Substance P (1-7) heptapeptide

What Is Heparin?

Heparin (heparin sodium injectable) is a heterogeneous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans that have anticoagulant properties used to help prevent clot formation (for example, venous thrombosis, pulmonary embolisms, coagulopathies and coronary artery clots). Heparin is available as generic heparin and under other generic brand names.

What Are Side Effects of Heparin?

Common side effects of Heparin are:

• easy bleeding and bruising;
• pain, redness, warmth, irritation, or skin changes where the medicine was injected;
• itching of your feet; or
• bluish-colored skin.

Heparin may cause serious side effects including:

• skin warmth or discoloration,
• chest pain,
• irregular heartbeats,
• shortness of breath,
• dizziness,
• anxiety,
• sweating,
• unusual bleeding or bruising,
• severe pain or swelling in your stomach, lower back or growing,
• dark or blue-colored skin on your hands or feet,
• nausea,
• vomiting,
• loss of appetite,
• unusual tiredness,
• bleeding that will not stop,
• nosebleed,
• blood in the urine or stool,
• black or tarry stools,
• coughing up blood or vomit that looks like coffee grounds,
• skin changes where the medication was injected,
• fever,
• chills,
• runny nose,
• watery eyes,
• easy bruising,
• purple or red spots under your skin,
• sudden numbness or weakness,
• problems with vision or speech,
• swelling or redness in an arm or leg
• Thrombocytopenia
• heparin-induced thrombocytopenia (HIT),and
• heparin-induced thrombocytopenia and thrombosis (HITT)

Get medical help right away, if you have any of the symptoms listed above.

Seek medical care or call 911 at once if you have the following serious side effects:

• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Heparin

• Heparin is available in vials at strengths of 1000, 5000, 10,000 and 20,000 units per ml.
• Dosage depends on the coagulation problem; many initial doses start with 5000 units IV, but this can change depending on the problem; guidelines for dosages are available.
• If benzyl alcohol is listed as a preservative for the Heparin preparation, do not use in neonates and infants or nursing mothers.
• If preparations without benzyl alcohol are used in pediatric patients, the initial dose is usually 50 units per Kg but a pediatric specialist should be consulted.

What Drugs, Substances, or Supplements Interact with Heparin?

Heparin may interact with aspirin or other NSAIDs (nonsteroidal anti-inflammatory drugs), other blood thinners, digoxin, dipyridamole, hydroxychloroquine, indomethacin, nicotine (cigarettes, gum, lozenges, or skin patches), nitroglycerin, antibiotics, and cold, allergy, or sleep medications. Tell your doctor all medications and supplements you use.

Heparin During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant while using Heparin. It is unknown if heparin will harm a fetus. Consult your doctor before breastfeeding.

Additional Information

Our Heparin Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Description for Heparin

Heparin Sodium Injection, USP is a sterile, nonpyrogenic solution of heparin sodium (derived from porcine intestinal mucosa) in water for injection. Each container contains 10000, 12500, 20000 or 25,000 USP Heparin Units; 40 or 80 mg sodium chloride added to render isotonic (see HOW SUPPLIED section for various sizes and strength). May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. pH 6.0 (5.0 to 7.5).

The solution contains no bacteriostat, antimicrobial agent or added buffer and is intended for use only as a single-dose injection. When smaller doses are required, the unused portion should be discarded.

Heparin sodium in the ADD-Vantage™ system is intended for intravenous administration only after dilution.

Heparin Sodium, USP is a heterogenous group of straight-chain anionic mucopolysaccharides, called glycosamino-glycans 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. The potency is determined by a biological assay using a USP reference standard based on units of heparin activity per milligram.

Structure of Heparin Sodium (representative subunits):

Uses for Heparin

Heparin sodium is indicated for:

• Prophylaxis and treatment of venous thromboembolism and pulmonary embolism;
• 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.

Dosage for Heparin

Preparation For Administration

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

Instructions for Use for the freeflex® Bag

Leave bag in the overwrap until time of use.

The intact port cap provides visual tamper evidence. Do not use if port cap is prematurely removed.

Maintain strict aseptic technique during handling.

To Open

• Always inspect the bag before and after removal from the overwrap.
• Place the bag on a clean, flat surface. Starting in the bottom corner, peel the overwrap open and remove the bag.
• Check the bag for leaks by squeezing firmly. If leaks are found, discard the bag.
• Do not use if the solution is cloudy or a precipitate is present.

To Prepare For Administration

• Immediately before connecting the infusion set, firmly grasp the BLUE infusion port cap with the arrow pointing away from the bag between index finger and thumb. Gently break off the port cap. The membrane of the infusion port is sterile, and disinfection before initial use is not necessary if proper aseptic handling technique is followed.
• Use a non-vented infusion set or close the air-inlet on a vented set. The BLUE infusion port is compatible with spike systems produced according to ISO 8536-4, with an external spike diameter of 5.5 to 5.7 mm.
• Close the roller clamp of the infusion set.
• Hold the base of the BLUE infusion port and insert the spike by rotating your wrist slightly until the spike is fully inserted.
• The port membrane contains a self-sealing septum that helps prevent leakage after removing the spike. The infusion port is not intended to be spiked more than once.
• Hang from the hole at the top of the bag.
• For Single Use Only. Discard unused portion.

Do not admix with other drugs.

Do not use flexible container in series connections.

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

Laboratory Monitoring For Efficacy and Safety

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.

Therapeutic Anticoagulant Effect With Full-Dose Heparin

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

* Based on 150 lb. (68 kg) patient.

Pediatric Use

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.

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.

Converting To Warfarin

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].

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.

Extracorporeal Dialysis

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

HOW SUPPLIED

Dosage Forms And Strengths

Heparin Sodium In 0.45% Sodium Chloride Injection Is Available As

• Injection: 50 USP units per mL in 0.45% Sodium Chloride clear solution (25,000 USP units per 500 mL) in single-dose freeflex® bag
• Injection: 100 USP units per mL in 0.45% Sodium Chloride clear solution (25,000 USP units per 250 mL) in single-dose freeflex® bag

Heparin Sodium In 5% Dextrose Injection Is Available As

• Injection: 50 USP units per mL in 5% Dextrose clear solution (25,000 USP units per 500 mL) in single-dose freeflex® bag
• Injection: 100 USP units per mL in 5% Dextrose clear solution (25,000 USP units per 250 mL) in single-dose freeflex® bag

Storage And Handling

Heparin Sodium in 0.45% Sodium Chloride Injection is supplied as follows:

Heparin Sodium in 5% Dextrose Injection is supplied as follows:

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid excessive heat.

Do not freeze.

The container closure is not made with natural rubber late