Heparin is a heterogeneous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans, having anticoagulant properties. Although others may be present, the main sugars occurring in heparin are: (1) α-L-iduronic acid 2-sulfate, (2) 2-deoxy-2-sulfamino-α-D-glucose 6-sulfate, (3) β-D-glucuronic acid, (4) 2-acetamido-2-deoxy-α-D-glucose and (5) α-L-iduronic acid. These sugars are present in decreasing amounts, usually in the order (2) > (1) > (4) > (3) > (5), and are joined by glycosidic linkages, forming polymers of varying sizes. Heparin is strongly acidic because of its content of covalently linked sulfate and carboxylic acid groups. In heparin sodium, the acidic protons of the sulfate units are partially replaced by sodium ions.

Structural formula of Heparin Sodium (representative sub-units):

HEP-LOCK U/P (Preservative-Free Heparin Lock Flush Solution, USP) is a sterile solution for intravenous flush only. It is not to be used for anticoagulant therapy. HEP-LOCK U/P is specially formulated for use in situations where the use of preservatives is not advisable. Each mL contains heparin sodium 10 or 100 USP units, derived from porcine intestines and standardized for use as an anticoagulant, sodium chloride 8 mg, monobasic sodium phosphate monohydrate 2.3 mg, and dibasic sodium phosphate anhydrous 0.5 mg in Water for Injection. pH 5.0-7.5. The potency is determined by biological assay using a USP reference standard based on units of heparin activity per milligram.

Last updated on RxList: 1/26/2009

HEP-LOCK U/P (Preservative-Free Heparin Lock Flush Solution, USP) is intended to maintain patency of an indwelling venipuncture device designed for intermittent injection or infusion therapy or blood sampling. Heparin Lock Flush Solution may be used following initial placement of the device in the vein, after each injection of a medication or after withdrawal of blood for laboratory tests. (See DOSAGE AND ADMINISTRATION, Maintenance of Patency of Intravenous Devices for directions for use.)

HEP-LOCK U/P is not to be used for anticoagulant therapy.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Slight discoloration does not alter potency.

Preservative-Free Heparin Lock Flush Solution in the 100 unit/mL concentration is not recommended for use in neonates and infants (see WARNINGS, Use In Neonates and Infants).

Maintenance of Patency of Intravenous Devices

To prevent clot formation in a heparin lock set or central venous catheter following its proper insertion, Preservative-Free Heparin Lock Flush Solution, USP is injected via the injection hub in a quantity sufficient to fill the entire device. This solution should be replaced each time the device is used. Aspirate before administering any solution via the device in order to confirm patency and location of needle or catheter tip. If the drug to be administered is incompatible with heparin, the entire device should be flushed with normal saline before and after the medication is administered; following the second saline flush, Preservative-Free Heparin Lock Flush Solution, USP may be reinstilled into the device. The device manufacturer's instructions should be consulted for specifics concerning its use. Usually this dilute heparin solution will maintain anticoagulation within the device for up to 4 hours.

NOTE: Since repeated injections of small doses of heparin can alter tests for activated partial thromboplastin time (APTT), a baseline value for APTT should be obtained prior to insertion of an intravenous device.

Withdrawal of Blood Samples

Preservative-Free Heparin Lock Flush Solution, USP may also be used after each withdrawal of blood for laboratory tests. When heparin would interfere with or alter the results of blood tests, the heparin solution should be cleared from the device by aspirating and discarding it before withdrawing the blood sample.

HEP-LOCK U/P (Preservative-Free Heparin Lock Flush Solution, USP)

10 USP units/mL

1 mL DOSETTE vials packaged in 25s (NDC 0641-0272-25)

100 USP units/mL

1 mL DOSETTE vials packaged in 25s (NDC 0641-0273-25)

Storage

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

REFERENCES

7. Tahata T, Shigehito M, Kusuhara K, Ueda Y, et al. Delayed-Onset of Heparin Induced Thrombocytopenia – A Case Report – J Jpn Assn Torca Surg.1992;40(3):110-111.

8. Warkentin T, Kelton J. Delayed-Onset Heparin-Induced Thrombocytopenia and Thrombosis. Annals of Internal Medicine. 2001;135:502-506.

9. Rice L, Attisha W, Drexler A, Francis J. Delayed-Onset Heparin Induced Thrombocytopenia. Annals of Internal Medicine, 2002;136:210-215.

10. Dieck J., C. Rizo-Patron, et al. (1990). “A New Manifestation and Treatment Alternative for Heparin-Induced Thrombosis.” Chest 98(1524-26).

11. Smythe M, Stephens J, Mattson. Delayed-Onset Heparin Induced Thrombocytopenia. Annals of Emergency Medicine, 2005;45(4):417-419.

12. Divgi A. (Reprint), Thumma S., Hari P., Friedman K., Delayed Onset Heparin-Induced Thrombocytopenia (HIT) Presenting After Undocumented Drug Exposure as Post-Angiography Pulmonary Embolism. Blood. 2003;102(11):127b.

ESI logo, Hep-Lock and Dosette are registered trademarks of Baxter International, Inc., or its subsidiaries.

Manufactured by : Baxter Healthcare Corporation, Deerfield, IL 60015 USA. For Product Inquiry 1 800 ANA DRUG (1-800-262-3784). FDA revision date: 10/4/2006

Last updated on RxList: 1/26/2009

Hemorrhage

Hemorrhage is the chief complication that may result from heparin use (see WARNINGS, Hemorrhage). An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug (see OVERDOSAGE).

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT) and Delayed Onset of HIT and HITT

See WARNINGS.

Local Irritation

Local irritation and erythema have been reported with the use of Heparin Lock Flush Solution.

Hypersensitivity

Generalized hypersensitivity reactions have been reported, with chills, fever and urticaria as the most usual manifestations, and asthma, rhinitis, lacrimation, headache, nausea and vomiting, and anaphylactoid reactions, including shock, occurring more rarely. Itching and burning, especially on the plantar side of the feet, may occur.

Thrombocytopenia has been reported to occur in patients receiving heparin, with a reported incidence of 0 to 30%. While often mild and of no obvious clinical significance, such thrombocytopenia can be accompanied by severe thromboembolic complications such as skin necrosis, gangrene of the extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke, and possibly death. (See WARNINGS and PRECAUTIONS.)

Certain episodes of painful, ischemic and cyanosed limbs have in the past been attributed to allergic vasospastic reactions. Whether these are in fact identical to the thrombocytopenia-associated complications remains to be determined.

Platelet Inhibitors

Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole, hydroxychloroquine 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.

Other Interactions

Digitalis, tetracyclines, nicotine or antihistamines may partially counteract the anticoagulant action of heparin sodium.

Last updated on RxList: 1/26/2009

Heparin is not intended for intramuscular use.

Hypersensitivity

Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations. (See ADVERSE REACTIONS, Hypersensitivity.)

Hemorrhage

Hemorrhage can occur at virtually any site in patients receiving heparin. An unexplained fall in hematocrit, fall in blood pressure or any other unexplained symptom should lead to serious consideration of a hemorrhagic event.

Heparin sodium should be used with extreme caution in infants and in patients with disease states in which there is increased danger of hemorrhage. Some of the conditions in which increased danger of hemorrhage exists are:

Cardiovascular

Subacute bacterial endocarditis, severe hypertension.

Surgical

During and immediately following (a) spinal tap or spinal anesthesia or (b) major surgery, especially involving the brain, spinal cord or eye.

Hematologic

Conditions associated with increased bleeding tendencies, such as hemophilia, thrombocytopenia and some vascular purpuras.

Gastrointestinal

Ulcerative lesions and continuous tube drainage of the stomach or small intestine.

Other

Menstruation, liver disease with impaired hemostasis.

Thrombocytopenia

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of 0 to 30%. Platelet counts should be obtained at baseline and periodically during heparin administration. Mild thrombocytopenia (count greater than 100,000/mm³) may remain stable or reverse even if heparin is continued. However, thrombocytopenia of any degree should be monitored closely. If the count falls below 100,000/mm³ or if recurrent thrombosis develops (see Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis), the heparin product should be discontinued and, if necessary, an alternative anticoagulant administered.

Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT)

Heparin-induced Thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as Heparin-induced Thrombocytopenia and Thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT. These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm³or if recurrent thrombosis develops, the heparin product should be promptly discontinued and alternative anticoagulants considered if patients require continued anticoagulation.

Delayed Onset of HIT and HITT

Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis 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 and HITT.

Use in Neonates and Infants

The 100 unit/mL concentration should not be used in neonates or in infants who weigh less than 10 kg because of the risk of systemic anticoagulation. Caution is necessary when using the 10 unit/mL concentration in premature infants who weigh less than 1 kg who are receiving frequent flushes since a therapeutic heparin dose may be given to the infant in a 24-hour period.

General

Precautions must be exercised when drugs that are incompatible with heparin are administered through an indwelling intravenous catheter containing Preservative-Free Heparin Lock Flush Solution. (See DOSAGE AND ADMINISTRATION, Maintenance of Patency of Intravenous Devices.) The concentration of phosphorus in the heparin solution is 0.63 mg/mL.

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT)

See WARNINGS.

Increased Risk to Older Patients, Especially Women

A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age.

Laboratory Tests

Periodic platelet counts, hematocrits and tests for occult blood in stool are recommended during the entire course of heparin use (see DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of heparin sodium. Also, no reproduction studies in animals have been performed concerning mutagenesis or impairment of fertility.

Pregnancy

Teratogenic Effects—Pregnancy Category C

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

Nonteratogenic Effects

Heparin does not cross the placental barrier.

Nursing Mothers

Heparin is not excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established (see WARNINGS, Use in Neonates and Infants).

Geriatric Use

A higher incidence of bleeding has been reported in patients over 60 years of age, especially women (see CLINICAL PHARMACOLOGY and PRECAUTIONS, General).

Last updated on RxList: 1/26/2009

Symptoms

Bleeding is the chief sign of heparin overdosage. Nosebleeds, blood in urine or tarry stools may be noted as the first sign of bleeding. Easy bruising or petechial formations may precede frank bleeding.

Treatment - 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 1/2 hour after intravenous injection.

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

For additional information consult the labeling of Protamine Sulfate Injection, USP products.

Heparin sodium should NOT be used in patients with the following conditions: severe thrombocytopenia; an uncontrollable active bleeding state (see WARNINGS), except when this is due to disseminated intravascular coagulation.

Last updated on RxList: 1/26/2009

Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.

Bleeding time is usually unaffected by heparin. Clotting time is prolonged by full therapeutic doses of heparin; in most cases, it is not measurably affected by low doses of heparin. Loglinear plots of heparin plasma concentrations with time, for a wide range of dose levels, are linear, which suggests the absence of zero order processes. Liver and the reticulo-endothelial system are the sites of biotransformation. The biphasic elimination curve, a rapidly declining alpha phase (t1/2 = 10 min), and after the age of 40 a slower beta phase, indicates uptake in organs. The absence of a relationship between anticoagulant half-life and concentration half-life may reflect factors such as protein binding of heparin.

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.

Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots.

Last updated on RxList: 1/26/2009

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 1/26/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

HEPARIN LOCK FLUSH-INJECTION

(HEP-uh-rin)

COMMON BRAND NAME(S): Hep-Lock

USES: This medication is used to keep IV catheters open and flowing freely. Heparin helps to keep blood flowing smoothly and from clotting in the catheter by making a certain natural substance in your body (anti-clotting protein) work better. It is known as an anticoagulant.

This form of heparin must not be used to treat or prevent blood clots in the body.

Some products should not be used in newborns due to increased risk of side effects. Check with your doctor or pharmacist for more details.

HOW TO USE: This medication is given by injection into the IV catheter by a health care professional. Learn all preparation and usage instructions for this product. Before using this product, check it visually for particles or discoloration. If either is present, do not use the liquid. If you have questions about the use of this medication, consult the doctor or pharmacist.

Do not inject this medication into the body.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same times each day.

SIDE EFFECTS: Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Although very unlikely, this medication can cause bleeding if it has too much effect on your blood. Tell your doctor immediately if you develop any signs of serious bleeding, including unusual pain/swelling/discomfort, prolonged bleeding from cuts or gums, persistent nosebleeds, unusually heavy/prolonged menstrual periods, unusual/easy bruising, dark urine, black stools, severe headache, unusual dizziness. (see also Precautions section regarding HIT)

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using heparin, tell your doctor or pharmacist if you are allergic to it; or to pork products; or if you have any other allergies.

This medication should not be used if you have a certain medical condition. Before using this medicine, consult your doctor or pharmacist if you have: uncontrollable bleeding.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: severe high blood pressure (hypertension), infection of the heart, recent surgery/procedure, bleeding/clotting disorders (e.g., hemophilia, antithrombin III deficiency, thrombocytopenia), stomach/intestinal ulcers or tube drainage, liver disease, kidney disease, current/recent bleeding (e.g., from wounds, menstrual period).

Some patients can have a certain bad reaction to heparin (Heparin-Induced Thrombocytopenia-HIT). This can occur during treatment and up to several weeks after treatment with heparin has stopped. See Side Effects section for symptoms to watch for and what to do if they occur.

Adults over 60 years of age, especially women, may be at greater risk for bleeding while using this drug.

Newborns and infants may be at greater risk for bleeding while using this drug. In addition, a preservative (benzyl alcohol) that might be found in this product can infrequently cause serious (sometimes fatal) problems if given in large amounts (more than 100 milligrams per kilogram daily) to an infant during the first months of life. The risk is greater with low-birth-weight infants. Symptoms include sudden gasping, low blood pressure, very slow heartbeat. If you notice any of these symptoms in your newborn, report them to the doctor immediately. If possible, a preservative-free product should be used when treating newborns.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication does not pass into breast milk. However, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other drugs that can cause bleeding/bruising (e.g., anticoagulants such as warfarin, antiplatelet drugs including NSAIDS such as ketorolac), mifepristone.

Check all prescription and nonprescription medicine labels carefully because many contain pain relievers/fever reducers (NSAIDs such as ibuprofen, naproxen, or aspirin) that can increase the risk of bleeding when used with heparin. Low-dose aspirin should be continued if it has been prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day). Consult your doctor or pharmacist for more details.

Flush the catheter/line with normal saline before and after infusing drugs that interact with heparin such as doxorubicin, droperidol, ciprofloxacin, and mitoxantrone.

This medication may interfere with certain laboratory tests (including prothrombin time), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: easy/unusual bruising, bleeding such as persistent nosebleeds, blood in urine, black stools.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: This medication must be stored properly. Review storage instructions with the pharmacist. Check the expiration date before using. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.