Rilutek

Before taking riluzole,

• tell your doctor and pharmacist if you are allergic to riluzole or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially amitriptyline (Elavil), caffeine-containing products, ciprofloxacin (Cipro), ofloxacin (Floxin), omeprazole (Prilosec), rifampin (Rifadin), theophylline (Theo-Dur), and vitamins.
• tell your doctor if you have or have ever had blood disorders or anemia or kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking riluzole, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking riluzole.
• you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how this drug affects you.
• remember that alcohol can add to the drowsiness caused by this drug.
• tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of this drug.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to riluzole.

Riluzole can affect your body's ability to fight infection. If you have any illness, especially one with a fever, call your doctor.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Dosage Forms & Strengths

tablet

• 50mg

Amyotrophic Lateral Sclerosis (ALS)

50 mg PO q12hr on empty stomach

Monitor: LFTs

Huntington Disease (Orphan)

Orphan indication sponsor

• Rhone-Poulenc Rorer Pharmaceuticals, Inc; 500 Arcola Road, PO Box 5096; Collegeville, PA 19426-0800

Ataxia (Orphan)

Orphan designation for treatment of spinocelebellar ataxia

Sponsor

• Biohaven Pharmaceutical Holding Company, Ltd; 234 Church Street, Suite 304; New Haven, Connecticut 06511

Amyotrophic Lateral Sclerosis (Orphan)

Oral suspension (Teglutik [brand name]) and orally dissolving tablet: Orphan designation for amyotrophic lateral sclerosis (ALS)

Sponsor

• Italfarmaco SpA; 54 Via dei Lavoratori; Cinisello Balsamo, Italy

Not recommended

Contraindications

Hypersensitivity to drug or any component of the formulation

Cautions

Caution in hepatic impairment; not recommended in patients with baseline elevations of serum aminotransferases greater than 5 times upper limit of normal; discontinue therapy if there is evidence of liver dysfunction

Case reports of clincial hepatitis reported

Interstitial lung disease reported (upon further investigation, many of these cases were hypersensitivity pneumonitis); discontinue immediately if dry cough or dyspnea develops

Neutropenia reported; advise patients to report any febrile illness

Caution in renal impairment

May cause drowsiness; use caution when performing hazardous tasks requiring alertness

Sedative effects may be potentiated when used concomitantly with other sedative drugs or ethanol

Use with caution in the elderly and in females as clearance may be reduced

Mechanism of Action

Benzathiazole; inhibits glutamate release, inactivates voltage-dependent Na+ channels, inhibits effects of excitatory neurotransmitters

Pharmacokinetics

Half-Life: 12 hr

Bioavailability: 60%

Protein Bound: 96%

Metabolism: CYP1A2

Metabolites: 6 major metabolites, some active

Excretion: Feces (5%); urine (90%)

Riluzole works by decreasing your body's levels of glutamate, an amino acid that affects nerves that send messages from your brain to your muscles. People with amyotrophic lateral sclerosis may have very high levels of glutamate, which can damage these nerve cells.

Riluzole is used to treat amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease.

Riluzole is not a cure for ALS, but it may delay progression of the disease and prolong your life.

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

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use riluzole if you are allergic to it.

To make sure riluzole is safe for you, tell your doctor if you have:

• liver disease.

Riluzole can cause liver problems, especially in women, older adults, and people with a history of liver disease, or people using certain other medications harmful to the liver, such as: antibiotics or antifungal medication; antiviral or HIV/AIDS medicine; birth control pills or hormone replacement therapy; pain or arthritis medications; seizure medicine such as carbamazepine or phenytoin; or "statin" cholesterol-lowering medication.

FDA pregnancy category C. It is not known whether riluzole 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 riluzole passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Do not give this medication to anyone under 18 years old without medical advice.

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

Stop using riluzole and call your doctor at once if you have:

• sudden chest pain or discomfort, wheezing, dry cough or hack, feeling short of breath;
• cough with mucus, stabbing chest pain;
• low white blood cells--fever, swollen gums, painful mouth sores, pain when swallowing, cold or flu symptoms; or
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• dizziness, spinning sensation;
• weakness, drowsiness;
• stomach pain, nausea, vomiting, loss of appetite;
• diarrhea; or
• numbness or tingling around your mouth.

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.

Riluzole works by decreasing your body's levels of glutamate, an amino acid that affects nerves that send messages from your brain to your muscles. People with amyotrophic lateral sclerosis may have very high levels of glutamate, which can damage these nerve cells.

Riluzole is used to treat amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease.

Riluzole is not a cure for ALS, but it may delay progression of the disease and prolong your life.

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

The most common side effects of Rilutek that occurred during medical studies were weakness, nausea, lung function decrease (not associated with a reduction in vital capacity), headache, nasal symptoms, muscle tightness, abdominal pain, and high blood pressure. If any side effects become troublesome, contact your doctor.

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if Rilutek is excreted in human breast milk or if it will harm your nursing baby.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Take this medicine exactly as directed. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Swallow the tablet whole. Do not break, crush, or chew it.

The tablet should be taken on an empty stomach. Take the tablet at least 1 hour before or 2 hours after meals.

This medicine works best if there is a constant amount in the blood. To keep blood levels constant, take this medicine at the same time each day (eg, in the morning and in the evening) and do not miss any doses.

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 ALS:
    • Adults—50 milligrams (mg) two times a day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, 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.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• A fast heartbeat.
• Swelling in the arms or legs.
• Lung problems have happened with Rilutek. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.
• Very bad and sometimes deadly liver problems have happened with this medicine. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Rilutek, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Rilutek (riluzole). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Rilutek.

Review Date: October 4, 2017

The recommended dosage for Rilutek is 50 mg taken orally twice daily. Rilutek should be taken at least 1 hour before or 2 hours after a meal [see Clinical Pharmacology (12.3)].

Measure serum aminotransferases before and during treatment with Rilutek [see Warnings and Precautions (5.1)].

Hepatic Injury

Cases of drug-induced liver injury, some of which were fatal, have been reported in patients taking Rilutek. Asymptomatic elevations of hepatic transaminases have also been reported, and in some patients have recurred upon rechallenge with Rilutek.

In clinical studies, the incidence of elevations in hepatic transaminases was greater in Rilutek-treated patients than placebo-treated patients. The incidence of elevations of ALT above 5 times the upper limit of normal (ULN) was 2% in Rilutek-treated patients. Maximum increases in ALT occurred within 3 months after starting Rilutek. About 50% and 8% of Rilutek-treated patients in pooled Studies 1 and 2, had at least one elevated ALT level above ULN and above 3 times ULN, respectively [see Clinical Studies (14)].

Monitor patients for signs and symptoms of hepatic injury, every month for the first 3 months of treatment, and periodically thereafter. The use of Rilutek is not recommended if patients develop hepatic transaminase levels greater than 5 times the ULN. Discontinue Rilutek if there is evidence of liver dysfunction (e.g., elevated bilirubin).

Neutropenia

Cases of severe neutropenia (absolute neutrophil count less than 500 per mm3) within the first 2 months of Rilutek treatment have been reported. Advise patients to report febrile illnesses.

Interstitial Lung Disease

Interstitial lung disease, including hypersensitivity pneumonitis, has occurred in patients taking Rilutek. Discontinue Rilutek immediately if interstitial lung disease develops.

Common side effects of Rilutek include: asthenia, nausea, and increased serum alanine aminotransferase. Other side effects include: vomiting. See below for a comprehensive list of adverse effects.