RIFAMATE is a combination capsule containing 300 mg rifampin and 150 mg isoniazid. The capsules also contain as inactive ingredients: colloidal silicon dioxide, FD&C Blue No. 1, FD&C Red No. 40, gelatin, magnesium stearate, sodium starch glycolate, and titanium dioxide.

Rifampin is a semisynthetic antibiotic derivative of rifamycin B. The chemical name for rifampin is 3-(4-methyl-1-piperazinyliminomethyl) rifamycin SV.

Isoniazid is the hydrazide of isonicotinic acid. It exists as colorless or white crystals or as a white, crystalline powder that is water soluble, odorless, and slowly affected by exposure to air and light.

Last updated on RxList: 2/24/2009

For pulmonary tuberculosis in which organisms are susceptible, and when the patient has been titrated on the individual components and it has therefore been established that this fixed dosage is therapeutically effective.

This fixed-dosage combination drug is not recommended for initial therapy of tuberculosis or for preventive therapy.

In the treatment of tuberculosis, small numbers of resistant cells, present within large populations of susceptible cells, can rapidly become the predominating type. Since rapid emergence of resistance can occur, culture and susceptibility tests should be performed in the event of persistent positive cultures.

This drug is not indicated for the treatment of meningococcal infections or asymptomatic carriers of N. meningitidis to eliminate meningococci from the nasopharynx.

In general, therapy should be continued until bacterial conversion and maximal improvement have occurred.

Adults: Two RIFAMATE (rifampin and isoniazid capsules USP) capsules (600 mg rifampin, 300 mg isoniazid) once daily, administered one hour before or two hours after a meal.

Concomitant administration of pyridoxine (B₆) is recommended in the malnourished, in those predisposed to neuropathy (e.g., diabetic), and in adolescents.

Susceptibility Testing

Rifampin

Rifampin susceptibility powders are available for both direct and indirect methods of determining the susceptibility of strains of mycobacteria. The MIC's of susceptible clinical isolates when determined in 7H10 or other non-egg-containing media have ranged from 0.1 to 2 mcg/mL.

Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure has been recommended for use with discs for testing susceptibility to rifampin. Interpretations correlate zone diameters from the disc test with MIC (minimal inhibitory concentration) values for rifampin.

Capsules (opaque red), imprinted “RIFAMATE” on both ends of the capsule, containing 300 mg rifampin and 150 mg isoniazid; bottles of 60 (NDC 0068-0509-60).

Storage

Keep tightly closed. Store in a dry place. Avoid excessive heat.

Manufactured for: sanofi-aventis U.S. LLC Bridgewater, NJ 08807. Rev. March 2007.

Last updated on RxList: 2/24/2009

Rifampin

Nervous system reactions: headache, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, visual disturbances, muscular weakness, pain in extremities, and generalized numbness

Gastrointestinal disturbances: in some patients heartburn, epigastric distress, anorexia, nausea, vomiting, gas, cramps, and diarrhea

Hepatic reactions: transient abnormalities in liver function tests (e.g., elevations in serum bilirubin, BSP, alkaline phosphatase, serum transaminases) have been observed. Rarely, hepatitis or a shocklike syndrome with hepatic involvement and abnormal liver function tests.

Renal reactions: elevations in BUN and serum uric acid have been reported. Rarely, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, renal insufficiency, and acute renal failure have been noted. These are generally considered to be hypersensitivity reactions. They usually occur during intermittent therapy or when treatment is resumed following intentional or accidental interruption of a daily dosage regimen, and are reversible when rifampin is discontinued and appropriate therapy instituted.

Hematologic reactions: thrombocytopenia, leukopenia, hemolytic anemia, eosinophilia, and decreased hemoglobin have been observed. Thrombocytopenia has occurred when rifampin and ethambutol were administered concomitantly according to an intermittent dose schedule twice weekly and in high doses. Agranulocytosis has been reported very rarely.

Allergic and immunological reactions:occasionally pruritus, urticaria, rash, pemphigoid reaction, eosinophilia, sore mouth, sore tongue, and exudative conjunctivitis. Rarely, hemolysis, hemoglobinuria, hematuria, renal insufficiency or acute renal failure have been reported which are generally considered to be hypersensitivity reactions. These have usually occurred during intermittent therapy or when treatment was resumed following intentional or accidental interruption of a daily dosage regimen and were reversible when rifampin was discontinued and appropriate therapy instituted.

Although rifampin has been reported to have an immunosuppressive effect in some animal experiments, available human data indicate that this has no clinical significance.

Metabolic reactions: elevations in BUN and serum uric acid have occurred.

Miscellaneous reactions: fever and menstrual disturbances have been noted.

Isoniazid

The most frequent reactions are those affecting the nervous system and the liver.

Nervous system reactions:peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics), and is usually preceded by paresthesias of the feet and hands. The incidence is higher in “slow inactivators.”

Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment, and toxic psychosis.

Gastrointestinal reactions: nausea, vomiting, and epigastric distress

Hepatic reactions:elevated serum transaminases (SGOT; SGPT), bilirubinemia, bilirubinuria, jaundice, and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms are anorexia, nausea, vomiting, fatigue, malaise, and weakness. Mild and transient elevation of serum transaminase levels occurs in 10 to 20 percent of persons taking isoniazid. The abnormality usually occurs in the first 4 to 6 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal with no necessity to discontinue medication. In occasional instances, progressive liver damage occurs, with accompanying symptoms. In these cases, the drug should be discontinued immediately. The frequency of progressive liver damage increases with age. It is rare in persons under 20, but occurs in up to 2.3 percent of those over 50 years of age.

Hematologic reactions:agranulocytosis, hemolytic sideroblastic or aplastic anemia, thrombocytopenia, and eosinophilia

Hypersensitivity reactions:fever, skin eruptions (morbilliform, maculopapular, purpuric, or exfoliative), lymphadenopathy, and vasculitis

Metabolic and endocrine reactions: pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis, and gynecomastia

Miscellaneous reactions: rheumatic syndrome and systemic lupus erythematosus-like syndrome

No information provided.

Last updated on RxList: 2/24/2009

RIFAMATE (rifampin and isoniazid capsules USP) is a combination of two drugs, each of which has been associated with liver dysfunction. Liver function tests should be performed prior to therapy with RIFAMATE and periodically during treatment.

Rifampin

Rifampin has been shown to produce liver dysfunction. There have been fatalities associated with jaundice in patients with liver disease or receiving rifampin concomitantly with other hepatotoxic agents. Since an increased risk may exist for individuals with liver disease, benefits must be weighed carefully against the risk of further liver damage.

Several studies of tumorigenicity potential have been done in rodents. In one strain of mice known to be particularly susceptible to the spontaneous development of hepatomas, rifampin given at a level 2-10 times the maximum dosage used clinically resulted in a significant increase in the occurrence of hepatomas in female mice of this strain after one year of administration.

There was no evidence of tumorigenicity in the males of this strain, in males or females of another mouse strain, or in rats.

Isoniazid

See the BOXED WARNING.

Rifampin

Rifampin is not recommended for intermittent therapy; the patient should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases.

Rifampin has been observed to increase the requirements for anticoagulant drugs of the coumarin type. The cause of the phenomenon is unknown. In patients receiving anticoagulants and rifampin concurrently, it is recommended that the prothrombin time be performed daily or as frequently as necessary to establish and maintain the required dose of anticoagulant.

Urine, feces, saliva, sputum, sweat, and tears may be colored red-orange by rifampin and its metabolites. Soft contact lenses may be permanently stained. Individuals to be treated should be made aware of these possibilities.

It has been reported that the reliability of oral contraceptives may be affected in some patients being treated for tuberculosis with rifampin in combination with at least one other antituberculosis drug. In such cases, alternative contraceptive measures may need to be considered.

It has also been reported that rifampin given in combination with other antituberculosis drugs may decrease the pharmacologic activity of methadone, oral hypoglycemics, digitoxin, quinidine, disopyramide, dapsone, and corticosteroids. In these cases, dosage adjustment of the interacting drugs is recommended.

Therapeutic levels of rifampin have been shown to inhibit standard microbiological assays for serum folate and vitamin B₁₂. Alternative methods must be considered when determining folate and vitamin B₁₂ concentrations in the presence of rifampin.

Since rifampin has been reported to cross the placental barrier and appear in cord blood and in maternal milk, neonates and newborns of rifampin-treated mothers should be carefully observed for any evidence of untoward effects.

Isoniazid

All drugs should be stopped and an evaluation of the patient should be made at the first sign of a hypersensitivity reaction.

Use of isoniazid should be carefully monitored in the following:

1. Patients who are receiving phenytoin (diphenylhydantoin) concurrently. Isoniazid may decrease the excretion of phenytoin or may enhance its effects. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant dose should be made.
2. Daily users of alcohol. Daily ingestion of alcohol may be associated with a higher incidence of isoniazid hepatitis.
3. Patients with current chronic liver disease or severe renal dysfunction. Periodic ophthalmoscopic examination during isoniazid therapy is recommended when visual symptoms occur.

Usage in Pregnancy and Lactation

Rifampin

Although rifampin has been reported to cross the placental barrier and appear in cord blood, the effect of rifampin, alone or in combination with other antituberculosis drugs, on the human fetus is not known. An increase in congenital malformations, primarily spina bifida and cleft palate, has been reported in the offspring of rodents given oral doses of 150-250 mg/kg/day of rifampin during pregnancy.

The possible teratogenic potential in women capable of bearing children should be carefully weighed against the benefits of therapy.

Isoniazid

It has been reported that in both rats and rabbits, isoniazid may exert an embryocidal effect when administered orally during pregnancy, although no isoniazid-related congenital anomalies have been found in reproduction studies in mammalian species (mice, rats, and rabbits). Isoniazid should be prescribed during pregnancy only when therapeutically necessary. The benefit of preventive therapy should be weighed against a possible risk to the fetus. Preventive treatment generally should be started after delivery because of the increased risk of tuberculosis for new mothers.

Since isoniazid is known to cross the placental barrier and to pass into maternal breast milk, neonates and breast-fed infants of isoniazid-treated mothers should be carefully observed for any evidence of adverse effects.

Carcinogenesis

Isoniazid has been reported to induce pulmonary tumors in a number of strains of mice.

Last updated on RxList: 2/24/2009

Rifampin

Signs and Symptoms

Nausea, vomiting, and increasing lethargy will probably occur within a short time after ingestion; actual unconsciousness may occur with severe hepatic involvement. Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces is proportional to amount ingested.

Liver enlargement, possibly with tenderness, can develop within a few hours after severe overdosage, and jaundice may develop rapidly. Hepatic involvement may be more marked in patients with prior impairment of hepatic function. Other physical findings remain essentially normal.

Direct and total bilirubin levels may increase rapidly with severe overdosage; hepatic enzyme levels may be affected, especially with prior impairment of hepatic function. A direct effect upon hemopoietic system, electrolyte levels, or acid-base balance is unlikely.

Isoniazid

Signs and Symptoms

Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours. Nausea, vomiting, dizziness, slurring of speech, blurring of vision, visual hallucinations (including bright colors and strange designs), are among the early manifestations. With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, are to be expected, along with severe, intractable seizures. Severe metabolic acidosis, acetonuria, and hyperglycemia are typical laboratory findings.

RIFAMATE (rifampin and isoniazid capsules USP)

Treatment

The airway should be secured and adequate respiratory exchange established. Only then should gastric emptying (lavage-aspiration) be attempted; this may be difficult because of seizures. Since nausea and vomiting are likely to be present, gastric lavage is probably preferable to induction of emesis.

Activated charcoal slurry instilled into the stomach following evacuation of gastric contents can help absorb any remaining drug in the GI tract. Antiemetic medication may be required to control severe nausea and vomiting.

Blood samples should be obtained for immediate determination of gases, electrolytes, BUN, glucose, etc. Blood should be typed and crossmatched in preparation for possible hemodialysis.

Rapid control of metabolic acidosis is fundamental to management. Intravenous sodium bicarbonate should be given at once and repeated as needed, adjusting subsequent dosage on the basis of laboratory findings (i.e., serum sodium, pH, etc.). At the same time, anticonvulsants should be given intravenously (i.e., barbiturates, diphenylhydantoin, diazepam) as required, and large doses of intravenous pyridoxine.

Forced osmotic diuresis must be started early and should be continued for some hours after clinical improvement to hasten renal clearance of drug and help prevent relapse. Fluid intake and output should be monitored.

Bile drainage may be indicated in presence of serious impairment of hepatic function lasting more than 24-48 hours. Under these circumstances and for severe cases, extracorporeal hemodialysis may be required; if this is not available, peritoneal dialysis can be used along with forced diuresis.

Along with measures based on initial and repeated determination of blood gases and other laboratory tests as needed, meticulous respiratory and other intensive care should be utilized to protect against hypoxia, hypotension, aspiration, pneumonitis, etc.

In patients with previously adequate hepatic function, reversal of liver enlargement and impaired hepatic excretory function probably will be noted within 72 hours, with rapid return toward normal thereafter.

Untreated or inadequately treated cases of gross isoniazid overdosage can terminate fatally, but good response has been reported in most patients brought under adequate treatment within the first few hours after drug ingestion.

Previous isoniazid-associated hepatic injury; severe adverse reactions to isoniazid, such as drug fever, chills, and arthritis; acute liver disease of any etiology. A history of previous hypersensitivity reaction to any of the rifamycins or to isoniazid, including drug-induced hepatitis.

Last updated on RxList: 2/24/2009

Rifampin

Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. This is the mechanism of action by which rifampin exerts its therapeutic effect. Rifampin cross-resistance has only been shown with other rifamycins.

In a study of 14 normal human adult males, peak blood levels of rifampin occurred 1 1/2 to 3 hours following oral administration of two RIFAMATE capsules. The peaks ranged from 6.9 to 14 mcg/mL with an average of 10 mcg/mL.

In normal subjects the T1/2 (biological half-life) of rifampin in blood is approximately 3 hours. Elimination occurs mainly through the bile and, to a much lesser extent, the urine.

Isoniazid

Isoniazid acts against actively growing tubercle bacilli.

After oral administration isoniazid produces peak blood levels within 1 to 2 hours which decline to 50% or less within 6 hours. It diffuses readily into all body fluids (cerebrospinal, pleural, and ascitic fluids), tissues, organs, and excreta (saliva, sputum, and feces). The drug also passes through the placental barrier and into milk in concentrations comparable to those in the plasma. From 50 to 70% of a dose of isoniazid is excreted in the urine in 24 hours.

Isoniazid is metabolized primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50% of Blacks and Caucasians are “slow inactivators”; the majority of Eskimos and Orientals are “rapid inactivators.”

The rate of acetylation does not significantly alter the effectiveness of isoniazid. However, slow acetylation may lead to higher blood levels of the drug, and thus an increase in toxic reactions.

Pyridoxine deficiency (B₆) is sometimes observed in adults with high doses of isoniazid and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.

Last updated on RxList: 2/24/2009

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 2/24/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

RIFAMPIN/ISONIAZID - ORAL

(riff-AM-pin/eye-so-NYE-uh-zid)

COMMON BRAND NAME(S): Rifamate

WARNING: Rarely, the isoniazid in this product has caused a severe (sometimes fatal) liver problem (hepatitis). Hepatitis can develop at any time while you are taking this medication. Immediately tell your doctor if you develop symptoms of liver problems (persistent nausea, vomiting, weakness, tiredness, stomach/abdominal pain, dark urine, yellowing eyes/skin). The risk of hepatitis increases with age (35 and older), persistent liver problems, and the use of alcohol and/or illegal injection drugs. Do not use alcohol or illegal injection drugs while taking this medication.

You will need certain blood tests (liver function tests) regularly to check for side effects. Keep all medical and laboratory appointments.

USES: This medication is a combination of 2 medicines (rifampin, isoniazid). This combination product should only be used if your doctor determines that the doses of each drug in this product are right for your condition. This medication is used to treat active tuberculosis (TB) infections. These medicines belong to a class of drugs known as antibiotics that are active against tuberculosis.

HOW TO USE: Take this medication by mouth without food, usually once daily or as directed by your doctor. This medication is usually taken for 2-9 months.

If you also take antacids, take this medication at least 1 hour before the antacid.

Dosage is based on your age, weight, medical condition, and response to therapy.

It is very important to continue taking this medication (and other TB medications) exactly as prescribed by your doctor.

This medication works best when the amount of drug in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals. To help you remember, take it same time each day.

Do not take more or less of this drug than prescribed or stop taking it (or other TB medicines) even for a short time unless directed to do so by your doctor. Skipping or changing your dose without approval from your doctor may cause the amount of TB bacteria to increase, make the infection more difficult to treat (resistant), or worsen side effects. If TB becomes resistant to this medication, it might also be resistant to other TB medications.

Your doctor may also direct you to take vitamin B6 (pyridoxine) to help prevent certain side effects (nerve problems) from isoniazid.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: See also Warning section.

Tingling/numbness in the hands/feet, headache, aching joints, diarrhea, stomach upset/pain, or nausea may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: persistent nausea/vomiting, weakness, tiredness, stomach/abdominal pain, yellowing eyes/skin, loss of appetite, bloody/pink/cloudy/dark urine, painful/swollen joints, swelling of hands/feet, changes in skin color, increase in the amount of urine, breast enlargement in males.

Tell your doctor immediately if any of these rare but very serious side effects occur: vision changes, confusion, seizures, sudden weakness, pale skin, fast breathing, easy bruising/bleeding, new fever, persistent sore throat, chills.

This medication may rarely cause a serious immune system problem (systemic lupus erythematosus). Tell your doctor immediately if you experience any of these unlikely but serious side effects: unusual tiredness, joint/muscle aches, unusual fever, butterfly-shaped facial rash, swollen glands, bloody/pink urine, swelling of the feet/ankles.

Tears, saliva, stool, sweat, and urine may be colored red-orange. This effect is harmless, but, clothing, dentures, and contact lenses may become permanently stained.

This medication may rarely cause a severe intestinal condition (pseudomembranous colitis) due to a type of resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have any of the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking rifampin/isoniazid, tell your doctor or pharmacist if you are allergic to either of these medications; or to other rifamycins (e.g., rifabutin, rifapentine); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe and persistent liver disease, alcoholism, new liver disease not yet diagnosed, HIV infection, a certain liver/blood condition (porphyria).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: HIV infection, cancer, gout, kidney problems, certain nerve problems (peripheral neuropathy), diabetes, seizures, recent childbirth (in women of African/Latina heritage), illegal injection drug use.

If you have diabetes, this product may make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst and urination. Your anti-diabetic medication or diet may need to be adjusted.

Before having surgery, tell your doctor or dentist that you are using this medication.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug, especially the liver effects.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Though there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: ketoconazole, itraconazole, voriconazole, HIV protease inhibitors (e.g., indinavir, ritonavir), delavirdine, nevirapine, etravirine.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting rifampin/isoniazid.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: acetaminophen, probenecid.

This drug can speed up the removal of other drugs from your body by affecting certain liver enzymes. These affected drugs include (not a complete list): antiarrhythmics (e.g., mexiletine, disopyramide, propafenone), certain antibiotics (e.g., fluoroquinolones such as ciprofloxacin, clarithromycin, erythromycin, doxycycline, chloramphenicol, cotrimoxazole, telithromycin), antidiabetics (e.g., glyburide, glimepiride, repaglinide), certain antimalarial drugs (e.g., mefloquine, atovaquone), anti-seizure medications (e.g., phenytoin, lamotrigine, valproic acid, carbamazepine), aprepitant, barbiturates (e.g., phenobarbital), benzodiazepines (e.g., diazepam, triazolam), digoxin, estrogens, certain cancer drugs (e.g., exemestane, sunitinib, gefitinib, erlotinib, imatinib, irinotecan, tamoxifen), certain drugs that suppress the immune system (e.g., cyclosporine, tacrolimus), corticosteroids (e.g., prednisone, dexamethasone), certain drugs to treat high blood pressure (e.g., beta blockers such as propranolol/metoprolol, calcium channel blockers such as verapamil/nifedipine, enalapril, losartan), certain other HIV-medications (e.g., efavirenz), methadone, nortriptyline, certain psychiatric medications (e.g., haloperidol, quetiapine, buspirone), certain "statin" cholesterol medications (e.g., simvastatin, fluvastatin), sulfasalazine, theophylline, thyroid medications (e.g., levothyroxine), warfarin, zolpidem.

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. You may need to use an additional form of reliable birth control while using this medication. Consult your doctor or pharmacist for details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. Symptoms of overdose may include: nausea/vomiting, slurred speech, blurred vision, hallucinations, trouble breathing, fainting, inability to wake up (coma), severe/persistent seizures.

NOTES: Do not share this medication with others.

Keep all medical and laboratory appointments.

Laboratory and/or medical tests (e.g., TB cultures, liver function tests, blood cell counts, blood chemistries) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

This medication may interfere with certain laboratory tests (including blood folate/B12, certain acetone/ketone urine tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.