Neonatal dose

All doses are based on birth weight. A course of therapy is three doses given at 24-hour intervals.

Dose adjustments

If urine output is less than 0.6 mL/kg/hr at any time a dose is to be given, withhold dose until lab studies confirm a return to normal renal function.

Dilution

Each single dose must be diluted to an appropriate volume for administration as an infusion over 15 minutes with dextrose or saline. Prepare for infusion and begin administration within 30 minutes of preparation. A fresh solution should be prepared just before each administration. Contains no preservatives; discard any unused portion.

Compatibility

Manufacturer states, “Should not be simultaneously administered in the same IV line with Total Parenteral Nutrition” (TPN). If required, interrupt TPN for 15 minutes before and after ibuprofen administration. Maintain IV line patency with dextrose or saline infusion.

Rate of administration

Administer via the IV port nearest the insertion site.

A single dose, properly diluted, and infused continuously over 15 minutes.

Actions

A nonsteroidal anti-inflammatory drug (NSAID). Mechanism of action by which it causes closure of a patent ductus arteriosus (PDA) is unknown; however, in adults it is an inhibitor of prostaglandin synthesis. By closing the patent ductus arteriosus, the need for surgical intervention is eliminated. Half-life varies inversely with postnatal age, but in general the half-life in infants is more than 10 times longer than in adults. In lower-birth-weight premature infants, half-life may range from 20 to 51 hours. Metabolism and excretion have not been studied in premature infants. In adults, it is metabolized in the liver and excreted in the urine and feces.

Indications and uses

Closure of a clinically significant patent ductus arteriosus in premature infants weighing between 500 and 1,500 Gm who are no more than 32 weeks’ gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support) is not effective. Consequences beyond 8 weeks after treatment have not been evaluated.

Contraindications

Bleeding (especially active intracranial hemorrhage or GI bleeding), coagulation defects, suspected necrotizing enterocolitis, infants with congenital heart disease (e.g., pulmonary atresia, severe coarctation of the aorta, severe tetralogy of Fallot) who require patency of the ductus arteriosus for satisfactory pulmonary or systemic blood flow, proven or suspected untreated infection, significant renal impairment, thrombocytopenia.

Precautions

For IV use only; see Monitor. ■ Reserve for infants with clear evidence of a clinically significant PDA. ■ For use only in a highly supervised setting such as an intensive care nursery. ■ No long-term evaluations available. Effects of ibuprofen on neurodevelopmental outcome and growth and on disease processes associated with prematurity (e.g., retinopathy of prematurity, chronic lung disease) have not been assessed. ■ May alter the usual signs of infection. Use with extreme caution in the presence of an existing controlled infection and in infants at risk for infection. ■ Can inhibit platelet aggregation. ■ Can prolong bleeding time in adults; use caution in infants with underlying hemostatic defects; see Contraindications. ■ Can displace bilirubin from albumin-binding sites; use with caution in infants with elevated total bilirubin.

Drug/lab interactions

Drug interactions have not been studied.

Side effects

The most commonly reported side effects include adrenal insufficiency, anemia, apnea, atelectasis, decreased urine output, edema, GI disorders (including nonnecrotizing enterocolitis), hematuria, hypernatremia, hypocalcemia, hypoglycemia, increased BUN and SCr, intraventricular hemorrhage and other bleeding, renal failure, renal insufficiency, respiratory failure, respiratory infection, sepsis, skin lesion or irritation, and urinary tract infection. Other side effects of unknown association include abdominal distension, cardiac failure, cholestasis, convulsions, feeding problems, gastritis, gastroesophageal reflux, hypotension, ileus, infections, inguinal hernia, injection site reactions, jaundice, lab abnormalities (e.g., hyperglycemia, neutropenia, thrombocytopenia), and tachycardia.

Antidote

Discontinue the drug and notify the physician of all side effects. Based on severity, side effects may be treated symptomatically or drug will be completely discontinued in favor of surgical intervention. In case of overdose, there is no specific antidote. Treat symptomatically and follow for several days after apparent recovery; GI ulceration and hemorrhage may occur. Resuscitate as necessary.

Usual dose

Discontinue infusion promptly when the presenting arrhythmia is terminated (desired effect). Must also be discontinued immediately if sustained or nonsustained ventricular tachycardia or marked prolongation of QT or QTc occurs (adverse effects). Postconversion treatment with appropriate antiarrhythmics (e.g., digoxin, verapamil, or propranolol) is usually required.

Dose adjustments

Dose selection should be cautious in the elderly. Reduced doses may be indicated based on the potential for decreased organ function and concomitant disease or drug therapy. ■ No adjustments required in patients with impaired hepatic or renal function; see Monitor. Lower doses may be indicated in post–cardiac surgery patients. In recent studies one or two infusions of 0.5 mg in patients weighing 60 kg or more or 0.005 mg/kg/dose for patients under 60 kg was effective in terminating atrial fibrillation and/or flutter.

Dilution

May be given undiluted or may be diluted in 50 mL of NS or D5W and given as an infusion. 1 mg (10 mL of a 0.1-mg/mL solution) of ibutilide in 50 mL diluent yields 0.017 mg/mL.

Compatibility

Manufacturer lists as compatible with NS and D5W packaged in glass, polyvinyl chloride, or polyolefin infusion containers. Additional information not available; consult pharmacist.

Rate of administration

A single dose by injection or infusion over 10 minutes.

Actions

A Class III antiarrhythmic agent that produces mild slowing of the sinus rate and atrioventricular conduction. Delays repolarization by activation of a slow inward current (sodium) rather than blocking outward potassium currents. Prolonged atrial and ventricular action potential duration and refractoriness result. Produces dose-related prolongation of the QT interval (may result from dose of ibutilide or rate of injection). Conversion of atrial flutter/fibrillation usually occurs within 30 minutes but may take up to 90 minutes after the start of the infusion. Most patients remain in normal sinus rhythm (NSR) for 24 hours. At recommended doses, ibutilide has no clinically significant effects on cardiac output, mean pulmonary arterial pressure, or pulmonary capillary wedge pressure. Rapidly distributed and metabolized. Elimination half-life is 6 hours (range 2 to 12 hours). Primarily excreted in urine (7% as unchanged drug). Excreted in small amounts in feces.

Indications and uses

Rapid conversion of recent-onset atrial fibrillation or atrial flutter to sinus rhythm. Patients with more recent onset of arrhythmia have a higher rate of conversion. Effectiveness was less in those with a longer-duration arrhythmia.

Contraindications

Known hypersensitivity to ibutilide or any of its components. ■ Not recommended in patients who have had a previous polymorphic ventricular tachycardia (e.g., torsades de pointes). ■ See Drug/Lab Interactions.

Precautions

For IV infusion only. ■ Usually administered by or under the direction of the physician specialist. ■ Skilled personnel and proper equipment (e.g., cardiac monitors, intracardiac pacing facilities, cardioverter/defibrillator, emergency drugs) must be immediately available. ■ May cause life-threatening arrhythmias (e.g., torsades de pointes) with or without documented QT prolongation. ■ Correct hypokalemia and hypomagnesemia before use; may exaggerate a prolonged QT and cause arrhythmias. ■ Adequate anticoagulation (usually at least 2 weeks) is required for any patient with atrial fibrillation of more than 2 to 3 days’ duration. ■ Select patients carefully; benefits (potential for maintaining sinus rhythm) must outweigh risks. Patients with chronic atrial fibrillation are more likely to revert back to atrial fibrillation after conversion to sinus rhythm. Patients with a QTc interval greater than 440 msec or a serum potassium less than 4.0 mEq/L are at very high risk to develop life-threatening arrhythmias. ■ Patients with a history of CHF may be more susceptible to sustained polymorphic VT. ■ Slightly more effective in atrial flutter than atrial fibrillation. ■ See Drug/Lab Interactions.

Drug/lab interactions

Should not be given concurrently with Class Ia antiarrhythmics (e.g., disopyramide [Norpace], procainamide [Pronestyl], quinidine) or other Class III antiarrhythmics (e.g., amiodarone [Nexterone], sotalol [Betapace]). Withhold any of these agents for at least 5 half-lives before ibutilide infusion and for 4 hours after. ■ Incidence of arrhythmia may be increased with other drugs that prolong the QT interval (e.g., phenothiazines [e.g., promethazine (Phenergan)], tricyclic antidepressants [e.g., amitriptyline (Elavil)], tetracyclic antidepressants [e.g., maprotiline (Ludiomil)]). ■ Monitor serum digoxin levels to avoid digoxin toxicity. ■ Use with digoxin, beta-blockers, or calcium channel blockers does not alter safety or effectiveness of ibutilide. However, sotalol is a beta-blocker, and its use with ibutilide is restricted because it has Class III antiarrhythmic activity; see first sentence above.

Side effects

Sustained polymorphic VT (1.7%) and nonsustained polymorphic VT (2.7%) can deteriorate into ventricular fibrillation and be fatal. May cause many other arrhythmias (e.g., first-, second-, or third-degree AV block [1.5%], bradycardia [1.2%], bundle branch block [1.9%], nonsustained monomorphic VT [4.9%], prolonged QT segment [1.2%], PVCs [5.1%], tachycardia [2.7%]), CHF (0.5%), headache (3.6%), hypertension (1.2%), hypotension (2%), nausea (1.9%), palpitation (1%).

Antidote

If proarrhythmias occur, discontinue ibutilide; correct electrolyte abnormalities (e.g., potassium and magnesium). Overdrive cardiac pacing, electrical cardioversion, or defibrillation may be required. Infusions of magnesium sulfate may be helpful. Avoid treatment with antiarrhythmic agents. VT that deteriorates to VF will require immediate defibrillation.

Usual dose

Dose adjustments

Delay second course until full recovery if severe mucositis has occurred and reduce dose by 25%. ■ Consider dose reductions in impaired liver and kidney function based on bilirubin and/or creatinine levels above the normal range. Do not administer if bilirubin is above 5 mg/dL. In one Phase III clinical trial, patients with bilirubin levels between 2.6 and 5 mg/dL received a 50% reduction in dose.

Dilution

Compatibility

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

Manufacturer states, “Should not be mixed with other drugs unless specific compatibility data are available,” and lists as incompatible with heparin. Prolonged contact with solutions of an alkaline pH (e.g., sodium lactate, sodium bicarbonate) will result in degradation of idarubicin.

One source suggests the following compatibilities:

Rate of administration

A single dose of properly diluted medication over 10 to 15 minutes through Y-tube or three-way stopcock of a free-flowing infusion of D5W or NS.

Actions

A highly toxic, synthetic, antibiotic, antineoplastic agent. An analog of daunorubicin. Rapidly distributed; has an increased rate of cellular uptake compared to other anthracyclines. It inhibits synthesis of DNA and interacts with the enzyme topoisomerase II. Results in a greater number of remissions and longer survival than previous protocols (daunorubicin and cytarabine). It is severely immunosuppressive. Extensive extrahepatic metabolism. Half-life averages 20 to 22 hours. Slowly excreted in bile and urine.

Indications and uses

Treatment of acute myeloid leukemia (AML) in adults in combination with other approved antileukemic drugs.

Contraindications

Not absolute; pre-existing bone marrow suppression, impaired cardiac function, preexisting infection; see Precautions/Monitor. ■ Do not administer if bilirubin above 5 mg/dL.

Precautions

Follow guidelines for handling cytotoxic agents. See Appendix A, p. 1331. ■ Administered by or under the direction of the physician specialist, with facilities for monitoring the patient and responding to any medical emergency. ■ For IV use only. Do not give IM or SC. ■ Use extreme caution in pre-existing drug-induced bone marrow suppression, existing heart disease, previous treatment with other anthracyclines (e.g., daunorubicin), other cardiotoxic agents (e.g., bleomycin), or radiation therapy encompassing the heart. ■ Myocardial toxicity may cause potentially fatal acute congestive heart failure, acute life-threatening arrhythmias, or other cardiomyopathies. Cardiac toxicity is more common in patients who have received prior anthracyclines (e.g., doxorubicin) or who have pre-existing cardiac disease. ■ May cause severe myelosuppression. ■ Use with caution in patients with hepatic or renal dysfunction. Metabolism and excretion of idarubicin may be impaired; see Dose Adjustments.

Drug/lab interactions

Bone marrow toxicity is additive with other chemotherapeutic agents. ■ Risk of cardiotoxicity increased in patients previously treated with maximum cumulative doses of other anthracyclines (e.g., doxorubicin [Adriamycin], mitoxantrone [Novantrone]) and/or radiation encompassing the heart. ■ Leukopenic and/or thrombocytopenic effects may be increased with drugs that cause blood dyscrasias (e.g., anticonvulsants [e.g., carbamazepine (Tegretol), phenytoin (Dilantin)], NSAIDs [e.g., ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn)]). Adjust dose based on differential and platelet count. ■ Do not administer live virus vaccines to patients receiving antineoplastic drugs. ■ See Precautions/Monitor.

Side effects

Acute congestive heart failure, alopecia (reversible), arrhythmias, bone marrow suppression (marked with average doses), cramping, decrease in systolic ejection fraction, depressed QRS voltage, diarrhea, erythema and tissue necrosis (if extravasation occurs), fever, headache, hemorrhage (severe), hepatic function changes, infection, mucositis, myocarditis, nausea, pericarditis, renal function changes, seizures, skin rash, urticaria (local), vomiting.

Antidote

Most side effects will be tolerated or treated symptomatically. Keep physician informed. Close monitoring of bone marrow, ECG, chest x-ray, echocardiography, and systolic ejection fraction may prevent most serious and potentially fatal side effects. There is no specific antidote, but adequate supportive care including platelet transfusions, antibiotics, and symptomatic treatment of mucositis is required. For extravasation, elevate the extremity and apply intermittent ice packs over the area immediately and 4 times a day for ¹/₂ hour. Continue for 3 days. Consider aspiration of as much infiltrated drug as possible, flooding of the site with NS, and injection of hydrocortisone sodium succinate (Solu-Cortef) throughout extravasated tissue. Use a 27- or 25-gauge needle. Site should be observed promptly by a reconstructive surgeon. If ulceration begins or there is severe persistent pain at the site, early wide excision of the involved area will be considered. Hemodialysis or peritoneal dialysis probably not effective in overdose.

Usual dose

5 Gm provided as two separate vials, each containing 2.5 Gm/50 mL. There are limited data to support administration of an additional 5-Gm dose of idarucizumab; see Precautions.

Dose adjustments

No dose adjustment is required in renally impaired patients. ​■ ​Formal studies in patients with hepatic impairment have not been conducted.

Dilution

A colorless to slightly yellow, clear to slightly opalescent solution available as a 2.5 Gm/50 mL injection in a single-use vial. Administer undiluted by withdrawing and injecting the contents of 2 vials with a syringe or by hanging and infusing the contents of 2 vials.

Compatibility

Manufacturer states, “Do not mix with other medicinal products. A pre-existing IV line may be used for administration. The line must be flushed with NS prior to infusion. No other infusion should be administered in parallel via the same IV access.”

Rate of administration

Administer by bolus injection by injecting both vials consecutively one after another via syringe. Alternatively, may administer as two rapid consecutive infusions by hanging and infusing each vial one after another. Flush IV line with NS before administration of idarucizumab.

Actions

A recombinant humanized monoclonal antibody fragment (Fab); it is derived from an IgG1 isotype molecule whose target is the direct thrombin inhibitor dabigatran. Idarucizumab is a specific reversal agent for dabigatran. It binds to dabigatran and its acyl glucuronide metabolites with a higher affinity than the binding affinity of dabigatran to thrombin, thereby neutralizing their anticoagulant effect. In studies, the plasma concentrations of unbound dabigatran were reduced to below the lower limit of quantification immediately after the administration of 5 Gm idarucizumab. Subjects’ diluted thrombin time (dTT), ecarin clotting time (ECT), activated partial thromboplastin time (aPTT), thrombin time (TT), and activated clotting time (ACT) parameters returned to baseline levels. Idarucizumab is rapidly eliminated with an initial half-life of 47 minutes and a terminal half-life of 10.3 hours. Some drug is recovered in the urine. The remaining part of the dose is assumed to be eliminated via protein catabolism, mainly in the kidney. Idarucizumab is thought to be metabolized via pathways that involve the biodegradation of the antibody to smaller peptides or amino acids, which are then reabsorbed and incorporated in the general protein synthesis.

Indications and uses

Reversal of the anticoagulant effects of dabigatran (Pradaxa) when reversal is needed for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding.

Contraindications

Manufacturer states, “None.”

Precautions

For IV use only. ​■ ​Idarucizumab treatment should be used in conjunction with standard supportive measures. ​■ ​Reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate. Dabigatran treatment can be initiated 24 hours after administration of idarucizumab. No changes in the pharmacokinetics or pharmacodynamics of dabigatran were noted upon re-initiation 24 hours after administration of idarucizumab. ​■ ​Elevated coagulation parameters (e.g., activated partial thromboplastin time [aPPT], ecarin clotting time [ECT]) have been observed 12 and 24 hours after administration of a 5-Gm dose of idarucizumab in a limited number of patients. Administration of an additional 5-Gm dose of idarucizumab may be considered if the reappearance of clinically relevant bleeding together with elevated coagulation parameters is observed after administration of the initial dose. Similarly, patients who require a second emergency surgery/urgent procedure and have elevated coagulation parameters may receive an additional 5-Gm dose of idarucizumab. The safety and effectiveness of repeat treatment with idarucizumab have not been established. ​■ ​Adverse events possibly indicative of hypersensitivity reactions have been reported. The risk of using idarucizumab in a patient with known hypersensitivity to idarucizumab (e.g., anaphylactic reaction) or to any of its excipients needs to be weighed cautiously against the potential benefit of such an emergency treatment. If an anaphylactic reaction or other serious reaction occurs, immediately discontinue administration of idarucizumab. ​■ ​The recommended dose of idarucizumab contains 4 Gm of sorbitol as an excipient. Patients with the condition of hereditary fructose intolerance (HFI) have experienced serious adverse reactions (e.g., acute liver failure, hypoglycemia, hypophosphatemia, increase in uric acid, metabolic acidosis) after receiving parenteral administration of sorbitol. When prescribing idarucizumab to patients with HFI, consider the combined daily metabolic load of sorbitol/fructose from all sources, including idarucizumab and other drugs containing sorbitol. The minimum amount of sorbitol at which serious adverse reactions may occur in these patients is not known. ​■ ​Idarucizumab is a specific reversal agent for dabigatran, with no impact on the effect of other anticoagulant or antithrombotic therapies. ​■ ​As with all proteins, there is a potential for immunogenicity with idarucizumab. Pre-existing antibodies with cross-reactivity to idarucizumab were detected in some subjects. No impact on the pharmacokinetics or the reversal effect of idarucizumab or on hypersensitivity reactions was observed in these subjects.

Drug/lab interactions

Formal drug interaction studies have not been conducted. ​■ ​In vitro data suggest that the inhibition of dabigatran by idarucizumab is not affected by coagulation factor concentrates (3-factor or 4-factor prothrombin complex concentrates [PCCs], activated PCC, or recombinant factor VIIa).

Side effects

The most frequently reported adverse reactions were constipation, delirium, fever, headache, hypokalemia, and pneumonia. Hypersensitivity reactions (e.g., bronchospasm, fever, hyperventilation, pruritus, and rash) and thromboembolic events have been reported.

Antidote

Notify physician of any side effects; most will be treated symptomatically. Discontinue administration at the first sign of a serious hypersensitivity reaction and treat as indicated (e.g., oxygen, diphenhydramine, epinephrine, corticosteroids, vasopressors, and/or fluids). Resuscitate as necessary.

Usual dose

Specific testing recommended before each dose; see Monitor.

1.2 Gm/M²/day for 5 consecutive days. Repeat every 3 weeks as hematologic recovery permits. To prevent hemorrhagic cystitis, ifosfamide should be given with extensive hydration (e.g., at least 2 liters of oral or IV fluid/day), and mesna should be administered with every dose. Ifosfamide dose has been mixed with the initial mesna dose each day in the same solution. Appears to be compatible.

Dose adjustments

Reduced dose may be required in renal or hepatic impairment. Adequate data not available. ■ Dosing should be cautious in the elderly. Consider decrease in cardiac, hepatic, and renal function; concomitant disease; or other drug therapy. See Elderly. ■ Severe myelosuppression is frequent, especially when ifosfamide is given with other chemotherapeutic agents. Dose adjustments of all agents may be required. Adjustment of dose interval may be required. Unless clinically essential, the dose should be held for WBCs less than 2,000/mm³ and/or platelets less than 50,000/mm³. See Monitor and Drug/Lab Interactions.

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.

One source suggests the following compatibilities:

Rate of administration

A single dose over a minimum of 30 minutes as an infusion. Extend administration time based on amount of diluent and patient condition.

Actions

An alkylating agent. Chemically related to the nitrogen mustards and a synthetic analog of cyclophosphamide. A prodrug that requires activation by hepatic cytochrome P₄₅₀ isoenzymes to exert its cytotoxic activity. Exact mechanism of action not determined, but its cytotoxic action is primarily through DNA cross-links caused by alkylation by isophosphoramide mustard at guanine N7 positions. The formation of inter- and intra-strand cross-links in the DNA results in cell death. Distribution takes place with minimal tissue binding and little plasma protein binding. Extensively bound by red blood cells. Extensively metabolized in the liver by cytochrome P₄₅₀ isoenzymes (considerable individual variation). Elimination half-life for a usual dose is about 7 hours. Half-life is extended with larger doses. Ifosfamide and its metabolites are excreted in urine. Secreted in breast milk.

Indications and uses

Used in combination with other specific antineoplastic agents for third-line chemotherapy of germ cell testicular cancer. Should be used in combination with mesna for prophylaxis of hemorrhagic cystitis.

Contraindications

Hypersensitivity to ifosfamide; urinary outflow obstruction.

Precautions

Follow guidelines for handling cytotoxic agents. See Appendix A, p. 1331. ■ Usually administered by or under the direction of the physician specialist. ■ Exclude or correct any urinary tract obstructions; see Contraindications. ■ Administer cautiously, if at all, to patients with an infection (including an active urinary tract infection), severe immunosuppression, or compromised bone marrow reserve as indicated by leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior treatment with other cytotoxic agents. ■ Myelosuppression can be severe and lead to fatal infections. Deaths have been reported. Risk of myelosuppression is dose-dependent and is increased in patients with reduced renal function and when ifosfamide is administered as a single high dose compared to fractionated doses. Severe myelosuppression is often observed when ifosfamide is used in combination with other chemotherapeutic/hematotoxic agents and/or radiation therapy. ■ CNS toxicities can be severe and result in encephalopathy and death. ■ Nephrotoxic and urotoxic. Acute tubular necrosis, acute renal failure, and chronic renal failure have been reported, and deaths have occurred. Benefits must outweigh risks if ifosfamide is used in patients with pre-existing renal impairment or reduced nephron reserve. Glomerular and tubular disorders of renal function are common and may become apparent during therapy or months and years after stopping treatment. They may resolve, remain stable, or progress even after completion of treatment. Hemorrhagic cystitis can be severe and may require blood transfusions. Urotoxic effects can be reduced by the prophylactic use of mesna. Risk of hemorrhagic cystitis is dose-dependent and increases with the administration of single high doses compared to fractionated administration. Past or concomitant radiation of the bladder or busulfan therapy may also increase risk. ■ Use caution in patients with risk factors for cardiotoxicity or pre-existing cardiac disease. Cardiotoxicity (e.g., supraventricular or ventricular arrhythmias, decreased QRS voltage and ST-segment or T-wave changes, toxic cardiomyopathy leading to heart failure with congestion and hypotension, pericardial effusion, fibrinous pericarditis, epicardial fibrosis), sometimes with fatal outcomes, has been reported. Risk is dose dependent and is increased with prior or concomitant treatment with other cardiotoxic agents or radiation of the cardiac region and, possibly, renal impairment. ■ Pulmonary toxicity (e.g., interstitial pneumonitis, pulmonary fibrosis, and other forms of pulmonary toxicity) has been reported, sometimes with fatal outcomes. ■ Hypersensitivity reactions, including anaphylaxis, have been reported. Cross-sensitivity between oxazaphosphorine cytotoxic agents (e.g., cyclophosphamide [Cytoxan]) has been reported. ■ May interfere with normal wound healing. ■ Risk of secondary malignancies has been reported. ■ Veno-occlusive liver disease has been reported. ■ Studies in patients with hepatic or renal impairment have not been conducted. Use with caution.

Drug/lab interactions

See Dose Adjustments. ■ A substrate for both CYP3A4 and CYP2B6. CYP3A4 inducers (e.g., carbamazepine [Tegretol], fosphenytoin [Cerebyx], phenytoin [Dilantin], phenobarbital [Luminal], rifampin [Rifadin], and St. John’s wort) may increase the metabolism of ifosfamide to its active alkylating metabolites and increase the formation of the neurotoxic/nephrotoxic metabolite chloroacetaldehyde. Monitor closely for signs of toxicity; consider dose adjustment. CYP3A4 inhibitors (e.g., aprepitant [Emend], fosaprepitant [Emend for injection], fluconazole [Diflucan], grapefruit and grapefruit juice, itraconazole [Sporanox], ketoconazole [Nizoral], sorafenib [Nexavar]) may decrease the metabolism of ifosfamide to its active alkylating metabolites, perhaps decreasing the effectiveness of treatment. ■ May have additive effects with other drugs that act on the CNS (e.g., antihistamines, antiemetics, narcotics, or sedatives). Use with caution or discontinue if encephalopathy occurs. ■ Do not administer live virus vaccines to patients receiving antineoplastic drugs.

Side effects

Hematuria, hemorrhagic cystitis, and bone marrow suppression are dose-limiting side effects. The most common side effects included alopecia, anemia, CNS toxicity, hematuria, infection, leukopenia, nausea, and vomiting. Other commonly reported side effects were anorexia, confusion, constipation, depressive psychosis with hallucinations, diarrhea, and somnolence. Cardiotoxicity, coagulopathy, coma, cranial nerve dysfunction, dermatitis, disorientation, dizziness, fatigue, fever of unknown origin, hypersensitivity reactions, hypertension, hypotension, liver dysfunction, malaise, neutropenia, osteomalacia, phlebitis, polyneuropathy, pulmonary symptoms, thrombocytopenia, or seizures may occur.

Antidote

Minor side effects will be treated symptomatically if necessary. Discontinue ifosfamide and notify physician immediately if hematuria, hemorrhagic cystitis, confusion, coma, WBC below 2,000 mm³, or platelets below 50,000/mm³ occur. Administration of whole blood products (e.g., packed RBCs, platelets, leukocytes) and/or blood modifiers (e.g., darbepoetin alfa [Aranesp], epoetin alfa [Epogen], filgrastim [Neupogen, Zarxio], pegfilgrastim [Neulasta], sargramostim [Leukine]) may be indicated to treat bone marrow suppression. Maintain supportive therapy for CNS symptoms until complete resolution; occasionally, recovery has been incomplete. Discontinue treatment if encephalopathy occurs. There is no specific antidote. Supportive therapy as indicated will help sustain the patient in toxicity. Cystitis prophylaxis with mesna may prevent or limit urotoxic effects. Ifosfamide and its metabolites are dialyzable.

Usual dose

Range is from 250 mg to 1 Gm every 6 to 8 hours. Dose based on severity of disease, susceptibility of pathogens, condition of the patient, age, weight, and CrCl. Adult doses in the following chart are limited to patients with a CrCl equal to or greater than 71 mL/min/1.73 M² and a body weight equal to or greater than 70 kg; see Dose Adjustments. Because of high antimicrobial activity, do not exceed the lower of 50 mg/kg/24 hr or 4 Gm/24 hr in adult or pediatric patients. Continue for at least 2 days after all symptoms of infection subside.

Pediatric dose

Not recommended for use in pediatric patients with CNS infections because of the risk of seizures, or in pediatric patients weighing less than 30 kg with impaired renal function (no data available). Because of high antimicrobial activity, do not exceed the lower of 50 mg/kg/24 hr or 4 Gm/24 hr in adult or pediatric patients.

Dose adjustments

Dose adjustments are extensive and required for all patients weighing less than 70 kg, as well as all patients with a CrCl less than 71 mL/min/1.73 M². Dose adjustments also vary based on total daily dose required (e.g., 1, 1.5, 2, 3, or 4 Gm). See charts in package insert. ■ Reduced doses may be required in the elderly based on weight and/or decreased renal function. ■ Cleared by hemodialysis; administer after hemodialysis and at 12-hour intervals thereafter. ■ See Precautions/Monitor and Drug/Lab Interactions.

Dilution

Reconstitute each single dose with 10 mL of compatible infusion solutions (e.g., D5W, D10W, NS [see chart on inside back cover or literature]); also compatible in D5W with 0.15% KCl and mannitol 5% and 10%. Shake well and transfer the resulting suspension to 100 mL of the same infusion solution. Rinse vial with an additional 10 mL of infusion solution to ensure complete transfer of vial contents to the infusion solution. Agitate until clear. Also available in ADD-Vantage vials for use with ADD-Vantage infusion containers.

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 mixed with or physically added to other antibiotics.” See Drug/Lab Interactions.

One source suggests the following compatibilities:

Rate of administration

Actions

A potent broad-spectrum antibacterial agent. Imipenem is a carbapenem antibiotic; cilastatin inhibits the kidney enzyme responsible for the metabolism of imipenem. Both components are present in equal amounts. Bactericidal to many gram-negative, gram-positive, and anaerobic organisms. Bactericidal activity results from the inhibition of bacterial wall synthesis. Effective against many otherwise resistant organisms. Has a high degree of stability in the presence of beta-lactamases produced by gram-negative and gram-positive bacteria. Rapidly and widely distributed into many body fluids and tissues. Metabolized in the kidneys. Half-life is approximately 1 hour. Excreted in the urine. May cross the placental barrier.

Indications and uses

Treatment of serious lower respiratory tract, urinary tract, skin and skin structure, bone and joint, gynecologic, intra-abdominal, and polymicrobic infections; bacterial septicemia; and endocarditis. Most effective against specific organisms (see literature).

Contraindications

Known sensitivity to any component of this product. ■ See Maternal/Child and Precautions.

Precautions

Specific sensitivity studies are indicated to determine susceptibility of the causative organism to imipenem-cilastatin. ■ To reduce the development of drug-resistant bacteria and maintain its effectiveness, imipenem-cilastatin should be used to treat or prevent only those infections proven or strongly suspected to be caused by bacteria. ■ Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving therapy with beta-lactams (e.g., carbapenems, cephalosporins, penicillins). More likely in patients with a history of sensitivity to multiple allergens; obtain a careful history. Cross-sensitivity is possible. ■ Avoid prolonged use of drug; superinfection caused by overgrowth of nonsusceptible organisms may result. ■ CNS adverse effects, including confusional states, myoclonic activity, and seizures, have been reported. Incidence increases with higher doses, compromised renal function, or pre-existing CNS disorders. ■ Not recommended in patients with a CrCl less than 5 mL/min/1.73 M² unless hemodialysis is instituted within 48 hours. ■ For patients on hemodialysis, benefits of use must outweigh risk of seizures. ■ 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 imipenem-cilastatin. ■ Safety and effectiveness for use in meningitis not established. ■ Clinical improvement has been observed in patients with cystic fibrosis, COPD, and lower respiratory tract infections caused by Pseudomonas aeruginosa; however, effective bacterial eradication may not occur. ■ See Maternal/Child and Drug/Lab Interactions.

Drug/lab interactions

Carbapenems may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Monitor valproic acid levels. Consider alternative antibacterial therapy. If administration of imipenem is necessary, supplemental anticonvulsant therapy should be considered. ■ May be used concomitantly with aminoglycosides and other antibiotics, but these drugs must never be mixed in the same infusion or given concurrently. ■ Use with ganciclovir (Cytovene) may cause generalized seizures. Use only if benefit outweighs risk. ■ Half-life and plasma levels slightly increased by probenecid. Avoid concurrent use. ■ Concurrent use with cyclosporine (Sandimmune) may decrease cyclosporine metabolism. Elevated cyclosporine levels and neurotoxicity (e.g., agitation, confusion, tremor) have been reported.

Side effects

Full scope of hypersensitivity reactions including anaphylaxis, pruritus, rash, and urticaria. Abdominal pain; abnormal clotting time; agitation; altered CBC and electrolytes; anuria; burning, discomfort, and pain at injection site; CDAD; confusion; diarrhea; dizziness; dyskinesia; dyspnea; elevated alkaline phosphatase, AST, ALT, bilirubin, creatinine, BUN, LDH; fever; gastroenteritis; glossitis; headache; heartburn; hemorrhagic colitis; hepatic failure; hepatitis (including fulminant hepatitis); hyperventilation; hypotension; increased salivation; myoclonus; nausea and vomiting; paresthesia; pharyngeal pain; polyarthralgia; polyuria; positive direct Coombs’ test; presence of WBCs or RBCs, protein casts, bilirubin, or urobilinogen in urine; seizures; somnolence; thrombophlebitis; tinnitus; tongue papillar hypertrophy; transient hearing loss in the hearing impaired; vertigo; and many others.

Antidote

Notify physician of any side effects. Discontinue the drug if indicated. Treat hypersensitivity reactions as indicated; may require epinephrine, airway management, oxygen, IV fluids, antihistamines (e.g., diphenhydramine [Benadryl]), corticosteroids (e.g., hydrocortisone sodium succinate [Solu-Cortef]), and pressor amines (e.g., dopamine). Resuscitate as necessary. Begin anticonvulsants if focal tremors, myoclonus, or seizures occur. If symptoms continue, decrease dose or discontinue the drug. Infusion rate reactions (e.g., dizziness, hypotension, N/V, and sweating) may respond to a decrease in rate of infusion. Mild cases of CDAD may respond to discontinuation of the 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 may be useful in overdose.

Usual dose

For all indications, ensure adequate hydration before administration.

Pediatric dose

Dose adjustments

Adjust dose according to IgG levels and clinical response. Frequency and dose will vary from patient to patient. No controlled clinical trials are available to determine optimum trough serum IgG level.

Dilution

Requirements for dilution of liquid and lyophilized powder preparations are brand specific and vary considerably; see manufacturer’s package insert. Some may be further diluted only with D5W or with D5W and/or NS; others cannot be diluted. Some require D5W or NS to flush the infusion line.

Compatibility

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

Manufacturers recommend administration through a separate IV line without admixture with other drugs and state, “Do not combine one IGIV product with an IGIV product from another manufacturer.” Gammagard Liquid, Gammaked, Gamunex-C, and Privigen are compatible only with D5W and are incompatible with NS. Flebogamma and Octagam should not be further diluted with any solution.

Most preparations may be infused sequentially into a primary IV of D5W or NS, or the tubing may be flushed with D5W or NS before and after administration.

One source suggests the following compatibilities: Not recommended by manufacturers.

Rate of administration

Actions

A preparation of concentrated human immunoglobulin G (IgG) antibodies. Obtained, purified, and standardized from human plasma. Specific methods during the manufacturing process (e.g., cold ethanol fractionation, detergents, solvents, nanofiltration) inactivate blood-borne viruses (e.g., hepatitis, HIV). Used as replacement therapy in primary and secondary immunodeficiencies. Active against bacterial, viral, parasitic, and mycoplasma antigens. Capable of both opsonization and neutralization of microbes and toxins.Also contains antibodies capable of interacting with and altering the activity of the immune system as well as antibodies capable of reacting with cells such as erythrocytes. (The role of these antibodies and the mechanisms of action of IgG have not been fully clarified.) Provides immediate antibody levels following infusion. The immediate peak in serum IgG is followed by a rapid decay due to equilibration between the plasma and extravascular fluid compartments. Half-life is variable (approximately 3 to 6 weeks) but may be decreased by fever or infection (increased catabolism or consumption). Crosses the placenta.

Indications and uses

Selected products are approved for different uses; see Usual Dose. All provide rapid-onset, short-term passive immunization. Labeled uses include: Primary immunodeficiency diseases: Replacement therapy in adults, adolescents, and other pediatric patients unable to produce adequate amounts of IgG antibodies, especially in the following situations: need for immediate increase in intravascular immunoglobulin levels, small muscle mass or bleeding tendencies that contraindicate IM injection, and selected disease states (e.g., congenital agammaglobulinemia, common variable immunodeficiency [CVID], combined immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome). ■ Treatment of acute and chronic idiopathic thrombocytopenic purpura (also called immune thrombocytopenic purpura or primary immune thrombocytopenia): Temporary increase in platelet counts in patients with idiopathic thrombocytopenic purpura and with thrombocytopenia associated with bone marrow transplant. ■ Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP): Improvement of neuromuscular disability and impairment and maintenance therapy to prevent relapse. ■ Adjunct in chronic lymphocytic leukemia: Prevention of bacterial infections in patients with hypogammaglobulinemia or recurrent bacterial infection associated with B-cell CLL. ■ Multifocal motor neuropathy (MMN): To improve muscle strength and disability in adult patients. ■ Kawasaki syndrome: Prevention of coronary artery aneurysms associated with Kawasaki syndrome. ■ Safety and effectiveness of Gammagard S/D, Gammaplex, and Octagam 10% in pediatric patients with chronic ITP have not been established; see Maternal/Child for additional limitations with other products. ■ Several formulations are approved for SC use in specific diagnoses; consult prescribing information.

Contraindications

Individuals known to have anaphylactic or severe hypersensitivity responses to the administration of human immune globulin. ■ IgA-deficient patients with pre-existing anti-IgA antibodies and a history of hypersensitivity. ■ Gammaplex is contraindicated in patients with hereditary intolerance to fructose; also contraindicated in infants and neonates for whom sucrose or fructose tolerance has not been established. ■ Octagam is contraindicated in patients with acute hypersensitivity to corn (contains maltose, which is derived from corn). ■ Privigen is contraindicated in patients with hyperprolinemia because it contains l-proline as a stabilizer.

Precautions

Check label; must state, “For IV use.” ■ Some formulations may be given SC; however, all products must be given by IV infusion for ITP patients. Do not administer SC due to a potential risk for hematoma. ■ Hypersensitivity reactions have occurred; 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. IgA-deficient patients, especially those with antibodies against IgA, are at greater risk for developing severe hypersensitivity reactions. ■ Some packaging of these products may contain latex; use caution in sensitive individuals. ■ 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 age 65 years 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 dose and rate of infusion practicable. Products containing sucrose as a stabilizer (e.g., Carimune NF) have demonstrated an increased risk for renal dysfunction. Consider benefit versus risk before use. ■ Increases in SCr and/or BUN may progress to oliguria and anuria requiring dialysis; however, some patients improve spontaneously with discontinuation of IGIV. ■ May cause aseptic meningitis syndrome (AMS), especially with high doses (greater than 1 Gm/kg) and/or rapid infusion. 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. Cerebrospinal fluid (CSF) studies are often positive with pleocytosis, predominantly from the granulocyte series and elevated protein levels. ■ Hyperproteinemia, with resultant changes in serum viscosity, and electrolyte imbalances (e.g., hyponatremia) may occur. Distinguish true hyponatremia from pseudohyponatremia to determine correct treatment. Decreasing serum-free water in patients with pseudohyponatremia may lead to volume depletion with a further increase in serum viscosity, which may predispose to thromboembolic events. ■ IGIV products have been associated with thrombotic events. Risk factors may include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheter, hyperviscosity, and cardiovascular risk factors (e.g., cerebrovascular disease, coronary artery disease, diabetes, hypertension). Thrombosis may occur in the absence of known risk factors. If used, should be administered at the minimum dose and rate of infusion practicable. Ensure adequate hydration before administration. ■ Baseline assessment of blood viscosity should be made in patients at risk for hyperviscosity, including those with cryoglobins, fasting chylomicronemia, markedly high triglycerides, or monoclonal gammopathies. ■ May rarely cause hemolysis, which can result in hemolytic anemia due to enhanced RBC sequestration. High doses (greater than 2 Gm/kg) and non-O blood group may be risk factors for hemolysis. Cases of severe hemolysis-related renal dysfunction/failure or DIC have occurred following infusion; see Monitor. ■ Consider risk/benefit before use of high-dose regimens (greater than 1 Gm/kg) in chronic ITP patients at increased risk for acute kidney injury, hemolysis, thrombosis, or volume overload. ■ Noncardiogenic pulmonary edema (transfusion-related acute lung injury [TRALI]) has been reported; see Monitor. ■ Derived from human blood. Despite purification processes, may carry risk of transmitting infectious agents (e.g., viruses [e.g., HIV, hepatitis] or Creutzfeldt-Jakob disease [CJD] agent). ■ Patients with gammaglobulinemia or extreme hypogammaglobulinemia who have never before received immunoglobulin substitution treatment or patients whose time from the last treatment is greater than 8 weeks may be at risk for developing inflammatory reactions (e.g., chills, fever, nausea, vomiting) on rapid infusion. Initiate slowly and increase rate as tolerated.

Drug/lab interactions

Do not administer live virus vaccines from 2 weeks before to at least 3 months after immune globulin IV. Passive transfer of antibodies may transiently interfere with the response to live virus vaccines, such as measles, mumps, rubella, and varicella; see prescribing information if there is a risk of measles exposure or if accidental exposure has occurred. ■ Provides immediate antibody levels that last for about 3 weeks. In selected patients, may have an immune-modulating effect that may alter their response to corticosteroids or antineoplastic agents. ■ Concurrent use with nephrotoxic drugs (e.g., aminoglycosides [e.g., gentamicin], amphotericin B [Amphotec, conventional], cidofovir [Vistide], rifampin [Rifadin]) may increase risk of renal insufficiency. ■ Products that contain maltose (Octagam) may interfere with blood and urine glucose tests. ■ Various antibody titers may be raised temporarily, resulting in false-positive serologic testing. ■ May cause a positive direct or indirect antiglobulin (Coombs’) test.

Side effects

Arthralgia, asthenia, back pain, chills, diarrhea, dizziness, fatigue, fever, flushing, headache, hyperhidrosis, hypertension, infusion site pain/reactions, lethargy, nausea and vomiting, pharyngitis, rash, sinusitis, upper abdominal pain, and urticaria were reported most commonly. Full range of hypersensitivity symptoms, including anaphylaxis, is possible. Angioedema, erythema, fever, and urticaria are most frequently observed. Anxiety, chest tightness, cough, decreased diastolic BP, difficulty breathing, elevated ALT and AST (temporary), hemolytic anemia (reversible), increased BUN and SCr (may occur as soon as 1 to 2 days following infusion), leg cramps, light-headedness, malaise, migraine, myalgia, pharyngolaryngeal pain, and tachycardia have been reported. Severe reactions (e.g., circulatory collapse, fever, loss of consciousness, nausea and vomiting, sudden onset of dyspnea) have occurred and are more common in patients with antibody deficiencies. Noncardiogenic pulmonary edema (transfusion-related acute lung injury [TRALI]) has been reported. Acute renal failure, acute tubular necrosis, osmotic nephrosis, and proximal tubular nephropathy have been reported; may result in death. Is made from human plasma; process attempts to eliminate risk of hepatitis or HIV infection. A precipitous hypotensive reaction can occur and is most frequently associated with too-rapid rate of injection. Aseptic meningitis syndrome and hemolysis occur infrequently. See Precautions.

Antidote

Reduce rate for patient discomfort, for any sign of adverse reaction, and in patients at risk for renal insufficiency or thrombosis. If symptoms subside promptly, the infusion may be resumed at a lower rate. Decreasing the volume of subsequent infusions may also prevent or decrease the incidence of adverse reactions. Loop diuretics (e.g., furosemide [Lasix]) may be helpful in the management of fluid overload. Patients who continue to experience adverse reactions after rate and/or volume have been reduced may be premedicated with hydrocortisone 1 to 2 mg/kg 30 minutes before the immune globulin infusion. Pretreatment with acetaminophen (Tylenol) and diphenhydramine (Benadryl) or trying a different brand of immune globulin may also be useful. Discontinue the drug immediately for any signs of a hypersensitivity reaction, thrombotic event, or renal insufficiency. 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.

Usual dose

Dose adjustments

If urine output is less than 0.6 mL/kg/hr at any time a dose is to be given, withhold dose until lab studies confirm normal renal function.

Dilution

Each 1 mg must be diluted with at least 1 mL NS or SWFI without preservatives (0.1 mg/0.1 mL); may be diluted with 2 mL diluent (0.05 mg/0.1 mL). The preservative benzyl alcohol is toxic in neonates. A fresh solution should be prepared just before each administration. Discard any unused portion.

Compatibility

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

Manufacturer states, “Prepare only with preservative-free NS or SWFI”; further dilution with IV solutions is not recommended and may precipitate with solutions with a pH below 6.

One source suggests the following compatibilities:

Rate of administration

A single dose, properly diluted, by IV injection over 20 to 30 minutes.

Actions

A potent inhibitor of prostaglandin synthesis. Through an unconfirmed method of action (thought to be inhibition of prostaglandin synthesis), it causes closure of a patent ductus arteriosus 75% to 80% of the time, eliminating the need for surgical intervention. Plasma half-life varies inversely with postnatal age and weight and ranges from 12 to 20 hours. Metabolized in the liver and eventually excreted in urine and bile.

Indications and uses

Closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1,750 Gm if usual medical management (e.g., fluid restriction, diuretics, digoxin, respiratory support) has not been effective after 48 hours.

Contraindications

Bleeding, especially active intracranial hemorrhage or GI bleeding; coagulation defects; necrotizing enterocolitis; infants with congenital heart disease (e.g., pulmonary atresia, severe coarctation of the aorta, severe tetralogy of Fallot) who require patency of the ductus arteriosus for satisfactory pulmonary or systemic blood flow; proven or suspected untreated infection; significant renal impairment; thrombocytopenia.

Precautions

Clinical evidence of a hemodynamically significant patent ductus arteriosus (respiratory distress, a continuous murmur, a hyperactive precordium, cardiomegaly and pulmonary plethora on chest x-ray) should be present before use is considered. ■ For use only in a highly supervised setting such as an intensive care nursery. ■ May increase potential for GI or intraventricular bleeding. ■ Use caution in presence of existing controlled infection; may mask signs and symptoms of exacerbation. ■ May suppress water excretion to a greater extent than sodium excretion. Hyponatremia may result. ■ For IV use only. ■ Surgery indicated if condition is not responsive to two courses of therapy.

Drug/lab interactions

May reduce elimination and increase serum concentrations of drugs that are renally excreted (e.g., aminoglycosides [e.g., gentamicin], digoxin [Lanoxin]). Monitor drug levels and adjust doses as needed to avoid toxicity. ■ Observe neonate closely for signs of digoxin toxicity; frequent monitoring of ECG and digoxin serum levels is indicated. ■ Use with furosemide (Lasix) may help to maintain renal function. ■ Concomitant use with anticoagulants may increase risk of bleeding; monitoring of PT suggested. ■ Coadministration with ACE inhibitors (e.g., enalapril [Vasotec]) may result in deterioration of renal function, including renal failure.

Side effects

Abdominal distension; acidosis; alkalosis; apnea; bleeding into the GI tract (gross or microscopic); bradycardia; DIC; elevated BUN or creatinine; exacerbation of preexisting pulmonary infection; fluid retention; gastric perforation; hyperkalemia; hypoglycemia; hyponatremia; intracranial bleeding; necrotizing enterocolitis; oliguria; oozing from needle puncture sites; pulmonary hemorrhage; pulmonary hypertension; reduced urine sodium, chloride, potassium, urine osmolality, free water clearance, or glomerular filtration rate; renal failure; retrolental fibroplasia; thrombocytopenia; transient ileus; uremia; vomiting.

Antidote

Discontinue the drug and notify the physician of all side effects. Based on severity, side effects may be treated symptomatically or drug will be completely discontinued in favor of surgical intervention. Resuscitate as necessary.

Usual dose

Preliminary patient evaluation required; see Monitor.

Pediatric dose

Preliminary patient evaluation required; see Monitor. See Maternal/Child.

Dose adjustments

Dilution

Compatibility

Rate of administration

Actions

Indications and uses

Contraindications

Precautions

Drug/lab interactions

Side effects

Antidote

Usual dose

Only regular insulin, insulin aspart, insulin glulisine, and insulin lispro may be given IV. Confirm by label or package insert that a particular insulin product is for IV use; see Precautions.

Dose varies greatly. Will be dependent on patient’s condition and response. Insulin requirements may be altered during stress or major illness or with changes in exercise, meal pattern, or coadministered drugs. It is imperative that dosing is individualized and adjusted based on blood glucose determinations because of the marked loss of insulin from adsorption to glass and plastic infusion containers and tubing; see Precautions.

Pediatric dose

Dose adjustments

A reduced dose of insulin may be indicated when infusions are discontinued and SC administration is indicated. As in Usual Dose, base on blood glucose determinations and patient’s response to therapy. ■ Dose requirements may be reduced in patients with renal or hepatic impairment. ■ Dose adjustment may be indicated if it is necessary to change from one insulin product to another.

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.

Manufacturer states, “Insulin glulisine is stable (compatible) only with NS; do not use other solutions for infusion and do not mix with other insulins for IV administration.”

One source suggests the following compatibilities:

These compatibilities refer to regular insulin only; information on specific compatibilities for insulin aspart, insulin glulisine, and insulin lispro are not available.

Rate of administration

Each 50 units or fraction thereof over 1 minute. When given in an IV infusion, the rate should be ordered by the physician and will depend on insulin and fluid needs; see Dilution for example. Decrease rate when plasma glucose reaches 300 mg/dL. Manufacturer recommends that the rate of insulin lispro be regularly adjusted to maintain blood glucose concentrations between 100 and 160 mg/dL.

Actions

A hormone produced by the pancreas that controls the storage and metabolism of carbohydrates, proteins, and fat. Responsible for regulation of glucose metabolism. Binds to insulin receptors on muscle and fat cells and lowers blood glucose by facilitating cellular uptake of glucose and inhibiting output of glucose from the liver. Also inhibits lipolysis, proteolysis, and gluconeogenesis and enhances protein synthesis and conversion of excess glucose into fat. Rapidly and widely distributed. The glucose-lowering activities of regular insulin, insulin aspart, insulin glulisine, and insulin lispro are equipotent when administered by the IV route. The average elimination half-life is dose dependent and ranges from 0.25 to 1 hour depending on dose and product.

Indications and uses

Contraindications

Contraindicated during episodes of hypoglycemia and in patients hypersensitive to regular human insulin, insulin aspart, insulin glulisine, insulin lispro, or one of the excipients of any of these products.

Precautions

Only regular insulin, insulin aspart, insulin glulisine, and insulin lispro may be given IV. All insulin formulations for IV use are standardized at 100 units/mL.

Drug/lab interactions

Hypoglycemic effect is potentiated by ACE inhibitors (e.g., enalapril [Vasotec], lisinopril [Zestril]), anabolic steroids (e.g., nandrolone [Durabolin]), disopyramide (Norpace), fluoxetine (Prozac), fibrates (e.g., fenofibrate [Tricor]), guanethidine, MAO inhibitors (e.g., selegiline [Eldepryl]), oral antidiabetic agents (e.g., glyburide [DiaBeta]), pentoxifylline (Trental), salicylates, sulfonamides, and many others. ■ Drugs that may reduce blood glucose–lowering effect include atypical antipsychotic medications (e.g., olanzapine [Zyprexa], clozapine [Clozaril]), corticosteroids, danazol (Cyclomen), diazoxide, diuretics (e.g., furosemide [Lasix]), glucagon, isoniazid (INH), niacin, oral contraceptives, phenothiazine derivatives (e.g., chlorpromazine [Thorazine]), protease inhibitors (e.g., indinavir [Crixivan]), somatropin (Humatrope), sympathomimetic agents (e.g., dobutamine, epinephrine [Adrenalin], albuterol [Ventolin]), thyroid preparations, and others. ■ Alcohol, beta-adrenergic blockers including ophthalmics (e.g., propranolol, metoprolol [Lopressor]), clonidine (Catapres), and lithium may either potentiate or inhibit the blood glucose–lowering effect of insulin. ■ Hypoglycemic effects may be decreased in smokers; dose adjustment may be required. ■ Will affect serum potassium levels; use caution in patients taking digoxin. ■ Octreotide (Sandostatin) may alter insulin, glucagon, and growth hormone secretion, resulting in hypoglycemia or hyperglycemia. Monitor serum glucose and adjust insulin dose as indicated. Octreotide also markedly increases adsorption of insulin to glass and plastic and reduces availability. ■ Pentamidine is toxic to the beta cells of the pancreas. Patients may develop hypoglycemia initially as insulin is released. This may be followed by hypoinsulinemia and hyperglycemia with continued pentamidine therapy. ■ S/S of hypoglycemia may be masked in the presence of beta-blockers, clonidine (Catapres), guanethidine (Ismelin), and reserpine. ■ Thiazolidinediones (TZDs [e.g., pioglitazone (Actos)]) can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients receiving concomitant therapy should be monitored for S/S of heart failure. Dose reduction or discontinuation of the TZD may be indicated if heart failure develops.

Side effects

Hypoglycemia with overdose. Mild to moderate: Abnormal behavior; anxiety; blurred vision; depressed mood; dizziness; drowsiness; headache; hunger; inability to concentrate; irritability; light-headedness; palpitation; personality changes; restlessness; sleep disturbances; slurred speech; sweating; tingling in the hands, feet, lips, or tongue; tremors; unsteady movement.

Severe: Coma, disorientation, hypokalemia (with ECG changes), seizures, unconsciousness, and death. Hypersensitivity reactions, including anaphylaxis, may occur; death is rare. Abdominal pain, chest pain, diarrhea, headache, hyporeflexia, nausea, and sensory disturbances have also been reported.

Antidote

Discontinue the drug immediately and notify physician of adverse reactions or hypoglycemia. Glucagon 1 to 2 mg IM or SC is the specific antidote for insulin overdose. It may be supplemented by glucose 50% IV and/or oral carbohydrates such as glucose gel or orange juice. Oral carbohydrates may be sufficient to combat early symptoms of hypoglycemia. Correct hypokalemia as indicated. Hypersensitivity reactions usually respond to symptomatic treatment.

Usual dose (international units [IU])

Pretreatment with acetaminophen may lessen flu-like side effects. To enhance tolerability, injections should be administered in the evening when possible. Not all dosage forms and strengths are appropriate for some indications; see Dilution.

Dose adjustments

Moderate to severe adverse events may require modification of the dosage regimen or, in some cases, termination of therapy. Temporarily discontinued for serious adverse reactions, if granulocytes decrease to less than 500/mm³, or ALT/AST increases to 5 to 10 times the ULN. When adverse reactions subside or improvement of granulocytes or liver function tests occurs, treatment can be restarted at 50% of the previous dose. Discontinue permanently if serious adverse reactions persist, if a severe adverse reaction recurs at a reduced dose, if granulocytes decrease to less than 250/mm³, if platelet counts decrease to less than 25,000/mm³, or if ALT/AST increases to more than 10 times the upper limit of normal. ■ See Elderly.

Dilution (international units [IU])

Intron A Solution for Injection is NOT recommended for IV administration and should not be used for the induction phase of malignant melanoma. Only the sterile powder is suitable for dilution for IV use. Do not use different brands of interferon in any single treatment regimen; variations exist and may adversely affect dosage and response to treatment. Powder for Injection is available in 10, 18, and 50 million IU vials; select one most appropriate for desired dose. Allow product to come to RT before use. Reconstitute immediately before use with 1 mL of SWFI (provided). (The SWFI supplied by the manufacturer contains 5 mL. Discard remaining 4 mL.) Gently swirl to dissolve. Withdraw desired dose and inject into 100 mL of NS. Final concentration should be at least 10 million IU/100 mL.

Compatibility

Specific information not available. Consider specific use; consult pharmacist. One source indicates compatibility with NS, LR, and R solutions and incompatibility with dextrose solutions.

Rate of administration

A single dose equally distributed over 20 minutes. Administration at bedtime and the use of acetaminophen may prevent or partially reduce common side effects (e.g., fever, headache, “flu-like” symptoms).

Actions

A naturally occurring small protein and glycoprotein of the interferon family produced by recombinant DNA techniques. It binds to specific membrane receptors on the cell surface and initiates a complex sequence of intracellular events (e.g., induction of specific enzymes, suppression of cell proliferation, immunomodulating activities [e.g., enhancement of phagocytic activity of macrophages, augmentation of the specific cytotoxicity of lymphocytes for target cells, inhibition of virus replication in virus-infected cells]). Peak concentration achieved within 30 minutes. Half-life about 2 hours; undetectable 4 hours after infusion. The kidney may be the site of interferon catabolism. Has produced a significant increase in relapse-free and overall survival in patients with malignant melanoma.

Indications and uses

Adjuvant to surgical treatment in patients with malignant melanoma who are free of disease but at high risk for systemic recurrence within 56 days of surgery. ■ Used IM or SC to treat hairy cell leukemia, follicular non-Hodgkin’s lymphoma, AIDS-related Kaposi’s sarcoma, chronic hepatitis B, chronic hepatitis C, and intralesionally to treat condylomata acuminata.

Contraindications

Hypersensitivity to interferon alfa or any of its components. ■ Decompensated liver disease or autoimmune hepatitis.

Precautions

May cause or aggravate life-threatening or fatal neuropsychiatric (e.g., depression, aggressive and/or suicidal behavior), autoimmune, ischemic, or infectious disorders. Close monitoring with periodic clinical and laboratory evaluations required. Discontinue therapy if S/S of any of the previous conditions are persistently severe or worsen. Symptoms resolve in most cases. ■ Because of fever and other flu-like symptoms associated with its use, interferon alfa should be used cautiously in patients with a history of pulmonary disease (e.g., COPD), diabetes mellitus prone to ketoacidosis, coagulation disorders (e.g., thrombophlebitis, pulmonary embolism), or severe myelosuppression. ■ Use cautiously in patients with a history of cardiovascular disease (e.g., unstable angina, recent MI, and previous or current arrhythmic disorder). Cardiovascular adverse events (e.g., arrhythmia, cardiomyopathy, hypotension, MI, tachycardia) have been reported. Supraventricular arrhythmias occurred rarely and appeared to be correlated with pre-existing conditions or prior therapy with cardiotoxic agents. ■ Depression and suicidal behavior (including suicidal ideation, suicidal attempts, and completed suicides), homicidal ideation, and aggressive behavior sometimes directed toward others have been reported; see Monitor and Maternal/Child. ■ Use with caution in patients with a history of psychiatric disorders and in patients with substance use disorders. Drug screening and periodic health evaluation, including psychiatric symptom monitoring, may be indicated. ■ Severe cytopenias, including rare cases of aplastic anemia, have been reported; see Monitor. ■ Ophthalmologic disorders (e.g., decrease or loss of vision; retinopathy, including macular edema, retinal artery or vein thrombosis, retinal hemorrhage, and cotton wool spots; optic neuritis; papilledema; and serous retinal detachment) may be induced or aggravated by treatment with interferons; see Monitor. ■ Use caution in patients with psoriasis and sarcoidosis; may exacerbate disease. ■ Rare cases of autoimmune diseases (e.g., lupus erythematosus, Raynaud’s phenomenon, rhabdomyolysis, rheumatoid arthritis, thrombocytopenia, and vasculitis) have been reported; may require discontinuation of therapy. ■ Serum neutralizing antibodies have been detected in some patients; clinical significance unknown. ■ Ischemic and hemorrhagic cerebrovascular events have been reported. A causal relationship between interferon therapy and these side effects is difficult to establish. ■ Endocrine disorders (e.g., hypothyroidism, hyperthyroidism, diabetes mellitus) have developed in patients receiving interferon alfa-2b. ■ Hepatotoxicity, including fatality, has been reported. Interferon alfa increases the risk of hepatic decompensation and death in patients with cirrhosis. ■ Pulmonary disorders (e.g., dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis), some resulting in respiratory failure and/or patient deaths, may be induced or aggravated by interferons. Recurrence of respiratory failure has been observed with interferon rechallenge. ■ Acute serious hypersensitivity reactions have been reported. ■ Elevated triglyceride levels have been observed. Hypertriglyceridemia may result in pancreatitis.

Drug/lab interactions

Specific information not available. Use caution with any other potentially myelosuppressive agent (e.g., cisplatin, zidovudine [AZT, Retrovir]). ■ May increase serum levels of theophylline; monitoring of theophylline levels recommended. ■ See Precautions.

Side effects

Occur in high percentages of patients; may be serious enough to require a decreased dose or discontinuation of drug. Usually rapidly reversible after therapy is discontinued, but may require up to 3 weeks to resolve. The most frequently reported adverse reactions were flu-like symptoms (chills, fatigue, fever, headache, and myalgia). In patients treated for malignant melanoma, the most frequently reported adverse reaction was fatigue. Adverse reactions that were reported in greater than 20% of patients included alopecia, altered taste sensation, anemia, anorexia, chills, depression, diarrhea, dizziness/vertigo, fever, headache, increased AST, myalgia, nausea/vomiting, and neutropenia. Severe adverse reactions (ECOG [Eastern Cooperative Oncology Group] Toxicity Criteria Grade 3 or 4) reported in greater than 10% of patients included chills, fatigue, fever, headache, increased AST, myalgia, and neutropenia/leukopenia. Many other side effects may occur.

Antidote

Keep physician informed of all side effects. Some will be tolerated or treated symptomatically. Discontinue interferon immediately for any acute serious hypersensitivity reactions and treat as appropriate; may require epinephrine, airway management, oxygen, IV fluids, antihistamines (e.g., diphenhydramine [Benadryl]), corticosteroids (e.g., hydrocortisone sodium succinate [Solu-Cortef]), and pressor amines (e.g., dopamine). Discontinue drug for any patient who develops severe depression or other psychiatric disorder. Close patient monitoring and psychiatric intervention may be indicated. Discontinue for myelosuppression that persists after dose reduction, endocrine abnormalities or persistently elevated triglycerides associated with symptoms of potential pancreatitis (e.g., abdominal pain, nausea, vomiting) not normalized by medication, serious liver function abnormalities (Grade 3 hepatic injury or hepatic decompensation [Child-Pugh score >6 (Class B and C)]), new or worsening ophthalmologic disorders, serious pulmonary function impairment, or pulmonary infiltrates. Treatment of overdose with hemodialysis or peritoneal dialysis is not considered effective. Resuscitate as necessary.

Usual dose

Dose adjustments

The recommended treatment modifications for immune-mediated adverse reactions to ipilimumab are outlined in the following chart.

Treatment Modifications of Ipilimumab for Immune-Mediated Adverse Reactions
Target/Organ System	Adverse Reaction (CTCAE, v3)	Treatment Modification
Endocrine	Symptomatic endocrinopathy	Withhold ipilimumab. Resume ipilimumab in patients with complete or partial resolution of adverse reactions (Grade 0 or 1) and who are receiving less than 7.5 mg prednisone or equivalent per day.
	• Symptomatic reactions lasting 6 weeks or longer • Inability to reduce corticosteroid dose to 7.5 mg prednisone or equivalent per day Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: acid Cisplatin L Index Stay updated, free articles. Join our Telegram channel Join Tags: 2017 Intravenous Medications Apr 25, 2017 | Posted by admin in NURSING | Comments Off on I Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access