Tylomix may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Tylosin tartrate (a derivative of Tylosin) is reported as an ingredient of Tylomix in the following countries:
International Drug Name Search
Chinogel may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Flumequine is reported as an ingredient of Chinogel in the following countries:
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Clarithromycine Biogaran may be available in the countries listed below.
Clarithromycin is reported as an ingredient of Clarithromycine Biogaran in the following countries:
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Inicox may be available in the countries listed below.
Meloxicam is reported as an ingredient of Inicox in the following countries:
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Generic Name: rabies immune globulin (Intramuscular route)
RAY-beez i-MUNE GLOB-ue-lin
In the U.S.
Available Dosage Forms:
Therapeutic Class: Immune Serum
Rabies immune globulin is used along with rabies vaccine to prevent infection caused by the rabies virus. Rabies immune globulin works by giving your body the antibodies it needs to protect it against the rabies virus. This is called passive protection. This passive protection lasts long enough to protect your body until your body can produce its own antibodies against the rabies virus.
Rabies immune globulin is given to persons who have been exposed (for example, by a bite, scratch, or lick) to an animal that is known, or thought, to have rabies. This is called post-exposure prophylaxis. Rabies immune globulin is used only in persons who have never before received the rabies vaccine.
Rabies infection is a serious, and often fatal, infection. In the U.S., rabies in wild animals, especially raccoons, skunks, and bats, accounts for most cases of rabies passed on to humans, pets, and other domestic animals. In Canada, the animals most often infected with rabies are foxes, skunks, bats, dogs, and cats. Horses, swine, and cattle also have been known to become infected with rabies. In much of the rest of the world, including Latin America, Africa, and Asia, dogs account for most cases of rabies passed on to humans.
If you are being (or will be) treated for a possible rabies infection while traveling outside of the U.S. or Canada, contact your doctor as soon as you return to the U.S. or Canada, since it may be necessary for you to have additional treatment.
Rabies immune globulin is to be administered only by or under the supervision of your doctor or other health care professional.
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.
Although there is no specific information comparing use of rabies immune globulin in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.
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 or if they cause different side effects or problems in older people. There is no specific information comparing use of rabies immune globulin in the elderly with use in other age groups.
| 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. |
Studies in women suggest that this medication poses minimal risk to the infant when used during 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 rabies immune globulin. It may not be specific to Bayrab. Please read with care.
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.
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.
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: Bayrab 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.
Rec.INN
G04BD06
0060569-19-9
C23-H29-N-O3
367
Parasympatholytic agent
Benzeneacetic acid, α-phenyl-α-propoxy-, 1-methyl-4-piperidinyl ester
International Drug Name Search
Glossary
| BAN | British Approved Name |
| BANM | British Approved Name (Modified) |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Apo-Indapamide may be available in the countries listed below.
Indapamide is reported as an ingredient of Apo-Indapamide in the following countries:
International Drug Name Search
Enteramid may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Formosulfathiazole is reported as an ingredient of Enteramid in the following countries:
Sulfadimidine is reported as an ingredient of Enteramid in the following countries:
Sulfaguanidine is reported as an ingredient of Enteramid in the following countries:
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Alcipro may be available in the countries listed below.
Ciprofloxacin is reported as an ingredient of Alcipro in the following countries:
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Leprofen may be available in the countries listed below.
Anastrozole is reported as an ingredient of Leprofen in the following countries:
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Colostat may be available in the countries listed below.
Atorvastatin calcium (a derivative of Atorvastatin) is reported as an ingredient of Colostat in the following countries:
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Caprolex may be available in the countries listed below.
Aminocaproic Acid is reported as an ingredient of Caprolex in the following countries:
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Keor may be available in the countries listed below.
Cefixime is reported as an ingredient of Keor in the following countries:
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betadrenol may be available in the countries listed below.
Bupranolol hydrochloride (a derivative of Bupranolol) is reported as an ingredient of betadrenol in the following countries:
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Niten may be available in the countries listed below.
Losartan potassium salt (a derivative of Losartan) is reported as an ingredient of Niten in the following countries:
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Diclofenac Duo 4% Spray Gel may be available in the countries listed below.
Diclofenac is reported as an ingredient of Diclofenac Duo 4% Spray Gel in the following countries:
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Zemitron may be available in the countries listed below.
Ondansetron is reported as an ingredient of Zemitron in the following countries:
Ondansetron hydrochloride (a derivative of Ondansetron) is reported as an ingredient of Zemitron in the following countries:
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Captopril comp. AbZ may be available in the countries listed below.
Captopril is reported as an ingredient of Captopril comp. AbZ in the following countries:
Hydrochlorothiazide is reported as an ingredient of Captopril comp. AbZ in the following countries:
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Silvazine may be available in the countries listed below.
Chlorhexidine digluconate (a derivative of Chlorhexidine) is reported as an ingredient of Silvazine in the following countries:
Sulfadiazine silver (a derivative of Sulfadiazine) is reported as an ingredient of Silvazine in the following countries:
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Hermes Cevitt may be available in the countries listed below.
Ascorbic Acid is reported as an ingredient of Hermes Cevitt in the following countries:
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Longicine may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Oxytetracycline is reported as an ingredient of Longicine in the following countries:
Oxytetracycline dihydrate (a derivative of Oxytetracycline) is reported as an ingredient of Longicine in the following countries:
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ben-da-MUS-teen
In the U.S.
Available Dosage Forms:
Pharmacologic Class: Alkylating Agent
Chemical Class: Nitrogen Mustard
Bendamustine belongs to the group of medicines called alkylating agents. It is used to treat a type of cancer of the white blood cells called chronic lymphocytic leukemia (CLL).
Bendamustine is also used to treat indolent B-cell non-Hodgkin's lymphoma (NHL) in patients who have already been treated with rituximab.
Bendamustine interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also be affected by the medicine, other effects may also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may occur after treatment with bendamustine has been stopped.
Before you begin treatment with bendamustine, you and your doctor should talk about the benefits bendamustine will have as well as the risks of using it.
bendamustine 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, bendamustine is used in certain patients with the following medical conditions:
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 bendamustine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to bendamustine 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 bendamustine in the pediatric population. Safety and efficacy have not been established.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of bendamustine in the elderly.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | D | Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. |
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 receiving bendamustine, 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 bendamustine 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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using bendamustine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use bendamustine, or give you special instructions about the use of food, alcohol, or tobacco.
The presence of other medical problems may affect the use of bendamustine. Make sure you tell your doctor if you have any other medical problems, especially:
You will receive bendamustine while you are in a hospital or cancer treatment center. A nurse or other trained health professional will give you bendamustine. bendamustine is given through a needle placed in one of your veins.
It is very important that your doctor check your progress at regular visits to make sure that bendamustine is working properly. Blood tests may be needed to check for unwanted effects.
Bendamustine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection (e.g., pneumonia). It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of an infection or bleeding:
bendamustine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have chills; fever; hives; hoarseness; itching; rash; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth after you receive the medicine.
bendamustine may cause a serious type of reaction called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this. Call your doctor right away if you have a decrease or change in urine amount; joint pain, stiffness, or swelling; lower back, side, or stomach pain; a rapid weight gain; swelling of the feet or lower legs; or unusual tiredness or weakness.
Using bendamustine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.
Serious skin reactions may occur during treatment with bendamustine. Tell your doctor right away if you have rashes or blisters while receiving bendamustine.
Bendamustine may cause some people to feel unusually tired or weak. Do not drive, use machines, or do anything else that could be dangerous while you are using bendamustine.
Cancer medicines can cause diarrhea, nausea, or vomiting in most people, sometimes even after receiving medicines to prevent it. Ask your doctor or nurse about other ways to control these side effects.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor 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: bendamustine Intravenous 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.
Romatim may be available in the countries listed below.
Diclofenac sodium salt (a derivative of Diclofenac) is reported as an ingredient of Romatim in the following countries:
International Drug Name Search
Dombaz may be available in the countries listed below.
Domperidone is reported as an ingredient of Dombaz in the following countries:
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bue-SUL-fan
Busulfan injection is a potent cytotoxic drug that causes profound myelosuppression at the recommended dosage. It should be administered under the supervision of a qualified physician who is experienced in allogeneic hematopoietic stem cell transplantation, the use of cancer chemotherapeutic drugs and the management patients with severe pancytopenia. Appropriate management of therapy and complications is only possible when adequate diagnostic and treatment facilities are readily available .
In the U.S.
Available Dosage Forms:
Therapeutic Class: Antineoplastic Agent
Pharmacologic Class: Alkylating Agent
Busulfan belongs to the group of medicines known as alkylating agents. It is used to treat some kinds of cancer of the blood. It may also be used as a conditioning regimen prior to progenitor cell transplantation for treatment of chronic myelogenous leukemia.
Busulfan seems to act by interfering with the function of the bone marrow. Since the growth of normal body cells may also be affected by busulfan, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.
Before you begin treatment with busulfan, you and your doctor should talk about the good busulfan will do as well as the risks of using it.
Busulfan 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 busulfan, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to busulfan 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 busulfan in children with use in other age groups, busulfan is not expected to cause different side effects or problems in children than it does in adults.
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 busulfan in the elderly with use in other age groups, busulfan is not expected to cause different side effects or problems in older people than it does in younger adults.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | D | Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. |
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 busulfan, 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 busulfan with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using busulfan 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.
Using busulfan with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
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 busulfan. Make sure you tell your doctor if you have any other medical problems, especially:
Take busulfan only as directed by your doctor. Do not take more or less of it, and do not take it more often than your doctor ordered. The exact amount of medicine you need has been carefully worked out. Taking too much may increase the chance of side effects, while taking too little may not improve your condition.
Take each dose at the same time each day to make sure it has the best effect.
While you are taking busulfan, your doctor may want you to drink extra fluids so that you will pass more urine. This will help prevent kidney problems and keep your kidneys working well.
busulfan sometimes causes nausea and vomiting. However, it is very important that you continue to use the medicine, even if you begin to feel ill. Do not stop taking busulfan without first checking with your doctor. Ask your health care professional for ways to lessen these effects.
If you vomit shortly after taking a dose of busulfan, check with your doctor. You will be told whether to take the dose again or to wait until the next scheduled dose.
Handle and dispose of busulfan with care as directed by your doctor.
The dose of busulfan 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 busulfan. 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 busulfan, 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.
It is very important that your doctor check your progress at regular visits to make sure that busulfan is working properly and to check for unwanted effects.
While you are being treated with busulfan, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Busulfan may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine within the last several months. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.
Busulfan can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:
Before you have any medical tests, tell the medical doctor in charge that you are taking busulfan. The results of some body tissue studies may be affected by busulfan.
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:
After you stop using busulfan, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:
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: busulfan Intravenous 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.
Satoren may be available in the countries listed below.
Losartan potassium salt (a derivative of Losartan) is reported as an ingredient of Satoren in the following countries:
International Drug Name Search
Rythmex may be available in the countries listed below.
Propafenone hydrochloride (a derivative of Propafenone) is reported as an ingredient of Rythmex in the following countries:
International Drug Name Search
Coltrax may be available in the countries listed below.
Thiocolchicoside is reported as an ingredient of Coltrax in the following countries:
International Drug Name Search
Pipermel may be available in the countries listed below.
Piperazine hexahydrate (a derivative of Piperazine) is reported as an ingredient of Pipermel in the following countries:
International Drug Name Search
Peptosyl may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Bentonite is reported as an ingredient of Peptosyl in the following countries:
Bismuth Subsalicylate is reported as an ingredient of Peptosyl in the following countries:
International Drug Name Search
Klacid Hp7 may be available in the countries listed below.
Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Klacid Hp7 in the following countries:
Clarithromycin is reported as an ingredient of Klacid Hp7 in the following countries:
Omeprazole is reported as an ingredient of Klacid Hp7 in the following countries:
International Drug Name Search
Micardis HCT is a brand name of hydrochlorothiazide/telmisartan, approved by the FDA in the following formulation(s):
No. There is currently no therapeutically equivalent version of Micardis HCT available.
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Micardis HCT. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
Patents are granted by the U.S. Patent and Trademark Office at any time during a drug's development and may include a wide range of claims.
Ticoflex may be available in the countries listed below.
Naproxen is reported as an ingredient of Ticoflex in the following countries:
International Drug Name Search
Metrima may be available in the countries listed below.
Clotrimazole is reported as an ingredient of Metrima in the following countries:
International Drug Name Search
Zemlon may be available in the countries listed below.
Sodium Alginate Sulfate is reported as an ingredient of Zemlon in the following countries:
International Drug Name Search
See also: Generic Kenalog-10
Kenalog-40 is a brand name of triamcinolone, approved by the FDA in the following formulation(s):
Yes. The following products are equivalent to Kenalog-40:
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Kenalog-40. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
There are no current U.S. patents associated with Kenalog-40.
Batroxobina may be available in the countries listed below.
Batroxobina (DCIT) is also known as Batroxobin (Rec.INN)
International Drug Name Search
Glossary
| DCIT | Denominazione Comune Italiana |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Pantoprazol Calox may be available in the countries listed below.
Pantoprazole is reported as an ingredient of Pantoprazol Calox in the following countries:
International Drug Name Search
In some countries, this medicine may only be approved for veterinary use.
Hygromycin B is reported as an ingredient of Hygromix Tylan in the following countries:
Tylosin is reported as an ingredient of Hygromix Tylan in the following countries:
International Drug Name Search
Neurelark may be available in the countries listed below.
Tiapride hydrochloride (a derivative of Tiapride) is reported as an ingredient of Neurelark in the following countries:
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Warfarin Sodium (BANM) is known as Warfarin in the US.
International Drug Name Search
Glossary
| BANM | British Approved Name (Modified) |
WARNING: LIFE THREATENING ADVERSE REACTIONS
Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When Depakote ER is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.
These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months [see Warnings and Precautions (5.1)].
Valproate can produce teratogenic effects such as neural tube defects (e.g., spina bifida). Accordingly, the use of Depakote ER in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus. This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is contemplated [see Warnings and Precautions(5.2)].
An information sheet describing the teratogenic potential of valproate is available for patients [see Patient Counseling Information(17)].
Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Patients and guardians should be warned that abdominal pain, nausea, vomiting and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated [see Warnings and Precautions (5.3)].
Depakote ER is a valproate and is indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. A mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode (depressed mood, loss of interest or pleasure in nearly all activities).
The efficacy of Depakote ER is based in part on studies of Depakote (divalproex sodium delayed release tablets) in this indication, and was confirmed in a 3-week trial with patients meeting DSM-IV TR criteria for bipolar I disorder, manic or mixed type, who were hospitalized for acute mania [see Clinical Studies (14.1)].
The effectiveness of valproate for long-term use in mania, i.e., more than 3 weeks, has not been demonstrated in controlled clinical trials. Therefore, healthcare providers who elect to use Depakote ER for extended periods should continually reevaluate the long-term risk-benefits of the drug for the individual patient.
Depakote ER is indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. Depakote ER is also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures in adults and children 10 years of age or older, and adjunctively in adults and children 10 years of age or older with multiple seizure types that include absence seizures.
Simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. Complex absence is the term used when other signs are also present.
Depakote ER is indicated for prophylaxis of migraine headaches. There is no evidence that Depakote ER is useful in the acute treatment of migraine headaches. Because it may be a hazard to the fetus, Depakote ER should be considered for women of childbearing potential only after this risk has been thoroughly discussed with the patient and weighed against the potential benefits of treatment [see Warnings and Precautions(5.2), Patient Counseling Information(17.3)].
Depakote ER is an extended-release product intended for once-a-day oral administration. Depakote ER tablets should be swallowed whole and should not be crushed or chewed.
Depakote ER tablets are administered orally. The recommended initial dose is 25 mg/kg/day given once daily. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In a placebo-controlled clinical trial of acute mania or mixed type, patients were dosed to a clinical response with a trough plasma concentration between 85 and 125 mcg/mL. The maximum recommended dosage is 60 mg/kg/day.
There is no body of evidence available from controlled trials to guide a clinician in the longer term management of a patient who improves during Depakote ER treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no data to support the benefits of Depakote ER in such longer-term treatment (i.e., beyond 3 weeks).
Depakote ER (divalproex sodium) extended release tablets are administered orally, and must be swallowed whole. As Depakote ER dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions (7.2)].
For adults and children 10 years of age or older.
Depakote ER has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.
The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.
Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 - 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.
Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of Depakote ER therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.
Depakote ER may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.
In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to valproate, no adjustment of carbamazepine or phenytoin dosage was needed [see Clinical Studies(14.3)]. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see Drug Interactions(7)].
Simple and Complex Absence Seizures
The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day.
A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentration for most patients with absence seizures is considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see Clinical Pharmacology(12.3)].
As Depakote ER dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see Drug Interactions(7.2)].
Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.
Depakote ER is indicated for prophylaxis of migraine headaches in adults.
The recommended starting dose is 500 mg once daily for 1 week, thereafter increasing to 1000 mg once daily. Although doses other than 1000 mg once daily of Depakote ER have not been evaluated in patients with migraine, the effective dose range of Depakote (divalproex sodium delayed-release tablets) in these patients is 500-1000 mg/day. As with other valproate products, doses of Depakote ER should be individualized and dose adjustment may be necessary. If a patient requires smaller dose adjustments than that available with Depakote ER, Depakote should be used instead.
In adult patients and pediatric patients 10 years of age or older with epilepsy previously receiving Depakote, Depakote ER should be administered once-daily using a dose 8 to 20% higher than the total daily dose of Depakote (Table 1). For patients whose Depakote total daily dose cannot be directly converted to Depakote ER, consideration may be given at the clinician’s discretion to increase the patient’s Depakote total daily dose to the next higher dosage before converting to the appropriate total daily dose of Depakote ER.
| Depakote | Depakote ER |
| Total Daily Dose (mg) | (mg) |
| 500* - 625 | 750 |
| 750* - 875 | 1000 |
| 1000*-1125 | 1250 |
| 1250-1375 | 1500 |
| 1500-1625 | 1750 |
| 1750 | 2000 |
| 1875-2000 | 2250 |
| 2125-2250 | 2500 |
| 2375 | 2750 |
| 2500-2750 | 3000 |
| 2875 | 3250 |
| 3000-3125 | 3500 |
| * These total daily doses of Depakote cannot be directly converted to an 8 to 20% higher total daily dose of Depakote ER because the required dosing strengths of Depakote ER are not available. Consideration may be given at the clinician's discretion to increase the patient's Depakote total daily dose to the next higher dosage before converting to the appropriate total daily dose of Depakote ER. | |
There is insufficient data to allow a conversion factor recommendation for patients with DEPAKOTE doses above 3125 mg/day. Plasma valproate Cmin concentrations for Depakote ER on average are equivalent to DEPAKOTE, but may vary across patients after conversion. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL) [see Clinical Pharmacology(12.2)].
Due to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Starting doses in the elderly lower than 250mg can only be achieved by the use of Depakote. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see Warnings and Precautions (5.12)].
Dose-Related Adverse Reactions
The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see Warnings and Precautions (5.6)]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.
Patients who experience G.I. irritation may benefit from administration of the drug with food or by slowly building up the dose from an initial low level.
Patients should be informed to take Depakote ER every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.
Depakote ER 250 mg is available as white ovaloid tablets with the corporate Abbott “A” logo, and the Abbo-Code (HF). Each Depakote ER tablet contains divalproex sodium equivalent to 250 mg of valproic acid.
Depakote ER 500 mg is available as gray ovaloid tablets with the corporate Abbott “A” logo, and the Abbo-Code HC. Each Depakote ER tablet contains divalproex sodium equivalent to 500 mg of valproic acid.
Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months. However, healthcare providers should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination.
Caution should be observed when administering valproic acid products to patients with a prior history of hepatic disease. Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk. Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions. When Depakote ER is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above this age group, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.
The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent. In some cases, hepatic dysfunction has progressed in spite of discontinuation of drug [see Boxed Warning and Contraindications (4)].
Use of Depakote ER during pregnancy can cause congenital malformations including neural tube defects. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Depakote ER should be considered for women of childbearing potential only after the risks have been thoroughly discussed with the patient and weighed against the potential benefits of treatment.
Data suggest that there is an increased incidence of congenital malformations associated with the use of valproate by women with seizure disorders during pregnancy when compared to the incidence in women with seizure disorders who do not use antiepileptic drugs during pregnancy, the incidence in women with seizure disorders who use other antiepileptic drugs, and the background incidence for the general population.
The data described below were gained almost exclusively from women who received valproate to treat epilepsy. There are multiple reports in the clinical literature that indicate the use of antiepileptic drugs during pregnancy results in an increased incidence of congenital malformations in offspring. Antiepileptic drugs, including valproate, should be administered to women of childbearing potential only if they are clearly shown to be essential in the management of their medical condition.
There have been reports of developmental delay, autism and/or autism spectrum disorder in the offspring of women exposed to valproate during pregnancy.
Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus [see Boxed Warning and Use in Specific Populations (8.1)].
Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death. Some cases have occurred shortly after initial use as well as after several years of use. The rate based upon the reported cases exceeds that expected in the general population and there have been cases in which pancreatitis recurred after rechallenge with valproate. In clinical trials, there were 2 cases of pancreatitis without alternative etiology in 2416 patients, representing 1044 patient-years experience. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, Depakote ER should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated [see Boxed Warning].
Depakote ER is contraindicated in patients with known urea cycle disorders (UCD). Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of Depakote ER therapy, evaluation for UCD should be considered in the following patients: 1) those with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2) those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance; 3) those with a family history of UCD or a family history of unexplained infant deaths (particularly males); 4) those with other signs or symptoms of UCD. Patients who develop symptoms of unexplained hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment (including discontinuation of valproate therapy) and be evaluated for underlying urea cycle disorders [see Contraindications (4) and Warnings and Precautions (5.7)].
Antiepileptic drugs (AEDs), including Depakote ER, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.
Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
| Indication | Placebo Patients with Events Per 1000 Patients | Drug Patients with Events Per 1000 Patients | Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients | Risk Difference: Additional Drug Patients with Events Per 1000 Patients |
| Epilepsy | 1.0 | 3.4 | 3.5 | 2.4 |
| Psychiatric | 5.7 | 8.5 | 1.5 | 2.9 |
| Other | 1.0 | 1.8 | 1.9 | 0.9 |
| Total | 2.4 | 4.3 | 1.8 | 1.9 |
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Depakote ER or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. In a clinical trial of valproate as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets ≤ 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males). The therapeutic benefit which may accompany the higher doses should therefore be weighed against the possibility of a greater incidence of adverse effects.
Because of reports of thrombocytopenia, inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters, (e.g., low fibrinogen), platelet counts and coagulation tests are recommended before initiating therapy and at periodic intervals. It is recommended that patients receiving Depakote ER be monitored for platelet count and coagulation parameters prior to planned surgery. Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy.
Hyperammonemia has been reported in association with valproate therapy and may be present despite normal liver function tests. In patients who develop unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. Hyperammonemia should also be considered in patients who present with hypothermia [see Warnings and Precautions (5.9)]. If ammonia is increased, valproate therapy should be discontinued. Appropriate interventions for treatment of hyperammonemia should be initiated, and such patients should undergo investigation for underlying urea cycle disorders [see Contraindications and Warnings and Precautions (4, 5.4, 5.8)].
During the placebo controlled pediatric mania trial, one (1) in twenty (20) adolescents (5%) treated with valproate developed increased plasma ammonia levels compared to no (0) patients treated with placebo.
Asymptomatic elevations of ammonia are more common and when present, require close monitoring of plasma ammonia levels. If the elevation persists, discontinuation of valproate therapy should be considered.
Concomitant administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. Clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting. Hypothermia can also be a manifestation of hyperammonemia [see Warnings and Precautions (5.9)]. In most cases, symptoms and signs abated with discontinuation of either drug. This adverse event is not due to a pharmacokinetic interaction. It is not known if topiramate monotherapy is associated with hyperammonemia. Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at an increased risk for hyperammonemia with or without encephalopathy. Although not studied, an interaction of topiramate and valproic acid may exacerbate existing defects or unmask deficiencies in susceptible persons. In patients who develop unexplained lethargy, vomiting, or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured [see Contraindications (4) and Warnings and Precautions (5.7)].
Hypothermia, defined as an unintentional drop in body core temperature to < 35° C (95° F), has been reported in association with valproate therapy both in conjunction with and in the absence of hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate with valproate after starting topiramate treatment or after increasing the daily dose of topiramate [see Drug Interactions (7.3)]. Consideration should be given to stopping valproate in patients who develop hypothermia, which may be manifested by a variety of clinical abnormalities including lethargy, confusion, coma, and significant alterations in other major organ systems such as the cardiovascular and respiratory systems. Clinical management and assessment should include examination of blood ammonia levels.
Multi-organ hypersensitivity reactions have been rarely reported in close temporal association to the initiation of valproate therapy in adult and pediatric patients (median time to detection 21 days: range 1 to 40 days). Although there have been a limited number of reports, many of these cases resulted in hospitalization and at least one death has been reported. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations may include lymphadenopathy, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, thrombocytopenia, neutropenia), pruritus, nephritis, oliguria, hepato-renal syndrome, arthralgia, and asthenia. Because the disorder is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If this reaction is suspected, valproate should be discontinued and an alternative treatment started. Although the existence of cross sensitivity with other drugs that produce this syndrome is unclear, the experience amongst drugs associated with multi-organ hypersensitivity would indicate this to be a possibility.
Carbapenem antibiotics (ertapenem, imipenem, meropenem) may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop significantly or seizure control deteriorates [see Drug Interactions (7.1)].
In a double-blind, multicenter trial of valproate in elderly patients with dementia (mean age = 83 years), doses were increased by 125 mg/day to a target dose of 20 mg/kg/day. A significantly higher proportion of valproate patients had somnolence compared to placebo, and although not statistically significant, there was a higher proportion of patients with dehydration. Discontinuations for somnolence were also significantly higher than with placebo. In some patients with somnolence (approximately one-half), there was associated reduced nutritional intake and weight loss. There was a trend for the patients who experienced these events to have a lower baseline albumin concentration, lower valproate clearance, and a higher BUN. In elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence [see Dosage and Administration(2.4)].
Since valproic acid may interact with concurrently administered drugs which are capable of enzyme induction, periodic plasma concentration determinations of valproate and concomitant drugs are recommended during the early course of therapy [see Drug Interactions (7)].
Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test.
There have been reports of altered thyroid function tests associated with valproate. The clinical significance of these is unknown.
There are in vitro studies that suggest valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequence, if any, is not known. Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. Nevertheless, these data should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Information on pediatric adverse reactions is presented in section 8.
The incidence of treatment-emergent events has been ascertained based on combined data from two three week placebo-controlled clinical trials of Depakote ER in the treatment of manic episodes associated with bipolar disorder.
Table 3 summarizes those adverse reactions reported for patients in these trials where the incidence rate in the Depakote ER-treated group was greater than 5% and greater than the placebo incidence.
| Adverse Event | Depakote ER (n=338) | Placebo (n=263) |
| Somnolence | 26% | 14% |
| Dyspepsia | 23% | 11% |
| Nausea | 19% | 13% |
| Vomiting | 13% | 5% |
| Diarrhea | 12% | 8% |
| Dizziness | 12% | 7% |
| Pain | 11% | 10% |
| Abdominal pain | 10% | 5% |
| Accidental injury | 6% | 5% |
| Asthenia | 6% | 5% |
| Pharyngitis | 6% | 5% |
| 1. The following adverse reactions/event occurred at an equal or greater incidence for placebo than for Depakote ER: headache | ||
The following additional adverse reactions were reported by greater than 1% but not more than 5% of the Depakote ER-treated patients in controlled clinical trials:
Body as a Whole: Back Pain, Flu Syndrome, Infection, Infection Fungal
Cardiovascular System: Hypertension
Digestive System: Constipation, Dry Mouth, Flatulence
Hemic and Lymphatic System: Ecchymosis
Metabolic and Nutritional Disorders Peripheral Edema
Musculoskeletal System: Myalgia
Nervous System: Abnormal Gait, Hypertonia, Tremor
Skin and Appendages: Pruritus, Rash
Special Senses: Conjunctivitis
Urogenital System: Urinary Tract Infection, Vaginitis
Based on a placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures, Depakote was generally well tolerated with most adverse reactions rated as mild to moderate in severity. Intolerance was the primary reason for discontinuation in the Depakote-treated patients (6%), compared to 1% of placebo-treated patients.
Table 4 lists treatment-emergent adverse reactions which were reported by ≥ 5% of Depakote-treated patients and for which the incidence was greater than in the placebo group, in the placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures. Since patients were also treated with other antiepilepsy drugs, it is not possible, in most cases, to determine whether the following adverse reactions can be ascribed to Depakote alone, or the combination of Depakote and other antiepilepsy drugs.
| Body System/Event | Depakote (%) (N=77) | Placebo (%) (N=70) |
| Body as a Whole | ||
| Headache | 31 | 21 |
| Asthenia | 27 | 7 |
| Fever | 6 | 4 |
| Gastrointestinal System | ||
| Nausea | 48 | 14 |
| Vomiting | 27 | 7 |
| Abdominal pain | 23 | 6 |
| Diarrhea | 13 | 6 |
| Anorexia | 12 | 0 |
| Dyspepsia | 8 | 4 |
| Constipation | 5 | 1 |
| Nervous System | ||
| Somnolence | 27 | 11 |
| Tremor | 25 | 6 |
| Dizziness | 25 | 13 |
| Diplopia | 16 | 9 |
| Amblyopia/Blurred Vision | 12 | 9 |
| Ataxia | 8 | |
