Lorbrena

Last updated on RxList: 3/17/2021
Lorbrena Side Effects Center

What Is Lorbrena?

Lorbrena (lorlatinib) is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or alectinib as the first ALK inhibitor therapy for metastatic disease; or ceritinib as the first ALK inhibitor therapy for metastatic disease.

What Are Side Effects of Lorbrena?

Common side effects of Lorbrena include:

Dosage for Lorbrena

The recommended dosage of Lorbrena is 100 mg orally once daily.

What Drugs, Substances, or Supplements Interact with Lorbrena?

Lorbrena may interact with rifampin, itraconazole, and strong CYP3A inducers. Tell your doctor all medications and supplements you use.

Lorbrena During Pregnancy and Breastfeeding

Lorbrena is not recommended for use during pregnancy; it may harm a fetus. Females who are able to become pregnant should use non-hormonal birth control during treatment with Lorbrena and for at least 6 months after the final dose. Birth control pills (oral contraceptives) and other hormonal forms of birth control may not be effective if used during treatment with Lorbrena. Because of the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended while using Lorbrena, and for 7 days after the final dose.

Additional Information

Our Lorbrena (lorlatinib) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Lung cancer is a disease in which lung cells grow abnormally in an uncontrolled way. See Answer
Lorbrena Consumer Information

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Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • sudden chest pain, wheezing, dry cough;
  • shortness of breath or rapid breathing;
  • fever, chills, cough with mucus;
  • sudden dizziness (like you might pass out);
  • numbness, tingling, or burning pain in your hands or feet;
  • unusual changes in mood or behavior, thoughts of hurting yourself;
  • hallucinations; or
  • problems with speech, thought, or memory.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • swelling in your arms, hands, legs, or feet;
  • numbness, tingling, or burning pain in your hands or feet;
  • mood changes;
  • feeling tired;
  • weight gain;
  • joint pain; or
  • diarrhea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Lorbrena (Lorlatinib Tablets)

SLIDESHOW

Lung Cancer: Early Signs, Symptoms, Stages See Slideshow
Lorbrena Professional Information

SIDE EFFECTS

The following adverse reactions are described elsewhere in the labeling:

  • Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers [see WARNINGS AND PRECAUTIONS]
  • Central Nervous System Effects [see WARNINGS AND PRECAUTIONS]
  • Hyperlipidemia [see WARNINGS AND PRECAUTIONS]
  • Atrioventricular Block [see WARNINGS AND PRECAUTIONS]
  • Interstitial Lung Disease/Pneumonitis [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]
  • Hyperglycemia [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The pooled safety population described in the Warnings and Precautions section reflects exposure to LORBRENA in 476 patients who received 100 mg LORBRENA once daily in Study B7461001 (N=327) and Study B7461006 (N=149). Among 476 patients who received LORBRENA, 75% were exposed for 6 months or longer and 61% were exposed for greater than 1 year. In this pooled safety population, the most frequent adverse reactions in ≥ 20% of 476 patients who received LORBRENA were edema (56%), peripheral neuropathy (44%), weight gain (31%), cognitive effects (28%), fatigue (27%), dyspnea (27%), arthralgia (24%), diarrhea (23%), mood effects (21%), and cough (21%). The most frequent Grade 3-4 laboratory abnormalities in ≥ 20% of 476 patients who received LORBRENA were hypercholesterolemia (21%) and hypertriglyceridemia (21%).

Previously Untreated ALK-Positive Metastatic NSCLC (CROWN Study)

The safety of LORBRENA was evaluated in 149 patients with ALK-positive NSCLC in a randomized, open-label, active-controlled trial for the treatment of patients with ALK-positive, locally advanced or metastatic, NSCLC who had not received previous systemic treatment for advanced disease [see Clinical Studies]. The median duration of exposure to LORBRENA was 16.7 months (4 days to 34.3 months) and 76% received LORBRENA for at least 12 months.

Serious adverse reactions occurred in 34% of patients treated with LORBRENA; the most frequently reported serious adverse reactions were pneumonia (4.7%), dyspnea (2.7%), respiratory failure (2.7%), cognitive effects (2.0%), and pyrexia (2.0%). Fatal adverse reactions occurred in 3.4% of patients treated with LORBRENA and included pneumonia (0.7%), respiratory failure (0.7%), cardiac failure acute (0.7%), pulmonary embolism (0.7%), and sudden death (0.7%).

Permanent discontinuation of LORBRENA due to adverse reactions occurred in 6.7% of patients. The most frequent adverse reaction that led to permanent discontinuation of LORBRENA was cognitive effects (1.3%). Adverse reactions leading to dose interruptions occurred in 49% of patients treated with LORBRENA. The most frequent adverse reactions that led to dose interruptions of LORBRENA were hypertriglyceridemia (7%), edema (5%), pneumonia (4.7%) cognitive effects (4.0%), mood effects (4.0%), and hypercholesterolemia (3.4%). Adverse reactions leading to dose reductions occurred in 21% of patients treated with LORBRENA. The most frequent adverse reactions that led to dose reductions were edema (5%), hypertriglyceridemia (4.0%), and peripheral neuropathy (3.4%).

Tables 2 and 3 summarize most frequent adverse reactions and laboratory abnormalities, respectively, in patients treated with LORBRENA in Study B7461006.

Table 2 : Adverse Reactions (≥10% for all NCI CTCAE Grades or ≥2% for Grades 3-4) in Patients Treated with LORBRENA in Study B7461006*

Adverse Reaction LORBRENA
N=149
Crizotinib
N=142
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Psychiatric
Mood effectsa 16 2 5 0
Nervous system
Peripheral neuropathyb 34 2 15 0.7
Cognitive effectsc 21 2 6 0
Headache 17 0 18 0.7
Dizziness 11 0 14 0
Sleep effectsd 11 1.3 10 0
Respiratory
Dyspnea 20 2.7 16 2.1
Cough 16 0 18 0
Respiratory failure 2.7 2 0 0
Vascular disorders
Hypertension 18 10 2.1 0
Ocular
Vision disordere 18 0 39 0.7
Gastrointestinal
Diarrhea 21 1.3 52 0.7
Nausea 15 0.7 52 2.1
Constipation 17 0 30 0.7
Vomiting 13 0.7 39 1.4
Musculoskeletal and connective tissue
Arthralgia 19 0.7 11 0
Myalgiaf 15 0.7 7 0
Back pain 15 0.7 11 0
Pain in extremity 17 0 8 0
General
Edemag 56 4 40 1.4
Weight gain 38 17 13 2.1
Fatigueh 19 1.3 32 2.8
Pyrexia 17 1.3 13 1.4
Chest pain 11 1.3 14 0.7
Infections
Upper respiratory tract infectioni 11 0.7 7.7 1.4
Pneumonia 7.4 2 8.5 3.5
Bronchitis 6.7 2 2.1 0
Skin
Rashj 11 0 8.5 0
* Adverse reactions were graded using NCI CTCAE version 4.03.
Abbreviations: NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; SOC=System organ class.
a Mood effects (including affective disorder, affect lability, agitation, anger, anxiety, bipolar I disorder, depressed mood, depression, depressive symptom, euphoric mood, intentional self-injury, irritability, mood altered, mood swings, stress).
b Peripheral neuropathy (including dysesthesia, gait disturbance, hypoesthesia, motor dysfunction, muscular weakness, neuralgia, neuropathy peripheral, paresthesia, peripheral motor neuropathy, peripheral sensory neuropathy).
c Cognitive effects (including events from SOC Nervous system disorders: amnesia, cognitive disorder, disturbance in attention, memory impairment, mental impairment; and also including events from SOC Psychiatric disorders: confusional state, delirium, disorientation).
d Sleep effects (including insomnia, nightmare, sleep disorder, somnambulism).
e Vision disorder (including diplopia, photophobia, photopsia, vision blurred, visual acuity reduced, visual impairment, vitreous floaters).
f Myalgia (including musculoskeletal pain, myalgia). g Edema (including edema, edema peripheral, eyelid edema, face edema, generalized edema, localized edema, periorbital edema, peripheral swelling, swelling).
h Fatigue (including asthenia, fatigue).
i Upper respiratory tract infection (including upper respiratory infection).
j Rash (including dermatitis acneiform, maculopapular rash, rash).

Additional clinically significant adverse reactions occurring at an incidence between 1% and 10% were speech effects (6.7%) and psychotic effects (3.4%).

Table 3 : Laboratory Abnormalities Worsening from Baseline in >20% of Patients in Study B7461006

Laboratory Abnormality LORBRENA
N=149
Crizotinib
N=142
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Chemistry
Hypertriglyceridemiaa,A 95 22 27 0
Hyp erchole sterolemi aa,A 91 19 12 0
Increased creatininea,A 81 0.7 99 2.1
Increased GGTa,A 52 6 41 6
Increased ASTa,A 48 2 75 3.5
Hyperglycemiaa,A 48 7 27 2.1
Increased ALTa,A 44 2.7 75 4.3
Increased CPKa,A 39 2 64 5
Hypoalbuminemiaa,A 36 0.7 61 6
Increased lipasea,A 28 7 34 5
Increased alkaline phosphatasea,A 23 0 50 0.7
HyperkalemiaaA 21 1.3 27 2.1
Increased amylasebA 20 1.4 32 1.4
Hematology
Anemiaa,A 48 2 38 2.8
Activated PTTc,B 25 0 14 0
Lymphopeniaa,A 23 2.7 43 6
Thrombocytopeniaa,A 23 0 7 0.7
* Grades using NCI CTCAE version 4.03. Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; GGT=gamma glutamyl transferase; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; PTT=partial thromboplastin time. N=number of patients who had at least one on-study assessment for the parameter of interest.
a N=149 (LORBRENA).
A N=141 (crizotinib).
b N=148 (LORBRENA).
B N=135 (crizotinib).
cN=138 (LORBRENA)

Previously Treated ALK-Positive Metastatic NSCLC

The data described below reflect exposure to LORBRENA in 295 patients with ALK-positive or ROS1-positive metastatic NSCLC who received LORBRENA 100 mg orally once daily in Study B7461001, a multi-cohort, non-comparative trial [see Clinical Studies]. The median duration of exposure to LORBRENA was 12.5 months (1 day to 35 months) and 52% received LORBRENA for ≥12 months. Patient characteristics were: median age of 53 years (19 to 85 years), age ≥65 years (18%), female (58%), White (49%), Asian (37%), and ECOG performance status 0 or 1 (96%).

The most frequent (≥20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. Of the worsening laboratory values occurring in ≥20% of patients, the most frequent were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.

Serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). Permanent discontinuation of LORBRENA for adverse reactions occurred in 8% of patients.

The most frequent adverse reactions that led to permanent discontinuation were respiratory failure (1.4%), dyspnea (0.7%), myocardial infarction (0.7%), cognitive effects (0.7%) and mood effects (0.7%). Approximately 48% of patients required dose interruption. The most frequent adverse reactions that led to dose interruptions were edema (7%), hypertriglyceridemia (6%), peripheral neuropathy (5%), cognitive effects (4.4%), increased lipase (3.7%), hypercholesterolemia (3.4%), mood effects (3.1%), dyspnea (2.7%), pneumonia (2.7%), and hypertension (2.0%). Approximately 24% of patients required at least 1 dose reduction for adverse reactions. The most frequent adverse reactions that led to dose reductions were edema (6%), peripheral neuropathy (4.7%), cognitive effects (4.1%), and mood effects (3.1%).

Tables 4 and 5 summarize most frequent adverse reactions and laboratory abnormalities, respectively, in patients treated with LORBRENA in Study B7461001.

Table 4 : Adverse Reactions Occurring in ≥10% of Patients in Study B7461001*

Adverse Reaction LORBRENA
(N=295)
All Grades (%) Grade 3 or 4 (%)
Psychiatric
Mood effectsa 23 1.7
Nervous system
Peripheral neuropathyb 47 2.7
Cognitive effectsc 27 2
Headache 18 0.7
Dizziness 16 0.7
Speech effectsd 12 0.3
Sleep effectse 10 0
Respiratory
Dyspnea 27 5
Cough 18 0
Ocular
Vision disorderf 15 0.3
Gastrointestinal
Diarrhea 22 0.7
Nausea 18 0.7
Constipation 15 0
Vomiting 12 1
Musculoskeletal and connective tissue
Arthralgia 23 0.7
Myalgiag 17 0
Back pain 13 0.7
Pain in extremity 13 0.3
General
Edemah 57 3.1
Fatiguei 26 0.3
Weight gain 24 4.4
Pyrexia 12 0.7
Infections
Upper respiratory tract infectionj 12 0
Skin
Rashk 14 0.3
* Adverse reactions were graded using NCI CTCAE version 4.03. Abbreviations: NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; SOC=System organ class.
a Mood effects (including affective disorder, affect lability, aggression, agitation, anxiety, depressed mood, depression, euphoric mood, irritability, mania, mood altered, mood swings, personality change, stress, suicidal ideation).
b Peripheral neuropathy (including burning sensation, carpal tunnel syndrome, dysesthesia, formication, gait disturbance, hypoesthesia, muscular weakness, neuralgia, neuropathy peripheral, neurotoxicity, paresthesia, peripheral sensory neuropathy, sensory disturbance).
c Cognitive effects (including events from SOC Nervous system disorders: amnesia, cognitive disorder, dementia, disturbance in attention, memory impairment, mental impairment; and also including events from SOC Psychiatric disorders: attention deficit/hyperactivity disorder, confusional state, delirium, disorientation, reading disorder).
d Speech effects (including aphasia, dysarthria, slow speech, speech disorder)
e Sleep effects (including abnormal dreams, insomnia, nightmare, sleep disorder, sleep talking, somnambulism)
f Vision disorder (including blindness, diplopia, photophobia, photopsia, vision blurred, visual acuity reduced, visual impairment, vitreous floaters).
g Myalgia (including musculoskeletal pain, myalgia).
h Edema (including edema, edema peripheral, eyelid edema, face edema, generalized edema, localized edema, periorbital edema, peripheral swelling, swelling).
i Fatigue (including asthenia, fatigue).
j Upper respiratory infection (including fungal upper respiratory infection, upper respiratory infection, viral upper respiratory infection).
k Rash (including dermatitis acneiform, maculopapular rash, pruritic rash, rash).

Additional clinically significant adverse reactions occurring at an incidence between 1% and 10% were psychotic effects (7%).

Table 5 : Worsening Laboratory Values Occurring in ≥20% of Patients in Study B7461001*

Laboratory Abnormality LORBRENA
All Grades (%) Grade 3 or 4 (%)
Chemistry
Hypercholesterolemiaa 96 18
Hypertriglyceridemiaa 90 18
Hyperglycemiab 52 5
Increased ASTa 37 2.1
Hypoalbuminemiac 33 1
Increased ALTa 28 2.1
Increased lipased 24 10
Increased alkaline phosphatasea 24 1
Increased amylasee 22 3.9
Hypophosphatemiaa 21 4.8
Hyperkalemiab 21 1
Hypomagnesemiaa 21 0
Hematology
Anemiab 52 4.8
Thrombocytop eniab 23 0.3
Lymphopeniaa 22 3.4
* Grades using NCI CTCAE version 4.03. Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events. N=number of patients who had at least one on-study assessment for the parameter of interest.
a N=292.
b N=293.
cN=291.
d N=290.
e N=284.

DRUG INTERACTIONS

Effect Of Other Drugs On LORBRENA

Strong CYP3A Inducers

Concomitant use of LORBRENA with a strong CYP3A inducer decreased lorlatinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may decrease the efficacy of LORBRENA.

Severe hepatotoxicity occurred in healthy subjects receiving LORBRENA with rifampin, a strong CYP3A inducer. In 12 healthy subjects receiving a single 100 mg dose of LORBRENA with multiple daily doses of rifampin, Grade 3 or 4 increases in ALT or AST occurred in 83% of subjects and Grade 2 increases in ALT or AST occurred in 8%. A possible mechanism for hepatotoxicity is through activation of the pregnane X receptor (PXR) by LORBRENA and rifampin, which are both PXR agonists.

LORBRENA is contraindicated in patients taking strong CYP3A inducers [see CONTRAINDICATION]. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA [see DOSAGE AND ADMINISTRATION].

Moderate CYP3A Inducers

Concomitant use of LORBRENA with a moderate CYP3A inducer decreased lorlatinib plasma concentrations, which may decrease the efficacy of LORBRENA [see CLINICAL PHARMACOLOGY]. Avoid concomitant use of moderate CYP3A inducers with LORBRENA. If concomitant use is unavoidable, increase the LORBRENA dose [see DOSAGE AND ADMINISTRATION].

Strong CYP3A Inhibitors

Concomitant use with a strong CYP3A inhibitor increased lorlatinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may increase the incidence and severity of adverse reactions of LORBRENA. Avoid concomitant use of LORBRENA with a strong CYP3A inhibitor. If concomitant use cannot be avoided, reduce the LORBRENA dosage [see DOSAGE AND ADMINISTRATION].

Fluconazole

Concomitant use of LORBRENA with fluconazole may increase lorlatinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may increase the incidence and severity of adverse reactions of LORBRENA. Avoid concomitant use of LORBRENA with fluconazole. If concomitant use cannot be avoided, reduce the LORBRENA dosage [see DOSAGE AND ADMINISTRATION].

Effect Of LORBRENA On Other Drugs

Certain CYP3A Substrates

LORBRENA is a moderate CYP3A inducer. Concomitant use of LORBRENA decreases the concentration of CYP3A substrates [see CLINICAL PHARMACOLOGY], which may reduce the efficacy of these substrates. Avoid concomitant use of LORBRENA with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.

Certain P-glycoprotein (P-gp) Substrates

LORBRENA is a moderate P-gp inducer. Concomitant use of LORBRENA decreases the concentration of P-gp substrates [see CLINICAL PHARMACOLOGY], which may reduce the efficacy of these substrates. Avoid concomitant use of LORBRENA with certain P-gp substrates for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the P-gp substrate dosage in accordance with approved product labeling.

Read the entire FDA prescribing information for Lorbrena (Lorlatinib Tablets)

© Lorbrena Patient Information is supplied by Cerner Multum, Inc. and Lorbrena Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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