Heparin Sodium Dailymed

1 Indications And Usage

Heparin Sodium Injection is indicated for:

• •Prophylaxis and treatment of venous thrombosis and pulmonary embolism;
• •Prevention of postoperative deep venous thrombosis and pulmonary embolism in patients undergoing major abdominothoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease;
• •Atrial fibrillation with embolization;
• •Treatment of acute and chronic consumptive 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.

HEPARIN SODIUM INJECTION is an anticoagulant indicated for (1)

• •Prophylaxis and treatment of venous thrombosis and pulmonary embolism
• •Prevention of postoperative deep venous thrombosis and pulmonary embolism in patients undergoing major abdominothoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease
• •Atrial fibrillation with embolization
• •Treatment of acute and chronic consumptive coagulopathies (disseminated intravascular coagulation)
• •Prevention of clotting in arterial and cardiac surgery
• •Prophylaxis and treatment of peripheral arterial embolism
• •Use as an anticoagulant in blood transfusions, extracorporeal circulation, and dialysis procedures

2 Dosage And Administration

Recommended Adult Dosages:

• •Therapeutic Anticoagulant Effect with Full-Dose Heparin^† (2.4)

Deep Subcutaneous (Intrafat) Injection Use a different site for each injection	Initial Dose	5,000 units by intravenous injection, followed by 10,000 to 20,000 units of a concentrated solution, subcutaneously
	Every 8 hoursor Every 12 hours	8,000 to 10,000 units of a concentrated solution 15,000 to 20,000 units of a concentrated solution
Intermittent Intravenous Injection	Initial dose	10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP
	Every 4 to 6 hours	5,000 to 10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP
Intravenous Infusion	Initial dose	5,000 units by intravenous injection
	Continuous	20,000 to 40,000 units/24 hours in 1000 mL of 0.9% Sodium Chloride Injection, USP (or in any compatible solution) for infusion
† Based on 150 lb (68 kg) patient. Adjust dose based on laboratory monitoring.

2.1 Preparation for Administration

Confirm the choice of the correct Heparin Sodium Injection vial to ensure that the 1 mL vial is not confused with a “catheter lock flush” vial or other 1 mL vial of incorrect strength [see Warnings and Precautions (5.1) ]. Confirm the selection of the correct formulation and strength prior to administration of the drug.

To lessen this risk, the 1 mL vial includes a red cautionary label that extends above the main label. Read the cautionary statement and confirm that you have selected the correct medication and strength. Then locate the “Tear Here” point on the label, and remove this red cautionary label prior to removing the flip-off cap.

When heparin is added to an infusion solution for continuous intravenous administration, invert the container repeatedly to ensure adequate mixing and prevent pooling of the heparin in the solution.

Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and the seal is intact. Do not use if solution is discolored or contains a precipitate.

Administer Heparin Sodium Injection  by intermittent intravenous injection, intravenous infusion, or deep subcutaneous (intrafat, i.e., above the iliac crest or abdominal fat layer) injection. Do not administer Heparin Sodium Injection by intramuscular injection because of the risk of hematoma at the injection site [see Adverse Reactions (6) ].

2.2 Instructions for Use of Prefilled Syringe

CAUTION: Certain glass syringes may malfunction, break or clog when connected to some Needleless Luer Access Devices (NLADs) and needles. This syringe has a larger internal syringe tip and an external collar (luer collar). The external collar must remain attached to the syringe. Data show that the syringe achieves acceptable connections with the BD Eclipse™ Needle and the Terumo SurGuard2™ Safety Needle and with the following non-center post NLADs: Alaris SMARTSITE™, B-Braun ULTRASITE™, BD-Q SYTE™, Maximum MAX PLUS™, and B-Braun SAFSITE™. The data also show acceptable connections are achieved to the center post ICU Medical CLAVE™. However, spontaneous disconnection of this glass syringe from needles and NLADs with leakage of drug product may occur. Assure that the needle or NLAD is securely attached before beginning the injection. Visually inspect the glass syringe-needle or glass syringe-NLAD connection before and during drug administration. Refer to Figure 1 for syringe diagram.

Figure 1

 

  

 

1. Inspect the outer packaging (plastic tube) by verifying:

- plastic tube integrity

- drug name

- drug strength

- dose volume

- route of administration

- expiration date to be sure that the drug has not expired

- sterile field applicability

Do not use if package has been damaged.

2. Remove the plastic tube cap of the outer packaging to access the syringe.

3. Remove the syringe from the plastic tube.

4. Perform visual inspection on the syringe by verifying:

- absence of syringe damage

- absence of external particles

- absence of internal particles

- proper drug color

- expiration date to be sure that the drug has not expired

- drug name

- drug strength

- dose volume

- route of administration

- sterile field applicability

5. Push plunger rod slightly to break the stopper loose while tip cap is still on.

6. Remove tip cap by twisting it off. (See Figure 2)

Figure 2

 

 

7. Discard the tip cap.

8. Expel air bubble.

9. Adjust  dose by expelling extra volume (where applicable) from the syringe into sterile material prior to administration.

10. Connect the syringe to appropriate injection connection depending on route of administration. Before injection, ensure that the syringe is securely attached to the needle or needleless luer access device (NLAD).

11. Depress plunger rod to deliver medication. Ensure that pressure is maintained on the plunger rod during the entire administration.

12. Remove syringe from NLAD (if applicable) and discard into appropriate receptacle. To prevent needle-stick injuries, needles should not be recapped.

NOTES:

- All steps must be done sequentially

- Do not autoclave syringe

- Do not use this product on a sterile field

- Do not introduce any other fluid into the syringe at any time

- This product is for single dose only; discard unused portion

2.3 Laboratory Monitoring for Efficacy and Safety

Adjust the dosage of Heparin Sodium Injection according to the patient’s coagulation test results. Dosage is considered adequate when the activated partial thromboplastin time (aPTT) is 1.5 to 2 times normal or when the whole blood clotting time is elevated approximately 2.5 to 3 times the control value. When initiating treatment with Heparin Sodium Injection by continuous intravenous infusion, determine the coagulation status (aPTT, INR, platelet count) at baseline and continue to follow aPTT approximately every 4 hours and then at appropriate intervals thereafter.  When the drug is administered intermittently by intravenous injection, perform coagulation tests before each injection during the initiation of treatment and at appropriate intervals thereafter. After deep subcutaneous (intrafat) injections, tests for adequacy of dosage are best performed on samples drawn 4 to 6 hours after the injection.

Periodic platelet counts and hematocrits are recommended during the entire course of heparin therapy, regardless of the route of administration.

2.4 Therapeutic Anticoagulant Effect with Full-Dose Heparin

The dosing recommendations in Table 1 are based on clinical experience.  Although dosages 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

METHOD OFADMINISTRATION	FREQUENCY	RECOMMENDED DOSE[based on 150 lb (68 kg) patient]
Deep Subcutaneous (Intrafat) Injection	Initial dose	5,000 units by intravenous injection, followed by 10,000 to 20,000 units of a concentrated solution, subcutaneously
A different site should be used for each injection to prevent the development of massive hematoma	Every 8 hoursor	8,000 to 10,000 units of a concentrated solution
	Every 12 hours	15,000 to 20,000 units of a concentrated solution
Intermittent Intravenous Injection	Initial dose	10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP
	Every 4 to 6 hours	5,000 to 10,000 units, either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection, USP
Intravenous Infusion	Initial dose	5,000 units by intravenous injection
	Continuous	20,000 to 40,000 units/24 hours in 1000 mL of 0.9% Sodium Chloride Injection, USP (or in any compatible solution) for infusion

2.5 Pediatric Use

Do not use benzyl alcohol-preserved drugs in neonates and infants. Use preservative-free Heparin Sodium Injection in neonates and infants [see Warnings and Precautions (5.4) ].

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:

Initial Dose	75 to 100 units/kg (Intravenous bolus over 10 minutes)
Maintenance Dose	Infants: 25 to 30 units/kg/hour;    Infants < 2 months have the highest requirements (average 28 units/kg/hour) Children > 1 year of age: 18 to 20 units/kg/hour;    Older children may require less heparin, similar to weight-adjusted adult dosage
Monitoring	Adjust heparin to maintain APTT of 60 to 85 seconds, assuming this reflects an anti-Factor Xa level of 0.35 to 0.70

2.6 Cardiovascular Surgery

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.

2.7 Low-Dose Prophylaxis of Postoperative Thromboembolism

The most widely used dosage has been 5,000 units 2 hours before surgery and 5,000 units every 8 to 12 hours thereafter for 7 days or until the patient is fully ambulatory, whichever is longer. Administer the heparin by deep subcutaneous (intrafat, i.e., above the iliac crest or abdominal fat layer, arm, or thigh) injection with a fine (25- to 26-gauge) needle to minimize tissue trauma.

2.8 Blood Transfusion

Add 450 USP units to 600 USP units of heparin sodium per 100 mL of whole blood to prevent coagulation. Usually, 7,500 USP units of heparin sodium are added to 100 mL of 0.9% Sodium Chloride Injection, USP (or 75,000 USP units per 1000 mL of 0.9% Sodium Chloride Injection, USP) and mixed; from this sterile solution, 6 mL to 8 mL are added per 100 mL of whole blood.

2.9 Converting to Warfarin

To ensure continuous anticoagulation when converting from Heparin Sodium Injection 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)].

2.10 Converting to Oral Anticoagulants other than Warfarin

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.

2.11 Extracorporeal Dialysis

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

3 Dosage Forms And Strengths

Heparin Sodium Injection, USP preserved with benzyl alcohol is available as follows:

• •1,000 USP units/mL single-dose vials
• •5,000 USP units/mL single-dose vials
• •10,000 USP units/mL single-dose vials
• •30,000 USP units per 30 mL (1,000 USP units/mL) multiple-dose vials
• •50,000 USP units per 10 mL (5,000 USP units/mL) multiple-dose vials

Heparin Sodium Injection, USP preservative-free is available as follows:

• •5,000 USP units/mL single-dose prefilled syringes
• •5,000 USP units/0.5 mL single-dose prefilled syringes

Injection (preserved with Benzyl Alcohol)

Single-dose Vials

• •1,000 USP units per mL
• •5,000 USP units per mL
• •10,000 USP units per mL

Multiple-dose Vials

• •30,000 USP units per 30 mL (1,000 USP units per mL)
• •50,000 USP units per 10 mL (5,000 USP units per mL)

Injection (Preservative-Free)

Single-dose Prefilled Syringes 

• •5,000 USP units per mL
• •5,000 USP units per 0.5 mL

The following clinically significant adverse reactions are described elsewhere in the labeling:

• •Hemorrhage [see Warnings and Precautions (5.2) ]
• •Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis [see Warnings and Precautions (5.3) ]
• •Risk of Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative [see Warnings and Precautions (5.4) ]
• •Thrombocytopenia [see Warnings and Precautions (5.5) ]
• •Heparin Resistance [see Warnings and Precautions (5.7) ]
• •Hypersensitivity [see Warnings and Precautions (5.8) ]

Most common adverse reactions are hemorrhage, thrombocytopenia, HIT and HITTS, injection site irritation, general hypersensitivity reactions, and elevations of aminotransferase levels. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Heparin Sodium Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• •Hemorrhage is the chief complication that may result from heparin therapy [see Warnings and Precautions (5.2) ]. Gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding can occur at any site but certain specific hemorrhagic complications may be difficult to detect:
  • •Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred with heparin therapy, including fatal cases.
  • •Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term heparin therapy.
  • •Retroperitoneal hemorrhage
• •HIT and HITT, including delayed onset cases [see Warnings and Precautions (5.3) ].
• •Local Irritation – Local irritation, erythema, mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat) injection of heparin sodium. Because these complications are much more common after intramuscular use, the intramuscular route is not recommended.
• •Histamine-like reactions – Such reactions have been observed at the site of injections. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin, occasionally requiring skin grafting [see Warnings and Precautions (5.3) ].
• •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 less frequently. Itching and burning, especially on the plantar side of the feet, may occur [see Warnings and Precautions (5.8) ].
• •Elevations of aminotransferases – Significant elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have occurred in patients who have received heparin.
• •Miscellaneous - Osteoporosis following long-term administration of high doses of heparin, cutaneous necrosis after systemic administration, suppression of aldosterone synthesis, delayed transient alopecia, priapism, and rebound hyperlipemia on discontinuation of heparin sodium have also been reported.