 25 mg, or guaifenesin 835 mg- phenylephrine 30 mg, or guaifenesin 900 mg- phenylephrine 25 mg, or guaifenesin 900 mg- phenylephrine 30 mg, or guaifenesin 1000 mg- phenylephrine 40 mg, or guaifenesin 1050 mg- phenylephrine 30 mg, or guaifenesin 1100 mg- phenylephrine 30 mg, or guaifenesin 1200 mg- phenylephrine 20 mg, or guaifenesin 1200 mg- phenylephrine 25 mg, or guaifenesin 1200 mg- phenylephrine 30 mg, or guaifenesin 1200 mg- phenylephrine 35 mg: 1 tablet orally every 12 hours not to exceed 2 tablets a day.
Guaifenesin 600 mg- phenylephrine 12.5 mg: 1 to 2 tablets orally every 12 hours or 1 tablet every 8 hours not to exceed 4 tablets a day.

Capsules, extended-release:
Guaifenesin 200 mg- phenylephrine 7.5 mg: 1 to 2 capsules orally every 12 hours.
Guaifenesin 300 mg- phenylephrine 10 mg or Guaifenesin 400 mg - phenylephrine 15 mg: 1 capsule orally every 12 hours.
Guaifenesin 375 mg- phenylephrine 20 mg: 1 to 2 capsules orally every 12 hours, up to 3 a day.

What other drugs will affect guaifenesin and phenylephrine?

Ask a doctor or pharmacist if it is safe for you to take guaifenesin and phenylephrine if you are also using any of the following drugs:

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  medicines to treat high blood pressure;

  
  


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  a beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others; or

  
  


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  an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan, Silenor), desipramine (Norpramin), imipramine (Janimine, Tofranil), nortriptyline (Pamelor), and others.

  
  

This list is not complete and other drugs may interact with guaifenesin and phenylephrine. 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 guaifenesin and phenylephrine resources

• Guaifenesin and phenylephrine Side Effects (in more detail)
• Guaifenesin and phenylephrine Use in Pregnancy & Breastfeeding
• Drug Images
• Guaifenesin and phenylephrine Drug Interactions
• Guaifenesin and phenylephrine Support Group
• 8 Reviews for Guaifenesin and phenylephrine - Add your own review/rating

Compare guaifenesin and phenylephrine with other medications

• Cough and Nasal Congestion
• Sinus Symptoms

Where can I get more information?

• Your pharmacist can provide more information about guaifenesin and phenylephrine.

See also: guaifenesin and phenylephrine side effects (in more detail)

Pegasys

Pronunciation: peg-IN-ter-FEER-on AL-fa
Generic Name: Peginterferon Alfa-2a
Brand Name: Pegasys

Pegasys may cause or worsen fatal or life-threatening medical conditions, including mental or mood problems (eg, depression, suicidal thoughts or behaviors), autoimmune diseases (eg, lupus, rheumatoid arthritis), blood vessel problems (eg, ischemia), and infection. These problems usually go away after stopping Pegasys, but not always. Your doctor will monitor you for these conditions. Be sure to keep all doctor and laboratory appointments. If you have a history of any of these problems or develop them while using Pegasys, tell your doctor immediately.

Pegasys is sometimes used with another medicine called ribavirin. Ribavirin may cause birth defects or fetal death and must not be used during pregnancy. Women who use ribavirin and female sexual partners of men who use ribavirin and are of childbearing potential must avoid becoming pregnant. They must also

• have a negative pregnancy test immediately before therapy with Pegasys is started.


• avoid becoming pregnant during therapy with Pegasys or within the first 6 months after Pegasys is stopped.

Two forms of effective birth control must be used during treatment with ribavirin and for 6 months after ribavirin treatment is stopped. Discuss any questions or concerns with your doctor.

Ribavirin can also cause a certain blood disorder called hemolytic anemia, which may worsen existing heart disease. Tell your doctor immediately if any serious symptoms or side effects occur.

Pegasys is used for:

Treating chronic hepatitis C infection in patients who have controlled liver disease and have not been previously treated with interferon alfa. Pegasys is used either alone or in combination with other medicines. It is also used to treat certain patients with hepatitis B. It may also be used for other conditions as determined by your doctor.

Pegasys is an interferon. It works by reducing the amount of hepatitis virus in the body. It also helps the immune system fight the virus.

Do NOT use Pegasys if:

• you are allergic to any ingredient in Pegasys or to another alpha interferon


• you have hepatitis caused by your immune system attacking your liver (autoimmune hepatitis) or you have unstable or severe liver disease


• you have uncontrolled thyroid or blood sugar problems


• you are taking telbivudine

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

Before using Pegasys:

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

• if you are planning to become pregnant


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


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


• if you have a history of heart problems or a heart attack, high blood pressure, kidney problems or if you are on dialysis, bone marrow problems (eg, low white blood cell levels, low platelet levels), blood or bleeding disorders, stroke, thyroid problems, lung or breathing problems (eg, asthma, pneumonia), stomach or bowel problems (eg, colitis, blood in the stools or vomit), pancreas problems, or eye or vision problems


• if you have a history of autoimmune disease (eg, psoriasis, lupus, rheumatoid arthritis), cancer, diabetes, high cholesterol or triglycerides in your blood, HIV infection, liver problems other than hepatitis (eg, cirrhosis), organ transplant, or seizures


• if you have a history of mental or mood problems (eg, depression, anxiety), suicidal thoughts or behaviors, or alcohol or other substance abuse


• if you are taking azathioprine or medicines for HIV

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

• Nucleoside reverse transcriptase inhibitors (eg, zidovudine) because the risk of anemia may be increased


• Telbivudine because the risk of burning, numbness, or tingling in the arms or legs may be increased


• Methadone or theophylline because the risk of their side effects may be increased by Pegasys

This may not be a complete list of all interactions that may occur. Ask your health care provider if Pegasys 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 Pegasys:

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

• Pegasys comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Pegasys refilled.


• Pegasys is sometimes used with another medicine called ribavirin, which comes with its own Medication Guide. If you are also using ribavirin, be sure to read its Medication Guide carefully each time you get it filled.


• Pegasys is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Pegasys at home, a health care provider will teach you how to use it. Be sure you understand how to use Pegasys. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.


• Do not use another brand of Pegasys or change your dose without talking with your doctor.


• Drinking extra fluids while you are taking Pegasys is recommended. Check with your doctor for instructions.


• Do not use Pegasys if the expiration date has passed, if it contains particles or is discolored, or if the vial or prefilled syringe is cracked or damaged.


• Do not shake Pegasys.


• Be sure to follow the procedure demonstrated to you to prevent contamination of the vial, syringe, or medicine. Never touch the rubber stopper of the vial or the needle of the syringe with your fingers. Carefully check that you have drawn the correct dose before administration.


• Each vial or prefilled syringe is for a single use only. Throw away any unused medicine.


• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.


• Use Pegasys on a regular schedule to get the most benefit from it. Using Pegasys at the same time each week will help you remember to use it.


• Continue to use Pegasys even if you feel well. Do not miss any doses.


• If you miss a dose of Pegasys and you remember within 2 days of the missed dose, use it as soon as possible and go back to your regular dosing schedule. If more than 2 days have passed, contact your doctor for instructions. Do not use 2 doses at once.

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

Important safety information:

• Pegasys may cause drowsiness, dizziness, or vision changes. These effects may be worse if you take it with alcohol or certain medicines. Use Pegasys with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


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


• Avoid drinking alcohol, including beer, wine, and liquor, because it could worsen liver disease.


• Pegasys may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.


• Pegasys may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• Pegasys is not a cure for hepatitis C infection and may not prevent you from spreading hepatitis C infection to others.


• Pegasys may cause high or low blood sugar (eg, thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, fruity breath odor, fast heartbeat, headache, chills, sweating, tremor, increased hunger, changes in vision, nervousness, weakness, dizziness, drowsiness, fainting). If these symptoms occur, tell your doctor immediately.


• Diabetes patients - Check your blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Tell your doctor or dentist that you take Pegasys before you receive any medical or dental care, emergency care, or surgery.


• Lab tests, including eye exams; pregnancy tests; blood counts; blood pressure; heart, liver, kidney, thyroid, and lung function tests; blood glucose levels; and other blood tests, may be performed while you use Pegasys. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Pegasys with caution in the ELDERLY; they may be more sensitive to its effects, especially heart effects, nervous system effects, and systemic side effects (eg, flu-like symptoms).


• Pegasys has benzyl alcohol in it. Do not use it in NEWBORNS or INFANTS. It may cause serious and sometimes fatal nervous system problems and other side effects.


• Pegasys should be used with extreme caution in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you are able to become pregnant, talk with your doctor or pharmacist about the use of effective birth control while using Pegasys. If you become pregnant, contact your doctor immediately. You will need to discuss the benefits and risks of using Pegasys while you are pregnant. Use of Pegasys with ribavirin during pregnancy has resulted in birth defects and fetal death. It is not known if Pegasys is found in breast milk. Do not breast-feed while taking Pegasys.

Possible side effects of Pegasys:

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:

Diarrhea; dizziness; drowsiness; dry mouth; dry or irritated skin; hair thinning; headache; loss of appetite; mild flu-like symptoms (fever, chills, muscle aches, or joint pain); nausea; pain, redness, itching, or swelling at the injection site; taste changes; temporary hair loss; tiredness; trouble sleeping; vomiting; weakness.

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, throat, or tongue; unusual hoarseness); blisters or sores in the eyes, nose, or mouth; bloody or black, tarry stools; burning, numbness, or tingling in the arms, hands, legs, or feet; chest pain; confusion; coughing up yellow or pink mucus; dark urine, change in the amount of urine produced, or burning or painful urination; decreased coordination; difficulty hearing or hearing loss; eye pain or redness; fainting; fast, slow, or irregular heartbeat; new or worsening mental or mood problems (eg, anxiety, aggressive or unusual behavior, depression, hallucinations, irritability, suicidal thoughts or actions); numbness of an arm or leg; one-sided weakness; pale stools; persistent loss of appetite; persistent or severe diarrhea, nausea, stomach or back pain, or vomiting; persistent or severe fever, chills, or sore throat; red, swollen, blistered, or peeling skin; severe or unusual tiredness or weakness; slurred speech; stomach bloating; sudden leg pain; sudden, severe dizziness, headache, or vomiting; sudden shortness of breath; unusual bruising or bleeding; vision loss or other vision changes; vomit that looks like coffee grounds; weight loss; worsening psoriasis; yellowing of the eyes or skin.

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: Pegasys side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Pegasys:

Store Pegasys in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do not freeze. Do not leave out of the refrigerator for more than 24 hours. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Pegasys out of the reach of children and away from pets.

General information:

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


• Pegasys 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 Pegasys. 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 Pegasys resources

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

• Pegasys Prescribing Information (FDA)


• Pegasys Advanced Consumer (Micromedex) - Includes Dosage Information


• Pegasys Consumer Overview


• Peginterferon Alfa-2a Professional Patient Advice (Wolters Kluwer)

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Zydol XL 150mg Tabs

1. Name Of The Medicinal Product

ZYDOL XL 150 mg tablets.

2. Qualitative And Quantitative Composition

Tablets containing tramadol hydrochloride 150 mg.

For excipients, see 6.1

3. Pharmaceutical Form

Prolonged release, white, film coated tablets, marked T 150.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of moderate to severe pain.

4.2 Posology And Method Of Administration

ZYDOL XL tablets should be taken at 24-hourly intervals and must be swallowed whole and not chewed.

As with all analgesic drugs, the dose of tramadol should be adjusted according to the severity of the pain and the clinical response of the individual patient. The correct dosage for any individual patient is that which controls the pain with no or tolerable side effects for a full 24 hours. Patients transferring from immediate release tramadol preparations should have their total daily dose calculated, and start on the nearest dose in the ZYDOL XL range. It is recommended that patients are slowly titrated to higher doses to minimise transient side effects. The need for continued treatment should be assessed at regular intervals as withdrawal symptoms and dependence have been reported. (See Section 4.4 Special Warnings and Precautions for Use). A total daily dose of 400 mg should not be exceeded except in special clinical circumstances.

Adults and children over 12 years: The usual initial dose is one 150 mg tablet daily. If pain relief is not achieved, the dosage should be titrated upwards until pain relief is achieved.

Elderly and patients with renal or hepatic impairment: Dosing as for adults. The elimination half-life of tramadol may be prolonged in patients over 75 years. A starting dose of 150 mg daily is recommended. Dose titration upwards should be carefully monitored.

Patients with renal or hepatic insufficiency:

The elimination half-life of tramadol may be prolonged in these patient populations. A starting dose of 150 mg daily is recommended. Dose titration upwards should be carefully monitored. Tramadol is not recommended for patients with severe renal impairment and/or severe hepatic impairment.

As tramadol is only removed very slowly by haemodialysis or by haemofiltration, post-dialysis administration to maintain analgesia is not usually necessary.

Children under 12 years: ZYDOL XL has not been studied in children. Safety and efficacy of ZYDOL XL have not been established and the product should not be used in children.

4.3 Contraindications

Hypersensitivity to tramadol or to any of the excipients; acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs. Tramadol should not be administered to patients who are receiving monoamine oxidase inhibitors or within two weeks of their withdrawal.

Tramadol must not be used for narcotic withdrawal treatment.

4.4 Special Warnings And Precautions For Use

Warnings

At therapeutic doses withdrawal symptoms have been reported at a frequency of 1 in 8,000. Reports of dependence and abuse have been less frequent. Because of this potential the clinical need for continued analgesic treatment should be reviewed regularly.

In patients with a tendency to drug abuse or dependence, treatment should be for short periods and under strict medical supervision.

Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms.

Precautions

Convulsions have been reported at therapeutic doses and the risk may be increased at doses exceeding the usual upper daily dose limit. Patients with a history of epilepsy or those susceptible to seizures should only be treated with tramadol if there are compelling reasons. The risk of convulsions may increase in patients taking tramadol and concomitant medication that can lower the seizure threshold. (See Section 4.5 Interactions with other Medicaments and other forms of Interaction).

Tramadol should be used with caution in patients with head injury, increased intracranial pressure, severe impairment of hepatic and renal function and in patients prone to convulsive disorders or in shock.

Care should be taken when treating patients with respiratory depression, or if concomitant CNS depressant drugs are being administered, as the possibility of respiratory depression cannot be excluded in these situations. At therapeutic doses respiratory depression has infrequently been reported.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concurrent administration of tramadol with other centrally acting drugs, including alcohol, may potentiate CNS depressant effects.

Simultaneous treatment with carbamazepine may shorten the analgesic effect as a result of a reduction in serum levels of tramadol and its active metabolite.

Co-administration with cimetidine is associated with a small prolongation of the half-life of tramadol, but this is not clinically relevant.

Tramadol can induce convulsions and increase the potential for both selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) anti-psychotics and other seizure threshold lowering drugs to cause convulsions (see Section 4.4 Special Warnings and Special Precautions for Use and 5.2 Pharmacokinetic Properties). Co-administration with SSRIs may lead to an increase in 5HT associated effects.

Co-administered ritonavir may increase serum concentrations of tramadol resulting in tramadol toxicity.

Digoxin toxicity has occurred rarely during co-administration of digoxin and tramadol.

MAO inhibitors: A serotoninergic syndrome is likely to occur: diarrhoea, tachycardia, sweating, tremor, confusion, coma. In case of recent treatment with MAOIs, treatment with tramadol should not be started until 15 days after cessation of treatment with MAOIs.

Other morphine derivatives (including anti-tussives, substitution treatments), benzodiazepines, barbiturates: Increased risk of respiratory depression, that may be fatal in overdosage.

Mixed agonists/antagonists (e.g. buprenorphine, nalbuphine and pentazocine): The analgesic effect of tramadol which is a pure agonist may be reduced, and a withdrawal syndrome may occur.

There have been isolated reports of interaction with coumarin anticoagulants resulting in an increased INR and so care should be taken when commencing treatment with tramadol in patients on anticoagulants.

4.6 Pregnancy And Lactation

There are no adequate data from the use of tramadol in pregnant women. Animal studies have shown reproductive toxicity, but not teratogenic effects (see section 5.3). Tramadol crosses the placental barrier and chronic use during pregnancy can cause withdrawal symptoms in the new-born baby. Therefore, it should not be used during pregnancy.

Tramadol administered before or during birth does not affect uterine contractility. In neonates it may induce changes in respiratory rate which are not usually clinically relevant.

During lactation very small amounts of tramadol and its metabolites (approximately 0.1% of an intravenous dose) are found in human breast milk. Therefore tramadol should not be administered during breast feeding.

4.7 Effects On Ability To Drive And Use Machines

Tramadol may cause drowsiness, blurred vision and dizziness which may be enhanced by alcohol or other CNS depressants. If affected, the patient should not drive or operate machinery.

4.8 Undesirable Effects

Nervous system disorders
Very Common (>10%)	Dizziness
Common (1 to 10%)	Muzziness
Uncommon (0.1 to 1%)	Headache
Rare (<0.1%)	Paraesthesia, Blurred vision Hallucinations Nightmares Changes in mood (usually elation, occasionally dysphoria) Changes in activity (usually suppression, occasionally an increase) Changes in cognitive and sensorial capacity (e.g. decision behaviour, perception disorders) Epileptiform convulsions have occurred after administration of high doses of tramadol or after concomitant treatment with drugs which can lower the seizure threshold or themselves induce cerebral convulsions (eg anti-depressants or anti-psychotics)
Cardiovascular
Uncommon (0.1 to 1%)	Palpitation Tachycardia Postural hypotension Cardiovascular collapse
Rare (<0.1%)	Hypertension Bradycardia
Respiratory disorders
Rare (<0.1%)	Dyspnoea Worsening of asthma has been reported, though a causal relationship has not been established. Respiratory depression. If the recommended doses are considerably exceeded and other centrally depressant substances are administered concomitantly, respiratory depression may occur.
Gastro-intestinal disorders
Very Common (>10%)	Nausea
Common (1 to 10%)	Vomiting Dry mouth
Uncommon (0.1 to 1%)	Retching Constipation Gastrointestinal irritation
Rare (<0.1%)	Anorexia Diarrhoea
Skin & appendages
Common (1 to 10%)	Sweating
Uncommon (0.1 to 1%)	pruritus, rash, urticaria
Urogenital
Rare (<0.1%)	Micturition disorders (difficulty in passing urine and urinary retention)
Body as a whole
Rare (<0.1%)	Muscle weakness Flushing Allergic reactions (eg dyspnoea, bronchospasm, wheezing, angioneurotic oedema) Anaphylaxis Dependence Withdrawal reactions, similar to those occurring during opiate withdrawal, may occur and include: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms. Increase in liver enzyme values have been reported in a temporal connection with the therapeutic use of tramadol

4.9 Overdose

Symptoms of overdosage are typical of other opioid analgesics, and include miosis, vomiting, cardiovascular collapse, sedation and coma, seizures and respiratory depression.

Supportive measures such as maintaining the patency of the airway and maintaining cardiovascular function should be instituted; naloxone should be used to reverse respiratory depression; fits can be controlled with diazepam.

Tramadol is minimally eliminated from the serum by haemodialysis or haemofiltration. Therefore treatment of acute intoxication with tramadol with haemodialysis or haemofiltration alone is not suitable for detoxification.

Emptying the gastric contents is useful to remove any unabsorbed drug, particularly when a prolonged release formulation has been taken.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Tramadol is a centrally acting analgesic (NO2A X 02). It is a non selective pure agonist at mu, delta and kappa opioid receptors with a higher affinity for the mu receptor. Other mechanisms that may contribute to its analgesic effect are inhibition of neuronal re-uptake of noradrenaline and 5HT.

5.2 Pharmacokinetic Properties

Following oral administration of a single dose, tramadol is almost completely absorbed and the absolute bioavailability is approximately 70%. Tramadol is metabolised to O-desmethyltramadol, which has been shown to have analgesic activity in rodents. The elimination half life of tramadol is around 6 hours, although this is extended to around 16 hours following prolonged absorption from the ZYDOL XL tablet.

Following administration of one ZYDOL XL tablet 200 mg in the fasting state, a mean peak plasma concentration (Cmax) of 192 ng.ml-1 was attained. This was associated with a median t_max of 6 hours (range 4-8 hours). The availability of tramadol from the ZYDOL XL tablet 200 mg was complete when compared with an immediate release tramadol solution 100 mg, after dose adjustment. In the presence of food, the availability and controlled release properties of ZYDOL XL tablets were maintained, with no evidence of dose-dumping.

A single dose-proportionality study has confirmed a linear pharmacokinetic response (in relation to tramadol and O-desmethyltramadol) following administration of the 200 mg, 300 mg and 400 mg tablets. A steady state study has confirmed the dose adjusted bioequivalence of the 150 mg and 200 mg tablets administered once-daily. This study also confirmed that the ZYDOL XL tablet 150 mg provided an equivalent peak concentration and extent of availability of tramadol to an immediate release capsule 50 mg administered 8-hourly. On this basis it is recommended that patients receiving immediate release tramadol should be transferred initially to the nearest daily dose of ZYDOL XL tablets. It may be necessary to titrate the dose thereafter.

A further steady state study has demonstrated that immediate release tramadol tablets 50 mg, administered 6-hourly, provided plasma concentrations that were greater than would have been anticipated following administration of a single dose. This observation is consistent with a non-linear elimination of the drug substance. In contrast, the plasma concentrations from ZYDOL XL tablet 200 mg administered once-daily were in line with single dose data, confirming that the controlled delivery of tramadol from ZYDOL XL minimises the non-linearity associated with faster-releasing preparations. The more predictable plasma concentrations may lead to a more manageable dose titration process.

5.3 Preclinical Safety Data

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential.

Studies in rats and rabbits have revealed no teratogenic effects. However, embryotoxicity was shown in the form of delayed ossification. Fertility, reproductive performance and development of offspring were unaffected.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet core

Hydrogenated vegetable oil

Talc

Magnesium stearate

Film coat

Lactose monohydrate

Hypromellose (E464)

Titanium dioxide (E171)

Macrogol 4000

6.2 Incompatibilities

None known.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Do not store above 30°C.

6.5 Nature And Contents Of Container

1) PVC blisters with aluminium backing foil (containing 2, 7, 14, 28, 30, 56 or 60 tablets).

2) Polypropylene containers with polyethylene lids (containing 2, 7, 14, 28, 30, 56 or 60 tablets).

Not all pack sizes may be marked.

6.6 Special Precautions For Disposal And Other Handling

None.

Administrative Data

7. Marketing Authorisation Holder

Napp Pharmaceuticals Ltd

Cambridge Science Park

Milton Road

Cambridge

CB4 0GW

8. Marketing Authorisation Number(S)

PL 16950/0089

9. Date Of First Authorisation/Renewal Of The Authorisation

14 June 1999

10. Date Of Revision Of The Text

14.12.2005