Symbicort 200 Turbuhaler

Generic Name: budesonide and formoterol (Inhalation route)

bue-DES-oh-nide, for-MOE-ter-ol FUE-ma-rate

Commonly used brand name(s)

In the U.S.

• Symbicort

In Canada

• Symbicort 100 Turbuhaler


• Symbicort 200 Turbuhaler

Available Dosage Forms:

• Aerosol Liquid


• Powder

Therapeutic Class: Antiasthma, Anti-Inflammatory/Bronchodilator Combination

Pharmacologic Class: Adrenal Glucocorticoid

Uses For Symbicort 200 Turbuhaler

Budesonide and formoterol is a combination of two medicines that are used to help control the symptoms of asthma and improve lung function. It is used when a patient's asthma has not been controlled sufficiently on other asthma medicines, or when a patient's condition is so severe that more than one medicine is needed every day. This medicine will not relieve an asthma attack that has already started.

This medicine is also used to treat air flow blockage and reduce the worsening of chronic obstructive pulmonary disease (COPD). This includes chronic bronchitis and emphysema.

Inhaled budesonide belongs to the family of medicines known as corticosteroids (cortisone-like medicines). It works by preventing inflammation (swelling) in the lungs that causes an asthma attack.

Inhaled formoterol belongs to the family of medicines known as bronchodilators. It works by helping the muscles around the airways in your lungs stay relaxed to prevent asthma symptoms, such as wheezing and shortness of breath.

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

Before Using Symbicort 200 Turbuhaler

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

Allergies

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

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of budesonide and formoterol combination in children. However, safety and efficacy have not been established in children younger than 12 years of age. .

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of budesonide and formoterol combination in the elderly. However, elderly patients with heart problems may require special caution when receiving budesonide and formoterol combination.

Pregnancy

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

Breast Feeding

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

Interactions with Medicines

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

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

• Acebutolol


• Alprenolol


• Arotinolol


• Atenolol


• Befunolol


• Betaxolol


• Bevantolol


• Bisoprolol


• Boceprevir


• Bopindolol


• Brofaromine


• Bucindolol


• Bupranolol


• Bupropion


• Carteolol


• Carvedilol


• Celiprolol


• Clorgyline


• Dilevalol


• Esmolol


• Furazolidone


• Iproniazid


• Isocarboxazid


• Labetalol


• Landiolol


• Lazabemide


• Levobetaxolol


• Levobunolol


• Linezolid


• Mepindolol


• Metipranolol


• Metoprolol


• Moclobemide


• Nadolol


• Nebivolol


• Nialamide


• Nipradilol


• Oxprenolol


• Pargyline


• Penbutolol


• Phenelzine


• Pindolol


• Procarbazine


• Propranolol


• Rasagiline


• Selegiline


• Sotalol


• Talinolol


• Telaprevir


• Tertatolol


• Timolol


• Toloxatone


• Tranylcypromine

Using this medicine 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.

• Erythromycin


• Itraconazole


• Ketoconazole

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Asthma attack, acute or


• Bronchospasm (difficulty with breathing), acute or


• COPD flare-up—Should not be used in patients with these conditions.

• Bone problems (e.g., osteoporosis) or


• Cataracts or


• Glaucoma or


• Heart or blood vessel disease or


• Heart rhythm problems or


• Hypertension (high blood pressure) or


• Hypokalemia (low potassium in the blood) or


• Immune system problem (e.g., Churg-Strauss syndrome) or


• Seizures or


• Thyroid problems—Use with caution. May make these conditions worse.

• Chickenpox (including recent exposure) or


• Measles or


• Herpes simplex (virus) infection of the eye or


• Infections (virus, bacteria, or fungus) or


• Tuberculosis, active or history of—Can reduce the body's ability to fight off these infections.

• Diabetes mellitus or


• Hyperglycemia (high glucose in the blood) or


• Ketoacidosis (high ketones in the blood)—Blood sugar levels may increase.

• Infection or


• Stress or


• Surgery or


• Trauma—Oral corticosteroids may be needed during these periods. Check with your doctor.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of budesonide and formoterol

This section provides information on the proper use of a number of products that contain budesonide and formoterol. It may not be specific to Symbicort 200 Turbuhaler. Please read with care.

This medicine is used with a special inhaler and usually comes with patient directions or a Medication Guide. Read the directions carefully before using this medicine. If you do not understand the directions or you are not sure how to use the inhaler, ask your doctor or pharmacist to show you what to do.

Use this medicine only as directed. Do not use more of it and do not use it more often than your doctor ordered. Also, do not stop taking this medicine without telling your doctor. To do so may increase the chance of side effects.

When you use the inhaler for the first time, or if you have not used it for 7 days or longer, or if the inhaler has been dropped, it may not deliver the right amount of medicine with the first puff. Therefore, before using the inhaler, prime it by spraying the medicine two times into the air away from the face, and shaking it well for 5 seconds before each spray.

How to use this medicine:

• Take the inhaler out of the moisture-protective foil pouch before you use it for the first time.


• Do not use the inhaler for this medicine with any other medicine.


• Prime the inhaler before use by shaking the inhaler well for 5 seconds and then releasing a test spray. Once again, shake the inhaler and release a second test spray.


• Breathe out to the end of a normal breath (exhale). Do not breathe into the inhaler.


• Holding the inhaler level, put the mouthpiece fully into your mouth and close your lips around it. Do not block the mouthpiece with your teeth or tongue.


• While pressing down firmly and fully on the grey top of the inhaler, breathe in through your mouth as deeply as you can until you have taken a full deep breath.


• Hold your breath and remove the mouthpiece from your mouth. Continue holding your breath as long as you can up to 10 seconds before breathing out slowly. This gives the medicine time to settle in your airways and lungs.


• Release your finger from the grey top and then turn your head away from the inhaler. Breathe out slowly to the end of a normal breath. Do not breathe into the inhaler.


• Shake the inhaler again for 5 seconds and take the second puff following exactly the same steps you used for the first puff.


• Replace the mouthpiece cover after using the medicine.


• Gargle and rinse your mouth with water after each dose; this will help prevent hoarseness, throat irritation, and infection in the mouth. Do not swallow the water after rinsing.

Each inhaler comes with a dose tracker card to track the number of puffs you have used. Mark off or punch through each of your morning and evening doses. You must discard the inhaler after you have used the number of inhalations on the product label and box, or within 3 months of opening the foil pouch.

Clean the inhaler every 7 days by wiping the mouthpiece with dry cloth. However, you must use a new inhaler with each refill of your medicine.

Dosing

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

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

• For inhalation dosage form (aerosol):
  
  • For preventing an asthma attack:
    
    • Adults and children 12 years of age and older—Two puffs in the morning and another 2 puffs in the evening. Each puff contains 80 or 160 micrograms (mcg) of budesonide and 4.5 mcg of formoterol.
    
    
    • Children younger than 12 years of age—Use and dose must be determined by your child's doctor.
    
    
  
  
  • For treatment of COPD:
    
    • Adults—Two puffs in the morning and another 2 puffs in the evening. Each puff contains 160 micrograms (mcg) of budesonide and 4.5 mcg of formoterol.
    
    
    • Children 12 years of age and older—Not used for COPD in this age group.
    
    
    • Children younger than 12 years of age—Not used for COPD in this age group.
    
    
  
  

Missed Dose

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

Storage

Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.

Keep 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.

When you store the inhaler, make sure to always place the mouthpiece down.

Precautions While Using Symbicort 200 Turbuhaler

It is very important that your doctor check the progress of you or your child at regular visits, to make sure that this medicine is working properly and to check for any unwanted effects that may be caused by this medicine. You may need to have your eyes checked at regular visits. Be sure to keep all appointments.

Although this medicine decreases the number of asthma episodes, it may increase the chances of a severe asthma episode when they do occur. Talk to your doctor about any questions or concerns that you have.

This should not be the first and only medicine you use for asthma or COPD. This medicine will not stop an asthma attack that has already started. Your doctor may prescribe another medicine for you to use in case of an acute asthma attack or an acute COPD flare-up. If the other medicine does not work as well, tell your doctor right away.

Take all of your COPD medicines as your doctor ordered. If you use any type of corticosteroid medicine to control your breathing, keep using it as ordered by your doctor. Do not change your doses or stop using your medicines without asking your doctor.

You or your child should not use this medicine if your asthma attack has already started or if you already have a severe asthma attack. Your doctor may prescribe another medicine (e.g., a short-acting inhaler) for you to use in case of an acute asthma attack. Call your doctor immediately for instructions.

Do not use any other asthma medicine or medicine for breathing problems without talking to your doctor. This medicine should not be used with salmeterol (Serevent®), formoterol (Perforomist™), or arformoterol (Brovana®) inhalers.

Talk to your doctor or get medical care right away if:

• Your or your child's symptoms do not improve after using this medicine for 1 week or if they become worse.


• Your short-acting inhaler does not seem to be working as well as usual and you need to use it more often (e.g.; you use 1 whole canister of your short-acting inhaler in 8 weeks time, or you need to use 4 or more inhalations of your short-acting inhaler for 2 or more days in a row).


• You or your child have a significant decrease in your peak flow when measured as directed by your doctor.

You may get infections more easily while using this medicine. Tell your doctor right away if you or your child have been exposed to someone with chickenpox or measles.

This medicine may cause fungus infection of the mouth or throat (thrush). Tell your doctor right away if you have white patches in the mouth or throat; or pain when eating or swallowing.

Patients with COPD may be more likely to have pneumonia when taking this medicine. Check with your doctor if you start having increased sputum (spit) production, change in sputum color, fever, chills, increased cough, or an increase in breathing problems.

Using too much of this medicine or using it for a long time may increase your risk of having adrenal gland problems. Talk to your doctor if you or your child have more than one of these symptoms while you are using this medicine: darkening of the skin; diarrhea; dizziness; fainting; loss of appetite; mental depression; nausea; skin rash; unusual tiredness or weakness; or vomiting.

This medicine may cause paradoxical bronchospasm, which may be life-threatening. Check with your doctor right away if you are having a cough, difficulty with breathing, shortness of breath, or wheezing.

If you or your child develop a skin rash, hives, or any allergic reaction to this medicine, stop taking the medicine and check with your doctor as soon as possible.

This medicine may decrease bone mineral density when used for a long time. A low bone mineral density can cause weak bones or osteoporosis. If you have any questions about this, ask your doctor.

This medicine may cause children to grow more slowly than usual. Talk to your child's doctor if you have any concerns.

This medicine may affect blood sugar and potassium levels. If you notice a change in the results of your blood or urine sugar or potassium tests or if you have any questions, check with your doctor.

Your doctor may want you to carry a medical identification card stating that you or your child are using this medicine and that you may need additional medicine during times of emergency, a severe asthma attack or other illness, or unusual stress.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Symbicort 200 Turbuhaler Side Effects

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

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

More common

• Body aches or pain


• chills


• cough, fever, sneezing, or sore throat


• difficulty with breathing


• ear congestion


• fever


• headache


• loss of voice


• muscle aches


• pain or tenderness around the eyes and cheekbones


• shortness of breath or troubled breathing


• stuffy or runny nose


• tightness of the chest or wheezing


• unusual tiredness or weakness

Less common

• Abdominal or stomach pain


• bladder pain


• bloody or cloudy urine


• congestion


• cough producing mucus


• diarrhea


• difficult, burning, or painful urination


• dryness of the throat


• fast, irregular, pounding, or racing heartbeat or pulse


• frequent urge to urinate


• general feeling of discomfort or illness


• hoarseness


• joint pain


• loss of appetite


• lower back or side pain


• nausea


• noisy breathing


• shakiness in the legs, arms, hands, or feet


• shivering


• sore mouth or tongue


• sweating


• tender, swollen glands in the neck


• trembling or shaking of the hands or feet


• trouble with swallowing


• trouble with sleeping


• voice changes


• vomiting


• white patches in the mouth or on the tongue

Rare

• Blurred vision


• confusion


• decreased urine


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


• dry mouth


• enlarged pupils


• fainting


• flushed, dry skin


• fruit-like breath odor


• increased hunger


• increased sensitivity of the eyes to light


• increased sweating, possibly with fever or cold, clammy skin


• increased thirst


• increased urination


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• mood changes


• muscle cramps


• nervousness


• numbness or tingling in the hands, feet, or lips


• pounding in the ears


• seizures


• severe chest pain


• severe headache


• slow, fast, pounding, or irregular heartbeat or pulse


• stiff or sore neck


• unexplained weight loss

Incidence not known

• Blindness


• decreased vision


• eye pain


• puffiness or swelling of the eyelids or around the eyes, face, lips or tongue


• tearing

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Arm, back, or jaw pain


• chest pain or discomfort


• darkening of the skin


• drowsiness


• mental depression


• rapid, deep breathing


• restlessness


• skin rash


• sleeplessness


• stomach cramps


• unable to sleep

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

More common

• Stomach discomfort

Less common

• Acid or sour stomach


• belching


• difficulty with moving


• heartburn


• indigestion


• muscle spasms or stiffness


• pain in the arms or legs


• stomach upset


• swollen joints

Rare

• Bad, unusual, or unpleasant (after) taste


• change in taste


• deep or fast breathing with dizziness, numbness to feet, hands, and around the mouth


• fear


• hives or welts


• irritability


• itching skin


• large, flat, blue, or purplish patches in the skin


• redness of the skin

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: Symbicort 200 Turbuhaler side effects (in more detail)

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

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

More Symbicort 200 Turbuhaler resources

• Symbicort 200 Turbuhaler Side Effects (in more detail)
• Symbicort 200 Turbuhaler Use in Pregnancy & Breastfeeding
• Symbicort 200 Turbuhaler Drug Interactions
• Symbicort 200 Turbuhaler Support Group
• 31 Reviews for Symbicort 200 Turbuhaler - Add your own review/rating

Compare Symbicort 200 Turbuhaler with other medications

• Asthma, Maintenance
• COPD
• COPD, Maintenance

Epivir A/F

Generic Name: lamivudine (Oral route)

la-MIV-ue-deen

Oral route(Tablet;Solution)

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Severe acute exacerbations of hepatitis B have been reported in patients who have hepatitis B infection or are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine; monitor hepatic function upon discontinuation of therapy. EPIVIR(R) tablets and oral solution (used to treat HIV-1 infection) contain a higher dose of the active ingredient (lamivudine) than EPIVIR-HBV(R) tablets and oral solution (used to treat chronic hepatitis B). Patients with HIV infection should receive only dosage forms appropriate for treatment of HIV-1. EPIVIR-HBV(R) tablets and oral solution contain a lower dose of the same active ingredient (lamivudine) as EPIVIR(R) tablets and oral solution used to treat HIV infection. If treatment with EPIVIR-HBV(R) is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely because of subtherapeutic dose and inappropriate monotherapy .

Commonly used brand name(s)

In the U.S.

• Epivir


• Epivir A/F


• Epivir HBV

In Canada

• 3tc


• Heptovir

Available Dosage Forms:

• Solution


• Tablet

Therapeutic Class: Antiretroviral Agent

Pharmacologic Class: Nucleoside Reverse Transcriptase Inhibitor

Uses For Epivir A/F

Lamivudine is used in the treatment of the infection caused by the human immunodeficiency virus (HIV) or hepatitis B virus. HIV is the virus that causes acquired immune deficiency syndrome (AIDS). Lamivudine is taken together with zidovudine (AZT) or other medications used to treat HIV.

Lamivudine will not cure or prevent HIV infection or AIDS; however, it helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay the development of problems usually related to AIDS or HIV disease. Lamivudine will not keep you from spreading HIV to other people. People who receive this medicine may continue to have other problems usually related to AIDS or HIV disease. Lamivudine is not a cure for the hepatitis B virus; the long-term effects of the drug on the infection and the liver are unknown at this time.

Lamivudine 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 this use is not included in product labeling, lamivudine is used in certain patients with the following medical condition:

• Human immunodeficiency virus (HIV) infection due to occupational exposure (possible prevention of)

Before Using Epivir A/F

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

Allergies

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

Pediatric

Lamivudine can cause serious side effects. In one study, children with advanced AIDS were more likely than children who were less ill to develop pancreatitis (inflammation of the pancreas) and peripheral neuropathy (a problem involving the nerves). Therefore, it is especially important that you discuss with your child's doctor the good that this medicine may do as well as the risks of using it. Your child must be seen frequently and your child's progress carefully followed by the doctor while the child is taking lamivudine.

Geriatric

Lamivudine has not been studied specifically in older people. Therefore, it is not known whether it causes different side effects or problems in the elderly than it does in younger adults. Talk to your doctor first if you have liver, kidney, heart problems or other diseases. Your doctor may need to adjust your dose.

Pregnancy

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

Breast Feeding

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

Interactions with Medicines

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

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

• Interferon Alfa


• Ribavirin


• Zalcitabine

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Combined infection of HIV and hepatitis B—May make the condition of either of these infections worse

• Diabetes mellitus (sugar diabetes)—Lamivudine oral solution contains sucrose

• Hepatitis C or


• Hepatitis delta—Caution should be used; lamivudine safety has not been determined in patients who have hepatitis infections

• Human immunodeficiency virus—For patients with hepatitis B virus, your physician will talk to you about HIV before you begin taking lamivudine. You may be tested for HIV. Lamivudine tablets and oral solution for hepatitis B virus contain lower amounts of the drug than the tablets and solution for HIV. If you start on the lower-dose medication and later learn that you have HIV, the higher-dose lamivudine may not then be effective against the infection caused by HIV.


• Inflamed pancreas or


• Problems with inflamed pancreas in the past or


• Other risk factors for developing an inflamed pancreas or


• Nerve damage—These conditions may occur or worsen when taking lamivudine

• Kidney disease—Patients with kidney disease may have an increased chance of side effects

• Liver disease or


• Risk factors for liver disease or


• Obesity (being overweight)—This medicine may make liver disease worse in patients with liver disease, obesity and other HIV medicine use.

• Organ transplant—Caution should be used; lamivudine safety has not been determined in patients who have received an organ transplant

Proper Use of lamivudine

This section provides information on the proper use of a number of products that contain lamivudine. It may not be specific to Epivir A/F. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not stop taking lamivudine or zidovudine without checking with your doctor first.

Keep taking lamivudine for the full time of treatment , even if you begin to feel better.

This medicine works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses . If you need help in planning the best times to take your medicine, check with your health care professional.

If you are using lamivudine oral suspension, use a specially marked measuring spoon or other device to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid. The lamivudine oral suspension contains sucrose. Tell your doctor if you are diabetic before you start taking this medicine.

Only take medicine that your doctor has prescribed specifically for you. Do not share your medicine with others.

Dosing

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

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

• For oral dosage forms (oral solution and tablets):
  
  • For treatment of hepatitis B infection:
    
    • Adults —100 milligrams (mg) once a day.
    
    
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.
    
    
  
  
  • For treatment of HIV infection or AIDS:
    
    • Adults weighing 50 kilograms (kg) (110 pounds) or more—150 milligrams (mg) twice a day together with other HIV medications.
    
    
    • Adults weighing less than 50 kg (110 pounds)—2 mg per kg of body weight twice a day together with other HIV medications.
    
    
    • Children 3 months to 16 years of age—4 mg per kg of body weight, up to 150 mg per dose, twice a day together with other HIV medications.
    
    
    • Children younger than 3 months of age—Use and dose must be determined by your doctor.
    
    
  
  

Note: Patients that require treatment for both hepatitis B and either AIDS or HIV should follow the dosing schedule for HIV or AIDS

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Epivir A/F

It is very important that your doctor check your progress at regular visits.

Do not take any other medicines without checking with your doctor first. To do so may increase the chance of side effects from lamivudine.

If you have both HIV and hepatitis B virus (HBV) infections, deterioration of liver disease has occurred when lamivudine treatment is stopped. Discuss any changes in your treatment and medicines with your doctor.

HIV may be acquired from or spread to other people through infected body fluids, including blood, vaginal fluid, or semen. If you are infected, it is best to avoid any sexual activity involving an exchange of body fluids with other people. If you do have sex, always wear (or have your partner wear) a condom (“rubber”). Only use condoms made of latex, and use them every time you have vaginal, anal, or oral sex. The use of a spermicide (such as nonoxynol-9) may also help prevent transmission of HIV if it is not irritating to the vagina, rectum, or mouth. Spermicides have been shown to kill HIV in lab tests. Do not use oil-based jelly, cold cream, baby oil, or shortening as a lubricant—these products can cause the condom to break. Lubricants without oil, such as K-Y Jelly, are recommended. Women may wish to carry their own condoms. Birth control pills and diaphragms will help protect against pregnancy, but they will not prevent someone from giving or getting the AIDS virus. If you inject drugs, get help to stop. Do not share needles or equipment with anyone. In some cities, more than half of the drug users are infected, and sharing even 1 needle or syringe can spread the virus. If you have any questions about this, check with your health care professional.

Epivir A/F Side Effects

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

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

More common—especially in children

• Abdominal or stomach pain (severe)


• feeling of fullness


• nausea


• sensation or pins and needles


• skin rash


• stabbing pain


• tingling, burning, numbness, or pain in the hands, arms, feet, or legs


• unsteadiness or awkwardness


• vomiting

Rare

• Abdominal discomfort


• decreased appetite


• diarrhea


• fast, shallow breathing


• feeling of fullness


• fever, chills, or sore throat


• general feeling of discomfort


• muscle pain or cramping


• nausea


• shortness of breath


• sleepiness


• unusual tiredness or weakness

Incidence not determined

• Cough


• dark urine


• difficulty swallowing


• dizziness


• fast heartbeat


• fever


• hives or welts


• itching


• light-colored stools


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• redness of skin


• tightness in chest


• upper right abdominal pain


• wheezing


• yellow eyes and skin

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

More common

• Canker sores


• difficulty in moving


• discouragement


• ear discharge


• ear swelling


• feeling sad or empty


• general feeling of discomfort or illness


• irritability


• loss of appetite


• loss of interest or pleasure


• nasal discharge or congestion


• pain in joints


• sores, ulcers, or white spots on lips or tongue or inside the mouth


• stomach pain or cramps


• swollen and painful spots on neck, armpit, or groin


• swollen joints


• trouble concentrating


• trouble sleeping


• unusually warm skin


• weight loss

Less common

• Acid or sour stomach


• belching


• cough


• heartburn


• indigestion


• stomach discomfort or upset

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: Epivir A/F side effects (in more detail)

Incidence not determined

• Body fat redistribution or accumulation


• blurred vision


• dry mouth


• flushed, dry skin


• fruit-like breath odor


• hair loss


• increased hunger or thirst


• increased urination


• sweating


• thinning of hair

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

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

More Epivir A/F resources

• Epivir A/F Side Effects (in more detail)
• Epivir A/F Use in Pregnancy & Breastfeeding
• Drug Images
• Epivir A/F Drug Interactions
• Epivir A/F Support Group
• 1 Review for Epivir A/F - Add your own review/rating

Compare Epivir A/F with other medications

• Hepatitis B
• HIV Infection
• Nonoccupational Exposure
• Occupational Exposure

Acetasol HC otic

Generic Name: acetic acid and hydrocortisone (otic) (as SEET ik AS sid and hy dro KOR ti zone)

Brand Names: Acetasol HC

What is Acetasol HC (acetic acid and hydrocortisone (otic))?

Acetic acid fights bacteria.

Hydrocortisone is a steroid. It reduces the actions of chemicals in the body that cause inflammation, redness, and swelling.

The combination of acetic acid and hydrocortisone otic is used to treat conditions inside the ear, such as redness, itching, or swelling.

Acetic acid and hydrocortisone otic may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Acetasol HC (acetic acid and hydrocortisone (otic))?

Before using this medication, tell your doctor if you have a ruptured ear drum. Tell your doctor if you have had any other ear infections or conditions before getting the condition for which you are now being treated. Hydrocortisone can make a pre-existing infection worse.

Do not use acetic acid and hydrocortisone otic on a child younger than 3 years old without a doctor's advice.

Use this medication exactly as it was prescribed for you. Do not use it in larger amounts or for longer than recommended by your doctor.

There may be other drugs that can affect acetic acid and hydrocortisone otic. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Stop using this medication and get emergency medical help if you think you have used too much medicine, or if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Less serious side effects are more likely, and you may have none at all. Talk to your doctor about any side effect that seems unusual or is especially bothersome.

Call your doctor if your symptoms do not improve or if they get worse during the first 5 to 7 days of treatment with acetic acid and hydrocortisone otic.

What should I discuss with my health care provider before using Acetasol HC (acetic acid and hydrocortisone (otic))?

Before using this medication, tell your doctor if you have a ruptured ear drum. Tell your doctor if you have had any other ear infections or conditions before getting the condition for which you are now being treated. Hydrocortisone can make a pre-existing infection worse.

This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. This medication can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not use acetic acid and hydrocortisone otic on a child younger than 3 years old without a doctor's advice.

How should I use Acetasol HC (acetic acid and hydrocortisone (otic))?

Use this medication exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Use this medicine only in the affected ear. You may not need to use it in both ears.

Use 3 to 5 drops of this medication in each affected ear every 4 to 6 hours, unless your doctor has told you otherwise.

To use the ear drops, first remove the cap from the dropper bottle. Lie down or tilt your head with your ear facing upward. Pull back on your ear gently to open up the ear canal. Hold the dropper upside down over your ear canal and drop the correct number of ear drops into the ear.

Do not place the dropper tip into your ear, or allow the tip to touch any surface. It may become contaminated.

After using the ear drops, stay lying down or with your head tilted for at least 5 minutes. You may use a small piece of cotton ball to plug the ear and keep the medicine from draining out. Follow your doctor's instructions about the use of cotton.

Wipe the tip of the medicine bottle with a clean tissue. Do not wash the dropper tip.

Call your doctor if your symptoms do not improve or if they get worse during the first 5 to 7 days of treatment with acetic acid and hydrocortisone otic.

Store this medication at room temperature away from moisture and heat. Do not allow the medicine to freeze.

What happens if I miss a dose?

Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and use the medicine at the next regularly scheduled time. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of acetic acid and hydrocortisone otic applied to the ears is not expected to produce life-threatening symptoms.

What should I avoid while using Acetasol HC (acetic acid and hydrocortisone (otic))?

This medicine is for use only in the ear. Avoid getting the medication in your eyes, mouth, and nose, or on your lips. If it does get into any of these areas, wash with water.

Do not use other ear drops unless your doctor has prescribed them.

Do not give the medicine to another person, even if you think they have the same skin condition you have. Do not use this medication for any ear condition that has not been checked by your doctor.

Acetasol HC (acetic acid and hydrocortisone (otic)) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Other less serious side effects are more likely to occur, such as:

• 
  

  mild stinging, itching, burning, or irritation in the ear;

  
  


• 
  

  loss of appetite;

  
  


• 
  

  weight loss (especially in a child); or

  
  


• 
  

  weakness.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Acetasol HC (acetic acid and hydrocortisone (otic))?

There may be other drugs that can affect acetic acid and hydrocortisone otic. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Acetasol HC resources

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

Compare Acetasol HC with other medications

• Otitis Externa

Where can I get more information?

• Your pharmacist can provide more information about acetic acid and hydrocortisone otic.

See also: Acetasol HC side effects (in more detail)

Topiramate 25mg Film-Coated Tablets

1. Name Of The Medicinal Product

Topiramate 25mg Film-Coated Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 25mg of Topiramate.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Film-Coated Tablets

Topiramate 25mg Film-Coated Tablets are white, round, biconvex tablets with 6mm diameter and engraved with the marking “V1”.

4. Clinical Particulars

4.1 Therapeutic Indications

Monotherapy in adults, adolescents and children over 6 years of age with partial seizures with or without secondary generalised seizures, and primary generalised tonic-clonic seizures.

Adjunctive therapy in children aged 2 years and above, adolescents and adults with partial onset seizures with or without secondary generalization or primary generalized tonic-clonic seizures and for the treatment of seizures associated with Lennox-Gastaut syndrome.

Topiramate is indicated in adults for the prophylaxis of migraine headache after careful evaluation of possible alternative treatment options. Topiramate is not intended for acute treatment.

4.2 Posology And Method Of Administration

General

It is recommended that therapy be initiated at a low dose followed by titration to an effective dose. Dose and titration rate should be guided by clinical response.

Topiramate is available in film-coated tablets and it is recommended that the film-coated tablets not be broken.

It is not necessary to monitor topiramate plasma concentrations to optimize therapy with topiramate. On rare occasions, the addition of topiramate to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and carbamazepine to adjunctive therapy with topiramate may require adjustment of the dose of topiramate.

Topiramate can be taken without regard to meals.

In patients with or without a history of seizures or epilepsy, antiepileptic drugs including topiramate should be gradually withdrawn to minimize the potential for seizures or increased seizure frequency. In clinical trials, daily dosages were decreased in weekly intervals by 50-100 mg in adults with epilepsy and by 25-50 mg in adults receiving topiramate at doses up to 100 mg/day for migraine prophylaxis. In paediatric clinical trials, topiramate was gradually withdrawn over a 2-8 week period.

Monotherapy epilepsy

General

When concomitant antiepileptic drugs (AEDs) are withdrawn to achieve monotherapy with topiramate, consideration should be given to the effects this may have on seizure control. Unless safety concerns require an abrupt withdrawal of the concomitant AED, a gradual discontinuation at the rate of approximately one-third of the concomitant AED dose every 2 weeks is recommended.

When enzyme inducing medicinal products are withdrawn, topiramate levels will increase. A decrease in topiramate dosage may be required if clinically indicated.

Adults

Dose and titration should be guided by clinical response. Titration should begin at 25 mg nightly for 1 week. The dosage should then be increased at 1- or 2-week intervals by increments of 25 or 50 mg/day, administered in two divided doses. If the patient is unable to tolerate the titration regimen, smaller increments or longer intervals between increments can be used.

The recommended initial target dose for topiramate monotherapy in adults is 100 mg/day to 200 mg/day in 2 divided doses. The maximum recommended daily dose is 500 mg/day in 2 divided doses. Some patients with refractory forms of epilepsy have tolerated topiramate monotherapy at doses of 1,000 mg/day. These dosing recommendations apply to all adults including the elderly in the absence of underlying renal disease.

Paediatric population (children over 6 years of age)

Dose and titration rate in children should be guided by clinical outcome. Treatment of children over 6 years of age should begin at 0.5 to 1 mg/kg nightly for the first week. The dosage should then be increased at 1 or 2 week intervals by increments of 0.5 to 1 mg/kg/day, administered in two divided doses. If the child is unable to tolerate the titration regimen, smaller increments or longer intervals between dose increments can be used.

The recommended initial target dose range for topiramate monotherapy in children over 6 years of age is 100 mg/day depending on clinical response, (this is about 2.0 mg/kg/day in children 6-16 years).

Adjunctive therapy epilepsy (partial onset seizures with or without secondary generalization, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome)

Adults

Therapy should begin at 25-50 mg nightly for one week. Use of lower initial doses has been reported, but has not been studied systematically. Subsequently, at weekly or bi-weekly intervals, the dose should be increased by 25-50 mg/day and taken in two divided doses. Some patients may achieve efficacy with once-a-day dosing.

In clinical trials as adjunctive therapy, 200 mg was the lowest effective dose. The usual daily dose is 200-400 mg in two divided doses.

These dosing recommendations apply to all adults, including the elderly, in the absence of underlying renal disease (see section 4.4).

Paediatric population (children aged 2 years and above)

The recommended total daily dose of topiramate as adjunctive therapy is approximately 5 to 9 mg/kg/day in two divided doses. Titration should begin at 25 mg (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response.

Daily doses up to 30 mg/kg/day have been studied and were generally well tolerated.

Migraine

Adults

The recommended total daily dose of topiramate for prophylaxis of migraine headache is 100 mg/day administered in two divided doses. Titration should begin at 25 mg nightly for 1 week. The dosage should then be increased in increments of 25 mg/day administered at 1-week intervals. If the patient is unable to tolerate the titration regimen, longer intervals between dose adjustments can be used.

Some patients may experience a benefit at a total daily dose of 50 mg/day. Patients have received a total daily dose up to 200 mg/day. This dose may be benefit in some patients, nevertheless, caution is advised due to an increase incidence of side effects

Paediatric population

Topiramate is not recommended for treatment or prevention of migraine in children due to insufficient data on safety and efficacy.

General dosing recommendations for topiramate in special patient populations

Renal impairment

In patients with impaired renal function (CL_CR

In patients with end-stage renal failure, since topiramate is removed from plasma by haemodialysis, a supplemental dose of topiramate equal to approximately one-half the daily dose should be administered on haemodialysis days. The supplemental dose should be administered in divided doses at the beginning and completion of the haemodialysis procedure. The supplemental dose may differ based on the characteristics of the dialysis equipment being used.

Hepatic impairment

In patients with moderate to severe hepatic impairment topiramate should be administered with caution as the clearance of topiramate is decreased.

Elderly

No dose adjustment is required in the elderly population providing renal function is intact.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Migraine prophylaxis in pregnancy and in women of childbearing potential if not using effective methods of contraception

4.4 Special Warnings And Precautions For Use

In situations where rapid withdrawal of topiramate is medically required, appropriate monitoring is recommended (see section 4.2 for further details).

As with other anti-epileptic drugs, some patients may experience an increase in seizure frequency or the onset of new types of seizures with topiramate. These phenomena may be the consequence of an overdose, a decrease in plasma concentrations of concomitantly used anti-epileptics, progress of the disease, or a paradoxical effect.

Adequate hydration while using topiramate is very important. Hydration can reduce the risk of nephrolithiasis (see below). Proper hydration prior to and during activities such as exercise or exposure to warm temperatures may reduce the risk of heat-related adverse reactions (see section 4.8).

Oligohydrosis (decreased sweating) has been reported in association with the use of topiramate. Decreased sweating and rise in body temperature may occur especially in young children exposed to high ambient temperature.

Mood disturbances/depression

An increased incidence of mood disturbances and depression has been observed during topiramate treatment.

Suicide/suicide ideation

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo-controlled trials of anti-epileptic drugs has shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for topiramate.

In double blind clinical trials, suicide related events (SREs) (suicidal ideation, suicide attempts and suicide) occurred at a frequency of 0.5 % in topiramate treated patients (46 out of 8,652 patients treated) and at a nearly 3 fold higher incidence than those treated with placebo (0.2 %; 8 out of 4,045 patients treated).

Patients therefore should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Nephrolithiasis

Some patients, especially those with a predisposition to nephrolithiasis, may be at increased risk for renal stone formation and associated signs and symptoms such as renal colic, renal pain or flank pain.

Risk factors for nephrolithiasis include prior stone formation, a family history of nephrolithiasis and hypercalciuria. None of these risk factors can reliably predict stone formation during topiramate treatment. In addition, patients taking other medicinal products associated with nephrolithiasis may be at increased risk.

Decreased hepatic function

In hepatically-impaired patients, topiramate should be administered with caution as the clearance of topiramate may be decreased.

Acute myopia and secondary angle closure glaucoma

A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving topiramate. Symptoms include acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior chamber shallowing, ocular hyperaemia (redness) and increased intraocular pressure. Mydriasis may or may not be present. This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Symptoms typically occur within 1 month of initiating topiramate therapy. In contrast to primary narrow angle glaucoma, which is rare under 40 years of age, secondary angle closure glaucoma associated with topiramate has been reported in paediatric patients as well as adults. Treatment includes discontinuation of topiramate, as rapidly as possible in the judgment of the treating physician, and appropriate measures to reduce intraocular pressure. These measures generally result in a decrease in intraocular pressure.

Elevated intraocular pressure of any aetiology, if left untreated, can lead to serious sequelae including permanent vision loss.

A determination should be made whether patients with history of eye disorders should be treated with topiramate.

Metabolic acidosis

Hyperchloremic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the normal reference range in the absence of respiratory alkalosis) is associated with topiramate treatment. Depending on underlying conditions, appropriate evaluation including measurement of serum bicarbonate levels is recommended with topiramate therapy. If signs or symptoms are present (e.g. Kussmaul's deep breathing, dyspnoea, anorexia, nausea, vomiting, excessive tiredness, tachycardia or arrhythmia), indicative of metabolic acidosis, measurement of serum bicarbonate is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate (using dose tapering).

This decrease in serum bicarbonate is due to the inhibitory effect of topiramate on renal carbonic anhydrase. Generally, the decrease in bicarbonate occurs early in treatment although it can occur at any time during treatment. These decreases are usually mild to moderate (average decrease of 4 mmol/l at doses of 100 mg/day or above in adults and at approximately 6 mg/kg/day in paediatric patients). Rarely, patients have experienced decreases to values below 10 mmol/l. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhoea, surgery, ketogenic diet, or certain medicinal products) may be additive to the bicarbonate lowering effects of topiramate.

Chronic metabolic acidosis increases the risk of renal stone formation and may potentially lead to osteopenia.

Chronic metabolic acidosis in paediatric patients can reduce growth rates. The effect of topiramate on bone-related sequelae has not been systematically investigated in paediatric or adult populations.

Depending on underlying conditions, appropriate evaluation including serum bicarbonate levels is recommended with topiramate therapy. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate (using dose tapering).

Topiramate should be used with caution in patients with conditions or treatments that represent a risk factor for the appearance of metabolic acidosis.

Nutritional supplementation

Some patients may experience weight loss whilst on treatment with topiramate. It is recommended that patients on topiramate treatment should be monitored for weight loss. A dietary supplement or increased food intake may be considered if the patient is losing weight while on topiramate.

Impairment of cognitive function

Cognitive impairment in epilepsy is multifactorial and may be due to the underlying aetiology, due to the epilepsy or due to the anti epileptic treatment.

There have been reports in the literature of impairment of cognitive function in adults on topiramate therapy which required reduction in dosage or discontinuation of treatment. However, studies regarding cognitive outcomes in children treated with topiramate are insufficient and its effect in this regard still needs to be elucidated.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Effects of topiramate on other antiepileptic medicinal products

The addition of topiramate to other antiepileptic drugs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) has no effect on their steady-state plasma concentrations, except in the occasional patient, where the addition of topiramate to phenytoin may result in an increase of plasma concentrations of phenytoin. This is possibly due to inhibition of a specific enzyme polymorphic isoform (CYP2C19). Consequently, any patient on phenytoin showing clinical signs or symptoms of toxicity should have phenytoin levels monitored.

A pharmacokinetic interaction study of patients with epilepsy indicated the addition of topiramate to lamotrigine had no effect on steady state plasma concentration of lamotrigine at topiramate doses of 100 to 400 mg/day. In addition, there was no change in steady state plasma concentration of topiramate during or after removal of lamotrigine treatment (mean dose of 327 mg/day).

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme (e.g., diazepam, imipramin, moclobemide, proguanil, omeprazol).

Effects of other antiepileptic medicinal products on topiramate

Phenytoin and carbamazepine decrease the plasma concentration of topimarate. The addition or withdrawal of phenytoin or carbamazepine to topiramate therapy may require an adjustment in dosage of the latter. This should be done by titrating to clinical effect. The addition or withdrawal of valproic acid does not produce clinically significant changes in plasma concentrations of topiramate and, therefore, does not warrant dosage adjustment of topiramate. The results of these interactions are summarized below:

AED Coadministered	AED Concentration	Topiramate Concentration
Phenytoin	↔**
Carbamazepine (CBZ)	↔
Valproic acid	↔	↔
Lamotrigine	↔	↔
Phenobarbital	↔	NS
Primidone	↔	NS
↔ = No effect on plasma concentration ( ** = Plasma concentrations increase in individual patients NS = Not studied AED = antiepileptic drug

Other medicinal product interactions

Digoxin

In a single-dose study, serum digoxin area under plasma concentration curve (AUC) decreased 12 % due to concomitant administration of topiramate. The clinical relevance of this observation has not been established. When topiramate is added or withdrawn in patients on digoxin therapy, careful attention should be given to the routine monitoring of serum digoxin.

CNS depressants

Concomitant administration of topiramate and alcohol or other CNS depressant medicinal products has not been evaluated in clinical studies. It is recommended that topiramate not be used concomitantly with alcohol or other CNS depressant medicinal products.

St John's Wort (Hypericum perforatum)

A risk of decreased plasma concentrations resulting in a loss of efficacy could be observed with co-administration of topiramate and St John's Wort. There have been no clinical studies evaluating this potential interaction.

Oral contraceptives

In a pharmacokinetic interaction study in healthy volunteers with a concomitantly administered combination oral contraceptive product containing 1 mg norethindrone (NET) plus 35 μg ethinyl estradiol (EE), topiramate given in the absence of other medications at doses of 50 to 200 mg/day was not associated with statistically significant changes in mean exposure (AUC) to either component of the oral contraceptive. In another study, exposure to EE was statistically significantly decreased at doses of 200, 400, and 800 mg/day (18 %, 21 %, and 30 %, respectively) when given as adjunctive therapy in epilepsy patients taking valproic acid. In both studies, topiramate (50-200 mg/day in healthy volunteers and 200-800 mg/day in epilepsy patients) did not significantly affect exposure to NET. Although there was a dose dependent decrease in EE exposure for doses between 200-800 mg/day (in epilepsy patients), there was no significant dose dependent change in EE exposure for doses of 50-200 mg/day (in healthy volunteers). The clinical significance of the changes observed is not known. The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with topiramate. Patients taking estrogen containing contraceptives should be asked to report any change in their bleeding patterns. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding.

Lithium

In healthy volunteers, there was an observed reduction (18 % for AUC) in systemic exposure for lithium during concomitant administration with topiramate 200 mg/day. In patients with bipolar disorder, the pharmacokinetics of lithium were unaffected during treatment with topiramate at doses of 200 mg/day; however, there was an observed increase in systemic exposure (26 % for AUC) following topiramate doses of up to 600 mg/day. Lithium levels should be monitored when co-administered with topiramate.

Risperidone

Drug-drug interaction studies conducted under single dose conditions in healthy volunteers and multiple dose conditions in patients with bipolar disorder, yielded similar results. When administered concomitantly with topiramate at escalating doses of 100, 250 and 400 mg/day there was a reduction in risperidone (administered at doses ranging from 1 to 6 mg/day) systemic exposure (16 % and 33 % for steady-state AUC at the 250 and 400 mg/day doses, respectively). However, differences in AUC for the total active moiety between treatment with risperidone alone and combination treatment with topiramate were not statistically significant. Minimal alterations in the pharmacokinetics of the total active moiety (risperidone plus 9-hydroxyrisperidone) and no alterations for 9-hydroxyrisperidone were observed. There were no significant changes in the systemic exposure of the risperidone total active moiety or of topiramate. When topiramate was added to existing risperidone (1-6 mg/day) treatment, adverse events were reported more frequently than prior to topiramate (250-400 mg/day) introduction (90 % and 54 % respectively). The most frequently reported AE's when topiramate was added to risperidone treatment were: somnolence (27 % and 12 %), paraesthesia (22 % and 0 %) and nausea (18 % and 9 % respectively).

Hydrochlorothiazide (HCTZ)

A drug-drug interaction study conducted in healthy volunteers evaluated the steady-state pharmacokinetics of HCTZ (25 mg q24h) and topiramate (96 mg q12h) when administered alone and concomitantly. The results of this study indicate that topiramate C_max increased by 27 % and AUC increased by 29 % when HCTZ was added to topiramate. The clinical significance of this change is unknown. The addition of HCTZ to topiramate therapy may require an adjustment of the topiramate dose. The steady-state pharmacokinetics of HCTZ were not significantly influenced by the concomitant administration of topiramate. Clinical laboratory results indicated decreases in serum potassium after topiramate or HCTZ administration, which were greater when HCTZ and topiramate were administered in combination.

Metformin

A drug-drug interaction study conducted in healthy volunteers evaluated the steady-state pharmacokinetics of metformin and topiramate in plasma when metformin was given alone and when metformin and topiramate were given simultaneously. The results of this study indicated that metformin mean C_max and mean AUC0-12h increased by 18 % and 25 %, respectively, while mean CL/F decreased 20 % when metformin was co-administered with topiramate. Topiramate did not affect metformin tmax. The clinical significance of the effect of topiramate on metformin pharmacokinetics is unclear. Oral plasma clearance of topiramate appears to be reduced when administered with metformin. The extent of change in the clearance is unknown. The clinical significance of the effect of metformin on topiramate pharmacokinetics is unclear.

When topiramate is added or withdrawn in patients on metformin therapy, careful attention should be given to the routine monitoring for adequate control of their diabetic disease state.

Pioglitazone

A drug-drug interaction study conducted in healthy volunteers evaluated the steady-state pharmacokinetics of topiramate and pioglitazone when administered alone and concomitantly. A 15 % decrease in the AUC of pioglitazone with no alteration in C_max,ss was observed. This finding was not statistically significant. In addition, a 13 % and 16 % decrease in C_max,ss and AUC respectively, of the active hydroxy-metabolite was noted as well as a 60 % decrease in C_max,ss and AUC of the active keto-metabolite. The clinical significance of these findings is not known. When topiramate is added to pioglitazone therapy or pioglitazone is added to topiramate therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.

Glyburide

A drug-drug interaction study conducted in patients with type 2 diabetes evaluated the steady-state pharmacokinetics of glyburide (5 mg/day) alone and concomitantly with topiramate (150 mg/day). There was a 25 % reduction in glyburide AUC₂₄ during topiramate administration. Systemic exposure of the active metabolites, 4-trans-hydroxy-glyburide (M1) and 3-cis-hydroxyglyburide (M2), were also reduced by 13 % and 15 %, respectively. The steady-state pharmacokinetics of topiramate were unaffected by concomitant administration of glyburide.

When topiramate is added to glyburide therapy or glyburide is added to topiramate therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.

Other forms of interactions

Agents predisposing to nephrolithiasis

Topiramate, when used concomitantly with other agents predisposing to nephrolithiasis, may increase the risk of nephrolithiasis. While using topiramate, agents like these should be avoided since they may create a physiological environment that increases the risk of renal stone formation.

Valproic acid

Concomitant administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either medicinal product alone. In most cases, symptoms and signs abated with discontinuation of either medicinal product. This adverse reaction is not due to a pharmacokinetic interaction. An association of hyperammonemia with topiramate monotherapy or concomitant treatment with other anti-epileptics has not been established.

Additional pharmacokinetic drug interaction studies

Clinical studies have been conducted to assess the potential pharmacokinetic drug interaction between topiramate and other agents. The changes in C_max or AUC as a result of the interactions are summarized below. The second column (concomitant drug concentration) describes what happens to the concentration of the concomitant drug listed in the first column when topiramate is added. The third column (topiramate concentration) describes how the coadministration of a drug listed in the first column modifies the concentration of topiramate.

Summary of Results from Additional Clinical Pharmacokinetic Drug Interaction Studies
Concomitant Drug	Concomitant Drug Concentrationa	Topiramate Concentrationa
Amitriptyline	↔ 20 % increase in Cmax and AUC of nortriptyline metabolite	NS
Dihydroergotamine (Oral and Subcutaneous)	↔	↔
Haloperidol	↔ 31 % increase in AUC of the reduced metabolite	NS
Propranolol	↔ 17 % increase in Cmax for 4-OH propranolol (TPM 50 mg q12h)	9 % and 16 % increase in Cmax, 9 % and17 % increase in AUC (40 and 80 mg propranolol q12h respectively)
Sumatriptan (Oral and Subcutaneous)	↔	NS
Pizotifen	↔	↔
Diltiazem	25 % decrease in AUC of diltiazem and 18 % decrease in DEA, and ↔ for DEM*	20 % increase in AUC
Venlafaxine	↔	↔
Flunarizine	16 % increase in AUC (TPM 50 mg q12h)b	↔
a % values are the changes in treatment mean Cmax or AUC with respect to monotherapy ↔ = No effect on Cmax and AUC ( NS = Not studied *DEA = des acetyl diltiazem, DEM = N-demethyl diltiazem b Flunarizine AUC increased 14 % in subjects taking flunarizine alone. Increase in exposure may be attributed to accumulation during achievement of steady state.

4.6 Pregnancy And Lactation

Topiramate was teratogenic in mice, rats and rabbits. In rats, topiramate crosses the placental barrier.

There are no adequate and well-controlled studies with topiramate in pregnant women.

Pregnancy registry data suggest that there may be an association between the use of topiramate during pregnancy and congenital malformations (e.g., craniofacial defects, such as cleft lip/palate, hypospadias, and anomalies involving various body systems). This has been reported with topiramate monotherapy and topiramate as part of a polytherapy regimen. This data should be interpreted with caution, as more data is needed to identify increased risks for malformations.

In addition, data from these registries and other studies suggest that, compared with monotherapy, there may be an increased risk of teratogenic effects associated with the use of anti-epileptic drugs in combination therapy.

It is recommended that women of child bearing potential use adequate contraception.

Animal studies have shown excretion of topiramate in milk. The excretion of topiramate in human milk has not been evaluated in controlled studies. Limited observations in patients suggest an extensive excretion of topiramate into breast milk. Since many medicinal products are excreted into human milk, a decision must be made whether to suspend breast-feeding or to discontinue/ abstain from topiramate therapy taking into account the importance of the medicinal product to the mother (section 4.4).

Indication Epilepsy

During pregnancy, topiramate should be prescribed after fully informing the woman of the known risks of uncontrolled epilepsy to the pregnancy and the potential risks of the medicinal product to the foetus.

Indication Migraine Prophylaxis

Topiramate is contraindicated in pregnancy, and in women of childbearing potential if an effective method of contraception is not used (see section 4.3 and 4.5 Interactions with oral contraceptives).

4.7 Effects On Ability To Drive And Use Machines

Topiramate acts on the central nervous system and may produce drowsiness, dizziness or other related symptoms. It may also cause visual disturbances and/or blurred vision. These adverse reactions could potentially be dangerous in patients driving a vehicle or operating machinery, particularly until such time as the individual patient's experience with the medicinal products established.

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable Effects

The safety of topiramate was evaluated from a clinical trial database consisting of 4,111 patients (3,182 on topiramate and 929 on placebo) who participated in 20 double-blind trials and 2,847 patients who participated in 34 open-label trials, respectively, for topiramate as adjunctive treatment of primary generalized tonic-clonic seizures, partial onset seizures, seizures associated with Lennox-Gastaut syndrome, monotherapy for newly or recently diagnosed epilepsy or migraine prophylaxis. The majority of ADRs were mild to moderate in severity. ADRs identified in clinical trials, and during post-marketing experience (as indicated by “*”) are listed by their incidence in clinical trials in Table 1. Assigned frequencies are as follows:

Very common

Common

Uncommon

Rare

Not known cannot be estimated from the available data

The most common ADRs (those with an incidence of >5 % and greater than that observed in placebo in at least 1 indication in double-blind controlled studies with topiramate) include: anorexia, decreased appetite, bradyphrenia, depression, expressive language disorder, insomnia, coordination abnormal, disturbance in attention, dizziness, dysarthria, dysgeusia, hypoesthesia, lethargy, memory impairment, nystagmus, paresthesia, somnolence, tremor, diplopia, vision blurred, diarrhoea, nausea, fatigue, irritability, and weight decreased.

Paediatric population

ADRs reported more frequently (

• decreased appetite

•  increased appetite

• acidosis hyperchloraemic

• hypokalaemia

• abnormal behaviour

• aggression

• apathy

• initial insomnia

• suicidal ideation

• disturbance in attention

• lethargy

• circadian rhythm sleep disorder

• poor quality sleep

• lacrimation increased

• sinus bradycardia

• feeling abnormal

• gait disturbance.

ADRs that were reported in children but not in adults in double-blind controlled studies include:

• eosinophilia

• psychomotor hyperactivity

• vertigo

• vomiting

• hyperthermia

• pyrexia

• learning disability.

Table 1: Topiramate Adverse Drug Reactions
System Organ Class	Very common	Common	Uncommon	Rare	Not known
Investigations	Weight decreased	Weight increased*	Crystal urine present, tandem gait test abnormal, white blood cell count decreased	Blood bicarbonate decreased
Cardiac disorders			Bradycardia, sinus bradycardia, palpitations
Blood and lymphatic system disorders		Anaemia	Leucopenia, thrombocytopenia lymphadenopathy, eosinophilia	Neutropenia*
Nervous system disorders	Paraesthesia, somnolence Dizziness	Disturbance in attention, memory impairment, amnesia, cognitive disorder, mental impairment, psychomotor skills impaired, convulsion, coordination abnormal, tremor, lethargy, hypoaesthesia, nystagmus, dysgeusia, balance disorder, dysarthria, intention tremor, sedation	Depressed level of consciousness, grand mal convulsion, visual field defect, complex partial seizures, speech disorder, psychomotor hyperactivity, syncope, sensory disturbance, drooling, hypersomnia, aphasia, repetitive speech, hypokinesia, dyskinesia, dizziness postural, poor quality sleep, burning sensation, sensory loss, parosmia, cerebellar syndrome, dysaesthesia, hypogeusia, stupor, clumsiness, aura, ageusia, dysgraphia, dysphasia, neuropathy peripheral, presyncope, dystonia, formication	Apraxia, circadian rhythm sleep disorder, hyperaesthesia, hyposmia, anosmia, essential tremor, akinesia, unresponsive to stimuli
Eye disorders		Vision blurred, diplopia, visual disturbance	Visual acuity reduced, scotoma, myopia*, abnormal sensation in eye*, dry eye, photophobia, blepharospasm, lacrimation increased, photopsia, mydriasis, presbyopia	Blindness unilateral, blindness transient, glaucoma, accommodation disorder, altered visual depth perception, scintillating scotoma, eyelid oedema*, night blindness, amblyopia	Angle closure glaucoma*, Maculopathy*, eye movement disorder*
Ear and labyrinth disorders		Vertigo, tinnitus, ear pain	Deafness, deafness unilateral, deafness neurosensory, ear discomfort, hearing impaired
Respiratory, thoracic and mediastinal disorders		Dyspnoea , epistaxis, nasal congestion, rhinorrhoea	Dyspnoea exertional, Paranasal sinus hypersecretion, dysphonia
Gastrointestinal disorders	Nausea, diarrhoea	Vomiting, constipation, abdominal pain upper, dyspepsia, abdominal pain, dry mouth, stomach discomfort, paraesthesia oral, gastritis, abdominal discomfort	Pancreatitis, flatulence, gastrooesophageal reflux disease, abdominal pain lower, hypoaesthesia oral, gingival bleeding, abdominal distension, epigastric discomfort, abdominal tenderness, salivary hypersecretion, oral pain, breath odour, glossodynia
Renal and urinary disorders		Nephrolithiasis, pollakiuria, dysuria	Calculus urinary, urinary incontinence, haematuria, incontinence, micturition urgency, renal colic, renal pain	Calculus ureteric, renal tubular acidosis*
Skin and subcutaneous tissue disorders		Alopecia, rash, pruritus