Usual dose

Confirm choice of the correct heparin product; see Precautions.

As of 2009 USP heparin has a new reference standard and a new test method for manufacturers to use in determining accurate potency. The adjustment in reference standard results in approximately a 10% reduction in the potency of heparin and makes it commensurate with the World Health Organization International Standard unit dose. In most situations this new reference standard will not require a dose adjustment; however, dose adjustments and more frequent monitoring may be indicated in selected clinical situations.

Pediatric dose

Read label carefully. Comes in many strengths. Confirm use of the correct strength. Fatal hemorrhages have occurred in pediatric patients, including neonates, as a result of medication errors in which heparin sodium injection vials have been confused with heparin-lock flush vials.

 Do not use products containing benzyl alcohol in neonates or infants. Preservative-free solution is required for neonates and infants. See Maternal/Child.

Dose adjustments

Reduction of initial dose indicated in low-birth-weight infants and may be indicated in patients 60 years of age and older (especially women). Adjust dose based on coagulation tests; see Monitor. ■ Increased dose may be required in smokers (half-life shortened and elimination rate increased).

Dilution

May be given undiluted or diluted in any given amount of NS, dextrose, or Ringer’s solution for infusion and given by IV injection, as an intermittent IV, or continuous IV infusion. When added to an infusion solution for continuous IV administration, invert container a minimum of 6 times to ensure adequate mixing and to prevent pooling of heparin in the solution. Available in several strengths for administration or dilution as well as in several premixed concentrations and volumes. Unit-dose heparin flush syringes are not for multiple use; discard unused portions.

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

Several sources recommend not mixing or administering through the same IV line with other drugs until compatibility confirmed. To avoid precipitation with heparin, they also caution to flush with SWFI or NS before and after any acidic or incompatible medication or solution. Manufacturer lists as incompatible in solution with alteplase (Activase, Cathflo), amikacin, atracurium (Tracrium), ciprofloxacin (Cipro IV), cytarabine (ARA-C), daunorubicin (Cerubidine), droperidol (Inapsine), erythromycin (Erythrocin), gentamicin, idarubicin (Idamycin), kanamycin, mitoxantrone (Novantrone), polymyxin B, promethazine (Phenergan), streptomycin, and tobramycin.

One source suggests the following compatibilities:

Rate of administration

A single injection (5,000 units or fraction thereof) may be given over 1 minute. A continuous IV infusion may be given over 4 to 24 hours, depending on specific dosage of heparin required, amount of heparin added, and amount of infusion fluid used as a diluent. Continuous IV infusion is the preferred method of administration. Use an infusion pump for accuracy.

Actions

An anticoagulant with immediate and predictable effects on the blood. Inhibits reactions that lead to clotting of blood and the formation of fibrin clots. Heparin combines with other factors in the blood to inhibit the conversion of prothrombin to thrombin and fibrinogen to fibrin. Adhesiveness of platelets is reduced. Well-established clots are not dissolved, but growth is prevented and newer clots may be dissolved. Duration of action is short, about 4 to 6 hours. Average plasma half-life is 30 to 180 minutes. The half-life of the anticoagulant effect of heparin is approximately 1.5 hours and does not increase with dose. Metabolic fate not fully determined. May be partially metabolized in the liver and the reticuloendothelial system. Small amount excreted as unchanged drug in the urine.

Indications and uses

Prevention and/or treatment of all types of thromboses and emboli, including deep vein thrombosis (DVT), pulmonary emboli (PE), thromboembolic complications associated with atrial fibrillation (AF), and peripheral arterial embolism. ■ Treatment of disseminated intravascular coagulation (DIC). ■ Prevention of clotting in arterial and cardiac surgery and during blood transfusion, extracorporeal circulation, and dialysis procedures. ■ Maintain patency of an indwelling venipuncture device designed for intermittent injection or infusion therapy or blood sampling (e.g., heparin-lock, catheter, or implanted port).

Contraindications

History of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis (HITT). ■ Severe thrombocytopenia. ■ Patients receiving full-dose heparin unless blood coagulation tests can be performed at appropriate intervals. ■ Hypersensitivity to heparin (or any of its components [may contain sulfites]) or pork products. ■ Uncontrolled bleeding except in DIC. ■ Do not administer heparin preparations preserved with benzyl alcohol to neonates, infants, pregnant women, or breast-feeding mothers.

Precautions

Read label carefully. Comes in many strengths. Confirm use of the correct strength. Fatal hemorrhages have occurred in pediatric patients, including neonates, as a result of medication errors in which heparin sodium injection vials have been confused with heparin-lock flush vials. ■ For IV or SC use only; avoid IM administration (may cause hematomas). ■ Derived from animal protein (pork). ■ Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks. ■ Use extreme caution in any disease state or clinical condition in which risk of hemorrhage may be increased, such as subacute bacterial endocarditis; severe hypertension; during or following spinal tap, spinal anesthesia, or major surgery (especially major surgery involving the brain, spinal cord, or eye); hemophilia; thrombocytopenia; gastrointestinal ulcerative lesions; vascular purpuras; continuous tube drainage of the stomach or small intestine; menstruation; severe liver disease with impaired hemostasis; severe renal disease; or in patients with indwelling catheters. ■ Resistance to heparin increased in cancer, fever, infections with thrombosing tendencies, MI, postsurgical patients, thrombophlebitis, and thrombosis. ■ May cause thrombocytopenia; monitor closely. ■ May develop heparin-induced thrombocytopenia (HIT), an antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to heparin-induced thrombocytopenia and thrombosis (HITT), which involves the development of venous and arterial thromboses. HIT and HITT may occur during heparin treatment or may be delayed for up to several weeks after heparin treatment is discontinued; see Monitor. ■ See Elderly for additional precautions. ■ Repeated flushing of an indwelling venipuncture device with heparin may result in a systemic anticoagulant effect. ■ Heparin-lock flush solution is intended for maintenance of patency of intravenous injection devices only and is not to be used for anticoagulant therapy. ■ See Maternal/Child.

Drug/lab interactions

Increased risk of bleeding with drugs that can interfere with platelet aggregation and/or increase the risk of bleeding (e.g., systemic salicylates [aspirin], NSAIDs including celecoxib [Celebrex] and ibuprofen [Motrin], platelet aggregation inhibitors [e.g., clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brilinta)], glycoprotein GPIIb/IIIa receptor antagonists [e.g., abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat)], some cephalosporins [e.g., cefotetan], dextran, or other thrombolytic agents [e.g., alteplase, streptokinase]); use heparin with caution in patients receiving such agents. ■ Anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) (Thrombate III). ■ Resistance to heparin anticoagulation may occur following administration of streptokinase as a systemic thrombolytic agent; adjust dose of heparin based on more frequent aPTTs. ■ Inhibited by antihistamines, digoxin, nicotine, nitrates, tetracyclines, and others; may counteract anticoagulant action of heparin. ■ Potentiates oral anticoagulants (e.g., apixaban [Eliquis], dabigatran [Pradaxa], rivaroxaban [Xarelto], warfarin [Coumadin]). ■ See Precautions/Monitor. ■ Use caution when administered with or around other anticoagulants. Lab data may not provide an accurate baseline. ■ Numerous lab values (e.g., aminotransferase levels [AST, ALT], PT) may be altered. Notify lab of heparin use. Diagnostic results may not be attainable. See Monitor. ■ When heparin is given concomitantly with warfarin (Coumadin), the PT may be prolonged. Wait at least 5 hours after IV bolus heparin dose before drawing PT. If heparin is being administered as a continuous infusion, may draw PT at any time.

Side effects

The most common side effects are elevations of aminotransferase levels and general hypersensitivity reactions, usually chills, fever, and urticaria (anaphylactoid reactions, including shock, asthma, headache, itching and burning on plantar side of feet, lacrimation, nausea and vomiting, and rhinitis may occur less frequently); hemorrhage (bruising, epistaxis, hematuria, tarry stools [adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage (corpus luteum hemorrhage that may be fatal), and/or retroperitoneal hemorrhage may be difficult to detect]); HIT and HITTS (including delayed-onset cases); injection site irritation; and thrombocytopenia.

Antidote

Discontinue drug and notify physician of any side effects. Protamine sulfate is a heparin antagonist and specifically indicated in overdose or desired heparin reversal. Each milligram of protamine neutralizes approximately 100 units heparin. No more than 50 mg should be administered, very slowly, in any 10-minute period. Administration of protamine can cause severe hypotension and anaphylactoid reactions. Use with caution and have emergency equipment and medications readily available. If HIT (with or without thrombosis) is diagnosed or strongly suspected, discontinue all sources of heparin, including heparin flushes. Use an alternative anticoagulant. Any future use of heparin should be avoided, especially within 3 to 6 months after the diagnosis of HIT or HITT and while patients test positive for HIT antibodies. Whole blood transfusion may be indicated. If heparin-induced thrombocytopenia or white clot syndrome occurs, discontinue heparin and administer a non-heparin anticoagulant (e.g., argatroban, bivalirudin [Angiomax]) as an alternate form of anticoagulation. Follow-up with oral anticoagulation (e.g., warfarin [Coumadin]) may also be indicated. Avoid use of heparin for at least 3 to 6 months or for as long as the patient tests positive for HIT antibodies.

Usual dose (international units [IU])

Dose adjustments (international units [IU])

Increased doses may be required in patients who fail to reach anti-HBs levels of 500 IU/L within the first week after liver transplantation. Particularly susceptible to an extensive decrease of circulated anti-HBs are patients who have surgical bleeding or abdominal fluid drainage (greater than 500 mL) or those who undergo plasmapheresis. If the desired anti-HBs levels are not reached, increase the dosing regimen to a half-dose (10,000 IU [calculated from the measured potency as stamped on the vial label]) and administer IV every 6 hours until the target anti-HBs level is reached.

Dilution

A ready-to-use liquid preparation; should be clear to opalescent. Multiple vials will be required. Do not shake vials; avoid foaming. Bring to room temperature before administration. Administer through a separate IV line using an IV administration set and an infusion pump.

Compatibility

Manufacturer states, “Administer through a separate IV line using an IV administration set via infusion pump.”

Rate of administration

Set infusion pump rate at 2 mL/min. Decrease to 1 mL/min or slower for patient discomfort, infusion-related adverse events, or concern about the speed of infusion.

Actions

A solvent/detergent-treated sterile solution of purified gamma globulin containing anti-HBs. Prepared from plasma donated by healthy, screened donors with high titers of anti-HBs. Purified by an anion-exchange column chromatography manufacturing method. It provides passive immunization for individuals exposed to the hepatitis B virus by binding to the surface antigen and reducing the rate of hepatitis B infection. Following liver transplantation, hepatitis B virus re-infection can occur immediately at the time of liver reperfusion due to a circulating virus or later from a virus retained in extrahepatic sites. Provides an immediate immune response to the hepatitis B virus. Mechanism of action is not known but may occur through several pathways (e.g., through blockage of a putative HBV receptor, neutralization of circulating virions through immune precipitation and immune complex formation, triggering of an antibody-dependent cell-mediated cytotoxicity response that results in target cell lysis, or binding to hepatocytes and interaction with HBsAg within cells). Clinical effectiveness is dependent on dose, length of administration, and viral replication status of the patient at the time of transplant. Bioavailability is complete and immediate and is distributed quickly between plasma and extravascular fluid. Immune globulins are metabolized by being broken down in the reticuloendothelial system. IM injection results in mean peak concentrations within 4 to 5 days of administration and an elimination half-life of 22 to 25 days. A slightly decreased half-life is expected following IV administration.

Indications and uses

Prevention of hepatitis B recurrence following liver transplantation in HBsAg-positive liver transplant patients. Recommended for use in patients who have no or low levels of viral replication at the time of liver transplantation. ■ Used IM for postexposure prophylaxis in the following settings: acute exposure to blood containing HBsAg, perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAg-positive persons, and household exposure to persons with acute HBV infection.

Contraindications

History of anaphylactic or severe systemic reactions to human globulins. ■ Weigh benefits versus risk of hypersensitivity reactions in IgA-deficient individuals; see Precautions.

Precautions

Administer in a facility with adequate equipment and supplies to monitor the patient and respond to any medical emergency. ■ Hypersensitivity and/or infusion reactions may occur. ■ Individuals deficient in IgA may have the potential to develop IgA antibodies and have an anaphylactoid reaction. ■ Contains maltose, which can interfere with select blood glucose monitoring systems (those based on the glucose dehydrogenase pyrroloquinequinone [GDH-PQQ] method). May cause falsely elevated glucose readings, result in inappropriate insulin administration, and cause life-threatening hypoglycemia. In contrast, cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated results. ■ Derived from human plasma. Despite screening and purification processes, may have the potential risk of transmitting infectious agents (e.g., viruses [e.g., HIV, hepatitis]) or the Creutzfeldt-Jakob disease agent. ■ Has not been evaluated in combination with antiviral therapy posttransplantation. ■ See Patient Education and Drug/Lab Interactions.

Drug/lab interactions

May reduce the effectiveness of live virus vaccines (e.g., measles, mumps, rubella, varicella). Vaccination with live virus vaccines should be deferred until approximately 3 months after administration of hepatitis B IGIV. ■ Contains maltose, which can interfere with select blood glucose monitoring systems (those based on the glucose dehydrogenase pyrroloquinequinone [GDH-PQQ] method). May cause falsely elevated glucose readings. Use only glucose-specific testing systems in patients receiving hepatitis B IGIV. ■ Passively transferred antibodies may cause a misleading positive result in serologic testing (e.g., Coombs’ test). ■ No data available on drug interactions with other medications.

Side effects

Arthralgia, chills, fever, headaches, hypersensitivity reactions, moderate or low back pain, nausea, and vomiting are the most common. Other reported side effects include agitation, amnesia, aphthous stomatitis, diarrhea, dyspepsia, edema, fatigue, gingival hyperplasia, hepatobiliary disease, hyperglycemia, hypertension, hypotension, infectious diarrhea, liver transplant rejection, nocturia, pleural effusion, pneumonia, presbyopia, pruritus, rash, sepsis, splenomegaly, tremors.

Antidote

Reduce rate of infusion for patient discomfort, infusion-related side effects, or other concerns. Discontinue the drug immediately for any signs of a hypersensitivity reaction. Notify the physician. Antihistamines (e.g., diphenhydramine [Benadryl]) or analgesic agents may be indicated for symptoms related to immune complex formation. Resume infusion at a slower rate if symptoms subside. Treat anaphylaxis immediately. Epinephrine, diphenhydramine (Benadryl), corticosteroids, and ventilation equipment must always be available.

Usual dose

Dose adjustments

Avoid use in patients with pre-existing renal impairment. Information on dose adjustment in hepatic impairment is not available.

Dilution

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

Rate of administration

Variable, depending on indication, present blood volume, and patient response. Initial 500 mL may be given at rates approaching 20 mL/kg of body weight per hour. If additional hydroxyethyl starch is required, reduce flow to lowest rate possible to maintain hemodynamic status. If pressure infusion is used (flexible containers), withdraw all air through medication port before infusing. If a pumping device is used for administration, discontinue pumping action before the container runs dry or air embolism may result.

Actions

A synthetic colloid solution. Pharmacologically classified as a plasma volume expander. The amount of plasma volume expansion produced approximates that of 5% albumin and decreases over the succeeding 24 to 36 hours. Hextend supports oncotic pressure and provides electrolytes. Its electrolyte content resembles that of normal plasma. Hespan supports oncotic pressure and increases erythrocyte sedimentation rate. Improves the efficiency of granulocyte collection by centrifugal means. Hetastarch molecules are rapidly eliminated by renal excretion.

Indications and uses

Contraindications

Do not use in critically ill adult patients, including patients with sepsis. ■ Severe liver disease. ■ Hypersensitivity to hetastarch. ■ Clinical conditions in which volume overload is a potential problem (such as CHF or renal disease with oliguria or anuria not related to hypovolemia). ■ Pre-existing coagulation or bleeding disorders. ■ Hextend contains lactate; not for use in leukapheresis or in the treatment of lactic acidosis.

Precautions

Drug/lab interactions

Use with caution in patients receiving other drugs that affect coagulation (e.g., anticoagulants [e.g., argatroban, bivalirudin (Angiomax), heparin, warfarin (Coumadin)], platelet aggregation inhibitors [e.g., clopidogrel (Plavix), dipyridamole (Persantine), ticlopidine (Ticlid)], glycoprotein GPIIb/IIIa receptor antagonists [e.g., abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat)], plicamycin [Mithracin], valproic acid [Depacon]). Close monitoring of aPTT and PT indicated. ■ May increase indirect bilirubin levels. Total bilirubin remained normal. ■ Elevated serum amylase levels have been observed, although no association with pancreatitis has been demonstrated.

Side effects

The most common adverse reactions are circulatory overload, coagulopathy, hemodilution, hypersensitivity (including anaphylaxis), and metabolic acidosis. Anemia and/or bleeding due to hemodilution and/or factor VIII deficiency, acquired von Willebrand’s–like syndrome, and other coagulopathies, including DIC; chills; congestive heart failure; elevated serum amylase; fever; headache; increased urine specific gravity; intracranial bleeding; itching; muscle pains; peripheral edema; pulmonary edema; submaxillary and parotid glandular enlargement; urticaria; and vomiting have been reported.

Antidote

Notify the physician of any side effect. Discontinue the drug immediately at the first sign of a hypersensitivity reaction, provided other means of sustaining the circulation are available. Antihistamines such as diphenhydramine (Benadryl) are helpful. Epinephrine (Adrenalin) may also be indicated. Not eliminated by dialysis. Many side effects can result in medical emergencies. Deaths from severe hypersensitivity reactions have occurred. Treat as indicated and resuscitate as necessary.

Usual dose

10 to 40 mg. Begin with a low dose. Increase gradually as indicated. Repeat every 3 to 6 hours as necessary. Maximum dose is 300 to 400 mg/24 hr.

Pediatric dose

See Maternal/Child (unlabeled).

0.1 to 0.5 mg/kg/dose every 4 to 6 hours. Initial dose should not exceed 20 mg. Maximum IV dose is 0.2 to 0.8 mg/kg/dose up to 40 mg. Another source suggests 0.1 to 0.2 mg/kg/dose (not to exceed 20 mg) every 4 to 6 hours as needed. Up to 1.7 to 3.5 mg/kg/day divided in 4 to 6 doses.

Dose adjustments

Reduced dose may be required with advanced renal disease and in the elderly. ■ See Drug/Lab Interactions.

Dilution

May be given undiluted. Do not add to IV solutions. May be given through Y-tube or three-way stopcock of infusion set. Color changes occur in most 10% dextrose solutions and after drawing through a metal filter. Use immediately after drawing up solution.

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

One source suggests the following compatibilities:

Rate of administration

Actions

A potent antihypertensive drug. It lowers BP by direct relaxation of smooth muscle of arteries and arterioles. Peripheral vasodilation and decreased peripheral vascular resistance result. HR, cardiac output, and stroke volume are all increased. Renal blood flow increased in some cases, while cerebral blood flow maintained. Onset of action is 5 to 20 minutes. Average duration of action is 2 to 6 hours. Metabolized by the liver and excreted in urine. Crosses placental barrier. Secreted in breast milk.

Indications and uses

Severe essential hypertension. ■ Vasodilation in cardiogenic shock. ■ Drug of choice for pregnancy-induced hypertension (eclampsia).

Contraindications

Hypersensitivity to hydralazine, coronary artery disease, mitral valvular rheumatic heart disease.

Precautions

IV use recommended only when the oral route is not feasible. ■ Rarely the drug of choice for hypertension unless used in combination (effectiveness increased and side effects decreased) with spironolactone (Aldactone), reserpine, guanethidine (Ismelin), and thiazide diuretics. ■ Tolerance is easily developed but subsides about 7 days after the drug is discontinued. ■ Use caution in advanced renal disease, cerebrovascular accidents, congestive heart failure, coronary insufficiency, headache, increased intracranial pressure, and tachycardia. ■ Use in pregnancy should be limited to treatment of eclampsia.

Drug/lab interactions

Sometimes used with a beta-adrenergic blocking drug (e.g., propranolol) or diuretics (e.g., hydrochlorothiazide [Aldactazide]); use caution; may potentiate effects. ■ Potentiated by anesthetics, MAO inhibitors (e.g., selegiline [Eldepryl]), and other antihypertensive agents. ■ Inhibits epinephrine, levarterenol (Levophed). ■ Use with diazoxide can cause profound hypotension. ■ NSAIDs (e.g., ibuprofen [Motrin]) may decrease antihypotensive effect.

Side effects

May often be minimized by initiating therapy with a small dose and increasing the dose gradually.

Anxiety, depression, dry mouth, flushing, headache, nausea, numbness, palpitations, paresthesia, postural hypotension, tachycardia, tingling, unpleasant taste, vomiting.

Antidote

If minor side effects occur, notify the physician, who will probably treat them symptomatically. Beta-adrenergic blocking agents (e.g., propranolol) will control tachycardia. Pyridoxine will relieve numbness, tingling, and paresthesia. Antihistamines, barbiturates, and salicylates may be required. Treat hypotension with a vasopressor that is least likely to precipitate cardiac arrhythmias. If side effects are progressive or any major side effects occur, discontinue the drug immediately and notify the physician. Treatment is symptomatic. Resuscitate as necessary. Occasionally methyldopa (Aldomet) will be used as a substitute because it is effective for the same indications but has fewer side effects.

Usual dose

The IV route is usually used in an emergency situation or when oral dosing is not feasible. The lowest possible dose should be used to control condition. When reduction in dosage is possible, reduction should be gradual. Larger doses may be justified by patient condition. Repeat until adequate response, then decrease dose as indicated. Doses must be individualized and are not always reduced for pediatric patients. High dose treatment is utilized until patient condition stabilizes, usually no longer than 48 to 72 hours. Complications secondary to treatment with corticosteroids are dependent on the size of dose and duration of therapy.

Average dose range is 100 to 500 mg repeated as necessary every 2, 4, or 6 hours. For severe shock, doses up to 2 Gm or more every 2 to 10 hours have been given. Maximum dose is 8 Gm/24 hr. A minimum dose of no less than 25 mg/24 hr is recommended. Increased doses are indicated in patients undergoing corticosteroid therapy who are subjected to any unusual stressful situation (e.g., illness, surgery).

Other sources recommend:

Pediatric dose

See Maternal/Child.

Average dose range in pediatric patients is 0.56 to 8 mg/kg/day in 3 to 4 divided doses (0.19 to 2.67 mg/kg every 8 hours or 0.14 to 2 mg/kg every 6 hours).

Other sources recommend:

Dose adjustments

Reduced dose may be required in the elderly. ■ See Drug/Lab Interactions.

Dilution

Available in Act-O-Vials and Univials, which are reconstituted by removing the protective cap, turning the rubber stopper a quarter turn, and pressing down, allowing the diluent into the lower chamber. Agitate gently. Using sterile techniques, a needle can be easily inserted through the center of the rubber stopper to withdraw the solution. Also available in flip-top vials. For these other preparations, reconstitute each 250 mg or fraction thereof with 2 mL bacteriostatic water for injection. Agitate gently to mix solution. May be given by IV injection, or each 100 mg (250 mg, 500 mg, or more) may be further diluted in at least 100 mL (250 mL, 500 mL, or more) but not more than 1,000 mL of D5W, NS, or D5NS.

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

Manufacturer states, “Should not be diluted or mixed with other solutions.”

One source suggests the following compatibilities:

Rate of administration

Each 100 mg or fraction thereof over 30 seconds to 1 minute. Extend to 10 minutes for larger doses (500 mg or more). IV injection is usually the route of choice and eliminates the possibility of overloading the patient with IV fluids. At the discretion of the physician, a continuous infusion may be given, properly diluted over the specified time desired.

Actions

Contains the principal hormone secreted by the adrenal cortex and has both glucocorticoid and mineralocorticoid properties. Has potent metabolic, anti-inflammatory, and innumerable other effects. Peak plasma levels achieved promptly. Metabolized in the liver and excreted as inactive metabolites in the urine. Elimination half-life is 1 to 2 hours. Crosses placental barrier. Secreted in breast milk.

Indications and uses

Agents of choice for adrenocortical insufficiency; total, relative, and operative. ■ Agents of choice for acute exacerbation of disease for patients on steroid therapy. ■ Occasionally used for asthma or shock, but nonmineralocorticoid steroids are preferred (e.g., dexamethasone, methylprednisolone).

Contraindications

Precautions

To avoid relative adrenocortical insufficiency, do not stop therapy abruptly. Taper off. Patient is observed carefully, especially under stress, for up to 2 years. The exception is very short-term therapy. ■ Anaphylactoid reactions have occurred (incidence is rare). ■ Increased doses are indicated in patients undergoing corticosteroid therapy who are subjected to any unusual stressful situation (e.g., illness, surgery). ■ Should not be used for treatment of traumatic brain injury. May increase mortality. ■ Use with caution in patients who have had a recent MI. May be associated with left ventricular free wall rupture. ■ Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, most often for chronic conditions. Clinical improvement may occur if therapy is discontinued. ■ Use with caution in patients with CHF, hypertension, or renal insufficiency; see Monitor. ■ Use with caution in patients with active or latent peptic ulcer disease, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis; may increase risk of perforation. Prophylactic antacids may prevent peptic ulcer complications. ■ May induce psychological side effects (e.g., euphoria, insomnia, mood swings, depression, psychosis) or may aggravate existing emotional instability or psychotic tendencies.

Drug/lab interactions

Aminoglutethimide (Cytadren) may increase the metabolism of hydrocortisone, thereby decreasing therapeutic effects. Monitor carefully if concurrent use is necessary. ■ Metabolism increased and effects reduced by hepatic enzyme–inducing agents (e.g., alcohol, barbiturates [e.g., phenobarbital], hydantoins [e.g., phenytoin (Dilantin)], and rifampin [Rifadin]); dose adjustment may be required when adding or deleting from drug profile. ■ Risk of hypokalemia increased with amphotericin B or potassium-depleting diuretics (e.g., thiazides, furosemide, ethacrynic acid). Monitor potassium levels and cardiac function. Increased risk of digoxin toxicity secondary to hypokalemia. ■ May also decrease effectiveness of potassium supplements; monitor serum potassium. ■ Diuretics decrease sodium and fluid retention effects of corticosteroids; corticosteroids decrease sodium excretion and diuretic effects of diuretics. ■ May antagonize effects of anticholinesterases (e.g., neostigmine), isoniazid (INH), salicylates, and somatrem; dose adjustments may be required. ■ Clearance decreased and effects increased with estrogens, oral contraceptives, macrolide antibiotics (e.g., azithromycin [Zithromax]), and ketoconazole (Nizoral). ■ May interact with anticoagulants, nondepolarizing muscle relaxants (e.g., atracurium [Tracrium]), or theophyllines; may inhibit or potentiate action. ■ Monitor patients receiving insulin or thyroid hormones carefully; dose adjustments of either or both agents may be required. ■ Increased activity of both hydrocortisone and cyclosporine may occur with concurrent use. Therapeutic use is beneficial for organ transplants; however, toxicity may also be increased, and convulsions have been reported. ■ Concurrent use with aspirin or NSAIDs (e.g., ibuprofen [Motrin], naproxen [Aleve, Naprosyn]) may increase the risk of GI side effects. ■ Administration of live or live-attenuated vaccines is contraindicated in patients receiving immunosuppressive dose of corticosteroids. Inactivated vaccines may be administered; however, the response to these vaccines cannot be predicted. ■ Altered protein-binding capacity will impact effectiveness of this drug. ■ Corticosteroids may suppress reactions to skin tests. ■ See Dose Adjustments.

Side effects

Do occur but are usually reversible: alteration of glucose metabolism including hyperglycemia and glycosuria; Cushing’s syndrome (e.g., moon face, fat pads); electrolyte and calcium imbalance; euphoria or other psychic disturbances; hypersensitivity reactions including anaphylaxis; increased BP; increased intracranial pressure; masking of infection; menstrual irregularities; perforation and hemorrhage from aggravation of peptic ulcer; protein catabolism with negative nitrogen balance; spontaneous fractures; sweating, headache, or weakness; thromboembolism; transitory burning or tingling; and many others.

Antidote

Notify the physician of any side effect. Will probably treat the side effect if necessary. Resuscitate as necessary for anaphylaxis and notify physician. Keep epinephrine immediately available.

Usual dose

Individualize dose based on age; general condition and medical status; degree of opioid tolerance; daily dose, potency, and specifics of previous opioids prescribed; concurrent medications; type and severity of pain; risk factors for abuse or addiction (e.g., previous or current abuse problem, family history of abuse, history of mental illness or depression); balance between pain control and adverse reactions.

Dispense with caution; dosing errors due to confusion between different concentrations and between mg and mL could result in accidental overdose and death. Oral and IV doses of hydromorphone and IV doses with doses of other opioids are NOT equivalent; see prescribing information for a discussion on opioid conversion and equianalgesic potency for conversion to hydromorphone injection.

Pediatric dose

Individualized on the basis of age and weight (unlabeled). One source suggests 0.015 mg/kg/dose every 4 to 6 hours as needed in pediatric patients; see Contraindications and Maternal/Child.

Dose adjustments

Dose selection should be cautious in the elderly and debilitated. Reduced initial doses may be indicated based on the potential for increased sensitivity, decreased organ function, and concomitant disease or drug therapy. ■ Depending on the degree of impairment, one-fourth to one-half the usual starting dose is recommended in patients with impaired renal or hepatic function. ■ Use lower initial doses in opiate-naïve patients. ■ Doses appropriate for the general population may cause serious respiratory depression in vulnerable patients. ■ Increase doses as required if analgesia is inadequate, tolerance develops, or pain severity increases. The first sign of tolerance is usually a reduced duration of effect. ■ Decrease dose if excessive side effects are observed early in the dosing interval. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may be shortened. ■ See Drug/Lab Interactions.

Dilution

Available in more than one concentration (1 mg/mL, 2 mg/mL, and 4 mg/mL) and hydromorphone-HP (a high-potency [10 mg/mL]) formulation. Do not confuse hydromorphone-HP with standard formulations of hydromorphone or other opioids; overdose and death could result. Hydromorphone-HP is usually reserved for compounding in the pharmacy or for use in opioid-tolerant patients. Verify concentration to avoid overdose and/or death.

Compatibility (underline indicates conflicting compatibility information)

Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.

One source suggests the following compatibilities:

Rate of administration

Rapid IV administration increases the possibility of hypotension and respiratory depression.

Actions

A mu-opioid receptor agonist closely related to morphine. Precise mode of action unknown, but opioids are believed to combine with specific CNS opiate receptors. Pharmacologic effects include analgesia, anxiolysis, cough suppression, euphoria, and feelings of relaxation. Seven times more potent than morphine milligram for milligram. Produces respiratory depression by direct effect on brainstem respiratory centers and reduces the responsiveness to increases in carbon dioxide. Causes a reduction of motility in the GI tract. May produce hypotension due to either peripheral vasodilation, release of histamine, or both. Onset of action is prompt, and half-life is about 2.3 hours. Hydromorphone is metabolized in the liver and excreted in the urine. Crosses placental barrier. Secreted in breast milk.

Indications and uses

Contraindications

Hypersensitivity to hydromorphone, any of its components, or sulfite-containing medications. ■ Acute or severe bronchial asthma, respiratory depression in the absence of resuscitation equipment or in unmonitored settings. ■ In patients with, or at risk for developing, GI obstruction, especially paralytic ileus. ■ Hydromorphone-HP is contraindicated in patients who are not opioid tolerant.

Precautions

Hydromorphone-HP is for use in opioid-tolerant patients only. ■ Use of hydromorphone and hydromorphone-HP carries the risk of respiratory depression, abuse, and medication errors. Do not confuse hydromorphone-HP formulations with standard formulations of hydromorphone or with other opioids; overdose and death could result. ■ Schedule II opioid agonists, including hydromorphone, morphine, oxymorphone, oxycodone, fentanyl, and methadone, have the highest potential for abuse and a risk of producing fatal overdose due to respiratory depression. Alcohol, CNS depressants, and other opioids potentiate the respiratory depressant effects of hydromorphone, increasing the risk for respiratory depression that might result in death; see Drug/Lab Interactions. ■ Use caution in elderly or debilitated patients and in patients with conditions accompanied by hypoxia or hypercapnia or upper airway obstruction. In these patients, even moderate therapeutic doses may dangerously decrease pulmonary ventilation. ■ Use with extreme caution in patients with COPD, cor pulmonale, a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. Usual therapeutic doses may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Consider using nonopioid analgesics, or administer under careful medical supervision at the lowest effective dose in these patients. ■ Use with alcohol and other CNS depressants increases the risk of respiratory depression, hypotension, or profound sedation and could result in coma or death; see Drug/Lab Interactions. ■ Use with caution and reduce initial doses in elderly or debilitated patients; in patients with severe impairment of hepatic, pulmonary, or renal function; and in patients with myxedema or hypothyroidism, adrenocortical insufficiency (e.g., Addison’s disease), CNS depression or coma, toxic psychoses, prostatic hypertrophy or urethral stricture, acute alcoholism, delirium tremens, or kyphoscoliosis associated with respiratory depression. ■ The respiratory depressant effects of hydromorphone promote carbon dioxide retention, resulting in increased intracranial pressure (ICP). This increase in ICP may be markedly exaggerated in the presence of head injury, intracranial lesions, or other conditions that predispose patients to ICP. The effects on pupillary response and consciousness can obscure the clinical course and neurologic signs of further pressure increases in patients with head injuries. ■ May cause severe hypotension in patients whose ability to maintain blood pressure is compromised by a depleted blood volume or a concurrent administration of drugs such as general anesthetics, phenothiazines, or other agents that compromise vasomotor tone; see Drug/Lab Interactions. ■ Use with caution in patients in circulatory shock. Vasodilation caused by the drug may further reduce cardiac output and BP. ■ May produce orthostatic hypotension in ambulatory patients. ■ Avoid administration in patients with GI obstruction. Use with caution in patients who are at risk for developing ileus. Diminishes peristalsis and may prolong obstruction. ■ Symptoms of acute abdominal conditions may be masked. Use with caution in patients with biliary tract disease, including acute pancreatitis; may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions. ■ Cough reflex may be suppressed. ■ Seizures and myoclonus have been reported in patients administered high parenteral doses. May also aggravate pre-existing seizures in patients with a convulsive disorder and may induce or aggravate seizures in some clinical settings. ■ Tolerance (the need to increase doses to maintain a defined effect such as analgesia) to the different effects of hydromorphone may develop to varying degrees and at varying rates. ■ A Schedule II controlled substance. Physical dependence can develop but is not a factor in the presence of chronic cancer and noncancer pain. Physical dependence is manifest by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. ■ Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse poses a hazard of overdose and death. Use with caution in patients with alcoholism and other drug dependencies. See prescribing information for further discussion regarding abuse, addiction, physical dependence, and tolerance. ■ Some products may use a latex stopper and some may contain sulfites; may cause a hypersensitivity reaction in susceptible patients. ■ See Maternal/Child.

Drug/lab interactions

Potentiated by phenothiazines and other CNS depressants such as opioid analgesics, alcohol, anticholinergics, antihistamines, barbiturates, centrally acting antiemetics, general anesthetics, hypnotics, sedatives, MAO inhibitors (e.g., selegiline [Eldepryl]), psychotropic agents (e.g., antidepressants, antianxiety agents), and skeletal muscle relaxants (e.g., cyclobenzaprine [Flexeril]). Side effects (e.g., CNS or respiratory depression, constipation, hypotension) may be additive. Reduced dosages of both drugs may be indicated. Hydromorphone may enhance the action of neuromuscular blocking agents (e.g., atracurium [Tracrium]) and produce an increased degree of respiratory depression. ■ Do not initiate treatment with hydromorphone within 14 days of use of a MAO inhibitor. ■ Administration of agonist/antagonist analgesics (e.g., butorphanol [Stadol], buprenorphine [Buprenex]) to an opiate-dependent patient receiving a pure opiate may precipitate withdrawal symptoms. ■ Concurrent use with anticholinergics (e.g., dimenhydrinate) or drugs with anticholinergic activity may cause urinary retention, severe constipation, and paralytic ileus. ■ Plasma amylase and lipase determinations may be unreliable for 24 hours following opioid administration.

Side effects

Most frequently occurring side effects include dizziness, dry mouth, dysphoria, euphoria, flushing, light-headedness, nausea, pruritus, sedation, sweating, and vomiting. Other side effects may include abnormal dreams; agitation; alteration of moods; anorexia; antidiuretic effects; anxiety; arrhythmias (e.g., bradycardia, palpitations, tachycardia); biliary colic; blurred or impaired vision; bronchospasm; chills; depression; disorientation and hallucination; drug abuse, addiction, and dependence; GI effects (e.g., abdominal pain, constipation, diarrhea, ileus) and effects in sphincter of Oddi; headache; hypotension; increased intracranial pressure; injection site pain and urticaria; insomnia; laryngospasm; miosis; muscle rigidity; nervousness; nystagmus; paresthesia; rash; seizures; shock; taste alteration; tremor; urinary retention or hesitancy; weakness.

Antidote

Notify the physician of any side effect. If minor side effects progress or any major side effect occurs, including the onset of symptoms of overdose, discontinue the drug and notify the physician. Naloxone will reverse serious cardiovascular, CNS, and respiratory reactions. Naloxone use should be reserved for situations in which clinically significant respiratory or circulatory depression is present. Titrate naloxone dose carefully to avoid precipitating an acute abstinence syndrome or uncontrolled pain. The duration of action of hydromorphone may exceed the duration of action of naloxone. Monitor patient carefully. Repeat doses of naloxone may be required. A patent airway, artificial ventilation, oxygen therapy, and other symptomatic treatment must be instituted promptly. Treat anaphylaxis as indicated or resuscitate as necessary.

Usual dose

Manufacturer provides a quick-use reference guide in carton to facilitate immediate administration. It covers reconstitution, mixing, infusion rate, common S/S of cyanide poisoning with or without smoke inhalation, incompatibilities, and alternate diluents.

Pediatric dose

Safety and effectiveness for use in pediatric patients not established but has been used outside the United States.

Dose adjustments

No dose adjustments required in the elderly. ■ Potential need for dose adjustment in patients with impaired hepatic or renal function has not been studied.

Dilution

Each kit contains one 5-Gm, 250-mL glass vial of lyophilized hydroxocobalamin, a sterile transfer spike, a sterile vented infusion tubing, a quick-use reference guide, and a package insert. The glass vial is marked with a fill line for diluent. Using a sterile spike, transfer 200 mL of NS diluent into the glass vial (to the fill line [25 mg/mL]). If NS is not available, LR or D5W may be used. Do Not Shake! Invert or rock vial for at least 60 seconds to mix. Solution should be clear and dark red. Attach infusion tubing and begin infusion of the first vial; see Rate of Administration.

Compatibility

Manufacturer lists as incompatible with ascorbic acid, blood products (whole blood, packed red cells, platelet concentrate, and/or fresh frozen plasma), diazepam (Valium), dobutamine, dopamine, fentanyl, nitroglycerin IV, pentobarbital (Nembutal), propofol (Diprivan), sodium nitrite, sodium thiosulfate. Do not administer simultaneously through the same IV line. Use of a separate line on the opposing extremity is recommended.

Rate of administration

Each 5-Gm dose properly diluted and evenly distributed over 15 minutes. The rate of infusion for the second 5-Gm dose may range from 15 minutes (for a patient in extremis) to 2 hours based on patient condition.

Actions

A high dose of cyanide can result in death within minutes by inhibiting the cells’ ability to use oxygen (inhibition of cytochrome oxidase results in arrest of cellular respiration). Specifically, cyanide binds with a component of cytochrome oxidase (cytochrome a3), prevents the cell from using oxygen, and forces anaerobic metabolism; this results in lactate production, cellular hypoxia, and metabolic acidosis. Each molecule of hydroxocobalamin can bind one cyanide ion to form cyanocobalamin (vitamin B₁₂) and reverse the toxic process. Cyanocobalamin is then excreted in urine.

Indications and uses

Treatment of known or suspected cyanide poisoning. Administer without delay if clinical suspicion of cyanide poisoning is high. Symptoms of cyanide poisoning include chest tightness, confusion, dyspnea, headache, nausea. Signs of cyanide poisoning include altered mental status (e.g., confusion, disorientation), seizures or coma, mydriasis (excessive dilation of the pupil of the eye), abnormally rapid or deep breathing (early), abnormally slow breathing or apnea (late), hypertension (early), hypotension (late), cardiovascular collapse, vomiting, plasma lactate concentration equal to or greater than 8 mmol/L. Smoke inhalation victims with cyanide poisoning have usually been exposed to fire and smoke in an enclosed area and may present with soot around mouth, nose, and/or oropharynx or an altered mental status. They may have a plasma lactate concentration equal to or greater than 10 mmol/L.

Contraindications

Manufacturer states, “None”; see Precautions.

Precautions

For IV use only. ■ In addition to treatment with hydroxocobalamin, immediate confirmation of airway patency, adequacy of oxygenation and hydration, cardiovascular support (may be hypotensive or hypertensive), and management of seizure activity is required. Decontamination measures may also be indicated. ■ Use caution in patients with known hypersensitivity to hydroxocobalamin or cyanocobalamin (vitamin B₁₂). Consider alternative treatments if available (e.g., sodium nitrite and sodium thiosulfate). ■ Collection of a pretreatment blood sample would be useful in confirming a diagnosis of cyanide poisoning but should not delay treatment. ■ May cause photosensitivity. ■ Use in patients with impaired hepatic or renal function has not been studied. ■ See Drug/Lab Interactions.

Drug/lab interactions

Formal drug interaction studies have not been conducted. ■ Sodium nitrite and sodium thiosulfate are also used to treat cyanide poisoning. They are incompatible with hydroxocobalamin and must be administered in a separate IV line if used concurrently. Safety of coadministration has not been established. ■ Because of its deep red color, hydroxocobalamin interferes with numerous clinical laboratory tests. Effects persist for varying lengths of time depending on test. See package insert for specifics. ■ Deep red color may cause hemodialysis machines to shut down (an erroneous detection of a “blood leak”). Consider before hemodialysis is initiated in patients treated with hydroxocobalamin.

Side effects

Most common side effects include chromaturia, decreased lymphocytes, erythema, headache, hypertension, injection site reactions, nausea, and rash. Hypersensitivity reactions and hypertension are the most serious side effects associated with hydroxocobalamin. Other reactions that may occur include abdominal discomfort, chest discomfort, diarrhea, dizziness, dry throat, dyspepsia, dysphagia, dyspnea, hematochezia (blood in stool), hot flashes, impaired memory, irritation, peripheral edema, pruritus, redness and swelling of the eyes, restlessness, throat tightness, urticaria, and vomiting.

Antidote

Keep physician informed of all side effects; will be treated symptomatically. Note Compatibility before treating hypertension or seizures; use an alternate IV line if indicated. Severe hypersensitivity reactions may require epinephrine (Adrenalin), antihistamines (e.g., diphenhydramine [Benadryl]), corticosteroids (e.g., hydrocortisone), or bronchodilators (e.g., albuterol, theophylline). Data on overdose not available; manage symptomatically. Hemodialysis may be effective and is indicated for significant hydroxocobalamin toxicity. Cardiac and/or respiratory arrest may occur before treatment has an effect; resuscitate as indicated.

Usual dose

Variable depending on patient’s blood loss, maintenance or restoration of hemodynamics, and hemodilution (dilution effect). Daily dose may be administered repetitively over several days. Titrate to individual colloid needs, hydration status, and hemodynamics.

Pediatric dose

See Usual Dose. Pediatric dose should be adjusted to the individual patient’s colloid needs, taking into account the patient’s underlying disease state and hemodynamic and hydration status. Doses used in clinical trials are listed in the following chart.

Pediatric Dosing of 6% Hydroxyethyl Starch 130/0.4 in 0.9% Sodium Chloride in Clinical Trials
	Recommended Daily Dose	Mean Daily Dose ± SD* in Clinical Trials
Pediatric Age-Groups	Up to 50 mL/kg body weight in all age-groups
<2 years		16 ± 9 mL/kg body weight
2 to 12 years		36 ± 11 mL/kg body weight
>12 years		Same as adult dose

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