Ibustrin may be available in the countries listed below.
Indobufen is reported as an ingredient of Ibustrin in the following countries:
International Drug Name Search
Class: Biologic Response Modifiers
VA Class: IM700
Chemical Name: N2-l-Methionyl-1-139-interferonγ (human lymphocyte protein moiety reduced)
Molecular Formula: C734H1166N204O216S5
CAS Number: 98059-61-1
Brands: Actimmune
Biologic response modifier; biosynthetic (recombinant DNA origin) form of endogenous human interferon gamma.1 5 6 7
Reduction of the frequency and severity of serious infections in patients with chronic granulomatous disease (designated an orphan drug by FDA for this use).1 5 10 13 20 21 22 24
Treatment to delay the time to disease progression in patients with severe, malignant osteopetrosis (designated an orphan drug by FDA for this use).1 6 7 13
Interferon gamma-1b was investigated in patients with idiopathic pulmonary fibrosis† (IPF) with mild-to-moderate lung function impairment in the INSPIRE study; the study was terminated early when interim data analysis indicated lack of benefit in patients receiving the drug.26 Interim analysis also indicated that 14.5% of patients receiving interferon gamma 1-b died compared with 12.7% of those receiving placebo.26
Interferon gamma-1b is not approved for use in patients with IPF.26 FDA suggests that health-care professionals should discuss the results of this trial with their patients receiving the drug for IPF and carefully consider whether they should continue to receive treatment with interferon gamma-1b.26
If home use is prescribed, carefully instruct patients and/or their caregivers in appropriate use; provide a puncture-resistant container for proper, safe disposal of used syringes and needles.1
Administer by sub-Q injection 3 times weekly (e.g., Monday, Wednesday, Friday).1
Optimum sites for sub-Q injection include right and left deltoid and anterior thigh.1
To minimize risk of flu-like syndrome, administer at bedtime and/or give acetaminophen to prevent or partially alleviate fever and headache.1 5
Vials contain no preservative; discard any residual solution remaining in the vial after administration of the single dose.1
Each mg of interferon gamma-1b is approximately equivalent to 20 million international units (equivalent to the amount that formerly was expressed as 30 million units).1
50 mcg/m2 (1 million international units per m2) 3 times weekly for patients with body surface area (BSA) >0.5 m2 and 1.5 mcg/kg 3 times weekly for those with body surface area ≤0.5 m2.1
If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1
50 mcg/m2 (1 million international units per m2) 3 times weekly for patients with body surface area >0.5 m2 and 1.5 mcg/kg 3 times weekly for those with body surface area ≤0.5 m2.1
If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1
50 mcg/m2 (1 million international units per m2) 3 times weekly.1
If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1
50 mcg/m2 (1 million international units per m2) 3 times weekly.1
If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1
Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1
Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1
Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1
Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1
Known hypersensitivity to interferon gamma-1b, products derived from Escherichia coli, or any ingredient in the formulation.1
Acute and transient flu-like syndrome or constitutional symptoms (e.g., chills, fever)20 24 that are associated with daily dosages ≥250 mcg/m2 (>10 times the weekly recommended dosage) may exacerbate preexisting cardiac conditions.1
Use with caution in patients with preexisting cardiac disease (e.g., arrhythmia, CHF, symptoms of ischemia).1
Possible seizures, decreased mental status, dizziness, and gait disturbance, particularly at daily dosages >250 mcg/m2 (>10 times the weekly recommended dosage).1
Use with caution in patients with known seizure disorders or compromised CNS function.1
Possibly severe, reversible, dose-limiting neutropenia and thrombocytopenia reported rarely.1
Use with caution in patients with myelosuppression and in those receiving drugs that may be myelosuppressive.1
Monitor blood cell and differential counts and platelet counts prior to initiating interferon gamma-1b and at 3-month intervals during therapy.1
Proteinuria reported rarely.1
Perform urinalysis and monitor appropriate blood chemistry tests prior to initiating interferon gamma-1b and at 3-month intervals during therapy.1
Possibly substantial (up to 25-fold) elevations of AST and/or ALT reported; children <1 year of age most at risk (see Pediatric Use under Cautions).1 Reversible with dosage reduction or interruption of therapy.1
Perform liver function tests prior to initiating interferon gamma-1b and at monthly (for children <1 year of age) or 3-month intervals during therapy.1 If severe hepatic enzyme elevations occur, modify dosages.1 (See Dosage under Dosage and Administration.)
If acute, serious hypersensitivity reactions occur, discontinue immediately and initiate appropriate therapy.1
Category C.1
Not known whether interferon gamma-1b is distributed into milk; discontinue nursing or the drug.1
Increased risk of elevations of AST and/or ALT in children <1 year of age.1 May occur as early as 7 days after starting treatment.1 (See Hepatic Effects under Cautions.)
Possibly reversible alkaline phosphatase elevation and hypokalemia.1
Flu-like syndrome (e.g., headache, fever, chills, myalgia, fatigue),1 3 5 8 10 18 erythema or tenderness at injection site,1 injection site hemorrhage,1 nausea,1 vomiting,1 rash.1
No formal drug interaction studies to date.1
Drug | Interaction | Comments |
|---|---|---|
Myelosuppressive agents | Possible additive myelosuppressive effects1 | Use with caution1 |
Following sub-Q injection, >89% of dose is slowly absorbed; peak plasma concentrations attained 7 hours after dose.1
5.9 hours following a single sub-Q dose.1
2–8°C; do not freeze.1 Unentered vials may be exposed to room temperature for up to 12 hours prior to use; discard vials not returned to refrigerator or used within 12 hours.1
Avoid shaking or excessively or vigorously agitating vials.1
Specific effects of interferon gamma include the enhancement of the oxidative metabolism of macrophages, antibody dependent cellular cytotoxicity (ADCC), activation of natural killer (NK) cells, and the expression of Fc receptors and major histocompatibility antigens.1 2
The exact mechanism(s) of action of interferon gamma-1b in patients with chronic granulomatous disease have not been fully elucidated;1 3 4 5 8 9 10 the drug appears to enhance phagocyte function to allow more effective killing of catalase-positive organisms.1 8 Changes in superoxide levels during therapy with interferon gamma-1b do not predict efficacy and should not be used to assess patient response to therapy.1
Mechanisms of action in treatment of osteopetrosis not fully elucidated1 12 15 but may involve enhanced superoxide production in leukocytes and osteoclasts.1 Changes in superoxide levels during therapy with interferon gamma-1b do not predict efficacy and should not be used to assess patient response to therapy.1
Importance of advising patients not to administer the drug until their clinician has thoroughly trained them on proper administration methods (including aseptic technique) and proper disposal of used needles and syringes.1 27
Advise patients to notify their clinician if injection site reactions (e.g., persistent lumps, swelling, bruising, signs of infection or inflammation [pus, redness, pain]) occur.27
Risk of myelosuppression and adverse hepatic effects.1
Importance of taking interferon gamma-1b as prescribed.1
Importance of women informing their clinician 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, as well as concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for subcutaneous use | 100 mcg/0.5 mL (2 million international units) | Actimmune | InterMune |
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 August 2010. 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.
1. InterMune, Inc. Actimmune (interferon gamma-1b) prescribing information. Brisbane, CA; 2009 Jan.
2. Gallin JI, Farber JM, Holland SM et al. Interferon-γ in the management of infectious diseases. Ann Intern Med. 1995; 123:216-24. [IDIS 350164] [PubMed 7598304]
3. Todd PA, Goa KL. Interferon gamma-1b. A review of its pharmacology and therapeutic potential in chronic granulomatous disease. Drugs. 1992; 43:111-22. [PubMed 1372855]
4. Lekstrom-Himes JA, Gallin JI. Immunodeficiency diseases caused by defects in phagocytes. N Engl J Med. 2000; 343:1703-14. [PubMed 11106721]
5. International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med. 1991; 324:509-16. [PubMed 1846940]
6. Key LL, Rodriguiz RM, Willi SM et al. Long-term treatment of osteopetrosis with recombinant-human interferon gamma. N Engl J Med. 1995; 332:1594-9. [IDIS 347518] [PubMed 7753137]
7. Key LL, Ries WL, Rodriguiz RM et al. Recombinant human interferon gamma therapy for osteopetrosis. J Pediatr. 1992; 121:119-24. [IDIS 299963] [PubMed 1320672]
8. Ahlin A, Elinder G, Palmblad J. Dose-dependent enhancement of interferon-γ on functional responses of neutrophils from chronic granulomatous disease patients. Blood. 1997; 89:3396-401. [IDIS 385789] [PubMed 9129047]
9. Ahlin A, Larfars G, Elinder G et al. Gamma interferon treatment of patients with chronic granulomatous disease is associated with augmented production of nitric oxide by polymorphonuclear neutrophils. Clin Diag Lab Immunol. 1999; 6:420-4.
10. Weening RS, Leitz GJ, Seger RA. Recombinant human interferon-gamma in patients with chronic granulomatous disease—European follow up study. Eur J Pediatr. 1995; 154:295-8. [PubMed 7607280]
11. Hayden FG. Antiviral drugs (other than antiretrovirals). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practices of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000:460-91.
12. Madyastha PR, Yang S, Ries WL et al. IFN-gamma enhances osteoclast generation in cultures of peripheral blood from osteopetrotic patients and normalizes superoxide production. J Interferon Cytokine Res. 2000; 20:645-52. [PubMed 10926207]
13. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2002 Oct 15. From FDA web site (). Accessed 2003 Apr 14.
14. Lajeunesse D, Busque L, Menard P et al. Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant. J Clin Invest. 1996; 98:1835-42. [PubMed 8878435]
15. Whyte MP. Chipping away at marble-bone disease. N Engl J Med. 1995; 332:1639-40. [IDIS 347523] [PubMed 7753145]
16. Janeway CA, Travers P, Walport M et al eds. Immunology. 5th ed. New York, NY: Garland Publishing; 2001. From the National Library of Medicine website ().
17. Tramont EC, Hoover DL. Innate (general or nonspecific) host defense mechanisms. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practices of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000:31-8.
18. Bemiller LS, Roberts DH, Starko KM et al. Safety and effectiveness of long-term interferon gamma therapy in patients with chronic granulomatous disease. Blood Cells Mol Dis. 1995; 21:239-247. [PubMed 8673477]
19. Intermune. Brisbane, CA: Personal communication.
20. Errante PR, Frazão JB, Condino-Neto A. The use of interferon-gamma therapy in chronic granulomatous disease. Recent Pat Antiinfect Drug Discov. 2008; 3:225-30. [PubMed 18991804]
21. Jones LBKR, McGrogan P, Flood TJ et al. Special Article: Chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry Clin Exp Immunol. 2008; 152: 211–218.
22. Kobayashi S, Murayama S, Takanashi S et al. Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan. . Eur J Pediatr. . 2008;167:1389-94.
23. Martire B, Rondelli R, Soresina A et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with Chronic Granulomatous Disease: an Italian multicenter study. Clin Immunol. 2008; 126:155-64. [PubMed 18037347]
24. Marciano BE, Wesley R, De Carlo ES et al. Long-term interferon-gamma therapy for patients with chronic granulomatous disease. Clin Infect Dis. 2004; 39:692-9. [PubMed 15356785]
25. Ma HR, Mu SC, Yang YH et al. Therapeutic effect of interferon-gamma for prevention of severe infection in X-linked chronic granulomatous disease. J Formos Med Assoc. 2003; 102:189-92. [PubMed 12783137]
26. Food and Drug Administration. Information for healthcare professionals–interferon gamma–1b (marketed as Actimmune) From FDA web site http: / / www.fda.gov / Drugs / DrugSafety / PostmarketDrugSafetyInformationforPatientsandProviders / / 2007 / march09.htm.
27. InterMune, Inc. Actimmune (interferon gamma-1b) Information for the patient/caregiver.. Brisbane, CA; 2006 Nov.
There are currently no drugs listed for "Whipple's Disease".
Definition of Whipple's Disease: A rare disorder of intestinal malabsorption that occurs as the result of the intestine.
Medical Encyclopedia:
Generic Name: albuterol (Inhalation route)
al-BUE-ter-ol
In the U.S.
In Canada
Available Dosage Forms:
Therapeutic Class: Bronchodilator
Pharmacologic Class: Sympathomimetic
Albuterol is used to treat or prevent bronchospasm in patients with asthma, bronchitis, emphysema, and other lung diseases. This medicine is also used to prevent wheezing caused by exercise (exercise-induced bronchospasm).
Albuterol belongs to the family of medicines known as adrenergic bronchodilators. Adrenergic bronchodilators are medicines that are breathed in through the mouth to open up the bronchial tubes (air passages) in the lungs. They relieve cough, wheezing, shortness of breath, and troubled breathing by increasing the flow of air through the bronchial tubes.
This medicine is available only with your doctor's prescription.
Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, albuterol is used in certain patients with the following medical condition:
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:
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.
Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of albuterol inhalation aerosol (e.g., Proair® HFA) in children 4 years of age and older and albuterol inhalation solution (e.g., Accuneb®) in children 2 years of age and older. However, safety and efficacy have not been established for the aerosol in children younger than 4 years of age and for the solution in children younger than 2 years of age.
No information is available on the relationship of age to the effects of albuterol inhalation solution (e.g., Accuneb®) in geriatric patients.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of albuterol inhalation aerosol (e.g., Proair® HFA) in geriatric patients. However, elderly patients are more likely to have age-related heart or kidney problems, which may require caution and an adjustment in the dose for patients receiving albuterol.
| 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. |
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.
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 this medicine, 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 this medicine 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.
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.
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:
This section provides information on the proper use of a number of products that contain albuterol. It may not be specific to Proventil. Please read with care.
Use this medicine only as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. Also, do not stop using this medicine or any asthma medicine without telling your doctor. To do so may increase the chance for breathing problems.
The albuterol inhalation solution (e.g., Accuneb®) should be used with a jet nebulizer that is connected to an air compressor with good air flow. The inhalation solution and nebulizer will come with patient instructions. Read and follow these instructions carefully. Ask your doctor if you have any questions.
To use the inhalation solution in the nebulizer:
The albuterol inhalation aerosol (e.g., Proair® HFA) is used with a special inhaler that comes with patient instructions. Read the directions carefully before using this medicine. If you or your child do not understand the directions or are not sure how to use the inhaler, ask your doctor to show you what to do. Also, ask your doctor to check you or your child on a regular basis to make sure you are using it properly.
To use the aerosol inhaler:
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.
If you miss a dose of this medicine, 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.
Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.
Keep the medicine in the foil pouch until you are ready to use it. Store at room temperature, away from heat and direct light. Do not freeze.
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.
Ask your healthcare professional how you should dispose of any medicine you do not use.
It is very important that your doctor check the progress of you or your child at regular visits. This will allow your doctor to see if the medicine is working properly and to check for any unwanted effects.
This medicine should not be used together with other inhaled medicines that are similar, such as isoproterenol (Isuprel®), levalbuterol (Xopenex™), metaproterenol (Alupent®), pirbuterol (Maxair®), or terbutaline (Brethaire®).
This medicine may cause paradoxical bronchospasm, which means your breathing or wheezing will get worse. Paradoxical bronchospasm may be life-threatening. Stop using this medicine and check with your doctor right away if you or your child have coughing, difficulty breathing, shortness of breath, or wheezing after using this medicine.
Talk to your doctor or get medical help right away if:
You or your child may also be taking an antiinflammatory medicine, such as a steroid (cortisone-like medicine), together with this medicine. Do not stop taking the antiinflammatory medicine, even if your asthma seems better, unless you are told to do so by your doctor.
Albuterol may cause serious types of allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Stop using this medicine and check with your doctor right away if you or your child develop a skin rash, hives, itching, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.
Hypokalemia (low potassium in the blood) may occur while you are using this medicine. Check with your doctor right away if you or your child have more than one of the following symptoms: convulsions; decreased urine; dry mouth; increased thirst; irregular heartbeat; loss of appetite; mood changes; muscle pain or cramps; nausea or vomiting; numbness or tingling in the hands, feet, or lips; shortness of breath; or unusual tiredness or weakness.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, and herbal or vitamin supplements.
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:
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:
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: Proventil Inhalation 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.
Generic Name: hyaluronic acid (Injection route)
hye-al-ure-ON-ate AS-id
In the U.S.
Available Dosage Forms:
Therapeutic Class: Cartilaginous Defect Repair Agent
Hyaluronic acid injection is used to treat knee pain caused by osteoarthritis (OA) in patients who have already been treated with pain relievers (e.g., acetaminophen) and other treatments that did not work well.
Hyaluronic acid is similar to a substance that occurs naturally in the joints. It works by acting like a lubricant and shock absorber in the joints and helps the joints to work properly.
This medicine is to be administered only by or under the immediate supervision of your doctor.
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:
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.
Appropriate studies have not been performed on the relationship of age to the effects of hyaluronic acid injection in the pediatric population. Safety and efficacy have not been established.
No information is available on the relationship of age to the effects of hyaluronic acid injection in geriatric patients.
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.
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.
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.
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:
This section provides information on the proper use of a number of products that contain hyaluronic acid. It may not be specific to Euflexxa. Please read with care.
A nurse or other trained health professional will give you this medicine. This medicine is given as a shot into your knee joint. It may take more than one injection for the pain to go away.
You will receive a series of shots of this medicine one week apart for a total of three or four injections.
Your doctor will check your progress closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it.
Do not strain your knee joint for two days after receiving this medicine. Avoid activities such as jogging, soccer, tennis, heavy lifting, or standing on your feet for a long time.
Temporary pain or swelling in the knee joint may occur after receiving hyaluronic acid injection. Call your doctor if the pain or swelling in the knee persists or becomes worse after receiving this medicine.
Do not use this medicine with disinfectants containing quaternary ammonium salts (e.g., benzalkonium chloride). This may prevent hyaluronic acid injection from working properly.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor or nurse immediately if any of the following side effects occur:
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:
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: Euflexxa Injection 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.
Treating acne, rosacea, and seborrhea. It may also be used for other conditions as determined by your doctor.
Sulfacetamide/Sulfur Gel is a sulfonamide antibiotic and keratolytic combination. It works by killing bacteria and shedding the top layer of skin.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Sulfacetamide/Sulfur Gel. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Sulfacetamide/Sulfur Gel. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Sulfacetamide/Sulfur Gel 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.
Use Sulfacetamide/Sulfur Gel as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Sulfacetamide/Sulfur Gel.
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 irritation, stinging, or burning of the skin.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); cracked or extremely dry skin; fever; joint pain; red, swollen, scaling, or blistered skin; severe diarrhea; severe skin irritation; sores in the mouth; unusual bruising; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Sulfacetamide/Sulfur Gel may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.
Store Sulfacetamide/Sulfur Gel at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not freeze. Keep Sulfacetamide/Sulfur Gel out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Sulfacetamide/Sulfur Gel. 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.
Treating inflammation and itching due to certain skin conditions when bacterial or fungal infection may be present. It may also be used for other conditions as determined by your doctor.
Vytone is a topical adrenocortical steroid and antibacterial/antifungal. It works by reducing skin inflammation (redness, swelling, itching, and irritation) in a way that is not clearly understood. The antibacterial/antifungal works by killing sensitive bacteria and fungi.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Vytone. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Vytone. Because little, if any, of Vytone is absorbed into the blood, the risk of it interacting with another medicine is low.
Ask your health care provider if Vytone 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.
Use Vytone as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Vytone.
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:
Dryness; itching.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); acne-like rash; burning, cracking, irritation, or peeling not present before you began using Vytone; excessive hair growth; inflamed hair follicles; inflammation around the mouth; muscle weakness; thinning, softening, or discoloration of the skin; unusual weight gain, especially in the face.
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: Vytone side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include increased thirst or urination; muscle weakness; unusual weight gain, especially in the face.
Store Vytone at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not freeze. Do not store in the bathroom. Keep Vytone out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Vytone. 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.
Generic Name: phenol (Oromucosal route)
FEE-nol
In the U.S.
Available Dosage Forms:
Therapeutic Class: Analgesic
Phenol is used to relieve pain and irritation caused by sore throat, sore mouth, or canker sores.
This medicine is available without a prescription; however, your doctor may have special instructions on the proper use and dose for your medical problem.
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:
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.
No information is available on the relationship of age to the effects of phenol in the pediatric population. Safety and efficacy have not been established in children below 3 years of age.
No information is available on the relationship of age to the effects of phenol in geriatric patients.
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.
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.
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:
This section provides information on the proper use of a number of products that contain phenol. It may not be specific to Assure Sore Throat. Please read with care.
Use this medicine exactly as directed by your doctor. Do not use more of this medicine, do not use it more often, and do not use it for a longer time than directed. To do so may increase the chance of absorption into the body and the risk of side effects.
This medicine should be used only for problems being treated by your doctor or conditions listed in the package directions. Check with your doctor before using it for other problems, especially if you think that an infection may be present.
Be careful not to get any of this medicine in your eyes because it can cause severe eye irritation. If any of the medicine does get in your eyes, wash it with water and check with your doctor right away. Also, be very careful not to inhale (breathe in) the medicine.
To use:
Do not use this medicine for more than 2 days without checking first with your doctor.
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.
If you miss a dose of this medicine, 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.
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.
Ask your healthcare professional how you should dispose of any medicine you do not use.
If your condition does not improve within 7 days, or if it becomes worse, check with your doctor.
After spraying this medicine to the mouth or throat of your child, watch the child carefully to make sure that he or she does not get any of the medicine into his or her eyes or he or she does not inhale the spray.
Stop using this medicine and check with your doctor right away if you have difficulty with breathing; fever; skin rash; or worsening of pain, redness, swelling, or irritation in or around the mouth.
Call your doctor right away if you start to have a severe sore throat or sore throat that occurs with a high fever, headache, nausea, or vomiting. These maybe signs of an infection.
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:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
Cimzia 200 mg solution for injection
Each pre-filled syringe contains 200 mg certolizumab pegol in one ml.
Certolizumab pegol is a recombinant, humanised antibody Fab' fragment against tumour necrosis factor alpha (TNFα) expressed in Escherichia coli and conjugated to polyethylene glycol (PEG).
For a full list of excipients, see section 6.1.
Solution for injection in pre-filled syringe.
Clear to opalescent, colourless to yellow solution. The pH of the solution is approximately 4.7.
Cimzia, in combination with methotrexate (MTX), is indicated for the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the response to disease-modifying antirheumatic drugs (DMARDs) including methotrexate, has been inadequate.
Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Cimzia has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate.
Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of rheumatoid arthritis. Patients should be given the special alert card.
Posology
The recommended starting dose of Cimzia for adult patients with rheumatoid arthritis is 400 mg (as 2 injections of 200 mg each on one day) at weeks 0, 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks. MTX should be continued during treatment with Cimzia where appropriate.
Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment.
Missed dose
Patients who miss a dose should be advised to inject the next dose of Cimzia as soon as they remember and then continue injecting subsequent doses every 2 weeks as originally instructed.
Paediatric population (< 18 years old)
The safety and efficacy of Cimzia in children and adolescents below age 18 years have not yet been established. No data are available.
Elderly (
No dose adjustment is required. Population pharmacokinetic analyses showed no effect of age (see section 5.2).
Renal and hepatic impairment
Cimzia has not been studied in these patient populations. No dose recommendations can be made (see section 5.2).
Method of administration
The total content (1 ml) of the pre-filled syringe should be administered as a subcutaneous injection only. Suitable sites for injection would include the thigh or abdomen.
After proper training in injection technique, patients may self-inject if their physician determines that it is appropriate and with medical follow-up as necessary.
Hypersensitivity to the active substance or to any of the excipients.
Active tuberculosis or other severe infections such as sepsis or opportunistic infections (see section 4.4).
Moderate to severe heart failure (NHYA classes III/IV) (see section 4.4).
Infections
Patients must be monitored closely for signs and symptoms of infections including tuberculosis before, during and after treatment with Cimzia. Because the elimination of Cimzia may take up to 5 months, monitoring should be continued throughout this period (see section 4.3).
Treatment with Cimzia must not be initiated in patients with a clinically important active infection, including chronic or localised infections, until the infection is controlled (see section 4.3).
Patients who develop a new infection while undergoing treatment with Cimzia should be monitored closely. Administration of Cimzia should be discontinued if a patient develops a new serious infection until the infection is controlled. Physicians should exercise caution when considering the use of Cimzia in patients with a history of recurring infection or with underlying conditions which may predispose patients to infections, including the use of concomitant immunosuppressive medications.
Patients with rheumatoid arthritis may not manifest typical symptoms of infection, including fever, due to their disease and concomitant medicinal products. Therefore, early detection of any infection, particularly atypical clinical presentations of a serious infection, is critical to minimise delays in diagnosis and initiation of treatment.
Serious infections, including sepsis and tuberculosis (including miliary, disseminated and extrapulmonary disease), and opportunistic infections (e.g. histoplasmosis, nocardia, candidiasis) have been reported in patients receiving Cimzia. Some of these events have been fatal.
Tuberculosis
Before initiation of therapy with Cimzia, all patients must be evaluated for both active or inactive (latent) tuberculosis infection. This evaluation should include a detailed medical history for patients with a personal history of tuberculosis, with possible previous exposure to others with active tuberculosis, and with previous and/or current use of immunosuppressive therapy. Appropriate screening tests, e.g. tuberculin skin test and chest X -ray, should be performed in all patients (local recommendations may apply). It is recommended that the conduct of these tests should be recorded in the patient's alert card. Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.
If active tuberculosis is diagnosed prior to or during treatment, Cimzia therapy must not be initiated and must be discontinued (see section 4.3).
If inactive ('latent') tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted. In all situations described below, the benefit/risk balance of Cimzia therapy should be very carefully considered.
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy must be started before initiating treatment with Cimzia and in accordance with local recommendations.
Use of anti-tuberculosis therapy should also be considered before the initiation of Cimzia in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and in patients who have significant risk factors for tuberculosis despite a negative test for latent tuberculosis. Biological tests for tuberculosis screening should be considered before starting Cimzia treatment if there is any potential latent tuberculosis infection, regardless of BCG vaccination.
Patients should be instructed to seek medical advice if signs/symptoms (e.g. persistent cough, wasting/weight loss, low grade fever, listlessness) suggestive of a tuberculosis infection occur during or after therapy with Cimzia.
Hepatitis B Virus (HBV) reactivation
Reactivation of HBV has occurred in patients who are chronic carriers of this virus receiving TNF antagonists. Some cases have had a fatal outcome. As HBV infection has also been reported with Cimzia, patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating Cimzia therapy. Adequate data on treating patients who are carriers of HBV with TNF antagonist therapy, in conjunction with anti-viral therapy, to prevent HBV reactivation are not available. Carriers of HBV who require treatment with TNF antagonists should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for 5 months following termination of therapy, especially if the patient is on concomitant corticosteroid therapy.
In patients who develop HBV reactivation, Cimzia should be discontinued and effective anti-viral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF antagonist therapy after HBV reactivation is controlled is not known. Therefore, prescribers should exercise caution when considering resumption of Cimzia therapy in this situation and monitor patients closely.
Malignancies and lymphoproliferative disorders
The potential role of TNF antagonist therapy in the development of malignancies is not known. Caution should be exercised when considering TNF antagonist therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop malignancy.
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF antagonist cannot be excluded.
In clinical trials with Cimzia and other TNF antagonists, more cases of lymphoma and other malignancies have been reported among patients receiving TNF antagonists than in control patients receiving placebo (see section 4.8). In the post marketing setting, cases of leukaemia have been reported in patients treated with a TNF antagonist. There is an increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation.
No trials have been conducted that include patients with a history of malignancy, or that continue treatment in patients who develop malignancy, while receiving Cimzia.
Paediatric malignancy
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF antagonists (initiation of therapy
Chronic obstructive pulmonary disease (COPD)
In an exploratory clinical trial evaluating the use of another TNF antagonist, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients. All patients had a history of heavy smoking. Therefore, caution should be exercised when using any TNF antagonist in COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking.
Congestive heart failure
Cimzia is contraindicated in moderate or severe heart failure (see section 4.3). In a clinical trial with another TNF antagonist, worsening congestive heart failure and increased mortality due to congestive heart failure have been observed. Cases of congestive heart failure have also been reported in rheumatoid arthritis patients receiving Cimzia. Cimzia should be used with caution in patients with mild heart failure (NYHA class I/II). Treatment with Cimzia must be discontinued in patients who develop new or worsening symptoms of congestive heart failure.
Haematological reactions
Reports of pancytopaenia, including aplastic anaemia, have been rare with TNF antagonists. Adverse reactions of the haematologic system, including medically significant cytopaenia (e.g. leukopaenia, pancytopaenia, thrombocytopaenia) have been reported with Cimzia (see section 4.8). All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on Cimzia. Discontinuation of Cimzia therapy should be considered in patients with confirmed significant haematological abnormalities.
Neurological events
Use of TNF antagonists has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease, including multiple sclerosis. In patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of TNF antagonist treatment should be carefully considered before initiation of Cimzia therapy. Rare cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have been reported in patients treated with Cimzia.
Hypersensitivity
Severe hypersensitivity reactions have been reported rarely following Cimzia administration in trials. If severe reactions occur, administration of Cimzia should be discontinued immediately and appropriate therapy instituted.
There are limited data on the use of Cimzia in patients who have experienced a severe hypersensitivity reaction towards another TNF antagonist; in these patients caution is needed.
Immunosuppression
Since tumour necrosis factor (TNF) mediates inflammation and modulates cellular immune responses, the possibility exists for TNF antagonists, including Cimzia, to cause immunosupression, affecting host defences against infections and malignancies.
Autoimmunity
Treatment with Cimzia may result in the formation of antinuclear antibodies (ANA) and, uncommonly, in the development of a lupus-like syndrome (see section 4.8). The impact of long-term treatment with Cimzia on the development of autoimmune diseases is unknown. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with Cimzia, treatment must be discontinued. Cimzia has not been studied specifically in a lupus population (see section 4.8).
Vaccinations
No data are available on the response to vaccinations or the transmission of infection by live vaccines in patients receiving Cimzia. Live vaccines or attenuated vaccines should not be administered concurrently with Cimzia.
Concomitant use with other biologics
Severe infections and neutropaenia were reported in clinical trials with concurrent use of anakinra (an interleukin-1 antagonist) or abatacept (a CD28 modulator) and another TNF antagonist, etanercept, with no added benefit compared to TNF antagonist therapy alone. Because of the nature of the adverse events seen with the combination of another TNF antagonist with either abatacept or anakinra therapy, similar toxicities may also result from the combination of anakinra or abatacept and other TNF antagonists. Therefore the use of Cimzia in combination with anakinra or abatacept is not recommended (see section 4.5).
Surgery
There is limited safety experience with surgical procedures in patients treated with Cimzia. The 14-day half-life of certolizumab pegol should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on Cimzia should be closely monitored for infections, and appropriate actions should be taken.
Activated partial thromboplastin time (aPTT) assay
Interference with certain coagulation assays has been detected in patients treated with Cimzia. Cimzia may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities. This effect has been observed with the PTT-Lupus Anticoagulant (LA) test and Standard Target Activated Partial Thromboplastin time (STA-PTT) Automate tests from Diagnostica Stago, and the HemosIL APTT-SP liquid and HemosIL lyophilised silica tests from Instrumentation Laboratories. Other aPTT assays may be affected as well. There is no evidence that Cimzia therapy has an effect on coagulation in vivo. After patients receive Cimzia, careful attention should be given to interpretation of abnormal coagulation results. Interference with thrombin time (TT) and prothrombin time (PT) assays have not been observed.
Elderly
In the clinical trials, there was an apparently higher incidence of infections among subjects
Concomitant treatment with methotrexate, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics showed no effect on the pharmacokinetics of certolizumab pegol based on a population pharmacokinetics analysis.
The combination of Cimzia and anakinra or abatacept is not recommended (see section 4.4).
Co-administration of Cimzia with methotrexate had no significant effect on the pharmacokinetics of methotrexate. In study-to-study comparison, the pharmacokinetics of certolizumab pegol appeared similar to those observed previously in healthy subjects.
Women of childbearing potential
Women of childbearing potential should use adequate contraception to prevent pregnancy and continue its use for at least 5 months after the last Cimzia administration.
Pregnancy
There are no adequate data from the use of Cimzia in pregnant women.
Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to the foetus. However, these are insufficient with respect to human reproductive toxicity (see section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal immune response in the newborn. Therefore, Cimzia should not be used in pregnancy.
Breast-feeding
There is insufficient information on the excretion of certolizumab pegol in human or animal breast milk. Since immunoglobulins are excreted into human breast milk, a risk to the breast-feeding child cannot be excluded. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Cimzia should be made taking into account the benefit of breast-feeding to the child and the benefit of Cimzia therapy to the woman.
Fertility
Effects on sperm motility measures and a trend of reduced sperm count in male rodents have been observed with no apparent effect on fertility (see section 5.3). The clinical relevance of this finding is unknown.
Cimzia may have a minor influence on the ability to drive and use machines. Dizziness (including vertigo, vision disorder and fatigue) may occur following administration of Cimzia (see section 4.8).
Cimzia was studied in 2,367 patients with rheumatoid arthritis in controlled and open label trials for up to 57 months. The data in Table 1 are based primarily on the pivotal controlled Studies involving 1,774 patients receiving Cimzia and 647 patients receiving placebo during the controlled period.
In the placebo-controlled studies, patients receiving Cimzia had an approximately 4 times greater duration of exposure compared with the placebo group. This difference in exposure is primarily due to patients on placebo being more likely to withdraw early. In addition, Studies RA-I and RA-II had a mandatory withdrawal for non-responders at Week 16, the majority of whom were on placebo.
The proportion of patients who discontinued treatment due to adverse events during the controlled trials was 5% for patients treated with Cimzia and 2.5% for patients treated with placebo.
The most common adverse reactions belonged to the system organ classes Infections and infestations, reported in 15.5% of patients on Cimzia and 7.6% of patients on placebo, and General disorders and administration site conditions, reported in 10.0% of patients on Cimzia and 9.7% of patients on placebo.
Adverse reactions reported in rheumatoid arthritis clinical trials and postmarketing at least possibly related to Cimzia are listed in Table 1 below, according to frequency and system organ class. Frequency categories are defined as follows: Very common (
Table :1 . Adverse drug reactions in clinical trials and postmarketing
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*These events have been related to the class of TNF-antagonists, but incidence with Cimzia is not known.
The additional following ADRs have been observed uncommonly with Cimzia in other indications: gastrointestinal stenosis and obstructions, general physical health deterioration, abortion spontaneous and azoospermia.
Infections
The incidence of new cases of infections in placebo-controlled clinical trials in rheumatoid arthritis was 0.91 per patient-year for all Cimzia-treated patients and 0.72 per patient-year for placebo-treated patients. The infections consisted primarily of upper respiratory tract infections, herpes infections, urinary tract infections, and lower respiratory tract infections (see sections 4.3 and 4.4).
In the placebo-controlled clinical trials, there were more new cases of serious infection in the Cimzia treatment groups (0.06 per patient-year; all doses), compared with placebo (0.02 per patient-year). Serious infections included tuberculosis and invasive opportunistic infections (e.g. pneumocystosis, fungal oesophagitis, nocardiosis and herpes zoster disseminated). There is no evidence of an increased risk of infections with continued exposure over time (see section 4.4).
Malignancies and lymphoproliferative disorders
Excluding non-melanoma of the skin, 30 malignancies including 3 cases of lymphoma were observed in the Cimzia RA clinical trials in which a total of 2,367 patients were treated, representing 4,136 patient-years. Cases of lymphoma occurred at an incidence rate of 0.07 per 100 patient-years and melanoma at an incidence rate of 0.02 per 100 patient-years with Cimzia in rheumatoid arthritis clinical trials (see section 4.4).
Autoimmunity
For subjects who were ANA negative at baseline, 16.7% of those treated with Cimzia developed positive ANA titers, compared with 12.0% of subjects in the placebo group. For subjects who were anti-dsDNA antibody negative at baseline, 2.2% of those treated with Cimzia developed positive anti-dsDNA antibody titers, compared with 1.0% of subjects in the placebo group. In both placebo-controlled and open-label follow-up clinical trials for rheumatoid arthritis, cases of lupus-like syndrome were reported uncommonly. There have been rare reports of other immune-mediated conditions; the causal relationship to Cimzia is not known. The impact of long-term treatment with Cimzia on the development of autoimmune diseases is unknown.
Injection site reactions
In the placebo-controlled rheumatoid arthritis clinical trials, 6.4% of patients treated with Cimzia developed injection site reactions (erythema, itching, haematoma, pain, swelling or bruising), compared to 6.5% of patients receiving placebo. Injection site pain was observed in 1.5% of patients treated with Cimzia with no cases leading to withdrawal.
No dose-limiting toxicity was observed during clinical trials. Multiple doses of up to 800 mg subcutaneously and 20 mg/kg intravenously have been administered. In cases of overdose, it is recommended that patients are monitored closely for any adverse reactions or effect, and appropriate symptomatic treatment initiated immediately.
Pharmacotherapeutic group: Tumour necrosis factor alpha (TNFα) inhibitors, ATC code: L04AB05
Mechanism of action
Cimzia has a high affinity for human TNFα and binds with a dissociation constant (KD) of 90 pM. TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Cimzia selectively neutralises TNFα (IC90 of 4 ng/ml for inhibition of human TNFα in the in vitro L929 murine fibrosarcoma cytotoxicity assay) but does not neutralise lymphotoxin α (TNFβ).
Cimzia was shown to neutralise membrane associated and soluble human TNFα in a dose-dependant manner. Incubation of monocytes with Cimzia resulted in a dose-dependant inhibition of lipopolysaccharide (LPS)-induced TNFα and IL1β production in human monocytes.
Cimzia does not contain a fragment crystallisable (Fc) region, which is normally present in a complete antibody, and therefore does not fix complement or cause antibody-dependent cell-mediated cytotoxicity in vitro. It does not induce apoptosis in vitro in human peripheral blood-derived monocytes or lymphocytes, or neutrophil degranulation.
Clinical efficacy
The efficacy and safety of Cimzia have been assessed in 2 randomised, placebo-controlled, double-blind clinical trials in patients
Table :2. Clinical trial description
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mTSS: modified Total Sharp Score
ACR response
The results of clinical trials RA-I and RA-II are shown in Table 3. Statistically significantly greater ACR 20 and ACR 50 responses were achieved from Week 1 and Week 2, respectively, in both clinical trials compared to placebo. Responses were maintained through Weeks 52 (RA-I) and 24 (RA-II). Of the 783 patients initially randomised to active treatment in RA-I, 508 completed 52 weeks of placebo-controlled treatment and entered the open-label extension study. Of these, 427 completed 2 years of open-label follow-up and thus had a total exposure to Cimzia of 148 weeks overall. The observed ACR20 response rate at this timepoint was 91%.The reduction (RA-I) from Baseline in DAS28 (ESR) also was significantly greater (p<0.001) at Week 52 (RA-I) and Week 24 (RA-II) compared to placebo and maintained through 2 years in the open-label extension trial to RA-I.
Table :3. ACR response in clinical trials RA-I and RA-II
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