Melanocyl

Melanocyl may be available in the countries listed below.

Ingredient matches for Melanocyl

Methoxsalen

Methoxsalen is reported as an ingredient of Melanocyl in the following countries:

• India

International Drug Name Search

Healtheries Vitamin C

Healtheries Vitamin C may be available in the countries listed below.

Ingredient matches for Healtheries Vitamin C

Ascorbic Acid

Ascorbic Acid is reported as an ingredient of Healtheries Vitamin C in the following countries:

• New Zealand

International Drug Name Search

Morixon

Morixon may be available in the countries listed below.

Ingredient matches for Morixon

Morphine

Morphine sulphate pentahydrate (a derivative of Morphine) is reported as an ingredient of Morixon in the following countries:

• Germany

International Drug Name Search

Serta

Serta may be available in the countries listed below.

Ingredient matches for Serta

Sertraline

Sertraline hydrochloride (a derivative of Sertraline) is reported as an ingredient of Serta in the following countries:

• India


• Sri Lanka


• Vietnam

International Drug Name Search

Lisinopril-Merck

Lisinopril Merck may be available in the countries listed below.

Ingredient matches for Lisinopril Merck

Lisinopril

Lisinopril is reported as an ingredient of Lisinopril Merck in the following countries:

• Luxembourg

Lisinopril dihydrate (a derivative of Lisinopril) is reported as an ingredient of Lisinopril Merck in the following countries:

• Netherlands


• Portugal


• Spain

International Drug Name Search

Lunis

Lunis may be available in the countries listed below.

Ingredient matches for Lunis

Flunisolide

Flunisolide is reported as an ingredient of Lunis in the following countries:

• Italy

International Drug Name Search

Bronchofyline

Bronchofyline may be available in the countries listed below.

Ingredient matches for Bronchofyline

Theophylline

Theophylline is reported as an ingredient of Bronchofyline in the following countries:

• Tunisia

International Drug Name Search

Robafen AC

Generic Name: codeine and guaifenesin (KOE deen and gwye FEN a sin)

Brand Names: Allfen CD, Allfen CDX, Brontex, Cheracol with Codeine, Cheratussin AC, Dex-Tuss, Diabetic Tussin C, Duraganidin NR, ExeClear-C, Guaiatussin AC, Guaifen-C, Guiatuss AC, Guiatussin with Codeine, Iophen-C NR, M-Clear WC, Mar-cof CG, Mytussin AC, Robafen AC, Robitussin-AC, Tussi-Organidin NR, Tussi-Organidin-S NR, Tussiden C, Tusso-C

What is Robafen AC (codeine and guaifenesin)?

Codeine is in a group of drugs called narcotics. It is a cough suppressant that affects the signals in the brain that trigger cough reflex.

Guaifenesin is an expectorant. It helps loosen mucus congestion in your chest and throat, making it easier to cough out through your mouth.

The combination of codeine and guaifenesin is used to treat cough and to reduce chest congestion caused by upper respiratory infections or the common cold.

Codeine and guaifenesin will not treat a cough that is caused by smoking, asthma, or emphysema.

Codeine and guaifenesin may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Robafen AC (codeine and guaifenesin)?

Ask a doctor or pharmacist before using any other cough or cold medicine. Guaifenesin is contained in many combination medicines. Taking certain products together can cause you to get too much guaifenesin. Check the label to see if a medicine contains an guaifenesin, or an expectorant. This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Codeine may be habit-forming and should be used only by the person it was prescribed for. This medication should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it. Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

What should I discuss with my healthcare provider before taking Robafen AC (codeine and guaifenesin)?

You should not take this medication if you are allergic to codeine or guaifenesin.

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

• 
  

  heart disease, heart rhythm disorder;

  
  


• 
  

  asthma, COPD, emphysema, or other breathing disorders;

  
  


• 
  

  a history of head injury or brain tumor;

  
  


• 
  

  epilepsy or other seizure disorder;

  
  


• 
  

  a stomach or intestinal disorder;

  
  


• 
  

  Addison's disease or other adrenal gland disorders;

  
  


• 
  

  curvature of the spine;

  
  


• 
  

  a thyroid disorder;

  
  


• liver or kidney disease;


• 
  

  enlarged prostate; or

  
  


• 
  

  a history of depression, mental illness, or drug addiction;

  
  

FDA pregnancy category C. It is not known whether codeine and guaifenesin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Codeine may be habit forming and should be used only by the person it was prescribed for. Never share this medication with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. Codeine can pass into breast milk and may harm a nursing baby. The use of codeine by some nursing mothers may lead to life-threatening side effects in the baby. Do not use this medication if you are breast-feeding a baby. Older adults may be more likely to have side effects from this medication.

Liquid forms of this medication may contain sugar or artificial sweetener (phenylalanine). Talk to your doctor before using this form of codeine and guaifenesin if you have diabetes or phenylketonuria (PKU).

How should I take Robafen AC (codeine and guaifenesin)?

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. Cough or cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Take codeine and guaifenesin with food if it upsets your stomach. Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Call your doctor if your symptoms do not improve after 7 days of treatment, or if you also have a fever, headache, or skin rash.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using codeine and guaifenesin.

Do not stop using this medication suddenly after long-term use or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using the medication. Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Keep track of the amount of medicine used from each new bottle. Codeine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

What happens if I miss a dose?

Since cough medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of codeine can be fatal.

Overdose symptoms may include extreme dizziness or drowsiness, nausea, vomiting, sweating, confusion, hallucinations, cold and clammy skin, blue-colored lips or fingernails, weak or limp muscles, pinpoint pupils, weak pulse, slow breathing, fainting, or seizures (convulsions).

What should I avoid while taking Robafen AC (codeine and guaifenesin)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Ask a doctor or pharmacist before using any other cough or cold medicine. Guaifenesin is contained in many combination medicines. Taking certain products together can cause you to get too much guaifenesin. Check the label to see if a medicine contains an guaifenesin, or an expectorant. Drinking alcohol can increase certain side effects of codeine and guaifenesin.

Robafen AC (codeine and guaifenesin) 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 taking this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  severe dizziness or drowsiness;

  
  


• 
  

  confusion, hallucinations, unusual thoughts or behavior;

  
  


• 
  

  urinating less than usual or not at all; or

  
  


• 
  

  slow heart rate, weak pulse, fainting, weak or shallow breathing.

  
  

Less serious side effects include:

• 
  

  dizziness, drowsiness, headache;

  
  


• 
  

  warmth, redness, or tingling under your skin;

  
  


• 
  

  nausea, vomiting, upset stomach;

  
  


• 
  

  constipation; or

  
  


• 
  

  skin rash or itching.

  
  

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.

What other drugs will affect Robafen AC (codeine and guaifenesin)?

Before taking this medication, tell your doctor if you regularly use other medicines that make you sleepy (such as allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by codeine and guaifenesin.

Also tell your doctor if you are using any of the following drugs:

• 
  

  cimetidine (Tagamet);

  
  


• 
  

  quinidine (Quin-G);

  
  


• 
  

  naloxone (Narcan); or

  
  


• 
  

  naltrexone (Vivitrol).

  
  

This list is not complete and other drugs may interact with codeine and guaifenesin. 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 Robafen AC resources

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

• Brontex MedFacts Consumer Leaflet (Wolters Kluwer)


• ExeClear-C Prescribing Information (FDA)


• Guiatuss AC Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Robafen AC with other medications

• Cough

Where can I get more information?

• Your pharmacist can provide more information about codeine and guaifenesin.

See also: Robafen AC side effects (in more detail)

Ranitidine Effervescent Tablets

Pronunciation: ra-NI-ti-deen
Generic Name: Ranitidine
Brand Name: Zantac 25 mg EFFERdose

Ranitidine Effervescent Tablets are used for:

Treating heartburn or irritation of the esophagus caused by gastroesophageal reflux disease (GERD). It may be used to treat severe irritation of the esophagus (erosive esophagitis) and to maintain healing of erosive esophagitis. It may be used for short-term treatment of stomach or small intestinal ulcers. It may be used to treat conditions that cause your body to make too much stomach acid (eg, Zollinger-Ellison syndrome). It may also be used for other conditions as determined by your doctor.

Ranitidine Effervescent Tablets are an H₂-receptor blocker. It works by blocking the action of histamine in the stomach. This reduces the amount of acid the stomach makes. Reducing stomach acid helps to reduce heartburn, heal irritation of the esophagus, and heal ulcers of the stomach or intestines.

Do NOT use Ranitidine Effervescent Tablets if:

• you are allergic to any ingredient in Ranitidine Effervescent Tablets


• you have a history of the blood disease porphyria


• you are taking dasatinib

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

Before using Ranitidine Effervescent Tablets:

Some medical conditions may interact with Ranitidine Effervescent Tablets. 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 a history of kidney or liver problems


• if you have phenylketonuria

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

• Certain benzodiazepines (eg, midazolam, triazolam), glipizide, procainamide, or warfarin because the risk of their side effects may be increased by Ranitidine Effervescent Tablets


• Anticoagulants (eg, warfarin) because the risk of their side effects may be increased or their effectiveness may be decreased by Ranitidine Effervescent Tablets


• Dasatinib, delavirdine, gefitinib, certain HIV protease inhibitors (eg, atazanavir), itraconazole, or ketoconazole because their effectiveness may be decreased by Ranitidine Effervescent Tablets

This may not be a complete list of all interactions that may occur. Ask your health care provider if Ranitidine Effervescent Tablets 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 Ranitidine Effervescent Tablets:

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

• Take Ranitidine Effervescent Tablets by mouth with or without food.


• Do not chew or swallow the tablet or dissolve it on the tongue. Place the tablet in a glass and add at least 5 mL (1 teaspoonful) of water, as directed by your doctor. Allow the tablet to dissolve completely, then drink all of the liquid. Rinse the container with an additional small amount of water and drink the contents to ensure the entire dose is taken. You may use a dropper or oral syringe to give Ranitidine Effervescent Tablets. Ask your pharmacist for help if you are unsure of how to prepare or use Ranitidine Effervescent Tablets.


• If you also take itraconazole or ketoconazole, ask your doctor or pharmacist how to take it with Ranitidine Effervescent Tablets.


• You may take antacids while you are using Ranitidine Effervescent Tablets if you are directed to do so by your doctor.


• Continue to take Ranitidine Effervescent Tablets even if you feel well. Do not miss any doses.


• If you miss a dose of Ranitidine Effervescent Tablets, 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 Ranitidine Effervescent Tablets.

Important safety information:

• Ranitidine Effervescent Tablets may rarely cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Ranitidine Effervescent Tablets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Some of these products contain phenylalanine. If you must have a diet that is low in phenylalanine, ask your pharmacist if it is in your product.


• Ranitidine Effervescent Tablets may interfere with certain lab tests, including urine protein tests. Be sure your doctor and lab personnel know you are taking Ranitidine Effervescent Tablets.


• Ranitidine Effervescent Tablets should not be used in CHILDREN younger than 1 month old; 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 using Ranitidine Effervescent Tablets while you are pregnant. Ranitidine Effervescent Tablets are found in breast milk. If you are or will be breast-feeding while you use Ranitidine Effervescent Tablets, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Ranitidine Effervescent Tablets:

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; diarrhea; headache; nausea; stomach upset.

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); change in the amount of urine produced; confusion; dark urine; depression; fast, slow, or irregular heartbeat; fever, chills, or sore throat; hallucinations; severe or persistent headache or stomach pain; unusual bruising or bleeding; yellowing of the eyes or skin.

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.

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 dizziness; trouble walking.

Proper storage of Ranitidine Effervescent Tablets:

Store Ranitidine Effervescent Tablets between 36 and 86 degrees F (2 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Ranitidine Effervescent Tablets out of the reach of children and away from pets.

General information:

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


• Ranitidine Effervescent Tablets are 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 Ranitidine Effervescent Tablets. 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 Ranitidine resources

• Ranitidine Use in Pregnancy & Breastfeeding
• Drug Images
• Ranitidine Drug Interactions
• Ranitidine Support Group
• 32 Reviews for Ranitidine - Add your own review/rating

Compare Ranitidine with other medications

• Duodenal Ulcer
• Duodenal Ulcer Prophylaxis
• Erosive Esophagitis
• Gastric Ulcer Maintenance Treatment
• Gastrointestinal Hemorrhage
• GERD
• Indigestion
• Pathological Hypersecretory Conditions
• Stomach Ulcer
• Stress Ulcer Prophylaxis
• Surgical Prophylaxis
• Zollinger-Ellison Syndrome

Latesyl

Latesyl may be available in the countries listed below.

Ingredient matches for Latesyl

Diethylamine Salicylate

Diethylamine Salicylate is reported as an ingredient of Latesyl in the following countries:

• Austria

Myrtecaine

Myrtecaine is reported as an ingredient of Latesyl in the following countries:

• Austria

International Drug Name Search

Robaxin-750

Generic Name: methocarbamol (Oral route)

meth-oh-KAR-ba-mol

Commonly used brand name(s)

In the U.S.

• Robaxin


• Robaxin-750

Available Dosage Forms:

• Tablet

Therapeutic Class: Skeletal Muscle Relaxant, Centrally Acting

Uses For Robaxin-750

Methocarbamol is used to relieve the discomfort caused by acute (short-term), painful muscle or bone conditions. However, this medicine does not take the place of rest, exercise, physical therapy, or other treatment that your doctor may recommend for your medical problem .

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

Before Using Robaxin-750

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 have not been performed on the relationship of age to the effects of methocarbamol in children below 16 years of age. Safety and efficacy have not been established .

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of methocarbamol in the elderly. However, elderly patients are more sensitive to the effects of this medicine than 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

Studies in women suggest that this medication poses minimal risk to the infant when used during 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.

• Adinazolam


• Alfentanil


• Alprazolam


• Amobarbital


• Anileridine


• Aprobarbital


• Bromazepam


• Brotizolam


• Butabarbital


• Butalbital


• Carisoprodol


• Chloral Hydrate


• Chlordiazepoxide


• Chlorzoxazone


• Clobazam


• Clonazepam


• Clorazepate


• Codeine


• Dantrolene


• Diazepam


• Estazolam


• Ethchlorvynol


• Fentanyl


• Flunitrazepam


• Flurazepam


• Halazepam


• Hydrocodone


• Hydromorphone


• Ketazolam


• Levorphanol


• Lorazepam


• Lormetazepam


• Medazepam


• Meperidine


• Mephenesin


• Mephobarbital


• Meprobamate


• Metaxalone


• Methocarbamol


• Methohexital


• Midazolam


• Morphine


• Morphine Sulfate Liposome


• Nitrazepam


• Nordazepam


• Oxazepam


• Oxycodone


• Oxymorphone


• Pentobarbital


• Phenobarbital


• Prazepam


• Primidone


• Propoxyphene


• Quazepam


• Remifentanil


• Secobarbital


• Sodium Oxybate


• Sufentanil


• Temazepam


• Thiopental


• Triazolam

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:

• Kidney disease or


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

• Myasthenia gravis—Use with caution. Methocarbamol may worsen this condition .

Proper Use of methocarbamol

This section provides information on the proper use of a number of products that contain methocarbamol. It may not be specific to Robaxin-750. 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 oral dosage form (tablets):
  
  • For relaxing stiff muscles:
    
    • Adults—At first, three tablets of 500 milligrams (mg) or two tablets of 750 mg (total dose of 1500 mg) four times a day. Your doctor may decrease your dose after you begin to feel better.
    
    
    • Children—Use and dose must be determined by your doctor .
    
    
  
  

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.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Robaxin-750

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects .

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; or anesthetics, including some dental anesthetics. Check with your medical doctor or dentist before taking any of the above while you are taking this medicine .

This medicine may cause some people to become dizzy or drowsy. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous.

This medicine may change the color of your urine. Before you have any medical tests, tell your doctor that you are taking this medicine .

Robaxin-750 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:

Incidence not known

• Abdominal or stomach pain


• black, tarry stools


• changes in skin color


• chest pain or discomfort


• chills


• clay-colored stools


• cough


• dark urine


• diarrhea


• difficulty swallowing


• dizziness


• fast heartbeat


• feeling of warmth


• fever


• headache


• hives


• itching


• joint or muscle pain


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


• lightheadedness, dizziness, or fainting


• loss of appetite


• loss of bladder control


• loss of consciousness


• loss of memory


• nausea


• numbness or tingling of face, hands, or feet


• pain, tenderness, or swelling of foot or leg


• painful or difficult urination


• problems with memory


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


• redness and soreness of eyes


• redness of the face, neck, arms, and occasionally, upper chest


• relaxed and calm


• shortness of breath


• skin rash


• sleepiness


• slow or irregular heartbeat


• sore throat


• sores, ulcers, or white spots on lips or in mouth


• swollen glands


• tightness in chest


• total body jerking


• unpleasant breath odor


• unusual bleeding or bruising


• unusual tiredness or weakness


• vomiting of blood


• wheezing


• yellow eyes or skin

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

Symptoms of Overdose

• Shaking or jerking of one area or side of the body


• sweating

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:

Incidence not known

• Acid or sour stomach


• belching


• double vision


• drowsiness


• feeling of constant movement of self or surroundings


• heartburn


• indigestion


• mood or mental changes


• seeing double


• sensation of spinning


• sleeplessness


• stomach discomfort, upset, or pain


• trouble sleeping


• unable to sleep


• uncontrolled eye movements

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: Robaxin-750 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 Robaxin-750 resources

• Robaxin-750 Side Effects (in more detail)
• Robaxin-750 Use in Pregnancy & Breastfeeding
• Drug Images
• Robaxin-750 Drug Interactions
• Robaxin-750 Support Group
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Rilutek

riluzole

Dosage Form: tablet, film coated
Rilutek®

(riluzole) Tablets

Rilutek Description

Rilutek® (riluzole) is a member of the benzothiazole class. Chemically, riluzole is 2-amino-6-(trifluoromethoxy)benzothiazole. Its molecular formula is C8H5F3N2OS and its molecular weight is 234.2. Its structural formula is as follows:

Riluzole is a white to slightly yellow powder that is very soluble in dimethylformamide, dimethylsulfoxide and methanol, freely soluble in dichloromethane, sparingly soluble in 0.1 N HCl and very slightly soluble in water and in 0.1 N NaOH. Rilutek is available as a capsule-shaped, white, film-coated tablet for oral administration containing 50 mg of riluzole. Each tablet is engraved with "RPR 202" on one side.

Inactive Ingredients

Core: anhydrous dibasic calcium phosphate, USP; microcrystalline cellulose, NF; anhydrous colloidal silica, NF; magnesium stearate, NF; croscarmellose sodium, NF.

Film coating: hypromellose, USP; polyethylene glycol 6000; titanium dioxide, USP.

Rilutek - Clinical Pharmacology

Mechanism of Action

The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective.

The mode of action of Rilutek is unknown. Its pharmacological properties include the following, some of which may be related to its effect: 1) an inhibitory effect on glutamate release, 2) inactivation of voltage-dependent sodium channels, and 3) ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors.

Riluzole has also been shown, in a single study, to delay median time to death in a transgenic mouse model of ALS. These mice express human superoxide dismutase bearing one of the mutations found in one of the familial forms of human ALS.

It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. In in vitro tests, riluzole protected cultured rat motor neurons from the excitotoxic effects of glutamic acid and prevented the death of cortical neurons induced by anoxia.

Due to its blockade of glutamatergic neurotransmission, riluzole also exhibits myorelaxant and sedative properties in animal models at doses of 30 mg/kg (about 20 times the recommended human daily dose) and anticonvulsant properties at a dose of 2.5 mg/kg (about 2 times the recommended human daily dose).

Pharmacokinetics

Riluzole is well-absorbed (approximately 90%), with average absolute oral bioavailability of about 60% (CV=30%). Pharmacokinetics are linear over a dose range of 25 to 100 mg given every 12 hours. A high fat meal decreases absorption, reducing AUC by about 20% and peak blood levels by about 45%. The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses. With multiple-dose administration, riluzole accumulates in plasma by about twofold and steady-state is reached in less than 5 days. Riluzole is 96% bound to plasma proteins, mainly to albumin and lipoproteins over the clinical concentration range.

The 50 mg market tablet was equivalent, with respect to AUC, to the tablet used in the dose ranging clinical trials, while the Cmax was approximately 30% higher. Both tablets have been used in clinical trials. However, if doses greater than those recommended are given, it is likely that higher plasma levels will be achieved, the safety of which has not been established (see DOSAGE AND ADMINISTRATION).

Metabolism and Elimination

Riluzole is extensively metabolized to six major and a number of minor metabolites, not all of which have been identified. Some metabolites appear pharmacologically active in in vitro assays. The metabolism of riluzole is mostly hepatic and consists of cytochrome P450-dependent hydroxylation and glucuronidation.

There is marked interindividual variability in the clearance of riluzole, probably attributable to variability of CYP 1A2 activity, the principal isozyme involved in N-hydroxylation.

In vitro studies using liver microsomes show that hydroxylation of the primary amine group producing N-hydroxyriluzole is the main metabolic pathway in human, monkey, dog and rabbit. In humans, cytochrome P450 1A2 is the principal isozyme involved in N-hydroxylation. In vitro studies predict that CYP 2D6, CYP 2C19, CYP 3A4 and CYP 2E1 are unlikely to contribute significantly to riluzole metabolism in humans. Whereas direct glucuroconjugation of riluzole (involving the glucurotransferase isoform UGT-HP4) is very slow in human liver microsomes, N-hydroxyriluzole is readily conjugated at the hydroxylamine group resulting in the formation of O- (>90%) and N-glucuronides.

Following a single 150 mg dose of 14C-riluzole to 6 healthy males, 90% and 5% of the radioactivity was recovered in the urine and feces respectively over a period of 7 days. Glucuronides accounted for more than 85% of the metabolites in urine. Only 2% of a riluzole dose was recovered in the urine as unchanged drug.

Special Populations

Hepatic Impairment

The area-under-the-curve (AUC) of riluzole, after a single 50 mg oral dose, increases by about 1.7-fold in patients with mild chronic liver insufficiency (n=6; Child-Pugh's score A) and by about 3-fold in patients with moderate chronic liver insufficiency (n=6; Child-Pugh's score B) compared to healthy volunteers (n=12) (see WARNINGS and PRECAUTIONS). The pharmacokinetics of riluzole have not been studied in patients with severe hepatic impairment.

Renal Impairment

There is no significant difference in pharmacokinetic parameters between patients with moderate (n=5; creatinine clearance 30–50 ml.min-1) and severe (n=7; creatinine clearance <30 ml.min-1) renal insufficiency and healthy volunteers (n=12) after a single oral dose of 50 mg riluzole. The pharmacokinetics of riluzole have not been studied in patients undergoing hemodialysis.

Age

The pharmacokinetic parameters of riluzole after multiple dose administration (4.5 days of treatment at 50 mg riluzole b.i.d.) are not affected in the elderly (≥ 70 years).

Gender

No gender effect on riluzole pharmacokinetics has been found in young or elderly healthy subjects. However, in one placebo-controlled clinical trial with population pharmacokinetics, riluzole mean clearance was found to be 30% lower in female patients (corresponding to an approximate increase in AUC of 45%) as compared to male patients. No favorable or adverse effects of riluzole in relation to gender were seen in controlled trials, however.

Smoking

Patients who smoke cigarettes eliminate riluzole 20% faster than non-smoking patients, based on a population pharmacokinetic analysis on data from 128 ALS patients, of whom 19 were smokers. However, there is no need for dosage adjustment in these patients.

Race

A clinical study conducted to evaluate the pharmacokinetics of riluzole and its metabolite following repeated oral administration twice daily in healthy Japanese and Caucasian adult males showed that there were no significant racial differences in pharmacokinetic parameters between the Japanese and Caucasian subjects.

Clinical Trials

The efficacy of Rilutek as a treatment of ALS was established in two adequate and well-controlled trials in which the time to tracheostomy or death was longer for patients randomized to Rilutek than for those randomized to placebo.

These studies admitted patients with either familial or sporadic ALS, a disease duration of less than 5 years, and a baseline forced vital capacity greater than or equal to 60%.

In one study, performed in France and Belgium, 155 ALS patients were followed for at least 13 months (maximum duration 18 months) after being randomized to either 100 mg/day (given 50 mg BID) of Rilutek or placebo.

Figure 1, which follows, displays the survival curves for time to death or tracheostomy. The vertical axis represents the proportion of individuals alive without tracheostomy at various times following treatment initiation (horizontal axis). Although these survival curves were not statistically significantly different when evaluated by the analysis specified in the study protocol (Logrank test p=0.12), the difference was found to be significant by another appropriate analysis (Wilcoxon test p=0.05). As seen, the study showed an early increase in survival in patients given riluzole. Among the patients in whom treatment failed during the study (tracheostomy or death) there was a difference between the treatment groups in median survival of approximately 90 days. There was no statistically significant difference in mortality at the end of the study.

In the second study, performed in both Europe and North America, 959 ALS patients were followed for at least 1 year (North American centers) and up to 18 months (European centers) after being randomized to either 50, 100, 200 mg/day of Rilutek or placebo.

Figure 2, which follows, displays the survival curves for time to death or tracheostomy for patients randomized to either 100 mg/day of Rilutek or placebo. Although these survival curves were not statistically significantly different when evaluated by the analysis specified in the study protocol (Logrank test p = 0.076), the difference was found to be significant by another appropriate analysis (Wilcoxon test p = 0.05). Not displayed in Figure 2 are the results of 50 mg/day of Rilutek which could not be statistically distinguished from placebo and the results of 200 mg/day which are essentially identical to 100 mg/day. As seen, the study showed an early increase in survival in patients given riluzole. Among the patients in whom treatment failed during the study (tracheostomy or death) there was a difference between the treatment groups in median survival of approximately 60 days. There was no statistically significant difference in mortality at the end of the study.

Although riluzole improved early survival in both studies, measures of muscle strength and neurological function did not show a benefit.

Indications and Usage for Rilutek

Rilutek is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy.

Contraindications

Rilutek is contraindicated in patients who have a history of severe hypersensitivity reactions to riluzole or any of the tablet components.

Warnings

Liver Injury / Monitoring Liver Chemistries

Rilutek should be prescribed with care in patients with current evidence or history of abnormal liver function indicated by significant abnormalities in serum transaminase (ALT/SGPT; AST/SGOT), bilirubin, and/or gamma-glutamate transferase (GGT) levels (see PRECAUTIONS and DOSAGE AND ADMINISTRATION sections). Baseline elevations of several LFTs (especially elevated bilirubin) should preclude the use of Rilutek.

Rilutek, even in patients without a prior history of liver disease, causes serum aminotransferase elevations. Treatment should be discontinued if ALT levels are ≥ 5 × ULN or if clinical jaundice develops.

Experience in almost 800 ALS patients indicates that about 50% of riluzole-treated patients will experience at least one ALT/SGPT level above the upper limit of normal, about 8% will have elevations > 3 × ULN, and about 2% of patients will have elevations > 5 × ULN. A single non-ALS patient with epilepsy treated with concomitant carbamazepine and phenobarbital experienced marked, rapid elevations of liver enzymes with jaundice (ALT 26 × ULN, AST 17 × ULN, and bilirubin 11 × ULN) four months after starting Rilutek; these returned to normal 7 weeks after treatment discontinuation.

Maximum increases in serum ALT usually occurred within 3 months after the start of riluzole therapy and were usually transient when < 5 times ULN. In trials, if ALT levels were < 5 times ULN, treatment continued and ALT levels usually returned to below 2 times ULN within 2 to 6 months. Treatment in studies was discontinued, however, if ALT levels exceeded 5 × ULN, so that there is no experience with continued treatment of ALS patients once ALT values exceed 5 times ULN. There were rare instances of jaundice. There is limited experience with rechallenge of patients who have had Rilutek discontinued for ALT > 5 × ULN, but there is the possibility of increased ALT values reoccurring (see PRECAUTIONS: Laboratory Tests). Therefore, rechallenge is not recommended.

In postmarketing experience, cases of clinical hepatitis associated with riluzole have been reported, including with fatal outcome.

Neutropenia

Among approximately 4000 patients given riluzole for ALS, there were three cases of marked neutropenia (absolute neutrophil count less than 500/mm3), all seen within the first 2 months of riluzole treatment. In one case, neutrophil counts rose on continued treatment. In a second case, counts rose after therapy was stopped. A third case was more complex, with marked anemia as well as neutropenia and the etiology of both is uncertain. Patients should be warned to report any febrile illness to their physicians. The report of a febrile illness should prompt treating physicians to check white blood cell counts.

Interstitial Lung Disease

Cases of interstitial lung disease (see ADVERSE REACTIONS) have been reported in patients treated with riluzole, some of them severe; upon further investigation, many of these cases were hypersensitivity pneumonitis. If respiratory symptoms develop such as dry cough and/or dyspnea, chest radiography should be performed, and in case of findings suggestive of interstitial lung disease or hypersensitivity pneumonitis (e.g., bilateral diffuse lung opacities), riluzole should be discontinued immediately. In the majority of the reported cases, symptoms resolved after drug discontinuation and symptomatic treatment.

Precautions

Use in Patients with Concomitant Disease

Rilutek should be used with caution in patients with concomitant liver insufficiency (see WARNINGS, CLINICAL PHARMACOLOGY). In particular, in cases of Rilutek-induced hepatic injury manifested by elevated liver enzymes, the effect of the hepatic injury on Rilutek metabolism is unknown.

Special Populations

Riluzole should be used with caution in elderly patients whose hepatic function may be compromised due to age. Also, female patients may possess a lower metabolic capacity to eliminate riluzole compared to males (see CLINICAL PHARMACOLOGY: Special Populations).

Information for the Patient

Patients should be advised to report any febrile illness to their physicians (see WARNINGS: Neutropenia).

Patients should be advised to report any cough or difficulties in breathing to their physicians (see WARNINGS: Interstitial Lung Disease).

Patients and caregivers should be advised that Rilutek should be taken on a regular basis and at the same time of the day (e.g., in the morning and evening) each day. If a dose is missed, take the next tablet as originally planned (see DOSAGE AND ADMINISTRATION).

Patients should be warned about the potential for dizziness, vertigo, or somnolence and advised not to drive or operate machinery until they have gained sufficient experience on Rilutek to gauge whether or not it affects their mental and/or motor performance adversely.

Whether alcohol increases the risk of serious hepatotoxicity with Rilutek is unknown; therefore, patients being treated with Rilutek should be discouraged from drinking excessive amounts of alcohol.

Patients should also be made aware that Rilutek should be stored at temperatures between 20°–25°C (68°–77°F) and protected from bright light.

Rilutek must be kept out of the reach of children.

Laboratory Tests

Serum aminotransferases including ALT levels should be measured before and during riluzole therapy. Serum ALT levels should be evaluated every month during the first 3 months of treatment, every 3 months during the remainder of the first year, and periodically thereafter. Serum ALT levels should be evaluated more frequently in patients who develop elevations (see WARNINGS).

As noted in the WARNINGS Section, there is no experience with continued treatment of patients once ALT exceeds 5 × ULN. Treatment should be discontinued if ALT levels are ≥ 5 × ULN or if clinical jaundice develops. There is limited experience with rechallenge of patients who have had Rilutek discontinued for ALT > 5 × ULN, but there is the possibility of increased ALT values reoccurring. Therefore, rechallenge is not recommended.

In the two controlled trials in patients with ALS, the frequency with which values for hemoglobin, hematocrit, and erythrocyte counts fell below the lower limit of normal was greater in Rilutek-treated patients than in placebo-treated patients; however, these changes were mild and transient. The proportions of patients observed with abnormally low values for these parameters showed a dose-response relationship. Only one patient was discontinued from treatment because of severe anemia. The significance of this finding is unknown.

Drug Interactions

There have been no clinical studies designed to evaluate the interaction of riluzole with other drugs.

As with all drugs, the potential for interaction by a variety of mechanisms is a possibility.

Hepatotoxic Drugs

The clinical trials in ALS excluded patients on concomitant medications which were potentially hepatotoxic, (e.g., allopurinol, methyldopa, sulfasalazine). Accordingly, there is no information about the safety of administering Rilutek in conjunction with such medications. If the practitioner chooses to prescribe such a combination, caution should be exercised.

Drugs Highly Bound To Plasma Proteins

Riluzole is highly bound (96%) to plasma proteins, binding mainly to serum albumin and to lipoproteins. The effect of riluzole (up to 5 mcg/mL) on warfarin (5 mcg/mL) binding did not show any displacement of warfarin. Conversely, riluzole binding was unaffected by the addition of warfarin, digoxin, imipramine and quinine at high therapeutic concentrations.

Effect of Other Drugs On Riluzole Metabolism

In vitro studies using human liver microsomal preparations suggest that CYP 1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole and, therefore, potential interactions may occur when riluzole is given concurrently with agents that affect CYP 1A2 activity. Potential inhibitors of CYP 1A2 (e.g., caffeine, phenacetin, theophylline, amitriptyline, and quinolones) could decrease the rate of riluzole elimination, while inducers of CYP 1A2 (e.g., cigarette smoke, charcoal-broiled food, rifampicin, and omeprazole) could increase the rate of riluzole elimination.

Effect of Riluzole On the Metabolism of Other Drugs

CYP 1A2 is the principal isoenzyme involved in the initial oxidative metabolism of riluzole; potential interactions may occur when riluzole is given concurrently with other agents which are also metabolized primarily by CYP 1A2 (e.g., theophylline, caffeine, and tacrine). Currently, it is not known whether riluzole has any potential for enzyme induction in humans.

Drug Laboratory Test Interactions

None known

Carcinogenesis, Mutagenesis, Impairment of Fertility

Riluzole was not carcinogenic in mice or rats when administered for 2 years at daily oral doses up to 20 mg/kg and 10 mg/kg, respectively, which are approximately equivalent to the maximum human dose on a mg/m2 basis.

The genotoxic potential of riluzole was evaluated in the bacterial mutagenicity (Ames) test, the mouse lymphoma mutation assay in L5178Y cells, the in vitro chromosomal aberration assay in human lymphocytes and the in vivo rat cytogenetic assay and in vivo mouse micronucleus assay in bone marrow. There was no evidence of mutagenic or clastogenic potential in the Ames test, the mouse lymphoma assay, or the in vivo assays in the mouse and rat. There was an equivocal clastogenic response in the in vitro human lymphocyte chromosomal aberration assay, which was not reproduced in a second assay performed at equal or higher concentrations; riluzole was therefore considered non-clastogenic in the human lymphocyte assay.

N-hydroxyriluzole, the major active metabolite of riluzole, caused chromosomal damage in the in vitro mammalian mouse lymphoma assay and in the in vitro micronucleus assay that used the same mouse lymphoma cell line, L5178Y. N-hydroxyriluzole was not mutagenic in this cell line when tested in the HPRT gene mutation assay, and was negative in the Ames bacterial gene mutation assay (with and without rat or hamster S9), the in vitro UDS assay in rat hepatocytes, the chromosomal aberration test in human lymphocytes, and the in vivo mouse bone marrow micronucleus test.

Riluzole impaired fertility when administered to male and female rats prior to and during mating at an oral dose of 15 mg/kg or 1.5 times the maximum daily dose on a mg/m2 basis (see PRECAUTIONS: "Pregnancy" for effects on fertility).

Pregnancy

Pregnancy category C

Oral administration of riluzole to pregnant animals during the period of organogenesis caused embryotoxicity in rats and rabbits at doses of 27 mg/kg and 60 mg/kg, respectively, or 2.6 and 11.5 times, respectively, the recommended maximum human daily dose on a mg/m2 basis. Evidence of maternal toxicity was also observed at these doses.

When administered to rats prior to and during mating (males and females) and throughout gestation and lactation (females), riluzole produced adverse effects on pregnancy (decreased implantations, increased intrauterine death) and offspring viability and growth at an oral dose of 15 mg/kg or 1.5 times the maximum daily dose on a mg/m2 basis.

There are no adequate and well-controlled studies in pregnant women. Riluzole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Women

In rat studies, 14C-riluzole was detected in maternal milk. It is not known whether riluzole is excreted in human breast milk. Because many drugs are excreted in human milk, and because the potential for serious adverse reactions in nursing infants from Rilutek® is unknown, women should be advised not to breast-feed during treatment with Rilutek.

Geriatric Use

Age-related compromised renal and hepatic function may cause a decrease in clearance of riluzole (see CLINICAL PHARMACOLOGY: Special Populations). In controlled clinical trials, about 30% of patients were over 65. There were no differences in adverse effects between younger and older patients.

Pediatric Use

The safety and the effectiveness of Rilutek in pediatric patients have not been established.

Adverse Reactions

The most commonly observed AEs associated with the use of Rilutek more frequently than placebo treated patients were: asthenia, nausea, dizziness, decreased lung function, diarrhea, abdominal pain, pneumonia, vomiting, vertigo, circumoral paresthesia, anorexia, and somnolence. Asthenia, nausea, dizziness, diarrhea, anorexia, vertigo, somnolence, and circumoral paresthesia were dose related.

Approximately 14% (n = 141) of the 982 individuals with ALS who received Rilutek in pre-marketing clinical trials discontinued treatment because of an adverse experience. Of those patients who discontinued due to adverse events, the most commonly reported were: nausea, abdominal pain, constipation, and ALT elevations. In a dose response study in ALS patients, the rates of discontinuation of Rilutek for asthenia, nausea, abdominal pain, and ALT elevation were dose related.

Incidence in Controlled ALS Clinical Studies

Table 1 lists treatment-emergent signs and symptoms that occurred in at least 2% of patients with ALS treated with Rilutek (n=794) participating in placebo-controlled trials and were numerically greater in the patients treated with Rilutek 100 mg/day than with placebo or for which a dose response relationship is suggested.

The prescriber should be aware that these figures cannot be used to predict the frequency of adverse experiences in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and non-drug factors to the AE incidences in the population studied.

Table 1 Adverse Events Occurring in Placebo-Controlled Clinical Trials

Body System / Adverse Event*	Riluzole 50 mg/day (N=237)	Riluzole 100 mg/day (N=313)	Riluzole 200 mg/day (N=244)	Placebo   (N=320)
* Percentage of patients reporting events
Body as a Whole
Asthenia	14.8	19.2	20.1	12.2
Headache	8.0	7.3	7.0	6.6
Abdominal pain	6.8	5.1	7.8	3.8
Back pain	1.7	3.2	4.1	2.5
Aggravation reaction	0.4	1.3	2.0	0.9
Malaise	0.4	0.6	1.2	0.0
Digestive
Nausea	12.2	16.3	20.5	10.6
Vomiting	4.2	4.2	4.5	1.6
Dyspepsia	2.5	3.8	6.1	5.0
Anorexia	3.8	3.2	8.6	3.8
Diarrhea	5.5	2.9	9.0	3.1
Flatulence	2.5	2.6	2.0	1.9
Stomatitis	0.8	1.0	1.2	0.0
Tooth disorder	0.0	1.0	1.2	0.3
Oral Moniliasis	0.4	0.6	1.2	0.3
Nervous
Hypertonia	5.9	6.1	5.3	5.9
Depression	4.2	4.5	6.1	5.0
Dizziness	5.1	3.8	12.7	2.5
Dry mouth	3.0	3.5	2.0	3.4
Insomnia	2.1	3.5	2.9	3.4
Somnolence	0.8	1.9	4.1	1.3
Vertigo	2.5	1.9	4.5	0.9
Circumoral paresthesia	1.3	1.6	3.3	0.0
Skin and Appendages
Pruritus	3.8	3.8	2.5	3.1
Eczema	0.8	1.6	1.6	0.6
Alopecia	0.0	1.0	1.2	0.6
Exfoliative dermatitis	0.0	0.6	1.2	0.0
Respiratory
Decreased lung function	13.1	10.2	16.0	9.4
Rhinitis	8.9	6.4	7.8	6.3
Increased cough	2.1	2.6	3.7	1.6
Sinusitis	0.4	1.0	1.6	0.9
Cardiovascular
Hypertension	6.8	5.1	3.3	4.1
Tachycardia	1.3	2.6	2.0	1.3
Phlebitis	0.4	1.0	0.8	0.3
Palpitation	0.4	0.6	1.2	0.9
Postural hypotension	0.8	0.0	1.6	0.6
Metabolic and Nutritional Disorders
Weight loss	4.6	4.8	3.7	4.7
Peripheral edema	4.2	2.9	3.3	2.2
Musculoskeletal System
Arthralgia	5.1	3.5	1.6	3.4
Urogenital System
Urinary tract infection	2.5	2.6	4.5	2.2
Dysuria	0.0	1.0	1.2	0.3

Other Adverse Events Observed

Other events which occurred in more than 2% of patients treated with Rilutek 100 mg/day but equally or more frequently in the placebo group included: accidental injury, apnea, bronchitis, constipation, death, dysphagia, dyspnea, flu syndrome, heart arrest, increased sputum, pneumonia, and respiratory disorder.

The overall adverse event profile for Rilutek was similar between females and males, and was independent of age. Because the largest non-white racial subgroup was only 2% of patients exposed to Rilutek (18/794) in placebo-controlled trials, there are insufficient data to support a statement regarding the distribution of adverse experience reports by race. In ALS studies, dizziness did occur more commonly in females (11%) than in males (4%). There was not a difference between females and males in the rates of discontinuation of Rilutek for individual adverse experiences.

Other Adverse Events Observed During All Clinical Trials

Rilutek has been administered to 1713 individuals during all clinical trials, some of which were placebo-controlled. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. The frequencies presented represent the proportion of the 1713 individuals exposed to Rilutek who experienced an event of the type cited on at least one occasion while receiving Rilutek. All reported events are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug.

Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare adverse events are those occurring in fewer than 1/1000 patients.

Body as a Whole: Frequent: Hostility1. Infrequent: Abscess1, sepsis1, photosensitivity reaction1, cellulitis, face edema1, hernia, peritonitis, attempted suicide, injection site reaction, chills1, flu syndrome, intentional injury, enlarged abdomen, neoplasm. Rare: Acrodynia, hypothermia, moniliasis1, rheumatoid arthritis.

Digestive System: Infrequent: Increased appetite, intestinal obstruction1, fecal impaction, gastrointestinal hemorrhage, gastrointestinal ulceration, gastritis1, fecal incontinence, jaundice, hepatitis, glossitis, gum hemorrhage1, pancreatitis, tenesmus, esophageal stenosis. Rare: Cheilitis1, cholecystitis, hematemesis, melena1, biliary pain, proctitis, pseudomembranous enterocolitis, enlarged salivary gland, tongue discoloration, tooth caries.

Immune System Disorders: Infrequent: Anaphylactoid reaction and anaphylaxis.

Nervous System: Frequent: Agitation1, tremor. Infrequent: Hallucinations, personality disorder1, abnormal thinking1, coma, paranoid reaction1, manic reaction, ataxia, extrapyramidal syndrome, hypokinesia, urinary retention, emotional lability, delusions, apathy, hypesthesia, incoordination, confusion1, convulsion, leg cramps, amnesia, dysarthria, increased libido, stupor, subdural hematoma, abnormal gait, delirium, depersonalization, facial paralysis, hemiplegia, decreased libido, myoclonus. Rare: Abnormal dreams, acute brain syndrome, CNS depression, dementia, cerebral embolism, euphoria1, hypotonia, ileus1, peripheral neuritis, psychosis1, psychotic depression, schizophrenic reaction, trismus, wristdrop.

Skin and Appendages: Infrequent: Skin ulceration, urticaria, psoriasis, seborrhea1, skin disorder, fungal dermatitis1. Rare: Angioedema, contact dermatitis, erythema multiforme, furunculosis1, skin moniliasis, skin granuloma, skin nodule.

Respiratory System: Infrequent: Hiccup, pleural disorder1, asthma, epistaxis, hemoptysis, yawn, hyperventilation1, lung edema1, hypoventilation1, lung carcinoma, hypoxia, laryngitis, pleural effusion, pneumothorax1, respiratory moniliasis, stridor, interstitial lung disease, hypersensitivity pneumonitis.

Cardiovascular System: Infrequent: Syncope1, hypotension, heart failure, migraine, peripheral vascular disease, angina pectoris1, myocardial infarction1, ventricular extrasystoles, cerebral hemorrhage, atrial fibrillation1, bundle branch block, congestive heart failure, pericarditis, lower extremity embolus, myocardial ischemia1, shock1. Rare: Bradycardia, cerebral ischemia, hemorrhage, mesenteric artery occlusion, subarachnoid hemorrhage, supraventricular tachycardia1, thrombosis, ventricular fibrillation, ventricular tachycardia.

Metabolic and Nutritional Disorders: Infrequent: Gout1, respiratory acidosis, edema, thirst1, hypokalemia, hyponatremia, weight gain1. Rare: Generalized edema, hypercalcemia, hypercholesteremia.

Endocrine System: Infrequent: Diabetes mellitus, thyroid neoplasia. Rare: Diabetes insipidus, parathyroid disorder.

Hemic and Lymphatic System: Infrequent: Anemia1, leukocytosis, leukopenia, ecchymosis. Rare: Neutropenia, aplastic anemia, cyanosis, hypochromic anemia, iron deficiency anemia, lymphadenopathy, petechiae1, purpura.

Musculoskeletal System: Infrequent: Arthrosis, myasthenia1, bone neoplasm. Rare: Bone necrosis, osteoporosis, tetany.

Special Senses: Infrequent: Amblyopia, ophthalmitis. Rare: Blepharitis, cataract, deafness, diplopia1, ear pain, glaucoma, hyperacusis, photophobia, taste loss, vestibular disorder.

Urogenital System: Infrequent: Urinary urgency, urine abnormality, urinary incontinence, kidney calculus, hematuria, impotence, prostate carcinoma, kidney pain, metrorrhagia, priapism. Rare: Amenorrhea, breast abscess, breast pain, nephritis1, nocturia, pyelonephritis, enlarged uterine fibroids, uterine hemorrhage, vaginal moniliasis.

Laboratory Tests: Infrequent: Increased gamma glutamyl transferase, abnormal liver function/tests, increased alkaline phosphatase, positive direct Coombs test, increased gamma globulins. Rare: increased lactic dehydrogenase.

1

= AE frequency ≤ to placebo

Overdosage

No specific antidote or information on treatment of overdosage with Rilutek is available. In the event of overdose, Rilutek therapy should be discontinued immediately. Experience with riluzole overdose in humans is limited. Neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma, and methemoglobinemia have been observed in isolated cases. Treatment should be supportive and directed toward alleviating symptoms.

Severe methemoglobinemia may be rapidly reversible after treatment with methylene blue.

The estimated oral median lethal dose is 94 mg/kg and 39 mg/kg for male mice and rats, respectively.

Rilutek Dosage and Administration

The recommended dose for Rilutek is 50 mg every 12 hours. No increased benefit can be expected from higher daily doses, but adverse events are increased.

Rilutek tablets should be taken at least an hour before, or two hours after, a meal to avoid a food-related decrease in bioavailability.

Special Populations

Patients with Impaired Hepatic Function

see WARNINGS, PRECAUTIONS, CLINICAL PHARMACOLOGY.

How is Rilutek Supplied

Rilutek 50 mg tablets are white, film-coated, capsule-shaped and engraved with "RPR 202" on one side. Rilutek is supplied in bottles of 60 tablets, NDC 0075-7700-60.

STORE AT CONTROLLED ROOM TEMPERATURE 20°–25°C (68°–77°F) AND PROTECT FROM BRIGHT LIGHT.

KEEP OUT OF THE REACH OF CHILDREN.

Revised August 2009

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

© 2009 sanofi-aventis U.S. LLC

PRINCIPAL DISPLAY PANEL - 50 mg - 60 Tablet Bottle

NDC 0075-7700-60

™Rilutek®

riluzole

Tablets

50 mg

60 Tablets

sanofi aventis

Rilutek  riluzole  tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0075-7700 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength riluzole (riluzole) riluzole 50 mg

Inactive Ingredients Ingredient Name Strength

Finacapil

Finacapil may be available in the countries listed below.

Ingredient matches for Finacapil

Finasteride

Finasteride is reported as an ingredient of Finacapil in the following countries:

• Switzerland

International Drug Name Search