Proleukin

Interleukins

For storage information, see specific product information within the How Supplied section.

Injectable Administration Intravenous Administration

Adverse events are common with aldesleukin therapy; monitor vital signs, weight, fluid intake, and fluid output daily.
Aldesleukin doses should be held rather than reduced if an adverse event occurs. If a serious adverse event occurs, discontinue all further treatment for that course and do not start a new course sooner than 7 weeks after cessation of the adverse event.
Do not administer using an in-line filter.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
 
Reconstitution:
Add 1.2 mL of sterile water for injection, USP to the side of the 22 million international units lyophilized powder vial and then gently swirl to avoid excess foaming; do not shake.
The resulting final vial concentration after reconstitution is 18 million international units (1.1 mg)/mL.
Further dilute the reconstituted solution in 5% dextrose injection, USP (D5W); do not reconstitute or dilute aldesleukin with Bacteriostatic Water for Injection, USP or 0.9% Sodium Chloride Injection, USP.
The use of plastic (polyvinyl chloride) bags for dilution is recommended because these containers offer a more consistent drug delivery compared with glass bottles.
Withdraw the appropriate aldesleukin dose; dilute doses > 1.5 mg in 50 mL of 5% Dextrose injection; discard any unused vial portion.
Doses <= 1.5 mg (corresponds with patent weight < 40 kg) should be diluted in a smaller volume of 5% Dextrose Injection. Avoid diluting to a concentration < 0.03 mg/mL or > 0.07 mg/mL because drug delivery varies at these concentrations. If aldesleukin concentration will be < 0.03 mg/mL after dilution, it is recommended that the drug be diluted in 50 mL 5% Dextrose Injection solution to which 50 mg of albumin has been added (to make 0.1% albumin human concentration); this helps prevent variability in the stability and bioactivity of the drug (manufacturer information).
Reconstituted or diluted aldesleukin solutions are stable for up to 48 hours when stored at 2—25 degrees Celsius (36—77 degrees Fahrenheit); do not freeze. Since this product contains no preservative, the reconstituted and diluted solutions should preferably be stored in the refrigerator at 2—8 degrees Celsius (36—46 degrees Fahrenheit) prior to use.
 
Intravenous infusion:
Allow the diluted solution to come to room temperature prior to administering it to the patient.
Administer the diluted dose over 15 minutes.
Do not co-administer aldesleukin with other drugs in the same container.
 
Continuous intravenous infusion:
Dilute appropriate dose of the reconstituted IV solution in a sufficient amount of 5% Dextrose Injection containing 0.1% albumin human to give a final concentration of 5—60 mcg/mL of aldesleukin.

Subcutaneous Administration

Inject subcutaneously taking care not to inject intradermally.

Severe

oliguria / Early / 6.0-63.0
exfoliative dermatitis / Delayed / 18.0-18.0
acute respiratory distress syndrome (ARDS) / Early / 3.0-11.0
anuria / Delayed / 5.0-5.0
hypotension / Rapid / 3.0-3.0
respiratory arrest / Rapid / 1.0-3.0
coma / Early / 2.0-2.0
diarrhea / Early / 2.0-2.0
hyperbilirubinemia / Delayed / 2.0-2.0
pericardial effusion / Delayed / 0-1.0
bradycardia / Rapid / 0-1.0
supraventricular tachycardia (SVT) / Early / 1.0-1.0
myocardial infarction / Delayed / 0-1.0
ventricular tachycardia / Early / 1.0-1.0
AV block / Early / 0-1.0
cardiac arrest / Early / 0-1.0
seizures / Delayed / 0-1.0
confusion / Early / 1.0-1.0
renal tubular necrosis / Delayed / 0-1.0
renal failure (unspecified) / Delayed / 1.0-1.0
thrombosis / Delayed / 0-1.0
anemia / Delayed / 0-1.0
thrombocytopenia / Delayed / 1.0-1.0
leukopenia / Delayed / 0-1.0
coagulopathy / Delayed / 1.0-1.0
hematemesis / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
GI bleeding / Delayed / 0-1.0
vomiting / Early / 0-1.0
GI perforation / Delayed / 0-1.0
fever / Early / 1.0-1.0
malignant hyperthermia / Rapid / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
dyspnea / Early / 1.0-1.0
pulmonary edema / Early / 0-1.0
pulmonary embolism / Delayed / 0-1.0
apnea / Delayed / 1.0-1.0
infection / Delayed / 1.0-1.0
metabolic acidosis / Delayed / 1.0-1.0
capillary leak syndrome / Early / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
atrial fibrillation / Early / Incidence not known
myocarditis / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
cardiomyopathy / Delayed / Incidence not known
cardiac tamponade / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
visual impairment / Early / Incidence not known
vasculitis / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
cerebral edema / Early / Incidence not known
interstitial nephritis / Delayed / Incidence not known
glomerulonephritis / Delayed / Incidence not known
intracranial bleeding / Delayed / Incidence not known
retroperitoneal bleeding / Delayed / Incidence not known
tracheoesophageal fistula / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known
bowel necrosis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
cholecystitis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
tissue necrosis / Early / Incidence not known

Moderate

antibody formation / Delayed / 66.0-74.0
peripheral edema / Delayed / 28.0-28.0
sinus tachycardia / Rapid / 23.0-23.0
stomatitis / Delayed / 22.0-22.0
edema / Delayed / 15.0-15.0
peripheral vasodilation / Rapid / 13.0-13.0
hypomagnesemia / Delayed / 12.0-12.0
hypocalcemia / Delayed / 11.0-11.0
psychosis / Early / 1.0-1.0
depression / Delayed / 0-1.0
delirium / Early / 0-1.0
bleeding / Early / 0-1.0
hypoxia / Early / 0-1.0
phlebitis / Rapid / 0-1.0
hyperuricemia / Delayed / 0-1.0
myopathy / Delayed / Incidence not known
angina / Early / Incidence not known
hypertension / Early / Incidence not known
palpitations / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
ataxia / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
hallucinations / Early / Incidence not known
encephalopathy / Delayed / Incidence not known
neuritis / Delayed / Incidence not known
hyperthyroidism / Delayed / Incidence not known
hypothyroidism / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
colitis / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
splenomegaly / Delayed / Incidence not known
hepatomegaly / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
tachypnea / Early / Incidence not known
bullous rash / Early / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known

Mild

chills / Rapid / 52.0-52.0
rash / Early / 42.0-42.0
nausea / Early / 35.0-35.0
malaise / Early / 27.0-27.0
pruritus / Rapid / 24.0-24.0
asthenia / Delayed / 23.0-23.0
drowsiness / Early / 22.0-22.0
weight gain / Delayed / 16.0-16.0
anxiety / Delayed / 12.0-12.0
dizziness / Early / 11.0-11.0
abdominal pain / Early / 11.0-11.0
cough / Delayed / 11.0-11.0
rhinitis / Early / 10.0-10.0
paranoia / Early / 0-1.0
agitation / Early / 0-1.0
syncope / Early / 0-1.0
leukocytosis / Delayed / 0-1.0
hypothermia / Delayed / 0-1.0
anorexia / Delayed / 20.0
lethargy / Early / Incidence not known
insomnia / Early / Incidence not known
irritability / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known

Cardiac disease, hepatic disease, organ transplant, pulmonary disease, renal disease, renal impairment, seizure disorder, seizures

Because of the serious adverse reactions associated with aldesleukin, IL-2 therapy, patient selection requires a thorough clinical evaluation of each patient before therapy initiation. Patients should have normal cardiac, pulmonary, hepatic, and CNS function at the start of therapy. Evaluation of clinical studies to date reveals that patients with more favorable ECOG performance status (ECOG PS 0) at treatment initiation respond better to aldesleukin, with a higher response rate and lower toxicity. Therefore, selection of patients for treatment should include assessment of performance status. Experience in patients with ECOG PS > 1 is extremely limited. Care should be taken to identify those patients with significant disease which would make aldesleukin treatment contraindicated. Such conditions may include those with significant CNS impairment, cardiac disease, pulmonary disease, renal disease, hepatic disease, abnormal thallium stress test or pulmonary function tests, and/or organ transplant (may increase risk of rejection due to improved cellular immune function). Restrict aldesleukin use to patients with normal cardiac and pulmonary function as defined by thallium stress testing and by formal pulmonary function testing. A baseline and daily on-treatment chest X-ray are also recommended. Document adequate pulmonary function defined as a FEV1 > 2 liters or at least 75% of predicted for height and age before aldesleukin initiation. Document normal ejection fraction and unimpaired wall motion. If a thallium stress test suggests minor wall motion abnormalities, further testing is suggested to exclude significant coronary artery disease. Extreme caution should be used in patients with a normal thallium stress test and a normal pulmonary function test who have a history of either cardiac disease or pulmonary disease, as patients with normal cardiovascular, pulmonary, hepatic, and CNS function may experience serious, life threatening or fatal adverse events. All patients need to have a serum creatinine concentration <= 1.5 mg/dl before aldesleukin initiation. Aldesleukin is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with renal impairment. All patients should have thorough evaluation and treatment of CNS metastases and have a negative scan before receiving aldesleukin. Aldesleukin should be used with extreme caution in patients with a history of seizure disorder, as aldesleukin may cause seizures. Aldesleukin is contraindicated for retreatment if repetitive or difficult to control seizures occur during an earlier course of therapy.

Angina, cardiac arrhythmias, cardiac tamponade, coma, GI bleeding, GI perforation, lethargy, myocardial infarction, psychosis, renal failure, respiratory insufficiency, ventricular tachycardia

Withhold aldesleukin, IL-2 administration in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma, and aldesleukin is contraindicated for retreatment if coma or toxic psychosis lasting longer than 48 hours occurs during an earlier course of therapy. Also, in patients considered for retreatment, aldesleukin is contraindicated if any of the following occur during an earlier course of therapy: sustained ventricular tachycardia (>=5 beats); uncontrolled or unresponsive cardiac arrhythmias; recurrent chest pain with ECG changes consistent with angina or myocardial infarction; respiratory insufficiency requiring intubation for > 72 hours; cardiac tamponade; renal failure requiring dialysis longer than 72 hours; difficult to control or repetitive seizures; GI perforation or GI ischemia; or GI bleeding requiring surgery.

Capillary leak syndrome, requires a specialized care setting, requires an experienced clinician

Aldesleukin, IL-2 administration has been associated with capillary leak syndrome (CLS), which is characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space. The potentially fatal syndrome may cause hypotension, reduced organ perfusion, cardiac arrhythmias, angina, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental status changes. Aldesleukin, IL-2 administration requires a specialized care setting, such as a hospital or intensive care facility, under the supervision of a qualified clinician. Aldesleukin, IL-2 therapy requires an experienced clinician knowledgeable in the use of anticancer agents and specialists skilled in cardiopulmonary or intensive care medicine must be available.

Proleukin

Rx

Recombinant formulation of interleukin-2 (IL-2); uses include metastatic renal cell CA (approved), acute myelogenous leukemia, non-Hodgkin's lymphoma, HIV infection, leprosy as well as to maintain response following bone marrow transplantation.

For the treatment of metastatic renal cell cancer or metastatic malignant melanoma.
NOTE: Aldesleukin has been designated an orphan drug by the FDA for these indications.
Intravenous dosage without LAK cells Adults

600,000 International Units/kg IV every 8 hours for up to 14 doses. After 9 days of rest, the schedule is repeated for up to 14 additional doses, for a maximum of 28 doses per course, as tolerated. If toxicity occurs, doses should be withheld rather than reduced. Patients should be evaluated for response approximately 4 weeks after completion of a course of therapy and immediately prior to the scheduled start of the next treatment course. Additional courses of treatment should be given only if there is tumor shrinkage following the last course and retreatment is not contraindicated (see Dosage Adjustments). Each treatment course should be separated by a rest period of at least 7 weeks from the date of hospital discharge.

Continuous IV infusion dosage† Adults

18 million International Units/m2/day IV for two 5-day cycles. Each cycle should be separated by a 3—7 day rest period. Repeat as tolerated and as tumor response occurs.

Subcutaneous dosage† Adults

Several studies have utilized subcutaneous aldesleukin. Dosages of 1800 International Units/m2 up to 18 million International Units/m2 once daily subcutaneously for 5 days, followed by a 2-day rest period, have been used. Repeat weekly for 6—8 weeks. Then, after a 3—4 week rest period, resume therapy.

Intravenous dosage with LAK cells† Adults

600,000 International Units/kg IV every 8 hours for 5 days. Patient rests days 6 and 7. LAK cells are harvested from the patient on days 8 through 12 and incubated with IL-2. On days 12, 13, and 15, the LAK cells are given back to the patient. IL-2 600,000 International Units/kg IV every 8 hours is given again on days 12—16. Repeat this 16-day cycle in 7 weeks.

For the treatment of acute myelogenous leukemia (AML)†.
NOTE: Aldesleukin has been designated an orphan drug by the FDA for this indication.
For consolidation treatment in patients with AML following chemotherapy or autologous bone marrow transplantation†. Intravenous dosage Adults

At time of review, evidence does not support the use of aldesleukin for this indication. As consolidation therapy, patients who achieved second remission following standard induction chemotherapy or autologous BMT received aldesleukin (IL-2) 9 million International Units/m2/day IV over 1 hour on days 1—5 and days 8—12 every 6 weeks, up to a maximum of 4 cycles. The median duration of disease-free survival was 11 (4—49+) months. In 24% of patients treated with IL-2, the duration of the second remission is greater than that of the first. Another study using different doses of IL-2 has been reported in AML and acute lymphocytic leukemia (ALL) patients following autologous BMT in first remission. In this study, the aldesleukin dosage was given at doses of 12, 16, 20, and 24 million International Units/m2/day as a continuous IV infusion for 5 cycles (cycle 1: 5 days, then cycles 2—5: 2 days starting on days 15, 29, 43, 57). Although aldesleukin therapy increased immune stimulation, it was not associated with increases in disease-free survival in these patients.

Children

At time of review, evidence does not support the use of aldesleukin for this indication. In a phase III clinical trial, 289 patients (ages 1 day – 20 years of age) with AML were randomized to receive a single course of aldesleukin, IL-2 (9 million International Units/m2/day continuous IV infusion on days 0—3 and 1.6 million International Units/m2/day continuous IV infusion on days 8—17) or no additional therapy after treatment that included induction, consolidation, and further chemotherapy intensification. The primary endpoint, disease-free survival, and overall survival were not significantly different between the 2 treatment arms.

For treatment of relapsed or refractory AML†. Intravenous dosage Adults

8 million International Units/m2 IV via bolus infusion was given every 8 hours during cycle 1 (days 1—5) and every 12 hours during cycles 2 (days 15—19) and 3 (days 29—33) in a phase II study of 49 patients with relapsed or refractory acute leukemia (30 AML, 19 ALL). Although immune activation was observed (increased circulating T-cells and NK-cells; increased LAK cytotoxic activity), tumor response was only 7% among patients with AML. Grade 4 neutropenia occurred in 46% of patients and grade 4 thrombocytopenia occurred in 84% of patients during therapy.

For the treatment of cutaneous T-cell lymphoma (CTCL)† including mycosis fungoides† and Sezary Syndrome†. Intravenous dosage Adults

20 million International Units/m2/day continuous IV infusion for 3 courses of 5, 4, and 3 days on weeks 1, 3, and 5, respectively, has been studied. After evaluation, a monthly maintenance treatment of IL-2 20 million International Units/m2/day continuous IV infusion for 5 days was optional. If the patient developed grade III toxicity, the infusion was held until parameters returned to baseline or grade I toxicity, and then treatment was resumed at the same dose. The dose was reduced to 10 million International Units/m2/day in case of subsequent grade III toxicity. Treatment was stopped if the patient developed grade IV toxicity. Of the patients with mycosis fungoides and/or Sezary syndrome, 5/7 patients responded, including one CR, and one patient had stable disease.

Subcutaneous dosage Adults

20 million International Units/m2/day subcutaneously on days 1—5 (week 1), days 1—4 (week 3), and days 1—3 (week 5); after evaluation, maintenance doses of 20 million International Units/m2/day subcutaneously on days 1—5 once monthly were optional. In a phase II clinical trial of 22 patients with relapsed or refractory mycosis fungoides and/or Sezary syndrome, interleukin-2 (IL-2) produced an overall response rate of 18% (all partial responses). The median time to response was 4 months.

For the treatment of leprosy (Hansen's disease)†. Intradermal dosage† Adults

180,000 International Units via intradermal injection into each lesion twice daily for 8 days.

For the treatment of steroid-refractory chronic graft-versus-host disease (GVHD)†. Subcutaneous dosage Adults

1 million international units/m2 subcutaneously daily was the maximum tolerated dose in a phase 1 study. Treatment was given for 8 weeks followed by a 4-week break; responding patients continued therapy for a median duration of 13 months (range, 2 to 36 months).[51014]

†Indicates off-label use

Hepatic Impairment

Hold the next dose for signs of hepatic failure including encephalopathy, increasing ascites, liver pain, hypoglycemia. Resume therapy once all signs of hepatic failure have resolved; however, it is recommended that further treatment for that course be discontinued. Consider starting a new course of treatment at least 7 weeks after cessation of adverse event.

Renal Impairment

Serum creatinine > 4.5 mg/dL: hold dose until SCr < 4 mg/dL and fluid and electrolyte status are stable.Serum creatinine >= 4 mg/dL in the presence of severe volume overload, acidosis, or hyperkalemia: hold dose until SCr < 4 mg/dL and fluid and electrolyte status are stable.
Persistent oliguria with urine output of < 10 mL/hour for 16—24 hours with a rising SCr: hold dose until urine output > 10 mL/hour with a decrease of SCr > 1.5 mg/dL or normalization of SCr.

Acebutolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Acetaminophen; Codeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Acetaminophen; Diphenhydramine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Acetaminophen; Hydrocodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Acetaminophen; Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Acetaminophen; Oxycodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Acyclovir: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as acyclovir, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Albuterol; Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Alfentanil: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Alpha interferons: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
Alprazolam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Altretamine: (Moderate) The safety and efficacy of aldesleukin, IL 2 in combination with any antineoplastic agents have not been established; however, concurrent or sequential use of these agents is common but results in various pharmacodynamic drug interaction risks.
Amikacin: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Aminoglycosides: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Amlodipine; Celecoxib: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Amobarbital: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Angiotensin II receptor antagonists: (Moderate) Angiotensin II receptor antagonists may potentiate the hypotension seen with aldesleukin, IL 2.
Angiotensin-converting enzyme inhibitors: (Moderate) Angiotensin converting enzyme inhibitors, like other antihypertensive agents, may potentiate the hypotension seen with aldesleukin, IL 2.
Antithymocyte Globulin: (Moderate) Because antithymocyte globulin is an immunosuppressant, additive affects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk of infection or other side effects.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Aripiprazole: (Moderate) Because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as aldesleukin, IL-2. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions, particularly CNS effects. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
Artemether; Lumefantrine: (Moderate) Aldesleukin, IL-2 is an inhibitor and artemether is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased artemether concentrations. Concomitant use warrants caution due to the potential for increased side effects. (Moderate) Aldesleukin, IL-2 is an inhibitor and lumefantrine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Aspirin, ASA; Oxycodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Atazanavir: (Moderate) Caution is warranted when atazanavir is administered with aldesleukin, IL-2 as there is a potential for elevated concentrations of atazanavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; atazanavir is a substrate of CYP3A4.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when atazanavir is administered with aldesleukin, IL-2 as there is a potential for elevated concentrations of atazanavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; atazanavir is a substrate of CYP3A4. (Moderate) Caution is warranted when cobicistat is administered with aldesleukin, IL-2 as there is a potential for elevated cobicistat concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4.
Atenolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Atenolol; Chlorthalidone: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with aldesleukin can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use with caution. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider.
Axitinib: (Moderate) Use caution if coadministration of axitinib with aldesleukin, IL-2 is necessary, due to the risk of increased axitinib-related adverse reactions. Axitinib is a CYP3A4 substrate. Aldesleukin increases IL-6 concentrations; IL-6 is a CYP3A4 inhibitor. Aldesleukin has also been shown to weakly inhibit CYP3A4 directly. Coadministration with a strong CYP3A4/5 inhibitor, ketoconazole, significantly increased the plasma exposure of axitinib in healthy volunteers. The manufacturer of axitinib recommends a dose reduction in patients receiving strong CYP3A4 inhibitors, but recommendations are not available for moderate or weak CYP3A4 inhibitors.
Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Belladonna; Opium: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Benzhydrocodone; Acetaminophen: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Benzodiazepines: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Beta-blockers: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Betaxolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Bisoprolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Brimonidine; Timolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and aldesleukin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; aldesleukin inhibits CYP3A4.
Bupivacaine; Meloxicam: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Buspirone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Butabarbital: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Butalbital; Acetaminophen: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Butalbital; Acetaminophen; Caffeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution. (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution. (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering aldesleukin, IL-2 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Aldesleukin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Calcium-channel blockers: (Moderate) Calcium channel blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Carbamazepine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity (e.g., mood stabilizing agents, like carbamazepine). Use with caution. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider. In addition, aldesleukin has significant thrombocytopenic effects and may possess hematologic toxicities similar to carbamazepine. Use together with caution and monitor blood counts as appropriate.
Carteolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Carvedilol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Celecoxib: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Celecoxib; Tramadol: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Central-acting adrenergic agents: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Chlordiazepoxide: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Chlordiazepoxide; Amitriptyline: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Chlordiazepoxide; Clidinium: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Chlorpheniramine; Codeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Chlorpheniramine; Hydrocodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Chlorthalidone; Clonidine: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cidofovir: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as cidofovir, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Clindamycin: (Moderate) Concomitant use of aldesleukin and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Major) Avoid the concomitant use of clofarabine and aldesleukin due to the risk of additive hepatotoxicity. Coadministration may also increase the risk of additive myelosuppression and nephrotoxicity.
Clonazepam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Clonidine: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Clorazepate: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist. In addition, Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity (e.g., antipsychotics). Use with caution. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with aldesleukin, IL-2 as there is a potential for elevated cobicistat concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4.
Cobimetinib: (Major) If concurrent use of cobimetinib and aldesleukin, IL-2 is necessary, use caution and monitor for increased cobimetinib-related adverse effects. Cobimetinib is a CYP3A substrate in vitro, and aldesleukin is a weak inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7). Simulations showed that predicted steady-state concentrations of cobimetinib at a reduced dose of 20 mg administered concurrently with short-term (less than 14 days) treatment of a moderate CYP3A inhibitor were similar to observed steady-state concentrations of cobimetinib 60 mg alone. The manufacturer of cobimetinib recommends avoiding coadministration with moderate to strong CYP3A inhibitors, and significantly reducing the dose of cobimetinib if coadministration with moderate CYP3A inhibitors cannot be avoided. Guidance is not available regarding concomitant use of cobimetinib with weak CYP3A inhibitors.
Codeine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Codeine; Guaifenesin: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Codeine; Phenylephrine; Promethazine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Codeine; Promethazine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cyclosporine: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as cyclosporine, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Darunavir: (Moderate) Caution is warranted when darunavir is administered with aldesleukin, IL-2 as there is a potential for elevated concentrations of darunavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with aldesleukin, IL-2 as there is a potential for elevated cobicistat concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with aldesleukin, IL-2 as there is a potential for elevated concentrations of darunavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with aldesleukin, IL-2 as there is a potential for elevated cobicistat concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with aldesleukin, IL-2 as there is a potential for elevated concentrations of darunavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; darunavir is a substrate of CYP3A4.
Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Dextromethorphan; Quinidine: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with CYP3A4 inhibitors such as aldesleukin, IL-2 may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
Diazepam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Dichlorphenamide: (Moderate) Use dichlorphenamide and aldesleukin, IL-2 together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Diclofenac; Misoprostol: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Diflunisal: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients.
Diphenhydramine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Diphenhydramine; Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Diphenhydramine; Naproxen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Diphenhydramine; Phenylephrine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with aldesleukin can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use with caution. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider.
Dolutegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering aldesleukin, IL-2 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Aldesleukin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Dorzolamide; Timolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Doxazosin: (Moderate) Doxazosin may potentiate the hypotension seen with aldesleukin, IL-2.
Doxylamine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Doxylamine; Pyridoxine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with aldesleukin, IL-2 is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; aldesleukin is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Moderate) Dronedarone is metabolized by CYP3A. Aldesleukin, IL-2 is an inhibitor CYP3A4. Repeated doses of ketoconazole, a strong CYP3A4 inhibitor, increased dronedarone exposure 17-fold and increased dronedarone Cmax 9-fold. Concomitant use of dronedarone with aldesleukin, IL-2 may also increase dronedarone concentrations. No data exist regarding the appropriate dose adjustment needed to allow safe administration of dronedarone with CYP3A4 inhibitors; therefore, use caution when coadministering dronedarone with CYP3A4 inhibitors such as aldesleukin, IL-2.
Droperidol: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with aldesleukin, IL-2 may cause the plasma concentrations of elbasvir and grazoprevir to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Aldesleukin, IL-2 increases IL-6 concentrations; IL-6 is a mild CYP3A inhibitor. Both elbasvir and grazoprevir are metabolized by CYP3A. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eliglustat: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of aldesleukin, IL-2 and eliglustat is not recommended. Aldesleukin, IL-2 is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with aldesleukin, IL-2 as there is a potential for elevated cobicistat concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when elvitegravir is administered with aldesleukin, IL-2 as there is a potential for elevated elvitegravir concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with aldesleukin, IL-2 as there is a potential for elevated cobicistat concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when elvitegravir is administered with aldesleukin, IL-2 as there is a potential for elevated elvitegravir concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering aldesleukin, IL-2 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Aldesleukin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Close clinical monitoring is advised when administering aldesleukin, IL-2 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Aldesleukin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Eplerenone: (Moderate) Eplerenone may potentiate the hypotension seen with aldesleukin, IL 2.
Epoprostenol: (Moderate) Epoprostenol may potentiate the hypotension seen with aldesleukin, IL 2.
Esmolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Estazolam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Eszopiclone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Ethiodized Oil: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Etodolac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Fenoprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Fentanyl: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including aldesleukin, IL-2, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Flurazepam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Flurbiprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Salmeterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Formoterol; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Foscarnet: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as foscarnet, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ganciclovir: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as ganciclovir, with Aldesleukin, IL-2 may increase the risk of kidney dysfunction.
Gentamicin: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Guaifenesin; Hydrocodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Guanfacine: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Haloperidol: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Homatropine; Hydrocodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Hydrocodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Hydrocodone; Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Hydrocodone; Pseudoephedrine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Hydromorphone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Hydroxyzine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Ibuprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ibuprofen; Famotidine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ibuprofen; Oxycodone: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from t

hose drugs. (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Ibuprofen; Pseudoephedrine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Iloprost: (Moderate) Iloprost may potentiate the hypotension seen with aldesleukin, IL 2.
Indinavir: (Moderate) In HIV-positive patients treated with aldesleukin, IL-2, and indinavir, the plasma AUC levels of indinavir increased 88% in 8 of 9 patients. The clearance of indinavir was decreased by 56% by day 5 of concurrent therapy. Treatment with IL-2 increased plasma levels of interleukin-6, which is an inhibitor of cytochrome P450 3A4, by 20-fold in these patients. Increased IL-6 levels may have inhibited CYP3A4, resulting in decreased clearance and increased serum levels of indinavir.
Indomethacin: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Interferon Alfa-2b: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
Interferon Alfa-n3: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
Intranasal Influenza Vaccine: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Iodipamide Meglumine: (Moderate) 'Recall reactions' to aldesleukin, IL-2 therapy and delayed reactions have been reported when ionic contrast media were administered to patients receiving interleukin therapy. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting 4 weeks between aldesleukin, IL-2 treatment and contrast agents.
Iodixanol: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Iohexol: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Iomeprol: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Ionic Contrast Media: (Moderate) 'Recall reactions' to aldesleukin, IL-2 therapy and delayed reactions have been reported when ionic contrast media were administered to patients receiving interleukin therapy. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting 4 weeks between aldesleukin, IL-2 treatment and contrast agents.
Iopamidol: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Iopromide: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Ioversol: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Ioxaglate Meglumine; Ioxaglate Sodium: (Moderate) 'Recall reactions' to aldesleukin, IL-2 therapy and delayed reactions have been reported when ionic contrast media were administered to patients receiving interleukin therapy. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting 4 weeks between aldesleukin, IL-2 treatment and contrast agents.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with aldesleukin, IL-2 may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of CYP3A4; aldesleukin is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH: (Moderate) Aldesleukin, IL-2 is associated with serious adverse reactions affecting many organ systems, including hepatotoxicity. Agents known to cause hepatotoxicity can add to the hepatic impairment produced by aldesleukin. Drugs with known risks of hepatotoxicity include, but are not limited to: isoniazid, INH. In addition, reduced hepatic function secondary to aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Aldesleukin, IL-2 is associated with serious adverse reactions affecting many organ systems, including hepatotoxicity. Agents known to cause hepatotoxicity can add to the hepatic impairment produced by aldesleukin. Drugs with known risks of hepatotoxicity include, but are not limited to: isoniazid, INH. In addition, reduced hepatic function secondary to aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Isoniazid, INH; Rifampin: (Moderate) Aldesleukin, IL-2 is associated with serious adverse reactions affecting many organ systems, including hepatotoxicity. Agents known to cause hepatotoxicity can add to the hepatic impairment produced by aldesleukin. Drugs with known risks of hepatotoxicity include, but are not limited to: isoniazid, INH. In addition, reduced hepatic function secondary to aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Isosulfan Blue: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Ketoprofen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Ketorolac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Labetalol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Lamotrigine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity, such as lamotrigine. Use with caution.
Levobunolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Levorphanol: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and aldesleukin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; aldesleukin inhibits CYP3A4.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and aldesleukin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; aldesleukin inhibits CYP3A4.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and aldesleukin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; aldesleukin inhibits CYP3A4.
Lithium: (Moderate) Aldesleukin may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity, such as lithium. Use with caution.
Live Vaccines: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of aldesleukin, IL-2 with ritonavir may result in increased plasma concentrations of ritonavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; ritonavir is a substrate of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Lorazepam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Loxapine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Lurasidone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity (e.g., antipsychotics). Use with caution. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider. Also, because lurasidone is primarily metabolized by CYP3A4, concurrent use of CYP3A4 inhibitors, such as aldesleukin, IL-2, can theoretically lead to an increased risk of lurasidone-related adverse reactions.
Maraviroc: (Minor) Use caution if coadministration of maraviroc with aldesleukin is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and aldesleukin is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Mecamylamine: (Moderate) Mecamylamine may potentiate the hypotension seen with aldesleukin, IL 2.
Meclofenamate Sodium: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Mefenamic Acid: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Meloxicam: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Meperidine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Meprobamate: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Metformin; Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Aldesleukin, IL-2 is a mild inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Methadone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Methotrexate: (Moderate) The safety and efficacy of aldesleukin, IL-2 in combination with chemotherapy agents have not been established; however, concurrent or sequential use of these agents is common but results in various pharmacodynamic drug interaction risks. Aldesleukin is associated with serious adverse reactions affecting many organ systems. Concurrent administration of antineoplastic agents possessing nephrotoxic, myelotoxic, or hepatotoxic effects (e.g., methotrexate), may increase toxicity in these organ systems.
Methyldopa: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Metoprolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Midazolam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Molindone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Morphine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Morphine; Naltrexone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Nabumetone: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Nadolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Naproxen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Naproxen; Esomeprazole: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Naproxen; Pseudoephedrine: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Nebivolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Nebivolol; Valsartan: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Nefazodone: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing hepatotoxic effects with Aldesleukin, such as nefazodone, may increase the risk of liver dysfunction. In addition, reduced liver function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of aldesleukin, IL-2 with ritonavir may result in increased plasma concentrations of ritonavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; ritonavir is a substrate of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Non-Ionic Contrast Media: (Moderate) Patients have reported 'recall reactions' of aldesleukin therapy and delayed reactions to contrast when used concomitantly with radiopaque contrast agents. The reactions responded to supportive therapy. Such recall reactions were minimized by using nonionic contrast media and waiting four weeks between aldesleukin treatment and radiopaque contrast agents.
Nonsteroidal antiinflammatory drugs: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Olanzapine: (Moderate) Both aldesleukin, IL 2 and olanzapine can cause significant CNS depression. Use with caution and monitor patients for additive CNS depression.
Olanzapine; Fluoxetine: (Moderate) Both aldesleukin, IL 2 and olanzapine can cause significant CNS depression. Use with caution and monitor patients for additive CNS depression.
Olanzapine; Samidorphan: (Moderate) Both aldesleukin, IL 2 and olanzapine can cause significant CNS depression. Use with caution and monitor patients for additive CNS depression.
Oliceridine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Olopatadine; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Opiate Agonists: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Oxaprozin: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Oxazepam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Oxycodone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Oxymorphone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Paromomycin: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Peginterferon Alfa-2a: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
Peginterferon Alfa-2b: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
Pentobarbital: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Phenobarbital: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Phenoxybenzamine: (Moderate) Phenoxybenzamine may potentiate the hypotension seen with aldesleukin, IL-2.
Pimozide: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Pindolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Piroxicam: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Plazomicin: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Potassium-sparing diuretics: (Moderate) Potassium sparing diuretics may potentiate the hypotension seen with aldesleukin, IL 2.
Prazosin: (Moderate) Prazosin may potentiate the hypotension seen with aldesleukin, IL-2.
Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Propranolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Pyrilamine: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Quazepam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Quetiapine: (Moderate) Aldesleukin may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity, such as quetiapine. Use with caution.
Quinidine: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with CYP3A4 inhibitors such as aldesleukin, IL-2 may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
Remifentanil: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Remimazolam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Aldesleukin, IL-2 is a mild inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Rilpivirine: (Moderate) Close clinical monitoring is advised when administering aldesleukin, IL-2 with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Aldesleukin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Risperidone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Ritonavir: (Moderate) Concurrent administration of aldesleukin, IL-2 with ritonavir may result in increased plasma concentrations of ritonavir. Aldesleukin, IL-2 increases IL-6 concentrations, and IL-6 is an inhibitor of the hepatic isoenzyme CYP3A4; ritonavir is a substrate of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Aldesleukin, IL-2 is a mild inhibitor of CYP3A4. Concurrent administration of romidepsin with a mild CYP3A4 inhibitor may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary.
Ropeginterferon alfa-2b: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
Rotavirus Vaccine: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as aldesleukin, IL-2 a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure.
Saquinavir: (Moderate) Both saquinavir boosted with ritonavir and aldesleukin are inhibitors of CYP3A4; an isoenzyme responsible for the metabolism of saquinavir. The use of saquinavir/ritonavir with aldesleukin may result in large increases in saquinavir plasma concentrations, which could cause adverse events such as life threatening cardiac arrhythmias (e.g., torsades de pointes [TdP]).
Secobarbital: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with aldesleukin, IL-2. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Aldesleukin increases IL-6 concentrations, and IL-6 is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with aldesleukin, IL-2. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Aldesleukin increases IL-6 concentrations, and IL-6 is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sotalol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Streptomycin: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Sufentanil: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Sulindac: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Sumatriptan; Naproxen: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Tacrolimus: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as tacrolimus, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Tapentadol: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Temazepam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Terazosin: (Moderate) Terazosin may potentiate the hypotension seen with aldesleukin, IL-2.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering aldesleukin, IL-2. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; aldesleukin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Thiazide diuretics: (Moderate) Thiazide diuretics may potentiate the hypotension seen with aldesleukin, IL 2.
Timolol: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Tobramycin: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Tolmetin: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Trabectedin: (Moderate) Use caution if coadministration of trabectedin and aldesleukin, IL-2 is necessary, due to the risk of increased trabectedin exposure. Trabectedin is a CYP3A substrate; aldesleukin increases IL-6 concentrations, and IL-6 is a CYP3A inhibitor. Coadministration with ketoconazole (200 mg twice daily for 7.5 days), a strong CYP3A inhibitor, increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% and the Cmax by 22% compared to a single dose of trabectedin (1.3 mg/m2) given alone. The manufacturer of trabectedin recommends avoidance of strong CYP3A inhibitors within 1 day before and 1 week after trabectedin administration; there are no recommendations for concomitant use of moderate or weak CYP3A inhibitors.
Tramadol: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Tramadol; Acetaminophen: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. In addition, aldesleukin, IL-2, is a CYP3A4 inhibitor and may increase oxycodone plasma concentrations and related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patients for an extended period and adjust oxycodone dosage as necessary.
Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Triazolam: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Typhoid Vaccine: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and Aldesleukin (IL-2) is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events. When used for emergency contraception, be alert for ulipristal-related side effects. Ulipristal is not recommended to be administered with moderate or potent CYP3A4 inhibitors when given chronically (e.g., daily for female hormonal conditions).
Valacyclovir: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as valacyclovir, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Valdecoxib: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Valproic Acid, Divalproex Sodium: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity, such as valproic acid. Also, aldesleukin, IL-2 may alter hepatic function, and this effect can be additive with other drugs that might cause hepatotoxicity. Use with caution.
Vancomycin: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as vancomycin, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Vasodilators: (Moderate) Vasodilators may potentiate the hypotension seen with aldesleukin, IL 2.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and aldesleukin, IL-2 may result in increased vemurafenib concentrations. Vemurafenib is CYP3A4 substrate and aldesleukin, IL-2 is a CYP3A4 inhibitor. Use caution and monitor patients for increased side effects.
Voclosporin: (Moderate) Concomitant use of voclosporin and aldesleukin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Yellow Fever Vaccine, Live: (Contraindicated) Aldesleukin, IL-2 is associated with impaired neutrophil function. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Zaleplon: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Ziprasidone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Zolpidem: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.

fer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Zaleplon: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
Ziprasidone: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Zolpidem: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.

Aldesleukin/Proleukin Intravenous Inj Pwd F/Sol: 22000000IU

Adults

600,000 International Units/kg IV every 8 hours; 18 million International Units/m2/day has been given off-label for renal cell cancer and metastatic malignant melanoma.

Elderly

600,000 International Units/kg IV every 8 hours; 18 million International Units/m2/day has been given off-label for renal cell cancer and metastatic malignant melanoma.

Adolescents

Safety and efficacy have not been established; up to 9 million International Units/m2/day continuous IV has been given off-label for AML.

Children

Safety and efficacy have not been established; up to 9 million International Units/m2/day continuous IV has been given off-label for AML.

Mechanism of Action: Aldesleukin's effects are essentially identical to those of endogenous interleukin-2. Aldesleukin interacts with the high-affinity IL-2 receptor expressed on cells of the immune system and stimulates a cytokine cascade involving various interferons, interleukins, and tumor necrosis factors. Aldesleukin along with other cytokines induce proliferation and differentiation of B and T-cells, monocytes, macrophages, and cytotoxic lymphocytes which include natural killer (NK) cells, cytotoxic T-cells, tumor-infiltrating lymphocytes (TIL), and lymphokine-activated killer (LAK) cells. Aldesleukin's antitumor activity is believed to result from activation of cytotoxic lymphocytes, however, the exact mechanism is unknown. Whether aldesleukin acts directly or through second messengers is also unclear, however, aldesleukin does elevate production of interleukin-1, tumor necrosis factors alpha and beta, interferon gamma, and interleukin-6.

Aldesleukin is administered parenterally. The pharmacokinetic parameters may be affected by sodium dodecyl sulfate, the solubilizing agent in the commercial formulation. Following distribution, aldesleukin is cleared from the systemic circulation by the kidneys through both glomerular filtration and peritubular extraction. It is then metabolized to amino acids by renal cells lining the proximal convoluted tubules. Very little drug is excreted unchanged in the urine.
 
Affected cytochrome P450 isoenzymes: CYP3A4/5
Aldesleukin, IL-2 is an inhibitor of the cytochrome P450 (CYP) 3A isoenzyme subfamily.

Intravenous Route

Following a short IV infusion, the drug is rapidly distributed to the extravascular and extracellular space as well as to the liver, spleen, kidneys, and lungs. Approximately 30% of an administered dose is distributed within the plasma. Following a 5 minute IV infusion, the serum distribution and elimination half-life in cancer patients was 13 and 85 minutes, respectively.

Subcutaneous Route

Subcutaneous administration with albumin produces slightly higher and more prolonged serum levels of aldesleukin.

Pregnancy

Aldesleukin, IL-2 is classified in FDA pregnancy risk category C; there are no adequate well-controlled studies of aldesleukin in pregnant women. The effects of aldesleukin therapy on fertility or pregnancy have not been studied, and it is unknown whether aldesleukin can affect reproduction capacity or cause fetal harm. Administration of aldesleukin to fertile persons of either gender not practicing effective contraception is not recommended, and aldesleukin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

According to the manufacturer, either aldesleukin, IL-2 or breast-feeding should be discontinued because of the potential for serious adverse reactions in nursing infants from aldesleukin exposure. Aldesleukin excretion into human milk is unknown. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.