heparin sodium injection, solution Hospira, Inc.
HEPARIN LOCK FLUSH Solution, USP
SOLUTION IS INTENDED FOR MAINTENANCE
OF PATENCY OF
ONLY AND IS NOT TO BE USED FOR
NOT FOR USE IN NEONATES
Heparin Lock Flush Solution, USP is a sterile, nonpyrogenic,
hypertonic preparation of heparin sodium injection, USP with sodium chloride
in water for injection.
Each milliliter (mL) contains:
Heparin sodium, 10 or 100 USP units (derived from porcine intestinal mucosa);
sodium chloride 9 mg; edetate disodium, anhydrous 0.1 mg added as a stabilizer;
and benzyl alcohol 9 mg added as preservative in water for injection. May
contain sodium hydroxide for pH adjustment. pH 6.5 (5.0 to 7.5). The osmolar
concentrations of these solutions are 392 mOsmol/L (calc). Repeated withdrawals
may be made from the multiple-dose vial.
Flush Solution, USP is intended for maintenance of patency of intravenous
injection devices only and is not to be used for anticoagulant therapy.
Sodium, USP is a heterogenous 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. 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):
Chloride, USP is chemically designated NaCl, a white crystalline compound
freely soluble in water.
The semi-rigid vials are fabricated
from a specially formulated polyolefin. It is a copolymer of ethylene and
propylene. The safety of the plastic has been confirmed by tests in animals
according to USP biological standards for plastic containers. The container
requires no vapor barrier to maintain the proper drug concentration.
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 in inhibiting the activation of the fibrin stabilizing
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.
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.
plasma levels of heparin are achieved 2 to 4 hours following subcutaneous
administration, although there are considerable individual variations. 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 reticuloendothelial system are the site of biotransformation. The
biphasic elimination curve, a rapidly declining alpha phase (t½
=10΄) 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 of half-life may reflect factors such as protein binding of
Heparin does not have fibrinolytic activity;
therefore, it will not lyse existing clots.
Lock Flush Solution does not induce systemic anticoagulant action at single
doses of 10 or 100 USP units per mL when used for maintenance of patency of
intravenous injection devices. It may interfere with laboratory tests on blood
samples withdrawn from such devices, unless the volume of in
situ heparin-saline, equal to that of the priming volume of the
catheter, is aspirated and discarded before such samples are taken.
concentrations of sodium chloride are suitable for parenteral replacement
of chloride losses that exceed or equal the sodium loss. Hypotonic concentrations
of sodium chloride are suited for parenteral maintenance of water requirements
when only small quantities of salt are desired.
chloride in water dissociates to provide sodium (Na+) and chloride
(Cl−) ions. Sodium (Na+) is the principal cation
of the extracellular fluid and plays a large part in the therapy of fluid
and electrolyte disturbances. Chloride (Cl−) has an integral
role in buffering action when oxygen and carbon dioxide exchange occurs in
the red blood cells. The distribution and excretion of sodium (Na+)
are largely under the control of the kidney which maintains a balance between
intake and output.
The small volume of fluid and amount
of sodium chloride provided by Heparin Lock Flush Solution, USP, when used
only as a vehicle for maintaining patency of an intravenous injection device,
is unlikely to exert a significant effect on fluid and electrolyte balance
except possibly in very small infants.
INDICATIONS AND USAGE
Heparin Lock Flush Solution, USP is indicated only to maintain
patency of an intravenous injection device. It 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 analysis.
solution is not to be used for anticoagulation therapy.
Due to the potential toxicity of benzyl alcohol in neonates,
solutions containing benzyl alcohol must not be used in this patient population.
preparations with benzyl alcohol should not be used for fluid or sodium chloride
Heparin sodium should not be used in patients:
hypersensitivity to heparin;
With an uncontrollable
active bleeding state (see WARNINGS),
except when this is due to disseminated intravascular coagulation;
inability to perform suitable blood-coagulation tests, e.g., whole-blood clotting
time, partial thromboplastin time, etc. at required intervals. There is usually
no need to monitor effect of low-dose heparin in patients with normal coagulation
Benzyl alcohol, a preservative in the multiple-dose vial
preparations of Heparin Lock Flush Solution, USP has been associated with
toxicity in neonates. Benzyl alcohol has been reported to be associated with
a fetal “Gasping Syndrome” in premature infants. Data are unavailable
on the toxicity of other preservatives in this age group. Preservative-free
Heparin Lock Flush Solution, USP should be used for maintaining patency of
intravenous injection devices in neonates.
Flush Solution, USP is not intended for intramuscular use, systemic anticoagulation
or injection by any parenteral route of administration.
Hypersensitivity: Patients with documented
hypersensitivity to heparin should be given the drug only in clearly life-threatening
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
Heparin sodium should be used with extreme caution
in 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
Hematologic — Conditions associated with
increased bleeding tendencies, such as hemophilia, thrombocytopenia, and some
Gastrointestinal — Ulcerative
lesions and continuous tube drainage of the stomach or small intestine.
Other— Menstruation, liver disease with impaired hemostasis.
Coagulation Testing: If the coagulation
test is unduly prolonged or if hemorrhage occurs, heparin sodium should be
discontinued promptly. Heparin solutions having a concentration of 10 USP
Heparin Units/mL may alter the results of blood coagulation tests. Heparin
concentrations greater than 10 USP Heparin Units/mL will alter the results
of blood coagulation tests.
Thrombocytopenia: Thrombocytopenia has been reported to occur in patients receiving
heparin with a reported incidence of 0 to 30%. 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 White Clot Syndrome, PRECAUTIONS), the heparin product should
be discontinued. If continued heparin therapy is essential, administration
of heparin from a different organ source can be reinstituted with caution.
containing sodium ions should be used with great care, if at all, in patients
with congestive heart failure, severe renal insufficiency and in clinical
states in which there exists edema with sodium retention.
Do not use unless solution is clear and container is undamaged.
Use aseptic technique for single or multiple entry and withdrawal from all
Since heparin sodium in this product is
derived from animal tissue, it should be used with caution in patients with
a history of allergy.
Interference with Laboratory Tests
Heparin interferes with competitive protein binding methods
for serum thyroxine determinations resulting in falsely elevated levels.
Lock Flush Solution may interfere with laboratory analyses or alter the results
of blood chemistry tests such as glucose, serum sodium and serum chloride,
blood coagulation studies, etc. (See CLINICAL PHARMACOLOGY.)
following information which pertains to the use of heparin sodium as a systemic
anticoagulant is included as a matter of interest only since it is not known
to apply to the use of the drug for heparin lock.
a. White Clot Syndrome:
has been reported that patients on heparin may develop new thrombus formation
in association with thrombocytopenia resulting from irreversible aggregation
of platelets induced by heparin, the so-called “white clot syndrome”.
The process may lead to severe thromboembolic complications like skin necrosis,
gangrene of the extremities that may lead to amputation, myocardial infarction,
pulmonary embolism, stroke, and possibly death. Therefore, heparin administration
should be promptly discontinued if a patient develops new thrombosis in association
Increased resistance to
heparin is frequently encountered in fever, thrombosis, thrombophlebitis,
infections with thrombosing tendencies, myocardial infarction, cancer and
in postsurgical patients.
Increased Risk in Older Patients, Especially Women:
higher incidence of bleeding has been reported in patients, particularly women,
over 60 years of age.
As Heparin Lock Flush Solution, USP is intended only for
use in maintaining patency of intravenous injection devices, no additives
should be made to multiple-dose vials.
anticoagulants: 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 should
elapse before blood is drawn if a valid PROTHROMBIN time is to be obtained.
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,
anti-histamines or I.V. nitroglycerin may partially counteract the anticoagulant
action of heparin sodium.
elevations of aminotransferase (SGOT [S-AST] and SGPT [S-ALT]) levels have
occurred in a high percentage of patients (and healthy subjects) who have
received heparin. Since aminotransferase determinations are important in the
differential diagnosis of myocardial infarction, liver disease, and pulmonary
emboli, rises that might be caused by drugs (like heparin) should be interpreted
Carcinogenesis, Mutagenesis, Impairment of Fertility:
No long-term studies in animals have been performed to evaluate
carcinogenic potential of heparin. Also, no reproduction studies in animals
have been performed concerning mutagenesis or impairment of fertility.
Teratogenic Effects: Pregnancy
Category C. Animal reproduction studies have not been conducted
with heparin sodium or sodium chloride. It is also not known whether heparin
sodium or sodium chloride can cause fetal harm when administered to a pregnant
woman or can affect reproduction capacity. Heparin sodium or sodium chloride
should be given to a pregnant woman only if clearly needed.
Effects: Heparin does not cross the placental barrier.
Heparin is not excreted in human milk.
Safety and effectiveness in pediatric patients have not
been established. Not for use in neonates (see WARNINGS).
A higher incidence of bleeding has been reported in patients
over 60 years of age, especially women (see PRECAUTIONS, General). Clinical
studies indicate that lower doses of heparin may be indicated in these patients
(see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).
Although adverse reactions to intravenous intramuscular or
subcutaneous injection of 0.9% benzyl alcohol are not known to occur in man,
experimental studies of small volume parenteral preparations containing 0.9%
benzyl alcohol in several species of animals have indicated that an estimated
intravenous dose up to 30 mL may be safely given to an adult without toxic
effects. Administration of an estimated 9 mL to 6 kg infant is potentially
capable of producing blood pressure changes.
Lock Flush Solution is not known to cause adverse local or systemic effects
of any kind. Although a remote possibility of hypersensitivity reaction exists
with entry of extremely small subtherapeutic amounts of the solution into
the circulation, such an occurrence has not been reported.
DOSAGE AND ADMINISTRATION
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. (See PRECAUTIONS.)
Lock Flush Solution, USP 10 or 100 USP Units/mL, is injected as a single dose
into an intravenous injection device using a volume of solution equivalent
to that of the indwelling venipuncture device.
dose should be injected following venipuncture when the indwelling device
is not to be used immediately. After each use of the indwelling venipuncture
device for injection or infusion of medication, or withdrawal of blood samples,
another dose should be injected to restore the effectiveness of the heparin
lock. The amount of heparin solution is sufficient to prevent clotting within
the lumen of indwelling venipuncture devices (usually not holding more than
0.2 to 0.3 mL) for up to twenty-four hours.
indwelling device is used to administer a drug which is incompatible with
heparin, the entire heparin lock set should be flushed with 0.9% Sodium Chloride
Injection, USP before and after the medication is administered. Following
the second flush, another dose of heparin solution should be injected to restore
the effectiveness of the heparin lock.
When the indwelling
device is used for repeated withdrawal of blood samples for laboratory analyses
and the presence of heparin or saline is likely to interfere with or alter
results of the desired blood tests, the in situ heparin flush solution should be cleared from the device by aspirating
and discarding 1 mL before the desired blood sample is drawn. (See PRECAUTIONS.)
Heparin Lock Flush Solution, USP is supplied in the following
Sodium (USP Units/mL)
Plastic Multiple-dose Fliptop Vial
Plastic Multiple-dose Fliptop Vial
Plastic Multiple-dose Fliptop Vial
Plastic Multiple-dose Fliptop Vial
All of the above may be used with sharp needles. In addition,
the LifeShield® products may be used with the LifeShield® Blunt
Store at controlled room temperature 15°
to 30°C (59° to 86°F). [See USP.]