(vack-SIN-ee-ah ih-MUNE GLAW-byoo-lin IV)
VIGIV
Immunizing agent (passive)
Usual dose
100 mg/kg (2 mL/kg) as a single-dose IV infusion; see Monitor. May be repeated based on the severity of symptoms and on individual patient response. Higher doses (200 mg/kg or 500 mg/kg) may be considered in patients who do not respond to the initial 100 mg/kg dose; see Precautions.
Dose adjustments
Because of sucrose content, doses higher than 400 mg/kg are not recommended in patients with potential renal problems.
Dilution
Contains sucrose; see Precautions. A ready-to-use liquid preparation supplied in a 50-mL vial containing 50 mg VIGIV/mL or 2,500 mg VIGIV/vial. Solution should be colorless, free of particulate matter, and not turbid. Do not shake vial; avoid foaming. Further dilution before or during administration is not recommended. Infusion should begin within 6 hours of entering the vial and be complete within 12 hours of entering the vial. Use of a dedicated IV line, a 0.22-micron in-line filter, and a constant infusion pump is recommended. If necessary, it may be piggybacked into a pre-existing IV line containing NS or D21/2W, D5W, D10W, or D20W with or without NaCl added; see Compatibility. VIGIV should not be diluted more than 1:2 (v/v) with any of these solutions.
Filters:
Use of a 0.22-micron in-line filter is recommended; see Dilution.
Storage:
Store between 2° and 8° C (35.6° and 46.4° F). Do not use after expiration date. Infusion must begin within 6 hours and be complete within 12 hours of entering the vial. Discard partially used vials. Do not use if turbid or has been frozen.
Compatibility
Manufacturer states, “Administer separately from other drugs or medications.” If necessary, it may be piggybacked into a pre-existing IV line containing NS or D21/2W, D5W, D10W, or D20W with or without NaCl added. Flush line before and after administration. VIGIV should not be diluted more than 1:2 (v/v) with any of these solutions.
Rate of administration
Flush line before and after administration.
Administer 1 mL/kg/hr for the first 30 minutes. If no discomfort or adverse effects, it may be increased to 2 mL/kg/hr for the next 30 minutes and then to 3 mL/kg/hr for the remainder of the infusion, as tolerated. Infusion of 100 mg/kg (2 mL/kg) should take approximately 70 minutes in a 70-kg patient. Do not exceed these rates. Too-rapid infusion may cause infusion rate–related reactions (e.g., arthralgia, back pain, chills, fever, flushing, muscle cramps, nausea, vomiting, wheezing). In patients at risk for developing renal dysfunction, administer at the minimum concentration available and the minimum rate of infusion practicable. Use of a dedicated IV line, a 0.22-micron in-line filter, and a constant infusion pump (i.e., an IVAC pump or equivalent) is recommended.
Actions
An immunoglobulin (Ig). Obtained from human plasma, purified, and standardized. Donors had received booster immunizations with the Dryvax smallpox vaccine. Specific methods (e.g., cold ethanol fractionation, detergents, nanofiltration, solvents) inactivate bloodborne viruses (e.g., hepatitis, HIV). Tested and found negative for antibodies against HIV, hepatitis, Creutzfeldt-Jakob disease, and others. Contains increased levels of protective antibodies against the vaccinia virus—the live virus used in the currently available smallpox vaccine. When use is necessary, can help to minimize possible risks associated with this highly effective smallpox vaccine. Half-life is approximately 22 days but may be decreased by fever or infection (increased catabolism or consumption).
Indications and uses
Treatment and/or modification of the following conditions: aberrant infections induced by the vaccinia virus that include accidental implantation in the eyes (excluding isolated keratitis; see Contraindications), mouth, or other areas where vaccinia infection would be hazardous; eczema vaccinatum; progressive vaccinia; severe generalized vaccinia; and vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy or in individuals who have eczematous skin lesions because of the activity or extensiveness of such lesions.
Contraindications
Presence of isolated vaccinia keratitis. ■ Individuals known to have an allergic response to this or other human immunoglobulin preparations. ■ Contains trace amounts of IgA. Patients with isolated or selective IgA deficiency can develop antibodies to IgA and have an increased risk of anaphylactic reactions with subsequent exposure to blood products that contain IgA. ■ Not considered effective for the treatment of postvaccinal encephalitis.
Precautions
For IV infusion only. ■ Hypersensitivity reactions are possible and have occurred with other IGIV preparations; administer in a facility with adequate equipment and supplies to monitor the patient and respond to any medical emergency. ■ Use extreme caution in individuals with a history of prior systemic hypersensitivity reactions. Incidence of anaphylaxis may be increased, especially with repeated injections. ■ Use caution when treating complications that include vaccinia keratitis; may cause increased corneal scarring. ■ IGIV products have been associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Use extreme caution in patients with any degree of renal insufficiency; in patients 65 years of age and older; in patients with diabetes mellitus, paraproteinemia, sepsis, or volume depletion; and/or in patients receiving known nephrotoxic drugs. If used, should be administered at the minimum concentration available and at the minimum rate of infusion practicable. Products containing sucrose as a stabilizer have demonstrated an increased risk of renal dysfunction. Consider benefit versus risk before use. ■ May cause aseptic meningitis syndrome (AMS), which may begin from 2 hours to 2 days after treatment. Symptoms are drowsiness, fever, headache (severe), nausea and vomiting, nuchal rigidity, painful eye movements, and photophobia. Symptoms resolve if VIGIV is discontinued. A neurologic exam to rule out other causes of meningitis is indicated. ■ IGIV products have been associated with thrombotic events; use caution in patients with a history of cardiovascular disease or thrombotic episodes and in patients with thrombotic risk factors (e.g., cerebrovascular disease, coronary artery disease, diabetes, hypertension). Baseline assessment of blood viscosity should be made in patients at risk for hyperviscosity, including chylomicronemia, markedly high triglycerides, or monoclonal gammopathies. ■ Hemolysis and hemolytic anemia may develop. ■ Noncarcinogenic pulmonary edema (transfusion-related acute lung injury ([TRALI]) has been reported with other IGIV preparations; see Monitor. ■ Interacts with some glucose-monitoring systems; see Monitor and Drug/Lab Interactions.
Monitor:
Use of larger veins may reduce infusion site discomfort. ■ Correct volume depletion before administration. ■ Recording the lot number on vials is helpful. ■ Monitor vital signs and observe patient continuously during infusion. A precipitous drop in BP or anaphylaxis can occur at any time. Emergency equipment and supplies must be at bedside. ■ Monitor renal function (e.g., BUN, SCr) and urine output in patients at increased risk for renal failure. Obtain baseline studies, monitor at intervals, and discontinue future VIGIV therapy if renal function deteriorates. See Precautions. ■ Monitor for S/S of hemolysis (e.g., anemia, lysis of red blood cells, liberation of hemoglobin). ■ Monitor for S/S of TRALI (e.g., fever, hypoxemia, normal left ventricular function, pulmonary edema, severe respiratory distress). Usually occurs within 1 to 6 hours after completion of the transfusion. Manage with oxygen and adequate ventilatory support. If TRALI is suspected, test for the presence of antineutrophil antibodies in product and patient serum. ■ Some types of blood glucose testing systems (e.g., those based on the glucose dehydrogenase pyrroloquinoline quinone [GDH-PQQ] or glucose-dye-oxidoreductase methods) could falsely interpret the maltose contained in VIGIV as glucose. To avoid this interference by maltose contained in VIGIV, blood glucose measurements in patients receiving VIGIV must be done with a glucose-specific method (monitor and test strips); see Drug/Lab Interactions.
Patient education:
Report a burning sensation in the head, chills, cyanosis, diaphoresis, dyspnea, faintness or light-headedness, fatigue, fever, hives, itching or rash, neck pain or difficulty moving neck, tachycardia, wheezing. ■ Report chest pain or tightness, difficulty passing urine, decreased urine output, edema, fluid retention, shortness of breath, or sudden weight gain.
Maternal/child:
Category C: use during pregnancy only if clearly needed. ■ Safety for use in breast-feeding not established. ■ Safety and effectiveness for use in pediatric patients not established.
Elderly:
Not tested for safety and effectiveness in the elderly. Use with caution. Incidence of renal insufficiency and other side effects may be increased due to age, potential for decreased organ function, and pre-existing medical conditions; see Precautions.
Drug/lab interactions
Defer administration of live virus vaccines for approximately 6 months after administration of VIGIV. ■ Concurrent use with nephrotoxic drugs (e.g., aminoglycosides [e.g., gentamicin], amphotericin B [Amphotec, conventional], cidofovir [Vistide], rifampin [Rifadin]) may increase the risk of renal insufficiency. ■ Maltose in IVIG products has been shown to give falsely high blood glucose levels. Use could result in inappropriate doses of insulin, resulting in life-threatening hypoglycemia or untreated hypoglycemia masked by falsely elevated glucose readings. Review product information of the blood glucose testing system, including test strips, to determine if the system is appropriate for use with maltose-containing parenteral products. ■ Additional drug/lab interaction studies have not been completed.
Side effects
Headache and mild to moderate urticaria are most frequently observed. A full range of hypersensitivity symptoms, including anaphylaxis, is possible. Backache, dizziness, injection site reaction, nausea, and upper respiratory infections also occur. A precipitous hypotensive reaction can occur and is most commonly associated with a too-rapid rate of injection. Serious side effects reported with other IGIV products should be considered and include acute renal failure, acute tubular necrosis, osmotic nephrosis, and proximal tubular nephropathy (may result in death); aseptic meningitis syndrome; hemolytic anemia (reversible); increased BUN and SCr (may occur as soon as 1 to 2 days following infusion); noncarcinogenic pulmonary edema (transfusion-related acute lung injury [TRALI]); severe reactions (e.g., circulatory collapse, fever, loss of consciousness, nausea and vomiting, sudden onset of dyspnea), which are more common in patients with antibody deficiencies; thromboembolism. Made from human plasma; the manufacturing process attempts to eliminate the risk of bloodborne viruses (e.g., hepatitis, HIV infection, Creutzfeldt-Jakob disease), but the potential for infection cannot be ruled out.
Antidote
Reduce rate or temporarily interrupt infusion for patient discomfort or any sign of adverse reaction. Reduce rate in patients at risk for renal insufficiency. Loop diuretics (e.g., furosemide [Lasix]) may be helpful in the management of fluid overload. If patient continues to experience adverse reactions after rate has been reduced, other IGIV preparations suggest premedicating with hydrocortisone 1 to 2 mg/kg 30 minutes before the immune globulin infusion. Pretreatment with acetaminophen (Tylenol) and diphenhydramine (Benadryl) may also be useful. Discontinue the drug immediately for any signs of a hypersensitivity reaction. Notify the physician. May be treated symptomatically and infusion resumed at slower rate if symptoms subside. Treat anaphylaxis immediately. Epinephrine (Adrenalin), diphenhydramine (Benadryl), oxygen, vasopressors (e.g., dopamine), corticosteroids, and ventilation equipment must always be available. Manage TRALI with oxygen and ventilatory support. Resuscitate as necessary.
Valproate sodium 
(val-PROH-ayt SO-dee-um)
Depacon
Anticonvulsant
pH 7.6
Usual dose
Adults and pediatric patients 10 years of age or older:
For all indications optimal clinical response is usually achieved with doses less than 60 mg/kg/24 hr. Usual therapeutic range of plasma levels is 50 to 100 mcg/mL. A total daily dose exceeding 250 mg should be given in divided doses every 6 hours (studies used an every-6-hour regimen). See Precautions, Monitor, and Drug/Lab Interactions. Use of IV formulation for more than 14 days has not been studied. Transfer to oral dosing as soon as practical. Oral and IV doses are considered to be equivalent and should be given at previously established intervals (e.g., every 6 or 8 hours). See Precautions.
Complex partial seizures (monotherapy [initial]):
Begin with an initial dose of 10 to 15 mg/kg/24 hr. May be increased by 5 to 10 mg/kg/week until desired clinical response achieved or until side effects are dose limiting.
Complex partial seizures (conversion to monotherapy):
Begin with an initial dose of 10 to 15 mg/kg/24 hr. May be increased by 5 to 10 mg/kg/week until desired clinical response achieved or until side effects are dose limiting. Concomitant antiepilepsy drug (AED) dosage can usually be reduced by 25% every 2 weeks. Dose of AEDs may be decreased at the beginning of valproate therapy or decrease may be delayed for 1 to 2 weeks to avoid unwanted seizures.
Complex partial seizures (adjunctive therapy):
Begin with an initial dose of 10 to 15 mg/kg/24 hr. May be increased by 5 to 10 mg/kg/week until desired clinical response achieved. Has been used in combination with either carbamazepine (Tegretol) or phenytoin (Dilantin). Dose adjustment of these drugs is not usually needed; however, drug interactions may occur; monitor plasma concentrations, especially during early therapy.
Simple and complex absence seizures:
Begin with an initial dose of 15 mg/kg/24 hr. May be increased by 5 to 10 mg/kg/week until seizures are controlled or side effects are dose limiting.
Pediatric dose
No IV dose recommendations available for pediatric patients under 10 years of age. See Maternal/Child.
Dose adjustments
Monitor plasma concentrations when transferring from oral to IV or IV to oral; dose increases or decreases may be indicated. ■ Reduce initial dose in the elderly; base subsequent doses on clinical response and/or development of side effects. ■ Reduced dose or discontinuation of therapy may be indicated if there is evidence of decreased food or fluid intake or excessive somnolence in the elderly. ■ Reduced dose or discontinuation of therapy may be indicated if there is evidence of bruising, hemorrhage, or a disorder of hemostasis/coagulation. ■ No dose adjustments required for impaired renal function, gender, or race. ■ See Maternal/Child.
Dilution
Each single dose should be diluted with at least 50 mL of D5W, NS, or LR.
Storage:
Store vials at CRT. Diluted solutions stable at CRT for 24 hours. No preservative added; discard unused contents of vial.
Compatibility
Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.
One source suggests the following compatibilities:
Additive:
Levetiracetam (Keppra).
Y-site:
Rate of administration
A single dose as an infusion over 60 minutes. Manufacturer has recommended that a rate of 20 mg/min not be exceeded; however, results of a single study suggest that selected patients tolerated rates from 1.5 to 3 mg/kg/min, allowing administration of up to 15 mg/kg/dose over 5 to 10 minutes. Incidence of side effects may be increased with too-rapid infusion.
Actions
An anticonvulsant. A sodium salt of valproic acid. Therapeutic effect in epilepsy may result from increased brain concentrations of gamma-aminobutyric acid (GABA). Peak effect occurs at the end of a 60-minute infusion or 4 hours after an oral dose. Plasma protein binding is high and is concentration dependent. Concentration in CSF is similar to unbound concentrations in plasma (10%). Half-life range is 13 to 19 hours. The half-life will be in the lower part of the range in patients receiving other enzyme-inducing antiepileptic agents (e.g., carbamazepine [Tegretol], phenobarbital [Luminal], phenytoin [Dilantin]). Metabolized in the liver. 30% to 50% excreted in changed form in urine. Crosses placental barrier. Secreted in breast milk.
Indications and uses
Use of IV product indicated in the following specific conditions when oral administration of valproate products (e.g., divalproex sodium [Depakote]) is temporarily not feasible. ■ Treatment of complex partial seizures occurring in isolation or with other seizures (monotherapy or adjunctive therapy). ■ Treatment of simple and complex absence seizures (monotherapy or adjunctive therapy). ■ Adjunctive treatment of multiple seizure types that include absence seizures.
Unlabeled uses:
Used alone or in combination with other antiepileptic drugs for treatment of patients with status epilepticus (refractory) who have not responded to other therapies.
Limitations of use:
Because of the risk to the fetus of decreased IQ, neural tube defects, and other major congenital malformations, valproate products should not be administered to a woman of childbearing potential unless it is essential to the management of her medical condition.
Contraindications
Known hypersensitivity to valproate products. ■ Patients with hepatic disease or significant hepatic dysfunction. ■ Patients known to have mitochrondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG) gene (e.g., Alpers-Huttenlocher syndrome), and children under 2 years of age who are suspected of having a POLG-related disorder. ■ Patients with known urea cycle disorders.
Precautions
Use of IV valproate for more than 14 days has not been studied. Safety of doses above 60 mg/kg/day is not known. ■ Has caused fatal hepatic failure. Incidents usually occur during the first 6 months of treatment. Patients with a history of hepatic disease, patients taking multiple anticonvulsants, pediatric patients, patients with congenital metabolic disorders, patients with severe seizure disorders accompanied by cognitive impairment, and patients with organic brain disease may be at particular risk. Pediatric patients under 2 years of age are at the greatest risk. If valproate is used in pediatric patients under 2 years of age with or without these increased risk factors, benefits must outweigh risks; use only as a sole agent and with extreme caution. Incidence of fatal hepatotoxicity decreases in progressively older patient groups. ■ Cases of life-threatening pancreatitis have been reported in both pediatric patients and adults receiving valproate. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death. May occur at any time from shortly after initiation of therapy to years later. If pancreatitis is diagnosed, valproate should be discontinued. ■ Patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA polymerase γ (POLG) gene (e.g., Alpers-Huttenlocher syndrome) have an increased risk of valproate-induced liver failure and death; see Contraindications and Monitor. ■ Hyperammonemic encephalopathy, sometimes fatal, has been reported in patients with urea cycle disorders (UCD). Before starting valproate, consider a possible diagnosis of UCD in patients with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy-related or postpartum encephalopathy, unexplained cognitive impairment, a history of elevated plasma ammonia or glutamine, cyclical vomiting or lethargy, episodic extreme irritability, ataxia, low BUN, protein avoidance, a family history of UCD or unexplained infant deaths, or any other S/S of UCD. ■ Hyperammonemia may be present even with normal liver function tests. Hyperammonemic encephalopathy should be considered in patients who present with lethargy and vomiting or altered mental status. Hyperammonemia should also be considered in patients who present with hypothermia (unintentional drop in body temperature to less than 35° C [95° F]). Elevation of ammonia may also be asymptomatic. ■ Hyperammonemia with or without encephalopathy has been reported with concomitant administration of valproic acid and topiramate (Topamax). Has occurred in patients who have tolerated either drug alone. S/S in most cases are abated with discontinuation of either drug. ■ Hypothermia has occurred with valproate therapy both in conjunction with and in the absence of hyperammonemia. Can also occur in patients using concomitant topiramate with valproate after starting topiramate therapy or after increasing the dose of topiramate. ■ Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Some behavioral changes resolved without intervention. Others required dose reduction or discontinuation of valproate. ■ The frequency of adverse events (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions. ■ Incidence of thrombocytopenia increases at total trough concentrations greater than 110 mcg/mL in females and greater than 135 mcg/mL in males. ■ Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients receiving valproate therapy. May be fatal or life threatening. Initial S/S include fever, rash, and/or lympadenopathy associated with other organ system involvement (e.g., arthralgia, hematologic abnormalities, hepatitis, myocarditis, myositis, nephritis). Eosinophilia is often present. Discontinue valproate and use alternative therapy. ■ Plasma protein binding is decreased and free fraction is increased in the elderly, in hyperlipidemic patients, in chronic hepatic disease, in impaired renal function, and in the presence of other drugs; see Drug/Lab Interactions. Total plasma concentrations may be normal, but free concentrations may be substantially elevated in these patients. ■ Antiepilepsy drugs should not be abruptly discontinued in patients being treated for major seizure activity. Reduce AED doses gradually to prevent status epilepticus. ■ Can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). Do not administer to a woman of childbearing potential unless essential to the management of her medical condition. Consider benefit versus risk to the fetus in women of childbearing age. Do not use to treat non–life-threatening conditions (e.g., migraine). See Maternal/Child. ■ In vitro studies suggest that valproate may stimulate the replication of the HIV and CMV viruses under certain experimental conditions. The clinical significance of this is unknown but should be kept in mind when evaluating patients with HIV or CMV. ■ Not recommended for use in patients with acute head trauma for the prophylaxis of posttraumatic seizures.
Monitor:
Thrombocytopenia, inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters (e.g., low fibrinogen, coagulation factor deficiencies, acquired von Willebrand disease) have been reported. Obtain baseline platelet counts and coagulation tests and monitor during therapy. Repeat before planned surgery and during pregnancy. ■ Obtain baseline serum liver testing and monitor frequently during therapy, especially during the first 6 months. ■ Observe closely for S/S of hepatotoxicity (e.g., anorexia, facial edema, lethargy, loss of seizure control, malaise, weakness, vomiting). ■ Abdominal pain, anorexia, nausea, and vomiting may be symptoms of pancreatitis and should be evaluated promptly. ■ Valproate products should be used only after other anticonvulsants have failed in patients over 2 years of age who are clinically suspected of having a hereditary mitochondrial disease. Closely monitor during treatment for the development of acute liver injury with regular clinical assessments and serum liver testing. Perform POLG mutation screening as indicated (e.g., family history, unexplained encephalopathy, refractory epilepsy [focal, myoclonic], status epilepticus at presentation, developmental delays, psychomotor regression, axonal sensorimotor neuropathy, myopathy cerebellar ataxia, ophthalmoplegia, or complicated migraine with occipital aura). ■ Therapeutic serum levels for most patients will range from 50 to 100 mcg/mL; however, a good correlation has not been established between daily dose, serum levels, and therapeutic effect. Some patients may be controlled with lower or higher serum concentrations. One contributing factor is the nonlinear, concentration-dependent protein binding of valproate, which affects the clearance of the drug. ■ Monitor antiepileptic concentrations more frequently whenever concomitant AEDs are being introduced or withdrawn, and observe closely for seizure activity. ■ When used as replacement therapy, the equivalence shown between the IV and oral formulations was evaluated only in an every-6-hour regimen. If valproate sodium is given twice or three times daily, close monitoring of trough plasma levels may be needed to ensure therapeutic levels are being maintained. ■ Monitor serum concentrations more frequently if any of the risk factors listed in Dose Adjustments or Precautions are present, and when any drugs that affect hepatic enzymes are introduced or discontinued; see Drug/Lab Interactions. ■ Evaluate for S/S of UCD; see Precautions and Antidote. ■ Consider hyperammonemia encephalopathy in patients who develop unexplained lethargy and vomiting or changes in mental status. Consider hyperammonemia in patients who present with hypothermia. Elevations of ammonia may be asymptomatic; monitor plasma ammonia levels closely; see Antidote. Treat hyperammonemia and assess for underlying UCD. ■ Observe patient closely for signs of CNS side effects; see Precautions. ■ Monitor for S/S of DRESS. ■ Total serum valproic acid concentration is affected by variable free-fractions of drug; consider hepatic metabolism and protein binding when interpreting valproic acid concentrations. ■ See Dose Adjustments, Precautions, and Drug/Lab Interactions for additional monitoring requirements.
Patient education:
May cause drowsiness; determine effects before driving or operating any machinery. ■ Avoid pregnancy; use effective contraception; see Maternal/Child. ■ Read the patient information leaflet provided by manufacturer, and discuss your medical history and concurrent prescription and nonprescription medications with your health care provider. ■ Promptly report symptoms such as abdominal pain, anorexia, changes in mental state, fever, jaundice, lethargy, lymphadenopathy, nausea, rash, unexplained lethargy, unintentional drop in body temperature to less than 35° C (95° F), or vomiting; may be symptoms of serious side effects (e.g., hepatotoxicity, hyperammonemia, hypersensitivity, pancreatitis) and require prompt evaluation and treatment. ■ May increase the risk of suicidal thoughts and behavior. Promptly report emergence or worsening of the S/S of depression, any unusual changes in mood or behavior, or thoughts about self-harm. ■ Women who are pregnant or who become pregnant should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. ■ See Maternal/Child.
Maternal/child:
Category D: avoid pregnancy. Valproate products should be used during pregnancy only if other anticonvulsants have failed to control symptoms or are otherwise unacceptable. There is an increased risk for major congenital malformations, particularly neural tube defects (e.g., spina bifida) and other birth defects such as craniofacial defects, cardiovascular malformation, hypospadias, and limb malformations; in addition, there is a risk for decreased IQ in infants exposed to valproate sodium and related products in utero. The incidence of congenital malformations associated with the use of valproate by women with seizure disorders during pregnancy is higher than in women with seizure disorders who use other AEDs. The increased teratogenic risk from valproate in women with epilepsy is expected to be reflected in an increased risk in other indications (e.g., bipolar disorder, migraine). Use during pregnancy only if essential for management of a serious medical condition (e.g., seizures). ■ Evidence suggests that folic acid supplementation before conception and during the first trimester decreases the risk for congenital neural tube defects in the general population. Tests to detect neural tube and other defects should be considered as part of routine prenatal care in pregnant women receiving valproate. Dietary folic acid supplementation before conception and during pregnancy is recommended. ■ To prevent major seizures, do not discontinue valproate abruptly in these patients; can precipitate status epilepticus, resulting in maternal and fetal hypoxia and a threat to life. ■ When used during pregnancy, valproate has caused clotting abnormalities in the mother that may result in hemorrhagic complications in the neonate. Deaths have been reported. If clotting parameters are abnormal in the mother, then these parameters should also be monitored in the neonate; see Monitor. ■ Has caused hepatic failure in infants exposed to valproate in utero. ■ Has caused hypoglycemia in infants exposed to valproate in utero. ■ Use with caution during breast-feeding. ■ Neonates under 2 months have a markedly decreased ability to eliminate valproate compared to older pediatric patients and adults. ■ Pediatric patients 3 months to 10 years of age have 50% higher clearance rates based on weight. ■ Younger pediatric patients, especially those receiving enzyme-inducing drugs (e.g., carbamazepine, phenobarbital, phenytoin) will require larger maintenance doses to achieve therapeutic valproic acid concentrations. ■ IV product has not been studied in pediatric patients under 2 years of age. If used, use as a sole agent with extreme caution. ■ Children under 2 years of age are at an increased risk for developing fatal hepatotoxicity. ■ See Precautions and Monitor.
Elderly:
May be more prone to adverse events. Initial dose should be lower, and dosage should be increased slowly. Rate of clearance decreased, free fraction increased; see Dose Adjustments. ■ Monitor for fluid and nutritional intake, dehydration, somnolence, and other adverse events. Dose reduction or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. ■ A higher percentage of patients over 65 years of age reported accidental injury, infection, pain, somnolence, and tremor.
Drug/lab interactions
Clearance increased and effectiveness reduced by drugs that induce hepatic enzymes (e.g., phenytoin [Dilantin], carbamazepine [Tegretol], phenobarbital [Luminal], primidone [Mysoline], ritonavir [Norvir]); increased monitoring of valproate and concomitant drug concentrations indicated. ■ Aspirin decreases protein binding, inhibits metabolism, and increases free concentration of valproate; use caution and monitor valproate concentrations if administered concomitantly. ■ Peak concentrations increased if coadministered with felbamate (Felbatol); reduced dose of valproate indicated. ■ Metabolism may be decreased and serum levels increased when given concurrently with erythromycin. ■ Carbapenem antibiotics (e.g., doripenem [Doribax], ertapenem [Invanz], meropenem [Merrem]) may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Monitor valproic acid levels. Consider alternative antibacterial or anticonvulsant therapy if serum valproate concentrations drop significantly or seizure control deteriorates. ■ Rifampin (Rifadin) may increase clearance of valproate and require dose adjustment. ■ Inhibits metabolism of barbiturates (e.g., phenobarbital) and primidone, increasing their effects. Monitor for neurologic toxicity; obtain barbiturate serum levels and reduce barbiturate dose as indicated. ■ May decrease serum levels of carbamazepine. Carbamazepine decreases plasma concentrations of valproate, and a loss of seizure control may occur; monitor carefully and increase valproate dose if indicated. ■ Concomitant use with clonazepam (Klonopin) may induce absence status in patients with a history of absence-type seizures. ■ Displaces some protein-bound drugs (e.g., carbamazepine, diazepam [Valium], phenytoin, tolbutamide, warfarin [Coumadin]). In addition to decreasing protein binding, may also decrease the metabolism of diazepam and phenytoin. Dose adjustments and serum concentrations may be indicated. ■ Phenytoin with valproate has caused breakthrough seizures in patients with epilepsy; adjust dose of phenytoin as indicated by serum concentrations. ■ Hyperammonemia with or without encephalopathy, as well as hypothermia, has been reported with concomitant administration of valproic acid and topiramate (Topamax); see Precautions. ■ Monitor coagulation tests if administered with anticoagulants (e.g., warfarin). ■ CNS effects may be increased when given concurrently with CNS depressants (e.g., benzodiazepines [e.g., diazepam (Valium)] and tricyclic antidepressants [e.g., amitriptyline (Elavil)]). ■ May decrease clearance and increase effects of amitriptyline (Elavil) and nortriptyline (Aventyl). Dose reduction of these drugs may be required. ■ Inhibits metabolism of ethosuximide (Zarontin); monitor serum concentrations of both drugs with concomitant administration. ■ Concurrent administration of lamotrigine (Lamictal) and valproate may increase lamotrigine levels. Serious skin reactions have been reported. Dose adjustments of lamotrigine may be required. ■ Decreases clearance and may increase toxicity of zidovudine (AZT, Retrovir). ■ Rufinamide (Banzel) clearance is decreased by valproate. Concentrations were increased by less than 16% to 70% depending on the concentration of valproate. Patients stabilized on rufinamide before initiating valproate therapy should begin valproate at a low dose and titrate to a clinically effective dose. Similarly, patients on valproate should begin rufinamide at a dose lower than 10 mg/kg/day (pediatric patients) or 400 mg/day (adults). ■ See package insert for additional information about many drugs that do not present significant clinical interactions. ■ May alter thyroid function tests. ■ May cause false-positive urine ketone test.
Side effects
Abdominal pain; alopecia; amblyopia/blurred vision; amnesia; anorexia with weight loss; asthenia; ataxia; bronchitis; constipation; depression; diarrhea; diplopia; dizziness; dyspepsia; dyspnea; ecchymosis; emotional lability; fever; flu syndrome; headache; increased appetite with weight gain; infection; insomnia; nausea; nervousness; nystagmus; peripheral edema; pharyngitis; rhinitis; somnolence; thinking abnormally; thrombocytopenia; tinnitus; tremor; and vomiting are most common. Accidental injury, back pain, chest pain, euphoria, hypesthesia, injection site inflammation, injection site pain, rash, sweating, taste perversion, and vasodilation were the next most commonly reported side effects. Psychiatric symptoms, including aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hallucinations, hostility, irritability, and suicidal tendencies, have also been reported. Frequency of elevated liver enzymes and thrombocytopenia may be dose related. Fatal hepatotoxicity (anorexia, facial edema, lethargy, loss of seizure control, malaise, sweating, vasodilation, vomiting, weakness) has occurred. Encephalopathy with or without fever has caused fatalities in patients with hyperammonemic encephalopathy and/or underlying UCD disorder. See Precautions for other reported serious adverse events.
Overdose:
Somnolence, deep coma, heart block, and hypernatremia. Some fatalities have been reported.
Post-marketing:
Many adverse reactions have been reported during postapproval use of valproate sodium. The frequency of reactions and/or causal relationship to valproate may be difficult to determine. Some of the reported reactions have included dermatologic reactions (e.g., erythema multiforme, nail and nail bed disorders, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis), endocrine abnormalities (e.g., elevated testosterone, hirsutism, hyperandrogenism, secondary amenorrhea), enuresis, Fanconi’s syndrome, hair color and texture changes, hematologic reactions (e.g., anemia including macrocytic with or without folate deficiency, aplastic anemia, bone marrow suppression), hypersensitivity reactions (including anaphylaxis), osteopenia, osteoporosis, reproductive reactions (e.g., aspermia, azoospermia, male infertility), and weight gain.
Antidote
Keep physician informed of all side effects. Some may respond to a decrease in the rate of administration. Discontinue immediately if signs of suspected or apparent significant hepatic dysfunction appear (e.g., hyperammonemia, elevated liver function tests) or S/S of underlying UCD. Hepatic dysfunction may progress after valproate is discontinued. Discontinue if S/S of DRESS occur. Initiate alternate therapy. Reduce dose or discontinue if bruising, hemorrhage, or abnormal coagulation parameters occur (e.g., thrombocytopenia). Discontinue if S/S of pancreatitis occur. All of the above situations may be life threatening and will require immediate symptomatic treatment. Maintain a patent airway and resuscitate as indicated. Support patient as required in treatment of overdose; monitor and maintain adequate urine output. Hemodialysis is effective in overdose. Naloxone may reverse CNS depressant effects in overdose but may also reverse antiepilepsy effects of valproate. Psychotic symptoms may require dose reduction or discontinuation of valproate.
Vancomycin hydrochloride
(van-koh-MY-sin hy-droh-KLOR-eyed)
Antibacterial (tricylic-glycopeptide)
pH 2.4 to 5
Usual dose
7.5 mg/kg or 500 mg every 6 hours or 15 mg/kg or 1 Gm every 12 hours for 7 to 10 days. Maximum dosage of 3 to 4 Gm/24 hr used only in extreme situations. Normal renal function required.
Prevention of bacterial endocarditis in selected penicillin-allergic patients having GI, biliary, or GU surgery or instrumentation:
Adults and adolescents:
1 Gm IV before the procedure. Give gentamicin 1.5 mg/kg IV concurrently in high-risk patients (not to exceed 120 mg). Infusion must be administered over at least 60 minutes and should be completed within 30 minutes of starting the procedure. Gentamicin may not be necessary in moderate-risk patients. Both doses may be repeated in 8 to 12 hours for high-risk patients. Vancomycin alone may be indicated in selected patients having dental procedures or upper respiratory tract surgery or instrumentation. Consult recent recommendations of the American Heart Association or the American Dental Association.
Treatment of patients with methicillin-resistant or methicillin-susceptible staphylococcal endocarditis who have a native cardiac valve:
30 mg/kg/24 hr equally divided into 2 doses (15 mg/kg every 12 hours) for 6 weeks or longer. If more than 2 Gm/day are required, monitoring of serum concentrations of vancomycin is recommended.
Treatment of patients with methicillin-resistant or methicillin-susceptible staphylococcal endocarditis who have a prosthetic valve or other prosthetic material:
30 mg/kg/24 hr equally divided into 2 doses (15 mg/kg every 12 hours) or 4 doses (7.5 mg/kg every 6 hours) for 6 weeks or longer. If more than 2 Gm/day are required, monitoring of serum concentrations of vancomycin is recommended. Given in conjunction with oral rifampin 300 mg every 8 hours for 6 weeks or longer and IM or IV gentamicin 1 mg/kg every 8 hours during the first 2 weeks of vancomycin therapy.
Treatment of endocarditis caused by viridans streptococci or streptococcus bovis:
30 mg/kg/24 hr equally divided into 2 doses (15 mg/kg every 12 hours) for 4 weeks. If more than 2 Gm/day are required, monitoring of serum concentrations of vancomycin is recommended.
Treatment of enterococcal endocarditis:
30 mg/kg/24 hr equally divided into 2 doses (15 mg/kg every 12 hours) for 4 to 6 weeks. If more than 2 Gm/day are required, monitoring of serum concentrations of vancomycin is recommended. Given in conjunction with IM or IV gentamicin 1 mg/kg every 8 hours for 4 to 6 weeks.
Perioperative prophylaxis in selected surgeries (e.g., cardiac, prosthetic valve, coronary artery bypass, joint replacement, craniotomy) when a cephalosporin cannot be used or there is a high incidence of methicillin-resistant staphylococci at the institution (unlabeled use):
1 Gm IV over 1 to 2 hours; should be completed within 30 minutes before the start of surgery. May be repeated one or more times if surgery is prolonged or major blood loss occurs. Postoperative doses are considered generally unnecessary and are not recommended.
Prevention of neonatal Group B streptococcal disease:
Used for women with penicillin hypersensitivity who should not receive β-lactam anti-infectives or if resistance to clindamycin or erythromycin is known or suspected. 1 Gm every 12 hours until delivery. Initiate at the beginning of labor or rupture of membranes.
Pediatric dose
Pediatric patients 1 month of age or older:
Mild to moderate infections:
40 mg/kg of body weight/24 hr equally divided and given every 6, 8, or 12 hours (10 mg/kg every 6 hours, 13.33 mg/kg every 8 hours, or 20 mg/kg every 12 hours) for 7 to 10 days.
Severe infections:
Up to 60 mg/kg/24 hr (15 mg/kg every 6 hours, 20 mg/kg every 8 hours, or 30 mg/kg every 12 hours) has been used if there is CNS involvement. Do not exceed 2 Gm in 24 hours.
Prevention of bacterial endocarditis in selected penicillin-allergic patients having GI, biliary, or GU surgery or instrumentation:
20 mg/kg before the procedure. Give gentamicin 1.5 mg/kg concurrently in high-risk patients (not to exceed 120 mg). Gentamicin may not be necessary in moderate-risk patients. Infusion must be administered over at least 60 minutes and should be complete within 30 minutes of starting the procedure. Both doses may be repeated in 8 to 12 hours for high-risk patients. Note comments about dental and upper respiratory surgery or instrumentation under Usual Dose.
Neonatal dose
15 mg/kg as an initial dose. See Maternal/Child. Follow with 10 mg/kg. Adjust interval based on age and/or weight as follows:
Infants up to 1 week of age:
Give every 12 hours.
Infants 1 week to 1 month of age:
Give every 8 hours.
The American Academy of Pediatrics recommends 10 to 15 mg/kg. Adjust dose and interval based on weight and/or age as follows:
| Postnatal Weight and Age | Dose and Interval |
| Less than 1.2 kg and less than 7 days of age | 15 mg/kg/dose every 24 hours |
| Less than 1.2 kg and 7 days of age or older | 15 mg/kg/dose every 24 hours |
| 1.2 to 2 kg and less than 7 days of age | 10 to 15 mg/kg/dose every 12 to 18 hours |
| 1.2 to 2 kg and 7 days of age or older | 10 to 15 mg/kg/dose every 8 to 12 hours |
| Over 2 kg and less than 7 days of age | 10 to 15 mg/kg/dose every 8 to 12 hours |
| Over 2 kg and 7 days of age or older | 15 to 20 mg/kg/dose every 6 to 8 hours |
Dose adjustments
Reduce total daily dose in premature infants and the elderly. Greater dose reductions than expected may be necessary in these patients because of impaired renal function. ■ Dose reduction required in impaired renal function. In all renal impaired patients (including functionally anephric and anuric patients), the initial dose should be no less than 15 mg/kg. See prescribing information; dose is reduced for every decrease of 10 mL/min in the CrCl. Subsequent doses of 250 to 1,000 mg every several days are suggested for functionally anephric patients. Subsequent doses of 1,000 mg every 7 to 10 days are suggested for anuric patients. Monitoring of serum levels is recommended.
Dilution
Available premixed, premixed and frozen, or reconstitute each 500-mg vial with 10 mL of SWFI. Each 500 mg must be further diluted with 100 mL of NS or D5W and given as an intermittent infusion. Also compatible in D5NS, LR, D5LR, D5 Normosol-M, Isolyte E, and acetated Ringer’s injection. Concentrations greater than 5 mg/mL are not recommended. If absolutely necessary, 1 to 2 Gm may be further diluted in sufficient amounts of the same infusion fluids and given over 24 hours. Not recommended. Also available in ADD-Vantage vials for use with ADD-Vantage infusion containers.
Storage:
Store in refrigerator after initial dilution. Maintains potency for 2 weeks in D5W or NS, 96 hours for other infusion solutions. Solutions prepared from ADD-Vantage vials stable at room temperature for 24 hours.
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 admixing with other drugs. They suggest it is incompatible with alkaline solutions (e.g., aminophylline, aztreonam [Azactam], barbiturates [e.g., pentobarbital (Nembutal)], chloramphenicol [Chloromycetin], dexamethasone [Decadron], sodium bicarbonate) and may form a precipitate with heavy metals. May inactivate aminoglycosides; should also not be combined in the same solution with albumin, selected cephalosporins, foscarnet (Foscavir), or selected penicillins; if administered concurrently, administer at separate sites or separate intervals (flush IV line with a compatible solution before and after administration).
One source suggests the following compatibilities:
Additive:
See general comments under Compatibility. Acetaminophen (Ofirmev), amikacin, aminophylline, atracurium (Tracrium), aztreonam (Azactam), calcium gluconate, cefepime (Maxipime), dimenhydrinate, famotidine (Pepcid IV), heparin, hydrocortisone sodium succinate (Solu-Cortef), meropenem (Merrem IV), potassium chloride (KCl), ranitidine (Zantac), verapamil.
Y-site:
See general comments under Compatibility. Acyclovir (Zovirax), aldesleukin (Proleukin), allopurinol (Aloprim), alprostadil, amifostine (Ethyol), amiodarone (Nexterone), ampicillin, ampicillin/sulbactam (Unasyn), anidulafungin (Eraxis), atracurium (Tracrium), aztreonam (Azactam), caspofungin (Cancidas), cefazolin (Ancef), cefepime (Maxipime), cefotaxime (Claforan), cefotetan, cefoxitin (Mefoxin), ceftazidime (Fortaz), ceftriaxone (Rocephin), cefuroxime (Zinacef), cisatracurium (Nimbex), cyclophosphamide (Cytoxan), dexmedetomidine (Precedex), diltiazem (Cardizem), docetaxel (Taxotere), doripenem (Doribax), doxapram (Dopram), doxorubicin liposomal (Doxil), enalaprilat (Vasotec IV), esmolol (Brevibloc), etoposide phosphate (Etopophos), fenoldopam (Corlopam), filgrastim (Neupogen), fluconazole (Diflucan), fludarabine (Fludara), foscarnet (Foscavir), gallium nitrate (Ganite), gemcitabine (Gemzar), granisetron (Kytril), heparin, hetastarch in electrolytes (Hextend), hydromorphone (Dilaudid), insulin (regular), labetalol, levofloxacin (Levaquin), linezolid (Zyvox), lorazepam (Ativan), magnesium sulfate, melphalan (Alkeran), meperidine (Demerol), meropenem (Merrem IV), methotrexate, midazolam (Versed), milrinone (Primacor), morphine, mycophenolate (CellCept IV), nafcillin (Nallpen), nicardipine (Cardene IV), ondansetron (Zofran), paclitaxel (Taxol), palonosetron (Aloxi), pancuronium, pemetrexed (Alimta), piperacillin/tazobactam (Zosyn), propofol (Diprivan), remifentanil (Ultiva), sargramostim (Leukine), sodium bicarbonate, tacrolimus (Prograf), teniposide (Vumon), theophylline, thiotepa, ticarcillin/clavulanate (Timentin), tigecycline (Tygacil), vecuronium, vinorelbine (Navelbine), warfarin (Coumadin), zidovudine (AZT, Retrovir).
Rate of administration
Severe hypotension, with or without red blotching of the face, neck, chest, and extremities, and cardiac arrest can occur with too-rapid injection.
A single dose properly diluted (concentration of no more than 5 mg/mL) at a rate not to exceed 10 mg/min or 60 minutes, whichever is longer. Another reference suggests infusion over 1 to 2 hours. This intermittent infusion is the preferred route of administration because of high incidence of thrombophlebitis.
Pediatric rate:
A single dose over a minimum of 60 minutes.
Actions
A very potent tricyclic glycopeptide antibiotic, it is bactericidal against gram-positive organisms. Bactericidal action results from the inhibition of cell wall synthesis. Also alters bacterial cell-membrane permeability and RNA synthesis. Well distributed in most body tissues and fluids, including pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Penetration into the CSF occurs when the meninges are inflamed. Half-life is 4 to 6 hours in patients with normal renal function. Vancomycin is excreted in biologically active form in the urine. Crosses the placental barrier. Secreted in breast milk.
Indications and uses
Serious gram-positive infections (e.g., staphylococcal infections), including endocarditis, septicemia, bone, lower respiratory tract, and skin and skin structure infections that do not respond or are resistant to other less toxic antibiotics, such as penicillins or cephalosporins (e.g., methicillin-resistant staphylococci). ■ Penicillin-allergic patients. ■ Treatment of endocarditis caused by Streptococcus viridans or S. bovis concurrently with an aminoglycoside antibiotic; endocarditis caused by diphtheroids or S. epidermidis concurrently with rifampin and/or an aminoglycoside. ■ Parenteral form used orally for pseudomembranous colitis/staphylococcal enterocolitis caused by C. difficile.
Unlabeled uses:
Prophylaxis against bacterial endocarditis in moderate or high-risk (prosthetic heart valves, congenital or rheumatic heart disease) penicillin-allergic patients undergoing GI, biliary, or GU surgery or instrumentation. Given in combination with gentamicin in GI or GU procedures.
Contraindications
Known hypersensitivity to vancomycin. Solutions containing dextrose may be contraindicated in patients with allergies to corn or corn products.
Precautions
To reduce the development of drug-resistant bacteria and maintain its effectiveness, vancomycin should be used only to treat or prevent infections proven or strongly suspected to be caused by bacteria. ■ Sensitivity studies necessary to determine susceptibility of the causative organism to vancomycin. ■ Prolonged use of drug may result in superinfection caused by overgrowth of nonsusceptible organisms. ■ May be ototoxic and nephrotoxic. Some clinicians feel the risk of ototoxicity and nephrotoxicity is minimal in patients with normal renal function who receive vancomycin as a single agent. ■ Use caution in impaired hearing, impaired renal function, pregnancy, breast-feeding, neonates, and the elderly. ■ Clostridium difficile–associated diarrhea (CDAD) has been reported. May range from mild diarrhea to fatal colitis. Consider in patients who present with diarrhea during or after treatment with vancomycin. ■ Oral vancomycin has a local effect only (e.g., in the bowel); not for systemic use. ■ A syndrome of chemical peritonitis has been reported in patients receiving intraperitoneal vancomycin during CAPD.
Monitor:
Monitoring of serum levels and SCr may be indicated in patients at increased risk for developing nephrotoxicity and/or ototoxicity (e.g., underlying renal dysfunction, or receiving concomitant aminoglycosides [e.g., gentamicin]). ■ Determine absolute patency of vein. Necrosis and sloughing will result from extravasation. Rotate injection sites every 2 to 3 days. ■ Observe for furry tongue, diarrhea, and foul-smelling stools. ■ Severe hypotension, with or without red blotching of the face, neck, chest, and extremities, and cardiac arrest can occur with too-rapid injection (red man or red neck syndrome). ■ Monitor BP continuously during infusion to prevent a precipitous drop. ■ Auditory testing indicated with prolonged use. ■ Periodic monitoring of leukocyte count recommended in prolonged therapy. ■ See Drug/Lab Interactions.
Patient education:
Report all side effects promptly. ■ Promptly report diarrhea or bloody stools that occur during treatment or up to several months after an antibiotic has been discontinued; may indicate CDAD and require treatment.
Maternal/child:
Category C: studies not conclusive. Use only if clearly needed. ■ Safety for use in breast-feeding not established; discontinue breast-feeding. ■ Neonates have immature renal function; blood levels may be excessive. Confirmation of desired serum concentrations suggested in premature and full-term neonates.
Elderly:
Systemic and renal clearance may be reduced; dosage reduction required.
Drug/lab interactions
Synergistic with aminoglycosides (e.g., amikacin, gentamicin, tobramycin) against many strains of Staphylococcus aureus and streptococci; see package insert. Combined use may increase risk of ototoxicity and nephrotoxicity. ■ Use caution with dimenhydrinate, which can mask ototoxicity. ■ Additive toxicities may occur with systemic or topical use of other nephrotoxic, neurotoxic, or ototoxic drugs (e.g., aminoglycosides, amphotericin B, bacitracin, cisplatin, colistin, ethacrynic acid [Edecrin], furosemide [Lasix], polymyxin B). Use with caution in combination with vancomycin; serial monitoring of renal and auditory systems indicated. ■ May enhance neuromuscular blockade with nondepolarizing muscle relaxants (e.g., pancuronium). ■ May cause erythema and histamine-like flushing in pediatric patients with anesthetics. Use with anesthetics may also increase the risk of hypersensitivity reactions, including anaphylaxis and infusion reactions. Administration of vancomycin as a 1-hour infusion before anesthetic induction may reduce this interaction. ■ May inhibit methotrexate excretion and increase methotrexate toxicity. May occur even if 10 days have elapsed since vancomycin was administered. Adjust methotrexate dose as indicated.
Side effects
Chills, dizziness, fever, macular rashes, pain at injection site, pruritus, tinnitus, urticaria.
Major:
Anaphylaxis, cardiac arrest, CDAD, dyspnea, eosinophilia, hearing loss, hypotension, infusion-related events (anaphylactoid reactions, dyspnea, flushing of the upper body, pruritus, urticaria, wheezing), interstitial nephritis, neutropenia, red neck or red man syndrome, renal failure, Stevens-Johnson syndrome (erythema multiforme [flu-like symptoms that can be fatal]), thrombophlebitis, wheezing.
Post-marketing:
Drug rash with eosinophilia and systemic symptoms (DRESS).
Antidote
Notify the physician of all side effects. Hearing loss may progress even if drug is discontinued. If minor side effects are progressive or any major side effect occurs, discontinue the drug, treat hypersensitivity reaction, or resuscitate as necessary. Prevent severe hypotension by slowing infusion rate to 2 hours. Fluids, antihistamines, corticosteroids, and vasopressors (e.g., dopamine) may be required. Mild cases of CDAD may respond to discontinuation of drug. Treat CDAD with fluids, electrolytes, protein supplements, and oral vancomycin (Vancocin) or metronidazole (Flagyl) as indicated. In severe cases, surgical evaluation may be indicated. Hemodialysis or CAPD will not decrease blood levels in toxicity.
Vasopressin injection
(vay-so-PRESS-in in-JEK-shun)
Pitressin, Pressyn 
Hormone
Antidiuretic
Vasopressor (unlabeled)
pH 2.5 to 4.5
Usual dose
All IV doses and uses are unlabeled.
Treatment of shock-resistant VF or pulseless VT during cardiac arrest in adult patients:
AHA Emergency Cardiovascular Care recommends 40 units by IV push or through the endotracheal tube for one dose only (may replace the first or second dose of epinephrine).
Hemodynamic support during vasodilatory shock (e.g., septic shock):
AHA guidelines recommend a continuous infusion of 0.02 to 0.04 units/min. Other sources in the literature recommend low-dose vasopressin infusions in vasodilatory shock refractory to catecholamines. 0.04 units/min as an infusion (range was 0.01 to 0.1 units/min). Doses greater than 0.08 units/min showed no added benefit. Continue infusion until the patient is stabilized. Mean duration in a study was 18 to 168 hours.
GI hemorrhage:
0.2 units/min as an infusion. Increase each hour by 0.2 units/min until hemorrhage is controlled. Doses up to 1 unit/min are suggested. Another source suggests 0.2 to 0.4 units/min as an infusion. Gradually increase dose as needed to a maximum dose of 0.9 units/min.
Pediatric dose
All IV doses and uses are unlabeled; however, studies in pediatric patients have been conducted.
Hemodynamic support during vasodilatory shock:
0.0003 to 0.002 units/kg/min as an infusion (range is 0.018 to 0.12 units/kg/hr). Continue infusion until the patient and concurrently administered catecholamine infusions are stabilized. Mean duration in a study was 6 to 144 hours. AHA guidelines recommend a continuous infusion of 0.0002 to 0.002 units/kg/min (0.2 to 2 milliunits/kg/min).
Treatment of shock-resistant VF or pulseless VT during cardiac arrest:
Recommended for use in adult patients only. AHA guidelines recommend 0.4 to 1 unit/kg IV push (maximum dose 40 units).
GI hemorrhage:
0.002 to 0.005 units/kg/min as an infusion. Gradually increase dose as needed to a maximum dose of 0.01 units/kg/min.
Dilution
AHA guidelines do not mention the use of a diluent, which suggests that vasopressin may be given undiluted. Another source recommends dilution for IV use to a 0.1 to 1 unit/mL dilution with NS or D5W. 38 mL diluent with 2 mL vasopressin (40 units) yields 1 unit/mL. 398 mL diluent with 2 mL vasopressin (40 units) yields 0.1 unit/mL.
Storage:
Store unopened vials at CRT.
Compatibility (underline indicates conflicting compatibility information)
Consider any drug NOT listed as compatible to be INCOMPATIBLE until consulting a pharmacist; specific conditions may apply.
Consider specific use and unlabeled IV use.
One source suggests the following compatibilities:
Additive:
Verapamil.
Y-site:
Amiodarone (Nexterone), argatroban, caspofungin (Cancidas), ceftaroline (Teflaro), ciprofloxacin (Cipro IV), diltiazem (Cardizem), dobutamine, dopamine, epinephrine (Adrenalin), fluconazole (Diflucan), gentamicin, heparin, 6% hydroxyethyl starch (Voluven), imipenem-cilastatin (Primaxin), insulin (regular), lidocaine, linezolid (Zyvox), meropenem (Merrem IV), metronidazole (Flagyl IV), micafungin (Mycamine), milrinone (Primacor), moxifloxacin (Avelox), nitroglycerin IV, norepinephrine (Levophed), pantoprazole (Protonix IV), phenylephrine (Neo-Synephrine), piperacillin/tazobactam (Zosyn), procainamide (Pronestyl), sodium bicarbonate, telavancin (Vibativ), voriconazole (VFEND IV).
Rate of administration
Injection:
A single dose IV push; see Precautions.
Infusion:
See Usual Dose for recommended rates for each diagnosis. Use of a central venous catheter is recommended. Titrate rate so that perfusion remains adequate while BP is optimized. Do not discontinue abruptly; one source recommends tapering over 2 to 3 hours while monitoring effects.
Actions
Synthetic vasopressin of the posterior pituitary gland standardized to 20 units/mL. An antidiuretic. Also a potent vasoconstrictor. Causes smooth muscle contraction of all parts of the vascular bed (e.g., capillaries, small arterioles, and venules). Has a lesser effect on the smooth muscles of larger arteries and veins. This direct contractile effect on the smooth muscle of the vascular system is not antagonized by adrenergic blocking agents (e.g., atenolol [Tenormin], metoprolol [Lopressor]) and is not prevented by vascular denervation (loss of nerve impulse to the vascular system). Its IV use is as an alternative pressor agent to epinephrine. Not effective in normotensive patients; however, promotes an effective increase in BP in hypotensive patients, even when other agents have failed. Rapidly degraded by enzymes in the liver and kidneys. Plasma half-life is 10 to 35 minutes. A small amount is excreted unchanged in the urine.
Indications and uses
Used IM or SC as an antidiuretic in central diabetes insipidus or as a diagnostic aid in diabetes insipidus.
Unlabeled uses:
The AHA Handbook of Emergency Cardiovascular Care recommends use in the treatment of adult shock-refractory ventricular fibrillation (Class IIb) (an alternative pressor agent to epinephrine) and for hemodynamic support in vasodilatory shock (e.g., septic shock). Has also been used for treatment of GI hemorrhage.
Contraindications
Hypersensitivity to vasopressin or any of its components; see Precautions. AHA guidelines state “not recommended for responsive patients with coronary heart disease.”
Precautions
IV uses are unlabeled. ■ May cause ischemia of other organs (e.g., GI tract, kidneys) if fluid intake is not adequate. ■ Use with extreme caution in patients with vascular disease, especially coronary artery disease; may cause cardiac ischemia. Small doses may precipitate anginal pain, and larger doses may cause myocardial infarction. ■ May produce water intoxication; use with caution in patients with asthma, chronic nephritis and nitrogen retention, epilepsy, heart failure, migraine, or any conditions in which a rapid addition to extracellular water could be hazardous.
Monitor:
In addition to management of airway, oxygenation, and blood gas determinations, the continuous monitoring of ECG, vital signs, and fluid and electrolyte status is mandatory. ■ Monitor IV site very closely, especially if it is a peripheral site; a central venous catheter is preferred. Produces intense vasoconstriction. Avoid extravasation; vasoconstriction that may result in severe tissue necrosis and gangrene can occur. ■ Maintain adequate fluid intake to avoid ischemia of other organs. ■ Use of vasopressin in vasodilatory shock may permit reduction or discontinuation of other vasopressors. ■ Use an indwelling urinary catheter to confirm urine output and monitor closely. ■ Fluid restriction may be indicated; initial signs of water intoxication include drowsiness, listlessness, and headache, which can rapidly progress to terminal coma and convulsions. ■ See Rate of Administration, Precautions, and Drug/Lab Interactions.
Maternal/child:
Category C: safety for use during pregnancy not established; use only if clearly needed. ■ Safety for use during breast-feeding not established. ■ Safety and effectiveness for use in pediatric patients not established; however, it has been used successfully in selected critically ill pediatric patients with catecholamine-resistant hypotension.
Elderly:
See Precautions; elderly may be more sensitive to adverse effects.
Drug/lab interactions
Vasodilators (e.g., nitroglycerin, nitroprusside sodium) counteract the vasoconstrictive effects of vasopressin. ■ Additive pressor response with ganglionic blocking agents (e.g., trimethaphan [Arfonad (rarely used antihypertensive)]). ■ Antidiuretic effect may be increased with concurrent use of carbamazepine (Tegretol), chlorpropamide (Diabinese), clofibrate (Atromid-S), fludrocortisone (Florinef), tricyclic antidepressants (e.g., amitriptyline [Elavil]), urea. ■ Antidiuretic effect may be decreased with concurrent use of alcohol, demeclocycline (Declomycin), heparin, lithium (Carbolith), norepinephrine (Levophed).
Side effects
Arrhythmias, bradycardia, hypertension, and MI have resulted from high doses. Abdominal cramps, angina, arrhythmias, bronchial constriction, cardiac arrest, circumoral pallor, cutaneous gangrene, decreased cardiac output, diaphoresis, flatus, gangrene, headache (pounding), hypersensitivity reactions (including anaphylaxis), hyponatremia, injection site ischemia resulting in severe tissue necrosis and gangrene, ischemic skin and mucous membrane lesions, myocardial ischemia, nausea, organ ischemia (e.g., GI, kidney), peripheral vasoconstriction, shock, sweating, tremor, urticaria, venous thrombosis, vertigo, and vomiting.
Overdose:
Water intoxication.
Antidote
In an emergency cardiac care situation, all side effects can present life-threatening additional problems. Monitor the patient closely and observe all S/S that may indicate further deterioration. Treat symptomatically according to AHA guidelines. Monitor fluid intake and urine output to ensure adequate hydration. Extravasation and/or ischemia at the injection site should be reported immediately to prevent tissue necrosis and gangrene. If water intoxication should occur, treat with water restriction and discontinue vasopressin. If possible, discontinue gradually as described in Rate of Administration to prevent a rapid fall in BP. If severe, may require osmotic diuresis with mannitol, hypertonic dextrose, or urea alone or with furosemide (Lasix).
Vecuronium bromide 
(veh-kyour-OH-nee-um BRO-myd)
Norcuron 
Neuromuscular blocking agent (nondepolarizing)
Anesthesia adjunct
pH 4
Usual dose
Adjunct to general anesthesia:
Must be individualized, depending on previous drugs administered and degree and length of muscle relaxation required. 0.08 to 0.1 mg/kg (80 to 100 mcg/kg) of body weight initially as an IV bolus. Must be used with adequate anesthesia and/or sedation and after unconsciousness induced. One source suggests using IBW for obese patients (equal to or greater than 30% of IBW). Determine need for maintenance dose based on beginning symptoms of neuromuscular blockade reversal determined by a peripheral nerve stimulator.
IV bolus injection:
0.01 to 0.015 mg/kg (10 to 15 mcg/kg) will be required in approximately 25 to 40 minutes and every 12 to 20 minutes thereafter to maintain muscle relaxation. Higher doses (0.15 to 0.28 mg/kg) at longer intervals have been given with proper ventilation without causing adverse cardiac effects.
Continuous infusion:
1 mcg/kg/min. Begin in 20 to 40 minutes after initial bolus dose.
Support of intubated, mechanically ventilated, or respiratory-controlled adult ICU patients (unlabeled):
IV bolus injection:
0.1 to 0.2 mg/kg (100 to 200 mcg/kg) every 1 hour.
Continuous infusion:
Begin with a loading dose of 0.1 mg/kg (100 mcg/kg) followed by a maintenance dose of 0.05 to 0.1 mg/kg/hr (50 to 100 mcg/kg/hr). A lower-end or reduced dose may be indicated if administered more than 5 minutes after the start of an inhalation agent, when steady-state has been achieved, or in patients with organ dysfunction (e.g., impaired liver function). Adjust dose according to clinical assessment of the patient’s response. Use of a peripheral nerve stimulator is recommended. Vecuronium may be the preferred agent for patients with renal failure.
Pediatric dose
Adjunct to general anesthesia: 1 to 10 years of age:
May require high end of initial adult dose, and maintenance dose may be required on a more frequent basis.
Dose adjustments
Reduce dose by 15% if administered more than 5 minutes after inhalation general anesthetics. ■ Reduce dose to 0.04 to 0.06 mg/kg if following succinylcholine administration. Succinylcholine must show signs of wearing off before vecuronium is given. Use caution. ■ Reduced dose required with numerous drugs; see Drug/Lab Interactions. ■ Reduced dose may be required in renal or hepatic impairment. Preparation by dialysis before surgery is recommended for patients with renal failure. In an emergency surgery when dialysis cannot be accomplished, consider a lower initial dose. ■ Infants between 7 weeks and 1 year may require a slightly lower dose, and recovery time will be extended.
Dilution
Each 10 mg must be diluted with 5 mL SWFI (supplied). May be given by IV injection or 10 (20) mg may be further diluted in up to 100 mL NS, D5W, D5NS, or LR and given as an infusion of 0.1 (0.2) mg/mL concentration. Titrated to symptoms of neuromuscular blockade reversal.
Storage:
Stable at room temperature before reconstitution. Store under refrigeration. Discard after 24 hours except if reconstituted with bacteriostatic water; stable refrigerated up to 5 days.
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, “Has an acid pH. Reconstituted vecuronium should not be mixed with alkaline solutions (e.g., barbiturates) in the same syringe or administered simultaneously during IV infusion through the same needle or the same IV line.”
One source suggests the following compatibilities:
Additive:
Ciprofloxacin (Cipro IV).
Y-site:
Alprostadil, aminophylline, amiodarone (Nexterone), cefazolin (Ancef), cefuroxime (Zinacef), dexmedetomidine (Precedex), diltiazem (Cardizem), dobutamine, dopamine, epinephrine (Adrenalin), esmolol (Brevibloc), fenoldopam (Corlopam), fentanyl, fluconazole (Diflucan), gentamicin, heparin, hetastarch in electrolytes (Hextend), hydrocortisone sodium succinate (Solu-Cortef), hydromorphone (Dilaudid), isoproterenol (Isuprel), labetalol, linezolid (Zyvox), lorazepam (Ativan), midazolam (Versed), milrinone (Primacor), morphine, nicardipine (Cardene IV), nitroglycerin IV, nitroprusside sodium, norepinephrine (Levophed), palonosetron (Aloxi), propofol (Diprivan), ranitidine (Zantac), sulfamethoxazole/trimethoprim, vancomycin.
Rate of administration
Adjunct to general anesthesia:
A single dose as an IV bolus over 30 to 60 seconds. If maintenance dose is given as an infusion, adjust rate to specific dose desired, usually 1 mcg/kg/min. See the following chart.
| Vecuronium Guidelines for Infusion During General Anesthesia | ||
| Desired Vecuronium Delivery Rate (mcg/kg/min) | Vecuronium Infusion Delivery Rate (mL/kg/min) | |
| 0.1 mg/mL* | 0.2 mg/mL† | |
| 0.7 mcg/kg/min | 0.007 mL/kg/min | 0.0035 mL/kg/min |
| 0.8 mcg/kg/min | 0.008 mL/kg/min | 0.0040 mL/kg/min |
| 0.9 mcg/kg/min | 0.009 mL/kg/min | 0.0045 mL/kg/min |
| 1.0 mcg/kg/min | 0.010 mL/kg/min | 0.0050 mL/kg/min |
| 1.1 mcg/kg/min | 0.011 mL/kg/min | 0.0055 mL/kg/min |
| 1.2 mcg/kg/min | 0.012 mL/kg/min | 0.0060 mL/kg/min |
| 1.3 mcg/kg/min | 0.013 mL/kg/min | 0.0065 mL/kg/min |
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