Gastrine may be available in the countries listed below.
Magaldrate is reported as an ingredient of Gastrine in the following countries:
Simeticone is reported as an ingredient of Gastrine in the following countries:
International Drug Name Search
Vincristin Richter may be available in the countries listed below.
Vincristine sulfate (a derivative of Vincristine) is reported as an ingredient of Vincristin Richter in the following countries:
International Drug Name Search
Lamotrigina Normon may be available in the countries listed below.
Lamotrigine is reported as an ingredient of Lamotrigina Normon in the following countries:
International Drug Name Search
In some countries, this medicine may only be approved for veterinary use.
In the US, Cyclophosphamide (cyclophosphamide systemic) is a member of the drug class alkylating agents and is used to treat Acute Lymphocytic Leukemia, Acute Nonlymphocytic Leukemia, Bladder Cancer, Brain Tumor, Breast Cancer, Bullous Pemphigoid, Cancer, Cervical Cancer, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Cogan's Syndrome, Dermatomyositis, Endometrial Cancer, Ewing's Sarcoma, Histiocytosis, Hodgkin's Lymphoma, IgA Nephropathy, Multiple Myeloma, Multiple Sclerosis, Mycosis Fungoides, Nephrotic Syndrome, Neuroblastoma, Non-Hodgkin's Lymphoma, Non-Small Cell Lung Cancer, Organ Transplant - Rejection Prophylaxis, Osteosarcoma, Ovarian Cancer, Pemphigoid, Pemphigus, Prostate Cancer, Rheumatoid Arthritis, Small Cell Lung Cancer, Systemic Lupus Erythematosus, Systemic Sclerosis, Testicular Cancer, Wegener's Granulomatosus and Wilms' Tumor.
US matches:
UK matches:
Rec.INN
L01AA01
0000050-18-0
C7-H15-Cl2-N2-O2-P
261
Disease-modifying antirheumatic drug, DMARD
Antineoplastic agent, alkylating agent
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| SPC | Summary of Product Characteristics (UK) |
Valproat Stada may be available in the countries listed below.
Valproic Acid sodium (a derivative of Valproic Acid) is reported as an ingredient of Valproat Stada in the following countries:
International Drug Name Search
Enalapril AL may be available in the countries listed below.
Enalapril maleate (a derivative of Enalapril) is reported as an ingredient of Enalapril AL in the following countries:
International Drug Name Search
Viabom may be available in the countries listed below.
Dimenhydrinate is reported as an ingredient of Viabom in the following countries:
International Drug Name Search
Spironolacton-ratiopharm may be available in the countries listed below.
Spironolactone is reported as an ingredient of Spironolacton-ratiopharm in the following countries:
International Drug Name Search
Allopurinol Zydus may be available in the countries listed below.
Allopurinol is reported as an ingredient of Allopurinol Zydus in the following countries:
International Drug Name Search
Bendazol may be available in the countries listed below.
Bendazol (DCF) is also known as Bendazol (Rec.INN)
Mebendazole is reported as an ingredient of Bendazol in the following countries:
International Drug Name Search
Glossary
| DCF | Dénomination Commune Française |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Deprexan may be available in the countries listed below.
Desipramine hydrochloride (a derivative of Desipramine) is reported as an ingredient of Deprexan in the following countries:
International Drug Name Search
Mercaptopurina may be available in the countries listed below.
Mercaptopurina (DCIT) is known as Mercaptopurine in the US.
International Drug Name Search
Glossary
| DCIT | Denominazione Comune Italiana |
Dextrifer may be available in the countries listed below.
Ferrous Oxalate dihydrate (a derivative of Ferrous Oxalate) is reported as an ingredient of Dextrifer in the following countries:
International Drug Name Search
Generic Name: bepotastine besilate (Ophthalmic route)
bep-oh-TAS-teen BES-i-late
In the U.S.
Available Dosage Forms:
Pharmacologic Class: Bepotastine
Bepotastine besilate ophthalmic (eye) preparation is used to treat itching of the eye caused by a condition known as allergic conjunctivitis. It works by preventing the effects of certain inflammatory substances, which are produced by cells in your eyes and sometimes cause allergic reactions.
This medicine is available only with your doctor's prescription.
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 bepostatine besilate in children. However, safety and efficacy have not been established in children younger than 2 years of age.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of bepostatine besilate in the elderly.
| 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. 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.
Your doctor will tell you how much of this medicine to use and how often. Do not use more medicine or use it more often than your doctor tells you to. This medicine is not for long-term use.
To use the eye drops:
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, apply 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.
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.
Your eye doctor will want to examine your eye(s) at regular visits to make sure the medicine is working properly and is not causing unwanted effects.
If you are wearing contact lenses, remove them before putting the drops in your eyes. Wait at least 10 minutes after using this medicine before putting your contact lenses back in. You should only wear contact lenses if your eyes are not red. This medicine should not be used for irritation caused by contact lenses.
If your symptoms do not improve within a few days or if they become worse, check with your doctor.
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: Bepreve 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: dextroamphetamine (DEX tro am FET a meen)
Brand Names: Dexedrine, Dexedrine Spansule, Dextrostat, Liquadd, ProCentra
Dextroamphetamine is a central nervous system stimulant. It affects chemicals in the brain and nerves that contribute to hyperactivity and impulse control.
Dextroamphetamine is used to treat narcolepsy and attention deficit hyperactivity disorder (ADHD).
Dextroamphetamine may also be used for other purposes not listed in this medication guide.
Long-term use of dextroamphetamine can slow a child's growth. Tell your doctor if the child using this medication is not growing or gaining weight properly.
Do not use this medication if you are allergic to dextroamphetamine or if you have:
heart disease or moderate to severe high blood pressure (hypertension);
arteriosclerosis (hardening of the arteries);
overactive thyroid;
glaucoma;
severe anxiety, tension, or agitation; or
if you have a history of drug or alcohol addiction.
a congenital heart defect;
high blood pressure;
heart failure, heart rhythm disorder, or recent heart attack;
a personal or family history of mental illness, psychotic disorder, bipolar illness, depression, or suicide attempt;
epilepsy or other seizure disorder;
an allergy to dyes used in drugs or manufactured foods; or
tics (muscle twitches) or Tourette's syndrome.
Long-term use of dextroamphetamine can slow a child's growth. Tell your doctor if the child using this medication is not growing or gaining weight properly.
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Your doctor may occasionally change your dose to make sure you get the best results.
Do not take dextroamphetamine in the evening because it may cause sleep problems (insomnia).
Measure liquid 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.
Your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.
This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using dextroamphetamine.
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose, or if it is already evening. Taking this medicine late in the day can cause sleep problems. Do not take extra medicine to make up the missed dose.
Overdose symptoms may include restlessness, tremor, muscle twitches, rapid breathing, confusion, hallucinations, panic, aggressiveness, muscle pain or tenderness, muscle weakness, fever or flu symptoms, and dark colored urine. These symptoms may be followed by depression and tiredness. Other overdose symptoms include nausea, vomiting, diarrhea, stomach pain, uneven heartbeats, feeling light-headed, fainting, seizure (convulsions), or coma.
Do not take dextroamphetamine late in the day. A dose taken too late in the day can cause sleep problems (insomnia).
Avoid drinking fruit juices or taking vitamin C at the same time you take dextroamphetamine. These can make your body absorb less of the medicine.
fast or pounding heartbeats;
feeling light-headed, fainting;
dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure); or
tremor, restlessness, hallucinations, unusual behavior, or motor tics (muscle twitches).
Less serious side effects may include:
headache or dizziness;
sleep problems (insomnia);
dry mouth or an unpleasant taste in your mouth;
diarrhea, constipation;
loss of appetite, weight loss; or
loss of interest in sex, impotence, or difficulty having an orgasm.
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.
Tell your doctor about all other medicines you use, especially:
blood pressure medications;
a diuretic (water pill);
cold or allergy medicines (antihistamines);
acetazolamide (Diamox);
chlorpromazine (Thorazine);
ethosuximide (Zarontin);
haloperidol (Haldol);
lithium (Eskalith, Lithobid);
methenamine (Hiprex, Mandelamine, Urex);
phenytoin (Dilantin), phenobarbital (Luminal, Solfoton);
propoxyphene (Darvon, Darvocet);
reserpine;
antacids, sodium bicarbonate (Alka-Seltzer);
stomach acid reducers such as cimetidine (Tagamet),esomeprazole (Nexium), famotidine (Pepcid), lansoprazole (Prevacid), nizatidine (Axid), omeprazole (Prilosec), or ranitidine (Zantac); or
an antidepressant such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), imipramine (Tofranil), or nortriptyline (Pamelor).
This list is not complete and other drugs may interact with dextroamphetamine. 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.
See also: Dexedrine Spansule side effects (in more detail)
Gonalef may be available in the countries listed below.
Follitropin Alfa is reported as an ingredient of Gonalef in the following countries:
International Drug Name Search
Verecolene C.M. may be available in the countries listed below.
Bisacodyl is reported as an ingredient of Verecolene C.M. in the following countries:
International Drug Name Search
Bactricida may be available in the countries listed below.
Sulfamethoxazole is reported as an ingredient of Bactricida in the following countries:
Trimethoprim is reported as an ingredient of Bactricida in the following countries:
International Drug Name Search
Quemicetina may be available in the countries listed below.
Chloramphenicol is reported as an ingredient of Quemicetina in the following countries:
Chloramphenicol stearate (a derivative of Chloramphenicol) is reported as an ingredient of Quemicetina in the following countries:
Chloramphenicol succinate (a derivative of Chloramphenicol) is reported as an ingredient of Quemicetina in the following countries:
Chloramphenicol succinate sodium (a derivative of Chloramphenicol) is reported as an ingredient of Quemicetina in the following countries:
International Drug Name Search
In the US, Enoxacin (enoxacin systemic) is a member of the drug class quinolones and is used to treat Epididymitis - Non-Specific, Gonococcal Infection - Uncomplicated, Kidney Infections, Prostatitis and Urinary Tract Infection.
US matches:
Rec.INN
J01MA04
0074011-58-8
C15-H17-F-N4-O3
320
Antibacterial: Gyrase inhibitor
1,8-Naphthyridine-3-carboxylic acid, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| DCIT | Denominazione Comune Italiana |
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Class Name: radiopaque agent- diagnostic (Injection, ureteral, Injection, intracervical)
Radiopaque agents are drugs used to help diagnose certain medical problems. They contain iodine, which blocks x-rays. Depending on how the radiopaque agent is given, it localizes or builds up in certain areas of the body. The resulting high level of iodine allows the x-rays to make a "picture" of the area.
The areas of the body in which the radiopaque agent localizes will appear white on the x-ray film. This creates the needed distinction, or contrast, between one organ and other tissues. The contrast will help the doctor see any special conditions that may exist in that organ or part of the body.
The local radiopaque agents are used in the diagnosis of:
A catheter or syringe is used to put the solution of the radiopaque agent into the bladder or ureters to help diagnose problems or diseases of the kidneys or other areas of the urinary tract. It may also be placed into the uterus and fallopian tubes to help diagnose problems or disease of those organs. After the test is done, the patient expels most of the solution by urinating (after bladder or ureter studies) or from the vagina (after uterine or fallopian tube studies).
Radiopaque agents are classified by their osmolality (a measure of concentration). There are high- and low-osmolality contrast agents. Low-osmolality agents are newer and more expensive than the high-osmolality ones. For most patients, a high-osmolality contrast agent is a good and safe choice. However, some patients are considered to be at a greater risk of having severe reactions to a radiopaque agent. Patients at risk are those who have had a severe reaction to radiopaque agents in the past. Also, patients with asthma or a history of allergies may be at a greater risk of severe reactions. For these patients, a low-osmolality contrast agent may be chosen. If you have any questions about this, check with the radiologist.
The doses of radiopaque agents will be different for different patients and depend on the type of test. The strength of the solution is determined by how much iodine it contains. Different tests will require a different strength and amount of solution depending on the age of the patient, the contrast needed, and the x-ray equipment used. Also, for tests of the kidneys and other areas of the urinary tract, the amount of solution to be used depends on the size of the bladder.
Radiopaque agents are to be used only by or under the supervision of a doctor in radiology or a radiologist.
In deciding to receive a diagnostic test, the risks of taking the test must be weighed against the good it will do. This is a decision you and your doctor will make. For these tests, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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.
Although there is no specific information comparing use of radiopaque agents in children with use in other age groups, these agents are not expected to cause different side effects or problems in children than they do in adults when used in the bladder or ureters. There is no specific information about the use of radiopaque agents in children for studies of the uterus or fallopian tubes.
Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of radiopaque agents for instillation into the bladder or ureters or into the uterus and fallopian tubes in the elderly with use in other age groups, these agents are not expected to cause different side effects or problems in older people than they do in younger adults.
Studies on effects in pregnancy when radiopaque agents are instilled into the bladder or ureters have not been done in women. Studies in animals have been done only with iothalamate, which has not been shown to cause birth defects or other problems.
Diagnostic tests of the uterus and fallopian tubes using radiopaque agents are not recommended during pregnancy or for at least 6 months after a pregnancy has ended. The test may cause other problems, such as infection in the uterus.
Also, radiopaque agents containing iodine have, on rare occasions, caused hypothyroidism (underactive thyroid) in the baby when they were injected into the amniotic sac late in the pregnancy. In addition, x-rays of the abdomen during pregnancy may have harmful effects on the fetus. Make sure your doctor knows if you are pregnant or if you suspect that you may be pregnant when you are to receive this radiopaque agent.
Although small amounts of radiopaque agents are absorbed into the body and may pass into the breast milk, these agents have not been shown to cause problems in nursing babies. However, it may be necessary for you to stop breast-feeding temporarily after receiving a radiopaque agent. Be sure you have discussed this with your doctor.
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 diagnostic tests in this class. Make sure you tell your doctor if you have any other medical problems, especially:
Your doctor may have special instructions for you in preparation for your test, such as the need for a special diet or for a laxative, enema, or vaginal douche, depending on the kind of test you are having done. If you have not received such instructions or if you do not understand them, check with your doctor in advance.
For your comfort and for the best test results, you may be instructed to urinate just before the procedure.
If you are on hemodialysis and treated with a gadolinium-containing contrast agent (GBCA), your doctor may perform hemodialysis immediately after you receive the contrast agent .
Make sure your doctor knows if you are planning to have any thyroid tests in the near future. Even after several weeks the results of the thyroid test may be affected by the iodine in this agent.
Seek immediate medical attention if you experience burning or itching of the skin; reddened or darkened patches; skin swelling, hardening and/or tightening; yellow raised spots on the whites of the eyes; joint stiffness; limited range of motion in the arms and legs; pain that is deep in the hip bone or ribs; or muscle weakness. These may be symptoms of a very serious disease called nephrogenic systemic fibrosis (NSF) .
Along with its needed effects, radiopaque agents can cause serious side effects such as allergic reactions. These effects may occur almost immediately or a few minutes after the radiopaque agent is given. Although these serious side effects appear only rarely, your health care professional will be prepared to give you immediate medical attention if needed. If you have any questions about this, check with your doctor.
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.
The information contained in the Thomson Healthcare (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 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 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 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 HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Healthcare does not assume any responsibility or risk for your use of the Thomson Healthcare products.
Dermomycin may be available in the countries listed below.
Fusidic Acid sodium (a derivative of Fusidic Acid) is reported as an ingredient of Dermomycin in the following countries:
International Drug Name Search
Clomactil may be available in the countries listed below.
Chlorpromazine is reported as an ingredient of Clomactil in the following countries:
International Drug Name Search
Viarex may be available in the countries listed below.
Beclometasone 17α,21-dipropionate (a derivative of Beclometasone) is reported as an ingredient of Viarex in the following countries:
International Drug Name Search
Omepra may be available in the countries listed below.
Omeprazole is reported as an ingredient of Omepra in the following countries:
International Drug Name Search
Omeprazol Toll Pharma may be available in the countries listed below.
Omeprazole is reported as an ingredient of Omeprazol Toll Pharma in the following countries:
International Drug Name Search
Generic Name: dexamethasone (oral) (dex a METH a sone)
Brand Names: Baycadron, Dexamethasone Intensol, DexPak 10 Day Taperpak, DexPak 13 DayTaperpak, DexPak 6 DayTaperpak, Dexpak Jr. Taperpak, Zema Pak 10-Day, Zema Pak 13-Day, Zema Pak 6-Day
Dexamethasone is a steroid that prevents the release of substances in the body that cause inflammation.
Dexamethasone is used to treat many different conditions such as allergic disorders, skin conditions, ulcerative colitis, arthritis, lupus, psoriasis, or breathing disorders.
Dexamethasone may also be used for purposes not listed in this medication guide.
Before taking dexamethasone, tell your doctor about all of your medical conditions, and about all other medicines you are using. There are many other diseases that can be affected by steroid use, and many other medicines that can interact with steroids.
Your steroid medication needs may change if you have any unusual stress such as a serious illness, fever or infection, or if you have surgery or a medical emergency. Tell your doctor about any such situation that affects you during treatment.
Steroid medication can weaken your immune system, making it easier for you to get an infection or worsening an infection you already have or have recently had. Tell your doctor about any illness or infection you have had within the past several weeks.
Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroid medication.
Do not receive a "live" vaccine while you are taking dexamethasone. Vaccines may not work as well while you are taking a steroid.
Steroid medication can weaken your immune system, making it easier for you to get an infection. Steroids can also worsen an infection you already have, or reactivate an infection you recently had. Before taking this medication, tell your doctor about any illness or infection you have had within the past several weeks.
To make sure you can safely take dexamethasone, tell your doctor if you have any of these other conditions:
liver disease (such as cirrhosis);
kidney disease;
a thyroid disorder;
diabetes;
a history of malaria;
tuberculosis;
osteoporosis;
a muscle disorder such as myasthenia gravis;
glaucoma or cataracts;
herpes infection of the eyes;
stomach ulcers, ulcerative colitis, or diverticulitis;
depression or mental illness;
congestive heart failure; or
high blood pressure
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Your doctor may occasionally change your dose to make sure you get the best results.
Your steroid medication needs may change if you have unusual stress such as a serious illness, fever or infection, or if you have surgery or a medical emergency. Tell your doctor about any such situation that affects you.
This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using dexamethasone.
Call your doctor for instructions if you miss a dose of dexamethasone.
Long-term use of high steroid doses can lead to symptoms such as thinning skin, easy bruising, changes in the shape or location of body fat (especially in your face, neck, back, and waist), increased acne or facial hair, menstrual problems, impotence, or loss of interest in sex.
Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroid medication.
problems with your vision;
swelling, rapid weight gain, feeling short of breath;
severe depression, unusual thoughts or behavior, seizure (convulsions);
bloody or tarry stools, coughing up blood;
pancreatitis (severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate);
low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling); or
dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).
Less serious side effects may include:
sleep problems (insomnia), mood changes;
acne, dry skin, thinning skin, bruising or discoloration;
slow wound healing;
increased sweating;
headache, dizziness, spinning sensation;
nausea, stomach pain, bloating;
muscle weakness; or
changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).
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.
Many drugs can interact with dexamethasone. Below is just a partial list. Tell your doctor if you are using:
aspirin (taken on a daily basis or at high doses);
a diuretic (water pill);
a blood thinner such as warfarin (Coumadin);
cyclosporine (Gengraf, Neoral, Sandimmune);
insulin or diabetes medications you take by mouth;
ketoconazole (Nizoral);
rifampin (Rifadin, Rifater, Rifamate, Rimactane); or
seizure medications such as phenytoin (Dilantin) or phenobarbital (Luminal, Solfoton).
This list is not complete and other drugs may interact with dexamethasone. 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.
See also: Baycadron side effects (in more detail)
Gentamed may be available in the countries listed below.
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In the US, Ambisome (amphotericin b liposomal systemic) is a member of the drug class polyenes and is used to treat Aspergillosis - Invasive, Candida Infections - Systemic, Cryptococcal Meningitis - Immunosuppressed Host, Cryptococcosis, Febrile Neutropenia and Leishmaniasis.
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| SPC | Summary of Product Characteristics (UK) |
Ondansetron Medis may be available in the countries listed below.
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Benlysta ® (belimumab) is indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy.
The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations.
Benlysta is for intravenous infusion only and must be reconstituted and diluted prior to administration [see Dosage and Administration (2.3)]. Do not administer as an intravenous push or bolus.
The recommended dosage regimen is 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter. Reconstitue, dilute and administer as an intravenous infusion only, over a period of 1 hour. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. The infusion must be discontinued immediately if the patient experiences a serious hypersensitivity reaction [seeContraindications (4), Warnings and Precautions (5.4)].
Prior to dosing with Benlysta, consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions. [seeWarnings and Precautions (5.4, 5.5) and Adverse Reactions (6.1)].
Benlysta is provided as a lyophilized powder in a single-use vial for intravenous infusion only and should be reconstituted and diluted by a healthcare professional using aseptic technique as follows:
Single-use vials of belimumab lyophilized powder for injection:
Benlysta is contraindicated in patients who have had anaphylaxis with belimumab.
There were more deaths reported with Benlysta than with placebo during the controlled period of the clinical trials. Out of 2133 patients in 3 clinical trials, a total of 14 deaths occurred during the placebo-controlled, double-blind treatment periods: 3/675 (0.4%), 5/673 (0.7%), 0/111 (0%), and 6/674 (0.9%) deaths in the placebo, Benlysta 1 mg/kg, Benlysta 4 mg/kg, and Benlysta 10 mg/kg groups, respectively. No single cause of death predominated. Etiologies included infection, cardiovascular disease and suicide.
Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including Benlysta. Physicians should exercise caution when considering the use of Benlysta in patients with chronic infections. Patients receiving any therapy for chronic infection should not begin therapy with Benlysta. Consider interrupting Benlysta therapy in patients who develop a new infection while undergoing treatment with Benlysta and monitor these patients closely.
In the controlled clinical trials, the overall incidence of infections was 71% in patients treated with Benlysta compared with 67% in patients who received placebo. The most frequent infections (>5% of patients receiving Benlysta) were upper respiratory tract infection, urinary tract infection, nasopharyngitis, sinusitis, bronchitis, and influenza. Serious infections occurred in 6.0% of patients treated with Benlysta and in 5.2% of patients who received placebo. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis. Infections leading to discontinuation of treatment occurred in 0.7% of patients receiving Benlysta and 1.0% of patients receiving placebo. Infections resulting in death occurred in 0.3% (4/1458) of patients treated with Benlysta and in 0.1% (1/675) of patients receiving placebo.
The impact of treatment with Benlysta on the development of malignancies is not known. In the controlled clinical trials, malignancies (including non-melanoma skin cancers) were reported in 0.4% of patients receiving Benlysta and 0.4% of patients receiving placebo. In the controlled clinical trials, malignancies, excluding non-melanoma skin cancers, were observed in 0.2% (3/1458) and 0.3% (2/675) of patients receiving Benlysta and placebo, respectively. As with other immunomodulating agents, the mechanism of action of Benlysta could increase the risk for the development of malignancies.
In the controlled clinical trials, hypersensitivity reactions (occurring on the same day of infusion) were reported in 13% (191/1458) of patients receiving Benlysta and 11% (76/675) of patients receiving placebo. Anaphylaxis was observed in 0.6% (9/1458) of patients receiving Benlysta and 0.4% (3/675) of patients receiving placebo. Manifestations included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea. Due to overlap in signs and symptoms, it was not possible to distinguish between hypersensitivity reactions and infusion reactions in all cases [see Warnings and Precautions (5.5)]. Some patients (13%) received premedication, which may have mitigated or masked a hypersensitivity response; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of hypersensitivity reactions.
Benlysta should be administered by healthcare providers prepared to manage anaphylaxis. In the event of a serious reaction, administration of Benlysta must be discontinued immediately and appropriate medical therapy administered. Patients should be monitored during and for an appropriate period of time after administration of Benlysta. Patients should be informed of the signs and symptoms of a hypersensitivity reaction and instructed to seek immediate medical care should a reaction occur.
In the controlled clinical trials, adverse events associated with the infusion (occurring on the same day of the infusion) were reported in 17% (251/1458) of patients receiving Benlysta and 15% (99/675) of patients receiving placebo. Serious infusion reactions (excluding hypersensitivity reactions) were reported in 0.5% of patients receiving Benlysta and 0.4% of patients receiving placebo and included bradycardia, myalgia, headache, rash, urticaria, and hypotension. The most common infusion reactions (≥ 3% of patients receiving Benlysta) were headache, nausea, and skin reactions. Due to overlap in signs and symptoms, it was not possible to distinguish between hypersensitivity reactions and infusion reactions in all cases [see Warnings and Precautions (5.4)]. Some patients (13%) received premedication, which may have mitigated or masked an infusion reaction; however there is insufficient evidence to determine whether premedication diminishes the frequency or severity of infusion reactions [seeAdverse Reactions (6.1)].
Benlysta should be administered by healthcare providers prepared to manage infusion reactions. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely.
In the controlled clinical trials, psychiatric events were reported more frequently with Benlysta (16%) than with placebo (12%), related primarily to depression-related events (6.3% Benlysta and 4.7% placebo), insomnia (6.0% Benlysta and 5.3% placebo), and anxiety (3.9% Benlysta and 2.8% placebo). Serious psychiatric events were reported in 0.8% of patients receiving Benlysta (0.6% and 1.2% with 1 and 10 mg/kg, respectively) and 0.4% of patients receiving placebo. Serious depression was reported in 0.4% (6/1458) of patients receiving Benlysta and 0.1% (1/675) of patients receiving placebo. Two suicides (0.1%) were reported in patients receiving Benlysta. The majority of patients who reported serious depression or suicidal behavior had a history of depression or other serious psychiatric disorders and most were receiving psychoactive medications. It is unknown if Benlysta treatment is associated with increased risk for these events.
Patients receiving Benlysta should be instructed to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or other mood changes.
Live vaccines should not be given for 30 days before or concurrently with Benlysta as clinical safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving Benlysta or the effect of Benlysta on new immunizations. Because of its mechanism of action, Benlysta may interfere with the response to immunizations.
Benlysta has not been studied in combination with other biologic therapies, including B-cell targeted therapies, or intravenous cyclophosphamide. Therefore, use of Benlysta is not recommended in combination with biologic therapies or intravenous cyclophosphamide.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The following have been observed with Benlysta and are discussed in detail in the Warnings and Precautions section:
The data described below reflect exposure to Benlysta plus standard of care compared with placebo plus standard in 2133 patients in 3 controlled studies. Patients received Benlysta at doses of 1 mg/kg (N=673), 4 mg/kg (N=111; Trial 1 only) or 10 mg/kg (N=674) or placebo (N=675) intravenously over a 1-hour period on Days 0, 14, 28, and then every 28 days. In two of the studies (Trial 1 and Trial 3), treatment was given for 48 weeks, while in the other study (Trial 2) treatment was given for 72 weeks [see Clinical Studies (14)]. Because there was no apparent dose-related increase in the majority of adverse events observed with Benlysta, the safety data summarized below are presented for the 3 doses pooled, unless otherwise indicated; the adverse reaction table displays the results for the recommended dose of 10 mg/kg compared with placebo.
The population had a mean age of 39 (range 18 – 75), 94% were female, and 52% were Caucasian. In these trials, 93% of patients treated with Benlysta reported an adverse reaction compared with 92% treated with placebo.
The most common serious adverse reactions were serious infections (6.0% and 5.2% in the groups receiving Benlysta and placebo, respectively) [ see Warnings and Precautions (5.2)].
The most commonly-reported adverse reactions, occurring in ≥5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis.
The proportion of patients who discontinued treatment due to any adverse reaction during the controlled clinical trials was 6.2% for patients receiving Benlysta and 7.1% for patients receiving placebo. The most common adverse reactions resulting in discontinuation of treatment (≥1% of patients receiving Benlysta or placebo) were infusion reactions (1.6% Benlysta and 0.9% placebo), lupus nephritis (0.7% Benlysta and 1.2% placebo), and infections (0.7% Benlysta and 1.0% placebo).
Table 1 lists adverse reactions, regardless of causality, occurring in at least 3% of patients with SLE who received Benlysta 10 mg/kg and at an incidence at least 1% greater than that observed with placebo in the 3 controlled studies.
| Preferred Term | Benlysta 10 mg/kg + Standard of Care (n = 674) % | Placebo + Standard of Care (n = 675) % |
| Nausea | 15 | 12 |
| Diarrhea | 12 | 9 |
| Pyrexia | 10 | 8 |
| Nasopharyngitis | 9 | 7 |
| Bronchitis | 9 | 5 |
| Insomnia | 7 | 5 |
| Pain in extremity | 6 | 4 |
| Depression | 5 | 4 |
| Migraine | 5 | 4 |
| Pharyngitis | 5 | 3 |
| Cystitis | 4 | 3 |
| Leukopenia | 4 | 2 |
| Gastroenteritis viral | 3 | 1 |
In Trials 2 and 3, anti-belimumab antibodies were detected in 4 of 563 (0.7%) patients receiving Benlysta 10 mg/kg and in 27 of 559 (4.8%) patients receiving Benlysta 1 mg/kg. The reported frequency for the group receiving 10 mg/kg may underestimate the actual frequency due to lower assay sensitivity in the presence of high drug concentrations. Neutralizing antibodies were detected in 3 patients receiving Benlysta 1 mg/kg. Three patients with anti-belimumab antibodies experienced mild infusion reactions of nausea, erythematous rash, pruritus, eyelid edema, headache, and dyspnea; none of the reactions was life-threatening. The clinical relevance of the presence of anti-belimumab antibodies is not known.
The data reflect the percentage of patients whose test results were positive for antibodies to belimumab in specific assays. The observed incidence of antibody positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to belimumab with the incidence of antibodies to other products may be misleading.
Formal drug interaction studies have not been performed with Benlysta. In clinical trials of patients with SLE, Benlysta was administered concomitantly with other drugs, including corticosteroids, antimalarials, immunomodulatory and immunosuppressive agents (including azathioprine, methotrexate, and mycophenolate), angiotensin pathway antihypertensives, HMG-CoA reductase inhibitors (statins), and NSAIDs without evidence of a clinically meaningful effect of these concomitant medications on belimumab pharmacokinetics. The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated [see Pharmacokinetics 12.3].
Pregnancy Category C. There are no adequate and well-controlled clinical studies using Benlysta in pregnant women. Immunoglobulin G (IgG) antibodies, including Benlysta, can cross the placenta. Because animal reproduction studies are not always predictive of human response, Benlysta should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Women of childbearing potential should use adequate contraception during treatment with Benlysta and for at least 4 months after the final treatment.
Nonclinical reproductive studies have been performed in pregnant cynomolgus monkeys receiving belimumab at doses of 0, 5 and 150 mg/kg by intravenous infusion (the high dose was approximately 9 times the anticipated maximum human exposure) every 2 weeks from gestation day 20 to 150. Belimumab was shown to cross the placenta. Belimumab was not associated with direct or indirect teratogenicity under the conditions tested. Fetal deaths were observed in 14%, 24% and 15% of pregnant females in the 0, 5 and 150 mg/kg groups, respectively. Infant deaths occurred with an incidence of 0%, 8% and 5%. The cause of fetal and infant deaths is not known. The relevance of these findings to humans is not known. Other treatment-related findings were limited to the expected reversible reduction of B cells in both dams and infants and reversible reduction of IgM in infant monkeys. B-cell numbers recovered after the cessation of belimumab treatment by about 1 year post-partum in adult monkeys and by 3 months of age in infant monkeys. IgM levels in infants exposed to belimumab in utero recovered by 6 months of age.
Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to Benlysta, a pregnancy registry has been established. Healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-681-6296.
It is not known whether Benlysta is excreted in human milk or absorbed systemically after ingestion. However, belimumab was excreted into the milk of cynomolgus monkeys. Because maternal antibodies are excreted in human breast milk, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of breastfeeding to the infant and the importance of the drug to the mother.
Safety and effectiveness of Benlysta have not been established in children.
Clinical studies of Benlysta did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects. Use with caution in elderly patients.
In Trial 2 and Trial 3, response rates for the primary endpoint were lower for black subjects in the Benlysta group relative to black subjects in the placebo group [see Clinical Studies (14)]. Use with caution in black/African-American patients.
There is no clinical experience with overdosage of Benlysta. Two doses of up to 20 mg/kg have been given by intravenous infusion to humans with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg.
Benlysta (belimumab) is a human IgG1λ monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab has a molecular weight of approximately 147 kDa. Belimumab is produced by recombinant DNA technology in a mammalian cell expression system.
Benlysta is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for intravenous infusion. Upon reconstitution with Sterile Water for Injection, USP, [see Dosage and Administration (2.3)] each single-use vial delivers 80 mg/mL belimumab in 0.16 mg/mL citric acid, 0.4 mg/mL polysorbate 80, 2.7 mg/mL sodium citrate, and 80 mg/mL sucrose, with a pH of 6.5.
Benlysta is a BLyS-specific inhibitor that blocks the binding of soluble BLyS, a B-cell survival factor, to its receptors on B cells. Benlysta does not bind B cells directly, but by binding BLyS, Benlysta inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.
In Trial 1 and Trial 2 in which B cells were measured, treatment with Benlysta significantly reduced circulating CD19+, CD20+, naïve, and activated B cells, plasmacytoid cells, and the SLE B-cell subset at Week 52. Reductions in naïve and the SLE B-cell subset were observed as early as Week 8 and were sustained to Week 52. Memory cells increased initially and slowly declined toward baseline levels by Week 52. The clinical relevance of these effects on B cells has not been established.
Treatment with Benlysta led to reductions in IgG and anti-dsDNA, and increases in complement (C3 and C4). These changes were observed as early as Week 8 and were sustained through Week 52. The clinical relevance of normalizing these biomarkers has not been definitively established.
The pharmacokinetic parameters displayed in Table 2 are based on population parameter estimates which are specific to the 563 patients who received belimumab 10 mg/kg in Trials 2 and 3 [see Clinical Studies (14)].
| Pharmacokinetic Parameter | Population Estimates (n = 563) |
| |
| Peak concentration (Cmax, µg/mL) | 313 |
| Area under the curve (AUC0-∞, day∙μg/mL) | 3,083 |
| Distribution half-life (t½, days) | 1.75 |
| Terminal half-life (t½, days) | 19.4 |
| Systemic clearance (CL, mL/day) | 215 |
| Volume of distribution (Vss, L) | 5.29 |
Drug Interactions: No formal drug interaction studies have been conducted with belimumab. Concomitant use of mycophenolate, azathioprine, methotrexate, antimalarials, NSAIDs, aspirin, and HMG-CoA reductase inhibitors did not significantly influence belimumab pharmacokinetics. Coadministration of steroids and angiotensin-converting enzyme (ACE) inhibitors resulted in an increase of systemic clearance of belimumab that was not clinically significant because the magnitude was well within the range of normal variability of clearance. The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated.
The following information is based on the population pharmacokinetic analysis.
Age: Age did not significantly influence belimumab pharmacokinetics in the study population, where the majority of subjects (70%) were between 18 and 45 years of age. No pharmacokinetic data are available in pediatric patients. Limited pharmacokinetic data are available for elderly patients as only 1.4% of the subjects included in the pharmacokinetic analysis were 65 years of age or older [see Use in Specific Populations (8.5)].
Gender: Gender did not significantly influence belimumab pharmacokinetics in the largely (94%) female study population.
Race: Race did not significantly influence belimumab pharmacokinetics. The racial distribution was 53% white/Caucasian, 16% Asian, 16% Alaska native/American Indian, and 14% black/African American.
Renal Impairment: No formal studies were conducted to examine the effects of renal impairment on the pharmacokinetics of belimumab. Belimumab has been studied in a limited number of patients with SLE and renal impairment (261 subjects with moderate renal impairment, creatinine clearance ≥30 and <60 mL/min; 14 subjects with severe renal impairment, creatinine clearance ≥15 and <30 mL/min). Although increases in creatinine clearance and proteinuria (>2 g/day) increased belimumab clearance, these effects were within the expected range of variability. Therefore, dosage adjustment in patients with renal impairment is not recommended.
Hepatic Impairment: No formal studies were conducted to examine the effects of hepatic impairment on the pharmacokinetics of belimumab. Belimumab has not been studied in patients with severe hepatic impairment. Baseline ALT and AST levels did not significantly influence belimumab pharmacokinetics.
Long-term animal studies have not been performed to evaluate the carcinogenic potential of belimumab. The mutagenic potential of belimumab was not evaluated.
Effects on male and female fertility have not been directly evaluated in animal studies.
The safety and effectiveness of Benlysta were evaluated in three randomized, double-blind, placebo-controlled studies involving 2133 patients with SLE according to the American College of Rheumatology criteria (Trial 1, 2, and 3). Patients with severe active lupus nephritis and severe active CNS lupus were excluded. Patients were on a stable standard of care SLE treatment regimen comprising any of the following (alone or in combination): corticosteroids, antimalarials, NSAIDs, and immunosuppressives. Use of other biologics and intravenous cyclophosphamide were not permitted.
Trial 1: Benlysta 1 mg/kg, 4 mg/kg, 10 mg/kg
Trial 1 enrolled 449 patients and evaluated doses of 1, 4, and 10 mg/kg Benlysta plus standard of care compared with placebo plus standard of care over 52 weeks in patients with SLE. Patients had to have a SELENA-SLEDAI score of ≥4 at baseline and a history of autoantibodies (anti-nuclear antibody (ANA) and/or anti-double-stranded DNA (anti-dsDNA), but 28% of the population was autoantibody negative at baseline. The co-primary endpoints were percent change in SELENA-SLEDAI score at Week 24 and time to first flare over 52 weeks. No significant differences between any of the Benlysta groups and the placebo group were observed. Exploratory analysis of this study identified a subgroup of patients (72%), who were autoantibody positive, in whom Benlysta appeared to offer benefit. The results of this study informed the design of Trials 2 and 3 and led to the selection of a target population and indication that is limited to autoantibody-positive SLE patients.
Trials 2 and 3: Benlysta 1 mg/kg and 10 mg/kg
Trials 2 and 3 were randomized, double-blind, placebo-controlled trials in patients with SLE that were similar in design except duration - Trial 2 was 76 weeks duration and Trial 3 was 52 weeks duration. Eligible patients had active SLE disease, defined as a SELENA-SLEDAI score ≥6, and positive autoantibody test results at screening. Patients were excluded from the study if they had ever received treatment with a B-cell targeted agent or if they were currently receiving other biologic agents. Intravenous cyclophosphamide was not permitted within the previous 6 months or during study. Trial 2 was conducted primarily in North America and Europe. Trial 3 was conducted in South America, Eastern Europe, Asia, and Australia.
Baseline concomitant medications included corticosteroids (Trial 2: 76%, Trial 3: 96%), immunosuppressives (Trial 2: 56%, Trial 3: 42%; including azathioprine, methotrexate and mycophenolate), and antimalarials (Trial 2: 63%, Trial 3: 67%). Most patients (>70%) were receiving 2 or more classes of SLE medications.
In Trial 2 and Trial 3, more than 50% of patients had 3 or more active organ systems at baseline. The most common active organ systems at baseline based on SELENA-SLEDAI were mucocutaneous (82% in both studies); immunology (Trial 2: 74%, Trial 3: 85%); and musculoskeletal (Trial 2: 73%, Trial 3: 59%). Less than 16% of patients had some degree of renal activity and less than 7% of patients had activity in the vascular, cardio-respiratory, or CNS systems.
At screening, patients were stratified by disease severity based on their SELENA-SLEDAI score (≤ 9 vs ≥10), proteinuria level (< 2 g/24 hr vs ≥ 2 g/24 hr), and race (African or Indigenous-American descent vs. other), and then randomly assigned to receive Benlysta 1 mg/kg, Benlysta 10 mg/kg, or placebo in addition to standard of care. The patients were administered study medication intravenously over a 1-hour period on Days 0, 14, 28, and then every 28 days for 48 weeks in Trial 3 and for 72 weeks in Trial 2.
The primary efficacy endpoint was a composite endpoint (SLE Responder Index or SRI) that defined response as meeting each of the following criteria at Week 52 compared with baseline:
The SRI uses the SELENA-SLEDAI score as an objective measure of reduction in global disease activity; the BILAG index to ensure no significant worsening in any specific organ system; and the PGA to ensure that improvements in disease activity are not accompanied by worsening of the patient’s condition overall.
In both Trials 2 and 3, the proportion of SLE patients achieving an SRI response, as defined for the primary endpoint, was significantly higher in the Benlysta 10 mg/kg group than in the placebo group in both studies. The effect on the SRI was not consistently significantly different for the Benlysta 1 mg/kg group relative to placebo in both trials. The 1 mg/kg dose is not recommended. The trends in comparisons between the treatment groups for the rates of response for the individual components of the endpoint were generally consistent with that of the SRI (Table 3). At Week 76 in Trial 2, the SRI response rate with Benlysta 10 mg/kg was not significantly different from that of placebo (39% and 32%, respectively).
| Trial 2 | Trial 3 | |||||
| ||||||
| Response* | Placebo + Standard of Care (n = 275) | Benlysta 1 mg/kg + Standard of CareT(n = 271) | Benlysta 10 mg/kg + Standard of Care (n = 273) | Placebo + Standard of Care (n = 287) | Benlysta 1 mg/kg + Standard of Care† (n = 288) | Benlysta 10 mg/kg + Standard of Care (n = 290) |
| SLE Responder Index | 34% | 41% (p = 0.104) | 43% (p = 0.021) | 44% | 51% (p = 0.013) | 58% (p < 0.001) |
| Odds Ratio (95% CI) vs. placebo | 1.3 (0.9, 1.9) | 1.5 (1.1, 2.2) | 1.6 (1.1, 2.2 ) | 1.8 (1.3, 2.6) | ||
| Components of SLE Responder Index | ||||||
| Percent of patients with reduction in SELENA-SLEDAI ≥4 | 36% | 43% | 47% | 46% | 53% | 58% |
| Percent of patients with no worsening by BILAG index | 65% | 75% | 69% | 73% | 79% | 81% |
| Percent of patients with no worsening by PGA | 63% | 73% | 69% | 69% | 79% | 80% |
The reduction in disease activity seen in the SRI was related primarily to improvement in the most commonly involved organ systems namely, mucocutaneous, musculoskeletal, and immunology.
Effect in Black/African-American Patients:
Exploratory sub-group analyses of SRI response rate in patients of black race were performed. In Trial 2 and Trial 3 combined, the SRI response rate in black patients (N=148) in the Benlysta groups was less than that in the placebo group (22/50 or 44% for placebo, 15/48 or 31% for Benlysta 1 mg/kg, and 18/50 or 36% for Benlysta 10 mg/kg). In Trial 1, black patients (N = 106) in the Benlysta groups did not appear to have a different response than the rest of the study population. Although no definitive conclusions can be drawn from these subgroup analyses, caution should be used when considering Benlysta treatment in black/African-American SLE patients.
Effect on Concomitant Steroid Treatment:
In Trial 2 and Trial 3, 46% and 69% of patients, respectively, were receiving prednisone at doses > 7.5 mg/day at baseline. The proportion of patients able to reduce their average prednisone dose by at least 25% to ≤ 7.5 mg/day during Weeks 40 through 52 was not consistently significantly different for Benlysta relative to placebo in both trials. In Trial 2, 17% of patients receiving Benlysta 10 mg/kg and 19% of patients receiving Benlysta 1 mg/kg achieved this level of steroid reduction compared with 13% of patients receiving placebo. In Trial 3, 19%, 21%, and 12% of patients receiving Benlysta 10 mg/kg, Benlysta 1 mg/kg, and placebo, respectively, achieved this level of steroid reduction.
The probability of experiencing a severe SLE flare, as defined by a modification of the SELENA Trial flare criteria which excluded severe flares triggered only by an increase of the SELENA-SLEDAI score to >12, was calculated for both Trials 2 and 3. The proportion of patients having at least 1 severe flare over 52 weeks was not consistently significantly different for Benlysta relative to placebo in both trials. In Trial 2, 18% of patients receiving Benlysta 10 mg/kg and 16% of patients receiving Benlysta 1 mg/kg had a severe flare compared with 24% of patients receiving placebo. In Trial 3, 14%, 18%, and 23% of patients receiving Benlysta 10 mg/kg, Benlysta 1 mg/kg and placebo, respectively, had a severe flare.
Benlysta is a sterile, preservative-free lyophilized powder for reconstitution, dilution, and intravenous infusion provided in single-use glass vials with a latex-free rubber stopper and a flip-off seal. Each 5-mL vial delivers 120 mg of belimumab. Each 20-mL vial delivers 400 mg of belimumab.
Benlysta is supplied as follows:
| 120 mg belimumab in a 5-mL single-use vial | NDC 49401-101-01 |
| 400 mg belimumab in a 20-mL single-use vial | NDC 49401-102-01 |
Store vials of Benlysta refrigerated between 2° to 8°C (36° to 46°F). Vials should be protected from light and stored in the original carton until use. Do not freeze. Avoid exposure to heat. Do not use beyond the expiration date.
