Version May 2024
Nilotinib prolongs the QT interval. Prior to nilotinib administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. Obtain ECGs to monitor the QTc at baseline, 7 days after initiation, and periodically thereafter, and following any dose adjustments. Sudden deaths have been reported in patients receiving nilotinib. Do not administer nilotinib to patients with hypokalemia, hypomagnesemia, or long QT syndrome. Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors. Avoid food 2 hours before and 1 hour after taking a nilotinib dose.
Note: Correct hypokalemia and/or hypomagnesemia prior to nilotinib initiation. Do not administer nilotinib to patients with long QT syndrome. Maintain adequate hydration and treat high uric acid levels prior to nilotinib initiation. If clinically indicated, nilotinib may be administered in combination with hematopoietic growth factors (eg, erythropoietin, filgrastim) and with hydroxyurea or anagrelide.
Acute lymphoblastic leukemia, Philadelphia chromosome-positive (Ph+), newly diagnosed (off-label use): Oral: 400 mg twice daily starting on day 8 of induction chemotherapy (in combination with daunorubicin, vincristine, and prednisolone); continue up to the start of stem cell transplant conditioning or until the end of consolidation therapy. Patients who completed 5 cycles of consolidation treatment received 2 years of nilotinib maintenance. Patients who underwent allogeneic stem cell transplant did not receive nilotinib after transplant (Ref).
Acute lymphoblastic leukemia, Philadelphia chromosome-positive, relapsed/refractory (off-label use): Oral: 400 mg twice daily (Ref).
Chronic myeloid leukemia, Philadelphia chromosome-positive, newly diagnosed in chronic phase: Oral: 300 mg twice daily (Ref).
Discontinuation of therapy (following a sustained molecular response [MR4.5]): May consider nilotinib discontinuation in patients who have been treated with nilotinib for at least 3 years, maintained a molecular response of at least MR4.0 (corresponding to BCR-ABL/ABL ≤0.01% IS) for 1 year (prior to discontinuation), achieved an MR4.5 (corresponding to BCR-ABL/ABL ≤0.0032% IS) for the last assessment taken immediately prior to discontinuation, been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2), no history of accelerated phase or blast crisis, and no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.
Reinitiation of therapy: Patients who lose major molecular response after nilotinib discontinuation must reinitiate treatment within 4 weeks at the dose used prior to discontinuation. Monitor BCR-ABL transcript levels monthly until major molecular response is re-established and every 12 weeks thereafter. BCR-ABL kinase domain mutation testing should be performed if major molecular response is not achieved after 3 months of therapy reinitiation.
Chronic myeloid leukemia, Philadelphia chromosome-positive, resistant or intolerant in accelerated phase: Oral: 400 mg twice daily (Ref).
Chronic myeloid leukemia, Philadelphia chromosome-positive, resistant or intolerant in chronic phase: Oral: 400 mg twice daily (Ref).
Discontinuation of therapy (following a sustained molecular response [MR4.5]): May consider nilotinib discontinuation in patients with chronic myeloid leukemia in chronic phase (resistant or intolerant to prior imatinib therapy) who have been treated with nilotinib for at least 3 years, been treated with imatinib (only) prior to nilotinib treatment, achieved an MR4.5 (corresponding to BCR-ABL/ABL ≤0.0032% IS), achieved a sustained MR4.5 for a minimum of 1 year immediately prior to discontinuation, been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2), no history of accelerated phase or blast crisis, and no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.
Reinitiation of therapy: Patients with confirmed loss of MR4.0 (2 consecutive readings separated by at least 4 weeks showing loss of MR4.0) or loss of major molecular response after nilotinib discontinuation must reinitiate treatment within 4 weeks at the dose used prior to discontinuation. Monitor BCR-ABL transcript levels monthly until previous major molecular response or MR4.0 is re-established and every 12 weeks thereafter. BCR-ABL kinase domain mutation testing should be performed if major molecular response is not achieved after 3 months of therapy reinitiation.
Gastrointestinal stromal tumor, refractory (off-label use): Oral: 400 mg twice daily until disease progression or unacceptable toxicity (Ref).
Missed doses: If a dose is missed, do not make up, resume with next scheduled dose.
Dosage adjustment for total gastrectomy: Consider alternative therapy or a dosage increase (with more frequent monitoring) in patients with total gastrectomy (nilotinib exposure is reduced).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, nilotinib and its metabolites have minimal renal excretion; dosage adjustments for renal dysfunction may not be necessary.
Hepatic impairment at baseline: Note: Consider alternative therapies first if possible; recommendations vary by indication. Monitor the QT interval closely in patients with hepatic impairment.
Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase: Mild, moderate, or severe impairment (Child-Pugh class A, B, or C): Initial: 200 mg twice daily; may increase to 300 mg twice daily based on tolerability
Resistant or intolerant Ph+ CML in chronic or accelerated phase:
Mild to moderate impairment (Child-Pugh class A or B): Initial: 300 mg twice daily; may increase to 400 mg twice daily based on tolerability
Severe impairment (Child-Pugh class C): Initial: 200 mg twice daily; may increase to 300 mg twice daily and then further increase to 400 mg twice daily based on tolerability
Hepatotoxicity occurring during treatment:
Elevated bilirubin ≥ grade 3: Withhold nilotinib, monitor bilirubin. If bilirubin returns to ≤ grade 1, resume nilotinib at 400 mg once daily.
Elevated ALT or AST ≥ grade 3: Withhold nilotinib, monitor transaminases. If ALT or AST returns to ≤ grade 1, resume nilotinib at 400 mg once daily.
|
Adverse event |
Severity |
Dosage modification |
|---|---|---|
|
a CML = chronic myeloid leukemia. | ||
|
Hematologic toxicity (unrelated to underlying leukemia): • Newly diagnosed Ph+ CMLa in chronic phase at 300 mg twice daily. • Resistant or intolerant Ph+ CML in chronic phase or accelerated phase at 400 mg twice daily. |
ANC <1,000/mm3 and/or platelets <50,000/mm3 |
Withhold nilotinib and monitor blood counts. If ANC >1,000/mm3 and platelets >50,000/mm3 within 2 weeks: Resume nilotinib at prior dose. If blood counts remain low for >2 weeks: Reduce nilotinib dose to 400 mg once daily. |
|
QT prolongation |
ECG with QTc prolongation >480 msec |
Withhold nilotinib and monitor and correct potassium and magnesium levels; review concurrent medications. If QTcF returns to <450 msec and to within 20 msec of baseline within 2 weeks: Resume nilotinib at prior dose. If QTcF returns to 450 to 480 msec after 2 weeks: Reduce nilotinib dose to 400 mg once daily. If QTcF returns to >480 msec after dosage reduction to 400 mg once daily: Discontinue nilotinib. Repeat ECG ~7 days after any nilotinib dosage adjustment. |
|
Amylase or lipase elevations |
≥ grade 3 |
Withhold nilotinib; monitor serum amylase or lipase. Resume nilotinib at 400 mg once daily when lipase or amylase returns to ≤ grade 1. |
|
Lipase increases in conjunction with abdominal symptoms |
Any |
Withhold nilotinib and consider diagnostics to exclude pancreatitis. |
|
Bleeding or hemorrhage |
Manage as medically indicated. | |
|
Fluid retention |
Evaluate etiology and treat accordingly. | |
|
Hypertension |
If indicated, initiate appropriate antihypertensive therapy to reduce the risk for cardiovascular complications (ASCO [Armenian 2017], ESC [Lyon 2022]). | |
|
Other clinically significant moderate or severe nonhematologic toxicity (including medically severe fluid retention) |
Withhold nilotinib. Upon resolution of toxicity, resume nilotinib at 400 mg once daily (if previous dose was 300 mg twice daily or 400 mg twice daily, depending on indication). Discontinue if previous dose was 400 mg once daily. May escalate back to initial dose (300 mg twice daily or 400 mg twice daily, depending on indication) if clinically appropriate. | |
|
Acute lymphoblastic leukemia, Ph+, newly diagnosed (off-label use): Nonhematologic toxicity |
≥ grade 3 |
Temporarily reduce nilotinib dose to 400 mg once daily for ≥ grade 3 nonhematologic toxicity (resume when improved to grade 1); severe recurrent adverse events despite dose reduction may require permanent discontinuation (Ref). |
Refer to adult dosing.
(For additional information see "Nilotinib: Pediatric drug information")
Note: Round dose to the nearest 50 mg increment; may combine different capsule strengths to achieve desired dose. Correct hypokalemia and/or hypomagnesemia prior to nilotinib initiation. Do not administer nilotinib to patients with long QT syndrome. Maintain adequate hydration and treat high uric acid levels prior to nilotinib initiation.
Chronic myeloid leukemia (CML), Philadelphia chromosome-positive, newly diagnosed in chronic phase: Children and Adolescents: Oral: 230 mg/m2/dose twice daily; maximum dose: 400 mg/dose. Continue therapy as long as observing clinical benefit or until unacceptable toxicity occurs.
Chronic myeloid leukemia, Philadelphia chromosome-positive, resistant or intolerant in chronic phase and accelerated phase: Children and Adolescents: Oral: 230 mg/m2/dose twice daily; maximum dose: 400 mg/dose. Continue therapy as long as observing clinical benefit or until unacceptable toxicity occurs.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity:
Children and Adolescents: Oral:
|
Adverse event |
Severity |
Dosage modification |
|---|---|---|
|
Hematologic toxicity (unrelated to underlying leukemia): |
ANC <1,000/mm3 and/or platelets <50,000/mm3 |
Withhold nilotinib and monitor blood counts. If ANC >1,500/mm3 and platelets >75,000/mm3 within 2 weeks: Resume nilotinib at prior dose. If blood counts remain low for >2 weeks: Reduce nilotinib dose to 230 mg/m2 once daily or if previous dose was 230 mg/m2 once daily, consider discontinuation of treatment. |
|
Nonhematologic toxicities | ||
|
QT prolongation |
ECG with QTc prolongation >480 msec |
Withhold nilotinib and monitor and correct potassium and magnesium levels; review concurrent medications. If QTcF returns to <450 msec and to within 20 msec of baseline within 2 weeks: Resume nilotinib at prior dose. If QTcF returns to 450 to 480 msec after 2 weeks: Reduce nilotinib dose to 230 mg/m2 once daily. If QTcF returns to >480 msec after dosage reduction to 230 mg/m2 once daily: Discontinue nilotinib. Repeat ECG ~7 days after any nilotinib dosage adjustment. |
|
Amylase or lipase elevations |
≥ Grade 3 |
Withhold nilotinib, monitor serum amylase and lipase until levels return to ≤ grade 1. If prior dose 230 mg/m2 once daily: Discontinue nilotinib. If prior dose 230 mg/m2 twice daily: Once ≤ grade 1, resume nilotinib at 230 mg/m2 once daily. |
|
Lipase increases in conjunction with abdominal symptoms |
Any |
Withhold nilotinib; consider diagnostics to exclude pancreatitis. |
|
Other clinically significant moderate or severe nonhematologic toxicity (including medically severe fluid retention) |
Withhold nilotinib until toxicity resolves. If prior dose is 230 mg/m2 once daily: Discontinue nilotinib. If prior dose 230 mg/m2 twice daily: Resume nilotinib at 230 mg/m2 once daily. May escalate back to 230 mg/m2 twice daily if clinically appropriate. | |
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, nilotinib and its metabolites have minimal renal excretion; dosage adjustments for renal dysfunction may not be necessary.
Children and Adolescents: Oral:
Baseline: A reduced dosage and close monitoring of ECG (for QT prolongation) is recommended; based on experience in adult patients, it is recommended to consider alternative therapies if possible.
Hepatotoxicity occurring during treatment:
If elevated ALT or AST ≥ grade 3: Withhold treatment and monitor transaminases; when ALT or AST elevation returns to ≤ grade 1, resume treatment at 230 mg/m2 once daily (if previous dose was 230 mg/m2 twice daily).
If previous dose was already 230 mg/m2 once daily and recovery to ≤ grade 1 was longer than 28 days, discontinue treatment.
If elevated bilirubin ≥ grade 2: Withhold treatment and monitor bilirubin; when bilirubin elevation returns to ≤ grade 1, resume treatment at 230 mg/m2/dose once daily (if previous dose was 230 mg/m2 twice daily).
If previous dose was already 230 mg/m2 once daily and recovery to ≤ grade 1 was longer than 28 days, discontinue treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise specified.
>10%:
Cardiovascular: Hypertension (10% to 11%), occlusive arterial disease (9% to 15%; including limb stenosis), peripheral edema (9% to 15%), prolonged QT interval on ECG (children and adolescents: >30 msec from baseline: 28%; adults: >60 msec from baseline: 4%; adults: >500 msec: <1%)
Dermatologic: Alopecia (11% to 13%), night sweats (12% to 27%), pruritus (20% to 32%), skin rash (children and adolescents: >20%; adults: 29% to 38%), xeroderma (12%)
Endocrine & metabolic: Hyperglycemia (50%), hypophosphatemia (grade 3/4: 8% to 17%), increased HDL cholesterol (≤28%), increased LDL cholesterol (≤28%), increased VLDL
Gastrointestinal: Abdominal pain (15% to 16%), constipation (19% to 26%), decreased appetite (including anorexia; 15% to 17%), diarrhea (children and adolescents: >20%; adults: 19% to 28%; grades 3/4: 1% to 3%), increased serum lipase (28%), nausea (children and adolescents: >20%; adults: 22% to 37%; grades 3/4: ≤2%), upper abdominal pain (12% to 18%), vomiting (children and adolescents: >20%; adults: 13% to 29%; grades 3/4: <1%)
Hematologic & oncologic: Anemia (8%; grades 3/4: 4% to 27%; decreased hemoglobin: children and adolescents: 38%), decreased absolute lymphocyte count (children and adolescents: 36%), decreased white blood cell count (children and adolescents: 54%), neutropenia (children and adolescents: grades 3/4: >5%; adults: 15%; grades 3/4: 12% to 42%, grade 3: 16%, grade 4: 15% to 26%; decrease in absolute neutrophil count: children and adolescents: 44%), thrombocytopenia (adults: 18%; grades 3/4: 10% to 42%, grade 3: 11% to 12%, grade 4: 18% to 32%; decreased platelet count: children and adolescents: 44%)
Hepatic: Hyperbilirubinemia (children and adolescents: >20%; adults: ≥10%), increased serum alanine aminotransferase (children and adolescents: >20%; adults: 72%), increased serum aspartate aminotransferase (children and adolescents: >20%; adults: 47%)
Infection: Influenza (13%)
Nervous system: Dizziness (12%), fatigue (23% to 32%), headache (children and adolescents: >20%; adults: 20% to 35%), insomnia (7% to 12%)
Neuromuscular & skeletal: Arthralgia (16% to 26%), asthenia (14% to 16%), back pain (15% to 19%), limb pain (children and adolescents: >20%; adults: 15% to 20%), muscle spasm (12% to 15%), musculoskeletal pain (11% to 12%), myalgia (16% to 19%), ostealgia (14% to 15%)
Respiratory: Cough (17% to 27%), dyspnea (9% to 15%), nasopharyngitis (children and adolescents: >20%; adults: 15% to 27%), oropharyngeal pain (7% to 12%), upper respiratory tract infection (children and adolescents: >20%; adults: 10% to 17%)
Miscellaneous: Fever (children and adolescents: >20%; adults: 14% to 28%)
1% to 10%:
Cardiovascular: Angina pectoris, cardiac arrhythmia (including AV block, atrial fibrillation, bradycardia, cardiac flutter, extrasystoles, and tachycardia), cerebral ischemia (1% to 3%), chest discomfort, chest pain, flushing, ischemic heart disease (5% to 9%), palpitations, pericardial effusion (≤2%), peripheral arterial disease (3% to 4%)
Dermatologic: Acne vulgaris, dermatitis (including allergic, exfoliative, and acneiform), eczema, erythema of skin, folliculitis, hyperhidrosis, urticaria
Endocrine & metabolic: Decreased serum albumin (grade 3/4: 3% to 4%), diabetes mellitus, fluid retention (grade 3/4: 3% to 4%), hypercalcemia, hyperkalemia (grade 3/4: 2% to 6%), hyperphosphatemia, hypertriglyceridemia, hypocalcemia (grade 3/4: ≤5%), hypokalemia (grade 3/4: ≤9%), hypomagnesemia, hyponatremia (grade 3/4: 1% to 7%), increased gamma-glutamyl transferase, weight gain, weight loss
Gastrointestinal: Abdominal distension, abdominal distress, dysgeusia, dyspepsia (4% to 10%), flatulence, gastroenteritis (7%), gastrointestinal hemorrhage (3% to 5%), increased serum amylase, pancreatitis
Genitourinary: Pollakiuria
Hematologic & oncologic: Bruise, change in serum protein (decreased globulins), cutaneous papilloma, eosinophilia, febrile neutropenia, hemophthalmos, hemorrhage (grade 3/4: 1% to 2%), leukopenia, lymphocytopenia, pancytopenia
Hepatic: Abnormal liver function, ascites (≤2%), increased serum alkaline phosphatase (grade 3/4: ≤1%)
Nervous system: Anxiety, depression, flank pain, hypoesthesia, malaise, myasthenia, noncardiac chest pain, pain, paresthesia, peripheral neuropathy, vertigo, voice disorder
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, linear skeletal growth rate below expectation (children and adolescents: 5%, including growth retardation and decreased plasma growth hormone level), musculoskeletal chest pain, neck pain
Ophthalmic: Conjunctivitis, eye pruritus, eyelid edema (1%), xerophthalmia
Respiratory: Dyspnea on exertion, epistaxis, pleural effusion (≤2%)
<1%:
Cardiovascular: Acute myocardial infarction, arteriosclerosis, cardiac failure, cerebral infarction, coronary artery disease, coronary artery disease, facial edema, heart murmur, hypertensive crisis, intermittent claudication, ischemic stroke, syncope, transient ischemic attacks
Dermatologic: Ecchymoses, exfoliative dermatitis, skin pain
Endocrine & metabolic: Dehydration, dependent edema, gout, gynecomastia, hyperthyroidism, hypothyroidism, increased lactate dehydrogenase
Gastrointestinal: Dental discomfort (sensitivity), esophageal pain, gastritis, gastroesophageal reflux disease, increased appetite, melena, oral candidiasis, oral mucosa ulcer, stomatitis, xerostomia
Genitourinary: Dysuria, erectile dysfunction, mastalgia, nocturia, urinary tract infection, urinary urgency
Hematologic & oncologic: Hematoma
Hepatic: Hepatotoxicity, jaundice, toxic hepatitis
Hypersensitivity: Fixed drug eruption
Infection: Candidiasis
Nervous system: Chills, disturbance in attention, facial nerve paralysis, hyperesthesia, intracranial hemorrhage, local alterations in temperature sensations, loss of consciousness, migraine
Neuromuscular & skeletal: Joint swelling, muscle rigidity, tremor
Ophthalmic: Blurred vision, conjunctival hemorrhage, conjunctival hyperemia, decreased visual acuity, eye irritation, injected sclera, ocular hyperemia, periorbital edema, photopsia, visual impairment
Renal: Increased blood urea nitrogen, increased serum creatinine (grade 3/4)
Respiratory: Bronchitis, cyanosis, flu-like symptoms, interstitial pulmonary disease, pharyngolaryngeal pain, pleurisy, pleuritic chest pain, pneumonia, pulmonary edema, throat irritation
Frequency not defined:
Cardiovascular: Hypotension, pericarditis, reduced ejection fraction, shock (hemorrhagic), thrombosis, ventricular dysfunction
Dermatologic: Cutaneous nodule (sebaceous hyperplasia), dermal ulcer, epidermal cyst of skin, erythema multiforme, erythema nodosum, exfoliation of skin, furuncle, hyperkeratosis, palmar-plantar erythrodysesthesia, psoriasis, skin atrophy, skin blister, skin discoloration, skin hyperpigmentation, skin hypertrophy, skin photosensitivity, tinea pedis
Endocrine & metabolic: Altered hormone level (insulin C-peptide decreased), heavy menstrual bleeding, hyperparathyroidism (secondary), hyperuricemia, hypoglycemia, thyroiditis
Gastrointestinal: Cholestasis, enterocolitis, gastric ulcer (perforation possible), gingivitis, hematemesis, hemorrhoids, hiatal hernia, intestinal obstruction, oral lesion (papilloma), ulcerative esophagitis
Genitourinary: Breast induration, hematuria, urinary incontinence, urine discoloration
Hematologic & oncologic: Leukocytosis, paraproteinemia, petechia, rectal hemorrhage, retroperitoneal hemorrhage, thrombocythemia
Hepatic: Hepatomegaly
Hypersensitivity: Hypersensitivity reaction
Infection: Anal abscess, reactivation of HBV, sepsis, subcutaneous abscess
Local: Local swelling (nipple), localized edema
Nervous system: Amnesia, brain edema, confusion, disorientation, dysesthesia, dysphoria, lethargy, restless leg syndrome
Neuromuscular & skeletal: Arthritis
Ophthalmic: Allergic conjunctivitis, blepharitis, diplopia, eye pain, optic neuritis, papilledema, photophobia, retinopathy (chorioretinopathy), swelling of eye
Otic: Auditory impairment, otalgia, tinnitus
Renal: Renal failure syndrome
Respiratory: Pulmonary hypertension, wheezing
Miscellaneous: Troponin increased in blood specimen
Postmarketing:
Endocrine & metabolic: Ascorbic acid deficiency (Oak 2016)
Hematologic & oncologic: Thrombotic microangiopathy, tumor lysis syndrome
Hypokalemia, hypomagnesemia, or long QT syndrome.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to nilotinib or any component of the formulation; persistent QTc >480 msec.
Concerns related to adverse effects:
• Bone marrow suppression: Nilotinib may cause myelosuppression, including grades 3 and 4 thrombocytopenia, neutropenia, and anemia; myelosuppression is generally reversible.
• Cardiovascular: Cardiovascular events such as ischemic heart disease-related events, arterial vascular occlusive events, peripheral arterial occlusive disease, and ischemic cerebrovascular accident have been reported. Assess patients for cardiovascular risk factors.
• Electrolyte imbalance: Electrolyte abnormalities may occur during treatment, including hypophosphatemia, hyper-/hypokalemia, hypocalcemia, and hyponatremia.
• Fluid retention: Fluid retention, including pleural and pericardial effusions, ascites, and pulmonary edema, were reported; may be severe. Signs/symptoms of fluid retention include rapid weight gain or swelling; symptoms of respiratory or cardiac distress include shortness of breath.
• Hemorrhage: Serious hemorrhagic events (including fatal events) have occurred in chronic myelogenous leukemia (CML) patients treated with nilotinib. In a clinical study comparing nilotinib and imatinib in the treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase CML, hemorrhagic events (eg, GI hemorrhage, including grade 3 or 4 events) occurred more frequently in the nilotinib arm.
• Hepatotoxicity: Nilotinib may cause hepatotoxicity, including elevations in bilirubin, transaminases, and alkaline phosphatase; grade 3 or 4 bilirubin, AST, and ALT elevations were observed more frequently in pediatric versus adult patients.
• Pancreatitis: Nilotinib may cause increases in serum lipase. Patients with a history of pancreatitis may be at increased risk for lipase increases.
• QT prolongation/sudden death: Nilotinib prolongs the QT interval; sudden deaths have been reported. Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors; also avoid concurrent use with antiarrhythmics; may increase the risk of potentially fatal arrhythmias. The sudden deaths reported appear to be related to dose-dependent ventricular repolarization abnormalities. Prolonged QT interval may result in torsade de pointes, which may cause syncope, seizure, and/or death. Patients with uncontrolled or significant cardiovascular disease were excluded from studies.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been reported in patients with resistant or intolerant CML; the majority of cases had malignant disease progression, high WBC counts, and/or dehydration.
Disease-related concerns:
• Gastrectomy: Consider alternative therapy or a dosage increase (with more frequent monitoring) in patients with total gastrectomy (nilotinib exposure is reduced).
Special populations:
• Pediatrics: Growth retardation has been reported in pediatric patients with Ph+ CML in chronic phase. Monitor bone growth/development in pediatric patients.
• Polymorphisms: UGT1A1 polymorphisms may be a risk factor for increased toxicity (eg, hyperbilirubinemia) (Shibata 2014).
Dosage form specific issues:
• Lactose: Capsules contain lactose; do not use with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption syndromes.
Other warnings/precautions:
• Appropriate administration: Food increased the bioavailability/serum levels, which may then prolong QTc. Nilotinib solubility is decreased at higher pH; concurrent use with proton pump inhibitors is not recommended.
• BCR-ABL transcript monitoring: Monitor BCR-ABL transcript levels in patients eligible for treatment discontinuation using an authorized test validated to measure molecular response levels with a sensitivity of at least MR4.5 (BCR-ABL/ABL ≤0.0032% IS). Information on authorized tests for detection and quantitation of BCR-ABL transcripts is available at http://www.fda.gov/CompanionDiagnostics.
With tyrosine-kinase inhibitor therapy, hyper- and hypothyroidism has been reported; pediatric-specific reports are lacking; however, thyroid function should be monitored in pediatric patients regularly during therapy since it is essential for normal growth and development (Hamnvik 2011; Kim 2010; Samis 2016)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Tasigna: 50 mg, 150 mg, 200 mg
No
Capsules (Tasigna Oral)
50 mg (per): $214.73
150 mg (per each): $214.73
200 mg (per each): $214.73
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as hydrochloride:
Tasigna: 50 mg [DSC], 150 mg, 200 mg
Oral: Administer twice daily with doses ~12 hours apart. Administer on an empty stomach, at least 1 hour before or 2 hours after food. Note: The prescribing information describes when to give food with respect to nilotinib; no food should be consumed for at least 2 hours before or for at least 1 hour after the nilotinib dose.
Capsules should be swallowed whole with water. If unable to swallow whole, may empty contents into 5 mL applesauce (puréed apple) and administer within 15 minutes (do not save for later use).
Oral: Administer twice daily with doses ~12 hours apart. Administer on an empty stomach; no food should be consumed for at least 2 hours before and for at least 1 hour after a dose. Capsules should be swallowed whole with water. If unable to swallow whole, may empty contents into 5 mL applesauce (puréed apple) and administer within 15 minutes (do not save for later use).
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022068s035s036lbl.pdf#page=36, must be dispensed with this medication.
Chronic myelogenous leukemia:
Treatment of newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in chronic phase in pediatric patients ≥1 year of age and adults.
Treatment of chronic- and accelerated-phase Philadelphia chromosome-positive CML in adults resistant or intolerant to prior therapy that included imatinib.
Treatment of chronic- and accelerated-phase Philadelphia chromosome-positive CML in pediatric patients ≥1 year of age with resistance or intolerance to prior tyrosine-kinase inhibitor therapy.
Acute lymphoblastic leukemia, Philadelphia chromosome-positive; Gastrointestinal stromal tumor (refractory)
Nilotinib may be confused with bosutinib, cabozantinib, dasatinib, enasidenib, imatinib, neratinib, nilutamide, nintedanib, niraparib, PONATinib, regorafenib, SUNItinib, tepotinib, vandetanib
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (moderate)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modification
ALfentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfuzosin. Risk C: Monitor therapy
Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic). Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antacids: May decrease the serum concentration of Nilotinib. Management: Separate the administration of nilotinib and any antacid by at least 2 hours whenever possible in order to minimize the risk of a significant interaction. Risk D: Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Risk C: Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Risk X: Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy
Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atogepant. Risk C: Monitor therapy
Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Avacopan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avacopan. Risk C: Monitor therapy
Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider therapy modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Barnidipine. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Benidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benidipine. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Risk X: Avoid combination
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapy
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor therapy
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of BusPIRone. Risk C: Monitor therapy
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider therapy modification
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cariprazine. Risk C: Monitor therapy
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Citalopram: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Citalopram. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider therapy modification
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Codeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Conivaptan. Risk C: Monitor therapy
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Copanlisib. Risk C: Monitor therapy
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Crizotinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Crizotinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Crizotinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Nilotinib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Nilotinib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Nilotinib. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Nilotinib. Management: Avoid if possible. If combination needed, decrease nilotinib to 300 mg once/day for patients with resistant or intolerant Ph+ CML or to 200 mg once/day for patients with newly diagnosed Ph+ CML in chronic phase. Risk D: Consider therapy modification
Dabrafenib: May enhance the QTc-prolonging effect of Nilotinib. Nilotinib may increase serum concentrations of the active metabolite(s) of Dabrafenib. Nilotinib may increase the serum concentration of Dabrafenib. Dabrafenib may decrease the serum concentration of Nilotinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Also monitor for decreased nilotinib efficacy and increased dabrafenib adverse effects. Risk C: Monitor therapy
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modification
Daridorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Darifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Darifenacin. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
DiazePAM: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy
Dienogest: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dienogest. Risk C: Monitor therapy
DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DilTIAZem. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Domperidone: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Domperidone. Risk X: Avoid combination
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DroNABinol. Risk C: Monitor therapy
Ebastine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ebastine. Risk C: Monitor therapy
Elacestrant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elacestrant. Risk X: Avoid combination
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor therapy
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider therapy modification
Encorafenib: May enhance the QTc-prolonging effect of Nilotinib. Nilotinib may increase the serum concentration of Encorafenib. Encorafenib may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Entrectinib. Risk X: Avoid combination
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider therapy modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Erlotinib. Risk C: Monitor therapy
Erythromycin (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Erythromycin (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Escitalopram: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor therapy
Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eszopiclone. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Etravirine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Risk C: Monitor therapy
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fedratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fedratinib. Risk C: Monitor therapy
Felodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Felodipine. Risk C: Monitor therapy
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combination
Fluconazole: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Fluorouracil Products: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Nasal). Risk C: Monitor therapy
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor therapy
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosamprenavir. Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gepirone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider therapy modification
Gilteritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gilteritinib. Risk C: Monitor therapy
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Glasdegib. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Nilotinib. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Histamine H2 Receptor Antagonists: May decrease the serum concentration of Nilotinib. Management: The nilotinib dose should be given 10 hours after or 2 hours before the H2 receptor antagonist in order to minimize the risk of a significant interaction. Risk D: Consider therapy modification
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider therapy modification
Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Infigratinib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Infigratinib. Risk X: Avoid combination
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Nilotinib. Management: Avoid this combination. Histamine H2 receptor antagonists (H2RAs) given 10 hours before or 2 hours after nilotinib, or antacids given 2 hours before or 2 hours after nilotinib are acceptable alternatives. Risk D: Consider therapy modification
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products. Risk C: Monitor therapy
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor therapy
Isradipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Isradipine. Risk C: Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider therapy modification
Ivosidenib: Nilotinib may enhance the QTc-prolonging effect of Ivosidenib. Nilotinib may increase the serum concentration of Ivosidenib. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant. Risk X: Avoid combination
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Leniolisib. Risk C: Monitor therapy
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lercanidipine. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomethadone. Risk C: Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levomilnacipran. Risk C: Monitor therapy
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lomitapide: Nilotinib may increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent nilotinib; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lonafarnib. Risk X: Avoid combination
Lovastatin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modification
Macitentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Macitentan. Risk C: Monitor therapy
Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Risk C: Monitor therapy
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Maraviroc. Risk C: Monitor therapy
Mavacamten: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a moderate CYP3A4 inhibitor. For those stable on mavacamten who are initiating a moderate CYP3A4 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification
Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
Methysergide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Methysergide. Risk X: Avoid combination
Midazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NIFEdipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider therapy modification
Oliceridine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider therapy modification
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Orelabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palbociclib. Risk C: Monitor therapy
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider therapy modification
Panobinostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Panobinostat. Risk C: Monitor therapy
PAZOPanib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of PAZOPanib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced. For the 125 mg capsules: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily. Reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimavanserin. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pirtobrutinib. Risk C: Monitor therapy
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
PONATinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of PONATinib. Risk C: Monitor therapy
Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination
Pralsetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Prazepam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Prazepam. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Praziquantel. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of Nilotinib. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of Nilotinib. Risk X: Avoid combination
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Nilotinib may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Nilotinib. Management: Avoid concomitant use of nilotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, nilotinib dose reductions are required. Monitor patients for nilotinib toxicities including QTc prolongation and arrhythmias. Risk D: Consider therapy modification
QUEtiapine: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QUEtiapine. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine. Management: Monitor for increased quetiapine toxicities including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider therapy modification
Red Yeast Rice: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Red Yeast Rice. Risk C: Monitor therapy
Regorafenib: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Regorafenib. Risk C: Monitor therapy
Repotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Ribociclib: Nilotinib may enhance the QTc-prolonging effect of Ribociclib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Rifabutin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rifabutin. Risk C: Monitor therapy
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider therapy modification
RisperiDONE: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Risk C: Monitor therapy
Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Risk C: Monitor therapy
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Risk C: Monitor therapy
Selumetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification
Sertindole: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Sertindole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Sertindole. Risk X: Avoid combination
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Risk C: Monitor therapy
Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider therapy modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Solifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Solifenacin. Risk C: Monitor therapy
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification
Sparsentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sparsentan. Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUFentanil. Risk C: Monitor therapy
SUNItinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of SUNItinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of SUNItinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Tadalafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tadalafil. Risk C: Monitor therapy
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider therapy modification
Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider therapy modification
Thiotepa: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Thiotepa. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Risk C: Monitor therapy
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Tolterodine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider therapy modification
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Risk C: Monitor therapy
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
TraZODone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of TraZODone. Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Risk C: Monitor therapy
Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Valbenazine. Risk C: Monitor therapy
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vamorolone. Risk C: Monitor therapy
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Verapamil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Verapamil. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy
VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine. Risk C: Monitor therapy
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine (Liposomal). Risk C: Monitor therapy
Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Risk C: Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vinflunine. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vorapaxar. Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Risk C: Monitor therapy
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuranolone. Risk C: Monitor therapy
Grapefruit and grapefruit juice may result in increased concentrations of nilotinib and potentiate QT prolongation. Management: Monitor for increased effects/toxicity with concomitant use.
Verify pregnancy status prior to initiating therapy in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 14 days after the last nilotinib dose.
Changes in menstrual patterns have been reported with tyrosine kinase inhibitor (TKI) therapy (Yu 2019).
Based on the mechanism of action, TKIs have the potential to adversely affect fertility by acting on receptors in the ovaries or testes; primarily when administered prior to puberty in males. Although there are cases showing difficulty conceiving, successful pregnancies have also been reported. Fertility data related to long-term TKI use are limited. Recommendations are available for fertility preservation prior to TKI treatment (ASCO [Oktay 2018]; Madabhavi 2019; Rambhatla 2021).
Patients planning to become pregnant but currently receiving a TKI should minimize the risk of first trimester exposure (Rambhatla 2021). Discontinuing TKI for chronic myelogenous leukemia can be considered if the patient is eligible for a tumor-free remission, allowing a washout period before attempting to conceive (Baccarani 2019; ELN [Hochhaus 2020]; Madabhavi 2019). Because the time to conception can be highly variable, treatment may also be discontinued at the first positive pregnancy test, prior to organogenesis in select patients (Abruzzese 2020).
Outcome data following male use of nilotinib prior to conception are available (Assi 2021; Carlier 2017; Szakács 2020). Based on available data, nilotinib does not need to be stopped prior to conception in patients planning to father a child (Abruzzese 2020; Baccarani 2019; ELN [Hochhaus 2020]).
Nilotinib crosses the placenta (Chelysheva 2018b).
Limited outcome data following use of nilotinib for the treatment of chronic myeloid leukemia (CML) during pregnancy are available (Assi 2021; Barkoulas 2018; Dou 2019; Lasica 2019; Madabhavi 2019). Based on data from animal reproduction studies and the mechanism of action, nilotinib may cause fetal harm if administered during pregnancy.
Treatment of CML in pregnant patients should be individualized based on gestational age, hematologic parameters, and clinical condition at presentation. If pregnancy is detected in the first trimester in patients already receiving a tyrosine kinase inhibitor (TKI), treatment should be discontinued as soon as pregnancy is confirmed. Treatments other than a TKI are recommended in pregnant patients not eligible for a tumor-free remission. If a TKI is needed, nilotinib may be considered after the first trimester; however, second generation TKIs such as nilotinib have less pregnancy outcome information and should be avoided until after delivery when possible. Close maternal and fetal monitoring is recommended (Abruzzese 2020; BSH [Smith 2020]; ELN [Hochhaus 2020]; Madabhavi 2019).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
Nilotinib is present in breast milk (Chelysheva 2018a).
Nilotinib breast milk concentrations were evaluated in a lactating patient diagnosed with chronic myeloid leukemia (CML) prior to pregnancy. Treatment was discontinued after the fourth week of pregnancy and during the postpartum period while breastfeeding. A single dose of nilotinib 400 mg/day was administered at 28 months postpartum. Breast milk was sampled at specified intervals from 1 to 24 hours after the maternal dose. The maximum concentration of nilotinib in breast milk (129 ng/mL) occurred 4 hours after the maternal dose (Chelysheva 2018a).
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 14 days after the last nilotinib dose. Patients diagnosed with CML requiring a tyrosine kinase inhibitor may consider short-term breastfeeding for the first 2 to 5 days postpartum to provide the benefits of colostrum to the newborn prior to starting or restarting therapy (Abruzzese 2020; Madabhavi 2019).
The bioavailability of nilotinib is increased with food.
Philadelphia chromosome status (prior to treatment); CBC with differential (every 2 weeks for first 2 months, then monthly); electrolytes (including potassium, calcium, and magnesium; baseline and periodic); lipid profile and glucose (baseline and periodically during the first year, then at least yearly), hepatic function (ALT/AST, bilirubin, alkaline phosphatase; baseline and monthly or as clinically indicated); serum lipase/amylase (baseline and monthly or as clinically indicated), uric acid (baseline); bone marrow assessments (as indicated). Evaluate pregnancy status prior to initiating therapy in patients who could become pregnant. Monitor ECG and QTc (baseline, 7 days after treatment initiation or dosage adjustments, and periodically thereafter). Assess patients for cardiovascular risk factors prior to treatment initiation. Monitor for signs/symptoms of cardiovascular events, bleeding/hemorrhage, and/or fluid retention (including symptoms of respiratory or cardiac compromise). Monitor bone growth and development in pediatric patients. Monitor adherence.
In patients who discontinue nilotinib after a sustained molecular response (MR4.5), monitor BCR-ABL transcript levels and CBC with differential monthly for 1 year, then every 6 weeks for the second year, and every 12 weeks thereafter. Upon the loss of MR4.0 (corresponding to BCR-ABL/ABL ≤0.01% IS) during the treatment-free phase, monitor BCR-ABL transcript levels every 2 weeks until the BCR-ABL levels remain lower than major molecular response (MMR, corresponding to MR3.0 or BCR-ABL/ABL ≤0.1% IS) for 4 consecutive measurements; patients can then proceed to the original monitoring schedule. In patients who have reinitiated nilotinib after loss of molecular response, monitor CBC and BCR-ABL transcript levels every 4 weeks until a major molecular response (MR4.0) is re-established, and then every 12 weeks thereafter.
Thyroid function testing (Hamnvik 2011):
Preexisting levothyroxine therapy: Obtain baseline thyroid-stimulating hormone (TSH) levels, then monitor every 4 weeks until levels and levothyroxine dose are stable, then monitor every 2 months.
Without preexisting thyroid hormone replacement: TSH at baseline, then monthly for 4 months, then every 2 to 3 months.
Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; repeat assessment every 3 months for the first year and then every 6 to 12 months thereafter (ASCO [Armenian 2017]; ESC [Lyon 2022]). Assess QTc at baseline, then at 2 to 4 weeks, as well as 2 weeks after any dose increase; check ECG at baseline, every 3 months for the first year and every 6 to 12 months thereafter. Consider baseline echocardiography in all patients; repeat every 3 months for high- and very high-risk patients (ESC [Lyon 2022]).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Nilotinib is a selective tyrosine kinase inhibitor that targets BCR-ABL kinase, c-KIT and platelet derived growth factor receptor (PDGFR); it does not have activity against the SRC family. Nilotinib inhibits BCR-ABL mediated proliferation of leukemic cell lines by binding to the ATP-binding site of BCR-ABL and inhibiting tyrosine kinase activity. Nilotinib has activity in imatinib-resistant BCR-ABL kinase mutations.
Protein binding: ~98%
Metabolism: Hepatic; oxidation and hydroxylation, via CYP3A4 to primarily inactive metabolites
Bioavailability: Capsule: ~50% (when compared to oral solution with pH of 1.2 to 1.3); two 200 mg capsules sprinkled on applesauce was determined to be bioequivalent to two 200 mg intact capsules. Bioavailability is increased 82% when administered 30 minutes after a high-fat meal
Half-life elimination: ~17 hours
Time to peak: 3 hours
Excretion: Feces (93%; 69% as parent drug)
Hepatic function impairment: Following a single 200 mg dose, the mean AUC increased 1.4-fold in patients with Child-Pugh classes A and B impairment and 1.6-fold in patients with Child Pugh class C impairment compared to subjects with normal hepatic function.
Total gastrectomy: Median steady-state trough concentrations are decreased by 53% (compared to patients who had not undergone gastric surgeries).
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