Lorlatinib

Lorlatinib Brand Name– Lorbrena

What is Lorlatinib

Lorlatinib is an oral kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) in patients whose disease has progressed on certain ALK kinase inhibitors.

It is also active against ROS1 and a variety of other chromosomal rearrangements, including mutant forms of ALK detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors.

It carries a risk of serious hepatotoxicity when administered with CYP3A inducers, and is contraindicated for use with strong CYP3A inducers. Hyperlipidemia is common while on therapy; a wide variety of central nervous system (CNS) effects have also been reported.

Indications

• non-small cell lung cancer (NSCLC)

For the treatment of metastatic, ALK-positive non-small cell lung cancer (NSCLC) with disease progression on either alectinib or ceritinib as the first ALK inhibitor for metastatic disease, or disease progression on crizotinib and at least one other ALK inhibitor for metastatic disease

NOTE: Lorlatinib has been designated an orphan drug by the FDA for this indication.

Side Effects

1. abnormal dreams
2. acneiform rash
3. agitation
4. amnesia
5. anemia
6. anemia
7. anxiety
8. aphasia
9. arthralgia
10. arthralgia
11. asthenia
12. AV block
13. back pain
14. back pain
15. blurred vision
16. carpal tunnel syndrome
17. confusion
18. constipation
19. cough
20. dementia
21. depression
22. diarrhea
23. diarrhea
24. diplopia
25. dizziness
26. dizziness
27. dysarthria
28. dysesthesia
29. dyspnea
30. dyspnea
31. edema
32. edema
33. elevated hepatic enzymes
34. elevated hepatic enzymes
35. emotional lability
36. euphoria
37. fatigue
38. fatigue
39. fever
40. fever
41. formication
42. hallucinations
43. hallucinations
44. headache
45. headache
46. hepatotoxicity
47. hyperactivity
48. hyperamylasemia
49. hyperamylasemia
50. hypercholesterolemia
51. hypercholesterolemia
52. hyperglycemia
53. hyperglycemia
54. hyperkalemia
55. hyperkalemia
56. hypertension
57. hypertriglyceridemia
58. hypertriglyceridemia
59. hypoalbuminemia
60. hypoalbuminemia
61. hypoesthesia
62. hypomagnesemia
63. hypophosphatemia
64. hypophosphatemia
65. impaired cognition
66. impaired cognition
67. infection
68. insomnia
69. irritability
70. lymphopenia
71. lymphopenia
72. maculopapular rash
73. mania
74. memory impairment
75. musculoskeletal pain
76. myalgia
77. myocardial infarction
78. nausea
79. nausea
80. neurotoxicity
81. nightmares
82. paresthesias
83. peripheral edema
84. peripheral neuropathy
85. peripheral neuropathy
86. photophobia
87. photopsia
88. pneumonitis
89. pneumonitis
90. PR prolongation
91. pulmonary edema
92. rash
93. rash
94. seizures
95. somnambulism
96. suicidal ideation
97. thrombocytopenia
98. thrombocytopenia
99. thromboembolism
100. visual impairment
101. visual impairment
102. vomiting
103. vomiting
104. weakness
105. weight gain
106. weight gain

Monitoring Parameters

• ECG
• pregnancy testing
• serum cholesterol
• serum triglycerides

Contraindications

• breast-feeding
• cardiac arrhythmias
• contraception requirements
• hepatotoxicity
• hypercholesterolemia
• hypertriglyceridemia
• infertility
• male-mediated teratogenicity
• neurological disease
• neurotoxicity
• pneumonitis
• pregnancy
• pregnancy testing
• pulmonary disease
• reproductive risk
• seizures

Interactions

• Abacavir; Dolutegravir; Lamivudine
• Abemaciclib
• Acetaminophen; Butalbital
• Acetaminophen; Butalbital; Caffeine
• Acetaminophen; Butalbital; Caffeine; Codeine
• Acetaminophen; Caffeine; Dihydrocodeine
• Acetaminophen; Codeine
• Acetaminophen; Hydrocodone
• Acetaminophen; Oxycodone
• Acetaminophen; Tramadol
• Afatinib
• Alfentanil
• Aliskiren; Amlodipine
• Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
• Amiodarone
• Amlodipine
• Amlodipine; Atorvastatin
• Amlodipine; Benazepril
• Amlodipine; Celecoxib
• Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
• Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
• Amlodipine; Olmesartan
• Amlodipine; Telmisartan
• Amlodipine; Valsartan
• Amobarbital
• Amoxicillin; Clarithromycin; Lansoprazole
• Amoxicillin; Clarithromycin; Omeprazole
• Apalutamide
• Aspirin, ASA; Butalbital; Caffeine
• Aspirin, ASA; Butalbital; Caffeine; Codeine
• Aspirin, ASA; Caffeine; Dihydrocodeine
• Aspirin, ASA; Carisoprodol; Codeine
• Aspirin, ASA; Oxycodone
• Atazanavir
• Atazanavir; Cobicistat
• Atropine; Hyoscyamine; Phenobarbital; Scopolamine
• Avanafil
• Avapritinib
• Axitinib
• Bedaquiline
• Belladonna Alkaloids; Ergotamine; Phenobarbital
• Benzhydrocodone; Acetaminophen
• Betrixaban
• Bexarotene
• Bosentan
• Brigatinib
• Bromocriptine
• Brompheniramine; Guaifenesin; Hydrocodone
• Brompheniramine; Hydrocodone; Pseudoephedrine
• Bupivacaine; Lidocaine
• Buprenorphine
• Buprenorphine; Naloxone
• Buspirone
• Butabarbital
• Capmatinib
• Carbamazepine
• Carbinoxamine; Hydrocodone; Phenylephrine
• Carbinoxamine; Hydrocodone; Pseudoephedrine
• Cariprazine
• Cenobamate
• Ceritinib
• Chloramphenicol
• Chlorpheniramine; Codeine
• Chlorpheniramine; Dihydrocodeine; Phenylephrine
• Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
• Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
• Chlorpheniramine; Hydrocodone
• Chlorpheniramine; Hydrocodone; Phenylephrine
• Chlorpheniramine; Hydrocodone; Pseudoephedrine
• Clarithromycin
• Clozapine
• Cobicistat
• Cobimetinib
• Codeine
• Codeine; Guaifenesin
• Codeine; Phenylephrine; Promethazine
• Codeine; Promethazine
• Conivaptan
• Conjugated Estrogens
• Conjugated Estrogens; Bazedoxifene
• Conjugated Estrogens; Medroxyprogesterone
• Cyclosporine
• Dabigatran
• Dabrafenib
• Daclatasvir
• Dapsone
• Darifenacin
• Darolutamide
• Darunavir
• Darunavir; Cobicistat
• Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
• Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
• Deflazacort
• Delavirdine
• Dexamethasone
• Diazepam
• Dienogest; Estradiol valerate
• Diethylstilbestrol, DES
• Digoxin
• Dihydrocodeine; Guaifenesin; Pseudoephedrine
• Diltiazem
• Diphenhydramine; Hydrocodone; Phenylephrine
• Dolutegravir
• Dolutegravir; Lamivudine
• Dolutegravir; Rilpivirine
• Doravirine
• Doravirine; Lamivudine; Tenofovir disoproxil fumarate
• Doxorubicin
• Dronabinol
• Drospirenone
• Drospirenone; Estradiol
• Drospirenone; Ethinyl Estradiol
• Drospirenone; Ethinyl Estradiol; Levomefolate
• Edoxaban
• Efavirenz
• Efavirenz; Emtricitabine; Tenofovir
• Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
• Elagolix
• Elagolix; Estradiol; Norethindrone acetate
• Elbasvir; Grazoprevir
• Elvitegravir
• Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
• Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
• Emtricitabine; Rilpivirine; Tenofovir alafenamide
• Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
• Encorafenib
• Entrectinib
• Enzalutamide
• Erdafitinib
• Erlotinib
• Eslicarbazepine
• Esterified Estrogens
• Esterified Estrogens; Methyltestosterone
• Estradiol
• Estradiol Cypionate; Medroxyprogesterone
• Estradiol; Levonorgestrel
• Estradiol; Norethindrone
• Estradiol; Norgestimate
• Estradiol; Progesterone
• Estrogens
• Estropipate
• Ethinyl Estradiol
• Ethinyl Estradiol; Desogestrel
• Ethinyl Estradiol; Ethynodiol Diacetate
• Ethinyl Estradiol; Etonogestrel
• Ethinyl Estradiol; Levonorgestrel
• Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
• Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
• Ethinyl Estradiol; Norelgestromin
• Ethinyl Estradiol; Norethindrone
• Ethinyl Estradiol; Norethindrone Acetate
• Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
• Ethinyl Estradiol; Norethindrone; Ferrous fumarate
• Ethinyl Estradiol; Norgestimate
• Ethinyl Estradiol; Norgestrel
• Etonogestrel
• Etravirine
• Fedratinib
• Fentanyl
• Flibanserin
• Flurazepam
• Fosamprenavir
• Fosphenytoin
• Glasdegib
• Glecaprevir; Pibrentasvir
• grapefruit juice
• Guaifenesin; Hydrocodone
• Guaifenesin; Hydrocodone; Pseudoephedrine
• Guanfacine
• Homatropine; Hydrocodone
• Hydrocodone
• Hydrocodone; Ibuprofen
• Hydrocodone; Phenylephrine
• Hydrocodone; Potassium Guaiacolsulfonate
• Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
• Hydrocodone; Pseudoephedrine
• Hydroxyprogesterone
• Ibuprofen; Oxycodone
• Idelalisib
• Ifosfamide
• Indinavir
• Isoniazid, INH; Pyrazinamide, PZA; Rifampin
• Isoniazid, INH; Rifampin
• Isradipine
• Itraconazole
• Ivabradine
• Ketoconazole
• Ledipasvir; Sofosbuvir
• Lefamulin
• Lemborexant
• Letermovir
• Leuprolide; Norethindrone
• Levonorgestrel
• Lidocaine
• Lidocaine; Prilocaine
• Lopinavir; Ritonavir
• Lumacaftor; Ivacaftor
• Lumacaftor; Ivacaftor
• Lumateperone
• Lurasidone
• Lurbinectedin
• Maraviroc
• Medroxyprogesterone
• Mefloquine
• Mephobarbital
• Mestranol; Norethindrone
• Methadone
• Methohexital
• Midazolam
• Mifepristone
• Mitotane
• Modafinil
• Nafcillin
• Nanoparticle Albumin-Bound Paclitaxel
• Nefazodone
• Nelfinavir
• Neratinib
• Nevirapine
• Nimodipine
• Nisoldipine
• Norethindrone
• Norgestrel
• Olaparib
• Ombitasvir; Paritaprevir; Ritonavir
• Omeprazole; Amoxicillin; Rifabutin
• Oxycodone
• Paclitaxel
• Pemigatinib
• Pentobarbital
• Perampanel
• Perindopril; Amlodipine
• Phenobarbital
• Phenytoin
• Pimavanserin
• Posaconazole
• Praziquantel
• Primidone
• Progesterone
• Progestins
• Ranolazine
• Ribociclib
• Ribociclib; Letrozole
• Rifabutin
• Rifampin
• Rifapentine
• Rifaximin
• Rilpivirine
• Rimegepant
• Risperidone
• Ritonavir
• Saquinavir
• Secobarbital
• Segesterone Acetate; Ethinyl Estradiol
• Selpercatinib
• Selumetinib
• Sildenafil
• Simeprevir
• Siponimod
• Sirolimus
• Sofosbuvir; Velpatasvir
• Sofosbuvir; Velpatasvir; Voxilaprevir
• Solifenacin
• Sonidegib
• St. John’s Wort, Hypericum perforatum
• Sufentanil
• Sunitinib
• Tacrolimus
• Tazemetostat
• Telithromycin
• Thiopental
• Tipranavir
• Tramadol
• Tucatinib
• Ubrogepant
• Ulipristal
• Venetoclax
• Voriconazole
• Voxelotor
• Warfarin
• Zanubrutinib