Indapamide CF

Indapamide CF may be available in the countries listed below.

Ingredient matches for Indapamide CF

Indapamide

Indapamide is reported as an ingredient of Indapamide CF in the following countries:

• Netherlands

International Drug Name Search

Factor IX

Class: Hemostatics
VA Class: BL500
CAS Number: 37224-63-8
Brands: AlphaNine SD, Bebulin VH, Mononine, Profilnine SD

Introduction

Factor IX (human): Preparation of blood coagulation factor IX derived from pooled human plasma.^{149 151 152}

Factor IX complex (human): Prothrombin complex concentrate (PCC); preparation of nonactivated blood coagulation factors II, VII, IX, and X derived from pooled human plasma.^{100 140 e}

Uses for Factor IX

Hemophilia B

Factor IX (human)^{151 152} and factor IX complex (human; also known as PCC)^{100 140} are used for prevention and control of hemorrhagic episodes in patients with a deficiency of coagulation factor IX associated with hemophilia B (Christmas disease).^{100 140 151 152 156 e f}

In patients with preexisting thromboembolic risk factors, factor IX preferred over factor IX complex for treatment of hemophilia B.^{148 151 156 c f} (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.^{155 156 j l} (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.) Recombinant and plasma-derived preparations of factor IX produce comparable hemostatic effects.^{156 p}

Maintenance of hemostasis in patients with hemophilia B undergoing surgery.^{100 140 151 152 e f}

Also used for routine prophylaxis (i.e., administration at regular intervals) to reduce frequency of hemorrhagic events and preserve joint function.^{100 c e j l} 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.^{c h}

Not indicated in the treatment of other coagulation factor deficiencies (e.g., factors II, VII, X).^{100 140 151 152}

Not indicated for the treatment^{151 152} or prevention ¹⁵² of hemophilia A in patients with inhibitors to factor VIII.^{151 152}

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.^{151 152}

Factor IX Dosage and Administration

General

• 
  

  Monitor factor IX frequently to individualize dosage and assess response to therapy.^{140 151 152} (See Laboratory Monitoring under Cautions.)

  
  

Administration

IV Administration

Administer factor IX (human) and factor IX complex (human) by slow IV injection or IV infusion.^{100 140 151 152}

Have been given as a continuous infusion†.^{c e f}

Manufacturers of Mononine and Profilnine SD recommend that drug be administered using plastic syringes only; factor IX (human) solution may adhere to glass.^{140 152}

Filter solution prior to administration.^{100 140 151 152 c}

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.^{100 140 151 152}

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).^{100 140 151 152}

Reconstitute factor IX (human) and factor IX complex (human) concentrates with diluent (sterile water for injection) provided by manufacturer.^{100 140 151 152}

Gently swirl solution to dissolve powder completely; do not shake.^{100 140 151 152}

Administer immediately or within 3 hours after reconstitution; discard any unused solution after 3 hours.^{100 140 151 152} Do not refrigerate reconstituted solutions.^{100 140 152 a}

Rate of Administration

Individualize infusion rates based on specific product and patient response and comfort.^{100 140 152} Administer slowly to avoid vasomotor reactions.^{140 151}

AlphaNine SD: Administer at a rate ≤10 mL/minute.¹⁵¹

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.^{152 a}

Bebulin VH: Administer at a rate ≤2 mL/minute.¹⁰⁰

Profilnine SD: Administer at a rate ≤10 mL/minute.¹⁴⁰

Dosage

Dosage (potency) of factor IX (human) and factor IX complex (human) expressed in terms of international units (IU, units) of factor IX activity.^{100 140 151 152 l} One unit is approximately equivalent to amount of factor IX activity in 1 mL of normal fresh pooled human plasma.^{100 140 151 152}

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.^{100 140 151 152 f n} (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.^{100 140 151 152}

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.^a The manufacturers’ dosage recommendations should be consulted for further information on dosage.^{100 140}

If calculated dosage is ineffective in achieving appropriate factor IX levels, consider the possibility that inhibitors to factor IX may have developed.^c Manufacturer of Mononine suggests that higher dosages may be required in such situations.¹⁵²

Administration of 1 unit/kg of AlphaNine SD, Mononine, or Profilnine SD generally increases factor IX activity by 1%.^{140 151 152} Administration of 1 unit/kg of Bebulin VH generally increases factor IX activity by 0.8%.¹⁰⁰

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:^{140 151 152}

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:¹⁰⁰

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

Pediatric Patients

Hemophilia B

AlphaNineSD (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.¹⁵¹

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.¹⁵¹

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.¹⁵¹ Use additional doses of 20 units/kg twice daily to maintain a plasma factor IX level of 20% of normal until healing occurs.¹⁵¹ Up to 10 days of treatment may be necessary.¹⁵¹

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.¹⁵¹ 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.¹⁵¹

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.¹⁵²

Major trauma: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary, depending on severity of bleeding.¹⁵²

Surgery: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary.¹⁵²

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.¹⁴⁰

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.¹⁴⁰

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.¹⁴⁰

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.¹⁴⁰

Prophylaxis

IV

Optimum dosage regimen not yet established; individualize dosage.^{c l}

Adults

Hemophilia B

AlphaNineSD (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.¹⁵¹

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.¹⁵¹

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.¹⁵¹ Use additional doses of 20 units/kg twice daily to maintain a plasma factor IX level of 20% of normal until healing occurs.¹⁵¹ Up to 10 days of treatment may be necessary.¹⁵¹

Surgery: Initially, 50–100 units/kg twice daily to achieve a plasma factor IX level of 50–100% of normal prior to surgery.¹⁵¹ 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.¹⁵¹

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.¹⁵²

Major trauma: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary, depending on severity of bleeding.¹⁵²

Surgery: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary.¹⁵²

BebulinVH (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.¹⁰⁰ Single administration usually sufficient; may repeat once after 24 hours, if necessary.¹⁰⁰

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.¹⁰⁰

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.¹⁰⁰ (See Thromboembolic Events under Cautions.) May repeat every 24 hours for 2–3 days or until adequate healing occurs.¹⁰⁰

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.¹⁰⁰ One dose is usually sufficient for single tooth extraction.¹⁰⁰ 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.¹⁰⁰ 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.¹⁰⁰

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.¹⁰⁰ (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.¹⁰⁰ 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.¹⁰⁰

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.¹⁴⁰

Severe hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 30–50% of normal; daily infusions usually required.¹⁴⁰

Surgery: Use appropriate dosage to achieve a plasma factor IX level of approximately 30–50% of normal for at least 1 week following surgery.¹⁴⁰

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.¹⁴⁰

Prophylaxis

IV

Optimum dosage regimen not yet established; individualize dosage.^{100 c l}

Prescribing Limits

Pediatric Patients

Hemophilia B

IV

AlphaNine SD (pediatric patients >16 years of age), ProfilnineSD (pediatric patients >16 years of age): Maximum rate of infusion 10 mL/minute.^{140 151}

Mononine: Infusion rates up to 225 units/minute have been well-tolerated.¹⁵²

Adults

Hemophilia B

IV

AlphaNine SD, ProfilnineSD: Maximum rate of infusion 10 mL/minute.^{140 151}

Bebulin VH: Maximum rate of infusion 2 mL/minute.¹⁰⁰

Mononine: Infusion rates up to 225 units/minute have been well-tolerated.¹⁵²

Cautions for Factor IX

Contraindications

• 
  

  Known hypersensitivity to murine protein (Mononine).¹⁵²

  
  

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.^{100 140 151 152 155 156}

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.^{100 130 140 151 152 155 156 l}

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).^{100 130 140 145 146 147 151 152 155 156 161 162}

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 B19¹⁵⁶ and HAV.^{155 156} Transmission of nonenveloped viruses, including HAV^{156 157} and parvovirus B19,¹⁵⁶ has been documented following administration of plasma-derived coagulation factors.^{151 152 156 d n} Monitor for signs and symptoms of parvovirus B19 and hepatitis A during therapy.^{100 152} (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.^{100 140 151 152 155}

Report any infections thought to be associated with factor IX (human) or factor IX complex (human) to the manufacturer, FDA, and CDC.^{100 140 151 152 156}

Risk of Hepatitis

Risk of hepatitis A or hepatitis B infection.^{100 140 151 152 156 j}

Monitor closely for signs and symptoms of hepatitis A during therapy.^{100 152} (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.^{100 140 141 151 156 160 j l} CDC recommends immunization with hepatitis A vaccine for all patients ≥12 months of age with a bleeding disorder.^b

Risk of HIV Infection

Potential vehicle for transmission of HIV.^{101 102 103 105 106 105 106 111 121 126 127 128 132 133 135 138 140 151} 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).^{101 102 103 108 121 125 128 129 131 136 137 138 j}

No reports to date of HIV transmission with currently available plasma-derived clotting factor preparations.^{151 152 156 j}

Risk of Creutzfeldt-Jakob Disease

Theoretic possibility of transmitting causative agent of CJD or vCJD.^{140 145 152 155 d j} Several probable cases of vCJD transmission reported from transfusion of human RBCs.^{155 167} However, no reports to date of CJD or vCJD transmission from commercially available factor IX products.^{145 146 155} For further information on CJD and vCJD precautions related to blood and blood products, consult the FDA’s guidance for industry ().¹⁴⁵

Risk of West Nile Virus

Evidence of West Nile virus (WNV) transmission through transplanted organs (e.g., heart, liver, kidney) and blood products.^{153 154 163 164} However, WNV transmission through commercially available factor IX preparations unlikely due to current viral-inactivating procedures.^{143 154}

For further information on WNV precautions related to blood and blood products, consult the FDA’s guidance for industry ().¹⁵⁴

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.^{140 151 152 f g} 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.^{100 140 152 f g} Exercise caution when factor IX (human) or factor IX complex (human) is used in such patients.¹⁵²

Weigh potential benefits of drug against risks of thrombotic complications.^{140 152 a} Consider using pure factor IX preparations that may be less thrombogenic than factor IX complex in high-risk patients.^{148 151 152 156 c f l} 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.^{100 140 151} Follow recommended dosage guidelines to decrease risk of thromboembolic complications;¹⁵¹ one manufacturer suggests that in high-risk patients, factor IX levels not exceed 60%.¹⁰⁰ If evidence of thrombosis or DIC occurs during therapy, discontinue factor IX complex immediately.¹⁰⁰

Renal Effects

Nephrotic syndrome reported in patients undergoing immune tolerance induction who have inhibitors and/or a history of hypersensitivity reactions to factor IX.^{151 152 d j k l} Safety and efficacy of factor IX products for immune tolerance induction not established.^{151 152}

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.^{100 151 152 d}

Increased risk in patients with certain genetic mutations of factor IX and those with inhibitors to factor IX.^{151 152 c d j k l m} Up to 50% of patients with inhibitors to factor IX may experience severe hypersensitivity reactions, including anaphylaxis.^c

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.^{c j k}

Closely observe for hypersensitivity reactions, especially during the initial phases of therapy.^{151 152}

If manifestations of hypersensitivity reactions or anaphylaxis occur, discontinue drug immediately and initiate appropriate therapy.^{100 140 151 152} Depending on severity of the reaction, use antihistamines, slow infusion rate, or switch to another factor IX product.^{100 140 151 152 c}

Antibody Formation

Mononine contains trace amounts of murine protein which may stimulate antibody latex insert production and cause hypersensitivity reactions.¹⁵² (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.^{c j k l m} Reported in about 1–5% of patients with hemophilia B, usually within the first 10–20 days of treatment.^{c e j m} Patients with certain genetic mutations of the factor IX gene may be at higher risk.^{152 c j k l m}

Consultation with a hemophilia treatment center strongly recommended for patients with inhibitors.^{156 c}

Laboratory Monitoring

Monitor factor IX levels at regular intervals (at least daily) to guide dosing and ensure adequate therapeutic response.^{100 140 151 152 c n}

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

Specific Populations

Pregnancy

Category C.^{100 140 151 152}

Lactation

Not known whether factor IX (human) or factor IX complex (human) is distributed into human milk.^{i o}

Pediatric Use

Use with caution in neonates because of potential thrombotic risk.¹⁵² (See Thromboembolic Events under Cautions.)

AlphaNine SD: Safety and efficacy not established in children ≤16 years of age.¹⁵¹ 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;¹⁵¹ adverse effects in these children were similar to those observed in patients >16 years of age.¹⁵¹

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

Mononine: Safety and efficacy established in pediatric patients between the ages of 1 day and 20 years; excellent hemostasis achieved with no thrombotic complications.¹⁵² Dosing in children is generally based on the same guidelines as for adults.¹⁵²

Profilnine SD: Safety and efficacy not established in children ≤16 years of age.¹⁴⁰ 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.¹⁴⁰

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.¹⁵² Select dosage with caution.¹⁵²

Common Adverse Effects

Fever,^{100 140 152} chills,^{140 151 152} nausea,^{100 140 151 152} vomiting,^{100 140 152} headache,^{140 152} somnolence,¹⁴⁰ lethargy,^{140 152} flushing,^{140 152} tingling,^{140 152} stinging or burning at infusion site.¹⁵²

Interactions for Factor IX

Specific Drugs

Drug	Interaction	Comments
Antifibrinolytics (e.g., tranexamic acid, aminocaproic acid)	Potential additive thrombotic effects and increased risk for thrombosis with factor IX complex preparationsc	Avoid concomitant usec

Factor IX 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.^e

Distribution

Extent

Readily diffuses through interstitial fluid; distributes through both intravascular and extravascular compartments.^{e f m}

Circulates in plasma as unbound drug.^e

Binds rapidly and reversibly to vascular endothelium.^e

Not known whether factor IX (human) and factor IX complex (human) are distributed into milk.^{i o}

Elimination

Half-life

Biphasic.^{a e}

Half-life subject to interindividual variation; approximately 18–25 hours for factor IX,^{151 152 c j} and 18–36 hours for factor IX complex.^{100 140 151}

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

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.¹⁵¹ Use solution within 3 hours of reconstitution.¹⁵¹

Bebulin VH: 2–8°C (avoid freezing to prevent damage to the diluent vial).¹⁰⁰ Do not use beyond expiration date.¹⁰⁰ Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.¹⁰⁰

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.¹⁵² Do not use beyond expiration date.¹⁵² Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.¹⁵²

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.¹⁴⁰ Use solution within 3 hours of reconstitution.¹⁴⁰

ActionsActions

• 
  

  Factor IX is a vitamin K-dependent coagulation factor synthesized in the liver.¹⁵²

  
  


• 
  

  Factor IX is essential for blood clotting and maintenance of hemostasis.^{152 f j}

  
  


• 
  

  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.^{152 c}

  
  


• 
  

  Clinical severity and frequency of bleeding in patients with hemophilia B correlate with the degree of deficiency of factor IX activity.^c 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.^{c d f j l}

  
  


• 
  

  Administration of factor IX (human) to patients with hemophilia B results in increased plasma levels of factor IX and temporarily corrects coagulation defect.¹⁵²

  
  


• 
  

  Factor IX is activated by Factor XIa in the intrinsic coagulation pathway.¹⁵² 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.^{152 f}

  
  


• 
  

  Factor IX (human) preparations are purified concentrates of factor IX derived from human plasma.^{151 152} Factor IX complex (human) preparations contain variable amounts of vitamin K-dependent clotting factors II, VII, IX, and X.^{100 140 e f}

  
  


• 
  

  Prepared using different methods (e.g., precipitation, gel filtration, chromatography, ultrafiltration) to isolate and purify factor IX.^{100 140 151 152 l} Undergoes viral inactivation processes (e.g., heat, solvent/detergent) to reduce risk of viral transmission.^{100 140 151 152 156 l}

  
  

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.^{100 140 151 152}

  
  


• 
  

  Risk of transmission of parvovirus B19 and/or hepatitis A from plasma-derived factor IX (human) and factor IX complex (human).^{100 140 151 152} 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.^{100 152}

  
  


• 
  

  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).^{100 140 151 152}

Indomethacin Suppositories

Pronunciation: IN-doe-METH-a-sin
Generic Name: Indomethacin
Brand Name: Indocin

Indomethacin Suppositories are a nonsteroidal anti-inflammatory drug (NSAID). It may cause an increased risk of serious and sometimes fatal heart and blood vessel problems (eg, heart attack, stroke). The risk may be greater if you already have heart problems or if you take Indomethacin Suppositories for a long time. Do not use Indomethacin Suppositories right before or after bypass heart surgery.

Indomethacin Suppositories may cause an increased risk of serious and sometimes fatal stomach ulcers and bleeding. Elderly patients may be at greater risk. This may occur without warning signs.

Indomethacin Suppositories are used for:

Treating moderate to severe rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. It is used to treat gout or certain types of bursitis and tendonitis. It may also be used for other conditions as determined by your doctor.

Indomethacin Suppositories are an NSAID. Exactly how it works is not known. It may block certain substances in the body that are linked to inflammation. NSAIDs treat the symptoms of pain and inflammation. They do not treat the disease that causes those symptoms.

Do NOT use Indomethacin Suppositories if:

• you are allergic to any ingredient in Indomethacin Suppositories


• you have had a severe allergic reaction (eg, severe rash, hives, trouble breathing, growths in the nose, dizziness) to aspirin or an NSAID (eg, ibuprofen, celecoxib)


• you have recently had or will be having bypass heart surgery


• you have a history of inflammation of the rectum or anus or recent rectal bleeding


• you are taking diflunisal, another NSAID (eg, ibuprofen), or triamterene


• you are in the last 3 months of pregnancy

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

Before using Indomethacin Suppositories:

Some medical conditions may interact with Indomethacin Suppositories. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of kidney or liver disease, diabetes, or stomach or bowel problems (eg, bleeding, perforation, ulcers, inflammation)


• if you have a history of swelling or fluid buildup, depression, mental or mood problems, seizures, Parkinson disease, asthma, growths in the nose (nasal polyps), or mouth inflammation


• if you have high blood pressure, a blood disorder, bleeding or clotting problems, heart problems (eg, heart failure), or blood vessel disease, or if you are at risk for any of these diseases


• if you have poor health, dehydration or low fluid volume, low blood sodium levels, or high blood potassium levels, you drink alcohol, or you have a history of alcohol abuse

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

• Anticoagulants (eg, warfarin), corticosteroids (eg, prednisone), diflunisal, heparin, other NSAIDs (eg, ibuprofen), salicylates (eg, aspirin), or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the risk of stomach bleeding may be increased


• Potassium-sparing diuretics (eg, spironolactone, triamterene) because the risk of kidney problems or increased blood potassium levels may be increased


• Cyclophosphamide because low blood sodium levels may occur


• Probenecid because it may increase the risk of Indomethacin Suppositories's side effects


• Cyclosporine, digoxin, lithium, methotrexate, quinolones (eg, ciprofloxacin), or sulfonylureas (eg, glipizide) because the risk of their side effects may be increased by Indomethacin Suppositories


• Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril), angiotensin receptor blockers (eg, losartan), beta-blockers (eg, propranolol), or diuretics (eg, furosemide, hydrochlorothiazide) because their effectiveness may be decreased by Indomethacin Suppositories

This may not be a complete list of all interactions that may occur. Ask your health care provider if Indomethacin Suppositories may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Indomethacin Suppositories:

Use Indomethacin Suppositories as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Indomethacin Suppositories comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Indomethacin Suppositories refilled.


• Wash your hands before and after using Indomethacin Suppositories.


• If the suppository is too soft to use, put it in the refrigerator for about 15 minutes. You may also run cold water over it.


• Remove the wrapper. Moisten the suppository with cool water. Lie down on your side. Insert the pointed end of the suppository into the rectum. Use your finger to push it in completely.


• If you miss a dose of Indomethacin Suppositories and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose. Go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Indomethacin Suppositories.

Important safety information:

• Indomethacin Suppositories may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Indomethacin Suppositories with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Serious stomach ulcers or bleeding can occur with the use of Indomethacin Suppositories. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking Indomethacin Suppositories with food will NOT reduce the risk of these effects. Contact your doctor or emergency room at once if you develop severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling.


• Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.


• Indomethacin Suppositories are an NSAID. Before you start taking any new medicine, read the ingredients. If it also has an NSAID (eg, ibuprofen) in it, check with your doctor. If you are not sure, check with your doctor or pharmacist.


• Do not take aspirin while you are using Indomethacin Suppositories unless your doctor tells you to.


• Indomethacin Suppositories may interfere with certain lab tests. Be sure your doctor and lab personnel know that you take Indomethacin Suppositories.


• Lab tests, including kidney function, complete blood cell counts, and blood pressure, may be done to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• Use Indomethacin Suppositories with caution in the ELDERLY; they may be more sensitive to its effects, including stomach bleeding, kidney problems, confusion, or mental changes.


• Indomethacin Suppositories should be used with extreme caution in CHILDREN younger than 15 year old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Indomethacin Suppositories may harm the fetus. Do not use it during the last 3 months of pregnancy. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Indomethacin Suppositories while you are pregnant. Indomethacin Suppositories are found in breast milk. Do not breast-feed while you are taking Indomethacin Suppositories.

Possible side effects of Indomethacin Suppositories:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; gas; headache; heartburn; nausea; rectal irritation; stomach upset.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; dark urine; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; inability to urinate or pass a stool even though you have the urge; mental or mood changes; numbness of an arm or leg; one-sided weakness; rectal bleeding; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe vomiting; shortness of breath; sudden or unexplained weight gain; swelling of hands, legs, or feet; unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; unusual vaginal bleeding; vision or speech changes; vomit that looks like coffee grounds; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Indomethacin side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include confusion; decreased urination; loss of consciousness; seizures; severe dizziness or drowsiness; severe headache; severe nausea or stomach pain; slow or troubled breathing; unusual bleeding or bruising; vomit that looks like coffee grounds.

Proper storage of Indomethacin Suppositories:

Store Indomethacin Suppositories at room temperature, below 86 degrees F (30 degrees C). Avoid temperatures above 104 degrees F (40 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Indomethacin Suppositories out of the reach of children and away from pets.

General information:

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


• Indomethacin Suppositories are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is summary only. It does not contain all information about Indomethacin Suppositories. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Indomethacin resources

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

Compare Indomethacin with other medications

• Ankylosing Spondylitis
• Back Pain
• Bartter Syndrome
• Bursitis
• Cluster Headaches
• Frozen Shoulder
• Gitelman Syndrome
• Gout, Acute
• Langerhans' Cell Histiocytosis
• Osteoarthritis
• Pain
• Patent Ductus Arteriosus
• Rheumatoid Arthritis
• Sciatica
• Tendonitis

Amenorrhea Medications

Definition of Amenorrhea:

The absence or discontinuation or abnormal stoppage of the menstrual periods.

Synonym: amenia.

More...

Drugs associated with Amenorrhea

The following drugs and medications are in some way related to, or used in the treatment of Amenorrhea. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Amenorrhea

Medical Encyclopedia:

• Amenorrhea - primary
• Secondary amenorrhea

Harvard Health Guide:

• Symptoms and treatment for Amenorrhea

Drug List:

Aygestin

Camila

Crinone-Gel

Depo-Provera

Depo-Provera-Contraceptive-Injectable

Depo-Subq-Provera-104-Injectable-Suspension-Subcutaneous

Endometrin

Errin

Factrel

First-Progesterone-Mc10

First-Progesterone-Mc5

Jolivette

Menopause-Formula-Progesterone

Nor-Qd

Nora-Be

Ortho-Micronor

Prochieve-Gel

Progest

Prometrium

Provera

ProAir HFA Aerosol

Pronunciation: al-BUE-ter-ol
Generic Name: Albuterol
Brand Name: ProAir HFA

ProAir HFA Aerosol is used for:

Treating or preventing breathing problems in patients who have asthma or certain other airway diseases. It may be used to prevent breathing problems caused by exercise. It may also be used for other conditions as determined by your doctor.

ProAir HFA Aerosol is a sympathomimetic (beta agonist) bronchodilator. It works by relaxing the smooth muscle in the airway, which allows air to flow in and out of the lungs more easily.

Do NOT use ProAir HFA Aerosol if:

• you are allergic to any ingredient in ProAir HFA Aerosol


• you are using another short-acting sympathomimetic bronchodilator (eg, metaproterenol)

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

Before using ProAir HFA Aerosol:

Some medical conditions may interact with ProAir HFA Aerosol. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of heart problems, (eg, fast or irregular heartbeat, low blood output), blood vessel problems, high blood pressure, or low blood potassium levels


• if you have a history of seizures, diabetes, an overactive thyroid, kidney problems, or an adrenal gland tumor (pheochromocytoma)


• if you have ever had an unusual reaction to another sympathomimetic medicine (eg, pseudoephedrine)


• if you are taking a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) or tricyclic antidepressant (eg, amitriptyline), or if you have taken either of these medicines within the last 14 days

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

• Diuretics (eg, furosemide, hydrochlorothiazide) because the risk of low blood potassium levels may be increased


• Catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), MAOIs (eg, phenelzine), short-acting sympathomimetic bronchodilators (eg, metaproterenol), stimulants (eg, amphetamine), sympathomimetics (eg, pseudoephedrine), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of ProAir HFA Aerosol's side effects


• Beta-blockers (eg, propranolol) because they may decrease ProAir HFA Aerosol's effectiveness


• Digoxin because its effectiveness may be decreased by ProAir HFA Aerosol

This may not be a complete list of all interactions that may occur. Ask your health care provider if ProAir HFA Aerosol may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use ProAir HFA Aerosol:

Use ProAir HFA Aerosol as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with ProAir HFA Aerosol. Talk to your pharmacist if you have questions about this information.


• ProAir HFA Aerosol is for oral inhalation only. Do not spray in the eyes. If you get ProAir HFA Aerosol in the eyes, rinse immediately with cool tap water.


• Prime the inhaler before the first use, any time it has not been used for more than 2 weeks, or if it has been dropped. To prime the inhaler, point it away from you and others. Spray 3 times, shaking well before each spray.


• Before using ProAir HFA Aerosol, be sure that the canister is properly placed in the inhaler unit. Shake well before each use. Remove the protective cap from the mouthpiece and check to make sure there are no hidden foreign objects. Breathe out slowly and completely. Place the mouthpiece fully into the mouth and close the lips around it, unless your doctor has told you otherwise. Your doctor may have told you to hold the inhaler 1 or 2 inches (2 or 3 centimeters) away from the open mouth or to use a special spacing device. As you start to take a slow deep breath, press the canister and mouthpiece together at exactly the same time. This will release a dose of ProAir HFA Aerosol. Continue breathing in slowly and deeply and hold for as long as comfortable (up to 10 seconds), then breathe out slowly through pursed lips or your nose. If more than 1 inhalation is to be used, wait a 1 minute and repeat the previous steps. Keep the spray away from your eyes.


• ProAir HFA Aerosol may cause dry mouth or an unpleasant taste in your mouth. Rinsing your mouth with water after each dose may help relieve these effects.


• Clean the plastic mouthpiece and cap at least once a week to prevent blockage. Remove the metal canister. Rinse mouthpiece in warm running water for 30 seconds. Shake off excess water, and then allow the mouthpiece to air dry completely (eg, overnight). After the plastic case and cap are dry, replace the canister. Spray 1 time into the air away from yourself and others. Place the cap back on the mouthpiece. Do NOT allow the metal canister to become wet.


• If you must use the inhaler before it is completely dry, shake the excess water off of the plastic mouthpiece. Shake the canister well, then insert into the plastic case and spray 1 time into the air away from yourself and others. You may then use a dose. After your dose, rewash the plastic case and air dry completely.


• If the inhaler becomes blocked, wash the plastic case as directed.


• This inhaler contains 200 sprays. Do not use this inhaler after 200 sprays have been used. It may not give the correct amount of medicine with each spray.


• Do not use ProAir HFA Aerosol with any other mouthpiece. Do not use this mouthpiece with any other medicine.


• Do not stop using ProAir HFA Aerosol without checking with your doctor.


• If you miss a dose of ProAir HFA Aerosol and you are using it regularly, use it as soon as possible. If several hours have passed or if it is nearing time for the next dose, do not double the dose to catch up, unless advised by your health care provider. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use ProAir HFA Aerosol.

Important safety information:

• ProAir HFA Aerosol may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use ProAir HFA Aerosol with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• ProAir HFA Aerosol may sometimes cause severe breathing problems right after you use a dose. When this problem occurs, it is often after the first use of a new canister or vial. If this happens, seek medical care at once.


• If your usual dose does not work well, your symptoms become worse, or you need to use it more often than normal, contact your doctor at once. This may be a sign of seriously worsening asthma. Your doctor may need to change your dose or medicine.


• ProAir HFA Aerosol should work for up to 4 to 6 hours. Do NOT use more than the recommended dose or use more often than prescribed without checking with your doctor. The risk of severe heart problems and sometimes death may be increased with overuse of ProAir HFA Aerosol.


• Some patients may have trouble using ProAir HFA Aerosol correctly. Some may also get mouth sores or a bad taste in the mouth after using it. If you have any of these problems, ask your health care provider if a spacing device may help.


• Tell your doctor or dentist that you take ProAir HFA Aerosol before you receive any medical or dental care, emergency care, or surgery.


• Talk with your doctor or pharmacist about all of your asthma medicines and how to use them. Do not start, stop, or change the dose of any asthma medicine unless your doctor tells you to.


• Keep track of how many inhalations you use. When your medicine supply begins to run low, call your doctor or pharmacy as soon as possible for a refill.


• Do NOT place the canister in water to try to determine how much medicine you have left.


• The contents of this canister are under pressure. Do NOT puncture, break, or burn container, even if it appears empty.


• Diabetes patients - ProAir HFA Aerosol may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Use ProAir HFA Aerosol with caution in the ELDERLY; they may be more sensitive to its effects.


• ProAir HFA Aerosol should be used with extreme caution in CHILDREN younger than 4 years old; safety and effectiveness in these children have not been confirmed.


• Caution is advised when using ProAir HFA Aerosol in CHILDREN; they may be more sensitive to its effects.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using ProAir HFA Aerosol while you are pregnant. It is not known if ProAir HFA Aerosol is found in breast milk. If you are or will be breast-feeding while you use ProAir HFA Aerosol, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of ProAir HFA Aerosol:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Cough; headache; nervousness; sinus inflammation; sore or dry throat; tremor; trouble sleeping; unusual taste in mouth.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; fast or irregular heartbeat; new or worsened trouble breathing; pounding in the chest; severe headache or dizziness; unusual hoarseness; wheezing.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: ProAir HFA side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include chest pain; fast or irregular heartbeat; seizures; severe headache or dizziness; severe or persistent nervousness or trouble sleeping; tremor.

Proper storage of ProAir HFA Aerosol:

Store ProAir HFA Aerosol upright between 59 and 77 degrees F (15 and 25 degrees C). Do not freeze. Contents are under pressure. Do not puncture. Do not use or store near heat or open flame. Do not expose the container to temperatures above 120 degrees F (48 degrees C). The container may burst. Store the inhaler with the mouthpiece down. Do not use after the expiration date on the container or box. Keep ProAir HFA Aerosol out of the reach of children and away from pets.

General information:

• If you have any questions about ProAir HFA Aerosol, please talk with your doctor, pharmacist, or other health care provider.


• ProAir HFA Aerosol is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about ProAir HFA Aerosol. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More ProAir HFA resources

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

Compare ProAir HFA with other medications

• Asthma, acute
• Asthma, Maintenance
• Bronchospasm Prophylaxis
• COPD, Acute
• COPD, Maintenance

De-Noltab

1. Name Of The Medicinal Product

DE-NOLTAB

2. Qualitative And Quantitative Composition

Tri-potassium di-citrato bismuthate equivalent to 120mg Bi₂O₃

3. Pharmaceutical Form

Film-coated tablet

4. Clinical Particulars

4.1 Therapeutic Indications

For the treatment of gastric and duodenal ulcers.

4.2 Posology And Method Of Administration

For Adults, and the Elderly:

One tablet to be taken four times a day, half an hour before each of the three main meals and two hours after the last meal of the day, or

Two tablets to be taken twice daily, half an hour before breakfast and half an hour before the evening meal, or

As directed by the physician

The maximum duration for one course of treatment is two months; De-Noltab should not be used for maintenance therapy.

For children:

Not recommended.

4.3 Contraindications

In cases of severe renal insufficiency.

Harmful to people on a low potassium diet.

Hypersensitivity to the active substance(s) or to any of the excipients.

4.4 Special Warnings And Precautions For Use

Prolonged use of high doses of bismuth compounds is not recommended because this has occasionally led to reversible encephalopathy. It is, not advisable to take other bismuth-containing drugs concomitantly.

Contains approximately 2 mmol (approximately 40 mg) potassium per tablet. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No other medicines, food or drink, in particular antacids, milk, fruit or fruit juices, should be consumed within half an hour before or after a dose of De-Nol as they may influence its effect. The efficacy of oral tetracyclines may be inhibited.

4.6 Pregnancy And Lactation

On theoretical grounds De-Noltab is contraindicated in pregnancy. No information is available on excretion in breast milk.

4.7 Effects On Ability To Drive And Use Machines

None reported.

4.8 Undesirable Effects

System Organ Class	Common >1/100, <1/10	Uncommon >1/1000, <1/100	Very rare <1/10,000, Not known (cannot be estimated from the available data)
Immune system disorders			anaphylactic reaction
Gastrointestinal disorders	blackening of the stool	nausea, vomiting, constipation, diarrhoea
Skin and subcutaneous tissue disorders		rash, pruritus

4.9 Overdose

Extremely few cases of overdosage have been reported; contact the company for further information.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

The active constituent exerts a local healing effect at the ulcer site, and by eradication or reduction of Helicobacter pylori defers relapse.

5.2 Pharmacokinetic Properties

The action is local in the gastro-intestinal tract.

5.3 Preclinical Safety Data

No relevant pre-clinical safety data has been generated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Povidone K 30

Polacrillin potassium

Macrogol 6000

Magnesium stearate

Maize starch

Hypromellose

6.2 Incompatibilities

None

6.3 Shelf Life

Four years

6.4 Special Precautions For Storage

Do not store above 25^oC

6.5 Nature And Contents Of Container

Amber glass bottles and/or aluminium foil strips, containing 112 tablets

6.6 Special Precautions For Disposal And Other Handling

None

7. Marketing Authorisation Holder

Astellas Pharma Ltd

Lovett House

Lovett Road

Staines

TW18 3AZ

United Kingdom

8. Marketing Authorisation Number(S)

PL0166/0124

9. Date Of First Authorisation/Renewal Of The Authorisation

1 December 1986;11^th January 2007.

10. Date Of Revision Of The Text

18 July 2008

11. LEGAL CATEGORY

P

Piroxicam

Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: 4-Hydroxy-2-methyl-N2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
Molecular Formula: C₁₅H₁₃N₃O₄S
CAS Number: 36322-90-4
Brands: Feldene

• Cardiovascular Risk


• 
  

  Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).¹ Risk may increase with duration of use.¹ Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.¹ (See Cardiovascular Effects under Cautions.)

  
  


• 
  

  Contraindicated for the treatment of pain in the setting of CABG surgery.¹

  
  

• GI Risk


• 
  

  Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).¹ Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.¹ Geriatric individuals are at greater risk for serious GI events.¹ (See GI Effects under Cautions.)

  
  

Introduction

Prototypical NSAIA; an oxicam derivative.^{1 2 3 4}

Uses for Piroxicam

Consider potential benefits and risks of piroxicam therapy as well as alternative therapies before initiating therapy with the drug.¹ Use lowest possible effective dosage and shortest duration of therapy consistent with patient's treatment goals.¹

Inflammatory Diseases

Symptomatic treatment of rheumatoid arthritis and osteoarthritis.¹

Has been used for the symptomatic relief of acute gouty arthritis†^{2 38} and ankylosing spondylitis†;^{2 40} has also been used for symptomatic treatment of acute musculoskeletal disorders†.^{2 3}

Pain

Has been used for symptomatic relief of postoperative†² or postpartum pain†.^{2 3}

Dysmenorrhea

Has been used for the management of dysmenorrhea†.⁴¹

Piroxicam Dosage and Administration

General

• 
  

  Consider potential benefits and risks of piroxicam therapy as well as alternative therapies before initiating therapy with the drug.¹

  
  

Administration

Oral Administration

Administered orally, usually as a single daily dose.¹ May be administered in divided doses daily.¹

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with patient's treatment goals.¹ Adjust dosage based on individual requirements and response; attempt to titrate to lowest effective dosage.¹

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

Initially, 20 mg daily.¹ Adjust dosage based on response and tolerance; 30 or 40 mg daily may be required for maintenance therapy, ² although 20 mg daily is usually adequate.^{1 2}

Prescribing Limits

Adults

Inflammatory Diseases

Oral

Dosages >20 mg daily associated with increased frequency of adverse GI effects.^{1 2 3}

Special Populations

Hepatic Impairment

Inflammatory Diseases

Oral

Dosage reduction may be required.¹

Cautions for Piroxicam

Contraindications

• 
  

  Known hypersensitivity to piroxicam or any ingredient in the formulation. ¹

  
  


• 
  

  History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.¹

  
  


• 
  

  Treatment of perioperative pain in the setting of CABG surgery.¹

  
  

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.¹¹² Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.^{115 116 117} Current evidence (based on limited data from observational studies) suggests that use of piroxicam is not associated with increased cardiovascular risk.¹¹⁵

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dose for the shortest duration necessary.¹

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).¹¹²

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.¹ (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.¹ Use with caution in patients with hypertension; monitor BP.¹ Impaired response to certain diuretics may occur.¹ (See Specific Drugs under Interactions.)

Fluid retention and edema reported.¹ Caution in patients with fluid retention or heart failure.¹

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.^{1 94 102 109}

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;^{16 47 68 94 102} alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)^{16 68 94} or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).¹⁶

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.¹

Potential for overt renal decompensation.^{1 31 48 49 50 65} Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.^{1 31 48 65 114} (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported. ¹

Immediate medical intervention and discontinuance for anaphylaxis.¹

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.¹

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.¹ Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).¹

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs. ¹

Elevations of serum ALT or AST reported.¹

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.¹ Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.¹

Hematologic Effects

Anemia reported rarely.¹ Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.¹

May inhibit platelet aggregation and prolong bleeding time. ¹

Ocular Effects

Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur. ¹

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.¹

May mask certain signs of infection.¹

Obtain CBC and chemistry profile periodically during long-term use.¹

Specific Populations

Pregnancy

Category C.¹ Avoid use in third trimester because of possible premature closure of the ductus arteriosus.¹

Lactation

Distributed into milk in humans; use not recommended.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

Caution advised.¹ Geriatric adults appear to tolerate NSAIA-induced adverse effects less well than younger individuals.⁹⁶ Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.⁹⁶

Consider lowest effective dosage for the shortest possible duration.¹

Hepatic Impairment

Monitor closely.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.¹

Common Adverse Effects

Dyspepsia, nausea, diarrhea, constipation, rash, dizziness, headache, edema, tinnitus.¹

Interactions for Piroxicam

Protein-bound Drugs

Pharmacokinetic interaction possible with other highly protein-bound drugs; monitor patient; dosage adjustment may be needed.¹

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Reduced BP response to ACE inhibitor1	Monitor BP1
Angiotensin II receptor antagonists	Reduced BP response to angiotensin II receptor antagonist118	Monitor BP118
Antacids (magnesium- or aluminum-containing)	Pharmacokinetic interaction unlikely1 13
Anticoagulants (warfarin)	Possible bleeding complications1	Use with caution;1 37 97 monitor PT; adjust anticoagulant dosage as needed1 97
Diuretics (furosemide, thiazides)	Reduced natriuretic effects1 98	Monitor for diuretic efficacy and renal failure1
Lithium	Increased plasma lithium concentrations1 72 73 74 75 76 77 78 79	Monitor plasma lithium concentrations when initiating or discontinuing piroxicam;1 72 73 76 77 79 monitor for lithium toxicity29 72 73 76
Methotrexate	Increased plasma methotrexate concentrations,1 100 particularly with high methotrexate dosage99 100	Use with caution1
NSAIAs	NSAIAs including aspirin: Increased risk of GI ulceration and other complications 1 Aspirin: No consistent evidence that use of low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs112 Decreased plasma piroxicam concentrations with concomitant use of 20 mg piroxicam and 3.9 g aspirin daily 1	Concomitant use not recommended1
Thrombolytic agents (streptokinase)	Possible bleeding complications26	Use with caution26

Piroxicam Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration;^{1 3} peak plasma concentrations usually attained within 3 to 5 hours.¹

Food

Decreases rate but not extent of absorption.^{2 12 28}

Distribution

Extent

Distributed into synovial fluid.³

Distributed into human milk.^{1 43 95}

May accumulate slowly in cartilage.^{2 5}

Plasma Protein Binding

99.3%.^{3 13}

Elimination

Metabolism

Extensively metabolized,² principally by hydroxylation and glucuronide conjugation of the hydroxy metabolite.^{1 28}

Elimination Route

Excreted principally in urine and feces, ¹ with urinary excretion approximately twice the fecal excretion.¹ Excreted principally as metabolites; <5% excreted unchanged.^{1 28}

Half-life

50 hours¹ (range: 14–158 hours).^{2 13}

Stability

Storage

Oral

Capsules

Tight, light-resistant containers^{34 35} at <30°C.^{34 36}

ActionsActions

• 
  

  Inhibits cyclooxygenase-1 (COX-1) and COX-2.^{88 89 90 91 92 93}

  
  


• 
  

  Pharmacologic actions similar to those of other prototypical NSAIAs;^{2 4} exhibits anti-inflammatory, analgesic, and antipyretic activity.^{1 2 4}

  
  

Advice to Patients

• 
  

  Importance of reading the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.¹

  
  


• 
  

  Risk of serious cardiovascular events with long-term use.¹

  
  


• 
  

  Risk of GI bleeding and ulceration.¹

  
  


• 
  

  Risk of serious skin reactions.¹ Risk of anaphylactoid and other sensitivity reactions.¹

  
  


• 
  

  Risk of hepatotoxicity.¹

  
  


• 
  

  Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.¹

  
  


• 
  

  Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.¹

  
  


• 
  

  Importance of discontinuing piroxicam and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.¹ Importance of seeking immediate medical attention if an anaphylactic reaction occurs.¹

  
  


• 
  

  Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Importance of avoiding piroxicam in late pregnancy (third trimester).¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Piroxicam

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	10 mg*	Feldene	Pfizer
		20 mg*	Feldene	Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Feldene 20MG Capsules (PFIZER U.S.): 30/$145.98 or 90/$429.95

Piroxicam 10MG Capsules (NOSTRUM LABORATORIES): 30/$39.99 or 60/$69.98

Piroxicam 20MG Capsules (TEVA PHARMACEUTICALS USA): 30/$89.99 or 60/$159.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. 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.

References

1. Pfizer Laboratories. Feldene (piroxicam) capsules prescribing information. New York, NY; 2006 Mar.

2. Dahl SL, Ward JR. Pharmacology, clinical efficacy, and adverse effects of piroxicam, a new nonsteroidal anti-inflammatory agent. Pharmacotherapy. 1982; 2:80-9. [IDIS 150330] [PubMed 6765393]

3. Brogden RN, Heel RC, Speight TM et al. Piroxicam: a review of its pharmacological properties and therapeutic efficacy. Drugs. 1981; 22:165-87. [IDIS 140930] [PubMed 7021122]

4. Wiseman EH. Pharmacologic studies with a new class of nonsteroidal anti-inflammatory agents–the oxicams–with special reference to piroxicam (Feldene). Am J Med. 1982; 72(2A):2-8.

5. Conner CS. Piroxicam. Drugdex. 1983; (Mar):1-36.

6. Simon LS, Mills JA. Nonsteroidal anti-inflammatory drugs. N Engl J Med. 1980; 302:1179-85. [IDIS 113555] [PubMed 6988717]

7. Flower RJ, Moncada S, Vane JR. Drug therapy of inflammation: analgesic-antipyretics and antiinflammatory agents; drugs employed in the treatment of gout. In: Gilman AG, Goodman L, Gilman A, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 6th ed. New York: Macmillan Publishing Company; 1980:682-93.

8. Wiseman EH. Review of preclinical studies with piroxicam: pharmacology, pharmacokinetics, and toxicology. In: O’Brien WM, Wiseman EH, eds. Royal Society of Medicine International Congress and Symposium Series. Number 1. New York: Grune & Stratton; 1978:11-23.

9. Ferreira SH, Lorenzetti BB, Correa FMA. Central and peripheral antianalgesic action of aspirin-like drugs. Eur J Pharmacol. 1978; 53:39-48. [PubMed 310771]

10. Atkinson DC, Collier HOJ. Salicylates: molecular mechanism of therapeutic action. Adv Pharmacol Chemother. 1980; 17:233-88. [PubMed 7004141]

11. Bernheim HA, Block LH, Atkins E. Fever: pathogenesis, pathophysiology, and purpose. Ann Intern Med. 1979; 91:261-70. [PubMed 223485]

12. Ishizaki T, Nomura T, Abe T. Pharmacokinetics of piroxicam, a new nonsteroidal anti-inflammatory agent, under fasting and postprandial states in man. J Pharmacokinet Biopharm. 1979; 7:369-81. [IDIS 104494] [PubMed 512843]

13. Hobbs DC, Twomey TM. Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies. J Clin Pharmacol. 1979; 19:270-81. [IDIS 104479] [PubMed 89124]

14. Pitts NE. Efficacy and safety of piroxicam. Am J Med. 1982; 72(2A):77-87.

15. Abruzzo JL, Gordon GV, Meyers AR. Double-blind study comparing piroxicam and aspirin in the treatment of osteoarthritis. Am J Med. 1982; 72(2A):45-9.

16. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis; 2002 update. Arthritis Rheum. 2002; 46:328-46. [IDIS 476480] [PubMed 11840435]

17. Willkens RF. The use of nonsteroidal anti-inflammatory agents. JAMA. 1978; 240:1632-5. [IDIS 87147] [PubMed 691156]

18. Willkens RF, Ward JR, Louie JS et al. Double-blind study comparing piroxicam and aspirin in the treatment of rheumatoid arthritis. Am J Med. 1982; 72(2A):23-6.

19. Turner R, April PA, Robbins DL. Double-blind multicenter study comparing piroxicam and ibuprofen in the treatment of rheumatoid arthritis. Am J Med. 1982; 72(2A):34-8.

20. Davies J, Dixon AS. Efficacy and safety of piroxicam compared with indomethacin in the management of rheumatoid arthritis. Am J Med. 1982; 72(2A):27-30.

21. Sydnes OA. Double-blind comparison of piroxicam and naproxen in the management of rheumatoid arthritis. Am J Med. 1982; 72(2A):31-3.

22. Hart FD. Rheumatic disorders. In: Avery GS, ed. Drug treatment: principles and practice of clinical pharmacology and therapeutics. 2nd ed. New York: ADIS Press; 1980:861-2.

23. Huskisson EC. European experience with piroxicam. Am J Med. 1982; 72(2A):70-6.

24. Pitts NE, Proctor RR. Summary: efficacy and safety of piroxicam. In O’Brien WM, Wiseman EH, eds. Royal Society of Medicine International Congress and Symposium Series. Number 1. New York: Grune & Stratton; 1978:97-108.

25. Mitnick PD, Klein WJ. Piroxicam-induced renal disease. Arch Intern Med. 1984; 144:63-4. [IDIS 179965] [PubMed 6691775]

26. Hoechst-Roussel. Streptase prescribing information. Somerville, NJ; 1980 Aug.

27. Pfizer. Feldene (piroxicam): the first one-a-day agent for rheumatoid arthritis and osteoarthritis. New York. 1983 Mar.

28. Wiseman EH, Hobbs DC. Review of pharmacokinetic studies with piroxicam. Am J Med. 1982; 72(2A):9-17. [IDIS 146274] [PubMed 6800256]

29. Reimann IW, Frolich JC. Effects of diclofenac on lithium kinetics. Clin Pharmacol Ther. 1981; 30:348-52. [IDIS 137530] [PubMed 7273598]

30. Rae SA, Williams IA, English J et al. Alteration of plasma prednisolone levels by indomethacin and naproxen. Br J Clin Pharmacol. 1982; 14:459-61. [IDIS 158831] [PubMed 7126420]

31. Merck, Sharp & Dohme. Indocin, Indocin SR prescribing information. West Point, PA. 1985 Oct.

32. Syntex. Naprosyn prescribing information. Palo Alto, CA. 1983 Apr.

33. Gosselin RE, Hodge HC, Smith RP et al. Clinical toxicology of commercial products. Acute poisoning. 5th ed. Baltimore: The Williams & Wilkins Co; 1984:I-10.

34. USP DI. Vol. 1: 1984 Drug information for the health care provider. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1983:896-7.

35. The United States Pharmacopeial Convention, Inc. Piroxicam. Pharmacopeial Forum. 1984; 10:4058-9.

36. D’Ambrosio GG (Pfizer Laboratories, New York): Personal communication; 1984 Mar 29, Apr 11.

37. Jacotot B. Interaction of piroxicam with oral anticoagulants. Proceedings of the IXth European Congress of Rheumatology; 1979 September 4; Wiesbaden. New York: Academy Professional Information Services; 1980:46-8.

38. Widmark PH. Piroxicam: its safety and efficacy in the treatment of acute gout. Am J Med. 1982; 72(2A):63-5. [IDIS 146285] [PubMed 7058825]

39. Weintraub M, Case K, Kroening B et al. Effects of piroxicam on platelet aggregation. Clin Pharmacol Ther. 1978; 23:134-5.

40. Pomberg O. Comparison of piroxicam with indomethacin in ankylosing spondylitis: a double-blind crossover trial. Am J Med. 1982; 72(2A):58-62. [IDIS 146284] [PubMed 7058824]

41. Cash HC, Humpston D, Kasap HS. Feldene in the symptomatic treatment of primary dysmenorrhoea. Practitioner. 1982; 226:1338-41. [IDIS 158943] [PubMed 7050953]

42. Abramson S, Edelson H, Kaplan H et al. The neutrophil in rheumatoid arthritis: its role and the inhibition of its activation by nonsteroidal antiinflammatory drugs. Semin Arthritis Rheum. 1983; 13(Suppl 1):148-52. [PubMed 6312608]

43. Ostensen M. Piroxicam in human breast milk. Eur J Clin Pharmacol. 1983; 25:829-30. [IDIS 181122] [PubMed 6662182]

44. Stefanini M, Claustro LZ, Mulkey P. Bleeding tendency possibly related to increased plasma antithrombin III activity in patient treated with piroxicam. South Med J. 1984; 77:633-4. [IDIS 185553] [PubMed 6609435]

45. Martin RL, McSweeney GW, Schneider J. Fatal pemphigus vulgaris in a patient taking piroxicam. N Engl J Med. 1983; 309:795-6. [IDIS 175915] [PubMed 6888461]

46. MacDougall LG, Taylor-Smith A, Rothberg AD et al. Piroxicam poisoning in a 2-year-old child. South Afr Med J. 1984; 66:31-3.

47. Lanza Fl, and the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol. 1998; 93:2037-46. [IDIS 417402] [PubMed 9820370]

48. The Upjohn Company. Motrin prescribing information. Kalamazoo, MI; 1985 Jul.

49. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal anti-inflammatory agents. N Engl J Med. 1984; 310:563-72. [IDIS 181748] [PubMed 6363936]

50. Adams DH, Michael J, Bacon PA et al. Non-steroidal anti-inflammatory drugs and renal failure. Lancet. 1986; 1:57-9. [IDIS 209841] [PubMed 2867313]

51. Fok KH, George PJM, Vicary FR. Peptic ulcers induced by piroxicam. BMJ. 1985; 290:117. [IDIS 195297] [PubMed 3917708]

52. Morgan AG. Peptic ulcers induced by piroxicam. BMJ. 1985; 290:564. [PubMed 3918675]

53. Emery P, Grahame R. Peptic ulcers induced by piroxicam. BMJ. 1985; 290:564. [PubMed 3918675]

54. Emery P, Grahame R. Gastrointestinal blood loss and piroxicam. Lancet. 1982; 1:1302-3. [IDIS 151182] [PubMed 6123039]

55. Laake K, Kjeldaas L, Borchgrevink CF. Side-effects of piroxicam (Feldene): a one-year material of 103 reports from Norway. Acta Med Scand. 1984; 215:81-3. [IDIS 181874] [PubMed 6695566]

56. Paulus HE. FDA Arthritis Advisory Committee Meeting: postmarketing surveillance of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1985; 28:1168-9. [IDIS 208792] [PubMed 4052129]

57. Settipane GA. Adverse reactions to aspirin and other drugs. Arch Intern Med. 1981; 141:328-32. [IDIS 142745] [PubMed 7008734]

58. Weinberger M. Analgesic sensitivity in children with asthma. Pediatrics. 1978; 62(Suppl):910-5. [IDIS 118712] [PubMed 103067]

59. Settipane GA. Aspirin and allergic diseases: a review. Am J Med. 1983; 74(Suppl):102-9. [IDIS 171763] [PubMed 6344621]

60. VanArsdel PP Jr. Aspirin idiosyncracy and tolerance. J Allergy Clin Immunol. 1984; 73:431-3. [IDIS 183975] [PubMed 6423718]

61. Stevenson DD. Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol. 1984; 74(4 Part 2):617-22. [IDIS 193318] [PubMed 6436354]

62. Stevenson DD, Mathison DA. Aspirin sensitivity in asthmatics: when may this drug be safe? Postgrad Med. 1985; 78:111-3,116-9. (IDIS 205854)

63. Pleskow WW, Stevenson DD, Mathison DA et al. Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol. 1982; 69(1 Part 1):11-9. [IDIS 144037] [PubMed 7054250]

64. Rossi AC, Hsu JP, Faich GA. Ulcerogenicity of piroxicam: an analysis of spontaneously reported data. BMJ. 1987; 294:147-50. [IDIS 225509] [PubMed 3109543]

65. Palmer JF. Letter sent to Wolleben J, of Pfizer Pharmaceutical regarding labeling revisions about gastrointestinal adverse reactions to Feldene (piroxicam). Rockville, MD: Food and Drug Administration, Division of Oncology and Radiopharmaceutical Drug Products. 1988 Sep.

66. Anon. Labeling revisions for NSAIDs. FDA Drug Bull. 1989; 19:3-4.

67. Searle. Cytotec (misoprostol) prescribing information. Skokie, IL; 1989 Jan.

68. Anon. Drugs for rheumatoid arthritis. Med Lett Drugs Ther. 2000; 42:57-64. [PubMed 10887424]

69. Saw KC, Quick CRG, Higgins AF. Ileocaecal perforation and bleeding are non-steroidal anti-inflammatory drugs (NSAIDs) responsible? J R Soc Med. 1990; 83:114-5.

70. Stubb S, Reitamo S. Fixed drug eruption caused by piroxicam. J Am Acad Dermatol. 1990; 22:1111-2. [PubMed 2142495]

71. Soll AH, Weinstein WM, Kurata J et al. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991; 114:307-19. [IDIS 277370] [PubMed 1987878]

72. Nonsteroidal anti-inflammatory drug interactions: Lithium. In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:609-10.

73. Lithium/NSAIDs. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1993(April):463.

74. Miller LG, Bowman RC, Bakht F. Sparing effect of sulindac on lithium levels. J Fam Prac. 1989; 28:592-3.

75. Stein G, Robertson M, Nadarajah J. Toxic interactions between lithium and non-steroidal anti-inflammatory drugs. Psych Med. 1988; 18:535-43.

76. Khan IH. Lithium and non-steroidal anti-inflammatory drugs. BMJ. 1991; 302:1537-8. [IDIS 282630] [PubMed 1855032]

77. Kerry RJ, Owen G, Michaelson S. Possible toxic interaction between lithium and piroxicam. Lancet. 1983; 1:418-9. [IDIS 165621] [PubMed 6130411]

78. Harrison TM, Davies DW, Norris CM. Lithium carbonate and piroxicam. Br J Psychiatry. 1986; 149:124-5. [PubMed 3096415]

79. Nadarajah J, Stein GS. Piroxicam induced lithium toxicity. Ann Rheum Dis. 1985; 44:502. [IDIS 204022] [PubMed 4026412]

80. Ciba Geigy, Ardsley, NY: Personal communication on diclofenac 28:08.04.

81. Reviewers’ comments (personal observations) on diclofenac 28:08.04.

82. Corticosteroid interactions: nonsteroidal anti-inflammatory drugs (NSAIDs). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:562.

83. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994; 343:769-72. [IDIS 328176] [PubMed 7907735]

84. Hollander D. Gastrointestinal complications of nonsteroidal anti-inflammatory drugs: prophylactic and therapeutic strategies. Am J Med. 1994; 96:274-81. [IDIS 328041] [PubMed 8154516]

85. Schubert TT, Bologna SD, Yawer N et al. Ulcer risk factors: interaction between Helicobacter pylori infection, nonsteroidal use, and age. Am J Med. 1993; 94:413-7. [IDIS 314155] [PubMed 8475935]

86. Piper JM, Ray WA, Daugherty JR et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991; 114:735-40. [IDIS 280191] [PubMed 2012355]

87. Bateman DN, Kennedy JG. Non-steroidal anti-inflammatory drugs and elderly patients: the medicine may be worse than the disease. BMJ. 1995; 310:817-8. [IDIS 345154] [PubMed 7711609]

88. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14. [IDIS 418284] [PubMed 9929039]

89. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8. [PubMed 8967954]

90. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmacol. 1997; 75:1088-95. [PubMed 9365818]

91. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.

92. Cryer B, Dubois A. The advent of highly selective inhibitors of syclooxygenase—a review. Prostaglandins Other Lipid Mediators. 1998; 56:341-61. [PubMed 9990677]

93. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(Suppl 5B):37-42S.

94. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999; 340:1888-99. [IDIS 426864] [PubMed 10369853]

95. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and lactation. 5th ed. Baltimore, MD: Williams & Wilkins; 1998:875-6.

96. Mylan. Meclofenamate sodium capsules prescribing information. Morgantown, WV; 1998 Jun.

97. Piroxicam (Feldene) interactions: warfarin (Coumadin). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1997:440-1.

98. Furosemide (Lasix) interactions: Indomethacin (Indocin). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1997:308-9.

99. Tracy TS, Worster T, Bradley JD et al. Methotrexate disposition following concomitant administration of ketoprofen, piroxicam, and flurbiprofen in patients with rheumatoid arthritis. Br J Clin Pharmac. 1994; 37:453-6.

100. Kremer JM and Hamilton RA. The effects of nonsteroidal antiinflammatory drugs on methotrexate (MTX) pharmacokinetics: impairment of renal clearance of MTX at weekly maintenance doses but not at 7.5 mg. J Rheumatol. 1995; 22:2072-7. [IDIS 358403] [PubMed 8596147]

101. Aspirin interactions: Captopril (Capoten). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1997:62-3.

102. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999; 26(suppl 56):18-24.

103. in’t Veld BA, Ruitenberg A, Hofman A et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med. 2001; 345:1515-21. [PubMed 11794217]

104. Breitner JCS, Zandi PP. Do nonsteroidal antiinflammatory drugs reduce the risk of Alzheimer’s disease? N Engl J Med. 2001; 345:1567-8. Editorial.

105. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996; 47:425-32. [IDIS 371394] [PubMed 8757015]

106. Beard CM, Waring SC, O’sBrien PC et al. Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease: a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc. 1998; 73:951-5. [IDIS 416502] [PubMed 9787743]

107. in’t Veld BA, Launer LJ, Hoes AW et al. NSAIDs and incident Alzheimer’s disease: the Rotterdam Study. Neurobiol Aging. 1998; 19:607-11. [PubMed 10192221]

108. Stewart WF, Kawas C, Corrada M et al. Risk of Alzheimer’s disease and duration of NSAID use. Neurology. 1997; 48:626-32. [IDIS 383303] [PubMed 9065537]

109. Pharmacia. Daypro (oxaprozin) caplets prescribing information. Chicago, IL; 2002 May.

110. Chan FKL, Hung LCT, Suen BY et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002; 347:2104-10. [IDIS 490812] [PubMed 12501222]

111. Graham DY. NSAIDs, Helicobacter pylori, and Pandora’s box. N Engl J Med. 2002; 347:2162-4. [IDIS 490815] [PubMed 12501230]

112. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.

113. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology website (). Accessed 2005 Oct 12.

114. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.

115. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44. [PubMed 16968831]

116. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5. [PubMed 16740558]

117. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6. [PubMed 16968830]

118. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

119. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at: .

More Piroxicam resources

• Piroxicam Side Effects (in more detail)
• Piroxicam Dosage
• Piroxicam Use in Pregnancy & Breastfeeding
• Drug Images
• Piroxicam Drug Interactions
• Piroxicam Support Group
• 15 Reviews for Piroxicam - Add your own review/rating

• Piroxicam MedFacts Consumer Leaflet (Wolter