Interactions between Enzalutamide and Lorbrena
1 drug interaction and 18 additional warnings found for the following 2 drugs:
- enzalutamide
- Lorbrena (lorlatinib)
Drug interactions
Major drug interactions
Major:
enzalutamide lorlatinib
Applies to: enzalutamide and Lorbrena (lorlatinib)
Contraindicated
Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of lorlatinib, which has been found to be metabolized primarily by CYP450 3A4 and UGT1A4 in vitro. In addition to the potential for diminished efficacy of lorlatinib, the risk of serious hepatotoxicity may be increased due to activation of the pregnane X receptor (PXR) by both lorlatinib and CYP450 3A4 inducers. When a single 100 mg oral dose of lorlatinib was administered to 12 healthy volunteers on day 8 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 8 days), mean lorlatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 76% and 85%, respectively. The AUC of the two active metabolites also decreased--one by 92% and the other by 59%. Severe hepatotoxicity was reported in 10 of the 12 subjects, with Grade 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations occurring in 50% of subjects, Grade 3 elevations in 33% of subjects, and Grade 2 elevations in 8% of subjects. ALT or AST elevations occurred within 3 days and returned to within normal limits within 7 to 34 days (median 15 days). The median time to recovery was 18 days in subjects with Grade 3 or 4 elevations and 7 days in subjects with Grade 2 elevations.
Management
Concomitant use of lorlatinib with potent CYP450 3A4 inducers is considered contraindicated. Lorlatinib should not be initiated until after discontinuation of potent CYP450 3A4 inducers for at least 3 plasma half-lives.
References (4)
- (2021) "Product Information. Lorviqua (lorlatinib)." Pfizer Australia Pty Ltd
- (2024) "Product Information. LORBRENA (lorlatinibe)." PFIZER BRASIL LTDA
- (2024) "Product Information. Lorviqua (lorlatinib)." Pfizer Ltd
- (2025) "Product Information. Lorbrena (lorlatinib)." Pfizer U.S. Pharmaceuticals Group
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
lorlatinib Food/Lifestyle
Applies to: Lorbrena (lorlatinib)
Generally avoid
Grapefruit and grapefruit juice may significantly increase the plasma concentrations of lorlatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
Management
Patients treated with lorlatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. If coadministration is unavoidable, some authorities recommend reducing the initial dosage of lorlatinib from 100 mg orally once daily to 75 mg orally once daily. In patients who have had a dosage reduction to 75 mg orally once daily due to adverse reactions, the lorlatinib dosage should be further reduced to 50 mg orally once daily upon initiation of a potent CYP450 3A4 inhibitor. After 3 plasma half-lives following discontinuation of the potent CYP450 3A4 inhibitor, the lorlatinib dosage may be increased to that used prior to initiation of the inhibitor.
References (2)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2018) "Product Information. Lorbrena (lorlatinib)." Pfizer U.S. Pharmaceuticals Group
Disease interactions
17 potential interactions Applies to: 16 conditions, including High Blood Pressure, High Cholesterol, Depression, Seizures, and Psychosis.
Brain Tumor
Moderate:
enzalutamide
Enzalutamide has a moderate potential interaction with Brain Tumor.
Seizures occurred in 0.5% of patients receiving enzalutamide in clinical trials. Patients with predisposing factors for seizures were generally excluded. Caution is advised if using in patients with possible predisposing factors such as history of seizures, history of trauma or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer's disease, meningioma or brain tumor or infection, and any unexplained loss of consciousness in the past 12 months. Enzalutamide should be discontinued permanently in any patient who develops a seizure during treatment.
Central Nervous System Disorders
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Central Nervous System Disorders.
A broad spectrum of central nervous system (CNS) effects can occur in patients receiving lorlatinib. These include seizures, hallucinations, changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Overall, CNS effects occurred in as many as 54% of patients receiving lorlatinib with some requiring treatment discontinuation. Caution and close monitoring of patients with history of seizures or any mental or psychiatric illness is recommended.
CNS Infection
Moderate:
enzalutamide
Enzalutamide has a moderate potential interaction with CNS Infection.
Seizures occurred in 0.5% of patients receiving enzalutamide in clinical trials. Patients with predisposing factors for seizures were generally excluded. Caution is advised if using in patients with possible predisposing factors such as history of seizures, history of trauma or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer's disease, meningioma or brain tumor or infection, and any unexplained loss of consciousness in the past 12 months. Enzalutamide should be discontinued permanently in any patient who develops a seizure during treatment.
Depression
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Depression.
A broad spectrum of central nervous system (CNS) effects can occur in patients receiving lorlatinib. These include seizures, hallucinations, changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Overall, CNS effects occurred in as many as 54% of patients receiving lorlatinib with some requiring treatment discontinuation. Caution and close monitoring of patients with history of seizures or any mental or psychiatric illness is recommended.
Diabetes Mellitus
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Diabetes Mellitus.
The use of lorlatinib might cause hyperglycemia. It is recommended to assess and control fasting serum glucose prior to initiation of treatment and monitor periodically thereafter. Caution should be exercised when treating diabetic patients. Withhold and resume at a reduced dose or permanently discontinue treatment based on severity.
Head Injury
Moderate:
enzalutamide
Enzalutamide has a moderate potential interaction with Head Injury.
Seizures occurred in 0.5% of patients receiving enzalutamide in clinical trials. Patients with predisposing factors for seizures were generally excluded. Caution is advised if using in patients with possible predisposing factors such as history of seizures, history of trauma or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer's disease, meningioma or brain tumor or infection, and any unexplained loss of consciousness in the past 12 months. Enzalutamide should be discontinued permanently in any patient who develops a seizure during treatment.
Heart Block
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Heart Block.
PR interval prolongation and atrioventricular (AV) block can occur in patients receiving lorlatinib, with some reports of Grade 3 AV block that required a pacemaker placement. Patients at risk should have a ECG prior to initiating lorlatinib and should be monitored periodically thereafter. Withhold treatment and resume at a reduced dose or at the same dose in patients who undergo pacemaker placement. Permanently discontinue for recurrence in patients without a pacemaker.
High Blood Pressure
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with High Blood Pressure.
The use of lorlatinib might cause hypertension. It is recommended to assess and control blood pressure prior to treatment initiation. Caution should be exercised when treating patients with prior history of hypertension, uncontrolled hypertension, and those at risk. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment. Withhold and resume lorlatinib at a reduced dose or permanently discontinue treatment based on severity.
High Cholesterol
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with High Cholesterol.
Increases in serum cholesterol and triglycerides have been reported in patients receiving lorlatinib. Grade 3 or 4 elevations in total cholesterol occurred in 17% and Grade 3 or 4 elevations in triglycerides occurred in 17% of the patients enrolled in a clinical trial with up to 80% percent of patients requiring initiation of lipid-lowering medications. Caution is advised in patients with hyperlipidemias. Monitor serum cholesterol and triglycerides before initiating treatment and 1 and 2 months after initiating, and periodically thereafter. Initiation or increase of the dose of lipid-lowering agents might be required on these patients.
History - Cerebrovascular Disease
Moderate:
enzalutamide
Enzalutamide has a moderate potential interaction with History - Cerebrovascular Disease.
Seizures occurred in 0.5% of patients receiving enzalutamide in clinical trials. Patients with predisposing factors for seizures were generally excluded. Caution is advised if using in patients with possible predisposing factors such as history of seizures, history of trauma or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer's disease, meningioma or brain tumor or infection, and any unexplained loss of consciousness in the past 12 months. Enzalutamide should be discontinued permanently in any patient who develops a seizure during treatment.
Interstitial Lung Disease
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Interstitial Lung Disease.
Patients treated with lorlatinib have reported severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis. It is recommended to investigate and monitor patients for pulmonary symptoms indicative of ILD/pneumonitis such as hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Withhold therapy for for suspected ILD/pneumonitis and permanently discontinue therapy for treatment-related ILD/pneumonitis of any severity.
Liver Disease
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Liver Disease.
The recommended dose of lorlatinib has not been established for patients with moderate or severe hepatic impairment, therefore, caution is advised if using in these patients. Additionally, severe hepatotoxicity has been reported in patients with risk factors for hepatotoxicity (e.g., taking hepatotoxic drugs such as strong CYP3A inducers). Caution and close monitoring of hepatic function is advised.
Psychosis
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Psychosis.
A broad spectrum of central nervous system (CNS) effects can occur in patients receiving lorlatinib. These include seizures, hallucinations, changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Overall, CNS effects occurred in as many as 54% of patients receiving lorlatinib with some requiring treatment discontinuation. Caution and close monitoring of patients with history of seizures or any mental or psychiatric illness is recommended.
Renal Dysfunction
Moderate:
enzalutamide
Enzalutamide has a moderate potential interaction with Renal Dysfunction.
Enzalutamide has not been assessed in patients with severe renal impairment or end-stage renal disease. Caution is advised if used on these patients. No initial dosage adjustment is required on patients with mild to moderate renal impairment.
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Renal Dysfunction.
The recommended dose of lorlatinib has not been established for patients with severe renal impairment. No dose adjustment is recommended for patients with mild or moderate renal impairment (creatinine clearance [CrCl] 30 to 89 mL/min estimated by Cockcroft-Gault).
Seizures
Moderate:
enzalutamide
Enzalutamide has a moderate potential interaction with Seizures.
Seizures occurred in 0.5% of patients receiving enzalutamide in clinical trials. Patients with predisposing factors for seizures were generally excluded. Caution is advised if using in patients with possible predisposing factors such as history of seizures, history of trauma or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer's disease, meningioma or brain tumor or infection, and any unexplained loss of consciousness in the past 12 months. Enzalutamide should be discontinued permanently in any patient who develops a seizure during treatment.
Sleep Disorders
Moderate:
Lorbrena
The lorlatinib in Lorbrena has a moderate potential interaction with Sleep Disorders.
A broad spectrum of central nervous system (CNS) effects can occur in patients receiving lorlatinib. These include seizures, hallucinations, changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Overall, CNS effects occurred in as many as 54% of patients receiving lorlatinib with some requiring treatment discontinuation. Caution and close monitoring of patients with history of seizures or any mental or psychiatric illness is recommended.
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enzalutamide
A total of 698 drugs are known to interact with enzalutamide.
- Enzalutamide is in the following drug classes: antiandrogens, hormones/antineoplastics.
- Enzalutamide is used to treat Prostate Cancer.
Lorbrena
A total of 614 drugs are known to interact with Lorbrena.
- Lorbrena is in the drug class multikinase inhibitors.
- Lorbrena is used to treat Non Small Cell Lung Cancer.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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