Hyaluronidase, recombinant; immune globulin is a subcutaneous immunoglobulin (SCIG) used with recombinant human hyaluronidase for the treatment of primary immunoglobulin deficiency in adults and pediatric patients 2 years and older and for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. At least 98% of the immune globulin protein is IgG. The product is a dual vial unit consisting of 1 vial of human immune globulin and 1 vial of recombinant human hyaluronidase. Hyaluronidase is subcutaneously infused prior to infusion of SCIG, which increases the absorption and dispersion of immune globulin. Lifelong replacement therapy with human immune globulin provides passive immunity to decrease susceptibility to life-threatening infections in patients with predominant antibody deficiencies. The use of SCIG may decrease the incidence of systemic adverse events compared to IVIG; however, local reactions are more common. Subcutaneous administration may be desirable for patients who have poor venous access. Patients or caregivers can self-administer the immune globulin and hyaluronidase infusions at home with proper training. Additionally, hyaluronidase, recombinant; immune globulin only needs to be infused every 4 weeks after initial ramp up, compared with other SCIG products which must be given every 2 weeks.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-If a patient misses a dose or appointment, administer the missed dose as soon as possible and then resume scheduled treatments as applicable.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration whenever solution and container permit. The appearance of the immune globulin product can vary from clear to slightly opalescent and colorless or pale yellow. The appearance of the hyaluronidase product should be clear and colorless. Do not use either component if the solution is cloudy or has particulates.
-Allow the refrigerated product to come to room temperature before use; do not use external heat sources.
-Do not shake the vials.
-Hyaluronidase and immune globulin are administered sequentially. Do not mix in the same container. Do not mix or administer with other parenteral products or use each component alone.
-Storage: Hyaluronidase, recombinant; immune globulin contains no preservative. Discard unused product immediately according to local standards for biohazard products.
Subcutaneous Administration
-Infuse the 2 components of hyaluronidase, recombinant; immune globulin sequentially, beginning with the hyaluronidase. If using two or three infusion sites, divide the hyaluronidase evenly between all sites.
Preparation of recombinant human hyaluronidase
-Attach a syringe to a needle or needle-less transfer device and draw the full contents of the vial into the syringe.
-Repeat for each additional hyaluronidase vial using the same syringe, if possible.
-Attach the syringe to the subcutaneous needle set and prime up to the needle hub.
Preparation of immune globulin
-Transfer contents of the vial(s) by pooling into a syringe or an infusion bag using a transfer device; attach and prime the pump administration tubing. Alternatively, directly spike the vial using a vented pump administration tubing and prime.
Subcutaneous infusion
-Infusion requires an infusion pump capable of infusing a therapeutic dose at infusion rates of up to 300 mL/hour/site. The ability to titrate the flow is needed.
-To ensure maximum flow rates, use a subcutaneous needle set that is 24-gauge and labeled for high flow rates.
-Suggested sites for infusion are the middle to upper abdomen and thighs. If 2 sites are used, the sites should be on the opposite side of the body. If 3 sites are used, the sites should be at least 10 cm apart. Avoid bony prominences, or areas that are scarred, inflamed, or infected.
-A bifurcated needle set may be used.
-Consider using longer needles (12 or 14 mm rather than 9 mm) to prevent infusion site leakage.
-Rotate infusion sites by choosing opposite sides of the body between successive infusions.
-Pinch at least 1 inch of skin between 2 fingers and insert the subcutaneous needle at a 90-degree angle. Secure the needle with sterile tape and check placement.
--If using the push method, gently pull back on the plunger of the attached syringe. If blood is seen in the tubing, discard the needle and repeat insertion with a new subcutaneous needle and infusion site.
-If using the pump method, close the clamp above the lower port of the pump tubing. Clean the lower port with alcohol swab and allow to dry for at least 30 seconds. Attach a 5 mL syringe to the lower port of the pump tubing. Pull back gently on the syringe plunger. If no blood, remove the syringe and open the lower port clamp.
-Secure the needle with a sterile dressing.
-Administer hyaluronidase. If more than 1 site is used, divide and administer the hyaluronidase equally between each site.
--If using the push method, infuse into 1 injection site at an initial rate of 1 to 2 mL/minute or as tolerated.
-If using the pump method, start at an initial rate of 60 mL to 120 mL/hour/site and may increase as tolerated up to 300 mL/hour.
-Begin the infusion of immune globulin through the same subcutaneous needle set within 10 minutes of the hyaluronidase infusion using a variable rate program of the infusion pump.
-For primary immunodeficiency (PI):
--Patients weighing 40 kg or more: For the first 2 infusions, initiate at a rate of 10 mL/hour/site; gradually increase the rate every 5 to 15 minutes as tolerated to a maximum of 120 mL/hour/site. If this is tolerated, may increase up to a maximum of 240 mL/hour/site for the remainder of the infusion. For subsequent infusions, initiate at 10 mL/hour/site; gradually increase every 5 to 15 minutes as tolerated to a maximum of 240 mL/hour/site. If this is tolerated, may increase up to a maximum of 300 mL/hour/site for the remainder of the infusion. Maximum volume is 600 mL per site.
-Patients weighing less than 40 kg: For the first 2 infusions, initiate at a rate of 5 mL/hour/site; gradually increase the rate every 5 to 15 minutes as tolerated to a maximum of 40 mL/hour/site. If this is tolerated, may increase up to a maximum of 80 mL/hour/site for the remainder of the infusion. For subsequent infusions, initiate at 10 mL/hour/site; gradually increase every 5 to 15 minutes as tolerated to a maximum of 80 mL/hour/site. If this is tolerated, may increase up to a maximum of 160 mL/hour/site for the remainder of the infusion. Maximum volume is 300 mL per site.
-For chronic inflammatory demyelinating polyneuropathy (CIDP):
--Patients weighing 40 kg or more: For the first 2 infusions, infuse at an initial rate of 10 mL/hour/site; gradually increase the rate every 5 to 15 minutes to a maximum infusion rate of 240 mL/hour/site. For subsequent infusions, gradually increase the rate to a maximum of 300 mL/hour/site. The maximum infusion volume should not exceed 1,200 mL.
-Patients weighing less than 40 kg: For the first 2 infusions, initiate at a rate of 5 mL/hour/site; gradually increase the rate every 5 to 15 minutes as tolerated to a maximum infusion rate of 80 mL/hr/site. For subsequent infusions, gradually increase the rate to a maximum of 160 mL/hour/site. The maximum infusion volume should not exceed 600 mL.
-If the maximum daily dose limit is exceeded or the patient cannot tolerate the infusion volume, the dose may be administered over multiple days in divided doses with 48 to 72 hours between doses to allow absorption of infusion fluid at the infusion site. The dose can be administered at 1 to 3 infusion sites with a maximum volume of 600 mL/site (or as tolerated). If using three sites, the maximum volume is 400 mL per site.
-At the end of the infusion, flush the infusion tubing up to the needle with 0.9% Sodium Chloride Injection or 5% Dextrose Injection, if needed.
Thromboembolism may occur with hyaluronidase, recombinant; immune globulin. A cerebrovascular accident occurred in 1 patient receiving hyaluronidase, recombinant; immune globulin in clinical trials; this patient had coexisting cardiovascular risk factors. Adverse reactions associated with thrombosis and reported with immune globulin products include palpitations, chest pain (unspecified), cardiovascular collapse, and cardiac arrest. Thromboembolism can occur in patients without any known risk factors. Risk factors may include age more than 65, multiple cardiovascular risk factors, prolonged immobilization, estrogen use, hypercoagulable conditions, history of venous or arterial thrombosis, indwelling central vascular catheters, and/or hyperviscosity. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity including those with cryoglobulins, chylomicronemia/markedly high triglycerides, or monoclonal gammopathies. For patients at risk of thrombosis, administer immune globulin at the minimum dose and infusion rate practicable. Ensure adequate hydration in all patients before administration, and monitor for signs and symptoms of thrombosis.
Severe hypersensitivity and infusion-related reactions, such as anaphylactic shock or anaphylactoid reactions, may occur with hyaluronidase, recombinant; immune globulin treatment; immediately discontinue the infusion and administer appropriate treatment for hypersensitivity reactions. Infusion reactions in clinical trials included fever (7% to 15%), fatigue (8% to 11%), back pain (5%), extremity pain (5%), pruritus (8%), erythema (8%), and hypertension (6% to 7%). Other symptoms reported with other immune globulin products have included swollen face or tongue, pharyngeal edema, chills, dizziness, hypotension, sinus tachycardia, malaise, myalgia, rigors, chest tightness, wheezing, and urticaria. Allergic dermatitis, bullous rash, epidermolysis, erythema multiforme, and Stevens-Johnson syndrome have also been observed with postmarketing use of immune globulin products.
Hemolysis and hemolytic anemia have been associated with IVIG administration and may also occur with hyaluronidase, recombinant; immune globulin. Delayed hemolytic anemia secondary to immune globulin can develop due to enhanced red blood cell sequestration, and acute hemolysis consistent with intravascular hemolysis has been reported. Blood group antibodies present in subcutaneous immune globulin may act as hemolysins and induce immunoglobulin adherence to red blood cells; positive direct antiglobulin (Coombs') test results have been reported with immune globulin usage. Monitor patients for clinical signs and symptoms of hemolysis. If signs and/or symptoms of hemolysis are present after infusion, perform appropriate confirmatory laboratory testing. Leukopenia and pancytopenia have also been observed with immune globulin products in postmarketing experience.
As with other products derived from or purified with human blood components, the possibility of transmitting a viral infection or variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent exists in patients receiving hyaluronidase, recombinant; immune globulin. The risk of infectious agent transmission has been reduced by screening plasma donors for prior exposure to certain viruses, testing for the presence of certain current virus infections, and including virus inactivation/removal steps in the manufacturing processes. Influenza-like illness has been reported with hyaluronidase; recombinant; immune globulin in postmarketing experience. Report all infections thought to be possibly transmitted by hyaluronidase, recombinant; immune globulin to the manufacturer by calling 1-877-825-3327.
Local adverse reactions to hyaluronidase, recombinant; immune globulin administration are common. During clinical trials, 24% to 52% of patients experienced an injection site reaction with subcutaneous immune globulin administration. Discomfort or pain, local erythema, swelling, and pruritus were the most frequent infusion reactions. Most local reactions were either mild or moderate in severity; 3 local reactions were considered severe and included injection site pain, swelling, and edema that extended from the abdominal infusion site to the genitalia; all reactions were transient and resolved without sequelae. In efficacy and long-term extension trials of hyaluronidase, recombinant; immune globulin, there were no observable changes in the skin or subcutaneous tissue. Infusion site leaking has been reported with postmarketing use of hyaluronidase, recombinant; immune globulin.
Renal dysfunction, renal failure (unspecified), renal tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death may occur with use of human immune globulin products given intravenously, especially those containing sucrose. Of note, hyaluronidase, recombinant; immune globulin does not contain sucrose. Administer subcutaneous immune globulin (SCIG) at the minimum rate of infusion practicable for patients judged to be at risk of developing renal dysfunction because of preexisting renal insufficiency or predisposition to acute renal failure. Patients predisposed to acute renal failure include those with diabetes mellitus, age greater than 65, volume depletion, obesity, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal function assessment including urine output, serum creatinine, and blood urea nitrogen concentrations before SCIG administration and periodically thereafter is recommended. Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk of developing acute renal failure. Also, correct hypovolemia before SCIG is infused. Discontinuation of SCIG may be warranted if renal function deteriorates. Instruct patients to immediately report oliguria, sudden weight gain, fluid retention/edema, and/or shortness of breath.
Nausea (7% to 11%), vomiting (7%), and abdominal pain (6%) were reported in patients receiving hyaluronidase, recombinant; immune globulin during clinical trials. An increase in lipase (5%) was also reported during clinical trials. Hepatic dysfunction has been observed with immune globulin products in postmarketing experience.
Hyaluronidase is antigenic and repeated injections of relatively large amounts of the enzyme may result in antibody formation of neutralizing antibodies. In clinical trials, 15% to 18% of subjects developed nonneutralizing antibodies to recombinant human hyaluronidase. These antibodies may cross-react with endogenous PH20, which is expressed in the adult male testes, epididymis, and sperm; however, it is unknown if these antibodies may interfere with fertilization.
Headache was reported in 7% to 21% of patients who received hyaluronidase, recombinant; immune globulin during clinical trials. Tremor, oral paresthesias, seizures, loss of consciousness, and coma have been observed with immune globulin products in postmarketing experience.
Non-cardiogenic pulmonary edema may occur in patients administered human immune globulin products such as hyaluronidase, recombinant; immune globulin. Dyspnea, apnea, acute respiratory distress syndrome (ARDS), cyanosis, hypoxia, pulmonary edema, and bronchospasm have been noted postmarketing with immune globulins. Pulmonary symptoms could be indicative of a hypersensitivity reaction or of transfusion-related acute lung injury (TRALI), which is a well-characterized clinical syndrome consisting of severe respiratory distress, dyspnea, hypoxemia, hypotension, fever, normal left ventricular function, and pulmonary edema. Radiographs show bilateral pulmonary infiltrates without evidence of cardiac compromise or fluid overload. Symptoms typically occur 1 to 6 hours after immune globulin receipt. The clinical presentation may be subtle or significant. Respiratory support may be necessary. Diuretics are not effective in TRALI, as the cause involves microvascular injury rather than fluid overload. The etiology of TRALI may be attributable to the presence of anti-HLA antibodies and/or anti-granulocyte antibodies in the plasma of multiparous females or donors who have received previous transfusions who serve as donors for the plasma-derived product. Monitor recipients of subcutaneous immune globulin for pulmonary adverse events. If TRALI is suspected, the product used and the patient's serum need to be tested for the presence of anti-neutrophil and anti-HLA antibodies.
Aseptic meningitis syndrome characterized by severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting has occurred with subcutaneous immune globulin and usually begins within several hours to 2 days after immune globulin treatment. Patients exhibiting such signs and symptoms should receive a thorough neurological examination, including cerebrospinal fluid studies, to rule out other causes of meningitis. Cerebrospinal fluid studies frequently show pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein concentrations up to several hundred mg/dl. Discontinuation of immune globulin treatment has resulted in remission of the syndrome within several days without sequelae. Aseptic meningitis syndrome may occur more frequently in association with high doses (greater than 2 g/kg) and/or rapid infusion of immune globulin product.
Thromboembolism is known to be associated with immune globulin therapy, regardless of the route of administration. Thrombosis can occur in patients without any known risk factors; however, patients most at risk include geriatric patients, those with multiple cardiovascular risk factors (known cardiac disease), impaired cardiac output (heart failure), prolonged immobilization, obesity, diabetes mellitus, use of estrogens, indwelling central venous catheters, acquired or inherited coagulation disorders, and patients with a history of a thrombotic event, vascular disease, atherosclerosis (coronary artery disease), and/or known or suspected hyperviscosity. Assessment of blood viscosity may be warranted for patients at risk for hyperviscosity, such as those with cryoglobulins, fasting chylomicronemia, hypertriglyceridemia, or monoclonal gammopathies. Rapid infusion rates and high doses may increase the risk in patients who are already at risk for thrombotic events. For patients at risk of developing thrombosis, use the minimum recommended dose administered at the minimum practicable rate. Hyperproteinemia, increased serum viscosity, and hyponatremia may also occur in patients receiving immune globulin therapy. Distinguish true hyponatremia from a pseudohyponatremia that is associated with or causally related to hyperproteinemia with concomitant decreased calculated serum osmolality or elevated osmolar gap. Treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thrombotic events. Ensure patients are not volume depleted prior to the initiation of hyaluronidase, recombinant; immune globulin therapy and monitor for signs and symptoms of thrombosis during and after each infusion. Encourage patients to report any pain, swelling, discoloration, and/or warmth of the arms or legs, unexplained shortness of breath, chest pain/discomfort, unexplained tachycardia, and numbness or weakness on 1 side of the body.
Hyaluronidase, recombinant; immune globulin is contraindicated for use in patients with IgA deficiency who have antibodies against IgA and a history of hypersensitivity. Patients with IgA deficiency can develop antibodies against IgA and have anaphylactic or immune-mediated adverse reactions to pooled immunoglobulin products that contain IgA such as immune globulin. The drug is also contraindicated for use in patients who have a history of anaphylactic or severe systemic reactions to immune globulin, and in patients with known systemic hypersensitivity to hyaluronidase or recombinant human hyaluronidase. Severe hypersensitivity reactions may occur in any patient, even if previous treatment with immune globulin was tolerated. If anaphylactic or anaphylactoid reactions are suspected, discontinue administration immediately. Treat any acute anaphylactoid reactions as medically appropriate.
There are only limited human data available to assess the presence or absence of drug-associated risk of hyaluronidase, recombinant; immune globulin in pregnancy and the potential for fetal harm or the effect on reproduction capacity is unknown. Immune globulins increasingly cross the placenta after 30 weeks of gestation. In a small postmarketing pregnancy study (n = 9), 2 out of 5 infants born to mothers taking hyaluronidase, recombinant; immune globulin during pregnancy had congenital abnormalities (1 cleft lip and 1 talipes calcaneovalgus); however, the data are insufficient to determine causality. According to the Advisory Committee on Immunization Practices (ACIP), fetal adverse events have not occurred following administration of immune globulin preparations to pregnant women. Administer hyaluronidase, recombinant; immune globulin during pregnancy only if clearly indicated. Animal reproduction studies have not been conducted with immune globulin. In studies of recombinant human hyaluronidase in mice, no adverse effects on fetal development were observed at a maternal dose of 3 mg/kg, which is 4,800 times higher than a typical monthly human dose. At maternal doses of 9 and 18 mg/kg, an increased number of fetal resorptions and reduced fetal weight occurred. In a peri- and post-natal reproduction study during which female mice received recombinant human hyaluronidase beginning with implantation through lactation, no adverse effects on gestation or parturition were observed at doses up to 9 mg/kg (14,400 times a typical human monthly dose).
Use of hyaluronidase, recombinant; immune globulin has not been evaluated in women who are breast-feeding and it is unknown if the drug is excreted in breast milk. Case reports of 2 nursing mothers receiving intravenous immune globulin therapy suggest transfer of IgG and IgM into the colostrum and breast milk. Consider the developmental and health benefits of breast-feeding along with the mother's need for hyaluronidase; recombinant; immune globulin and any potential adverse effects on the breast-fed infant or the underlying maternal condition.
The immune globulins present in hyaluronidase, recombinant; immune globulin may interfere with the immune response to vaccination, specifically with live virus vaccines including measles, mumps, rubella, and varicella. The recommended interval of time before administration of an antibody-containing product after receipt of a live antigen is 2 weeks. Administration of measles- or varicella-containing vaccines, if indicated, is recommended to be delayed 8 or more months from the time of IVIG administration; due to similar pharmacokinetic properties between IV and subcutaneous immune globulin following administration, the equivalent interval is recommended with SCIG therapy. If simultaneous administration of an antibody-containing product and measles-containing vaccine or varicella vaccine is unavoidable, administer at different sites and revaccinate or test for seroconversion after the recommended interval. The duration of interference of antibody-containing products with the immune response to the measles component of measles-containing vaccine, and possibly varicella vaccine, is dose-related. Yellow fever, oral Ty21a typhoid vaccine, and live-attenuated influenza vaccine are exceptions to these recommendations. These live-attenuated vaccines can be administered at any time before, after, or simultaneously with an antibody-containing product without substantially decreasing the antibody response.
Hyaluronidase, recombinant; immune globulin is for administration by subcutaneous (SC) injection only. Do not use hyaluronidase, recombinant; immune globulin for intravenous administration or intramuscular administration.
Avoid infusion of hyaluronidase, recombinant; immune globulin into or around a localized, infected area as this may cause the infection to spread. Hyaluronidase, recombinant; immune globulin is a derivative of human blood. As with other products derived from or purified with human blood components, the remote possibility of contamination with hepatitis, Creutzfeldt-Jakob disease (CJD), and other bacterial or viral infection exists. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents. The manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present in this product. Some viruses, such as parvovirus B19, are particularly difficult to remove or inactivate. Parvovirus B19 most seriously affects pregnant women and immune compromised individuals and symptoms include fever, drowsiness, chills, and rhinitis followed in about 2 weeks with rash and joint pain. Patients should be encouraged to call their health care provider if they develop these symptoms. All infections thought by a physician to have been possibly transmitted by immune globulin should be reported to the manufacturer. The health care provider should discuss the risks and benefits of this product with the patient.
Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur with the use of human immune globulin products such as hyaluronidase, recombinant; immune globulin. To reduce the risk of acute renal failure, caution should be undertaken in patients at increased risk (e.g., patients with any degree of renal impairment or renal disease, diabetes mellitus, patients greater than 65 years old, dehydration or hypovolemia, sepsis, paraproteinemia, or concomitant nephrotoxic drug therapy); periodic monitoring of renal function tests and urinary output are particularly important. Adequately hydrate the patient before the initiation of the initial infusion; assess the blood urea nitrogen (BUN) concentration and serum creatinine concentration at initial immune globulin receipt and at appropriate intervals thereafter. In patients who are at risk of developing renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure, consider lower, more frequent dosing. If renal function deteriorates, consider product discontinuation.
General dosing information:
-Initiate treatment using an interval/dosage ramp-up schedule, which allows for dosage escalation over 7 weeks to a target dose to be given every 3 to 4 weeks. During dosage escalation, the time intervals between doses increases.
-A full therapeutic dose may be administered in 1 site up to every 4 weeks.
-Consider drug volume, total infusion time, and tolerability when adjusting dosage frequency and number of infusion sites. Adjust the frequency of administration so that the patient receives the same weekly equivalent dose.
For the treatment of primary immunoglobulin deficiency (e.g., common variable immunodeficiency, agammaglobulinemia, hypogammaglobulinemia, Wiskott-Aldrich syndrome):
NOTE: Only initiate treatment using a gradual upward titration of the dose with increasing time intervals between doses. Initiation with a full monthly dose has not been studied.
-for the treatment of primary immunoglobulin deficiency in patients naive to IgG treatment or switching from subcutaneous immune globulin:
Subcutaneous dosage (Initial dose titration):
Adults: Administer the first dose of hyaluronidase, recombinant; immune globulin subcutaneously 1 week after the last infusion of previous treatment according to the following schedule. Week 1 (first infusion): 25% of target dose; Week 2 (second infusion): 50% of target dose; Week 3: no infusion; Week 4 (third infusion): 75% of target dose; Weeks 5 and 6: no infusion; Week 7 (fourth infusion if required): target dose.
Children and Adolescents 2 to 17 years: Administer the first dose of hyaluronidase, recombinant; immune globulin subcutaneously 1 week after the last infusion of previous treatment according to the following schedule. Week 1 (first infusion): 25% of target dose; Week 2 (second infusion): 50% of target dose; Week 3: no infusion; Week 4 (third infusion): 75% of target dose; Weeks 5 and 6: no infusion; Week 7 (fourth infusion if required): target dose.
Subcutaneous dosage (Maintenance):
Adults: 300 to 600 mg/kg/dose subcutaneously every 3 to 4 weeks. Adjust dose according to clinical response.
Children and Adolescents 2 to 17 years: 300 to 600 mg/kg/dose subcutaneously every 3 to 4 weeks. Adjust dose according to clinical response.
-for the treatment of primary immunoglobulin deficiency in patients switching from intravenous immune globulin (IVIG):
Subcutaneous dosage (Initial dose titration):
Adults: Administer the first dose of hyaluronidase, recombinant; immune globulin subcutaneously 1 week after the last infusion of previous treatment according to the following schedule. Week 1 (first infusion): 25% of target dose; Week 2 (second infusion): 50% of target dose; Week 3: no infusion; Week 4 (third infusion): 75% of target dose; Weeks 5 and 6: no infusion; Week 7 (fourth infusion if required): target dose (same dose and frequency as previous IVIG treatment).
Children and Adolescents 2 to 17 years: Administer the first dose of hyaluronidase, recombinant; immune globulin subcutaneously 1 week after the last infusion of previous treatment according to the following schedule. Week 1 (first infusion): 25% of target dose; Week 2 (second infusion): 50% of target dose; Week 3: no infusion; Week 4 (third infusion): 75% of target dose; Weeks 5 and 6: no infusion; Week 7 (fourth infusion if required): target dose (same dose and frequency as previous IVIG treatment).
Subcutaneous dosage (Maintenance):
Adults: Administer hyaluronidase, recombinant; immune globulin subcutaneously at the same dose and frequency as previous IVIG treatment. Adjust dose according to clinical response and IgG serum trough concentrations, as serum concentrations should be comparable with IVIG concentrations with the same dosing regimen. Calculate the difference between the current serum IgG concentration and the IgG concentration during previous IVIG therapy. Use the table provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the dose per dosing interval based on the patient's weight. If administered at a different interval than previous treatment, then adjust dose by clinical response.
Children and Adolescents 2 to 17 years: Administer hyaluronidase, recombinant; immune globulin subcutaneously at the same dose and frequency as previous IVIG treatment. Adjust dose according to clinical response and IgG serum trough concentrations, as serum concentrations should be comparable with IVIG concentrations with the same dosing regimen. Calculate the difference between the current serum IgG concentration and the IgG concentration during previous IVIG therapy. Use the table provided in the product labeling to find the difference and the corresponding amount in mL by which to increase or decrease the dose per dosing interval based on the patient's weight. If administered at a different interval than previous treatment, then adjust dose by clinical response.
For the maintenance treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment:
NOTE: Patients switching from intravenous administration of immune globulin must be on stable doses of IVIG.
NOTE: Hyaluronidase, recombinant; immune globulin has been designated an orphan drug by the FDA for this indication.
Subcutaneous dosage:
Adults: Administer the first dose of hyaluronidase, recombinant; immune globulin subcutaneously 2 weeks after the last infusion of previous treatment according to the following schedule. Week 1: no infusion. Weeks 2 and 3 (first and second infusion): 25% of the target dose. Week 4 (third infusion): 50% of the target dose. Week 5: no infusion. Week 6 (fourth infusion): 75% of the target dose. Weeks 7 and 8: no infusion. Week 9 (fifth infusion): target dose (same dose and frequency as previous IVIG treatment.
For measles prophylaxis in patients with immunoglobulin deficiency who have been exposed to measles or are at risk of measles exposure:
Subcutaneous dosage:
Adults: 400 mg/kg/dose subcutaneously as soon as possible and within 6 days of exposure. This dose should provide a serum concentration more than 240 milli-International Units/mL of measles antibodies for at least two weeks. If a patient is at risk of future measles exposure and receives a dose less than 530 mg/kg/dose subcutaneously every 3 to 4 weeks, increase the weekly dose to at least 530 mg/kg/dose. This should provide a serum concentration of 240 milli-International Units/mL of measles antibodies for at least 22 days after infusion.
Children and Adolescents 2 to 17 years: 400 mg/kg/dose subcutaneously as soon as possible and within 6 days of exposure. This dose should provide a serum concentration more than 240 milli-International Units/mL of measles antibodies for at least two weeks. If a patient is at risk of future measles exposure and receives a dose less than 530 mg/kg/dose subcutaneously every 3 to 4 weeks, increase the weekly dose to at least 530 mg/kg/dose. This should provide a serum concentration of 240 milli-International Units/mL of measles antibodies for at least 22 days after infusion.
Maximum Dosage Limits:
-Adults
Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin or hyaluronidase.
-Geriatric
Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin or hyaluronidase.
-Adolescents
Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin or hyaluronidase.
-Children
2 to 12 years: Dosage must be individualized and is highly variable depending on the nature and severity of the disease and on the individual patient response. There is no absolute maximum dosage of immune globulin or hyaluronidase.
younger than 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available. In patients who are at risk of developing renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure, consider lower, more frequent dosing. If renal function deteriorates, consider discontinuation.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Aspirin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Caffeine; Pyrilamine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Chlorpheniramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Diphenhydramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acetaminophen; Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acrivastine; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Acyclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like acyclovir. Administer IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential risk for developing acute renal failure.
Adefovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like adefovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amide local anesthetics: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Amikacin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Aminoglycosides: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Aminosalicylate sodium, Aminosalicylic acid: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Amlodipine; Celecoxib: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amphotericin B lipid complex (ABLC): (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amphotericin B liposomal (LAmB): (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Amphotericin B: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like amphotericin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Articaine; Epinephrine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Aspirin, ASA: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Caffeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Dipyridamole: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Omeprazole: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Aspirin, ASA; Oxycodone: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Bacitracin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like bacitracin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Bismuth Subsalicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Brompheniramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Brompheniramine; Phenylephrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Brompheniramine; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Bupivacaine Liposomal: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Bupivacaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Bupivacaine; Epinephrine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Bupivacaine; Lidocaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Bupivacaine; Meloxicam: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects. (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Capreomycin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like capreomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Carbinoxamine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Celecoxib: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Celecoxib; Tramadol: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Chlophedianol; Dexbrompheniramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorcyclizine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chloroprocaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Chlorpheniramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Codeine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Dextromethorphan: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Hydrocodone: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Phenylephrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Chlorpheniramine; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Choline Salicylate; Magnesium Salicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Cidofovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cidofovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Cisplatin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and immune globulin products (IVIG) are necessary. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Cisplatin can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins. IVIG has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death.
Clemastine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Cocaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Colistimethate, Colistin, Polymyxin E: (Moderate) Use caution with concomitant Immune Globulin (IG) products and colistimethate sodium. IG products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Colistin: (Moderate) Use caution with concomitant Immune Globulin (IG) products and colistimethate sodium. IG products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Conjugated Estrogens: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Corticotropin, ACTH: (Minor) Corticosteroids (e.g., cortisone, corticotropin, ACTH), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Cortisone: (Minor) Corticosteroids (e.g., cortisone, corticotropin, ACTH), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Cyclosporine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cyclosporine. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Cyproheptadine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Dexbrompheniramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Dexbrompheniramine; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Dexchlorpheniramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Diclofenac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Diclofenac; Misoprostol: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Dienogest; Estradiol valerate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Diflunisal: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Dimenhydrinate: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Diphenhydramine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Diphenhydramine; Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Diphenhydramine; Naproxen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Diphenhydramine; Phenylephrine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Doxylamine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Doxylamine; Pyridoxine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Drospirenone; Estetrol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Drospirenone; Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Efgartigimod Alfa: (Moderate) Monitor for reduced efficacy of immune globulin during coadministration with efgartigimod. Concomitant use of efgartigimod with medications that bind to the human neonatal Fc receptor (FcRn), such as immune globulin, may reduce immune globulin exposure and efficacy. Consider efgartigimod discontinuation and the use of alternative therapies if long-term therapy with immune globulin is needed.
Efgartigimod Alfa; Hyaluronidase: (Moderate) Monitor for reduced efficacy of immune globulin during coadministration with efgartigimod. Concomitant use of efgartigimod with medications that bind to the human neonatal Fc receptor (FcRn), such as immune globulin, may reduce immune globulin exposure and efficacy. Consider efgartigimod discontinuation and the use of alternative therapies if long-term therapy with immune globulin is needed.
Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ester local anesthetics: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Esterified Estrogens: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Estradiol; Levonorgestrel: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Estradiol; Norethindrone: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Estradiol; Norgestimate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Estradiol; Progesterone: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Estrogens: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Estropipate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Etodolac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Fenoprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Flurbiprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Foscarnet: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like foscarnet. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ganciclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like ganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Gentamicin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Hydrocodone; Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydroxyzine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ibuprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ibuprofen; Famotidine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ibuprofen; Oxycodone: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ibuprofen; Pseudoephedrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indomethacin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ketoprofen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Ketorolac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Lidocaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Lidocaine; Epinephrine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Lidocaine; Prilocaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Magnesium Salicylate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. There should be an interval of at least 5 months following administration of immune globulin, including varicella-zoster immune globulin, VZIG, before varicella vaccination. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations. (Major) Rubella virus vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of blood, plasma, and/or immunoglobulins because antibodies in these products can neutralize the vaccine.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Rubella virus vaccine or Measles/mumps/rubella vaccines, MMR should not be given for at least 3 months following administration of blood, plasma, and/or immunoglobulins because antibodies in these products can neutralize the vaccine.
Meclizine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Meclofenamate Sodium: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Mefenamic Acid: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Meloxicam: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Mepivacaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Methenamine; Sodium Salicylate: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Nabumetone: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Naproxen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Naproxen; Esomeprazole: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Naproxen; Pseudoephedrine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Nonsteroidal antiinflammatory drugs: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Oxaprozin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Pamidronate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pamidronate. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Paromomycin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Pentamidine: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pentamidine. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Piroxicam: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Plazomicin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Polymyxin B: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like polymyxin B. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Pozelimab: (Major) Avoid concomitant use of pozelimab and intravenous immune globulin (IVIG). If use is necessary, monitor for reduced clinical efficacy of pozelimab. Concomitant use may decrease serum pozelimab concentrations.
Prilocaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Prilocaine; Epinephrine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Pseudoephedrine; Triprolidine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ravulizumab: (Major) Administer a supplemental dose of ravulizumab and monitor for reduced efficacy of ravulizumab during concurrent use with immune globulin. Consult the manufacturer's recommendations for the supplemental dosage. Concomitant use of immune gloublin with ravulizumab may reduce ravulizumab exposure and efficacy.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Ropivacaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Rotavirus Vaccine: (Major) Efficacy of live attenuated virus vaccines such as Rotavirus may be impaired by immune globulin administration; revaccination may be necessary. As the passive transfer of antibodies may impair the efficacy of live attenuated virus vaccines, defer vaccination with live virus vaccines until approximately 3 months after immune globulin administration. Inform the immunizing physician of recent therapy with immune globulin so that appropriate measures can be taken.
Salicylates: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Salsalate: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Sedating H1-blockers: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Streptomycin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Streptozocin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like streptozocin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Sulindac: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Sumatriptan; Naproxen: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Tacrolimus: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like tacrolimus. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Tetracaine: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
Tobramycin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
Tolmetin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Triprolidine: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Valacyclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like valacyclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Valganciclovir: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like valganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Vancomycin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Varicella-Zoster Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. There should be an interval of at least 5 months following administration of immune globulin, including varicella-zoster immune globulin, VZIG, before varicella vaccination. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations.
Zoledronic Acid: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like zoledronic acid. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Mechanism of Action:-Immune globulin: Immunoglobulins are antibodies synthesized by B lymphocytes. Subcutaneous immune globulin (SCIG) supplies a broad spectrum of IgG antibodies capable of opsonization and neutralization of many toxins and microbes as well as complement activation. The amount of each IgG subclass is similar to that of human plasma. The Fc fragment of the IgG molecule allows the molecule to interact with and signal through Fc- gamma receptors on B cells and other cells of the phagocytic system. The Fc fragment also interacts with the Fc-binding plasma proteins, which is essential for complement activation and microorganism clearance. The passive immunity imparted by SCIG is capable of attenuating or preventing infectious diseases or deleterious reactions from toxins, mycoplasma, parasites, bacteria, and viruses. In immunomodulatory disease states, it is believed the Fc fragment of IgG and the Fc-gamma receptors on target cells (e.g., macrophages, B cells, natural killer cells, plasma cells, eosinophils, neutrophils, platelets) interact to up-regulate or down-regulate immune responses. In autoimmune cytopenias, blockade of Fc-gamma receptors on macrophages blocks the clearance of opsonized target cells. Immunomodulatory response may be facilitated by the immunoregulatory effects of anti-idiotypic antibodies on B cells and autoantibodies, regulation of helper T cell production, and apoptosis of immune system gene expression. The mechanism of action of immunoglobulins in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) is not fully clear but may include immunomodulatory effects.
-Hyaluronidase: Hyaluronidase is a dispersion agent that breaks down hyaluronic acid in connective tissue resulting in increased permeability and enhanced diffusion of concurrently administered parenteral agents. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of the glucosamine moiety and C4 of glucuronic acid. This temporarily decreases the viscosity of the cellular cement and promotes diffusion of injected fluids or of localized transudates or exudates, thus facilitating their absorption. When no spreading factor is present, material injected subcutaneously spreads very slowly, but hyaluronidase causes rapid spreading of other materials, provided local interstitial pressure is adequate to furnish the necessary mechanical impulse. The rate of diffusion is proportionate to the amount of enzyme administered, and the extent is proportionate to the volume of solution.
Hyaluronidase, recombinant; immune globulin is administered by subcutaneous injection.
-Immune globulin: Systemic availability of immune globulin can be affected by several factors, including the site of administration and the rate of IgG catabolism. Catabolism of IgG is affected by the size and timing of a dose.
-Hyaluronidase: The rate of hyaluronidase-induced diffusion of concurrently administered drugs is proportionate to the amount of enzyme administered, while the extent of diffusion is proportionate to the volume of solution. Knowledge of the mechanisms involved in the clearance of injected hyaluronidase is limited. Studies have demonstrated that repeated injections of relatively large amounts may result in the formation of neutralizing antibodies. After intradermal administration of hyaluronidase in adults, the drug effect completely dissipates within 48 hours.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Subcutaneous Route
The absolute bioavailability of subcutaneous immune globulin is 93.3% relative to IVIG. In weekly equivalent doses of hyaluronidase; recombinant; immune globulin, mean serum IgG trough concentrations are comparable to IVIG. IgG Tmax following hyaluronidase, recombinant; immune globulin administration is 5 (3.3 to 5.1) days. The mean concentration-time profile of IgG with hyaluronidase; recombinant; immune globulin is similar to that of IVIG without a high peak concentration. The AUC was 20% higher with dosing of hyaluronidase; recombinant; immune globulin compared to conventional subcutaneous immune globulin administration.
-Special Populations
Pediatrics
In pediatric patients 2 to 16 years, no clinically meaningful differences were seen in total IgG pharmacokinetics (AUC and body-weight-normalized apparent clearance) and serum trough concentrations.