Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1731
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Heparin Sodium (Injection)
|
| dailymed-instance:dosage |
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. Confirm the choice
of the correct Heparin Sodium Injection vial prior to administration of
the drug to a patient. (See WARNINGS, Fatal
Medication Errors.) The 1 mL vial must not be confused
with a���catheter lock flush���vial or other 1 mL vial
of inappropriate strength. 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,
the container should be inverted at least six times to ensure adequate
mixing and prevent pooling of the heparin in the solution. Heparin sodium is
not effective by oral administration and should be given by intermittent
intravenous injection, intravenous infusion, or deep subcutaneous
(intrafat, i.e., above the iliac crest or abdominal fat layer)
injection. The intramuscular route of
administration should be avoided because of the frequent occurrence
of hematoma at the injection site. The dosage of
heparin sodium should be adjusted according to the patient's
coagulation test results. When heparin is given by continuous
intravenous infusion, the coagulation time should be determined
approximately every 4 hours in the early stages of treatment. When the
drug is administered intermittently by intravenous injection,
coagulation tests should be performed 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 normal or when the whole blood clotting
time is elevated approximately 2.5 to 3 times the control value. 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, hematocrits and tests for occult blood in stool are recommended
during the entire course of heparin therapy, regardless of the route of
administration.<br/>Converting to Oral
Anticoagulant: When an oral anticoagulant of the coumarin or similar type is to be
begun in patients already receiving heparin sodium, baseline and
subsequent tests of prothrombin activity must be determined at a
time when heparin activity is too low to affect the prothrombin
time. This is about 5 hours after the last intravenous bolus and
24 hours after the last subcutaneous dose. If continuous IV
heparin infusion is used, prothrombin time can usually be
measured at any time. In
converting from heparin to an oral anticoagulant, the dose of
the oral anticoagulant should be the usual initial amount and
thereafter prothrombin time should be determined at the usual
intervals. To ensure continuous anticoagulation, it is advisable
to continue full heparin therapy for several days after the
prothrombin time has reached the therapeutic range. Heparin
therapy may then be discontinued without tapering.<br/>Therapeutic
Anticoagulant Effect With Full-Dose Heparin: 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:<br/>Pediatric Use: Follow
recommendations of appropriate pediatric reference texts. In
general, the following dosage schedule may be used as a
guideline:<br/>Initial
Dose: 50
units/kg (IV, drip)<br/>Maintenance
Dose: 100
units/kg (IV, drip) every 4 hours, or 20,000 units/m/24 hours continuously<br/>Geriatric Use: Patients
over 60 years of age may require lower doses of
heparin.<br/>Surgery of the
Heart and Blood Vessels: 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.<br/>Low-Dose
Prophylaxis of Postoperative Thromboembolism: A number of
well-controlled clinical trials have demonstrated that low-dose
heparin prophylaxis, given just prior to and after surgery, will
reduce the incidence of postoperative deep vein thrombosis in
the legs (as measured by the I-125 fibrinogen technique and
venography) and of clinical pulmonary embolism. The most widely
used dosage has been 5000 units 2 hours before surgery and 5000
units every 8 to 12 hours thereafter for 7 days or until the
patient is fully ambulatory, whichever is longer. The heparin is
given by deep subcutaneous injection in the arm or abdomen with
a fine needle (25- to 26-gauge) to minimize tissue trauma. A
concentrated solution of heparin sodium is recommended. Such
prophylaxis should be reserved for patients over the age of 40
who are undergoing major surgery. Patients with bleeding
disorders and those having neurosurgery, spinal anesthesia, eye
surgery or potentially sanguineous operations should be excluded, as should patients receiving oral anticoagulants or
platelet-active drugs . The value of such prophylaxis in hip
surgery has not been established. The possibility of increased
bleeding during surgery or postoperatively should be bornein
mind. If such bleeding occurs, discontinuance of heparin and
neutralization with protamine sulfate are advisable. If clinical
evidence of thromboembolism develops despite low-dose
prophylaxis, full therapeutic doses of anticoagulants should be
given unless contraindicated. All patients should be screened
prior to heparinization to rule out bleeding disorders, and
monitoring should be performed with appropriate coagulation
tests just prior to surgery. Coagulation test values should be
normal or only slightly elevated. There is usually no need for
daily monitoring of the effect of low-dose heparin in patients
with normal coagulation parameters.<br/>Extracorporeal
Dialysis: Follow
equipment manufacturers' operating directions
carefully.<br/>Blood Transfusion: Addition of
400 to 600 USP units per 100 mL of whole blood is usually
employed to prevent coagulation. Usually, 7500 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 to 8 mL are added per 100 mL of whole blood.<br/>Laboratory Samples: Addition of
70 to 150 units of heparin sodium per 10 to 20 mL sample of
whole blood is usually employed to prevent coagulation of the
sample. Leukocyte counts should be performed on heparinized
blood within 2 hours after addition of the heparin. Heparinized
blood should not be used for isoagglutinin, complement, or
erythrocyte fragility tests or platelet counts.
|
| dailymed-instance:descripti... |
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)��-L-iduronic acid 2-sulfate, (2)
2-deoxy-2-sulfamino-��-D-glucose 6-sulfate, (3)��-D-glucuronic acid, (4)
2-acetamido-2-deoxy-��-D-glucose and (5)��-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): Heparin Sodium
Injection, USP is a sterile solution of heparin sodium derived from
porcine intestinal mucosa, standardized for anticoagulant activity. It
is to be administered by intravenous or deep subcutaneous routes. The
potency is determined by a biological assay using a USP reference
standard based on units of heparin activity per milligram. Heparin Sodium
Injection, USP is available in the following concentrations/mL: pH 5.0-7.5; sodium hydroxide and/or hydrochloric acid added,
if needed, for pH adjustment.
|
| dailymed-instance:clinicalP... |
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. 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. Peak 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 sites
of biotransformation. The biphasic elimination curve, a rapidly
declining alpha phase (t=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. Heparin does not
have fibrinolytic activity; therefore, it will not lyse existing
clots.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Heparin sodium
should NOT be used in patients with the following conditions: Severe
thrombocytopenia; When suitable blood
coagulation tests, e.g., the whole blood clotting time, partial
thromboplastin time, etc., cannot be performed at appropriate intervals
(this contraindication refers to full-dose heparin; there is usually no
need to monitor coagulation parameters in patients receiving low-dose
heparin); An uncontrolled
active bleeding state , except when this is due to disseminated
intravascular coagulation.
|
| dailymed-instance:supply |
Heparin Sodium
Injection, USP 1000 USP units/mL 1 mL vial packaged
in 25s (NDC 0641-0391-02) 10 mL Multiple Dose
vial packaged in 25s (NDC 0641-2440-45) 30 mL Multiple Dose
vial packaged in 25s (NDC 0641-2450-45) 5000 USP units/mL 1 mL vial packaged
in 25s (NDC 0641-0400-02) 10 mL Multiple Dose
vial packaged in 25s (NDC 0641-2460-45) 10,000 USP units/mL 1 mL vial packaged
in 25s (NDC 0641-0410-02) 4 mL Multiple Dose
vial packaged in 25s (NDC 0641-2470-45) Also available from
Baxter: HEP-LOCK (Heparin Lock Flush Solution, USP) and HEP-LOCK U/P
(Preservative-Free Heparin Lock Flush Solution, USP).<br/>Storage: Store at 20��-25��C
(68��-77��F) [see USP Controlled Room
Temperature].
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
General:<br/>Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT)
and Heparin-induced Thrombocytopenia and Thrombosis (HITT): SeeWARNINGS.<br/>Heparin
Resistance: Increased resistance to heparin is frequently
encountered in fever, thrombosis, thrombophlebitis,
infections with thrombosing tendencies, myocardial
infarction, cancer and in postsurgical
patients.<br/>Increased
Risk to Older Patients, Especially Women: A
higher incidence of bleeding has been reported in
patients, particularly women, over 60 years of
age.<br/>Laboratory Tests: Periodic
platelet counts, hematocrits, and tests for occult blood in
stool are recommended during the entire course of heparin
therapy, regardless of the route of administration. (SeeDOSAGE AND
ADMINISTRATION.)<br/>Drug Interactions:<br/>Oral
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 or 24 hours after
the last subcutaneous dose should elapse before blood is
drawn, if a valid prothrombin time is to be
obtained.<br/>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.<br/>Other
Interactions: Digitalis, tetracyclines, nicotine or antihistamines
may partially counteract the anticoagulant action of
heparin sodium. Intravenous nitroglycerin administered
to heparinized patients may result in a decrease of the
partial thromboplastin time with subsequent rebound
effect upon discontinuation of nitroglycerin. Careful
monitoring of partial thromboplastin time and adjustment
of heparin dosage are recommended during
coadministration of heparin and intravenous
nitroglycerin.<br/>Drug/Laboratory
Test Interactions:<br/>Hyperaminotransferasemia: Significant 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, increases that might becaused by drugs (like
heparin) should be interpreted with caution.<br/>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.<br/>Pregnancy:<br/>Teratogenic
Effects:<br/>Nonteratogenic Effects: Heparin does not cross the placental
barrier.<br/>Nursing Mothers: Heparin is
not excreted in human milk.<br/>Pediatric Use: SeeDOSAGE AND
ADMINISTRATION���Pediatric
Use.<br/>Geriatric Use: A higher
incidence of bleeding has been reported in patients over 60
years of age, especially women . Clinical studies indicate
that lower doses of heparin may be indicated in these patients
(see CLINICAL
PHARMACOLOGY and DOSAGE AND
ADMINISTRATION).
|
| dailymed-instance:overdosag... |
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.<br/>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.
|
| dailymed-instance:genericMe... |
Heparin Sodium
|
| dailymed-instance:fullName |
Heparin Sodium (Injection)
|
| dailymed-instance:adverseRe... |
Hemorrhage: Hemorrhage
is the chief complication that may result from heparin therapy.
An overly prolonged clotting time or
minor bleeding during therapy can usually be controlled by
withdrawing the drug. It should be
appreciated that 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:<br/>Thrombocytopenia,
Heparin-induced Thrombocytopenia (HIT) and Heparin-induced
Thrombocytopenia and Thrombosis (HITT) and Delayed Onset of HIT and
HITT: SeeWARNINGS.<br/>Local Irritation: Local
irritation, erythema, mild pain, hematoma or ulceration may
follow deep subcutaneous (intrafat) injection of heparin sodium.
These complications are much more common after intramuscular
use, and such use is not recommended.<br/>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 up 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. 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.<br/>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. Significant
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.
|
| dailymed-instance:warning |
Heparin is not
intended for intramuscular use.<br/>Fatal Medication
Errors: Do not use
Heparin Sodium Injection as a���catheter lock
flush���product. Heparin Sodium Injection is supplied
in vials containing various strengths of heparin, including
vials that contain a highly concentrated solution of 10,000
units in 1 mL. Fatal hemorrhages have occurred in pediatric
patients due to medication errors in which 1 mL Heparin Sodium
Injection vials were confused with 1 mL���catheter lock
flush���vials. Carefully examine all Heparin Sodium
Injection vials to confirm the correct vial choice prior to
administration of the drug.<br/>Hypersensitivity: Patients
with documented hypersensitivity to heparin should be given the
drug only in clearly life-threatening situations. (See ADVERSE
REACTIONS, Hypersensitivity.)<br/>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 disease states in
which there is increased danger of hemorrhage. Some of the
conditions in which increased danger of hemorrhage exists
are:<br/>Cardiovascular: Subacute bacterial endocarditis, severe
hypertension.<br/>Surgical: During and immediately following (a) spinal tap or spinal anesthesia or (b) major surgery, especially
involving the brain, spinal cord, or eye.<br/>Hematologic: Conditions associated with increased bleeding
tendencies, such as hemophilia, thrombocytopenia and
some vascular purpuras.<br/>Gastrointestinal: Ulcerative lesions and continuous tube drainage of the
stomach or small intestine.<br/>Other: Menstruation, liver disease with impaired
hemostasis.<br/>Coagulation Testing: When
heparin sodium is administered in therapeutic amounts, its
dosage should be regulated by frequent blood coagulation tests.
If the coagulation test is unduly prolonged or if hemorrhage
occurs, heparin sodium should be promptly discontinued.<br/>Thrombocytopenia: Thrombocytopenia has been reported to occur in patients
receiving heparin with a reported incidence of up to 30%.
Platelet counts should be obtained at baseline and periodically
during heparin administration. Mild thrombocytopenia (count
greater than 100,000/mm) 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/mmor 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.<br/>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/mmor if
recurrent thrombosis develops, the heparin product should be
promptly discontinued and alternative anticoagulants considered
if patients require continued anticoagulation.<br/>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.<br/>Use in Neonates: This
product contains the preservative benzyl alcohol and is not
recommended for use in neonates. There have been reports of
fatal���gasping syndrome' in neonates
(children less than one month of age) following the
administration of intravenous solutions containing the
preservative benzyl alcohol. Symptoms include a striking onset
of gasping respiration, hypotension, bradycardia, and
cardiovascular collapse. Carefully
examine all Heparin Sodium Injection vials to confirm choice of
the correct strength prior to administration of the drug.
Pediatric patients, including neonates, have died as a result of
medication errors in which Heparin Sodium Injection vials have
been confused with���catheter lock flush���vials. (See WARNINGS,
Fatal Medication Errors.)
|
| dailymed-instance:indicatio... |
Heparin Sodium
Injection is indicated for: Anticoagulant
therapy in prophylaxis and treatment of venous thrombosis and its
extension; Low-dose regimen
for 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 (seeDOSAGE AND
ADMINISTRATION); Prophylaxis and
treatment of pulmonary embolism; Atrial fibrillation
with embolization; Diagnosis and
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. Heparin may also be
employed as an anticoagulant in blood transfusions, extracorporeal
circulation, and dialysis procedures and in blood samples for laboratory
purposes.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Heparin Sodium
|