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Intravenous Dilution Guidelines

Abciximab  (Reopro ®)

The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.

Usual Diluents

NS, D5W

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

Stability data:

Drug Stability
Refrigerated
Stability
Room Temp.
Reconstituted
Vial/Powder
Notes P-Insert
Updated
Abciximab (Reopro) Vials should be stored at 2 to 8 °C (36 to 46 °F). Do not freeze.   Solution Do not freeze. Do not shake. Do not use beyond the expiration date. Discard any unused portion left in the vial. 08 22 16

Dosing
:
The recommended dosage of Abciximab in adults is a 0.25 mg/kg intravenous bolus administered 10-60 minutes before the start of PCI, followed by a continuous intravenous infusion of 0.125 µg/kg/min (to a maximum of 10 µg/min) for 12 hours.

Patients with unstable angina not responding to conventional medical therapy and who are planned to undergo PCI within 24 hours may be treated with an Abciximab 0.25 mg/kg intravenous bolus followed by an 18- to 24-hour intravenous infusion of 10 µg/min, concluding one hour after the PCI.

Instructions for Administration
  1. Parenteral drug products should be inspected visually for particulate matter prior to administration. Preparations of Abciximab containing visibly opaque particles should NOT be used.
  2. Hypersensitivity reactions should be anticipated whenever protein solutions such as Abciximab are administered. Epinephrine, dopamine, theophylline, antihistamines and corticosteroids should be available for immediate use. If symptoms of an allergic reaction or anaphylaxis appear, the infusion should be stopped and appropriate treatment given see WARNINGS: Allergic Reactions).
  3. As with all parenteral drug products, aseptic procedures should be used during the administration of Abciximab.
  4. Bolus: Withdraw the necessary amount of Abciximab for bolus injection into a syringe. Filter the bolus injection using a sterile, non-pyrogenic, low protein-binding 0.2 or 5 µm syringe filter (Millipore SLGV025LS or SLSV025LS or equivalent).
  5. Continous infusion:  Withdraw the necessary amount of Abciximab for the continuous infusion into a syringe. Inject into an appropriate container of sterile 0.9% saline or 5% dextrose and infuse at the calculated rate via a continuous infusion pump. The continuous infusion should be filtered either upon admixture using a sterile, non-pyrogenic, low protein-binding 0.2 or 5 µm syringe filter (Millipore SLGV025LS or SLSV025LS or equivalent) or upon administration using an in-line, sterile, non-pyrogenic, low protein-binding 0.2 or 0.22 µm filter (Abbott #4524 or equivalent). Discard the unused portion at the end of the infusion.
  6. No incompatibilities have been shown with intravenous infusion fluids or commonly used cardiovascular drugs. Nevertheless, Abciximab should be administered in a separate intravenous line whenever possible and not mixed with other medications.
  7. No incompatibilities have been observed with glass bottles or polyvinyl chloride bags and administration sets.


Sample Admixture:
Standard Dilutions  [Amount of drug] [Infusion volume] [Infusion rate]
[Calculated dose] [250 ml] [Over 12 - 24 hrs depending on indication]

Some hospitals use the following dilution based on the standard vial size:
[10 mg] [250 ml] [Infuse as directed: 0.125 µg/kg/min (to a maximum of 10 µg/min)]



See comments below.

Dosage and administration

Stability / Miscellaneous



Filter all infusions.

CLINICAL PHARMACOLOGY:

General- Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. The mechanism of action is thought to involve steric hindrance and/or conformational effects to block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa.

Abciximab binds with similar affinity to the vitronectin receptor, also known as the avß3 integrin. The vitronectin receptor mediates the procoagulant properties of platelets and the proliferative properties of vascular endothelial and smooth muscle cells. In in vitro studies using a model cell line derived from melanoma cells, Abciximab blocked avß3-mediated effects including cell adhesion (IC50 = 0.34 µg/mL). At concentrations which, in vitro, provide > 80% GPIIb/IIIa receptor blockade, but above the in vivo therapeutic range, Abciximab more effectively blocked the burst of thrombin generation that followed platelet activation than select comparator antibodies which inhibit GPIIb/IIIa alone (1). The relationship of these in vitro data to clinical efficacy is unknown.

Abciximab also binds to the activated Mac-1 receptor on monocytes and neutrophils (2). In in vitro studies, Abciximab and 7E3 IgG blocked Mac-1 receptor function as evidenced by inhibition of monocyte adhesion (3). In addition, the degree of activated Mac-1 expression on circulating leukocytes and the numbers of circulating leukocyte-platelet complexes has been shown to be reduced in patients treated with Abciximab compared to control patients (4). The relationship of these in vitro data to clinical efficacy is uncertain.


Pre-clinical experience- Maximal inhibition of platelet aggregation was observed when greater than or equal 80% of GPIIb/IIIa receptors were blocked by Abciximab. In non-human primates, Abciximab bolus doses of 0.25 mg/kg generally achieved a blockade of at least 80% of platelet receptors and fully inhibited platelet aggregation. Inhibition of platelet function was temporary following a bolus dose, but receptor blockade could be sustained at greater than or equal 80% by continuous intravenous infusion. The inhibitory effects of Abciximab were substantially reversed by the transfusion of platelets in monkeys. The antithrombotic efficacy of prototype antibodies [murine 7E3 Fab and F(ab´ )2] and Abciximab was evaluated in dog, monkey and baboon models of coronary, carotid, and femoral artery thrombosis. Doses of the murine version of 7E3 or Abciximab sufficient to produce high-grade (greater than or equal 80%) GPIIb/IIIa receptor blockade prevented acute thrombosis and yielded lower rates of thrombosis compared with aspirin and/or heparin.


Pharmacokinetics- Following intravenous bolus administration, free plasma concentrations of Abciximab decrease rapidly with an initial half-life of less than 10 minutes and a second phase half-life of about 30 minutes, probably related to rapid binding to the platelet GPIIb/IIIa receptors. Platelet function generally recovers over the course of 48 hours (5,6), although Abciximab remains in the circulation for 15 days or more in a platelet-bound state. Intravenous administration of a 0.25 mg/kg bolus dose of Abciximab followed by continuous infusion of 10 µg/min (or a weight-adjusted infusion of 0.125 µg/kg/min to a maximum of 10 µg/min) produces approximately constant free plasma concentrations throughout the infusion. At the termination of the infusion period, free plasma concentrations fall rapidly for approximately six hours then decline at a slower rate.


Pharmacodynamics- Intravenous administration in humans of single bolus doses of Abciximab from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function as measured by ex vivo platelet aggregation in response to adenosine diphosphate (ADP) or by prolongation of bleeding time. At the two highest doses (0.25 and 0.30 mg/kg) at two hours post injection (the first time point evaluated), over 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation in response to 20 µM ADP was almost abolished. The median bleeding time increased to over 30 minutes at both doses compared with a baseline value of approximately five minutes.

Intravenous administration in humans of a single bolus dose of 0.25 mg/kg followed by a continuous infusion of 10 µg/min for periods of 12 to 96 hours produced sustained high-grade GPIIb/IIIa receptor blockade (greater than or equal 80%) and inhibition of platelet function (ex vivo platelet aggregation in response to 5 µM or 20 µM ADP less than 20% of baseline and bleeding time greater than 30 minutes) for the duration of the infusion in most patients. Similar results were obtained when a weight-adjusted infusion dose (0.125 µg/kg/min to a maximum of 10 µg/min) was used in patients weighing up to 80 kg. Results in patients who received the 0.25 mg/kg bolus followed by a 5 µg/min infusion for 24 hours showed a similar initial receptor blockade and inhibition of platelet aggregation, but the response was not maintained throughout the infusion period. The onset of Abciximab-mediated platelet inhibition following a 0.25 mg/kg bolus and 0.125 µg/kg/min infusion was rapid and platelet aggregation was reduced to less than 20% of baseline in 8 of 10 patients at 10 minutes after treatment initiation.

Low levels of GPIIb/IIIa receptor blockade are present for more than 10 days following cessation of the infusion. After discontinuation of Abciximab infusion, platelet function returns gradually to normal. Bleeding time returned to less than or equal 12 minutes within 12 hours following the end of infusion in 15 of 20 patients (75%), and within 24 hours in 18 of 20 patients (90%). Ex vivo platelet aggregation in response to 5 µM ADP returned to greater than or equal 50% of baseline within 24 hours following the end of infusion in 11 of 32 patients (34%) and within 48 hours in 23 of 32 patients (72%). In response to 20 µM ADP, ex vivo platelet aggregation returned to greater than or equal 50% of baseline within 24 hours in 20 of 32 patients (62%) and within 48 hours in 28 of 32 patients (88%).




INDICATIONS AND USAGE:
Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications

in patients undergoing percutaneous coronary intervention
in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours
Safety and efficacy of Abciximab use in patients not undergoing percutaneous coronary intervention have not been established.

Abciximab is intended for use with aspirin and heparin and has been studied only in that setting, as described in CLINICAL STUDIES (See package insert).


CONTRAINDICATIONS:
Because Abciximab may increase the risk of bleeding, Abciximab is contraindicated in the following clinical situations:

  • Active internal bleeding
  • Recent (within six weeks) gastrointestinal (GI) or genitourinary (GU) bleeding of clinical significance.
  • History of cerebrovascular accident (CVA) within two years, or CVA with a significant residual neurological deficit
  • Bleeding diathesis
  • Administration of oral anticoagulants within seven days unless prothrombin time is less than or equal 1.2 times control
  • Thrombocytopenia (< 100,000 cells/µL)
  • Recent (within six weeks) major surgery or trauma
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Severe uncontrolled hypertension
  • Presumed or documented history of vasculitis
  • Use of intravenous dextran before PCI, or intent to use it during an intervention
Abciximab is also contraindicated in patients with known hypersensitivity to any component of this product or to murine proteins.

WARNINGS:

Bleeding Events
Abciximab has the potential to increase the risk of bleeding, particularly in the presence of anticoagulation, e.g., from heparin, other anticoagulants, or thrombolytics (see ADVERSE REACTIONS: Bleeding).

The risk of major bleeds due to Abciximab therapy is increased in patients receiving thrombolytics and should be weighed against the anticipated benefits.

Should serious bleeding occur that is not controllable with pressure, the infusion of Abciximab and any concomitant heparin should be stopped.


Allergic Reactions (including anaphylaxis)
Allergic reactions, some of which were anaphylaxis (sometimes fatal), have been reported rarely in patients treated with ReoPro. Patients with allergic reactions should receive appropriate treatment. Treatment of anaphylaxis should include immediate discontinuation of ReoPro administration and initiation of resuscitative measures.


PRECAUTIONS:

Bleeding Precautions- To minimize the risk of bleeding with Abciximab, it is important to use a low-dose, weight-adjusted heparin regimen, a weight-adjusted Abciximab bolus and infusion, strict anticoagulation guidelines, careful vascular access site management, discontinuation of heparin after the procedure and early femoral arterial sheath removal.

Therapy with Abciximab requires careful attention to all potential bleeding sites including catheter insertion sites, arterial and venous puncture sites, cutdown sites, needle puncture sites, and gastrointestinal, genitourinary, pulmonary (alveolar), and retroperitoneal sites.

Arterial and venous punctures, intramuscular injections, and use of urinary catheters, nasotracheal intubation, nasogastric tubes and automatic blood pressure cuffs should be minimized. When obtaining intravenous access, non-compressible sites (e.g., subclavian or jugular veins) should be avoided. Saline or heparin locks should be considered for blood drawing. Vascular puncture sites should be documented and monitored. Gentle care should be provided when removing dressings.


Femoral artery access site: Arterial access site care is important to prevent bleeding. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Femoral vein sheath placement should be avoided unless needed. While the vascular sheath is in place, patients should be maintained on complete bed rest with the head of the bed less than or equal 30° and the affected limb restrained in a straight position. Patients may be medicated for back/groin pain as necessary.

Discontinuation of heparin immediately upon completion of the procedure and removal of the arterial sheath within six hours is strongly recommended if APTT less than or equal 50 sec or ACT less than or equal 175 sec (see PRECAUTIONS: Laboratory Tests). In all circumstances, heparin should be discontinued at least two hours prior to arterial sheath removal.

Following sheath removal, pressure should be applied to the femoral artery for at least 30 minutes using either manual compression or a mechanical device for hemostasis. A pressure dressing should be applied following hemostasis. The patient should be maintained on bed rest for six to eight hours following sheath removal or discontinuation of Abciximab, or four hours following discontinuation of heparin, whichever is later. The pressure dressing should be removed prior to ambulation. The sheath insertion site and distal pulses of affected leg(s) should be frequently checked while the femoral artery sheath is in place and for six hours after femoral artery sheath removal. Any hematoma should be measured and monitored for enlargement.

The following conditions have been associated with an increased risk of bleeding and may be additive with the effect of Abciximab in the angioplasty setting: PCI within 12 hours of the onset of symptoms for acute myocardial infarction, prolonged PCI (lasting more than 70 minutes) and failed PCI.


Use of Thrombolytics, Anticoagulants and Other Antiplatelet Agents- In the EPIC, EPILOG, CAPTURE, and EPISTENT trials, Abciximab was used concomitantly with heparin and aspirin. For details of the anticoagulation algorithms used in these clinical trials, see CLINICAL STUDIES (See package insert): Anticoagulation. Because Abciximab inhibits platelet aggregation, caution should be employed when it is used with other drugs that affect hemostasis, including thrombolytics, oral anticoagulants, non-steroidal anti-inflammatory drugs, dipyridamole, and ticlopidine.

In the EPIC trial, there was limited experience with the administration of Abciximab with low molecular weight dextran. Low molecular weight dextran was usually given for the deployment of a coronary stent, for which oral anticoagulants were also given. In the 11 patients who received low molecular weight dextran with Abciximab, five had major bleeding events and four had minor bleeding events. None of the five placebo patients treated with low molecular weight dextran had a major or minor bleeding event (see CONTRAINDICATIONS).

Because of observed synergistic effects on bleeding, Abciximab therapy should be used judiciously in patients who have received systemic thrombolytic therapy. The GUSTO V trial randomized patients with acute myocardial infarction to treatment with combined Abciximab and half-dose Reteplase, or full-dose Reteplase alone (15). In this trial, the incidence of moderate or severe nonintracranial bleeding was increased in those patients receiving Abciximab and half-dose Reteplase versus those receiving Reteplase alone (4.6% versus 2.3%, respectively).


Thrombocytopenia- Thrombocytopenia, including severe thrombocytopenia, has been observed with Abciximab administration (see ADVERSE REACTIONS: Thrombocytopenia). Platelet counts should be monitored prior to, during, and after treatment with Abciximab. Acute decreases in platelet count should be differentiated between true thrombocytopenia and pseudothrombocytopenia (see PRECAUTIONS: Laboratory Tests). If true thrombocytopenia is verified, Abciximab should be immediately discontinued and the condition appropriately monitored and treated.

In clinical trials, patients who developed thrombocytopenia were followed with daily platelet counts until their platelet count returned to normal. Heparin and aspirin were discontinued for platelet counts below 60,000 cells/µL and platelets were transfused for a platelet count below 50,000 cells/µL. Most cases of severe thrombocytopenia (< 50,000 cells/µL) occurred within the first 24 hours of Abciximab administration.

In a registry study of Abciximab readministration, a history of thrombocytopenia associated with prior use of Abciximab was predictive of an increased risk of recurrent thrombocytopenia (see ADVERSE REACTIONS: Thrombocytopenia). Readministration within 30 days was associated with an increased incidence and severity of thrombocytopenia, as was a positive human anti-chimeric antibody (HACA) test at baseline, compared to the rates seen in studies with first administration.


Restoration of Platelet Function- In the event of serious uncontrolled bleeding or the need for emergency surgery, Abciximab should be discontinued. If platelet function does not return to normal, it may be restored, at least in part, with platelet transfusions.



--------------------------------------------------
Laboratory Tests
--------------------------------------------------

-Before infusion of Abciximab, prothrombin time, ACT, APTT, and platelet count should be measured to identify pre-existing hemostatic abnormalities.

-Based on an integrated analysis of data from all studies, the following guidelines may be utilized to minimize the risk for bleeding:

-When Abciximab is initiated 18 to 24 hours before PCI, the APTT should be maintained between 60 and 85 seconds during the Abciximab and heparin infusion period.

-During PCI the ACT should be maintained between 200 and 300 seconds.

-If anticoagulation is continued in these patients following PCI, the APTT should be maintained between 55 and 75 seconds.

-The APTT or ACT should be checked prior to arterial sheath removal. The sheath should not be removed unless APTT </= 50 seconds or ACT </= 175 seconds.

-Platelet counts should be monitored prior to treatment, two to four hours following the bolus dose of Abciximab and at 24 hours or prior to discharge, whichever is first. If a patient experiences an acute platelet decrease (e.g., a platelet decrease to less than 100,000 cells/uL and a decrease of at least 25% from pre-treatment value), additional platelet counts should be determined. Platelet monitoring should continue until platelet counts return to normal.

-To exclude pseudothrombocytopenia, a laboratory artifact due to in vitro anticoagulant interaction, blood samples should be drawn in three separate tubes containing ethylenediaminetetraacetic acid (EDTA), citrate and heparin, respectively. A low platelet count in EDTA but not in heparin and/or citrate is supportive of a diagnosis of pseudothrombocytopenia.




Readministration- Administration of Abciximab may result in the formation of HACA that could potentially cause allergic or hypersensitivity reactions (including anaphylaxis), thrombocytopenia or diminished benefit upon readministration of Abciximab - Package Insert: (see WARNINGS: Allergic Reactions; see ADVERSE REACTIONS: Immunogenicity).

Readministration of Abciximab to patients undergoing PCI was assessed in a registry that included 1342 treatments in 1286 patients. Most patients were receiving their second Abciximab exposure; 15% were receiving the third or subsequent exposure. The overall rate of HACA positivity prior to the readministration was 6% and increased to 27% post-readministration. There were no reports of serious allergic reactions or anaphylaxis (see WARNINGS: Allergic Reactions). Thrombocytopenia was observed at higher rates in the readministration study than in the phase 3 studies of first-time administration - Package Insert: (see PRECAUTIONS: Thrombocytopenia and ADVERSE REACTIONS: Thrombocytopenia), suggesting that readministration may be associated with an increased incidence and severity of thrombocytopenia.


Drug Interactions- Formal drug interaction studies with Abciximab have not been conducted. Abciximab has been administered to patients with ischemic heart disease treated concomitantly with a broad range of medications used in the treatment of angina, myocardial infarction and hypertension. These medications have included heparin, warfarin, beta-adrenergic receptor blockers, calcium channel antagonists, angiotensin converting enzyme inhibitors, intravenous and oral nitrates, ticlopidine, and aspirin. Heparin, other anticoagulants, thrombolytics, and antiplatelet agents are associated with an increase in bleeding. Patients with HACA titers may have allergic or hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.


Carcinogenesis, Mutagenesis and Impairment of Fertility-In vitro and in vivo mutagenicity studies have not demonstrated any mutagenic effect. Long-term studies in animals have not been performed to evaluate the carcinogenic potential or effects on fertility in male or female animals.


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


Nursing Mothers- It is not known whether this drug is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, caution should be exercised when Abciximab is administered to a nursing woman.


Pediatric Use- Safety and effectiveness in pediatric patients have not been studied.


Geriatric Use- Of the total number of 7860 patients in the four Phase 3 trials, 2933 (37%) were 65 and over, while 653 (8%) were 75 and over. No overall differences in safety or efficacy were observed between patients of age 65 to less than 75 as compared to younger patients. The clinical experience is not adequate to determine whether patients of age 75 or greater respond differently than younger patients.


DOSAGE AND ADMINISTRATION:    [Top]
The safety and efficacy of Abciximab have only been investigated with concomitant administration of heparin and aspirin as described in CLINICAL STUDIES (See package insert).

In patients with failed PCIs, the continuous infusion of Abciximab should be stopped because there is no evidence for Abciximab efficacy in that setting.

In the event of serious bleeding that cannot be controlled by compression, Abciximab and heparin should be discontinued immediately.

The recommended dosage of Abciximab in adults is a 0.25 mg/kg intravenous bolus administered 10-60 minutes before the start of PCI, followed by a continuous intravenous infusion of 0.125 µg/kg/min (to a maximum of 10 µg/min) for 12 hours.

Patients with unstable angina not responding to conventional medical therapy and who are planned to undergo PCI within 24 hours may be treated with an Abciximab 0.25 mg/kg intravenous bolus followed by an 18- to 24-hour intravenous infusion of 10 µg/min, concluding one hour after the PCI.


Instructions for Administration
  1. Parenteral drug products should be inspected visually for particulate matter prior to administration. Preparations of Abciximab containing visibly opaque particles should NOT be used.
  2. Hypersensitivity reactions should be anticipated whenever protein solutions such as Abciximab are administered. Epinephrine, dopamine, theophylline, antihistamines and corticosteroids should be available for immediate use. If symptoms of an allergic reaction or anaphylaxis appear, the infusion should be stopped and appropriate treatment given see WARNINGS: Allergic Reactions).
  3. As with all parenteral drug products, aseptic procedures should be used during the administration of Abciximab.
  4. Withdraw the necessary amount of Abciximab for bolus injection into a syringe. Filter the bolus injection using a sterile, non-pyrogenic, low protein-binding 0.2 or 5 µm syringe filter (Millipore SLGV025LS or SLSV025LS or equivalent).
  5. Withdraw the necessary amount of Abciximab for the continuous infusion into a syringe. Inject into an appropriate container of sterile 0.9% saline or 5% dextrose and infuse at the calculated rate via a continuous infusion pump. The continuous infusion should be filtered either upon admixture using a sterile, non-pyrogenic, low protein-binding 0.2 or 5 µm syringe filter (Millipore SLGV025LS or SLSV025LS or equivalent) or upon administration using an in-line, sterile, non-pyrogenic, low protein-binding 0.2 or 0.22 µm filter (Abbott #4524 or equivalent). Discard the unused portion at the end of the infusion.
  6. No incompatibilities have been shown with intravenous infusion fluids or commonly used cardiovascular drugs. Nevertheless, Abciximab should be administered in a separate intravenous line whenever possible and not mixed with other medications.
  7. No incompatibilities have been observed with glass bottles or polyvinyl chloride bags and administration sets.


HOW SUPPLIED:
Abciximab (ReoPro®) 2 mg/mL is supplied in 5 mL vials containing 10 mg (NDC 0002-7140-01).

Vials should be stored at 2 to 8 °C (36 to 46 °F). Do not freeze. Do not shake. Do not use beyond the expiration date. Discard any unused portion left in the vial.

Manufactured by:
Centocor B.V.
Leiden, The Netherlands
U.S. License Number: 1178

Distributed by:
Eli Lilly and Company
Indianapolis, IN 46285
Revision Date: November 16, 2005

Source: Package Insert
Disclaimer
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.
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