Generic Name:

Uses

Hemophilia B

Factor IX (human) and factor IX complex (human; also known as PCC) are used for prevention and control of hemorrhagic episodes in patients with a deficiency of coagulation factor IX associated with hemophilia B (Christmas disease).

In patients with preexisting thromboembolic risk factors, factor IX preferred over factor IX complex for treatment of hemophilia B. (See Thromboembolic Events under Cautions.)

Factor IX (human), factor IX complex (human), and factor IX (recombinant) may be used in patients with hemophilia B; however, because of an increased risk of transmission of human viruses (e.g., HIV viruses, hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV]) and other transmissible disease agents (e.g., agents for Creutzfeldt-Jakob disease [CJD], variant CJD [vCJD]) with plasma-derived factor IX preparations compared with factor IX (recombinant), the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation recommends factor IX (recombinant) as the preparation of choice for individuals with hemophilia B. (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.) Recombinant and plasma-derived preparations of factor IX produce comparable hemostatic effects.

Maintenance of hemostasis in patients with hemophilia B undergoing surgery.

Also used for routine prophylaxis (i.e., administration at regular intervals) to reduce frequency of hemorrhagic events and preserve joint function. MASAC and the World Federation of Hemophilia recommend primary prophylaxis for patients with severe hemophilia B (factor IX activity <1%) after careful consideration of risks versus benefits.

Not indicated in the treatment of other coagulation factor deficiencies (e.g., factors II, VII, X).

Not indicated for the treatment or prevention of hemophilia A in patients with inhibitors to factor VIII.

Not indicated in the treatment or reversal of coumarin-induced anticoagulation or hemorrhagic states caused by hepatitis-induced lack of production of liver-dependent coagulation factors.

Dosage and Administration

General

• Monitor factor IX frequently to individualize dosage and assess response to therapy. (See Laboratory Monitoring under Cautions.)

Administration

IV Administration

Administer factor IX (human) and factor IX complex (human) by slow IV injection or IV infusion.

Have been given as a continuous infusion†.

Manufacturers of Mononine^® and Profilnine^® SD recommend that drug be administered using plastic syringes only; factor IX (human) solution may adhere to glass.

Filter solution prior to administration.

Instructions on reconstitution, dilution, and administration vary according to preparation; consult manufacturer's labeling for specific information on each factor IX (human) or factor IX complex (human) product.

Reconstitution

Prior to reconstitution of factor IX (human) and factor IX complex (human), allow injection concentrate and diluent to warm to room temperature (≤37°C).

Reconstitute factor IX (human) and factor IX complex (human) concentrates with diluent (sterile water for injection) provided by manufacturer.

Gently swirl solution to dissolve powder completely; do not shake.

Administer immediately or within 3 hours after reconstitution; discard any unused solution after 3 hours. Do not refrigerate reconstituted solutions.

Rate of Administration

Individualize infusion rates based on specific product and patient response and comfort. Administer slowly to avoid vasomotor reactions.

AlphaNine^® SD: Administer at a rate ≤10 mL/minute.

Mononine^®: Administer solutions of 100 units/mL at a rate of approximately 2 mL/minute; has been administered at rates up to 225 units/minute without unusual adverse effects.

Bebulin^® VH: Administer at a rate ≤2 mL/minute.

Profilnine^® SD: Administer at a rate ≤10 mL/minute.

Dosage

Dosage (potency) of factor IX (human) and factor IX complex (human) expressed in terms of international units (IU, units) of factor IX activity. One unit is approximately equivalent to amount of factor IX activity in 1 mL of normal fresh pooled human plasma.

Individualize dosage and duration of therapy based on severity and location of hemorrhage, degree of factor IX deficiency, desired factor IX levels, presence of factor IX inhibitors, and clinical response. (See Laboratory Monitoring under Cautions.)

Use the following calculations and dosage guidelines (based on the degree of hemorrhage or type of surgery) for administering the drug.

These calculations and suggested dosage regimens are only approximations and should not preclude appropriate laboratory determinations and individualization of dosage based on the hemostatic requirements of patients. The manufacturers’ dosage recommendations should be consulted for further information on dosage.

If calculated dosage is ineffective in achieving appropriate factor IX levels, consider the possibility that inhibitors to factor IX may have developed. Manufacturer of Mononine^® suggests that higher dosages may be required in such situations.

Administration of 1 unit/kg of AlphaNine^® SD, Mononine^®, or Profilnine^® SD generally increases factor IX activity by 1%. Administration of 1 unit/kg of Bebulin^® VH generally increases factor IX activity by 0.8%.

Use the following formula for AlphaNine^® SD, Mononine^®, or Profilnine^® SD to determine dose of factor IX (human) or factor IX complex (human) required to achieve a particular percentage increase in plasma factor IX level:

Units required = body weight (in kg) × 1 (unit/kg) × desired factor IX increase (in % of normal)

Calculate dosages of Bebulin^® VH using the following formula:

Units required = body weight (in kg) × 1.2 (unit/kg) × desired factor IX increase (in % of normal)

Pediatric Patients

Hemophilia B

AlphaNine^®SD (Factor IX [human])

IV

Pediatric patients >16 years of age with minor hemorrhage (e.g., bruises, cuts, scrapes, uncomplicated joint hemorrhage): 20–30 units/kg twice daily to achieve a plasma factor IX level of at least 20–30% of normal until bleeding resolves or healing occurs, usually 1–2 days.

Pediatric patients >16 years of age with moderate hemorrhage (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25–50 units/kg twice daily to achieve a plasma factor IX level of 25–50% of normal until healing occurs, average 2–7 days.

Pediatric patients >16 years of age with major hemorrhage (e.g., joint or muscle bleeding [especially in large muscles], major trauma, hematuria, intracranial bleeding, intraperitoneal bleeding): Initially, 30–50 units/kg twice daily to achieve a plasma factor IX level of 50% of normal for at least 3–5 days. Use additional doses of 20 units/kg twice daily to maintain a plasma factor IX level of 20% of normal until healing occurs. Up to 10 days of treatment may be necessary.

Pediatric patients >16 years of age undergoing surgery: Initially, 50–100 units/kg twice daily to achieve a plasma factor IX level of 50–100% of normal prior to surgery. Use additional doses of 50–100 units/kg twice daily for 7–10 days (or until healing achieved) to maintain factor IX levels of 50–100% of normal.

Mononine^® (Factor IX [human])

IV

Minor (spontaneous) hemorrhage or prophylaxis: Initially, up to 20–30 units/kg to achieve a plasma factor IX level of 15–25% of normal; repeat once at 24 hours, if necessary.

Major trauma: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal. Up to 10 days of treatment may be necessary, depending on severity of bleeding.

Surgery: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal. Up to 10 days of treatment may be necessary.

Profilnine^® SD (Factor IX Complex [human])

IV

Pediatric patients >16 years of age with mild to moderate hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 20–30% of normal; single administration usually sufficient.

Pediatric patients >16 years of age with severe hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 30–50% of normal; daily infusions usually required.

Pediatric patients >16 years of age undergoing surgery: Use appropriate dosage to achieve a plasma factor IX level of approximately 30–50% of normal for at least 1 week following procedure.

Pediatric patients >16 years of age undergoing tooth extractions: Use appropriate dosage to achieve a plasma factor IX level of 50% of normal prior to procedure; may give additional doses if bleeding recurs.

Prophylaxis

IV

Optimum dosage regimen not yet established; individualize dosage.

Adults

Hemophilia B

AlphaNine^®SD (Factor IX [human])

IV

Minor hemorrhage (e.g., bruises, cuts, scrapes, uncomplicated joint hemorrhage): 20–30 units/kg twice daily to achieve a plasma factor IX level of at least 20–30% of normal until bleeding resolves or healing occurs, usually 1–2 days.

Moderate hemorrhage (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25–50 units/kg twice daily to achieve a plasma factor IX level of 25–50% of normal until healing occurs, average 2–7 days.

Major hemorrhage (e.g., joint or muscle bleeding [especially in large muscles], major trauma, hematuria, intracranial bleeding, intraperitoneal bleeding): Initially, 30–50 units/kg twice daily to achieve a plasma factor IX level of 50% of normal for at least 3–5 days. Use additional doses of 20 units/kg twice daily to maintain a plasma factor IX level of 20% of normal until healing occurs. Up to 10 days of treatment may be necessary.

Surgery: Initially, 50–100 units/kg twice daily to achieve a plasma factor IX level of 50–100% of normal prior to surgery. Use additional doses of 50–100 units/kg twice daily for 7–10 days (or until healing achieved) to maintain a factor IX level of 50–100% of normal.

Mononine^® (Factor IX [human])

IV

Minor (spontaneous) hemorrhage or prophylaxis: Initially, up to 20–30 units/kg to achieve a plasma factor IX level of 15–25% of normal; repeat once at 24 hours, if necessary.

Major trauma: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal. Up to 10 days of treatment may be necessary, depending on severity of bleeding.

Surgery: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal. Up to 10 days of treatment may be necessary.

Bebulin^®VH (Factor IX Complex [human])

IV

Minor hemorrhage (e.g., early hemarthrosis, minor epistaxis, gingival bleeding, mild hematuria): Initially, 25–35 units/kg to achieve a plasma factor IX level of 20% of normal. Single administration usually sufficient; may repeat once after 24 hours, if necessary.

Moderate hemorrhage (e.g., severe joint bleeding, early hematoma, major open bleeding, minor trauma, minor hemoptysis, minor hematemesis, minor melena, major hematuria): Initially, 40–55 units/kg to achieve a plasma factor IX level of approximately 40% of normal; may repeat every 24 hours for 2 days or until adequate healing occurs.

Major hemorrhage (e.g., severe hematoma, major trauma, severe hemoptysis, severe hematemesis, severe melena): Initially, 60–70 units/kg to achieve a plasma factor IX level of ≥60% of normal, unless patient has a high risk for thrombosis. (See Thromboembolic Events under Cautions.) May repeat every 24 hours for 2–3 days or until adequate healing occurs.

Minor surgery (e.g., tooth extraction): Initially 50–60 units/kg to achieve a plasma factor IX level of approximately 40–60% of normal 1 hour prior to surgery. One dose is usually sufficient for single tooth extraction. For extraction of several teeth and other minor surgical procedures, use additional doses of 25–55 units/kg for 1–2 weeks after surgery to maintain a plasma factor IX level of approximately 20–40% of normal. More frequent (e.g., every 12 hours) dosing may be required for initial treatments, while longer intervals (e.g., every 24 hours) usually sufficient during later postoperative period.

Major surgery: Initially, 70–95 units/kg to achieve a plasma factor IX level of ≥60% of normal 1 hour prior to surgery, unless patient has a high risk for thrombosis. (See Thromboembolic Events under Cautions.) Use additional doses of 35–70 units/kg for 1–2 weeks postoperatively to maintain a plasma factor IX level of approximately 20–60% of normal, then 25–35 units/kg from week 3 onward to maintain a plasma factor IX level of approximately 20% of normal. More frequent (e.g., every 12 hours) dosing may be required for initial treatments, while longer intervals (e.g., every 24 hours) usually sufficient during later postoperative period.

Profilnine^® SD (Factor IX Complex [human])

IV

Mild to moderate hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 20–30% of normal; single administration usually sufficient.

Severe hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 30–50% of normal; daily infusions usually required.

Surgery: Use appropriate dosage to achieve a plasma factor IX level of approximately 30–50% of normal for at least 1 week following surgery.

Tooth extractions: Use appropriate dosage to achieve a factor IX level of 50% of normal prior to procedure; may give additional doses if bleeding recurs.

Prophylaxis

IV

Optimum dosage regimen not yet established; individualize dosage.

Prescribing Limits

Pediatric Patients

Hemophilia B

IV

AlphaNine^® SD (pediatric patients >16 years of age), Profilnine^®SD (pediatric patients >16 years of age): Maximum rate of infusion 10 mL/minute.

Mononine^®: Infusion rates up to 225 units/minute have been well-tolerated.

Adults

Hemophilia B

IV

AlphaNine^® SD, Profilnine^®SD: Maximum rate of infusion 10 mL/minute.

Bebulin^® VH: Maximum rate of infusion 2 mL/minute.

Mononine^®: Infusion rates up to 225 units/minute have been well-tolerated.

Cautions

Contraindications

• Known hypersensitivity to murine protein (Mononine^®).

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Potential vehicle for transmission of human viruses (e.g., HIV, HAV, HBV, HCV) and other infectious agents.

Improved donor screening, viral-inactivating procedures (e.g., solvent/detergent, heat-treatment) and/or immunoaffinity chromatography procedures have reduced but not completely eliminated risk of pathogen transmission with plasma-derived factor IX and factor IX complex preparations.

Possibility still exists for transmission of human viruses (e.g., HIV, HAV, HBV, HCV) and other infectious agents (e.g., unknown viruses; other disease agents including transfusion-transmitted virus [TTV], CJD, vCJD, transmissible spongiform encephalopathy [TSE] diseases).

Current viral-depleting methods apparently can inactivate lipid-encapsulated viruses, such as HBV, HIV-1, HIV-2, and HCV; however, these methods are less effective against viruses that do not have a lipid envelope, such as parvovirus B19 and HAV. Transmission of nonenveloped viruses, including HAV and parvovirus B19, has been documented following administration of plasma-derived coagulation factors. Monitor for signs and symptoms of parvovirus B19 and hepatitis A during therapy. (See Advice to Patients.)

Carefully weigh risk of pathogen transmission versus benefits of factor IX (human) and factor IX complex (human) prior to initiating therapy.

Report any infections thought to be associated with factor IX (human) or factor IX complex (human) to the manufacturer, FDA, and CDC.

Risk of Hepatitis

Risk of hepatitis A or hepatitis B infection.

Monitor closely for signs and symptoms of hepatitis A during therapy. (See Advice to Patients.)

MASAC and other experts recommend administration of hepatitis B vaccine to all individuals with a bleeding disorder at birth or at time of diagnosis. CDC recommends immunization with hepatitis A vaccine for all patients ≥12 months of age with a bleeding disorder.

Risk of HIV Infection

Potential vehicle for transmission of HIV. HIV seroconversion reported in the past in patients who received factor IX complex (human) from donors not screened for HIV and/or prepared using suboptimal viral-inactivating procedures (e.g., heat-treatment only).

No reports to date of HIV transmission with currently available plasma-derived clotting factor preparations.

Risk of Creutzfeldt-Jakob Disease

Theoretic possibility of transmitting causative agent of CJD or vCJD. Several probable cases of vCJD transmission reported from transfusion of human RBCs. However, no reports to date of CJD or vCJD transmission from commercially available factor IX products. For further information on CJD and vCJD precautions related to blood and blood products, consult the FDA's guidance for industry (http://www.fda.gov/cber/gdlns/cjdvcjd.pdf).

Risk of West Nile Virus

Evidence of West Nile virus (WNV) transmission through transplanted organs (e.g., heart, liver, kidney) and blood products. However, WNV transmission through commercially available factor IX preparations unlikely due to current viral-inactivating procedures.

For further information on WNV precautions related to blood and blood products, consult the FDA’s guidance for industry (http://www.fda.gov/cber/gdlns/wnvguid.pdf).

Thromboembolic Events

Serious and potentially fatal thromboembolic events (e.g., MI, venous thrombosis, PE, disseminated intravascular coagulopathy [DIC]) reported with use of factor IX complex preparations. Increased risk in patients with preexisting thrombotic risk factors (e.g., liver disease, concomitant use of thrombogenic drugs, history of thrombosis, DIC) and in those receiving prolonged therapy and/or high dosages of factor IX complex; also increased risk during postoperative period in patients undergoing surgery, and in neonates. Exercise caution when factor IX (human) or factor IX complex (human) is used in such patients.

Weigh potential benefits of drug against risks of thrombotic complications. Consider using pure factor IX preparations that may be less thrombogenic than factor IX complex in high-risk patients. Patients undergoing surgery and those with other predisposing risk factors should be monitored closely for manifestations of thromboembolism (e.g., changes in BP or pulse rate, respiratory distress, chest pain, cough) and DIC. Follow recommended dosage guidelines to decrease risk of thromboembolic complications; one manufacturer suggests that in high-risk patients, factor IX levels not exceed 60%. If evidence of thrombosis or DIC occurs during therapy, discontinue factor IX complex immediately.

Renal Effects

Nephrotic syndrome reported in patients undergoing immune tolerance induction who have inhibitors and/or a history of hypersensitivity reactions to factor IX. Safety and efficacy of factor IX products for immune tolerance induction not established.

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (hives, pruritus, edema, tightness of chest, angioedema, dyspnea, wheezing, faintness, hypotension, tachycardia, urticaria, shock) reported with use of all factor IX products.

Increased risk in patients with certain genetic mutations of factor IX and those with inhibitors to factor IX. Up to 50% of patients with inhibitors to factor IX may experience severe hypersensitivity reactions, including anaphylaxis.

In patients with inhibitors or with known genetic defects associated with inhibitor development, administer initial (e.g., approximately 10–20) infusions in a hospital setting where severe allergic reactions can be managed.

Closely observe for hypersensitivity reactions, especially during the initial phases of therapy.

If manifestations of hypersensitivity reactions or anaphylaxis occur, discontinue drug immediately and initiate appropriate therapy. Depending on severity of the reaction, use antihistamines, slow infusion rate, or switch to another factor IX product.

Antibody Formation

Mononine^® contains trace amounts of murine protein which may stimulate antibody latex insert production and cause hypersensitivity reactions. (See Contraindications under Cautions.)

General Precautions

Development of Inhibitors to Factor IX

Risk for development of inhibitors (IgG antibodies) to factor IX following treatment with factor IX preparations. Reported in about 1–5% of patients with hemophilia B, usually within the first 10–20 days of treatment. Patients with certain genetic mutations of the factor IX gene may be at higher risk.

Consultation with a hemophilia treatment center strongly recommended for patients with inhibitors.

Laboratory Monitoring

Monitor factor IX levels at regular intervals (at least daily) to guide dosing and ensure adequate therapeutic response.

Monitor for development of inhibitors during treatment and prior to surgery. (See Development of Inhibitors to Factor IX under Cautions.)

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether factor IX (human) or factor IX complex (human) is distributed into human milk.

Pediatric Use

Use with caution in neonates because of potential thrombotic risk. (See Thromboembolic Events under Cautions.)

AlphaNine^® SD: Safety and efficacy not established in children ≤16 years of age. In a well-controlled clinical study in patients who previously received factor IX concentrates for hemophilia B, and in an ongoing safety and efficacy clinical trial in patients who did not previously receive factor IX concentrates, pediatric patients responded similarly to adult patients; adverse effects in these children were similar to those observed in patients >16 years of age.

Bebulin^® VH: Safety and efficacy not established; studies evaluating use in pediatric patients with hemophilia B not available.

Mononine^®: Safety and efficacy established in pediatric patients between the ages of 1 day and 20 years; excellent hemostasis achieved with no thrombotic complications. Dosing in children is generally based on the same guidelines as for adults.

Profilnine^® SD: Safety and efficacy not established in children ≤16 years of age. In a well-controlled clinical study in patients who previously received factor IX complex for hemophilia B, pediatric patients responded similarly to adult patients; no adverse effects were reported in children.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. Select dosage with caution.

Common Adverse Effects

Fever, chills, nausea, vomiting, headache, somnolence, lethargy, flushing, tingling, stinging or burning at infusion site.

Interactions

Specific Drugs

Pharmacokinetics

Absorption

Plasma Concentrations

Following IV infusion over 5–15 minutes, plasma concentrations of factor IX increase by approximately 0.01–0.014 units/mL per unit/kg administered.

Distribution

Extent

Readily diffuses through interstitial fluid; distributes through both intravascular and extravascular compartments.

Circulates in plasma as unbound drug.

Binds rapidly and reversibly to vascular endothelium.

Not known whether factor IX (human) and factor IX complex (human) are distributed into milk.

Elimination

Half-life

Biphasic.

Half-life subject to interindividual variation; approximately 18–25 hours for factor IX, and 18–36 hours for factor IX complex.

Factor IX complex (human) is rapidly cleared from plasma.

Stability

Storage

Parenteral

Powder for Injection

AlphaNine^® SD: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤30°C for up to 1 month. Use solution within 3 hours of reconstitution.

Bebulin^® VH: 2–8°C (avoid freezing to prevent damage to the diluent vial). Do not use beyond expiration date. Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.

Mononine^®: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤25°C for up to 1 month. Do not use beyond expiration date. Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.

Profilnine^® SD: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤30°C for up to 3 months. Use solution within 3 hours of reconstitution.

Actions

• Factor IX is a vitamin K-dependent coagulation factor synthesized in the liver.
• Factor IX is essential for blood clotting and maintenance of hemostasis.
• Patients with hemophilia B (Christmas disease) have decreased levels of endogenous factor IX, resulting in a hemorrhagic tendency and clinical manifestations such as bleeding into soft tissues, muscles, joints, and internal organs.
• Clinical severity and frequency of bleeding in patients with hemophilia B correlate with the degree of deficiency of factor IX activity. Patients with mild hemophilia B generally have >5% of normal activity, those with moderate disease generally have 1–5% of normal activity, and those with severe disease have <1% of normal activity.
• Administration of factor IX (human) to patients with hemophilia B results in increased plasma levels of factor IX and temporarily corrects coagulation defect.
• Factor IX is activated by Factor XIa in the intrinsic coagulation pathway. Activated factor IX, in combination with activated factor VIII, activates factor X to Xa, resulting ultimately in the conversion of factor II (prothrombin) to thrombin and formation of a fibrin clot.
• Factor IX (human) preparations are purified concentrates of factor IX derived from human plasma. Factor IX complex (human) preparations contain variable amounts of vitamin K-dependent clotting factors II, VII, IX, and X.
• Prepared using different methods (e.g., precipitation, gel filtration, chromatography, ultrafiltration) to isolate and purify factor IX. Undergoes viral inactivation processes (e.g., heat, solvent/detergent) to reduce risk of viral transmission.

Advice to Patients

• Importance of discontinuing therapy and immediately informing clinician if fever, rash, urticaria, nausea, vomiting, or other manifestations of hypersensitivity reactions or anaphylaxis occur or, alternatively, seeking immediate emergency care depending on severity of such reactions.
• Risk of transmission of parvovirus B19 and/or hepatitis A from plasma-derived factor IX (human) and factor IX complex (human). Importance of informing clinician promptly if symptoms of potential parvovirus B19 infection (fever, drowsiness, chills and rhinorrhea followed by rash and joint pain 2 weeks later) or hepatitis A infection (low-grade fever, anorexia, nausea, vomiting, fatigue, jaundice, dark urine, abdominal pain) occur.
• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., liver disease).
• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions June 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.