Strattera

Pronunciation: A-toe-MOX-e-teen
Generic Name: Atomoxetine
Brand Name: Strattera

Strattera may increase the risk of suicidal thoughts or actions in children and teenagers with attention-deficit/hyperactivity disorder (ADHD). Be sure that the benefits of using Strattera outweigh the risks. Talk with the patient's doctor if you have any questions.

Families and caregivers must closely watch patients who take Strattera. It is important to keep in close contact with the patient's doctor. Tell the doctor right away if the patient has symptoms like worsened depression, suicidal thoughts, or changes in behavior. Discuss any questions with the patient's doctor.

Strattera is used for:

Treating ADHD.

Strattera is a selective norepinephrine reuptake inhibitor. Exactly how it works to treat ADHD is not known. Strattera increases certain chemicals (eg, norepinephrine) in the brain, which may affect attention span and behavior.

Do NOT use Strattera if:

• you are allergic to any ingredient in Strattera


• you have certain heart problems (eg, heart defect, heart muscle problems), certain types of irregular heartbeat, severe blood vessel problems, or narrow-angle glaucoma


• you have or have a history of a certain type of adrenal gland tumor (pheochromocytoma)


• you are taking or have taken a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the last 14 days

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

Before using Strattera:

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

• if you are pregnant, planning to become pregnant, or are breast-feeding


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


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


• if you or a family member has a history of bipolar disorder (manic depression), other mental or mood problems, suicidal thoughts or attempts, or alcohol or substance abuse


• if you or a family member has a history of heart problems (eg, heart failure; fast, slow, or irregular heartbeat), a heart attack, an abnormal electrocardiogram (ECG), a stroke or bleeding in the brain, blood or bleeding problems, high or low blood pressure, or sudden death


• if you have a history of seizures


• if you have liver problems, trouble urinating, or Raynaud syndrome


• if you take a decongestant (eg, pseudoephedrine, phenylephrine) or medicine for high blood pressure

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

• MAOIs (eg, phenelzine) because severe and sometimes fatal side effects, including severe high blood pressure, high fever, muscle problems, severe agitation, and coma, may occur


• Quinidine or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine, paroxetine) because they may increase the risk of Strattera's side effects


• Albuterol because the risk of its side effects may be increased by Strattera

This may not be a complete list of all interactions that may occur. Ask your health care provider if Strattera may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Strattera:

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

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


• Take Strattera by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• Swallow Strattera whole. Do not break, crush, chew, or open the capsules.


• Taking Strattera at the same time each day will help you remember to take it.


• Continue to take Strattera even if you feel well. Do not miss any doses.


• If you miss a dose of Strattera, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

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

Important safety information:

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


• Strattera may cause dizziness, light-headedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Strattera should be used as part of a complete treatment program. Be sure to follow the program given to you by your doctor or health care provider.


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


• Serious side effects, including a heart attack, a stroke, and sudden death, have occurred with the use of the medicine in patients with heart defects or other serious heart problems. If you have a heart defect or other serious problem, talk with your doctor about other therapies to treat your condition.


• Children and teenagers who take Strattera may be at increased risk of suicidal thoughts or actions. Adults may also be affected. The risk may be greater in patients who have had suicidal thoughts or actions in the past. The risk may also be greater in patients who have had bipolar (manic-depressive) illness, or if their family members have had it. Watch patients who take Strattera closely. Contact the doctor at once if new, worsened, or sudden symptoms, such as depressed mood; anxious, restless, or irritable behavior; panic attacks; or any unusual change in mood or behavior, occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur.


• Do not try to open the capsules or take them apart. If a capsule breaks, do not touch it. Wash your hands and any surfaces that touched a broken capsule. Do not get Strattera in your eye; it may irritate your eye if you do. If you get Strattera in your eyes or nose, rinse at once with cool water.


• Strattera may rarely cause a prolonged, painful erection. This could happen even when you are not having sex. If this is not treated right away, it could lead to permanent sexual problems such as impotence. Contact your doctor right away if this happens.


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


• Lab tests, including heart rate, blood pressure, and liver function, may be performed while you take Strattera. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Strattera with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness.


• Strattera may affect growth rate in CHILDREN and teenagers in some cases. They may need regular growth checks while they take Strattera.


• Strattera should be used with extreme caution in CHILDREN younger than 6 years; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Strattera while you are pregnant. It is not known if Strattera is found in breast milk. If you are or will be breast-feeding while you take Strattera, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Strattera:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; coughing; decreased appetite; decreased sexual desire; dizziness; drowsiness; dry mouth; fatigue; flushing; headache; increased sweating; mild stomach pain or upset; nausea; tiredness; trouble sleeping; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts or elevated mood (mania); change in feeling of touch or other senses (eg, smell, taste); chest pain; confusion; decreased or difficult urination; decreased sexual ability (eg, impotence, ejaculation problems); fainting; fast or irregular heartbeat; fever, chills, or sore throat; hallucinations; menstrual cycle changes; mental or mood changes (eg, agitation, anxiety, depression, irritability, persistent crying, unusual sadness); new or worsening behavior changes (eg, aggression, hostility, impulsivity, restlessness); numbness or tingling; one-sided weakness; panic attacks; prolonged or painful erection; seizure; severe or persistent headache or dizziness; severe or persistent trouble sleeping, fatigue, or tiredness; shortness of breath; stomach pain or tenderness; suicidal thoughts or attempts; symptoms of liver damage (eg, yellowing of the skin or eyes, itching, dark urine, pale stools, loss of appetite, right upper stomach pain, unexplained flu-like symptoms); tics; unusual vision or speech changes; unusually cold or blue fingers or toes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Strattera side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include abnormal behavior; agitation; enlarged pupils; fast or irregular heartbeat; hyperactivity; mental changes (eg, disorientation, hallucinations); nausea, vomiting, or diarrhea; seizures; severe dizziness, sleepiness, or drowsiness; severe dry mouth; severe or persistent headache; tremor.

Proper storage of Strattera:

Store Strattera at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Strattera out of the reach of children and away from pets.

General information:

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


• Strattera is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Strattera. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Strattera resources

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

• Strattera Prescribing Information (FDA)


• Strattera Consumer Overview


• Strattera Monograph (AHFS DI)


• Strattera Advanced Consumer (Micromedex) - Includes Dosage Information


• Atomoxetine Prescribing Information (FDA)

Compare Strattera with other medications

• ADHD
• Depression
• Fibromyalgia
• Social Anxiety Disorder

Gatifloxacin

Generic Name: Gatifloxacin (ga-ti-FLOKS-a-sin)
Brand Name: Tequin

Gatifloxacin is used for:

Treating infections caused by certain bacteria.

Gatifloxacin is a fluoroquinolone antibiotic. It works by stopping the production of essential proteins needed by the bacteria to survive.

Do NOT use Gatifloxacin if:

• you are allergic to any ingredient in Gatifloxacin or to similar medicines (eg, ciprofloxacin)


• you have low blood potassium or diabetes


• you or a family member have a rare heart condition known as congenital prolongation of the QTc interval


• you are taking certain medicines for heart rhythm disturbances (eg, quinidine, procainamide, amiodarone, sotalol), cisapride, a ketolide antibiotic (eg, telithromycin), a macrolide antibiotic (eg, erythromycin), pimozide, or ziprasidone

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

Before using Gatifloxacin:

Some medical conditions may interact with Gatifloxacin. Tell your health care provider if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


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


• if you have allergies to medicines or other substances


• if you have heart problems, including a slow heartbeat, a history of lack of blood supply to your heart, or hardening of the arteries


• if you have a history of low blood potassium levels, diabetes, or kidney or liver problems


• if you have Alzheimer disease, tendonitis, a history of seizures, or other central nervous system problems or increased pressure in the head

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

• Antidepressants (eg, amitriptyline), antihistamines (eg, diphenhydramine, loratadine), arsenic, azole antifungals (eg, ketoconazole), certain medicines for heart rhythm disturbances (eg, quinidine, procainamide, amiodarone, sotalol), cisapride, diuretics (eg, hydrochlorothiazide, furosemide), droperidol, ketolide antibiotics (eg, telithromycin, macrolide antibiotics (eg, erythromycin), phenothiazines (eg, chlorpromazine), pimozide , or ziprasidone because the risk of side effects, such as racing heartbeat, dizziness, fainting, life-threatening irregular heartbeat leading to unconsciousness, may be increased


• Probenecid because it may increase the risk of Gatifloxacin's side effects


• Digoxin because the risk of its side effects may be increased by Gatifloxacin


• Anticoagulants (eg, warfarin) because the risk of side effects, including bleeding, may be increased by Gatifloxacin


• Insulin, sulfonylureas (eg, glyburide), or other medicines for diabetes because the risk of blood sugar changes may be increased

This may not be a complete list of all interactions that may occur. Ask your health care provider if Gatifloxacin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Gatifloxacin:

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

• Gatifloxacin is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Gatifloxacin at home, carefully follow the injection procedures taught to you by your health care provider.


• If Gatifloxacin contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.


• To clear up your infection completely, continue using Gatifloxacin for the full course of treatment even if you feel better in a few days.


• Gatifloxacin works best if it is taken at the same time each day.


• When possible, you will be switched to medicine you can take by mouth.


• Drinking extra fluids while you are taking Gatifloxacin is recommended. Check with your doctor for instructions. If you are unable to take fluids by mouth, you will be given fluids through a vein.


• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for proper disposal.


• If you miss a dose of Gatifloxacin, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

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

Important safety information:

• Gatifloxacin may cause dizziness, drowsiness, or changes in vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Gatifloxacin. Using Gatifloxacin alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Gatifloxacin is effective only against bacteria. It is not effective for treating viral infections (eg, the common cold).


• It is important to use Gatifloxacin for the full course of treatment. Failure to do so may decrease the effectiveness of Gatifloxacin and may increase the risk that the bacteria will no longer be sensitive to Gatifloxacin and will not be able to be treated by this or certain other antibiotics in the future.


• Long-term or repeated use of Gatifloxacin may cause a second infection. Your doctor may want to change your medicine to treat the second infection. Contact your doctor if signs of a second infection occur.


• If severe diarrhea, stomach pain/cramps, or bloody stools occur, contact your doctor immediately. This could be a symptom of a serious side effect requiring immediate medical attention. Do not treat diarrhea without consulting your doctor.


• Gatifloxacin may cause increased sensitivity to the sun. Avoid exposure to the sun, sunlamps, or tanning booths until you know how you react to Gatifloxacin. Use a sunscreen or wear protective clothing if you must be outside for a prolonged period.


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


• Lab tests, including liver function, kidney function, and complete blood cell counts, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• Use Gatifloxacin with caution in the ELDERLY because they may be more sensitive to its effects, especially blood sugar changes.


• Gatifloxacin is not recommended for use in CHILDREN younger than 18 years of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Gatifloxacin during pregnancy. It is unknown if Gatifloxacin is excreted in breast milk. If you are or will be breast-feeding while you are using Gatifloxacin, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Gatifloxacin:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Back pain; change in taste; constipation; depression; diarrhea; dizziness; gas; headache; indigestion; itching; nausea; pain; pain or redness at the injection site; restlessness; runny nose; sinus inflammation; sleeplessness; sore throat; tiredness; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody stools; chest pain or pounding in the chest; confusion; excessive hunger, thirst, or urination; fainting; fast or irregular heartbeat; hoarseness; lightheadedness; loss of consciousness; nightmares; paranoia; seizures; severe or continuous diarrhea; stomach pain/cramps; sudden onset of sweating, pale skin, or blurred vision; tendon or joint pain or swelling; tremors; unusual or severe drowsiness or dizziness.

This is not a complete list of all side effects that may occur. If you have questions or need medical advice about side effects, contact your doctor or health care provider. You may report side effects to the FDA at 1-800-FDA-1088 (1-800-332-1088) or at http://www.fda.gov/medwatch.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center (http://www.aapcc.org/DNN/), or emergency room immediately.

Proper storage of Gatifloxacin:

Store Gatifloxacin at room temperature, 77 degrees F (25 degrees C). Store away from heat, moisture, and light. Do not freeze. Keep Gatifloxacin out of the reach of children and away from pets.

General information:

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


• Gatifloxacin is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.

This information is a summary only. It does not contain all information about Gatifloxacin. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Gatifloxacin resources

• Gatifloxacin Use in Pregnancy & Breastfeeding
• Gatifloxacin Drug Interactions
• Gatifloxacin Support Group
• 0 Reviews for Gatifloxacin - Add your own review/rating

• Gatifloxacin Professional Patient Advice (Wolters Kluwer)


• Gatifloxacin Monograph (AHFS DI)


• gatifloxacin Ophthalmic Advanced Consumer (Micromedex) - Includes Dosage Information


• Tequin Consumer Overview

Compare Gatifloxacin with other medications

• Anthrax
• Anthrax Prophylaxis
• Bladder Infection
• Bronchitis
• Gonococcal Infection, Uncomplicated
• Kidney Infections
• Otitis Media
• Pneumonia
• Sinusitis
• Skin Infection
• Tuberculosis, Active
• Urinary Tract Infection

Tetanus Toxoid Adsorbed

Generic Name: tetanus toxoid (Intramuscular route, Injection route)

TET-n-us TOX-oyd

Commonly used brand name(s)

In the U.S.

• TE Anatoxal Berna

In Canada

• Tetanus Toxoid Adsorbed

Available Dosage Forms:

• Suspension


• Solution

Therapeutic Class: Toxoid

Uses For Tetanus Toxoid Adsorbed

Tetanus Toxoid is used to prevent tetanus (also known as lockjaw). Tetanus is a serious illness that causes convulsions (seizures) and severe muscle spasms that can be strong enough to cause bone fractures of the spine. Tetanus causes death in 30 to 40 percent of cases.

Immunization against tetanus is recommended for all infants 6 to 8 weeks of age and older, all children, and all adults. Immunization against tetanus consists first of a series of either 3 or 4 injections, depending on which type of tetanus toxoid you receive. In addition, it is very important that you get a booster injection every 10 years for the rest of your life. Also, if you get a wound that is unclean or hard to clean, you may need an emergency booster injection if it has been more than 5 years since your last booster. In recent years, two-thirds of all tetanus cases have been in persons 50 years of age and older. A tetanus infection in the past does not make you immune to tetanus in the future.

This vaccine is to be administered only by or under the supervision of your doctor or other health care professional.

Before Using Tetanus Toxoid Adsorbed

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:

In deciding to receive this vaccine, the risks of receiving the vaccine must be weighed against the good it will do. This is a decision you and your doctor will make. For tetanus toxoid, 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

Use is not recommended for infants up to 6 weeks of age. For infants and children 6 weeks of age and older, tetanus toxoid is not expected to cause different side effects or problems than it does in adults.

Geriatric

This vaccine is not expected to cause different side effects or problems in older people than it does in younger adults. However, the vaccine may be slightly less effective in older persons than in younger adults.

Pregnancy

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

Breast Feeding

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

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking 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 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.

• Chloramphenicol

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:

• A severe reaction or a fever greater than 103 °F (39.4 °C) following a previous dose of tetanus toxoid—May increase the chance of side effects with future doses of tetanus toxoid; be sure your doctor knows about this before you receive the next dose of tetanus toxoid

• Bronchitis, pneumonia, or other illness involving lungs or bronchial tubes, or


• Severe illness with fever—Possible side effects from tetanus toxoid may be confused with the symptoms of the condition

Proper Use of tetanus toxoid

This section provides information on the proper use of a number of products that contain tetanus toxoid. It may not be specific to Tetanus Toxoid Adsorbed. Please read with care.

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 injection dosage forms:
  
  • For prevention of tetanus (lockjaw):
    
    • Adults, children, and infants 6 weeks of age and older—One dose is given at your first visit, then a second dose is given four to eight weeks later. Depending on the product given, you may receive a third dose four to eight weeks after the second dose, and a fourth dose six to twelve months after that; or you may receive a third dose six to twelve months after the second dose. Everyone should receive a booster dose every ten years. The doses are injected under the skin or into a muscle. In addition, if you get a wound that is unclean or hard to clean, you may need an emergency booster injection if it has been more than 5 years since your last booster dose.
    
    
  
  

Tetanus Toxoid Adsorbed 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:

Symptoms of allergic reaction

• Difficulty in breathing or swallowing


• hives


• itching, especially of feet or hands


• reddening of skin, especially around ears


• swelling of eyes, face, or inside of nose


• unusual tiredness or weakness (sudden and severe)

Check with your doctor as soon as possible if any of the following side effects occur:

Rare

• Confusion


• convulsions (seizures)


• fever over 103 °F (39.4 °C)


• headache (severe or continuing)


• sleepiness (excessive)


• swelling, blistering, or pain at place of injection (severe or continuing)


• swelling of glands in armpit


• unusual irritability


• vomiting (severe or continuing)

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

• Redness or hard lump at place of injection

Less common

• Chills, fever, irritability, or unusual tiredness


• pain, tenderness, itching, or swelling at place of injection


• skin rash

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: Tetanus Toxoid Adsorbed 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 Tetanus Toxoid Adsorbed resources

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

• Tetanus Toxoid Adsorbed Concise Consumer Information (Cerner Multum)


• Tetanus Toxoid Professional Patient Advice (Wolters Kluwer)

Compare Tetanus Toxoid Adsorbed with other medications

• Tetanus Prophylaxis

alendronate

Generic Name: alendronate (a LEN dro nate)

Brand Names: Fosamax

What is alendronate?

Alendronate is in the group of medicines called bisphosphonates (bis FOS fo nayts). It alters the cycle of bone formation and breakdown in the body. Alendronate slows bone loss while increasing bone mass, which may prevent bone fractures.

Alendronate is used in men and women to treat or prevent osteoporosis that is caused by menopause or by taking steroids. Alendronate is also used to increase bone mass in men who have osteoporosis, and to treat Paget's disease of bone in men and women.

Alendronate may also be used for purposes not listed in this medication guide.

What is the most important information I should know about alendronate?

Do not take an alendronate tablet if you cannot sit upright or stand for at least 30 minutes. Alendronate can cause serious problems in the stomach or esophagus (the tube that connects your mouth and stomach). You will need to stay upright for at least 30 minutes after taking this medication.

Take the alendronate tablet first thing in the morning, at least 30 minutes before you eat or drink anything or take any other medicine.

Take each dose with a full glass (6 to 8 ounces) of water. Use only plain water (not mineral water, coffee, tea, or juice) when taking an alendronate tablet.

For at least the first 30 minutes after taking an alendronate tablet, do not lie down or recline; do not eat or drink anything other than plain water; and do not take any other medicines including vitamins, calcium, or antacids.

Some people using medicines similar to alendronate have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums. You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and a pre-existing dental problem.

If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are using alendronate. You may need to stop using the medicine for a short time.

Talk with your doctor about the risks and benefits of using this medication.

What should I discuss with my healthcare provider before taking alendronate?

Do not take an alendronate tablet if you cannot sit upright or stand for at least 30 minutes. Alendronate can cause serious problems in the stomach or esophagus (the tube that connects your mouth and stomach). You will need to stay upright for at least 30 minutes after taking this medication. You should not take alendronate if you are allergic to it, or if you have low levels of calcium in your blood (hypocalcemia), or a problem with the movement of muscles in your esophagus.

To make sure you can safely take alendronate, tell your doctor if you have any of these other conditions:

• 
  

  trouble swallowing;

  
  


• 
  

  a vitamin D deficiency;

  
  


• 
  

  a dental problem;

  
  


• 
  

  kidney disease; or

  
  


• 
  

  an ulcer or other problem in your stomach or esophagus.

  
  

Some people using medicines similar to alendronate have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums.

You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and dental surgery or pre-existing dental problems.

Talk with your doctor about the risks and benefits of using this medication.

FDA pregnancy category C. It is not known whether alendronate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether alendronate passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take alendronate?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Alendronate tablets are taken either once each day or once each week.

Take the alendronate tablet first thing in the morning, at least 30 minutes before you eat or drink anything or take any other medicine. If you take an alendronate tablet only once a week, take it on the same day each week and always first thing in the morning.

Take each alendronate tablet with a full glass (6 to 8 ounces) of water. Use only plain water (not mineral water) when taking an alendronate tablet. Do not crush, chew, or suck the alendronate tablet. Swallow the pill whole.

After taking an alendronate tablet, carefully follow these instructions:

• Do not lie down or recline for at least 30 minutes after taking alendronate.


• Do not eat or drink anything other than plain water.


• Do not take any other medicines including vitamins, calcium, or antacids for at least 30 minutes after taking alendronate. It may be best to take your other medicines at a different time of the day. Talk with your doctor about the best dosing schedule for your other medicines.

To be sure this medication is helping your condition, your bone mineral density will need to be tested on a regular basis. Visit your doctor regularly.

If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are using alendronate. You may need to stop using the medicine for a short time.

Alendronate is only part of a complete program of treatment that may also include diet changes, exercise, and taking calcium and vitamin supplements. Follow your diet, medication, and exercise routines very closely.

Store at room temperature away from moisture and heat.

See also: Alendronate dosage (in more detail)

What happens if I miss a dose?

If you take alendronate tablets once daily: If you forget to take this medicine first thing in the morning, do not take it later in the day. Wait until the following morning to take the medicine and skip the missed dose. Do not take two (2) tablets in one day.

If you take alendronate tablets once a week: If you forget to take alendronate on your scheduled day, take it first thing in the morning on the day after you remember the missed dose. Then return to your regular weekly schedule on your chosen dose day. Do not take two (2) tablets in one day.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Drink a full glass of milk and call your local poison control center or emergency room right away. Do not make yourself vomit and do not lie down.

Overdose symptoms may include nausea, heartburn, stomach pain, diarrhea, muscle cramps, numbness or tingling, tight muscles in your face, seizure (convulsions), irritability, and unusual thoughts or behavior.

What should I avoid while taking alendronate?

Avoid taking any other medicines including vitamins, calcium, or antacids for at least 30 minutes after taking an alendronate tablet. Some medicines can make it harder for your body to absorb alendronate. Do not lie down for at least 30 minutes after you take an alendronate tablet.

Alendronate side effects

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

• 
  

  chest pain;

  
  


• 
  

  difficulty or pain when swallowing;

  
  


• 
  

  pain or burning under the ribs or in the back;

  
  


• 
  

  severe heartburn, burning pain in your upper stomach, or coughing up blood;

  
  


• 
  

  new or worsening heartburn;

  
  


• 
  

  fever, body aches, flu symptoms;

  
  


• 
  

  severe joint, bone, or muscle pain;

  
  


• 
  

  new or unusual pain in your thigh or hip;

  
  


• 
  

  jaw pain, numbness, or swelling.

  
  

Less serious side effects may include:

• 
  

  mild heartburn, bloating;

  
  


• 
  

  mild nausea, vomiting, or stomach pain;

  
  


• 
  

  diarrhea, gas, or constipation;

  
  


• 
  

  mild joint pain or swelling;

  
  


• 
  

  swelling in your hands or feet; or

  
  


• 
  

  dizziness, eye pain, headache.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Alendronate Dosing Information

Usual Adult Dose for Osteoporosis:

10 mg orally once a day.

-or-

70 mg orally once a week.

For glucocorticoid induced osteoporosis the initial dosage recommended is 5 mg orally once a day, except for postmenopausal women not receiving estrogen, for whom the recommended dosage is 10 mg orally once a day. Patients treated with glucocorticoids should receive adequate supplements of calcium and vitamin D.

Usual Adult Dose for Paget's Disease:

40 mg orally once a day.

Therapy for Paget's disease should continue for 6 months and may need to be repeated for another 6 months if relapse occurs.

Usual Adult Dose for Prevention of Osteoporosis:

For the prevention of postmenopausal osteoporosis:

5 mg orally once a day.

-or-

35 mg orally once a week.

What other drugs will affect alendronate?

Tell your doctor about all other medicines you use, especially aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as:

• 
  

  celecoxib (Celebrex);

  
  


• 
  

  diclofenac (Voltaren);

  
  


• 
  

  diflunisal (Dolobid);

  
  


• 
  

  ibuprofen (Motrin, Advil);

  
  


• 
  

  indomethacin (Indocin);

  
  


• 
  

  ketoprofen (Orudis)

  
  


• 
  

  ketorolac (Toradol);

  
  


• 
  

  naproxen (Aleve, Naprosyn); or

  
  


• 
  

  piroxicam (Feldene), and others.

  
  

This list is not complete and other drugs may interact with alendronate. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More alendronate resources

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

• alendronate Advanced Consumer (Micromedex) - Includes Dosage Information


• Alendronate Prescribing Information (FDA)


• Alendronate MedFacts Consumer Leaflet (Wolters Kluwer)


• Alendronate Sodium Monograph (AHFS DI)


• Fosamax Prescribing Information (FDA)


• Fosamax Consumer Overview

Compare alendronate with other medications

• Aseptic Necrosis
• Osteoporosis
• Paget's Disease
• Prevention of Osteoporosis

Where can I get more information?

• Your pharmacist can provide more information about alendronate.

See also: alendronate side effects (in more detail)

Skelid

Pronunciation: TYE-loo-DROE-nate
Generic Name: Tiludronate
Brand Name: Skelid

Skelid is used for:

Treating adults with Paget disease. It may also be used for other conditions as determined by your doctor.

Skelid is a bisphosphonate. It works by slowing the resorption of bone and allowing new bone to be formed.

Do NOT use Skelid if:

• you are allergic to any ingredient in Skelid


• you have severe kidney problems


• you are unable to stand or sit for at least 30 minutes

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

Before using Skelid:

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

• if you are pregnant, planning to become pregnant, or are breast-feeding


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


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


• if you have esophagus problems (eg, Barrett esophagus, narrow or blocked esophagus), trouble swallowing, pain or burning with swallowing, or stomach or intestinal problems (eg, ulcers, inflammation)


• if you have a history of kidney problems, heartburn, chest pain, or low blood calcium levels

Some MEDICINES MAY INTERACT with Skelid. However, no specific interactions with Skelid are known at this time.

Ask your health care provider if Skelid may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Skelid:

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

• Skelid is effective only if taken on an empty stomach. Do not take Skelid within 2 hours of eating or drinking.


• Take Skelid by mouth with a full glass of water (6 to 8 oz/180 to 240 mL). Do not lie down for at least 30 minutes after you take Skelid.


• If you are also taking calcium or iron supplements, vitamins, antacids containing calcium, aspirin, or indomethacin, they may interfere with the absorption of Skelid. Do not take Skelid within 2 hours of these medicines.


• If you are also taking an antacid that has aluminum or magnesium in it, take it at least 2 hours after you take Skelid.


• Continue to take Skelid even if you feel well. Do not miss any doses.


• If you miss a dose of Skelid, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses on the same day.

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

Important safety information:

• Skelid may cause drowsiness. This effect may be worse if you take it with alcohol or certain medicines. Use Skelid with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


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


• Do not drink alcohol, smoke, or use other tobacco products while taking Skelid.


• It is important to have enough calcium and vitamin D in your diet. Ask your doctor or pharmacist if you have questions about your diet or about taking dietary supplements such as calcium or vitamin D.


• Talk to your doctor about weight-bearing exercises to increase the calcium density of your bones.


• Skelid may cause jaw bone problems in some patients. Your risk may be greater if you have cancer, poor dental hygiene, or certain other conditions (eg, anemia, blood clotting problems, infections, dental problems). Your risk may also be greater if you use certain medicines or therapies (eg, chemotherapy, corticosteroids, radiation). Talk to your doctor about having a dental exam before you start to use Skelid. Ask your doctor any questions you may have about dental treatment while you use Skelid.


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


• Lab tests, including calcium levels, may be performed while you use Skelid. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Skelid should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Skelid while you are pregnant. It is not known if Skelid is found in breast milk. If you are or will be breast-feeding while you use Skelid, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Skelid:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Abnormal skin sensations; diarrhea; gas; nausea; stomach upset; stuffy nose; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black or bloody stools; chest pain; difficulty swallowing; new, worsening, or severe heartburn; pain when swallowing; red, swollen, blistered, or peeling skin; severe bone, muscle, or joint pain; severe or persistent stomach pain; swelling of the hands or feet; swelling or pain in the jaw; throat pain or irritation; vision changes; vomit that looks like coffee grounds.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Skelid side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Do not lie down. Symptoms may include heartburn; pain upon swallowing; stomach upset or pain; ulcers.

Proper storage of Skelid:

Store Skelid at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Skelid out of the reach of children and away from pets.

General information:

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


• Skelid is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Skelid. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Skelid resources

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

• Skelid Prescribing Information (FDA)


• Skelid Concise Consumer Information (Cerner Multum)


• Skelid Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Skelid with other medications

• Paget's Disease

MultiHance

1. Name Of The Medicinal Product

MultiHance, 0.5 M solution for injection

2. Qualitative And Quantitative Composition

1 ml of solution for injection contains: gadobenic acid 334 mg (0.5M) as the dimeglumine salt.

[Gadobenate dimeglumine 529 mg = gadobenic acid 334 mg + meglumine 195 mg].

5 ml of solution for injection contain: gadobenic acid 1670 mg (2.5 mmol) as dimeglumine salt. [gadobenate dimeglumine 2645 mg = gadobenic acid 1670 mg + meglumine 975 mg]

10 ml of solution for injection contain: gadobenic acid 3340 mg (5 mmol) as dimeglumine salt. [gadobenate dimeglumine 5290 mg = gadobenic acid 3340 mg + meglumine 1950 mg]

15 ml of solution for injection contain: gadobenic acid 5010 mg (7.5 mmol) as dimeglumine salt. [gadobenate dimeglumine 7935= gadobenic acid 5010 mg + meglumine 2925 mg]

20 ml of solution for injection contain: gadobenic acid 6680 mg (10 mmol) as dimeglumine salt. [gadobenate dimeglumine 10580 mg = gadobenic acid 6680 mg + meglumine 3900 mg]

For excipients, see 6.1.

3. Pharmaceutical Form

Solution for injection

Clear aqueous solution filled into colourless glass vials.

Osmolality at 37°C: 1.97 osmol/kg

Viscosity at 37°C: 5.3 mPa.s

4. Clinical Particulars

4.1 Therapeutic Indications

This medicinal product is for diagnostic use only.

MultiHance is a paramagnetic contrast agent for use in diagnostic magnetic resonance imaging (MRI) indicated for :

• MRI of the liver for the detection of focal liver lesions in patients with known or suspected primary liver cancer (eg. hepatocellular carcinoma) or metastatic disease.

• MRI of the brain and spine where it improves the detection of lesions and provides diagnostic information additional to that obtained with unenhanced MRI.

• Contrast-enhanced MR- angiography where it improves the diagnostic accuracy for detecting clinically significant steno-occlusive vascular disease in patients with suspected or known vascular disease of the abdominal or peripheral arteries.

4.2 Posology And Method Of Administration

MRI of the liver: the recommended dose of MultiHance injection in adult patients is 0.05 mmol/kg body weight. This corresponds to 0.1 mL/kg of the 0.5 M solution.

MRI of the brain and spine : the recommended dose of MultiHance injection in adult and in paediatric patients greater than 2 years of age is 0.1 mmol/kg body weight. This corresponds to 0.2 mL/kg of the 0.5 M solution.

MRA: the recommended dose of MultiHance injection in adult patients is 0.1 mmol/kg body weight. This corresponds to 0.2 mL/kg of the 0.5 M solution.

MultiHance should be drawn up into the syringe immediately before use and should not be diluted. Any unused product should be discarded and not be used for other MRI examinations.

To minimise the potential risks of soft tissue extravasation of MultiHance, it is important to ensure that the i.v. needle or cannula is correctly inserted into a vein.

Liver and Brain and Spine: the product should be administered intravenously either as a bolus or slow injection (10 mL/min.).

MRA: the product should be administered intravenously as a bolus injection, either manually or using an automatic injector system.

The injection should be followed by a saline flush.

Post-contrast imaging acquisition:

Liver	Dynamic imaging:	Immediately following bolus injection.
Delayed imaging:	between 40 and 120 minutes following the injection, depending on the individual imaging needs.
Brain and Spine	up to 60 minutes after the administration.
MRA	immediately after the administration, with scan delay calculated on the basis of test bolus or automatic bolus detection technique. If an automatic contrast detection pulse sequence is not used for bolus timing, then a test bolus injection <2 mL of the agent should be used to calculate the appropriate scan delay.

Special Populations

Impaired renal function

Use of MultiHance should be avoided in patients with severe renal impairment (GFR < 30 ml/min/1.73m²) and in patients in the perioperative liver transplantation period unless the diagnostic information is essential and not available with non-contrast enhanced MRI (see section 4.4). If use of MultiHance cannot be avoided, the dose should not exceed 0.1 mmol/kg body weight when used for MR of the brain and spine or MR-angiography and should not exceed 0.05 mmol/kg body weight when used for MR of the liver. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, MultiHance injections should not be repeated unless the interval between injections is at least 7 days.

Elderly (aged 65 years and above)

No dosage adjustment is considered necessary. Caution should be exercised in elderly patients (see section 4.4).

Paediatric population

No dosage adjustment is considered necessary.

Use for MRI of the brain and spine is not recommended in children less than 2 years of age.

Use for MRI of the liver and MRA is not recommended in children less than 18 years of age.

4.3 Contraindications

MultiHance is contra-indicated in:

• patients with hypersensitivity to any of the ingredients.

• in patients with a history of allergic or adverse reactions to other gadolinium chelates.

4.4 Special Warnings And Precautions For Use

Patients should be kept under close supervision for 15 minutes following the injection as the majority of severe reactions occur at this time. The patient should remain in the hospital environment for one hour after the time of injection.

The accepted general safety procedures for Magnetic Resonance Imaging, in particular the exclusion of ferromagnetic objects, for example cardiac pace-makers or aneurysm clips, are also applicable when MultiHance is used.

Caution is advised in patients with cardiovascular disease.

The use of diagnostic contrast media, such as MultiHance, should be restricted to hospitals or clinics staffed for intensive care emergencies and where cardiopulmonary resuscitation equipment is readily available.

Small quantities of benzyl alcohol (<0.2%) may be released by gadobenate dimeglumine during storage. Thus MultiHance should not be used in patients with a history of sensitivity to benzyl alcohol.

As with other gadolinium-chelates, a contrast-enhanced MRI should not be performed within 7 hours of a MultiHance-enhanced MRI examination to allow for clearance of MultiHance from the body.

Impaired renal function

Prior to administration of MultiHance, it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some gadolinium containing contrast agents in patients with acute or chronic severe renal impairment (GFR<30ml/min/1.73m²).

Patients undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with MultiHance, it should therefore be avoided in patients with severe renal impairment and in patients in the perioperative liver transplantation period unless the diagnostic information is essential and not available with non-contrast enhanced MRI.

Haemodialysis shortly after MultiHance administration may be useful at removing MultiHance from the body. There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis.

Elderly

As the renal clearance of gadobenate dimeglumine may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Interaction studies with other medicinal products were not carried out during the clinical development of MultiHance. However no drug interactions were reported during the clinical development programme.

4.6 Pregnancy And Lactation

Pregnancy

There are no data from the use of gadobenate dimeglumine in pregnant women. Animal studies have shown reproductive toxicity at repeated high doses (see section 5.3).MultiHance should not be used during pregnancy unless the clinical condition of the woman requires use of gadobenate dimeglumine.

Lactation

Gadolinium containing contrast agents are excreted into breast milk in very small amounts (see section 5.3). At clinical doses, no effects on the infant are anticipated due to the small amount excreted into milk and poor absorption from the gut. Continuing or discontinuing breast feeding for a period of 24 hours after administration of MultiHance should be at the discretion of the doctor and lactating mother.

4.7 Effects On Ability To Drive And Use Machines

On the basis of the pharmacokinetic and pharmacodynamic profiles, no or negligible influence is expected with the use of MultiHance on the ability to drive or use machines.

4.8 Undesirable Effects

The following adverse events were seen during the clinical development of MultiHance among 2637 adult subjects. There were no adverse reactions with a frequency greater than 2%.

System organ classes	Common (	Uncommon (	Rare (
Infections and infestations		Nasopharyngitis
Nervous system disorders	Headache	Paraesthesia, dizziness, syncope, parosmia	Hyperaesthesia, tremor,intracranial hypertension, hemiplegia
Eye disorders			Conjunctivitis
Ear and labyrinth disorders			Tinnitus
Cardiac disorders		Tachycardia, atrial fibrillation, first-degree atrioventricular block, ventricular extrasystoles, sinus bradycardia,	Arrhythmia, myocardial ischaemia, prolonged PR interval
Vascular disorders		Hypertension, hypotension
Respiratory, thoracic and mediastinal disorders		Rhinitis,	Dyspnoea N.O.S., laryngospasm, wheezing, pulmonary congestion, pulmonary oedema
Gastrointestinal disorders	Nausea	Dry mouth, taste perversion, diarrhoea, vomiting, dyspepsia, salivation, abdominal pain	Constipation, faecal incontinence, necrotising pancreatitis
Skin & subcutaneous tissue disorders		Pruritus, rash, face oedema, urticaria, sweating
Musculoskeletal, connective tissue and bone disorders		Back pain, myalgia
Renal and urinary disorders			Urinary incontinence, urinary urgency
General disorders and administration site conditions	Injection Site Reaction, feeling hot	Asthenia, fever, chills, chest pain, pain, injection site pain, injection site extravasation	injection site inflammation
Investigations		Abnormal laboratory tests, abnormal ECG, prolonged QT

Laboratory abnormalities cited above include hypochromic anaemia, leukocytosis, leukopenia, basophilia, hypoproteinaemia, hypocalcaemia, hyperkalaemia, hyperglycaemia or hypoglycaemia, albuminuria, glycosuria, haematuria, hyperlipidaemia, hyperbilirubinaemia, serum iron increased, and increases in serum transaminases, alkaline phosphatase, lactic dehydrogenase, and in serum creatinine and were reported in equal or less than 0.4% of patients following the administration of MultiHance. However these findings were mostly seen in patients with evidence of pre-existing impairment of hepatic function or pre-existing metabolic disease.

The majority of these events were non-serious, transient and spontaneously resolved without residual effects. There was no evidence of any correlation with age, gender or dose administered.

Paediatric

In paediatric patients enrolled in clinical trials the most commonly reported adverse reactions included vomiting (1.4%), pyrexia (0.9%) and hyperhydrosis (0.9%). The frequency and nature of adverse reactions was similar to that in adults.

In marketed use, adverse reactions were reported in fewer than 0.1 % of patients.

Most commonly reported were: nausea, vomiting, signs and symptoms of hypersensitivity reactions including anaphylactic shock, anaphylactoid reactions, angioedema, laryngeal spasm and rash.

Injection site reactions due to extravasation of the contrast medium leading to local pain or burning sensations, swelling and blistering have been reported.

Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with MultiHance in patients co-administered other gadolinium-containing contrast agents (see Section 4.4).

4.9 Overdose

There have been no cases of overdose reported. Therefore, the signs and symptoms of overdosage have not been characterised. Doses up to 0.4 mmol/kg were administered to healthy volunteers, without any serious adverse events. However, doses exceeding the specific approved dosage are not recommended. In the event of overdosage, the patient should be carefully monitored and treated symptomatically.

MultiHance can be removed by haemodialysis. However there is no evidence that haemodialysis is suitable for prevention of nephrogenic systemic fibrosis (NSF).

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: paramagnetic contrast media, ATC code V08CA08

In liver imaging, MultiHance may detect lesions not visualised in pre-contrast enhanced MRI examination of patients with known or suspected hepatocellular cancer or metastatic disease. The nature of the lesions visualised after contrast enhancement with MultiHance has not been verified by pathological anatomical investigation. Furthermore, where the effect on patient management was assessed, the visualisation of post-contrast-enhanced lesions was not always associated with a change in the patient management.

The gadolinium chelate, gadobenate dimeglumine, shortens longitudinal (T1), and, to a lesser extent, transversal (T2) relaxation times of tissue water protons.

The relaxivities of gadobenate dimeglumine in aqueous solution are r₁ = 4.39 and r₂ = 5.56 mM^-1s^-1 at 20 MHz.

Gadobenate dimeglumine experiences a strong increase in relaxivity on going from aqueous solution to solutions containing serum proteins, r₁ and r₂ values were 9.7 and 12.5 respectively in human plasma.

In the liver MultiHance provides strong and persistent signal intensity enhancement of normal parenchyma on T1-weighted imaging. The signal intensity enhancement persists at high level for at least two hours after the administration of doses of either 0.05 or 0.10 mmol/kg. Contrast between focal liver lesions and normal parenchyma is observed almost immediately after bolus injection (up to 2-3 minutes) on T1-weighted dynamic imaging. Contrast tends to decrease at later time points because of non-specific lesion enhancement. However, progressive washout of MultiHance from the lesions and persistent signal intensity enhancement of normal parenchyma are considered to result in enhanced lesion detection and a lower detection threshold for lesion site between 40 and 120 minutes after MultiHance administration.

Data from pivotal Phase II and Phase III studies in patients with liver cancer indicate that, compared with other reference imaging modalities (e.g. intraoperative ultrasonography, computed tomographic angio-portography, CTAP, or computed tomography following intra-arterial injection of iodized oil), with MultiHance enhanced MRI scans there was a mean sensitivity of 95% and a mean specificity of 80% for detection of liver cancer or metastasis in patients with a high suspicion of these conditions.

In MRI of the brain and spine, MultiHance enhances normal tissues lacking a blood-brain barrier, extra axial tumours and regions in which the blood-brain-barrier has broken down. In the pivotal phase III clinical trials conducted in adults for this indication, designed as parallel-group comparisons, off-site readers reported an improvement in level of diagnostic information in 32-69% of images with MultiHance, and 35-69% of images with the active comparator.

In two studies designed as intra-individual, crossover comparisons of 0.1 mmol/kg body weight MultiHance vs 0.1 mmol/kg body weight of two active comparators (gadopentetate dimeglumine or gadodiamide), conducted in patients with known or suspected brain or spine disease undergoing MRI of the central nervous system (CNS), MultiHance provided significantly (p<0.001) higher increase in lesion signal intensity, contrast-to-noise ratio, and lesion-to-brain ratio, as well as significantly (p<0.001) better visualisation of CNS lesions in images obtained with 1.5 Tesla scanners as tabulated below.

Visualisation of CNS Lesions Endpoints	Improvement Provided by MultiHance Over gadopentetate dimeglumine (Study MH-109) (n=151)	p-value	Improvement Provided by MultiHance Over gadodiamide (Study MH-130) (n=113)	p-value
Definition of extent of CNS Disease	25% to 30%	<0.001	24% to 25%	<0.001
Visualisation of Lesion Internal Morphology	29% to 34%	<0.001	28% to 32%	<0.001
Delineation of Borders of Intra- and Extra-axial Lesions	37% to 44%	<0.001	35% to 44%	<0.001
Lesion Contrast Enhancement	50% to 66%	<0.001	58% to 67%	<0.001
Global Diagnostic Preference	50% to 68%	<0.001	56% to 68%	<0.001

In the trials MH-109 and MH-130, the impact of improved visualization of CNS lesions with MultiHance versus gadodiamide or gadopentetate dimeglumine on diagnostic thinking and patient management was not studied.

In MRA, MultiHance improves image quality by increasing blood signal to noise ratio as a result of blood T1 shortening, reduces motion artifacts by shortening scan times and eliminates flow artifacts. In the phase III clinical trials in MRA of arteries extending from the supra-aortic territory to the pedal circulation, off-site readers reported an improvement in diagnostic accuracy ranging from 8% to 28% for the detection of clinically significant steno-occlusive disease (i.e. stenosis of >51% or >60% depending on the vascular territory) with MultiHance-enhanced images compared to time of flight (TOF) MRA, on the basis of conventional angiographic findings.

5.2 Pharmacokinetic Properties

Modelling of the human pharmacokinetics was well described using a biexponential decay model. The apparent distribution and elimination half-times range from 0.085 to 0.117 h and from 1.17 to 1.68 respectively. The apparent total volume of distribution, ranging from 0.170 to 0.248 L/kg body weight, indicates that the compound is distributed in plasma and in the extracellular space.

Gadobenate ion is rapidly cleared from plasma and is eliminated mainly in urine and to a lesser extent in bile. Total plasma clearance, ranging from 0.098 to 0.133 L/h kg body weight, and renal clearance, ranging from 0.082 to 0.104 L/h kg body weight, indicate that the compound is predominantly eliminated by glomerular filtration. Plasma concentration and area under the curve (AUC) values show statistically significant linear dependence on the administered dose. Gadobenate ion is excreted unchanged in urine in amounts corresponding to 78%-94% of the injected dose within 24 hours. Between 2% and 4% of the dose is recovered in the faeces.

Gadobenate ion does not cross the intact blood-brain barrier and, therefore, does not accumulate in normal brain or in lesions that have a normal blood-brain barrier. However, disruption of the blood-brain barrier or abnormal vascularity allows gadobenate ion penetration into the lesion.

Population pharmacokinetic analysis was performed on systemic drug concentration-time data from 80 subjects (40 adult healthy volunteers and 40 paediatric patients) aged 2 to 47 years following intravenous administration of gadobenate dimeglumine. The kinetics of gadolinium down to the age of 2 years could be described by a two compartment model with standard allometric coefficients and a covariate effect of creatinine clearance (reflecting glomerular filtration rate) on gadolinium clearance. The pharmacokinetic parameter values (referenced to adult body weight) were consistent with previously reported values for MultiHance and consistent with the physiology presumed to underlie MultiHance distribution and elimination: distribution into extracellular fluid (approximately 15 L in an adult, or 0.21 L/kg) and elimination by glomerular filtration (approximately 130 mL plasma per minute in an adult, or 7.8 L/h and 0.11 L/h/kg). Clearance and volume of distribution decreased progressively for younger subjects due to their smaller body size. This effect could largely be accounted for by normalising pharmacokinetic parameters for body weight. Based on this analysis, weight based dosing for MultiHance in paediatric patients gives similar systemic exposure (AUC) and maximum concentration (Cmax) to those reported for adults, and confirms that no dose adjustment is necessary for the paediatric population over the proposed age range (2 years and above).

5.3 Preclinical Safety Data

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

Indeed, preclinical effects were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

Animal experiments revealed a poor local tolerance of MultiHance, especially in case of accidental paravenous application where severe local reaction, such as necrosis and eschars, could be observed.

Local tolerance in case of accidental intra-arterial application has not been investigated, so that it is particularly important to ensure that the i.v. needle or cannula is correctly inserted into a vein (see section 4.2).

Pregnancy and lactation

In animal studies no untoward effects on the embryonic or foetal development were exerted by daily intravenous administration of gadobenate dimeglumine in rats. Also, no adverse effects on physical and behavioural development were observed in the offspring of rats. However, after repeated daily dosing in rabbit, isolated cases of skeletal variations and two cases of visceral malformations were reported.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Water for injections.

6.2 Incompatibilities

MultiHance should not be admixed with any other drug.

6.3 Shelf Life

3 years

From a microbiological point of view, the product should be used immediately after drawing into the syringe.

6.4 Special Precautions For Storage

Do not freeze.

6.5 Nature And Contents Of Container

5 mL, 10 mL, 15 mL and 20 mL of a clear aqueous solution filled into single dose colourless type I glass vials with elastomeric closures, aluminium sealing crimps and polypropylene caps.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

MultiHance should be drawn up into the syringe immediately before use and should not be diluted.

Before use, examine the product to assure that the container and closure have not been damaged, the solution is not discoloured and no particulate matter is present.

When MultiHance is used in conjunction with an injector system, the connecting tubes to the patient and the relevant disposable parts should be disposed after each patient examination. Any additional instructions from the respective equipment manufacturer must also be adhered to.

The peel-off tracking label on the vials should be stuck onto the patient records to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded.

For single use only. Any unused product should be discarded.

7. Marketing Authorisation Holder

Bracco spa

Via Egidio Folli 50

20134 Milan - Italy

8. Marketing Authorisation Number(S)

PL 06099/0006

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 22 July 1997

Date of last renewal: 21 July 2007

10. Date Of Revision Of The Text

10/08/2011