Mesnex® (mesna) is a detoxifying agent to inhibit the hemorrhagic cystitis induced by ifosfamide (IFEX®).The active ingredient mesna is a synthetic sulfhydryl compound designated as sodium-2-mercaptoethane sulfonate with a molecular formula of C₂H₅NaO₃S₂ and a molecular weight of 164.18.Its structural formula is as follows:

HS-CH₂-CH₂SO₃–Na⁺

Mesnex Injection is a sterile, nonpyrogenic, aqueous solution of clear and colorless appearance in clear glass multi-dose vials for intravenous administration.Mesnex Injection contains 100 mg/mL mesna, 0.25 mg/mL edetate disodium and sodium hydroxide for pH adjustment.Mesnex Injection multidose vials also contain 10.4 mg of benzyl alcohol as a preservative. The solution has a pH range of 7.5-8.5.

Mesnex Tablets are white, oblong, scored biconvex film coated tablets with the imprint M4. They contain 400 mg mesna. Excipients include lactose, microcrystalline cellulose, calcium phosphate, cornstarch, povidone, magnesium stearate, hydroxypropylmethylcellulose, polyethylene glycol, titanium dioxide, and simethicone.

Mesnex is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis.

For the prophylaxis of ifosfamide induced hemorrhagic cystitis, Mesnex may be given on a fractionated dosing schedule of three bolus intravenous injections or a single bolus injection followed by two oral administrations of Mesnex Tablets as outlined below.

Intravenous Schedule

Mesnex is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration and 4 and 8 hours after each dose of ifosfamide. The total daily dose of mesna is 60% of the ifosfamide dose.

The recommended dosing schedule is outlined below:

Intravenous and Oral Dosing

Mesnex Injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration. Mesnex Tablets are given orally in a dosage equal to 40% of the ifosfamide dose 2 and 6 hours after each dose of ifosfamide. The total daily dose of mesna is 100% of the ifosfamide dose.

The recommended dosing schedule is outlined below:

Patients who vomit within two hours of taking oral mesna should repeat the dose or receive intravenous mesna. The efficacy and safety of this ratio of IV and PO mesna has not been established as being effective for daily doses of IFEX® higher than 2.0 g/m².

The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifos-famide is adjusted (either increased or decreased), the ratio of Mesnex to IFEX should be maintained.

Preparation of Intravenous Solutions/Stability

The Mesnex multidose vials may be stored and used for up to 8 days.

For IV administration the drug can be diluted by adding the Mesnex Injection solution to any of the following fluids obtaining final concentrations of 20 mg mesna/mL: 5% Dextrose Injection, USP

5% Dextrose and 0.2% Sodium Chloride Injection, USP
5% Dextrose and 0.33% Sodium Chloride Injection, USP
5% Dextrose and 0.45% Sodium Chloride Injection, USP
0.92% Sodium Chloride Injection, USP
Lactated Ringer's Injection, USP

For example:

One mL of Mesnex Injection multidose vial 100 mg/mL may be added to 4 mL of any of the solutions listed above to create a final concentration of 20 mg mesna/mL.

Diluted solutions are chemically and physically stable for 24 hours at 25° C (77° F).

Mesna is not compatible with cisplatin or carboplatin.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Mesnex® (mesna) Injection 100 mg/mL

NDC 0015-3563-02 - 1 g Multidose Vial, Box of 1 vial of 10 mL

NDC 0015-3563-03 - 1 g Multidose Vial, Box of 10 vials of 10 mL

Mesnex® (mesna) Tablets

NDC 0015-3565-12 - 400 mg scored tablets, Boxes containing 10 blisters per card Store at controlled room temperature 20° C to 25° C (68° F to 77° F).

Distributed by: Bristol-Myers Squibb Company Princeton, New Jersey 08543 USA. Mesnex® (mesna) Tablets manufactured for: Baxter Healthcare Corporation, Deerfield, IL 60015 USA. Issued May 2002. FDA rev date: 1/30/2003

Mesnex adverse reaction data are available from four phase I studies in which single IV bolus doses of 600-1200 mg Mesnex Injection without concurrent chemotherapy were administered to a total of 53 subjects and single oral doses of 600-2400 mg of Mesnex Tablets were administered to a total of 82 subjects.

The most frequently reported side effects (observed in two or more patients) for patients receiving single doses of Mesnex IV were headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperaesthesia, influenza-like symptoms, and coughing. Among patients who received a single 1200-mg dose as an oral solution, rigors, back pain, rash, conjunctivitis, and arthralgia were also reported. In two phase I multiple-dose studies where patients received Mesnex Tablets alone or IV Mesnex followed by repeated doses of Mesnex Tablets, flatulence and rhinitis were reported. In addition, constipation was reported by patients who had received repeated doses of IV Mesnex.

Because mesna is used in combination with ifosfamide or ifosfamide-containing chemotherapy regimens, it is difficult to distinguish the adverse reactions which may be due to Mesnex from those caused by the concomitantly administered cytotoxic agents.

Adverse reactions reasonably associated with mesna administered IV and orally in four controlled studies in which patients received ifosfamide or ifosfamide-containing regimens are presented in Table 3.

Table 3: Incidence of Adverse Events and Incidence of Most Frequently Reported Adverse Events in Controlled Studies

Postmarketing Surveillance

Allergic reactions, decreased platelet counts associated with allergic reactions, hypertension, hypotension, increased heart rate, increased liver enzymes, injection site reactions (including pain and erythema), limb pain, malaise, myal-gia, ST-segment elevation, tachycardia, and tachypnea have been reported as part of postmarketing surveillance.

No clinical drug studies have been conducted.

Allergic reactions to mesna ranging from mild hypersensitivity to systemic anaphylactic reactions have been reported. Patients with autoimmune disorders who were treated with cyclophosphamide and mesna appeared to have a higher incidence of allergic reactions. The majority of these patients received mesna orally.

Mesnex has been developed as an agent to reduce the risk of ifosfamide induced hemorrhagic cystitis. It will not prevent or alleviate any of the other adverse reactions or toxicities associated with ifosfamide therapy.

Mesnex does not prevent hemorrhagic cystitis in all patients. Up to 6% of patients treated with mesna have developed hematuria (>50 RBC/hpf or WHO grade 2 and above). As a result, a morning specimen of urine should be examined for the presence of hematuria (microscopic evidence of red blood cells) each day prior to ifosfamide therapy. If hematuria develops when Mesnex is given with ifosfamide according to the recommended dosage schedule, depending on the severity of the hematuria, dosage reductions or discontinuation of ifosfamide therapy may be initiated.

In order to reduce the risk of hematuria, Mesnex must be administered with each dose of ifosfamide as outlined in the DOSAGE AND ADMINISTRATION section. Mesnex is not effective in reducing the risk of hematuria due to other pathological conditions such as thrombocytopenia.

Because of the benzyl alcohol content, the multidose vial should not be used in neonates or infants and should be used with caution in older pediatric patients.

Information for Patients

Healthcare providers should advise patients taking Mesnex to drink at least a quart of liquid a day. Patients should be informed to report if their urine has turned a pink or red color, if they vomit within 2 hours of taking oral Mesnex, or if they miss a dose of oral Mesnex. See PATIENT INFORMATION Leaflet for Mesnex Tablets.

Laboratory Tests

A false positive test for urinary ketones may arise in patients treated with Mesnex. In this test, a red-violet color develops which, with the addition of glacial acetic acid, will return to violet.

Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis

No long-term studies in animals have been performed to evaluate the carcinogenic potential of Mesnex.

Mutagenesis

Mesna was not genotoxic in the in vitro Ames bacterial mutagenicity assay, the in vitro mammalian lymphocyte chro-mosomal aberration assay or the in vivo mouse micronucleus assay.

Impairment of Fertility

No studies on male or female fertility were conducted. No signs of male or female reproductive organ toxicity were seen in 6-month oral rat studies (at doses up to 2000 mg/kg/day) or 29-week oral dog studies (520 mg/kg/day; both studies approximately 10-fold higher than the maximum recommended human dose on a body surface area basis).

Pregnancy

Pregnancy Category B.Reproduction studies have been performed in rats and rabbits at oral doses of 1000 mg/kg in rabbits and 2000 mg/kg in rats (approximately 10 times the maximum recommended total daily IV-oral-oral human dose on a body surface area basis) and have revealed no evidence of harm to the fetus due to mesna. There are how-ever, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether mesna or dimesna is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from mesna, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of Mesnex Tablets in pediatric patients have not been established.

Because of the benzyl alcohol content in Mesnex Injection, the multidose vial should not be used in neonates or infants and should be used with caution in older pediatric patients.

Geriatric Use

Clinical studies of mesna did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. However, the ratio of ifosfamide to mesna should remain unchanged.

There is no known antidote for Mesnex. Oral doses of 6.1 and 4.3 g/kg were lethal to mice and rats, respectively. These doses are approximately 15 and 22 times the maximum recommended human dose on a body surface area basis. Death was preceded by diarrhea, tremor, convulsions, dyspnea, and cyanosis.

Mesnex is contraindicated in patients known to be hypersensitive to mesna or other thiol compounds.

Mechanism of Action

Mesnex was developed as a prophylactic agent to reduce the risk of hemorrhagic cystitis induced by ifosfamide.

Analogous to the physiological cysteine-cystine system, mesna is rapidly oxidized to its major metabolite, mesna disulfide (dimesna).Mesna disulfide remains in the intravascular compartment and is rapidly eliminated by the kidneys.

In the kidney, the mesna disulfide is reduced to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfamide metabolites (acrolein and 4-hydroxy-ifosfamide) resulting in their detoxification. The first step in the detoxification process is the binding of mesna to 4-hydroxy-ifosfamide forming a nonurotoxic 4-sul-foethylthioifosfamide. Mesna also binds to the double bonds of acrolein and to other urotoxic metabolites.

In multiple human xenograft or rodent tumor model studies of limited scope, using IV or IP routes of administration, mesna in combination with ifosfamide (at dose ratios of up to 20-fold as single or multiple courses) failed to demonstrate interference with antitumor efficacy.

Pharmacokinetics

At doses of 2-4 g/m², the terminal elimination half-life of ifosfamide is about 4-8 hours. As a result, in order to maintain adequate levels of mesna in the urinary bladder during the course of elimination of the urotoxic ifosfamide metabolites, repeated doses of Mesnex are required.

IV-IV-IV Regimen

After intravenous administration of an 800-mg dose, the half-lives of mesna and dimesna in the blood are 0.36 hours and 1.17 hours, respectively. Approximately 32% and 33% of the administered dose was eliminated in the urine in 24 hours as mesna and dimesna, respectively. The majority of the dose recovered was eliminated within 4 hours. Mesna has a plasma clearance of 1.23 L/h/kg.

IV-Oral-Oral Regimen

The half-life of mesna ranged from 1.2-8.3 hours after administration of intravenous plus oral doses of Mesnex, as recommended in the DOSAGE AND ADMINISTRATION section. The urinary bioavailability of oral mesna ranged from 45-79% of intravenously administered mesna. Food does not affect the urinary availability of orally administered mesna. Approximately 18-26% of the combined intravenous and oral mesna dose appears as free mesna in the urine. When compared to intravenously administered mesna, the intravenous plus oral dosing regimen increases systemic exposures (150%) and provides more sustained excretion of mesna in the urine over a 24-hour period. Approximately 5% of the mesna dose is excreted during the 12-24 hour interval, as compared to negligible amounts in patients given the IV regimen. The fraction of the administered dose of mesna excreted in the urine is independent of dose. Protein binding of mesna is in a moderate range (69-75%).

Special Populations

Gender Effect

An analysis was conducted in four male and four female volunteers; no differences in plasma pharmacokinetics were detected.

Pediatrics and Geriatrics

Pharmacokinetic data of Mesnex in pediatric and geriatric patients are not available.

Hepatic and Renal Insufficiency

No clinical studies were conducted to evaluate the effect of hepatic impairment or renal impairment on the phar-macokinetics of Mesnex.

Drug-Drug Interaction

No clinical drug interaction studies have been conducted with Mesnex.

Clinical Studies

IV Mesna

Hemorrhagic cystitis produced by ifosfamide is dose dependent (Table 1). At a dose of 1.2 g/m² ifosfamide administered daily for 5 days, 16-26% of the patients who received conventional uroprophylaxis (high fluid intake, alkalin-ization of the urine, and the administration of diuretics) developed hematuria (>50 RBC/hpf or macrohematuria) (Morgan, Einhorna, Costanzi). In contrast, none of the patients who received Mesnex Injection together with this dose of ifosfamide developed hematuria (Einhorna, b). In two randomized studies, (Fukuoka, Scheef), higher doses of ifos-famide, from 2 to 4 g/m² administered for 3-5 days, produced hematuria in 31-100% of the patients. When Mesnex was administered together with these doses of ifosfamide, the incidence of hematuria was less than 7%.

Table 1: Percent of Mesnex Patients Developing Hematuria ( ≥ 50 RBC/hpf or macrohematuria)

Oral Mesna

Clinical studies comparing recommended intravenous and oral mesna dosing regimens demonstrated incidences of grade 3-4 hematuria of <5%. Study D07093-0018 was an open label, randomized, two-way crossover study comparing three IV doses with an initial IV dose followed by two oral doses of mesna in patients with cancer treated with ifosfamide at a dose of 1.2-2.0 g/m² for 3-5 days. Study MED504 was a randomized, multicenter study in cancer patients receiving ifosfamide at 2.0 g/m² for 5 days. In both studies, development of grade 3 or 4 hematuria was the primary efficacy endpoint. The percent of patients developing hematuria in each of these studies is presented in Table 2.

Table 2: Percent of Mesnex Patients Developing Grade 3 or 4 Hematuria

A crossover pharmacokinetic study supports the low incidence of grade 3 or 4 hematuria with the recommended intravenous and oral mesna dosing regimens used in the two controlled studies.

Mesnex®
(mesna) Tablets

Read this information carefully before you start taking Mesnex (MES-nex) and each time you get more Mesnex. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about Mesnex, ask your doctor. Only your doctor can determine if Mesnex is right for you.

What is the most important information I should know?

• It is important to drink at least a quart (4 cups) of liquid a day whenever you take Mesnex, whether it is intravenous (through a tube placed in a vein) or oral (by mouth).
• A small number of patients who take Mesnex get blood in their urine (hematuria). Therefore, it is important that your doctor check your urine in the laboratory each day that you get Mesnex. The laboratory test can find low levels of blood in the urine that you cannot see just by looking at it.
• If you notice that your urine has turned a pink or red color, contact your doctor as soon as possible. Certain prescription medicines and foods, such as red beets, may also cause your urine to change color. A laboratory test of your urine will show if the source of the color is due to one of these causes or hematuria.
• You need to take your Mesnex Tablets at the exact times your doctor tells you. If you miss a dose, take it as soon as you remember, and contact your doctor for more instructions. Do not double your dose to make up for the missed dose.
• If you vomit within 2 hours of taking oral Mesnex, contact your doctor right away.

What is Mesnex?

Mesnex reduces the chance of your getting one of the side effects of another medicine, IFEX® (ifosfamide) for Injection.

IFEX is used to treat certain types of cancers. Mesnex should only be given with IFEX.

Mesnex reduces the chance of your getting hemorrhagic cystitis from IFEX. This condition causes bloody urine from damage to the bladder lining. The damage to the bladder may show up as blood in your urine (hematuria). If a very small amount of blood is in your urine, you may not be able to see it, but your doctor or nurse can test for it in the laboratory. If there is a larger amount of blood in your urine, you will see that the urine has turned a pink or red color. Mesnex does not reduce the chance of getting other side effects of cancer chemotherapy.

When IFEX is given without Mesnex, hematuria occurs in a large number of patients. Therefore, it is very important to always take Mesnex when getting IFEX treatment.

Who should not take Mesnex?

Do not take Mesnex if you have had an allergic reaction to Mesnex or other medicines that contain sulfur.

Before beginning treatment with Mesnex, check with your doctor if you are:

• Pregnant. You and your doctor should discuss if Mesnex is right for you.
• Breast-feeding. Your doctor may advise you to stop breast-feeding or not to use Mesnex.
• Have an autoimmune disorder such as rheumatoid arthritis, systemic lupus erythematosis (SLE), or nephritis (a type of kidney problem).You may be more likely to get an allergic reaction from Mesnex.

How should I take Mesnex?

Take Mesnex at the exact times in the exact amounts your doctor tells you to. If your first dose is intravenous and the other doses are oral, you will get the intravenous dose at the same time as the IFEX. You should take the tablets 2 and 6 hours after the IFEX.

• The dose of Mesnex depends on the amount of the IFEX dose. Pay careful attention to the number of tablets your doctor instructs you to take. You may need to take half tablets for your dose. Each tablet has a groove in the middle that makes it easy to break the tablets in half.

For more information about how to take Mesnex, see the section "What is the most important information I should know?"

What are the most common side effects of Mesnex?

The most common side effects reported for Mesnex Tablets are headache; digestive symptoms such as nausea (feeling sick to your stomach), vomiting (throwing up), diarrhea (frequent or watery stools or bowel movements), stomach pain and low or no appetite; flu-like symptoms including dizziness, flushing, and fever; sensitive skin; sleepiness; coughing; sore throat; cold-like symptoms; injection site reactions. Some patients may get allergic reactions, rash, con-stipation, paleness, fluid retention (water stays in your body), and decreased blood pressure. These are not all the possible side effects of Mesnex. For a complete list, ask your doctor.

If you suspect that someone may have taken more than the prescribed dose of Mesnex, contact your local poison control center or emergency room right away.

Storage

Store Mesnex Tablets in a cool, dry place protected from excess moisture and heat. If possible do not store in the kitchen or bathroom. Throw away any unused portion after the expiration date.

General advice about prescription medicines

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Mesnex for a condition for which it was not prescribed. Do not give Mesnex to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Mesnex. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Mesnex that is written for health professionals.

• IFEX® is a registered trademark of Bristol-Myers Squibb Company.

This Patient Information Leaflet has been approved by the U.S. Food and Drug Administration.

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.

MESNA - ORAL

(MESS-na)

COMMON BRAND NAME(S): Mesnex

USES: This medication is used to reduce the risk of bleeding in the bladder (hemorrhagic cystitis), which is a very serious side effect of treatment with a cancer chemotherapy drug called ifosfamide. Mesna helps to protect the lining of the bladder against damage from ifosfamide. The body breaks down ifosfamide to form a product that can harm the bladder, and mesna works by making this product less harmful. However, mesna does not change ifosfamide's anti-cancer effects.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to reduce the risk of bleeding in the bladder caused by another cancer chemotherapy drug called cyclophosphamide.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start taking mesna and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth. Follow the dosing schedule as directed by your doctor. Dosage is based on your body size and your dose of ifosfamide (or cyclophosphamide).

While taking this medication, drink at least a quart (4 cups or 1 liter) of liquid each day unless directed otherwise by your doctor. Doing so will also help to reduce the bladder side effects from ifosfamide.

Tell your doctor immediately if you vomit within 2 hours of taking a dose. Your doctor will determine if you should repeat the dose or receive mesna by injection into a vein.

Mesna is very effective in reducing the risk of hemorrhagic cystitis in most patients. However, it may not work in a small number of patients. Therefore, tell your doctor immediately if you notice that your urine is pink, red, or bloody.

SIDE EFFECTS: Headache, flushing, dizziness, drowsiness, nausea, vomiting, loss of appetite, diarrhea, constipation, sensitive skin, or flu-like symptoms (e.g., sore throat, fever, chills, shivering, cough, body aches) 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: chest pain, fast heartbeat, swelling ankles/feet, muscle weakness.

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 mesna, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: overactive immune system diseases (autoimmune disorders) that may increase your risk for a mesna allergy (e.g., rheumatoid arthritis, lupus, nephritis).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

Kidney function declines as you grow older. This medication is removed by the kidneys. The elderly may be more sensitive to the effects of this drug.

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

It is not known whether this drug passes into breast milk. Since this medication is given with a cancer chemotherapy drug, breast-feeding while using mesna is not recommended. 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.

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

This medication may interfere with a certain laboratory test (for urinary ketones), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

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 can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

This medication does not protect you from other side effects of ifosfamide. Consult your doctor or pharmacist for more information on how to manage other side effects.

Small amounts of blood in the urine cannot be seen without a microscope. Therefore, a laboratory test to check for blood in your urine should be performed before each dose of ifosfamide to monitor how well mesna is working. Consult your doctor for more details.

MISSED DOSE: It is important to take each dose of this medication as scheduled. If you miss a dose, take it as soon as you remember and contact your doctor for further instructions. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from heat 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.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

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