Aminocaproic Acid Injection

Aminocaproic Acid Injection, USP

Rx Only

DESCRIPTION

Aminocaproic Acid is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis.  The structural formula is:

NH2CH2(CH2)3CH2COOH

The molecular formula is:  C6H13NO2 Molecular Weight: 131.17

Aminocaproic Acid is soluble in water, acid and alkaline solutions; it is sparingly soluble in methanol and practically insoluble in chloroform.

Aminocaproic Acid Injection, USP, for intravenous administration, is a sterile pyrogen-free solution containing 250 mg/mL of Aminocaproic Acid with Benzyl Alcohol 0.9%, as a preservative, and Water for Injection q.s.  The pH is adjusted to approximately 6.8 with Hydrochloric Acid and/or Sodium Hydroxide.

CLINICAL PHARMACOLOGY

The fibrinolysis-inhibitory effects of aminocaproic acid appear to be exerted principally via inhibition of plasminogen activators and to a lesser degree through antiplasmin activity.

In adults, oral absorption appears to be a zero-order process with an absorption rate of 5.2 g/hr. The mean lag time in absorption is 10 minutes. After a single oral dose of 5 g, absorption was complete (F=1). Mean ± SD peak plasma concentrations (164 ± 28 mcg/mL) were reached within 1.2 ± 0.45 hours.

After oral administration, the apparent volume of distribution was estimated to be 23.1 ± 6.6 L (mean ± SD).  Correspondingly, the volume of distribution after intravenous administration has been reported to be 30.0 ± 8.2 L.  After prolonged administration, aminocaproic acid has been found to distribute throughout extravascular and intravascular compartments of the body, penetrating human red blood cells as well as other tissue cells.

Renal excretion is the primary route of elimination, whether aminocaproic acid is administered orally or intravenously. Sixty-five percent of the dose is recovered in the urine as unchanged drug and 11% of the dose appears as the metabolite adipic acid.  Renal clearance (116 mL/min) approximates endogenous creatinine clearance. The total body clearance is 169 mL/min. The terminal elimination half-life for aminocaproic acid is approximately 2 hours.

INDICATIONS AND USAGE

Aminocaproic Acid Injection is useful in enhancing hemostasis when fibrinolysis contributes to bleeding. In life-threatening situations, fresh whole blood transfusions, fibrinogen infusions, and other emergency measures may be required.

Fibrinolytic bleeding may frequently be associated with surgical complications following heart surgery (with or without cardiac bypass procedures), and portacaval shunt; hematological disorders such as aplastic anemia; acute and life-threatening abruptio placentae; hepatic cirrhosis; and neoplastic disease such as carcinoma of the prostate, lung, stomach, and cervix.

Urinary fibrinolysis, usually a normal physiological phenomenon, may frequently be associated with life-threatening complications following severe trauma, anoxia, and shock.  Symptomatic of such complications is surgical hermaturia (following prostatectomy and nephrectomy) or nonsurgical hematuria (accompanying polycystic or neoplastic diseases of the genitourinary system).  (See WARNINGS.)

CONTRAINDICATIONS

Aminocaproic acid should not be used when there is evidence of an active intravascular clotting process.

When there is uncertainty as to whether the cause of bleeding is primary fibrinolysis or disseminated intravascular coagulation (DIC), this distinction must be made before administering aminocaproic acid.

The following tests can be applied to differentiate the two conditions:

• Platelet count is usually decreased in DIC but normal in primary fibrinolysis.


• Protamine paracoagulation test is positive in DIC; a precipitate forms when protamine sulfate is dropped into citrated plasma.  The test is negative in the presence of primary fibrinolysis.


• The euglobulin clot lysis test is abnormal in primary fibrinolysis but normal in DIC.

Aminocaproic acid must not be used in the presence of DIC without concomitant heparin.

WARNINGS

Aminocaproic Acid Injection, USP contains benzyl alcohol as a preservative. The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal “Gasping Syndrome”.  (See PRECAUTIONS, Pediatric Use.)

In patients with upper urinary tract bleeding, aminocaproic acid administration has been known to cause intrarenal obstruction in the form of glomerular capillary thrombosis or clots in the renal pelvis and ureters.  For this reason, aminocaproic acid should not be used in hematuria of upper urinary tract origin, unless the possible benefits outweigh the risk.

Subendocardial hemorrhages have been observed in dogs given intravenous infusions of 0.2 times the maximum human therapeutic dose of aminocaproic acid and in monkeys given 8 times the maximum human therapeutic dose of aminocaproic acid.

Fatty degeneration of the myocardium has been reported in dogs given intravenous doses of aminocaproic acid at 0.8 to 3.3 times the maximum human therapeutic dose and in monkeys given intravenous doses of aminocaproic acid at 6 times the maximum human therapeutic dose.

Rarely, skeletal muscle weakness with necrosis of muscle fibers has been reported following prolonged administration.  Clinical presentation may range from mild myalgias with weakness and fatigue to a severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure. Muscle enzymes, especially creatine phosphokinase (CPK) are elevated.  CPK levels should be monitored in patients on long-term therapy.  Aminocaproic acid administration should be stopped if a rise in CPK is noted.  Resolution follows discontinuation of aminocaproic acid; however, the syndrome may recur if aminocaproic acid is restarted.

The possibility of cardiac muscle damage should also be considered when skeletal myopathy occurs. One case of cardiac and hepatic lesions observed in man has been reported.  The patient received 2 g of aminocaproic acid every 6 hours for a total dose of 26 g.  Death was due to continued cerebrovascular hemorrhage.  Necrotic changes in the heart and liver were noted at autopsy.

PRECAUTIONS

General

Aminocaproic acid inhibits both the action of plasminogen activators and to a lesser degree, plasmin activity.  The drug should NOT be administered without a definite diagnosis and/or laboratory finding indicative of hyperfibrinolysis (hyperplasminemia).*

Rapid intravenous administration of the drug should be avoided since this may induce hypotension, bradycardia, and/or arrhythmia.

Inhibition of fibrinolysis by aminocaproic acid may theoretically result in clotting or thrombosis.  However, there is no definite evidence that administration of aminocaproic acid has been responsible for the few reported cases of intravascular clotting which followed this treatment.  Rather, it appears that such intravascular clotting was most likely due to the patient’s preexisting clinical condition, e.g., the presence of DIC.  It has been postulated that extravascular clots formed in vivo may not undergo spontaneous lysis as do normal clots.

Reports have appeared in the literature of an increased incidence of certain neurological deficits such as hydrocephalus, cerebral ischemia, or cerebral vasospasm associated with the use of antifibrinolytic agents in the treatment of subarachnoid hemorrhage (SAH).  All of these events have also been described as part of the natural course of SAH, or as a consequence of diagnostic procedures such as angiography.  Drug relatedness remains unclear.

Thrombophlebitis, a possibility with all intravenous therapy, should be guarded against by strict attention to the proper insertion of the needle and the fixing of its position.

Epsilon-aminocaproic acid should not be administered with Factor IX Complex concentrates or Anti-Inhibitor Coagulant concentrates, as the risk of thrombosis may be increased.

Laboratory Tests

The use of aminocaproic acid should be accompanied by tests designed to determine the amount of fibrinolysis present.  There are presently available: (a) general tests such as those for the determination of the lysis of a clot of blood or plasma; and (b) more specific tests for the study of various phases of fibrinolytic mechanisms. These latter tests include both semiquantitative and quantitative techniques for the determination of profibrinolysin, fibrinolysin, and antifibrinolysin.

DRUG & OR LABORATORY TEST INTERACTIONS

Prolongation of the template bleeding time has been reported during continuous intravenous infusion of aminocaproic acid at dosages exceeding 24 g/day.  Platelet function studies in these patients have not demonstrated any significant platelet dysfunction.  However, in vitro studies have shown that at high concentrations (7.4 mMol/L or 0.97 mg/mL and greater) EACA inhibits ADP and collagen-induced platelet aggregation, the release of ATP and serotonin, and the binding of fibrinogen to the platelets in a concentration-response manner.  Following a 10 g bolus of aminocaproic acid, transient peak plasma concentrations of 4.6 mMol/L or 0.60 mg/mL have been obtained.  The concentration of aminocaproic acid necessary to maintain inhibition of fibrinolysis is 0.99 mMol/L or 0.13 mg/mL.  Administration of a 5 g bolus followed by 1 to 1.25 g/hr should achieve and sustain plasma levels of 0.13 mg/mL.  Thus, concentrations which have been obtained in vivo clinically in patients with normal renal function are considerably lower than the in vitro concentrations found to induce abnormalities in platelet function tests.  However, higher plasma concentrations of aminocaproic acid may occur in patients with severe renal failure.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate the carcinogenic potential of aminocaproic acid and studies to evaluate its mutagenic potential have not been conducted.  Dietary administration of an equivalent of the maximum human therapeutic dose of aminocaproic acid to rats of both sexes impaired fertility as evidenced by decreased implantations, litter sizes and number of pups born.

Pregnancy

Pregnancy Category C.  Animal reproduction studies have not been conducted with aminocaproic acid.  It is also not known whether aminocaproic acid can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.  Aminocaproic acid should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk.  Because many drugs are excreted in human milk, caution should be exercised when aminocaproic acid is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Aminocaproic Acid Injection, USP contains benzyl alcohol as a preservative.  Benzyl alcohol has been associated with a fatal “gasping syndrome” in neonates.  The “gasping syndrome”, characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine, has been associated with exposure to benzyl alcohol in neonates and low-birth weight neonates.  Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse (see WARNINGS).

ADVERSE REACTIONS

Aminocaproic acid is generally well tolerated. The following adverse experiences have been reported:

General: Edema, headache, malaise.

Hypersensitivity Reactions: Allergic and anaphylactoid reactions, anaphylaxis.

Local Reactions: Injection site reactions, pain and necrosis.

Cardiovascular: Bradycardia, hypotension, peripheral ischemia, thrombosis.

Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting.

Hematologic: Agranulocytosis, coagulation disorder, leukopenia, thrombocytopenia.

Musculoskeletal: CPK increased, muscle weakness, myalgia, myopathy (see WARNINGS), myositis, rhabdomyolysis.

Neurologic: Confusion, convulsions, delirium, dizziness, hallucinations, intracranial hypertension, stroke, syncope.

Respiratory: Dyspnea, nasal congestion, pulmonary embolism.

Skin: Pruritus, rash.

Special Senses: Tinnitus, vision decreased, watery eyes.

Urogenital: BUN increased, renal failure. There have been some reports of dry ejaculation during the period of aminocaproic acid treatment. These have been reported to date only in hemophilia patients who received the drug after undergoing dental surgical procedures. However, this symptom resolved in all patients within 24 to 48 hours of completion of therapy.

OVERDOSAGE

A few cases of acute overdosage with aminocaproic acid administered intravenously have been reported. The effects have ranged from no reaction to transient hypotension to severe acute renal failure leading to death. One patient with a history of brain tumor and seizures experienced seizures after receiving an 8 gram bolus injection of aminocaproic acid. The single dose of aminocaproic acid causing symptoms of overdosage or considered to be life-threatening is unknown. Patients have tolerated doses as high as 100 grams while acute renal failure has been reported following a dose of 12 grams.

The intravenous and oral LD50 of aminocaproic acid were 3 and 12 g/kg, respectively, in the mouse and 3.2 and 16.4 g/kg, respectively, in the rat.  An intravenous infusion dose of 2.3 g/kg was lethal in the dog.  On intravenous administration, tonic-clonic convulsions were observed in dogs and mice.

No treatment for overdosage is known, although evidence exists that aminocaproic acid is removed by hemodialysis and may be removed by peritoneal dialysis.  Pharmacokinetic studies have shown that total body clearance of aminocaproic acid is markedly decreased in patients with severe renal failure.

DOSAGE AND ADMINISTRATION

Aminocaproic Acid Injection, USP is administered by infusion, utilizing the usual compatible intravenous vehicles (e.g., Sterile Water for Injection, Sodium Chloride Injection 0.9%, Dextrose Injection 5% or Ringer’s Injection).  Although Sterile Water for Injection is compatible for intravenous injection, the resultant solution is hypo-osmolar.  RAPID INJECTION OF Aminocaproic Acid Injection, USP UNDILUTED INTO A VEIN IS NOT RECOMMENDED.

For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that 16 to 20 mL (4 to 5 g) of Aminocaproic Acid Injection, USP in 250 mL of diluent be administered by infusion during the first hour of treatment, followed by a continuing infusion at the rate of 4 mL (1 g) per hour in 50 mL of diluent.  This method of treatment would ordinarily be continued for about 8 hours or until the bleeding situation has been controlled.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Oral Therapy:

If the patient is able to take medication by mouth, an identical dosage regimen may be followed by administering aminocaproic acid tablets or aminocaproic acid syrup, 25% as follows: For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that 5 grams of aminocaproic acid tablets or syrup be administered during the first hour of treatment, followed by a continuing rate of 1 gram of aminocaproic acid tablets or 1.25 grams of aminocaproic acid syrup per hour. This method of treatment would ordinarily be continued for about 8 hours or until the bleeding situation has been controlled.

HOW SUPPLIED

Aminocaproic Acid Injection, USP, 250 mg/mL.

For intravenous infusion after dilution.

NDC 0517-9120-25 20 mL multiple dose vial Boxes of 25

Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) (See USP Controlled Room Temperature).

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

REFERENCES

*Stefanini M. Dameshek W: The Hemorrhagic Disorders, Ed.2, New York, Grune and Stratton.  1962; pp. 510-514.

IN9120

Rev. 6/07

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL – 20 mL Carton

AMINOCAPROIC ACID

INJECTION, USP

250 mg/mL (5 g/20 mL)

NDC 0517-9120-25

25 x 20 mL MULTIPLE DOSE VIALS

FOR INTRAVENOUS INFUSION AFTER DILUTION

Rx Only

Each mL contains: Aminocaproic Acid 250 mg, Benzyl Alcohol 0.9%, Water for Injection q.s.

Sodium Hydroxide and/or Hydrochloric Acid to adjust pH. Sterile, nonpyrogenic.

Initial Adult Dosage: 4 to 5 grams (16-20 mL) intravenously followed by 1 gram (4 mL) at hourly intervals thereafter. See enclosed insert.

Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) (See USP Controlled Room Temperature). Directions for Use: See Package Insert.

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Rev. 11/05

AMINOCAPROIC ACID  aminocaproic acid  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0517-9120 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMINOCAPROIC ACID (AMINOCAPROIC ACID) AMINOCAPROIC ACID 250 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength BENZYL ALCOHOL   SODIUM HYDROXIDE   HYDROCHLORIC ACID   WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0517-9120-25 25 VIAL In 1 TRAY contains a VIAL, MULTI-DOSE 1 20 mL In 1 VIAL, MULTI-DOSE This package is contained within the TRAY (0517-9120-25)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA071192	09/30/1990

Labeler - American Regent, Inc. (622781813)

Revised: 10/2011American Regent, Inc.

More Aminocaproic Acid Injection resources

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

Compare Aminocaproic Acid Injection with other medications

• Fibrinolytic Bleeding

anti-inhibitor coagulant complex Intravenous

AN-tee in-HIB-i-ter co-AG-yoo-lant kom-plex

Intravenous route(Powder for Solution)

Thrombotic and thromboembolic events have been reported during post-marketing surveillance following infusion of anti-inhibitor coagulation complex, vapor heated (VH) or anti-inhibitor coagulation complex, nanofiltered (NF), particularly following the administration of high doses and/or in patients with thrombotic risk factors .

Commonly used brand name(s)

In the U.S.

• Autoplex T


• Feiba NF


• Feiba-VH

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antihemophilic Agent

Uses For anti-inhibitor coagulant complex

Anti-inhibitor coagulant complex injection is used to control bleeding episodes or bleeding during surgery in patients with hemophilia A and hemophilia B.

Anti-inhibitor coagulant complex contains substances called coagulation factors (e.g., non-activated Factors II, IX, and X, and activated Factor VII) that are normally produced in the body. These substances are used to stop bleeding of injuries for patients with hemophilia by helping the blood to clot.

anti-inhibitor coagulant complex is to be administered only by or under the supervision of your doctor.

Before Using anti-inhibitor coagulant complex

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For anti-inhibitor coagulant complex, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to anti-inhibitor coagulant complex or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

No information is available on the relationship of age to the effects of anti-inhibitor coagulation complex injection in newborn babies. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of anti-inhibitor coagulation complex injection in geriatric patients. However, it should be used with caution in elderly patients.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving anti-inhibitor coagulant complex, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using anti-inhibitor coagulant complex with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminocaproic Acid


• Tranexamic Acid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of anti-inhibitor coagulant complex. Make sure you tell your doctor if you have any other medical problems, especially:

• Atherosclerosis (hardening of the arteries) or


• Blood clotting problems (e.g., venous thrombosis, pulmonary embolism) or history of or


• Heart attack, history of or


• Injury, serious or


• Septicemia (serious blood infection) or


• Stroke, history of—Use with caution. May increase the risk of a blood clot.

• Bleeding problems caused by coagulation factor VIII or coagulation factor IX deficiencies or


• Disseminated intravascular coagulation or DIC (blood clotting problem) or


• Fibrinolysis or


• If your blood clots normally—Should not be used in patients with these conditions.

• Coronary heart disease, history of or


• Liver disease (including hepatitis A) or


• Parvovirus B19 infection or


• Weak immune system—Use with caution. May make these conditions worse.

• Non-hemophilic patients (who have acquired inhibitors against Factors VIII, IX, or XII)—May increased risk for both bleeding and blood clotting problems.

Proper Use of anti-inhibitor coagulant complex

A doctor or other trained health professional will give you anti-inhibitor coagulant complex. anti-inhibitor coagulant complex is given through a needle placed in one of your veins.

Precautions While Using anti-inhibitor coagulant complex

It is very important that your doctor check you closely while you are receiving anti-inhibitor coagulant complex to make sure it is working properly. Blood tests may be needed to check for unwanted effects.

anti-inhibitor coagulant complex may increase your chance of having blood clots or bleeding, especially in patients with atherosclerosis (hardening of the arteries), injury, a serious blood infection (septicemia), or a history of blood clotting problems, heart attack, or stroke. Patients who stay in bed for a long time because of surgery or illness are also at risk for blood clots. Check with your doctor right away if you suddenly have chest pain, shortness of breath, a severe headache, leg pain, or problems with vision, speech, or walking.

anti-inhibitor coagulant complex may cause serious types of allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash; itching; hoarseness; trouble with breathing; trouble with swallowing; lightheadedness or dizziness; or any swelling of your hands, face, or mouth after you have receive anti-inhibitor coagulant complex.

anti-inhibitor coagulant complex is made from donated human blood. Some human blood products have transmitted certain viruses to people who have received them. The risk of getting a virus from medicines made from human blood has been greatly reduced in recent years. This is the result of required testing of human donors for certain viruses, and testing during the making of these medicines. Although the risk is low, talk with your doctor if you have concerns.

Stop using anti-inhibitor coagulant complex and check with your doctor right away if you have chest pain, cough, fast or slow heartbeat, shortness of breath, trouble with breathing, or wheezing after receiving anti-inhibitor coagulant complex.

Check with your doctor right away if you develop pain or tenderness in the upper stomach; pale stools; dark urine; loss of appetite; nausea; unusual tiredness or weakness; or yellow eyes or skin. These could be symptoms of a serious liver problem.

Check with your doctor right away if you have fever, chills, drowsiness, joint pain, rash, or runny nose.

Certain components of the packaging material contain dry natural rubber (a derivative of latex), which may cause allergic reactions in people who are sensitive to latex. Tell your doctor if you have a latex allergy before you start using anti-inhibitor coagulant complex.

anti-inhibitor coagulant complex Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

Incidence not known

• Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• chest pain or discomfort


• cough


• difficulty with swallowing


• dizziness


• fast heartbeat


• fever


• hives or welts


• hoarseness


• irritation


• itching


• joint pain, stiffness, or swelling


• nausea


• pain in the injection site


• pain or discomfort in the arms, jaw, back, or neck


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• redness of the skin


• shortness of breath


• skin rash


• sweating


• swelling of the eyelids, face, lips, hands, or feet


• tightness in the chest


• troubled breathing or swallowing


• unusual tiredness or weakness


• vomiting


• wheezing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: anti-inhibitor coagulant complex Intravenous side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More anti-inhibitor coagulant complex Intravenous resources

• Anti-inhibitor coagulant complex Intravenous Side Effects (in more detail)
• Anti-inhibitor coagulant complex Intravenous Use in Pregnancy & Breastfeeding
• Anti-inhibitor coagulant complex Intravenous Drug Interactions
• Anti-inhibitor coagulant complex Intravenous Support Group
• 0 Reviews for Anti-inhibitor coagulant complex Intravenous - Add your own review/rating

Compare anti-inhibitor coagulant complex Intravenous with other medications

• Hemophilia A

Ala-Quin Cream

Pronunciation: klye-oh-KWIN-ole/hye-droe-KOR-ti-sone
Generic Name: Clioquinol/Hydrocortisone
Brand Name: Ala-Quin

Ala-Quin Cream is used for:

Treating skin inflammation and itching due to certain skin conditions, including eczema.

Ala-Quin Cream is an anti-infective and corticosteroid combination. The anti-infective works by killing sensitive bacteria or fungi. The corticosteroid works by reducing skin inflammation (eg, redness, swelling, itching, irritation).

Do NOT use Ala-Quin Cream if:

• you are allergic to any ingredient in Ala-Quin Cream, including iodine


• you have tuberculosis of the skin or viral conditions of the skin (eg, cold sores or other herpes simplex infection, vaccinia, chickenpox, shingles)

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

Before using Ala-Quin Cream:

Some medical conditions may interact with Ala-Quin Cream. 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 any kind of skin infection, cuts, scrapes, thinning of the skin, or lessened blood flow to skin


• if you have had a recent vaccination; have measles or tuberculosis; or have had a positive tuberculosis test

Some MEDICINES MAY INTERACT with Ala-Quin Cream. Because little, if any, of Ala-Quin Cream is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Ala-Quin Cream 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 Ala-Quin Cream:

Use Ala-Quin Cream as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Before using Ala-Quin Cream, thoroughly wash the affected area with soap and water. Gently dry.


• Apply a thin film of medicine to the affected area and rub in gently until it is evenly distributed.


• Wash your hands immediately after using Ala-Quin Cream, unless your hands are part of the treated area.


• Do not cover or wrap the treated area unless otherwise directed by your doctor.


• If you miss a dose of Ala-Quin Cream, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Ala-Quin Cream.

Important safety information:

• Ala-Quin Cream is for external use only. Do not get it in your eyes, nose, or mouth. If you get Ala-Quin Cream in your eyes, rinse immediately with cool tap water.


• If Ala-Quin Cream was prescribed to treat the diaper area of a child, avoid using tight-fitting diapers or plastic pants unless otherwise directed by your doctor.


• Avoid getting Ala-Quin Cream on clothes and linens because it will stain them. Ala-Quin Cream may also stain your skin.


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


• Do not use Ala-Quin Cream for other skin conditions at a later time without first checking with your doctor.


• Talk with your doctor before you receive any vaccine while using Ala-Quin Cream.


• Ala-Quin Cream may cause harm if it is swallowed. If you may have taken it by mouth, contact your poison control center or emergency room right away.


• Ala-Quin Cream may interfere with certain lab tests. Be sure your doctor and lab personnel know you are using Ala-Quin Cream.


• Ala-Quin Cream should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• Corticosteroids may affect growth rate in CHILDREN and teenagers in some cases. They may need regular growth checks while they use Ala-Quin Cream.


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

Possible side effects of Ala-Quin Cream:

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:

Dryness; itching.

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); acne-like rash; burning, cracking, irritation, or peeling not present before you began using Ala-Quin Cream; excessive hair growth; inflamed hair follicles; inflammation around the mouth; muscle weakness; thinning, softening, or discoloration of the skin; unusual weight gain, especially in the face.

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: Ala-Quin 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 increased thirst or urination; muscle weakness; unusual weight gain, especially in the face.

Proper storage of Ala-Quin Cream:

Store Ala-Quin Cream at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Do not freeze. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Ala-Quin Cream out of the reach of children and away from pets.

General information:

• If you have any questions about Ala-Quin Cream, please talk with your doctor, pharmacist, or other health care provider.


• Ala-Quin Cream 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 Ala-Quin Cream. 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 Ala-Quin resources

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

Compare Ala-Quin with other medications

• Dermatitis
• Eczema
• Pruritus

Alti-Orciprenaline

Generic Name: metaproterenol (Oral route)

met-a-proe-TER-e-nol

Commonly used brand name(s)

In the U.S.

• Alupent

In Canada

• Alti-Orciprenaline

Available Dosage Forms:

• Syrup


• Tablet

Therapeutic Class: Bronchodilator

Pharmacologic Class: Beta-2 Adrenergic Agonist

Uses For Alti-Orciprenaline

Metaproterenol is used to treat asthma and bronchospasm in patients with bronchitis, emphysema, and other lung diseases.

Metaproterenol belongs to the family of medicines known as adrenergic bronchodilators. Adrenergic bronchodilators are medicines that open up the bronchial tubes (air passages) in the lungs. They relieve cough, wheezing, shortness of breath, and troubled breathing by increasing the flow of air through the bronchial tubes.

This medicine is available only with your doctor's prescription.

Before Using Alti-Orciprenaline

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of metaproterenol oral solution and tablets in children younger than 6 years of age. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of metaproterenol in geriatric patients.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol


• Alprenolol


• Arotinolol


• Atenolol


• Befunolol


• Betaxolol


• Bevantolol


• Bisoprolol


• Bopindolol


• Bucindolol


• Bupranolol


• Carteolol


• Carvedilol


• Celiprolol


• Dilevalol


• Esmolol


• Labetalol


• Landiolol


• Levobetaxolol


• Levobunolol


• Mepindolol


• Metipranolol


• Metoprolol


• Nadolol


• Nebivolol


• Nipradilol


• Oxprenolol


• Penbutolol


• Pindolol


• Propranolol


• Sotalol


• Talinolol


• Tertatolol


• Timolol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetes or


• Heart or blood vessel disease or


• Hypertension (high blood pressure) or


• Hyperthyroidism (overactive thyroid) or


• Seizures—Use with caution. May make these conditions worse.

• Heart rhythm problems (e.g., arrhythmia) or


• Tachycardia (fast or rapid heartbeat)—Should not be used in patients with these conditions.

Proper Use of metaproterenol

This section provides information on the proper use of a number of products that contain metaproterenol. It may not be specific to Alti-Orciprenaline. Please read with care.

Use this medicine only as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. Also, do not stop using this medicine or any asthma medicine without telling your doctor. To do so may increase the chance for breathing problems.

Measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For asthma and bronchospasm:
  
  • For oral dosage form (solution):
    
    • Adults—Two teaspoonfuls (10 milliliters [mL]) three or four times a day. Your doctor may adjust your dose as needed.
    
    
    • Children older than 9 years of age or weighing more than 60 pounds (lbs)—Two teaspoonfuls (10 mL) three or four times a day. Your doctor may adjust your dose as needed.
    
    
    • Children 6 to 9 years of age or weighing less than 60 lbs—One teaspoonful (5 mL) three or four times a day. Your doctor may adjust your dose as needed.
    
    
    • Children younger than 6 years of age—Use and dose must be determined by your child's doctor.
    
    
  
  
  • For oral dosage form (tablets):
    
    • Adults—20 milligrams (mg) three or four times a day. Your doctor may adjust your dose as needed.
    
    
    • Children older than 9 years of age or weighing more than 60 pounds (lbs)—20 mg three or four times a day. Your doctor may adjust your dose as needed.
    
    
    • Children 6 to 9 years of age or weighing less than 60 lbs—10 mg three or four times a day. Your doctor may adjust your dose as needed.
    
    
    • Children younger than 6 years of age—Use is not recommended.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Alti-Orciprenaline

It is very important that your doctor check your progress or your child's progress at regular visits. This will allow your doctor to see if the medicine is working properly and to check for any unwanted effects.

Check with your doctor at once if you or your child continue to have breathing problems after using a dose of this medicine or if your condition gets worse.

Do not change your dose or stop using this medicine without asking your doctor first.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, and herbal or vitamin supplements.

Alti-Orciprenaline Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Fast, pounding, or irregular heartbeat or pulse

Less common

• Shakiness in the legs, arms, hands, or feet


• trembling or shaking of the hands or feet


• worsening of asthma

Rare

• Blurred vision


• chest pain


• chills


• cough


• diarrhea


• dizziness


• fainting


• fever


• general feeling of discomfort or illness


• headache


• increased sweating


• joint pain


• loss of appetite


• muscle aches and pains


• nausea


• nervousness


• pounding in the ears


• puffiness of the face and fingers


• runny nose


• shivering


• slow or fast heartbeat


• sore throat


• sweating


• swelling


• trouble sleeping


• unusual tiredness or weakness


• vomiting

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Arm, back, or jaw pain


• chest discomfort


• chest tightness or heaviness


• confusion


• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position


• dry mouth


• general feeling of discomfort or illness


• shortness of breath


• sleeplessness


• unable to sleep

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Abdominal or stomach pain

Rare

• Bad, unusual, or unpleasant (after) taste


• change in appetite


• drowsiness


• dry mouth or throat


• itching skin


• pain


• raised red swellings on the skin, lips, tongue, or in the throat


• tightening of the muscles


• weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Alti-Orciprenaline side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Alti-Orciprenaline resources

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

Compare Alti-Orciprenaline with other medications

• Asthma, acute
• Asthma, Maintenance
• COPD, Acute
• COPD, Maintenance

Alphanine SD

coagulation factor ix (human)

Dosage Form: injection, powder, lyophilized, for solution
Coagulation Factor IX (Human)

AlphaNine® SD

Solvent Detergent Treated/Virus Filtered

DESCRIPTION

Coagulation Factor IX (Human), AlphaNine® SD, is a purified, solvent detergent treated, virus filtered preparation of Factor IX derived from human plasma.1 It contains a minimum of 150 IU Factor IX/mg protein; levels of Factor VII (proconvertin), Factor II (prothrombin) and Factor X (Stuart-Prower Factor) which are below the limit of detection (less than 0.04 Factor VII unit, less than 0.05 Factor II unit, and less than 0.05 Factor X unit per IU Factor IX). Alphanine SD is a sterile, lyophilized preparation intended for intravenous administration only. Each vial is a single dose container.

Alphanine SD is labeled with the Factor IX potency expressed in International Units (IU). Alphanine SD contains not more than (NMT) 0.04 unit of heparin, NMT 0.2 mg of dextrose, NMT 1.0 μg polysorbate 80 and NMT 0.10 μg tri(n-butyl) phosphate/IU of Factor IX.

CLINICAL PHARMACOLOGY

Alphanine SD is a purified formulation of Factor IX containing not less than 150 IU Factor IX activity/mg of total protein.2 Alphanine SD contains non-therapeutic levels of Factor II, Factor VII and Factor X.

Thrombogenicity of Alphanine SD in animals is markedly lower than that of Factor IX Complex, Profilnine® Heat-Treated. Five lots of Alphanine SD (three lots of non-virus filtered product and two lots of virus filtered product) failed to show any evidence of thrombogenicity when tested directly in the Wessler rabbit stasis model for thrombogenicity3-6 at a dose of 200 IU Factor IX/kg body weight. When various lots of Alphanine SD were further tested at doses between 300 and 650 IU Factor IX/kg, only 5 out of 40 animals (12.5%) showed evidence of thrombus formation (Wessler scores of +1, +2, +1, +1, +1 out of +4 maximum). In comparison, Factor IX Complex concentrate, Profilnine, was thrombogenic in 100% of the animals tested at a dose of 100 IU Factor IX/kg.

At a dose of 200 IU Factor IX/kg body weight in a porcine model, the heptane heat-treated formulation of this product (AlphaNine) showed little evidence of disseminated intravascular coagulation (DIC) following infusion.7 This model exhibited no depletion of coagulation factors, a minimal increase in fibrin monomer (+1 in protamine test), a slight temporary decrease in platelet counts, and no evidence of intravascular coagulation upon gross autopsy.8 In contrast, Harrison, et al., report that all Factor IX Complex concentrates studied in the same porcine model were thrombogenic at doses between 50 and 100 IU of Factor IX/kg animal weight.9

A clinical evaluation of Alphanine SD half-life and recovery characteristics was performed. A total of 18 patients with severe to moderate hemophilia B each received a single infusion of 40 to 50 IU Factor IX/kg body weight of Alphanine SD. Following the administration of Alphanine SD, the mean half-life of Factor IX observed was approximately 21 hours.2 This half-life value was computed using the biphasic linear regression model recommended by the International Society of Thrombosis and Haemostasis.10 The half-life obtained for the solvent detergent treated product is comparable to that of AlphaNine (approximately 19 hours) as well as the range of 18 to 36 hours reported for Factor IX Complex preparations.11 The mean recovery observed in clinical trials was approximately 48% and was comparable to that of AlphaNine (approximately 51%).2

A clinical trial was conducted using the heptane heat-treated product, AlphaNine, to evaluate the efficacy of the product in providing hemostatic protection during and after surgery in 13 patients with hemophilia B. The types of surgical procedures performed included bilateral knee replacement (1), total knee replacement with synovectomy (2), hip replacement (1), below the knee amputation (1), herniorrhaphy (2), hemorrhoidectomy (1), rhinoplasty (2), oral surgery (2) and Hickman catheter insertion with temporalis muscle transfer (1). Presurgery doses ranged from 30.1 to 65.0 IU Factor IX/kg; postsurgery replacement therapy doses ranged from approximately 9.4 to 52.0 IU Factor IX/kg. The number of postsurgery days of treatment ranged from 1 to 23; the number of postsurgery infusions ranged from 2 to 26. No bleeding episodes were reported and hemostasis was maintained during the course of postsurgery therapy. None of the hematologic parameters examined (hematocrit, partial thromboplastin time, prothrombin time, fibrinogen/fibrin degradation products, fibrin monomers, D-dimers and platelet counts) provided any evidence that AlphaNine possessed thrombogenic potential.12

A randomized crossover study with 11 hemophilia B patients was conducted with the heptane heat-treated version of the product, AlphaNine, to determine whether an infusion of AlphaNine caused less activation of the hemostatic system than the Factor IX Complex concentrate preparation, Profilnine Heat-Treated. Each subject received a single infusion of either AlphaNine or Profilnine Heat-Treated for the treatment of a bleeding episode, at a dose of 50 IU Factor IX/kg body weight. Each subject received the other Factor IX concentrate for the treatment of a subsequent bleeding episode, separated by an interval of not less than 10 days. The level of prothrombin fragment 1+2 (F1+2) is a sensitive index of the cleavage of prothrombin by activated Factor X. The level of fibrinopeptide A (FPA) released into the plasma measures the activity of thrombin on fibrinogen in the formation of fibrin. Following infusion of Factor IX Complex, statistically significant increases in F1+2 and in FPA were detected at all monitored time points (15, 60, 90, 120 and 240 minutes postinfusion). The statistically significant elevation in these two hemostatic parameters indicates increased activation of the coagulation cascade. Administration of AlphaNine resulted in no increase in F1+2 at any monitored time points, and a statistically non-significant increase in FPA at 15, 60, and 90 minutes following infusion. Only at 120 and 240 minutes after infusion of AlphaNine were statistically significant increases in FPA levels detected. These results suggest that the infusion of a high purity factor IX, such as AlphaNine, may result in a lower level of activation of the coagulation cascade than does Factor IX Complex.13

The ability of the manufacturing process to inactivate and eliminate virus from the Coagulation Factor IX (Human) products was evaluated at key stages in the process (see Table 1). Known amounts of different viruses were added to samples obtained prior to those steps most likely to reduce virus load (DEAE Chromatography, Solvent Detergent, Dual Affinity Chromatography and nanofiltration) in the AlphaNine and Alphanine SD processes to determine the level of viral inactivation/elimination of these specific steps in the process.

Table 1

**Porcine NT=Not tested NLT=Not less than *Lower 95% confidence interval
Process Step	Virus Reduction (log10)
	Sindbis	VSV	HIV-1	HIV-2	Parvo**	EMC	Reo	HAV
DEAE Chromatography	1.4	NT	NT	NT	1.5*	NT	NT	NT
Solvent- Detergent	NLT 5.3	NLT 4.9	NLT 12.2	6.0	NT	NT	NT	NT
Dual Affinity Chromatography	4.7	NT	NT	NT	2.2*	NT	NT	NT
Nanofiltration	NT	NT	NT	NT	3.6	3.4	4.1	≥ 4.4

The retrovirus known as human immunodeficiency virus (HIV) has been identified as a causative agent of Acquired Immunodeficiency Syndrome (AIDS) and has been shown to be transmissible via blood or blood products. The solvent detergent process used in the manufacture of Alphanine SD, was shown to inactivate greater than 12.2 logs of HIV-1 when the retrovirus was intentionally added to product samples under laboratory evaluation (as measured by virus antigen capture and reverse transcriptase assays). In addition, this process was shown to inactivate 6 logs of HIV-2 (as measured by reverse transcriptase assays) when the retrovirus was intentionally added to product samples.2 In an on going efficacy and safety study of 26 patients, no subjects tested positive for HIV or viral hepatitis in relation to the investigation drug.2

In order to assess the ability of the solvent detergent treatment process to inactivate other viruses such as hepatitis B and C virus, the inactivation of the model viruses, Sindbis virus, a model virus for hepatitis C virus, and vesicular stomatitis virus (VSV), a model RNA virus for lipid enveloped viruses, by solvent detergent treatment was studied. Prior to solvent detergent treatment, samples were inoculated with a titer of either Sindbis or VSV. The results demonstrated that a minimum of 5.3 logs of Sindbis and a minimum of 4.9 logs of VSV were inactivated after 180 minutes of incubation with solvent detergent (when compared to an untreated control). It should be noted that the incubation time in the actual Alphanine SD process is twice (360 minutes total) that used in the model virus studies.

The ability of the Alphanine SD process to eliminate virus, by physically partitioning virus from product, was evaluated at key stages of the manufacturing process. Studies were performed using a lipid-enveloped model virus (Sindbis) and non-lipid model viruses (porcine parvovirus, encephalomyocarditis virus, and reovirus). Known amounts of these viruses were added to samples obtained from the Alphanine SD process. The amount of virus removed at each subsequent purification step was then determined by plaque assay.

Addition of Sindbis or porcine parvovirus prior to Factor IX Complex adsorption by DEAE chromatography showed this step to eliminate 1.4 logs of Sindbis and 1.5 logs (95% confidence interval: 1.51-2.33) of added porcine parvovirus. When Sindbis or parvovirus was introduced into the process after the barium citrate precipitation step of the Alphanine SD process, the subsequent dual affinity chromatography step was found to eliminate 4.7 logs of Sindbis and 2.2 logs (95% confidence interval: 2.25-2.75) of added parvovirus. When parvovirus, encephalomyocarditis virus (EMC), or Reovirus was introduced into the process after the dual affinity chromatography step, the subsequent nanofiltration step of the AlphaNine SD process was found to eliminate 3.6 logs of parvovirus, 3.4 logs of EMC and 4.1 logs of added Reovirus. The studies mentioned above indicate that the manufacturing process of Alphanine SD is capable of reducing viruses by approximately 6 logs, in addition to virus reduction achieved by the solvent detergent process.14 In another study, the nanofiltration step removed ≥ 4.4 logs of hepatitis A virus (HAV), a non-lipid enveloped virus. Table 1 summarizes the reduction factors obtained for each virus when individual steps in the manufacturing process for Alphanine SD were validated for virus removal/inactivation.

INDICATIONS AND USAGE

Alphanine SD is indicated for the prevention and control of bleeding in patients with Factor IX deficiency due to hemophilia B. Alphanine SD contains low, non-therapeutic levels of Factors II, VII, and X, and, therefore, is not indicated for the treatment of Factor II, VII or X deficiencies. This product is also not indicated for the reversal of coumarin anticoagulant-induced hemorrhage, nor in the treatment of hemophilia A patients with inhibitors to Factor VIII.

CONTRAINDICATIONS

None known.

WARNINGS

Because Coagulation Factor IX (Human), Alphanine SD is made from pooled human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. Stringent procedures designed to reduce the risk of adventitious agent transmission have been employed in the manufacture of this product, from the screening of plasma donors and the collection and testing of plasma to the application of viral elimination/reduction steps such as column chromatography, solvent detergent treatment and nanofiltration in the manufacturing process. Despite these measures, such product can potentially transmit disease, therefore the risk of infectious agents cannot be totally eliminated. The physician should weigh the risks and benefits of the use of this product and should discuss these with the patient. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections. Scientific opinion encourages hepatitis B and hepatitis A vaccinations at birth or diagnosis for patients with hemophilia.

Incidences of thrombosis or disseminated intravascular coagulation (DIC), have been reported following administration of Factor IX Complex concentrates which contain high amounts of Factor II, VII and X.

Following administration of Coagulation Factor IX (Human), Alphanine SD in surgery patients and individuals with known liver disease, the physician should closely observe the patient for signs or symptoms of potential disseminated intravascular coagulation (DIC). Continued administration of the product should be left to the discretion of the physician.

Allergic type hypersensitivity reactions, including anaphylaxis, have been reported for all factor IX products. Frequently these events have occurred in close temporal association with the development of factor IX inhibitors. Patients should be informed of the early symptoms and signs of hypersensitivity reactions, including hives, generalized urticaria, angioedema, chest tightness, dyspnea, wheezing, faintness, hypotension, tachycardia and anaphylaxis. Patients should be advised to discontinue use of the product and contact physician and/or seek immediate emergency care, depending on the severity of the reactions, if any of these symptoms occur.

Nephrotic syndrome has been reported following attempted immune tolerance induction with factor IX products in Hemophilia B patients with factor IX inhibitors and a history of severe allergic reactions to Factor IX. The safety and efficacy of using Alphanine SD in attempted immune tolerance induction has not been established.

In Previously Untreated Patients (PUPs), it is possible that anaphylaxis may occur after a median exposure of eleven (11) days.15 It is recommended that these patients are monitored closely between the tenth and twentieth exposure day.

PRECAUTIONS

General

In order to minimize the possibility of thrombogenic complications, dosing guidelines should be strictly followed. Refer to “Dosage and Administration” section for recommended amount of product to be administered. Alphanine SD should not be administered at a rate exceeding 10 mL/minute. Rapid administration may result in vasomotor reactions.

Nursing personnel and others who administer this material should exercise appropriate caution in handling due to the risk of exposure to viral infection.

Discard any unused contents into the appropriate safety container. Discard administration equipment after single use into the appropriate safety container. Do not resterilize components.

Information for Patients

Patients should be informed of the early symptoms and signs of hypersensitivity reaction, including hives, generalized urticaria, chest tightness, dyspnea, wheezing, faintness, hypotension, and anaphylaxis. Patients should be advised to discontinue use of the product and contact their physician and/or seek immediate emergency care, depending on the severity of the reaction, if these symptoms occur.

Some viruses, such as parvovirus B19 or hepatitis A, are particularly difficult to remove or inactivate at this time. Parvovirus B19 may most seriously affect sero-negative pregnant women, or immunocompromised individuals. The majority of parvovirus B19 and hepatitis A infections are acquired by environmental (natural) sources.

Preliminary information suggests a relationship may exist between the presence of major deletion mutations in the Factor IX gene and an increased risk of inhibitor formation and of acute hypersensitivity reactions. Patients known to have major deletion mutations of the Factor IX gene should be observed closely for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of initial exposure to product.

Pregnancy Category C

Animal reproduction studies have not been conducted with Alphanine SD. It is also not known whether Alphanine SD can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Alphanine SD should be given to a pregnant woman only if clearly indicated.

Pediatric Use

Clinical trials for safety and effectiveness in pediatric patients 16 years of age and younger have not been conducted. Across a well controlled half-life and recovery clinical trial in patients previously treated with Factor IX concentrates of Hemophilia B, the three pediatric patients receiving Alphanine SD (solvent detergent treated) responded similarly when compared with 15 adult patients.2 In an ongoing safety and efficacy clinical trial in patients not previously treated with Factor IX concentrates for Hemophilia B, 21 pediatric patients received Alphanine SD (solvent detergent treated) responded similarly when compared with the five adult patients above the age of 16 years. Adverse events were similar in this group compared to the patients above the age of 16 years. Anecdotal evaluation of the results indicates no safety and efficacy differences between pediatric and adult populations.

Adverse Reactions

The administration of plasma preparations may cause allergic reactions, mild chills, nausea or stinging at the infusion site. For most reactive individuals, slowing the infusion rate relieves the symptoms. For those highly reactive individuals, a different lot may be satisfactory.

Adverse reactions, characterized by either thrombosis or disseminated intravascular coagulation (DIC), have been reported following administration of Factor IX Complex concentrates. Patients who receive Coagulation Factor IX (Human), AlphaNine SD, following operation, or those with known liver disease, should be kept under close observation for potential signs or symptoms of intravascular coagulation. Continued administration should be left to the discretion of the physician.

In the clinical study that compared the in vivo half-life and recovery of Alphanine SD and HT products, no adverse events were associated with 18 infusions of Alphanine SD administered to 18 individuals with severe to moderate hemophilia B.2 Short term safety of the earlier version of this product, AlphaNine, was demonstrated by an absence of adverse events after 225 infusions of this product were received by 31 patients participating in three clinical trials. In the clinical trial to evaluate efficacy of AlphaNine in providing hemostatic protection during and after surgery, 13 patients received a total of 370,655 IU of AlphaNine. In 208 total infusions, each patient received approximately 15,000 IU (range 3,295 to 52,200 IU Factor IX) in an average of 16 infusions (range 2 to 26 infusions). Results from this study showed no bleeding episodes during the course of postsurgery therapy. There was no hematological evidence (measured by hematocrit, partial thromboplastin time, prothrombin time, fibrinogen/fibrin degradation products, fibrin monomers, D-dimers and platelet counts) of thrombogenicity.12

To report SUSPECTED ADVERSE REACTIONS, contact Grifols at 1-888-GRIFOLS (1-888-474-3657) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DOSAGE AND ADMINISTRATION

For adult usage:

Alphanine SD should be administered intravenously promptly following reconstitution. Administration of Alphanine SD within three hours after reconstitution is recommended to avoid the potential ill effect of any inadvertent bacterial contamination occurring during reconstitution. Discard any unused contents into the appropriate safety container.

Each vial of Alphanine SD is labeled with the total units expressed as International Units (IU) of Factor IX, which is referenced to the WHO International Standard. One unit approximates the activity in one mL of pooled normal human plasma.

The amount of Alphanine SD required to establish hemostasis will vary with each patient and depend upon the circumstances. The following formula may be used as a guide in determining the number of units to be administered.16

In clinical practice there is variability between patients and their clinical response. Therefore, the Factor IX level of each patient should be monitored frequently during replacement therapy.

For pediatric usage: See PRECAUTIONS

Treatment Guidelines for Hemorrhagic Events and Surgery in Patients Diagnosed with Hemophilia B

Type of Hemorrhage or Surgical Procedure	Examples	Treatment Guidelines
Minor Hemorrhages	Bruises, cuts or scrapes, uncomplicated joint hemorrhage	FIX levels should be brought to at least 20-30% (20-30 IU FIX/kg/twice daily) until hemorrhage stops and healing has been achieved (1-2 days).17,18,19
Moderate Hemorrhages	Nose bleeds, mouth and gum bleeds, dental extractions, hematuria	FIX levels should be brought to 25-50% (25-50 IU FIX/kg/twice daily) until healing has been achieved (2-7 days, on average).17,18,19,20,21
Major Hemorrhages	Joint and muscle hemorrhages (especially in the large muscles), major trauma, hematuria, intracranial and intraperitoneal bleeding	FIX levels should be brought to 50% for at least 3-5 days (30-50 IU FIX/kg/twice daily). Following this treatment period, FIX levels should be maintained at 20% (20 IU FIX/kg/twice daily) until healing has been achieved. Major hemorrhages may require treatment for up to 10 days.17,18,19,20,21
Surgery		Prior to surgery, FIX should be brought to 50-100% of normal (50-100 IU FIX/kg/twice daily). For the next 7 to 10 days, or until healing has been achieved, the patient should be maintained at 50-100% FIX levels (50-100 IU FIX/kg/twice daily).17,18,19,20,21

Dosing requirements and frequency of dosing is calculated on the basis of an initial response of 1% FIX increase achieved per IU of FIX infused per kg body weight and an average half-life for FIX of 18 hours. If dosing studies have revealed that a particular patient exhibits a lower response, the dose should be adjusted accordingly.

For pediatric usage: See PRECAUTIONS

RECONSTITUTION

Use Aseptic Technique

1. Warm diluent (Sterile Water for Injection, USP) and concentrate (Alphanine SD) to at least room temperature (but not above 37 °C).


2. Remove the plastic flip off cap from the diluent vial.


3. Gently swab the exposed stopper surface with a cleansing agent such as alcohol trying to avoid leaving any excess cleansing agent on the stopper.


4. Open the Mix2Vial® package by peeling away the lid (Figure 1). Leave the Mix2Vial in the clear outer packaging.


5. Place the diluent vial upright on an even surface and hold the vial tight and pick up the Mix2Vial in its clear outer packaging. Holding the diluent vial securely, push the blue end of the Mix2Vial vertically down through the diluent vial stopper (Figure 2).


6. While holding onto the diluent vial, carefully remove the clear outer packaging from the Mix2Vial set, ensuring the Mix2Vial remains attached to the diluent vial (Figure 3).


7. Place the product vial upright on an even surface, invert the diluent vial with the Mix2Vial attached.


8. While holding the product vial securely on a flat surface, push the clear end of the Mix2Vial set vertically down through the product vial stopper (Figure 4). The diluent will automatically transfer out of its vial into the product vial. (NOTE: If the Mix2Vial is connected at an angle, the vacuum may be released from the product vial and the diluent will not transfer into the product vial.)


9. With the diluent and product vials still attached to the Mix2Vial, gently swirl the product vial to ensure the product is fully dissolved (Figure 5). Reconstitution requires less than 5 minutes. Do not shake the vial.


10. Disconnect the Mix2Vial into two separate pieces (Figure 6) by holding each vial adapter and twisting counterclockwise. After separating, discard the diluent vial with the blue end of the Mix2Vial.


11. Draw air into an empty, sterile syringe. Keeping the product vial upright with the clear end of the Mix2Vial attached, screw the disposable syringe onto the luer lock portion of the Mix2Vial device by pressing and twisting clockwise. Inject air into the product vial.


12. While keeping the syringe plunger depressed, invert the system upside down and draw the reconstituted product into the syringe by pulling the plunger back slowly (Figure 7).


13. When the reconstituted product has been transferred into the syringe, firmly hold the barrel of the syringe and the clear vial adapter (keeping the syringe plunger facing down) and unscrew the syringe from the Mix2Vial (Figure 8). Hold the syringe upright and push the plunger until no air is left in the syringe. Attach the syringe to a venipuncture set.


14. NOTE: If the same patient is to receive more than one vial of concentrate, the contents of two vials may be drawn into the same syringe through a separate unused Mix2Vial set before attaching to the venipuncture set.


15. Use the prepared drug as soon as possible within three hours after reconstitution.


16. After reconstitution, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. When reconstitution procedure is strictly followed, a few small particles may occasionally remain. The Mix2Vial set will remove particles and the labeled potency will not be reduced.


17. Discard all administration equipment after use into the appropriate safety container. Do not reuse.

HOW SUPPLIED

Alphanine SD is supplied in sterile, lyophilized form in single dose vials accompanied by 10 mL diluent (Sterile Water for Injection, USP). Factor IX activity, expressed in International Units (IU) which is referenced to WHO International Standard, is stated on the label of each concentrate vial. Alphanine SD is packaged with a Mix2Vial filter transfer set for use in administration.

It is available in the following potencies, and the product is also color coded based upon assay on the carton and vial label as follows:

Potency	NDC	Assay Color Code
500 IU FIX/10 mL single dose vial	68516-3601-2	500 IU FIX Range - blue box
1000 IU FIX/10 mL single dose vial	68516-3602-2	1000 IU FIX Range - red box
1500 IU FIX/10 mL single dose vial	68516-3603-2	1500 IU FIX Range - black box

STORAGE

Alphanine SD should be stored at temperatures between 2 and 8 °C. Do not freeze to prevent damage to diluent vial. May be stored at room temperature not to exceed 30 °C for 1 month. When removed from refrigeration, record the date removed on the space provided on the carton.

Rx only

REFERENCES

1. Plasma Fraction Purification Serial No. 902.155 Patent issued.


2. Data on file at Grifols Biologicals Inc.


3. Giles, A.R., Johnston, M., Hoogendoorn, H., Blajchman, M. & Hirsch, J. The Thrombogenicity of Prothrombin Complex Concentrates: I. The Relationship Between In Vitro Characteristics and In Vivo Thrombogenicity in Rabbits. Thromb Res 17:353-366, 1980.


4. Kingdon, H.S., Lundblad, R.L., Veltkamp, J.J. & Aronson, D.L. Potentially Thrombogenic Materials in Factor IX Concentrates. Thromb Diath Haemorrh (Stuttg) 33:617-631, 1975.


5. Prowse, C.V. & Williams, A.E. A Comparison of the In Vitro and In Vivo Thrombogenic Activity of Factor IX Concentrate Using Stasis (Wessler) and Non-Stasis Rabbit Models. Thromb Hemostas 44:81-86, 1980.


6. Wessler, S., Reimer, S.M. & Sheps, M.C. Biologic Assay of a Thrombosis-Inducing Activity in Human Serum. J Appl Physiol 14:943-946, 1959.


7. Herring, S.W. & Heldebrant, C.M. Heat-Treated Pure Factor IX. Proc 5th Int Symp HT, 1986, pp. 151-158.


8. Herring, S.W., Abildgaard, C., Shitanishi, K.T., Harrison, J., Gendler, S. & Heldebrant, C.M. Human Coagulation Factor IX Assessment of Thrombogenicity in Animal Models and Viral Safety. J. Lab. Clin Med. 121: 394-405, 1993.


9. Harrison, J., Abildgaard, C., Lazerson, J., Culbertson, R. & Anderson, G. Assessment of Thrombogenicity of Prothrombin Complex Concentrates in a Porcine Model. Throm Res 38(2): 173-188, 1985.


10. Lee, M., Poon, W., & Kingdon, H. A Two-Phase Linear Regression Model for Biologic Half-Life Data. J Lab Clin Med 115(6): 745-748, 1990.


11. White, G.C., Lundblad, R.L., & Kingdon, H.S. Prothrombin Complex Concentrates: Preparation, Properties, and Clinical Uses. Curr Topic in Hematol 2:203-244, 1979.


12. Goldsmith, J.C., Kasper, C.K., et al. Coagulation Factor IX: Successful Surgical Experience With a Purified Factor IX Concentrate. Amer J Hematol 40: 210-215, 1992.


13. Mannucci, P.M., Bauer, K.A., Gringeri, A., Barzegar, S., Bottasso, B., Simoni L. & Rosenberg, R.D. Thrombin Generation Is Not Increased in the Blood of Hemophilia B Patients After the Infusion of a Purified Factor IX Concentrate. Blood 76(12): 2540-2545, December 15, 1990.


14. Herring, S., Peddada, L., Shitanishi, K., Chavez, D., Chio, A., & Heldebrant, C. Elimination of Virus During Manufacture of a Coagulation Factor IX Concentrate. Abstract presented at XIX International Congress World Federation of Hemophilia, Washington, DC, USA, August 14-19, 1990.


15. Warrier, I., Ewenstein, B.M., Koerper, M.A., Shapiro, A., Key, N., DiMichele, D., Miller, R.T., Pasi, J., Rivard, G.E., Sommer, S.S., Katz, J., Bergmann, F., Ljung, R., Petrini, P., Lusher, J.M. Journal of Pediatric Hematology/Oncology 19(1):23-27, 1997.


16. Zauber, N.P. & Levine, J. Factor IX Levels in Patients with Hemophilia B (Christmas Disease) Following Transfusion with Concentrates of Factor IX or Fresh Frozen Plasma (FFP). Medicine 56:213-224, 1977.


17. Nillson, I.M.: Hemorrhagic and Thrombotic Diseases: London, John Wiley and Sons, 1974.


18. Roberts, H.R. and Eberst, M.E.: Current Management of Hemophilia B. Hematology/Oncology Clinics of North America 7(6): 1269-1280, 1993.


19. Roberts, H.R. and Gray, T.F.: Clinical Aspects of Hemophilia B. In Hematology: Basic Principles and Practice, 2nd Edition, pp 1678-1685, Churchill Livingston.


20. Hedner, U. and Davie, E.W.: In “Hemostasis and Thrombosis: Basic Principles and Clinical Practice”, eds. Colman, R.W., Hirsh, J., Marder, V.J., Salzman, E.W., 2nd Edition, Philadelphia, J.B. Lippincot Co, 1987.


21. Levin, P.H.: In “Hemostasis and Thrombosis: Basic Principles and Clinical Practice”, eds. Colman, R.W., Hirsh, J., Marder, V.J., Salzman, E.W., 2nd Edition, Philadelphia, J.B, Lippincot Co, 1987.

Manufactured and Distributed by:

Grifols Biologicals Inc.

Los Angeles, CA 90032, U.S.A.

U.S. License No. 1694

DATE OF REVISION: August 2010

3031647

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 500 IU VIAL

GRIFOLS

NDC 68516-3601-2

Coagulation Factor IX (Human)

AlphaNine® SD

Solvent Detergent Treated / Virus Filtered 10 mL

MID

Storage : Store between 2 and 8 °C. May be stored at room temperature not to exceed 30 °C for 1 month.

Rx only. Single dose container for intravenous administration only.

Grifols Biologicals Inc. Los Angeles, CA 90032, USA

U.S. License No. 1694

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 500 IU CARTON

GRIFOLS

NDC 68516-3601-2

Coagulation Factor IX (Human)

AlphaNine® SD

Solvent Detergent Treated / Virus Filtered

10 mL

MID

Alphanine SD  coagulation factor ix (human)  kit

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68516-3601

Packaging # NDC Package Description Multilevel Packaging 1 68516-3601-2 1 KIT In 1 CARTON None

QUANTITY OF PARTS Part # Package Quantity Total Product Quantity Part 1 1 VIAL   10 mL Part 2 1 VIAL, SINGLE-DOSE   10 mL

Part 1 of 2 Alphanine SD  coagulation factor ix (human)  injection, powder, lyophilized, for solution

Product Information       Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Coagulation Factor IX Human (Coagulation Factor IX Human) Coagulation Factor IX Human 50 [iU]  in 1 mL

Inactive Ingredients Ingredient Name Strength Dextrose   Heparin   Sodium Chloride   Sodium Citrate

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 10 mL In 1 VIAL None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103249 12/31/1990

Part 2 of 2 STERILE WATER  water  injection

Product Information NDC Product Code (Source) 63323-185     Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength No Active Ingredients Found

Inactive Ingredients Ingredient Name Strength Water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 63323-185-10 10 mL In 1 VIAL, SINGLE-DOSE None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103249 12/31/1990

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA103249	12/31/1990

Alphanine SD  coagulation factor ix (human)  kit

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68516-3602

Packaging # NDC Package Description Multilevel Packaging 1 68516-3602-2 1 KIT In 1 CARTON None

QUANTITY OF PARTS Part # Package Quantity Total Product Quantity Part 1 1 VIAL   10 mL Part 2