Heparin Sodium in 0.45% Sodium Chloride Injection is indicated for:

{ "type": "p", "children": [], "text": "Heparin Sodium in 0.45% Sodium Chloride Injection is indicated for:" }

{ "type": "ul", "children": [ "Prophylaxis and treatment of venous thrombosis and pulmonary embolism;", "Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation;", "Treatment of acute and chronic consumption coagulopathies (disseminated intravascular coagulation);", "Prevention of clotting in arterial and cardiac surgery;", "Prophylaxis and treatment of peripheral arterial embolism;", "Anticoagulant use in blood transfusions, extracorporeal circulation, and dialysis procedures." ], "text": "" }

Confirm the selection of the correct formulation and strength prior to administration of the drug.

This product should be administered by intravenous infusion only.

Do not use Heparin Sodium in 0.45% Sodium Chloride Injection as a “catheter lock flush” product.

Do not admix with other drugs.

Discard unused portion.

Do not use plastic containers in series connection.

This product should not be infused under pressure.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and container and seals are intact.

Adjust the dosage of heparin sodium according to the patient’s coagulation test results. When heparin is given by continuous intravenous infusion, determine the coagulation time approximately every 4 hours in the early stages of treatment. When the drug is administered intermittently by intravenous injection, perform coagulation tests before each injection during the early stages of treatment and at appropriate intervals thereafter. Dosage is considered adequate when the activated partial thromboplastin time (APTT) is 1.5 to 2 times the normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value.

Periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy.

The dosing recommendations in Table 1 are based on clinical experience. Although dosage must be adjusted for the individual patient according to the results of suitable laboratory tests, the following dosage schedules may be used as guidelines:

Table 1: Recommended Adult Full-Dose Heparin Regimens for Therapeutic Anticoagulant Effect

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col width="167.4pt"/> <col width="1.5in"/> <col width="202.5pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Method of Administration </span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Frequency</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Recommended Dose*</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Intermittent Intravenous Injection </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Initial Dose </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10,000 Units </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Subsequent Doses</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5,000 Units to 10,000 Units every 4 to 6 hours</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Continuous <br/> Intravenous Infusion </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Initial Dose </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5,000 Units by intravenous injection </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Continuous </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20,000 Units to 40,000 Units every 24 hours </p> </td> </tr> </tbody> </table></div>

* Based on 150 lb. (68 kg) patient. 

There are no adequate and well-controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience. In general, the following dosage schedule may be used as a guideline in pediatric patients:

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col width="77.4pt"/> <col width="401.4pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Initial Dose</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">75 units/kg to 100 units/kg (intravenous bolus over 10 minutes)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Maintenance Dose</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Infants: 25 units/kg/hour to 30 units/kg/hour;</p> <p>Infants less than 2 months have the highest requirements (average 28 units/kg/hour)</p> <p>Children greater than 1 year of age: 18 units/kg/hour to 20 units/kg/hour; </p> <p>Older children may require less heparin, similar to weight-adjusted adult dosage</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitoring</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Adjust heparin to maintain APTT of 60 to 85 seconds, assuming this reflects an anti-Factor Xa level of 0.35 to 0.70.</p> </td> </tr> </tbody> </table></div>

Patients undergoing total body perfusion for open-heart surgery should receive an initial dose of not less than 150 units of heparin sodium per kilogram of body weight. Frequently, a dose of 300 units per kilogram is used for procedures estimated to last less than 60 minutes or 400 units per kilogram for those estimated to last longer than 60 minutes.

To ensure continuous anticoagulation when converting from HEPARIN SODIUM to warfarin, continue full heparin therapy for several days until the INR (prothrombin time) has reached a stable therapeutic range. Heparin therapy may then be discontinued without tapering [see Drug Interactions (7.1)].

For patients currently receiving intravenous heparin, stop intravenous infusion of heparin sodium immediately after administering the first dose of oral anticoagulant; or for intermittent intravenous administration of heparin sodium, start oral anticoagulant 0 to 2 hours before the time that the next dose of heparin was to have been administered.

Follow equipment manufacturer’s operating directions carefully. A dose of 25 units to 30 units/kg followed by an infusion rate of 1,500 units to 2,000 units/hour is suggested based on pharmacodynamic data if specific manufacturers’ recommendations are not available.

HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION is a sterile, single-dose, clear, nonpyrogenic solution available as:

{ "type": "p", "children": [], "text": "HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION is a sterile, single-dose, clear, nonpyrogenic solution available as:" }

{ "type": "ul", "children": [ "Heparin Sodium 25,000 USP units per 500 mL (50 USP units per mL) in 0.45% Sodium Chloride Injection.", "Heparin Sodium 25,000 USP units per 250 mL (100 USP units per mL) in 0.45% Sodium Chloride Injection." ], "text": "" }

The use of HEPARIN SODIUM in 0.45% SODIUM CHLORIDE INJECTION is contraindicated in patients with the following conditions:

{ "type": "p", "children": [], "text": "The use of HEPARIN SODIUM in 0.45% SODIUM CHLORIDE INJECTION is contraindicated in patients with the following conditions:" }

{ "type": "ul", "children": [ "History of heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis (HITT) [see Warnings and Precautions (5.3)]\n" ], "text": "" }

{ "type": "ul", "children": [ "Known hypersensitivity to heparin or pork products (e.g., anaphylactoid reactions) [see Warnings and Precautions (5.7) and Adverse Reactions (6.1)]\n", "In whom suitable blood coagulation tests — e.g., the whole blood clotting time, partial thromboplastin time, etc., — cannot be performed at appropriate intervals (this contraindication refers to full-dose heparin; there is usually no need to monitor coagulation parameters in patients receiving low-dose heparin) [see Warnings and Precautions (5.5)]\n", "Uncontrollable active bleeding state except when this is due to disseminated intravascular coagulation [see Warnings and Precautions (5.2)]\n" ], "text": "" }

Do not use this product as a “catheter lock flush” product. Heparin is supplied in various strengths. Fatal hemorrhages have occurred due to medication errors. Carefully examine all heparin products to confirm the correct container choice prior to administration of the drug.

Hemorrhage, including fatal events, has occurred in patients receiving HEPARIN SODIUM. Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks.

Hemorrhage can occur at virtually any site in patients receiving heparin. Adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage, and retroperitoneal hemorrhage have occurred during anticoagulant therapy with heparin [see Adverse Reactions (6.1)]. A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age [see Clinical Pharmacology (12.3)]. An unexplained fall in hematocrit or fall in blood pressure should lead to serious consideration of a hemorrhagic event.

Use heparin sodium with caution in disease states in which there is increased risk of hemorrhage, including:

HIT is a serious immune-mediated reaction resulting from irreversible aggregation of platelets. HIT occurs in patients treated with heparin and is due to the development of antibodies to a platelet Factor 4-heparin complex that induce in vivo platelet aggregation. HIT may progress to the development of venous and arterial thromboses, a condition known as HITT. Thrombotic events may also be the initial presentation for HIT. These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, thrombus formation on a prosthetic cardiac valve, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death.

Once HIT or HITT is diagnosed or strongly suspected, discontinue all heparin sources (including heparin flushes) and use an alternative anticoagulant.

Immune-mediated HIT is diagnosed based on clinical findings supplemented by laboratory tests confirming the presence of antibodies to heparin, or platelet activation induced by heparin. Obtain platelet counts at baseline and periodically during heparin administration. A drop in platelet count greater than 50% from baseline is considered indicative of HIT. Platelet counts begin to fall 5 to 10 days after exposure to heparin in heparin–naive individuals and reach a threshold by days 7 to 14. In contrast, “rapid onset” HIT can occur very quickly (within 24 hours following heparin initiation), especially in patients with a recent exposure to heparin (i.e., previous 3 months).

Thrombosis development shortly after documenting thrombocytopenia is a characteristic finding in almost half of all patients with HIT.

Monitor thrombocytopenia of any degree closely. If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT and HITT, and, if necessary, administer an alternative anticoagulant.

HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT or HITT.

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of up to 30%. It can occur 2 to 20 days (average 5 to 9) following the onset of heparin therapy. Obtain platelet counts before and periodically during heparin therapy. Monitor thrombocytopenia of any degree closely. If the count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT, and, if necessary, administer an alternative anticoagulant [see Warnings and Precautions (5.3)].

When using a full dose heparin regimen, adjust the heparin dose based on frequent blood coagulation tests. If the coagulation test is unduly prolonged or if hemorrhage occurs, heparin sodium should be discontinued promptly [see Overdosage (10)]. Periodic platelet counts, hematocrits are recommended during the entire course of heparin therapy [see Dosage and Administration (2.2)].

Increased resistance to heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer and in postsurgical patients, and patients with antithrombin III deficiency.

Consider measurement of anti-thrombin levels if heparin resistance is suspected. Monitor coagulation tests frequently in such patients. It may be necessary to adjust the dose of heparin based on coagulation test monitoring, such as anti-Factor Xa levels and/or partial thromboplastin time.

Hypersensitivity reactions with chills, fever and urticaria as the most usual manifestations and also asthma, rhinitis, lacrimation, and anaphylactoid reactions have been reported. Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations [see Adverse Reactions (6.1)].

Because Heparin Sodium in 0.45% Sodium Chloride Injection is derived from animal tissue, monitor for signs and symptoms of hypersensitivity when it is used in patients with a history of allergy to pork products.

Heparin can suppress adrenal secretion of aldosterone leading to hyperkalemia, particularly in patients with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium, or taking potassium sparing drugs. The risk of hyperkalemia appears to increase with duration of therapy but is usually reversible upon discontinuation of heparin.

Measure plasma potassium in patients at risk of hyperkalemia before starting heparin therapy and periodically in all patients treated for more than 5 days or earlier as deemed fit by the clinician.

Significant elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have occurred in patients who have received heparin. Elevation of these enzymes in patients receiving heparin should be interpreted with caution. These elevations typically resolve upon heparin discontinuation.

The following adverse reactions have been identified during post-approval use of heparin sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Heparin sodium may prolong the one-stage prothrombin time. Therefore, when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours after the last intravenous dose or 24 hours after the last subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained.

Drugs such as NSAIDS (including acetylsalicylic acid, ibuprofen, indomethacin, and celecoxib), dextran, phenylbutazone, thienopyridines, dipyridamole, hydroxychloroquine, glycoprotein IIv/IIa antagonists (including abciximab, eptifibatide, and tirofiban), and others that interfere with platelet-aggregation reactions (the main hemostatic defense of heparinized patients) may induce bleeding and should be used with caution in patients receiving heparin sodium. To reduce the risk of bleeding, a reduction in the dose of antiplatelet agent or heparin is recommended.

Digitalis, tetracyclines, nicotine, antihistamines, or intravenous nitroglycerin may partially counteract the anticoagulant action of heparin sodium. Intravenous nitroglycerin administered to heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of heparin dosage are recommended during coadministration of heparin and intravenous nitroglycerin.

Antithrombin III (human) – The anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency. To reduce the risk of bleeding, a reduced dosage of heparin is recommended during treatment with antithrombin III (human).

In published reports, heparin exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes in humans. No teratogenicity was observed in animal reproduction studies with administration of heparin sodium to pregnant rats and rabbits during organogenesis at doses up to 10,000 USP units/kg/day, approximately 10 times the maximum recommended human dose (MRHD) of 40,000 USP units/24 hours infusion [see Data]. In pregnant animals, doses up to 10 times higher than the maximum human daily dose based on body weight resulted in increased resorptions. Consider the benefits and risks of HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION to a pregnant woman and possible risks to the fetus when prescribing HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

The maternal and fetal outcomes associated with uses of heparin via various dosing methods and administration routes during pregnancy have been investigated in numerous studies. These studies generally reported normal deliveries with no maternal or fetal bleeding and no other complications.

In a published study conducted in rats and rabbits, pregnant animals received heparin intravenously during organogenesis at a dose of 10,000 USP units/kg/day, approximately 10 times the maximum human daily dose based on body weight. The number of early resorptions increased in both species. There was no evidence of teratogenic effects.

There is no information regarding the presence of HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION in human milk, the effects on the breastfed infant, or the effects on milk production. Due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a nursing infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION and any potential adverse effects on the breastfed infant from HEPARIN SODIUM IN 0.45% SODIUM CHLORIDE INJECTION or from the underlying maternal condition [see Use in Specific Populations (8.4)].

There are no adequate and well controlled studies on heparin use in pediatric patients. Pediatric dosing recommendations are based on clinical experience [see Dosage and Administration (2.4)].

There are limited adequate and well-controlled studies in patients 65 years and older. However, a higher incidence of bleeding has been reported in patients over 60 years of age, especially women [see Warnings and Precautions (5.2)]. Lower doses of heparin may be indicated in these patients [see Clinical Pharmacology (12.3)].

An overdose requires immediate medical attention and treatment.

{ "type": "p", "children": [], "text": "An overdose requires immediate medical attention and treatment." }

Symptoms

{ "type": "p", "children": [], "text": "\nSymptoms\n" }

Bleeding is the chief sign of heparin overdosage. Easy bruising, petechial formations, nosebleeds, blood in urine or tarry stools may be the first signs or symptoms of a heparin overdose. In the event of symptomatic heparin overdose, consider stopping heparin infusion.

{ "type": "p", "children": [], "text": "Bleeding is the chief sign of heparin overdosage. Easy bruising, petechial formations, nosebleeds, blood in urine or tarry stools may be the first signs or symptoms of a heparin overdose. In the event of symptomatic heparin overdose, consider stopping heparin infusion." }

Treatment

{ "type": "p", "children": [], "text": "\nTreatment\n" }

Neutralization of heparin effect:

{ "type": "p", "children": [], "text": "Neutralization of heparin effect:" }

When clinical circumstances (bleeding) require reversal of heparinization, protamine sulfate (1% solution) by slow infusion will neutralize heparin sodium. No more than 50 mg should be administered, very slowly, in any 10 minute period. Each mg of protamine sulfate neutralizes approximately 100 USP Heparin units. The amount of protamine required decreases over time as heparin is metabolized. Although the metabolism of heparin is complex, it may, for the purpose of choosing a protamine dose, be assumed to have a half-life of about 30 minutes after intravenous injection.

{ "type": "p", "children": [], "text": "When clinical circumstances (bleeding) require reversal of heparinization, protamine sulfate (1% solution) by slow infusion will neutralize heparin sodium. No more than 50 mg should be administered, very slowly, in any 10 minute period. Each mg of protamine sulfate neutralizes approximately 100 USP Heparin units. The amount of protamine required decreases over time as heparin is metabolized. Although the metabolism of heparin is complex, it may, for the purpose of choosing a protamine dose, be assumed to have a half-life of about 30 minutes after intravenous injection." }

Ideally, the dose required to neutralize the action of heparin should be guided by blood coagulation tests or calculated from a protamine neutralization test.

{ "type": "p", "children": [], "text": "Ideally, the dose required to neutralize the action of heparin should be guided by blood coagulation tests or calculated from a protamine neutralization test." }

Because fatal reactions often resembling anaphylaxis have been reported, protamine sulfate should be given only when resuscitation techniques and treatment of anaphylactoid shock are readily available.

{ "type": "p", "children": [], "text": "Because fatal reactions often resembling anaphylaxis have been reported, protamine sulfate should be given only when resuscitation techniques and treatment of anaphylactoid shock are readily available. " }

For additional information, consult the prescribing information for Protamine Sulfate Injection, USP.

{ "type": "p", "children": [], "text": "For additional information, consult the prescribing information for Protamine Sulfate Injection, USP. " }

Blood or plasma transfusions may be necessary; these dilute but do not neutralize heparin.

{ "type": "p", "children": [], "text": " Blood or plasma transfusions may be necessary; these dilute but do not neutralize heparin." }

Heparin is a heterogenous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans having anticoagulant properties. It is composed of polymers of alternating derivations of alpha-L-iduronic acid 2-sulfate (1), 2-deoxy-2-sulfamino- alpha-D-glucose 6-sulfate (2), beta-D-glucuronic acid (3), 2-acetamido-2- deoxy-alpha-D-glucose (4), and alpha-L-iduronic acid (5).

{ "type": "p", "children": [], "text": "Heparin is a heterogenous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans having anticoagulant properties. It is composed of polymers of alternating derivations of alpha-L-iduronic acid 2-sulfate (1), 2-deoxy-2-sulfamino- alpha-D-glucose 6-sulfate (2), beta-D-glucuronic acid (3), 2-acetamido-2- deoxy-alpha-D-glucose (4), and alpha-L-iduronic acid (5). " }

Structure of Heparin Sodium (representative subunits):

{ "type": "p", "children": [], "text": " Structure of Heparin Sodium (representative subunits):" }

Heparin Sodium in 0.45% Sodium Chloride Injection is a sterile, single-dose, clear, nonpyrogenic solution prepared from Heparin Sodium USP (derived from porcine intestinal mucosa and standardized for use as an anticoagulant) in 0.45% Sodium Chloride Injection. It is to be administered by intravenous injection. The potency is determined by a biological assay using a USP reference standard based on units of heparin activity per milligram.

{ "type": "p", "children": [], "text": "Heparin Sodium in 0.45% Sodium Chloride Injection is a sterile, single-dose, clear, nonpyrogenic solution prepared from Heparin Sodium USP (derived from porcine intestinal mucosa and standardized for use as an anticoagulant) in 0.45% Sodium Chloride Injection. It is to be administered by intravenous injection. The potency is determined by a biological assay using a USP reference standard based on units of heparin activity per milligram." }

The pH range is 7.0 (6.8-7.2) and the osmolarity mOsmol/L (calc.) is 206. The concentration of electrolytes is 109 mEq/L Sodium, 77 mEq/L Chloride, 32 mEq/L Phosphate, and 6 mEq/L Citrate.

{ "type": "p", "children": [], "text": "The pH range is 7.0 (6.8-7.2) and the osmolarity mOsmol/L (calc.) is 206. The concentration of electrolytes is 109 mEq/L Sodium, 77 mEq/L Chloride, 32 mEq/L Phosphate, and 6 mEq/L Citrate." }

50 USP units/mL: Each 100 mL of the 25,000 USP units per 500 mL preparation contains: 5,000 USP units of heparin sodium, 0.45 g Sodium Chloride USP, 0.43 g Dibasic Sodium Phosphate USP, 0.037 g Citric Acid Anhydrous USP, and Water for Injection USP until quantity sufficient.

{ "type": "p", "children": [], "text": "50 USP units/mL: Each 100 mL of the 25,000 USP units per 500 mL preparation contains: 5,000 USP units of heparin sodium, 0.45 g Sodium Chloride USP, 0.43 g Dibasic Sodium Phosphate USP, 0.037 g Citric Acid Anhydrous USP, and Water for Injection USP until quantity sufficient." }

100 USP units/mL: Each 100 mL of the 25,000 USP units per 250 mL preparation contains: 10,000 USP units of heparin sodium, 0.45 g Sodium Chloride USP, 0.43 g Dibasic Sodium Phosphate USP, 0.037 g Citric Acid Anhydrous USP, and Water for Injection USP until quantity sufficient.

{ "type": "p", "children": [], "text": "100 USP units/mL: Each 100 mL of the 25,000 USP units per 250 mL preparation contains: 10,000 USP units of heparin sodium, 0.45 g Sodium Chloride USP, 0.43 g Dibasic Sodium Phosphate USP, 0.037 g Citric Acid Anhydrous USP, and Water for Injection USP until quantity sufficient." }

The plastic container is made from a multilayered film specifically developed for parenteral drugs. The solution contact layer is a rubberized copolymer of ethylene and propylene. The container is nontoxic and biologically inert. The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary.

{ "type": "p", "children": [], "text": "The plastic container is made from a multilayered film specifically developed for parenteral drugs. The solution contact layer is a rubberized copolymer of ethylene and propylene. The container is nontoxic and biologically inert. The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary." }

The plastic container is not made with natural rubber latex, PVC or DEHP.

{ "type": "p", "children": [], "text": "The plastic container is not made with natural rubber latex, PVC or DEHP." }

The closure system has two ports; the one for the administration set has a tamper evident plastic protector.

{ "type": "p", "children": [], "text": " The closure system has two ports; the one for the administration set has a tamper evident plastic protector. " }

Heparin interacts with the naturally occurring plasma protein, Antithrombin III, to induce a conformational change, which markedly enhances the serine protease activity of Antithrombin III, thereby inhibiting the activated coagulation factors involved in the closing sequence, particularly Xa and IIa. Small amounts of heparin inhibit Factor Xa, and larger amounts inhibit thrombin (Factor IIa). Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots.

Various times (activated clotting time, activated partial thromboplastin time, prothrombin time, whole blood clotting time) are prolonged by full therapeutic doses of heparin; in most cases, they are not measurably affected by low doses of heparin. Bleeding time is usually unaffected by heparin.

Absorption

Heparin is not absorbed through the gastrointestinal tract and therefore administered via parenteral route. Peak plasma concentration and the onset of action are achieved immediately after intravenous administration.

Distribution

Heparin is highly bound to antithrombin, fibrinogens, globulins, serum proteases and lipoproteins. The volume of distribution is 0.07 L/kg.

Elimination

Metabolism

Heparin does not undergo enzymatic degradation.

Excretion

Heparin is mainly cleared from the circulation by liver and reticuloendothelial cells mediated uptake into extravascular space. Heparin undergoes biphasic clearance, a) rapid saturable clearance (zero order process due to binding to proteins, endothelial cells and macrophages) and b) slower first order elimination. Low doses of heparin are cleared mostly by a saturable, rapid, zero-order process. Slower first order elimination usually occurs with very high doses of heparin and is dependent on renal function. The plasma half-life is dose-dependent, and it ranges from 0.5 to 2 hours.

Specific Populations

Geriatric Patients

Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of heparin and longer activated partial thromboplastin times (APTTs) compared with patients under 60 years of age [see Use in Specific Populations (8.5)].

Renal and Hepatic Impairment

The rate of clearance of unfractionated heparin may be decreased in patients with renal or hepatic impairment. Patients with renal or hepatic impairment, following similar doses of heparin may have higher plasma levels of heparin compared with patient with normal renal and hepatic function [see Warnings and Precautions (5.2)].

Long term studies in animals to evaluate the carcinogenic potential, reproduction studies in animals to determine effects on fertility of males and females, and the studies to determine mutagenic potential have not been conducted.

Heparin Sodium in 0.45% Sodium Chloride Injection is a clear solution and is supplied sterile and nonpyrogenic in single-dose EXCEL® Containers packaged 24 per case.

{ "type": "p", "children": [], "text": "Heparin Sodium in 0.45% Sodium Chloride Injection is a clear solution and is supplied sterile and nonpyrogenic in single-dose EXCEL® Containers packaged 24 per case." }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col width="81.9pt"/> <col width="45pt"/> <col width="279pt"/> <col width="55.9pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">NDC</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">REF</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Concentration</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Size</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">0264-3301-10</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">P3301</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Heparin Sodium 25,000 USP units per 500 mL (50 USP units per mL) in 0.45% Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">500 mL</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">0264-3462-20</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">P3462</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Heparin Sodium 25,000 USP units per 250 mL (100 USP units per mL) in 0.45% Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">250 mL</p> </td> </tr> </tbody> </table></div>

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Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing.

{ "type": "p", "children": [], "text": "Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. " }

Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.]

{ "type": "p", "children": [], "text": " Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.]" }

Hemorrhage

{ "type": "p", "children": [], "text": "\nHemorrhage\n" }

Inform patients that it may take them longer than usual to stop bleeding, that they may bruise and/or bleed more easily when they are treated with heparin, and that they should report any unusual bleeding or bruising to their physician. Hemorrhage can occur at virtually any site in patients receiving heparin. Fatal hemorrhages have occurred [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Inform patients that it may take them longer than usual to stop bleeding, that they may bruise and/or bleed more easily when they are treated with heparin, and that they should report any unusual bleeding or bruising to their physician. Hemorrhage can occur at virtually any site in patients receiving heparin. Fatal hemorrhages have occurred [see Warnings and Precautions (5.2)].\n" }

Prior to Surgery

{ "type": "p", "children": [], "text": "\nPrior to Surgery\n" }

Advise patients to inform physicians and dentists that they are receiving heparin before any surgery is scheduled [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to inform physicians and dentists that they are receiving heparin before any surgery is scheduled [see Warnings and Precautions (5.2)].\n" }

Heparin-Induced Thrombocytopenia

{ "type": "p", "children": [], "text": "\nHeparin-Induced Thrombocytopenia\n" }

Inform patients of the risk of heparin-induced thrombocytopenia (HIT). HIT may progress to the development of venous and arterial thromboses, a condition known as heparin-induced thrombocytopenia and thrombosis (HITT). HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy [see Warnings and Precautions (5.3 and 5.4)].

{ "type": "p", "children": [], "text": "Inform patients of the risk of heparin-induced thrombocytopenia (HIT). HIT may progress to the development of venous and arterial thromboses, a condition known as heparin-induced thrombocytopenia and thrombosis (HITT). HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy [see Warnings and Precautions (5.3 and 5.4)]." }

Hypersensitivity

{ "type": "p", "children": [], "text": "\nHypersensitivity\n" }

Inform patients that generalized hypersensitivity reactions have been reported. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin [see Warnings and Precautions (5.7), Adverse Reactions (6)].

{ "type": "p", "children": [], "text": "Inform patients that generalized hypersensitivity reactions have been reported. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin [see Warnings and Precautions (5.7), Adverse Reactions (6)]. \n" }

Other Medications

{ "type": "p", "children": [], "text": "\nOther Medications\n" }

Because of the risk of hemorrhage, advise patients to inform their physicians and dentists of all medications they are taking, including non-prescription medications, and before starting any new medication [see Drug Interactions (7.2)].

{ "type": "p", "children": [], "text": " Because of the risk of hemorrhage, advise patients to inform their physicians and dentists of all medications they are taking, including non-prescription medications, and before starting any new medication [see Drug Interactions (7.2)]." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

EXCEL is a registered trademark of B. Braun Medical Inc.

{ "type": "p", "children": [], "text": "EXCEL is a registered trademark of B. Braun Medical Inc." }

B. Braun Medical Inc. Bethlehem, PA 18018-3524 USA 1-800-227-2862

{ "type": "p", "children": [], "text": "\nB. Braun Medical Inc.\nBethlehem, PA 18018-3524 USA\n1-800-227-2862" }

Y36-003-101     LD-787-2

{ "type": "p", "children": [], "text": "Y36-003-101     LD-787-2" }

NDC 0264-3301-10

{ "type": "p", "children": [], "text": "\nNDC 0264-3301-10\n" }

HEPARIN SODIUM in 0.45% Sodium Chloride Injection 25,000 USP units per 500 mL (50 USP units per mL)

{ "type": "p", "children": [], "text": "\nHEPARIN SODIUM in\n0.45% Sodium Chloride Injection\n25,000 USP units per 500 mL\n(50 USP units per mL)" }

LD-789-2   Y94-003-515

{ "type": "p", "children": [], "text": "LD-789-2   Y94-003-515" }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Each 100 mL contains: Heparin Sodium USP (porcine intestinal mucosa) 5,000 USP Heparin units; Sodium Chloride USP 0.45 g; Dibasic Sodium Phosphate•7H2O USP 0.43 g; Citric Acid Anhydrous USP 0.037 g; Water for Injection USP qs

{ "type": "p", "children": [], "text": "\nEach 100 mL contains: Heparin Sodium USP (porcine intestinal mucosa) \n5,000 USP Heparin units; Sodium Chloride USP 0.45 g; \nDibasic Sodium Phosphate•7H2O USP 0.43 g; Citric Acid Anhydrous USP 0.037 g;\nWater for Injection USP qs\n" }

Electrolytes (mEq/liter):    Sodium 109;     Phosphate (HPO) 32;

{ "type": "p", "children": [], "text": "\nElectrolytes (mEq/liter):    Sodium 109;     Phosphate (HPO) 32;\n" }

      Citrate 6;          Chloride 77

{ "type": "p", "children": [], "text": "\n      Citrate 6;          Chloride 77\n" }

WARNING: Do not admix with other drugs.

{ "type": "p", "children": [], "text": "\nWARNING: Do not admix with other drugs.\n" }

Sterile. Single dose container. Discard unused portion.

{ "type": "p", "children": [], "text": "Sterile. Single dose container. Discard unused portion." }

Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Avoid excessive heat. Protect from freezing. Recommended Dosage: see Prescribing Information. Do not remove overwrap until ready for use.

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Avoid excessive heat. Protect from freezing. Recommended Dosage: see Prescribing Information. Do not remove overwrap until ready for use." }

Not made with natural rubber latex, PVC or DEHP.

{ "type": "p", "children": [], "text": "Not made with natural rubber latex, PVC or DEHP." }

500 mL EXCEL® CONTAINER

{ "type": "p", "children": [], "text": "\n500 mL EXCEL® CONTAINER\n" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

REF P3301

{ "type": "p", "children": [], "text": "\nREF P3301\n" }

EXCEL is a registered trademark of B. Braun Medical Inc.

{ "type": "p", "children": [], "text": "EXCEL is a registered trademark of B. Braun Medical Inc." }

B. Braun Medical Inc. Bethlehem, PA 18018-3524 USA 1-800-227-2862

{ "type": "p", "children": [], "text": "\nB. Braun Medical Inc.\nBethlehem, PA 18018-3524 USA\n1-800-227-2862" }

Prepared in USA. API from Spain.

{ "type": "p", "children": [], "text": "Prepared in USA. API from Spain." }

Y94-003-514   LD-788-2

{ "type": "p", "children": [], "text": "Y94-003-514   LD-788-2" }

EXP

{ "type": "p", "children": [], "text": "EXP" }

LOT

{ "type": "p", "children": [], "text": "LOT" }

NDC 0264-3462-20

{ "type": "p", "children": [], "text": "\nNDC 0264-3462-20\n" }

HEPARIN SODIUM in 0.45% Sodium Chloride Injection 25,000 USP units per 250 mL (100 USP units per mL)

{ "type": "p", "children": [], "text": "\nHEPARIN SODIUM in\n0.45% Sodium Chloride Injection\n25,000 USP units per 250 mL\n(100 USP units per mL)" }

LD-791-1   Y94-003-502

{ "type": "p", "children": [], "text": "LD-791-1   Y94-003-502" }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Each 100 mL contains: Heparin Sodium USP (porcine intestinal mucosa) 10,000 USP Heparin units; Sodium Chloride USP 0.45 g; Dibasic Sodium Phosphate•7H2O USP 0.43 g; Citric Acid Anhydrous USP 0.037 g; Water for Injection USP qs

{ "type": "p", "children": [], "text": "\nEach 100 mL contains: Heparin Sodium USP (porcine intestinal mucosa) \n10,000 USP Heparin units; Sodium Chloride USP 0.45 g; \nDibasic Sodium Phosphate•7H2O USP 0.43 g; Citric Acid Anhydrous USP 0.037 g;\nWater for Injection USP qs\n" }

 Electrolytes (mEq/liter):     Sodium 109;     Phosphate (HPO) 32;                                               Citrate 6;     Chloride 77

{ "type": "p", "children": [], "text": "\n Electrolytes (mEq/liter):     Sodium 109;     Phosphate (HPO) 32;\n\n                                              Citrate 6;     Chloride 77\n" }

WARNING: Do not admix with other drugs.

{ "type": "p", "children": [], "text": "\nWARNING: Do not admix with other drugs.\n" }

Sterile. Single dose container. Discard unused portion.

{ "type": "p", "children": [], "text": "Sterile. Single dose container. Discard unused portion." }

Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Avoid excessive heat. Protect from freezing. Recommended Dosage: see Prescribing Information. Do not remove overwrap until ready for use.

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Avoid excessive heat. Protect from freezing. Recommended Dosage: see Prescribing Information. Do not remove overwrap until ready for use." }

Not made with natural rubber latex, PVC or DEHP.

{ "type": "p", "children": [], "text": "Not made with natural rubber latex, PVC or DEHP." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

EXCEL is a registered trademark of B. Braun Medical Inc.

{ "type": "p", "children": [], "text": "EXCEL is a registered trademark of B. Braun Medical Inc." }

250 mL EXCEL® CONTAINER

{ "type": "p", "children": [], "text": "\n250 mL EXCEL® CONTAINER\n" }

REF P3462

{ "type": "p", "children": [], "text": "\nREF P3462\n" }

B. Braun Medical Inc. Bethlehem, PA 18018-3524 USA 1-800-227-2862

{ "type": "p", "children": [], "text": "\nB. Braun Medical Inc.\nBethlehem, PA 18018-3524 USA\n1-800-227-2862" }

Prepared in USA. API from Spain.

{ "type": "p", "children": [], "text": "Prepared in USA. API from Spain." }

Y94-003-501   LD-790-1

{ "type": "p", "children": [], "text": "Y94-003-501   LD-790-1" }

EXP

{ "type": "p", "children": [], "text": "EXP" }

LOT

{ "type": "p", "children": [], "text": "LOT" }

RECOTHROM Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age.

{ "type": "p", "children": [], "text": "RECOTHROM Thrombin topical (Recombinant), is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adults and pediatric populations greater than or equal to one month of age. " }

RECOTHROM may be used in conjunction with an absorbable gelatin sponge, USP.

{ "type": "p", "children": [], "text": "RECOTHROM may be used in conjunction with an absorbable gelatin sponge, USP." }

The volume of reconstituted RECOTHROM Thrombin topical (Recombinant) required will vary depending on the size and number of bleeding sites to be treated and the method of application.

Inspect the integrity of the RECOTHROM package and contents. Do not use if the packaging or contents have been damaged or opened.

Reconstitute the lyophilized powder using the supplied diluent. Use aseptic technique when handling vials and syringes.

5,000-unit RECOTHROM Thrombin topical (Recombinant) Reconstitution

Units used herein represent international units of potency determined using a reference standard that has been calibrated against the World Health Organization Second International Standard for Thrombin.

20,000-unit RECOTHROM Thrombin topical (Recombinant) Reconstitution

For topical use only. DO NOT INJECT.

RECOTHROM solution should remain in the vial until ready for transfer to a labeled sterile bowl or basin.

RECOTHROM Thrombin topical (Recombinant) solution is now ready to use, either with an absorbable gelatin sponge, FLOSEAL NT or used with the RECOTHROM Spray Applicator Kit for surface application. DO NOT INJECT.

The amount required depends upon the area of tissue to be treated and the method of application.

Vials are for single use only. Discard unused contents.

Use with Absorbable Gelatin Sponge

Refer to the absorbable gelatin sponge labeling for safety information and instructions on appropriate use.

Use with RECOTHROM Spray Applicator Kit

The RECOTHROM Spray Applicator Kit is double-packaged to allow for the aseptic transfer of the inner sterile package into a sterile field. Refer to Spray Applicator Kit instructions for use.

Use in conjunction with FLOSEAL NT Hemostatic Matrix, 5mL

RECOTHROM Thrombin topical (Recombinant) is available as a sterile lyophilized powder in 5,000- and 20,000-unit single-use vials. When reconstituted with the sterile 0.9% sodium chloride, USP provided, the powder yields a solution containing 1,000 units/mL of Thrombin topical (Recombinant).

{ "type": "p", "children": [], "text": "RECOTHROM Thrombin topical (Recombinant) is available as a sterile lyophilized powder in 5,000- and 20,000-unit single-use vials. When reconstituted with the sterile 0.9% sodium chloride, USP provided, the powder yields a solution containing 1,000 units/mL of Thrombin topical (Recombinant)." }

{ "type": "", "children": [], "text": "" }

RECOTHROM Thrombin topical (Recombinant) causes thrombosis if it enters the circulatory system. Apply topically. DO NOT INJECT.

Hypersensitivity reactions, including anaphylaxis, may occur.

RECOTHROM Thrombin topical (Recombinant) is produced in a genetically modified Chinese Hamster Ovary (CHO) cell line and may contain hamster or snake proteins [see Contraindications (4) and Description (11)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug product cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Clinical trials have been performed with RECOTHROM Thrombin topical (Recombinant) applied with absorbable gelatin sponge and applied with a spray applicator. A total of 644 patients were exposed to RECOTHROM in these studies.

RECOTHROM Thrombin topical (Recombinant) Used in Conjunction with Absorbable Gelatin Sponge

Four hundred eleven (411) patients were treated in a randomized, double-blind, controlled trial that compared RECOTHROM to bovine thrombin. Both thrombins were applied with a gelatin sponge in patients undergoing spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access.1 The incidence of thromboembolic adverse reactions was similar between the RECOTHROM and bovine thrombin treatment groups (see Table 1).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Incidence of Adverse Reactions with RECOTHROM Thrombin topical (Recombinant) and Bovine Thrombin</span> </caption> <col width="39%"/> <col width="29%"/> <col width="32%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>THROMBIN-JMI Thrombin, Topical (Bovine)</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Adverse Reaction Category</span> </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">RECOTHROM </span> </p> <p> <span class="Bold">(N=205) </span> </p> <p> <span class="Bold">n (%)</span> </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Bovine Thrombin</span><a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </p> <p> <span class="Bold">(N=206) </span> </p> <p> <span class="Bold">n (%)</span> </p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule" valign="top"> <p class="First">Thromboembolic events</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">11 (5%)</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">12 (6%)</p> </td> </tr> </tbody> </table></div>

In an open-label, single-group trial (N=209), patients with documented or highly likely prior exposure to bovine thrombin within the previous three years were treated with RECOTHROM when undergoing surgeries (spinal, peripheral arterial bypass, or arteriovenous graft formation for hemodialysis access).2 The incidence of thromboembolic adverse reactions in this study was 9%.

In an open-label, single-group trial of re-exposure to RECOTHROM (N=31), patients with documented prior exposure to RECOTHROM were treated with RECOTHROM during surgery (spinal, peripheral arterial bypass, arteriovenous graft formation, or other procedures).3 The incidence of thromboembolic adverse reactions in this study was 3%.

In other randomized, double-blind trials across a range of surgical settings (N=130; spinal surgery, hepatic resection, peripheral arterial bypass surgery, or arteriovenous graft formation for hemodialysis access), the safety of RECOTHROM (n=88 patients) was compared to placebo (RECOTHROM excipients reconstituted with sterile 0.9% sodium chloride, USP) (n=42 patients). The incidence of thromboembolic adverse reactions in this study was 5% for RECOTHROM and 12% for placebo.

RECOTHROM Thrombin topical (Recombinant) Applied with Spray Applicator

RECOTHROM was applied with a spray applicator in two open-label clinical trials: a single-group trial in adult and pediatric burn patients (N=72; ≤16 years of age, (n=4) and ≥17 years of age, (n=68)) treated with RECOTHROM applied to the wound excision site prior to autologous skin grafting4; and in a single-group trial in pediatric patients (one month to 17 years of age) undergoing synchronous burn wound excision and autologous skin grafting (N=30; ≤16 years of age, (n=26); ≥17 years of age, (n=4)).5 In the first study, the incidence of thromboembolic adverse reactions was 1%. In the second study, there were no reported thromboembolic adverse reactions [see Use in Specific Populations (8.4)].

The detection of antibody formation is highly dependent upon the sensitivity and specificity of the assay. The absolute immunogenicity rates reported here are difficult to compare with the results from other products due to differences in assay methodology, patient populations, and other underlying factors.

The potential for development of antibodies to RECOTHROM Thrombin topical (Recombinant) was evaluated in multiple clinical trials and included patients with a single exposure to RECOTHROM as well as patients who were re-exposed to RECOTHROM during a subsequent surgical procedure. Only patients with both baseline and post-treatment antibody specimens available were evaluated for the development of specific anti-RECOTHROM product antibodies, which was defined as seroconversion or a ≥1.0 titer unit (≥10-fold) increase in antibody levels after study treatment. Five of 609 (0.8%; 95% CI, 0.4%-2.8%) evaluable patients developed specific anti-RECOTHROM product antibodies. None of these antibodies were found to neutralize native human thrombin. There was no difference in anti-RECOTHROM product antibody formation incidence among patients exposed to RECOTHROM applied with absorbable gelatin sponge, USP or with spray applicator.

In a clinical trial comparing RECOTHROM to bovine thrombin (N=411; n=398 antibody evaluable) for the development of specific anti-product antibodies, blood samples were collected at baseline and at Day 29 in both treatment groups and were analyzed by ELISA.1 At baseline, 1.5% of RECOTHROM patients (n=3/198) had positive anti-product antibody titers compared with 5% of bovine thrombin patients (n=10/200). Of these patients, none of the RECOTHROM group and eight in the bovine thrombin group exhibited ≥1.0 titer unit (≥10-fold) increases in anti-product antibody levels after study treatment.

At Day 29, three of 198 (1.5%; 95% CI, 0%-4%) patients in the RECOTHROM group developed specific anti-product antibodies (one patient also developed anti-CHO host cell protein antibodies); 43 of 200 patients in the bovine thrombin group (22%; 95% CI, 16%-28%) developed specific antibodies to bovine thrombin product. Treatment with RECOTHROM resulted in a statistically significant lower incidence of specific anti-product antibody development. Because the study was not powered to detect a difference in clinical outcomes attributable to antibody formation, no conclusions can be drawn regarding the clinical significance of the difference in antibody formation based on the results of this study. None of the antibodies in the RECOTHROM group neutralized native human thrombin. Antibodies against bovine thrombin product were not tested for neutralization of native human thrombin.

In a trial of patients with a high likelihood of prior exposure to bovine thrombin, 15.6% of patients (n=32/205) had anti-bovine thrombin product antibodies and 2% of patients (n=4/200) had anti-RECOTHROM product antibodies at baseline.2 Following treatment, none of the 200 evaluable patients (patients for whom post-treatment specimens were available) developed antibodies to RECOTHROM.

In a trial of patients previously exposed to RECOTHROM, 31 patients were re-exposed toRECOTHROM during a subsequent surgery.3 None of the evaluable patients (n=30) had anti-RECOTHROM product antibodies at baseline and none developed antibodies at Day 29.

In a trial of RECOTHROM, including 26 pediatric patients (aged one month to 16 years) and four patients 17 years of age, one patient without prior thrombin exposure had pre-existing anti-RECOTHROM product antibodies at baseline.5 None of the 27 evaluable patients developed anti-RECOTHROM product antibodies at Day 29.

Risk Summary There are no available data regarding RECOTHROM Thrombin topical (Recombinant) in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with RECOTHROM.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Risk Summary There is no information regarding the presence of RECOTHROM Thrombin topical (Recombinant) in human milk, the effects on the breastfed infant, and the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RECOTHROM and any potential adverse effects on the breastfed child from RECOTHROM or from underlying maternal condition.

A total of 30 pediatric patients, ages 0 to 16 years (one month to 2 years, n=10; 2 to 12 years, n=12; 12 to 16 years, n=8), were treated in clinical trials with RECOTHROM Thrombin topical (Recombinant) using a spray applicator to burn wound excision sites prior to autologous skin grafting. No patient experienced a thromboembolic adverse reaction. The safety of RECOTHROM in pediatric patients greater than or equal to one month of age is supported by these data and by extrapolation of efficacy from adequate and well-controlled studies of RECOTHROM in adults. Safety and efficacy have not been established in neonates [see Adverse Reactions (6)].

Of 644 patients in clinical studies of RECOTHROM Thrombin topical (Recombinant), 36% (n=232/644) were ≥65 years old and 15% (n=95/644) were ≥75 years old.

No differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

RECOTHROM Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture RECOTHROM has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of RECOTHROM employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance.

{ "type": "p", "children": [], "text": "RECOTHROM Thrombin topical (Recombinant), is a human coagulation protein produced via recombinant DNA technology from a genetically modified CHO cell line. RECOTHROM is identical in amino acid sequence and structurally similar to naturally occurring human thrombin. RECOTHROM precursor is secreted to culture medium as single chain form that is proteolytically converted to a two-chain active form (using a protein derived from snakes) and is purified by a chromatographic process that yields a product having hemostatic activities similar to native human thrombin. The cell line used to manufacture RECOTHROM has been tested and shown to be free of known infectious agents. The cell culture process used in the manufacture of RECOTHROM employs no additives of human or animal origin. The purification process includes solvent-detergent treatment and nano-filtration steps dedicated to viral clearance." }

RECOTHROM is provided as a sterile, white to off-white, preservative-free, lyophilized powder in vials for reconstitution with diluent (sterile 0.9% sodium chloride, USP). Reconstitution with the provided diluent, as described [see Dosage and Administration (2.1)], yields a solution with a pH of 6.0 containing 1,000 units/mL of recombinant thrombin for topical use. The formulated product is a clear, colorless solution upon reconstitution and contains the following excipients: histidine, mannitol, sucrose, polyethylene glycol 3350, sodium chloride, and calcium chloride dihydrate, USP.

{ "type": "p", "children": [], "text": "RECOTHROM is provided as a sterile, white to off-white, preservative-free, lyophilized powder in vials for reconstitution with diluent (sterile 0.9% sodium chloride, USP). Reconstitution with the provided diluent, as described [see Dosage and Administration (2.1)], yields a solution with a pH of 6.0 containing 1,000 units/mL of recombinant thrombin for topical use. The formulated product is a clear, colorless solution upon reconstitution and contains the following excipients: histidine, mannitol, sucrose, polyethylene glycol 3350, sodium chloride, and calcium chloride dihydrate, USP." }

RECOTHROM Thrombin topical (Recombinant), is a specific human serine protease that promotes hemostasis and acts locally when applied topically to a site of bleeding.

RECOTHROM activates platelets and catalyzes the conversion of fibrinogen to fibrin, which are steps that are essential for blood clot formation.

In vitro cytotoxicity studies have been performed in mouse L929 fibroblast cell cultures anddemonstrate a concentration-dependent effect on cell morphology. The thrombin-inducedmorphological changes were similar to those seen with bovine thrombin.

In a study in nonhuman primates, RECOTHROM Thrombin topical (Recombinant) was applied directly to a liver wound with an absorbable gelatin sponge, USP. In a second study, RECOTHROM was administered subcutaneously once weekly for four weeks to nonhuman primates following repeat doses of 5405 units/m2. In both studies, RECOTHROM had no effect on clinical signs, serum chemistry, coagulation parameters, or histopathology; only normal postsurgical findings were observed. No animals developed anti-RECOTHROM product antibodies in either study.

RECOTHROM was found to be non-irritating when instilled in the eyes (200 units) or applied to normal or abraded skin of rabbits (up to 1,000 units/site).

To evaluate RECOTHROM inhibition and clearance from the bloodstream, radiolabeled RECOTHROM was administered intravenously or subcutaneously to nonhuman primates and applied with an absorbable gelatin sponge, USP, in a rabbit hepatic wound model. RECOTHROM did not circulate in the blood as free, active molecule, but was rapidly inactivated (<5 minutes) after formation of complexes with endogenous inhibitors (e.g., antithrombin III); these complexes were cleared by the liver. RECOTHROM applied with an absorbable gelatin sponge, USP, was shown to decrease time to hemostasis (TTH) when compared to saline in a rabbit hepatic wound model and rat heminephrectomy model. RECOTHROM also reduced TTH when directly applied in a porcine partial-thickness excisional skin-wound model as compared to saline control (or no treatment).

RECOTHROM applied with a gauze sponge decreased TTH in a concentration-dependent manner in both the rabbit and rat models. Concentrations of RECOTHROM >1,000 units/mL were no different than 1,000 units/mL while the effect of RECOTHROM diluted to a concentration of 100 units/mL on TTH was indistinguishable from placebo.

The performance of RECOTHROM mixed with gelatin matrix (FLOSEAL NT Hemostatic Matrix, 5mL) was compared to FLOSEAL Hemostatic Matrix, 5mL (human plasma-derived thrombin mixed with gelatin matrix) in a blinded nonclinical study using a heparinized porcine liver punch model of moderate to severe bleeding. The analysis demonstrated that the performance of RECOTHROM mixed with gelatin matrix was non-inferior to human plasma-derived thrombin mixed with gelatin matrix.

RECOTHROM Thrombin topical (Recombinant) was evaluated in a randomized, double-blind comparative clinical trial to bovine thrombin. Each thrombin was topically applied to bleeding sites with an absorbable gelatin sponge at a nominal concentration of 1,000 units/mL.1 Patients (N=411) were a heterogeneous surgical population undergoing surgery in one of four surgical settings: spinal surgery (n=122, 30%), hepatic resection (n=125, 30%), peripheral arterial bypass surgery (n=88, 21%), and arteriovenous graft formation for hemodialysis access (n=76, 18%). Patients with prior heparin-induced thrombocytopenia were excluded. Patient ages ranged from 21 to 89 years, gender was 53% male and 47% female, and the distribution by race was 68% white, 18% black or African American, and 14% other. The distribution of these characteristics was similar in both the RECOTHROM and bovine thrombin treatment groups.

{ "type": "p", "children": [], "text": "RECOTHROM Thrombin topical (Recombinant) was evaluated in a randomized, double-blind comparative clinical trial to bovine thrombin. Each thrombin was topically applied to bleeding sites with an absorbable gelatin sponge at a nominal concentration of 1,000 units/mL.1 Patients (N=411) were a heterogeneous surgical population undergoing surgery in one of four surgical settings: spinal surgery (n=122, 30%), hepatic resection (n=125, 30%), peripheral arterial bypass surgery (n=88, 21%), and arteriovenous graft formation for hemodialysis access (n=76, 18%). Patients with prior heparin-induced thrombocytopenia were excluded. Patient ages ranged from 21 to 89 years, gender was 53% male and 47% female, and the distribution by race was 68% white, 18% black or African American, and 14% other. The distribution of these characteristics was similar in both the RECOTHROM and bovine thrombin treatment groups. " }

The objectives of the study were to evaluate the comparative efficacy, safety, and immunogenicity of RECOTHROM and bovine thrombin in combination with an absorbable gelatin sponge as adjuncts to hemostasis in surgery. Efficacy was evaluated by the incidence of hemostasis within 10 minutes. Bleeding appropriate for evaluation was defined as mild to moderate bleeding, either on its own or remaining after brisk bleeding was controlled by standard surgical modalities. Although multiple bleeding sites could be treated, only one bleeding site per patient was selected to determine effectiveness.

{ "type": "p", "children": [], "text": "The objectives of the study were to evaluate the comparative efficacy, safety, and immunogenicity of RECOTHROM and bovine thrombin in combination with an absorbable gelatin sponge as adjuncts to hemostasis in surgery. Efficacy was evaluated by the incidence of hemostasis within 10 minutes. Bleeding appropriate for evaluation was defined as mild to moderate bleeding, either on its own or remaining after brisk bleeding was controlled by standard surgical modalities. Although multiple bleeding sites could be treated, only one bleeding site per patient was selected to determine effectiveness." }

Table 2 summarizes the incidence of hemostasis within 10 minutes for each treatment for the 401efficacy evaluable patients. The incidence of hemostasis within 10 minutes was comparable for the RECOTHROM and bovine thrombin groups.

{ "type": "p", "children": [], "text": "Table 2 summarizes the incidence of hemostasis within 10 minutes for each treatment for the 401efficacy evaluable patients. The incidence of hemostasis within 10 minutes was comparable for the RECOTHROM and bovine thrombin groups." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2: Hemostasis Within 10 Minutes<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></span> </caption> <col width="42%"/> <col width="28%"/> <col width="30%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Evaluation of hemostasis at ≤ 10 minutes for patients treated at 1 of 4 primary TTH bleeding site types: epidural venous plexus, hepatic resection site, peripheral arterial bypass proximal anastomosis, and arteriovenous graft arterial anastomosis.</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">†</a> </dt> <dd>THROMBIN-JMI Thrombin, Topical (Bovine)</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Toprule" valign="top"></td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">RECOTHROM</span> </p> <p> <span class="Bold">(N=198)</span> </p> <p> <span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Bovine Thrombin</span><a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a> </p> <p> <span class="Bold">(N=203)</span> </p> <p> <span class="Bold">(%)</span> </p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">Overall</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">95%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">95%</p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">Spinal surgery</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">98%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">98%</p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">Hepatic resection</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">98%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">97%</p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">Peripheral arterial bypass</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">85%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">86%</p> </td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">Arteriovenous graft formation</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">97%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">97%</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 2: Hemostasis Within 10 Minutes<a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">*</a></span>\n</caption>\n<col width=\"42%\"/>\n<col width=\"28%\"/>\n<col width=\"30%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"3\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">*</a>\n</dt>\n<dd>Evaluation of hemostasis at ≤ 10 minutes for patients treated at 1 of 4 primary TTH bleeding site types: epidural venous plexus, hepatic resection site, peripheral arterial bypass proximal anastomosis, and arteriovenous graft arterial anastomosis.</dd>\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">†</a>\n</dt>\n<dd>THROMBIN-JMI Thrombin, Topical (Bovine)</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Toprule\" valign=\"top\"></td><td align=\"center\" class=\"Botrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">RECOTHROM</span>\n</p>\n<p>\n<span class=\"Bold\">(N=198)</span>\n</p>\n<p>\n<span class=\"Bold\">(%)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Bovine Thrombin</span><a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">†</a>\n</p>\n<p>\n<span class=\"Bold\">(N=203)</span>\n</p>\n<p>\n<span class=\"Bold\">(%)</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">Overall</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">95%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">95%</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">Spinal surgery</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">98%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">98%</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">Hepatic resection</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">98%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">97%</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">Peripheral arterial bypass</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">85%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">86%</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">Arteriovenous graft formation</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">97%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">97%</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

The percentage of patients achieving hemostasis at 1.5, 3, 6, and 10 minutes is listed in Table 3.

{ "type": "p", "children": [], "text": "The percentage of patients achieving hemostasis at 1.5, 3, 6, and 10 minutes is listed in Table 3." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3: Cumulative Incidence of Hemostasis Over Time</span> </caption> <col width="31%"/> <col width="33%"/> <col width="36%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>THROMBIN-JMI Thrombin, Topical (Bovine)</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time (Minutes)</span> </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">RECOTHROM</span> </p> <p> <span class="Bold">(N=198)</span> </p> <p> <span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Bovine Thrombin</span><a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a> </p> <p> <span class="Bold">(N=203)</span> </p> <p> <span class="Bold">(%)</span> </p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">1.5</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">48%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">46%</p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">3</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">81%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">72%</p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">6</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">92%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">88%</p> </td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">10</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">95%</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">95%</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 3: Cumulative Incidence of Hemostasis Over Time</span>\n</caption>\n<col width=\"31%\"/>\n<col width=\"33%\"/>\n<col width=\"36%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"3\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">*</a>\n</dt>\n<dd>THROMBIN-JMI Thrombin, Topical (Bovine)</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Time (Minutes)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">RECOTHROM</span>\n</p>\n<p>\n<span class=\"Bold\">(N=198)</span>\n</p>\n<p>\n<span class=\"Bold\">(%)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Bovine Thrombin</span><a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">*</a>\n</p>\n<p>\n<span class=\"Bold\">(N=203)</span>\n</p>\n<p>\n<span class=\"Bold\">(%)</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">1.5</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">48%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">46%</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">3</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">81%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">72%</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">6</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">92%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">88%</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule\" valign=\"top\">\n<p class=\"First\">10</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">95%</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\">\n<p class=\"First\">95%</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

{ "type": "", "children": [], "text": "" }

RECOTHROM Thrombin topical (Recombinant), is supplied in single-use, preservative-free vials in the following packages:

{ "type": "p", "children": [], "text": "RECOTHROM Thrombin topical (Recombinant), is supplied in single-use, preservative-free vials in the following packages:" }

NDC 0338-0322-01A 5,000-unit vial of RECOTHROM with a 5-mL prefilled diluent syringe (containing sterile 0.9% sodium chloride, USP), a sterile needle-free vial access device, and a 5-mL sterile empty transfer syringe.

{ "type": "p", "children": [], "text": "NDC 0338-0322-01A 5,000-unit vial of RECOTHROM with a 5-mL prefilled diluent syringe (containing sterile 0.9% sodium chloride, USP), a sterile needle-free vial access device, and a 5-mL sterile empty transfer syringe." }

NDC 0338-0326-01A 20,000-unit vial of RECOTHROM with a 20-mL vial of diluent (containing sterile 0.9% sodium chloride, USP), 2 sterile needle-free vial access devices, and a 20-mL sterile empty transfer syringe.

{ "type": "p", "children": [], "text": "NDC 0338-0326-01A 20,000-unit vial of RECOTHROM with a 20-mL vial of diluent (containing sterile 0.9% sodium chloride, USP), 2 sterile needle-free vial access devices, and a 20-mL sterile empty transfer syringe." }

NDC 0338-0330-01The 20,000-unit RECOTHROM kit co-packaged with RECOTHROM Spray Applicator Kit.

{ "type": "p", "children": [], "text": "NDC 0338-0330-01The 20,000-unit RECOTHROM kit co-packaged with RECOTHROM Spray Applicator Kit." }

No RECOTHROM kit components contain latex.

{ "type": "p", "children": [], "text": "No RECOTHROM kit components contain latex." }

Store RECOTHROM sterile powder vials at 2°C to 25°C (36°F to 77°F). Do not freeze.

{ "type": "p", "children": [], "text": "Store RECOTHROM sterile powder vials at 2°C to 25°C (36°F to 77°F). Do not freeze." }

Reconstituted solutions of RECOTHROM prepared with sterile 0.9% sodium chloride, USP, may be stored for up to 24 hours at 2°C to 25°C (36°F to 77°F). Discard reconstituted solution after 24 hours.

{ "type": "p", "children": [], "text": "Reconstituted solutions of RECOTHROM prepared with sterile 0.9% sodium chloride, USP, may be stored for up to 24 hours at 2°C to 25°C (36°F to 77°F). Discard reconstituted solution after 24 hours." }

Because topical thrombin may cause the formation of clots in blood vessels if absorbed systemically, advise patients to consult their physician if they experience leg tenderness or swelling, chest pain, shortness of breath, or difficulty speaking or swallowing [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Because topical thrombin may cause the formation of clots in blood vessels if absorbed systemically, advise patients to consult their physician if they experience leg tenderness or swelling, chest pain, shortness of breath, or difficulty speaking or swallowing [see Warnings and Precautions (5.1)]. " }

Baxter and Recothrom are registered trademarks of Baxter International Inc.Thrombin-JMI is a registered trademark of King Pharmaceuticals Research and Development, LLC.

{ "type": "p", "children": [], "text": "Baxter and Recothrom are registered trademarks of Baxter International Inc.Thrombin-JMI is a registered trademark of King Pharmaceuticals Research and Development, LLC." }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USAUS License No. 0140

{ "type": "p", "children": [], "text": "Manufactured for:\nBaxter Healthcare Corporation \nDeerfield, IL 60015 USAUS License No. 0140" }

XX-XX-XX-XXXX

{ "type": "p", "children": [], "text": "XX-XX-XX-XXXX" }

{ "type": "", "children": [], "text": "" }

PS 5,000 units NDC: 0338-0322-01

{ "type": "p", "children": [], "text": "PS\n5,000 units\n\nNDC: 0338-0322-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL(RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL(RECOMBINANT)" }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA US License No. 0140Made in Italy

{ "type": "p", "children": [], "text": "Manufactured for: \nBaxter Healthcare Corporation \nDeerfield, IL 60015 USA US License No. 0140Made in Italy" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

5,000 units

{ "type": "p", "children": [], "text": "\n5,000 units\n" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

CONTENTS:

{ "type": "p", "children": [], "text": "\nCONTENTS:\n" }

• One single-use vial containing 5,000 International Units of sterile Thrombin topical (Recombinant)

{ "type": "p", "children": [], "text": "• One single-use vial containing 5,000 International Units of sterile Thrombin topical (Recombinant)" }

• One 5-mL prefilled diluent syringe (containing sterile 0.9% sodium chloride injection, USP)

{ "type": "p", "children": [], "text": "• One 5-mL prefilled diluent syringe (containing sterile 0.9% sodium chloride injection, USP)" }

• One sterile needle-free transfer device

{ "type": "p", "children": [], "text": "• One sterile needle-free transfer device" }

• One sterile 5-mL empty syringe for transfer

{ "type": "p", "children": [], "text": "• One sterile 5-mL empty syringe for transfer" }

PS

{ "type": "p", "children": [], "text": "PS" }

5,000 units NDC: 0338-0322-01

{ "type": "p", "children": [], "text": "\n5,000 units\n\nNDC: 0338-0322-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA US License No. 0140 Baxter and Recothrom are registered trademarks of Baxter International Inc. Made in Italy

{ "type": "p", "children": [], "text": "Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA US License No. 0140 Baxter and Recothrom are registered trademarks of Baxter International Inc. Made in Italy" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

CONTENTS:

{ "type": "p", "children": [], "text": "CONTENTS:" }

• One single-use vial containing 5,000 International Units of sterile Thrombin topical (Recombinant)

{ "type": "p", "children": [], "text": "• One single-use vial containing 5,000 International Units of sterile Thrombin topical (Recombinant)" }

• One 5-mL prefilled diluent syringe (containing sterile 0.9% sodium chloride injection, USP)

{ "type": "p", "children": [], "text": "• One 5-mL prefilled diluent syringe (containing sterile 0.9% sodium chloride injection, USP)" }

• One sterile needle-free transfer device

{ "type": "p", "children": [], "text": "• One sterile needle-free transfer device" }

• One sterile 5-mL empty syringe for transfer

{ "type": "p", "children": [], "text": "• One sterile 5-mL empty syringe for transfer" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

5,000 UNITS

{ "type": "p", "children": [], "text": "5,000 UNITS" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information.

{ "type": "p", "children": [], "text": "\nRx only Store at 2-25°C (36-77°F). Do not freeze. \nSee package insert Full Prescribing Information.\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "Baxter Logo" }

07-01-00-1475

{ "type": "p", "children": [], "text": "07-01-00-1475" }

5,000 units NDC: 0338-0322-01

{ "type": "p", "children": [], "text": "\n5,000 units\n\nNDC: 0338-0322-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA US License No. 0140Made in Italy Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information. No componentscontain latex.No preservative.

{ "type": "p", "children": [], "text": "Manufactured for: \nBaxter Healthcare Corporation \nDeerfield, IL 60015 USA US License No. 0140Made in Italy\nRx only Store at 2-25°C (36-77°F). Do not freeze.\n\nSee package insert Full Prescribing Information.\n\nNo componentscontain latex.No preservative.\n" }

{ "type": "", "children": [], "text": "" }

20,000 units NDC: 0338-0326-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0326-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\n\nSee package insert\n\nFull Prescribing Information.\n" }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USAUS License No. 0140Made in Italy

{ "type": "p", "children": [], "text": "Manufactured for:\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USAUS License No. 0140Made in Italy" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

20,000 units NDC: 0338-0326-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0326-01\n" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\n\nSee package insert\n\nFull Prescribing Information.\n" }

CONTENTS:

{ "type": "p", "children": [], "text": "\nCONTENTS:\n" }

• One single-use vial containing 20,000International Units of sterile Thrombintopical (Recombinant)

{ "type": "p", "children": [], "text": "• One single-use vial containing 20,000International Units of sterile Thrombintopical (Recombinant)" }

• One vial diluent (containing 20-mL sterile0.9% sodium chloride injection, USP)

{ "type": "p", "children": [], "text": "• One vial diluent (containing 20-mL sterile0.9% sodium chloride injection, USP)" }

• Two sterile needle-free transfer devices

{ "type": "p", "children": [], "text": "• Two sterile needle-free transfer devices" }

• One sterile 20-mL empty syringe for transfer

{ "type": "p", "children": [], "text": "• One sterile 20-mL empty syringe for transfer" }

20,000 units NDC: 0338-0326-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0326-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL(RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL(RECOMBINANT)" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\n\nSee package insert\n\nFull Prescribing Information.\n" }

CONTENTS:

{ "type": "p", "children": [], "text": "CONTENTS:" }

• One single-use vial containing 20,000International Units of sterile Thrombintopical (Recombinant)

{ "type": "p", "children": [], "text": "• One single-use vial containing 20,000International Units of sterile Thrombintopical (Recombinant)" }

• One vial diluent (containing 20-mL sterile0.9% sodium chloride injection, USP)

{ "type": "p", "children": [], "text": "• One vial diluent (containing 20-mL sterile0.9% sodium chloride injection, USP)" }

• Two sterile needle-free transfer devices

{ "type": "p", "children": [], "text": "• Two sterile needle-free transfer devices" }

• One sterile 20-mL empty syringe for transfer

{ "type": "p", "children": [], "text": "• One sterile 20-mL empty syringe for transfer" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

20,000 units NDC: 0338-0326-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0326-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\n\nSee package insert\n\nFull Prescribing Information.\n" }

07-01-00-1478

{ "type": "p", "children": [], "text": "07-01-00-1478" }

20,000 units NDC: 0338-0326-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0326-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USAUS License No. 0140Made in Italy

{ "type": "p", "children": [], "text": "Manufactured for:\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USAUS License No. 0140Made in Italy" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\n\nSee package insert\n\nFull Prescribing Information.\n" }

No Components contain latex.No preservative.

{ "type": "p", "children": [], "text": "\nNo Components contain latex.No preservative.\n" }

Baxter and Recothrom are registered trademarks of Baxter International Inc.

{ "type": "p", "children": [], "text": "Baxter and Recothrom are registered trademarks of Baxter International Inc." }

{ "type": "", "children": [], "text": "" }

20,000 units NDC: 0338-0330-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0330-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

RECOTHROM THROMBIN TOPICAL(RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL(RECOMBINANT)" }

20,000 units

{ "type": "p", "children": [], "text": "20,000 units" }

WITH SPRAY APPLICATOR KIT

{ "type": "p", "children": [], "text": "WITH SPRAY APPLICATOR KIT" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insertFull Prescribing Information. No components contain latex. No preservative.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\nSee package insertFull Prescribing Information.\nNo components contain latex.\n\nNo preservative.\n" }

RECOTHROM CONTENTS: • One single-use vial containing 20,000 InternationalUnits of sterile Thrombin topical (Recombinant)

{ "type": "p", "children": [], "text": "\nRECOTHROM CONTENTS:\n• One single-use vial containing 20,000 InternationalUnits of sterile Thrombin topical (Recombinant)" }

• One vial diluent (containing 20-mL sterile 0.9%sodium chloride injection, USP)

{ "type": "p", "children": [], "text": "• One vial diluent (containing 20-mL sterile 0.9%sodium chloride injection, USP)" }

• Two sterile needle-free transfer devices

{ "type": "p", "children": [], "text": "• Two sterile needle-free transfer devices" }

• One sterile 20-mL empty syringe for transfer

{ "type": "p", "children": [], "text": "• One sterile 20-mL empty syringe for transfer" }

SPRAY APPLICATOR CONTENTS:

{ "type": "p", "children": [], "text": "\nSPRAY APPLICATOR CONTENTS:\n" }

• One spray pump

{ "type": "p", "children": [], "text": "• One spray pump" }

• One spray bottle

{ "type": "p", "children": [], "text": "• One spray bottle" }

• One syringe spray tip

{ "type": "p", "children": [], "text": "• One syringe spray tip" }

• One 20-mL syringe

{ "type": "p", "children": [], "text": "• One 20-mL syringe" }

• One 30-mL bowl

{ "type": "p", "children": [], "text": "• One 30-mL bowl" }

• Two blank labels

{ "type": "p", "children": [], "text": "• Two blank labels" }

• Instructions for use

{ "type": "p", "children": [], "text": "• Instructions for use" }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USAUS License No. 0140Made in Italy

{ "type": "p", "children": [], "text": "Manufactured for:\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USAUS License No. 0140Made in Italy" }

Baxter LogoBaxter and Recothrom are registered trademarks of Baxter International Inc.

{ "type": "p", "children": [], "text": "\nBaxter LogoBaxter and Recothrom are registered trademarks of Baxter International Inc." }

20,000 units NDC: 0338-0330-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0330-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

20,000 units

{ "type": "p", "children": [], "text": "20,000 units" }

WITH SPRAY APPLICATOR KIT

{ "type": "p", "children": [], "text": "WITH SPRAY APPLICATOR KIT" }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USAUS License No. 0140Made in Italy

{ "type": "p", "children": [], "text": "Manufactured for:\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USAUS License No. 0140Made in Italy" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo" }

07-03-00-1214

{ "type": "p", "children": [], "text": "07-03-00-1214" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

20,000 units NDC: 0338-0330-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0330-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

20,000 units

{ "type": "p", "children": [], "text": "20,000 units" }

WITH SPRAY APPLICATOR KIT

{ "type": "p", "children": [], "text": "WITH SPRAY APPLICATOR KIT" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insertFull Prescribing Information. No components contain latex. No preservative.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\nSee package insertFull Prescribing Information.\nNo components contain latex.\n\nNo preservative.\n" }

07-03-00-1214

{ "type": "p", "children": [], "text": "07-03-00-1214" }

20,000 units NDC: 0338-0330-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0330-01\n" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

RECOTHROM THROMBIN TOPICAL(RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL(RECOMBINANT)" }

20,000 units

{ "type": "p", "children": [], "text": "20,000 units" }

WITH SPRAY APPLICATOR KIT

{ "type": "p", "children": [], "text": "WITH SPRAY APPLICATOR KIT" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insertFull Prescribing Information. No components contain latex. No preservative.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\nSee package insertFull Prescribing Information.\nNo components contain latex.\n\nNo preservative.\n" }

RECOTHROM CONTENTS: • One single-use vial containing 20,000 InternationalUnits of sterile Thrombin topical (Recombinant)

{ "type": "p", "children": [], "text": "\nRECOTHROM CONTENTS:\n• One single-use vial containing 20,000 InternationalUnits of sterile Thrombin topical (Recombinant)" }

• One vial diluent (containing 20-mL sterile 0.9%sodium chloride injection, USP)

{ "type": "p", "children": [], "text": "• One vial diluent (containing 20-mL sterile 0.9%sodium chloride injection, USP)" }

• Two sterile needle-free transfer devices

{ "type": "p", "children": [], "text": "• Two sterile needle-free transfer devices" }

• One sterile 20-mL empty syringe for transfer

{ "type": "p", "children": [], "text": "• One sterile 20-mL empty syringe for transfer" }

SPRAY APPLICATOR CONTENTS:

{ "type": "p", "children": [], "text": "\nSPRAY APPLICATOR CONTENTS:\n" }

• One spray pump

{ "type": "p", "children": [], "text": "• One spray pump" }

• One spray bottle

{ "type": "p", "children": [], "text": "• One spray bottle" }

• One syringe spray tip

{ "type": "p", "children": [], "text": "• One syringe spray tip" }

• One 20-mL syringe

{ "type": "p", "children": [], "text": "• One 20-mL syringe" }

• One 30-mL bowl

{ "type": "p", "children": [], "text": "• One 30-mL bowl" }

• Two blank labels

{ "type": "p", "children": [], "text": "• Two blank labels" }

• Instructions for use

{ "type": "p", "children": [], "text": "• Instructions for use" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

FPO

{ "type": "p", "children": [], "text": "FPO" }

20,000 units NDC: 0338-0330-01

{ "type": "p", "children": [], "text": "\n20,000 units\n\nNDC: 0338-0330-01\n" }

Baxter Logo

{ "type": "p", "children": [], "text": "\nBaxter Logo\n" }

RECOTHROM THROMBIN TOPICAL (RECOMBINANT)

{ "type": "p", "children": [], "text": "\nRECOTHROM\nTHROMBIN TOPICAL (RECOMBINANT)" }

20,000 units

{ "type": "p", "children": [], "text": "20,000 units" }

WITH SPRAY APPLICATOR KIT

{ "type": "p", "children": [], "text": "WITH SPRAY APPLICATOR KIT" }

FOR TOPICAL USE ONLY - DO NOT INJECT

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY - DO NOT INJECT\n" }

Rx only Store at 2-25°C (36-77°F). Do not freeze. See package insert Full Prescribing Information. No components contain latex. No preservative.

{ "type": "p", "children": [], "text": "\nRx only\n\nStore at 2-25°C (36-77°F).\n\nDo not freeze.\n\nSee package insert\n\nFull Prescribing Information.\n\nNo components contain latex.\n\nNo preservative.\n" }

RECOTHROM CONTENTS: • One single-use vial containing 20,000 InternationalUnits of sterile Thrombin topical (Recombinant)

{ "type": "p", "children": [], "text": "\nRECOTHROM CONTENTS:\n• One single-use vial containing 20,000 InternationalUnits of sterile Thrombin topical (Recombinant)" }

• One vial diluent (containing 20-mL sterile 0.9%sodium chloride injection, USP)

{ "type": "p", "children": [], "text": "• One vial diluent (containing 20-mL sterile 0.9%sodium chloride injection, USP)" }

• Two sterile needle-free transfer devices

{ "type": "p", "children": [], "text": "• Two sterile needle-free transfer devices" }

• One sterile 20-mL empty syringe for transfer

{ "type": "p", "children": [], "text": "• One sterile 20-mL empty syringe for transfer" }

SPRAY APPLICATOR CONTENTS:

{ "type": "p", "children": [], "text": "\nSPRAY APPLICATOR CONTENTS:\n" }

• One spray pump

{ "type": "p", "children": [], "text": "• One spray pump" }

• One spray bottle

{ "type": "p", "children": [], "text": "• One spray bottle" }

• One syringe spray tip

{ "type": "p", "children": [], "text": "• One syringe spray tip" }

• One 20-mL syringe

{ "type": "p", "children": [], "text": "• One 20-mL syringe" }

• One 30-mL bowl

{ "type": "p", "children": [], "text": "• One 30-mL bowl" }

• Two blank labels

{ "type": "p", "children": [], "text": "• Two blank labels" }

• Instructions for use

{ "type": "p", "children": [], "text": "• Instructions for use" }