Lorlatinib is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK), and C-ros oncogene 1 (Ros1), with potential antineoplastic activity. Upon administration, lorlatinib binds to and inhibits both ALK and ROS1 kinases. The kinase inhibition leads to disruption of ALK- and ROS1-mediated signaling and eventually inhibits tumor cell growth in ALK- and ROS1-overexpressing tumor cells. In addition, PF-06463922 is able to cross the blood-brain barrier. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells.
Lorlatinib is a selective tyrosine kinase receptor inhibitor used in the therapy of selected cases of advanced non-small cell lung cancer. Lorlatinib is associated with transient elevations in serum aminotransferase levels during treatment but has not been linked to instances of clinically apparent acute liver injury that have been described with other similar kinase inhibitors.
Lorlatinib is a cyclic ether that is 16,17-dihydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecin-15(10H)-one substituted by methyl groups at positions 2 and 10R, and by cyano, amino and fluoro groups at positions 3, 7 and 12 respectively. It is a small molecule inhibitor of ALK and ROS1 kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer. It has a role as an antineoplastic agent and an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor. It is a member of pyrazoles, a member of monofluorobenzenes, an aromatic ether, a nitrile, a member of benzamides, an aza macrocycle, an aminopyridine, a cyclic ether, and an organic hetero tetracyclic compound.
Lorlatinib is a third-generation ALK tyrosine kinase inhibitor (TKI) for patients with ALK-positive metastatic non-small cell lung cancer11 which was first approved by the US FDA in November of 2018. It was subsequently approved by the EMA in 2019 for the treatment of select patients with previously treated advanced ALK-positive non-small cell lung cancer, followed by an expanded approval in 2022 to include lorlatinib as a first-line treatment option in advanced ALK-positive NSCLC
Mechanism of Action
Non-small cell lung cancer (NSCLC) accounts for up to 85% of lung cancer cases worldwide and remains a particularly difficult to treat condition. The gene rearrangement of anaplastic lymphoma kinase (ALK) is a genetic alteration that drives the development of NSCLC in a number of patients. Ordinarily, ALK is a natural endogenous tyrosine kinase receptor that plays an important role in the development of the brain and elicits activity on various specific neurons in the nervous system. Subsequnetly, lorlatinib is a kinase inhibitor with in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well. The overall antitumor activity of lorlatinib in in-vivo models appears to be dose-dependent and correlated with the inhibition of ALK phosphorylation. Although many ALK-positive metastatic NSCLC patients respond to initial tyrosine kinase therapies, such patients also often experience tumor progression. Various clinical trials performed with lorlatinib, however, have demonstrated its utility to effect tumor regression in ALK-positive metastatic NSCLC patients who experience tumor progression despite current use or having already used various first and second-generation tyrosine kinase inhibitors like crizotinib, alectinib, or ceritinib.
Based on data from Study B7461001, exposure-response relationships for Grade 3 or 4 hypercholesterolemia and for any Grade 3 or 4 adverse reaction were observed at steady-state exposures achieved at the recommended dosage, with higher probability of the occurrence of adverse reactions with increasing lorlatinib exposure. In 295 patients who received lorlatinib at the recommended dosage of 100 mg once daily and had an ECG measurement in the same Study B7461001, the maximum mean change from baseline for their PR interval was 16.4 ms (2-sided 90% upper confidence interval [CI] 19.4 ms). Among the 284 patients with PR interval <200 ms at baseline, 14% had PR interval prolongation ≥200 ms after starting use with lorlatinib. The prolongation of PR interval occurred in a concentration-dependent manner and atrioventricular block occurred in 1% of patients. Finally, in 275 patients who received lorlatinib at the recommended dosage in the activity-estimating portion of Study B7461001, no large mean increases from baseline in the QTcF interval (i.e., >20 ms) were detected.
Indications
- Lorlatinib is indicated for the treatment of adult patients with ALK-positive metastatic non-small cell lung cancer (NSCLC). In the EU, it is indicated for the treatment of adult patients with ALK-positive advanced NSCLC not previously treated with an ALK inhibitor, or whose disease has progressed after using either [alectinib] or [ceritinib], or [crizotinib] and at least one other ALK inhibitor.
- Lorviqua as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)‑positive advanced non‑small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.
- Lorviqua as monotherapy is indicated for the treatment of adult patients with ALK‑positive advanced NSCLC whose disease has progressed after: alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy; or crizotinib and at least one other ALK TKI.
- Lorlatinib is a selective tyrosine kinase receptor inhibitor used in the therapy of selected cases of advanced non-small cell lung cancer.
- Lorlatinib is approved in the US and in Europe for the second- or third-line treatment of ALK-positive metastatic non-small-cell lung cancer (NSCLC). It is the only ALK inhibitor with meaningful activity against ALK G1202R mutation in lung cancer.
- Advanced Non-Small Cell Lung Cancer (NSCLC)
- Metastatic Non-Small Cell Lung Cancer
Use in Cancer
Lorlatinib is approved to treat adults with:
- Non-small cell lung cancer that is ALK-positive and has metastasized (spread to other parts of the body).
- Lorlatinib is an anaplastic lymphoma kinase inhibitor used to treat anaplastic lymphoma kinase positive metastatic non small cell lung cancer.
Lorlatinib is also being studied in the treatment of other types of cancer.
Contraindications
- Lorlatinib must not be combined with strong inducers (i.e. activators) of the liver enzymes CYP3A4/5 if it can be avoided, as serious cases of liver toxicity have been observed under combination with the CYP3A4/5 inducer rifampicin
- high cholesterol
- high amount of triglyceride in the blood
- suicidal thoughts
- high blood pressure
- atrioventricular block, a type of slow heart rhythm disorder
- a type of infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation of the lung called interstitial pneumonitis
- seizures
- pregnancy
- a patient who is producing milk and breastfeeding
- chronic kidney disease stage 4 (severe)
- chronic kidney disease stage 5 (failure)
Dosage
Strengths: 25 mg; 100 mg
Non-Small Cell Lung Cancer
- 100 mg orally once a day
- Select patients for the treatment of metastatic non-small cell lung cancer (NSCLC) based on the presence of ALK positivity in tumor specimens.
- Therapy should be continued until disease progresses or unacceptable toxicity.
- For the treatment of adult patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test
Renal Dose Adjustments
- Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment is recommended.
- Severe renal dysfunction (CrCl 15 to less than 30 mL/min): 75 mg orally once a day
Liver Dose Adjustments
- Mild liver dysfunction (total jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।" data-rx-term="bilirubin" data-rx-definition="Bilirubin is a yellow pigment that can build up in jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।">bilirubin less than or equal to the upper limit of normal (ULN) with AST greater than ULN or total bilirubin greater than 1 to 1.5 x ULN with any AST): No adjustment recommended.
- Moderate or severe live dysfunction: Data not available
Dose Adjustments
Dose Modifications for Adverse Reactions:
- First dose reduction: 75 orally once a day
- Second dose reduction: 50 mg orally once a day
- Permanently discontinue therapy in patients who are unable to tolerate 50 mg orally once daily.
Central Nervous System Adverse Effects:
- Grade 1: Continue at the same dose or withhold the dose until recovery to baseline; resume at the same dose or at reduced dose.
- Grade 2 or 3: Withhold dose until recovery to Grade 0 or 1; resume at a reduced dose.
- Grade 4: Permanently discontinue therapy.
Hyperlipidemia:
Grade 4 hypercholesterolemia OR Grade 4 hypertriglyceridemia: Withhold until recovery to Grade 2 or less; resume at the same dose. If severe hypercholesterolemia and/or hypertriglyceridemia recurs, resume at a reduced dose.
Atrioventricular (AV) Block:
- Second-degree AV block: Withhold until PR interval is less than 200 ms; resume at a reduced dose.
- The first occurrence of complete AV block: Withhold until pacemaker placed OR PR interval is less than 200 ms; if a pacemaker is placed, resume at same dose; if no pacemaker is placed, resume at a reduced dose.
- Recurrent complete AV block: Place pacemaker or permanently discontinue this drug.
Interstitial Lung Disease (ILD)/Pneumonitis:
- Any Grade treatment-related ILD/pneumonitis: Permanently discontinue this drug.
Hypertension:
- Grade 3 (SBP greater than or equal to 160 mmHg or DBP greater than or equal to 100 mmHg; medical intervention indicated; more than one antihypertensive drug, or more intensive therapy than previously used indicated): Withhold until hypertension has recovered to Grade 1 or less (SBP less than 140 mmHg and DBP less than 90 mmHg), then resume at the same dose.
- If Grade 3 hypertension recurs, withhold until recovery to Grade 1 or less, and resume at a reduced dose. Permanently discontinue, if adequate hypertension control cannot be achieved with optimal medical management.
Grade 4 (life-threatening consequences, urgent intervention indicated): Withhold until recovery to Grade 1 or less, and resume at a reduced dose or permanently discontinue. Permanently discontinue, if Grade 4 hypertension recurs.
Hyperglycemia:
Grade 3 (greater than 250 mg/dL) despite optimal anti-hyperglycemic therapy OR Grade 4: Withhold until hyperglycemia is adequately controlled, then resume at the next lower dosage. If adequate hyperglycemic control cannot be achieved with optimal medical management, permanently discontinue
Other Adverse Reactions:
- Grade 1 or 2: Continue at the same or reduced dose.
- Grade 3 or 4: Withhold until symptoms resolve to Grade 2 or less or baseline; resume at a reduced dose.
Concomitant Use of Strong CYP450 3A Inducers:
- This drug is contraindicated in patients taking strong CYP450 3A inducers. Discontinue strong CYP450 3A inducers for 3 plasma half-lives prior to initiating this drug.
Concomitant Use of Moderate CYP450 3A Inducers:
- Avoid concomitant use of this drug with moderate CYP450 3A inducers.
- If concomitant use with moderate CYP450 3A inducers is unavoidable, increase the dose of this drug to 125 mg once a day.
Dose Modification for Strong CYP450 3A Inhibitors:
- Avoid concomitant use of this drug with strong CYP450 3A inhibitors. If concomitant use with a strong CYP450 3A inhibitor cannot be avoided, reduce the starting dose of this drug from 100 mg once a day to 75 mg orally once a day.
- In patients who have had a reduction to 75 mg orally once a day due to adverse reactions and who initiate a strong CYP450 3A inhibitor, reduce the dose of this drug to 50 mg orally once a day.
- If concomitant use of a strong CYP450 3A inhibitor is discontinued, increase the dose of this drug (after 3 plasma half-lives of the strong CYP450 3A inhibitor) to the dose that was used before starting the strong inhibitor.
Administration advice:
- This drug may be taken with or without food.
- Swallow tablets whole, do not chew, crush or split.
- Do not ingest if tablets are broken, cracked, or otherwise not intact.
- If a dose is missed, take the missed dose unless the next dose is due within 4 hours; do not take 2 doses at the same time to make up for a missed dose.
- Do not take an additional dose if vomiting occurs but continue with the next scheduled dose
Monitoring:
- Monitor blood pressure after 2 weeks and then at least monthly during treatment.
- Monitor serum cholesterol and triglycerides before initiating treatment, after 1 and 2 months during treatment, and periodically thereafter.
- Monitor ECG prior to initiating treatment and periodically thereafter.
- Obtain fasting serum glucose prior to initiating treatment and monitor periodically thereafter.
Patient advice:
- Advise the patient to read the FDA-approved patient labeling (Patient Information).
- Inform patients of the potential risk of hepatotoxicity with the concomitant use of strong CYP450 3A inducers.
- Advise patients to inform their healthcare providers of all medications they are taking, including prescription medicines, over-the-counter drugs, vitamins, and herbal products (e.g., St. John’s wort).
- Advise patients to notify their healthcare provider if they experience new or worsening CNS symptoms.
- Advise patients that initiation or an increase in the dose of lipid-lowering agents may be required, depending on measured readings.
- Advise patients to contact their healthcare provider immediately to report new or worsening cardiac symptoms.
- Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms.
- Advise patients of the risks of hypertension and to promptly report signs or symptoms of hypertension to their healthcare provider and that antihypertension medications may need to be initiated or adjusted during treatment.
- Advise patients with newly occurring hyperglycemia during treatment that antihyperglycemic medications may need to be initiated.
- Inform patients with insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes mellitus or glucose intolerance to monitor glucose levels periodically and that antihyperglycemic medications may need to be adjusted during treatment , depending on reading.
- Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy.
- Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for at least 6 months after the final dose.
- Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose
- Advise women not to breastfeed during treatment and for 7 days after the final dose.
- Advise males of reproductive potential that this drug may transiently impair fertility.
Side Effects
The Most Common
- weight gain
- muscle, joint, or pain: Back pain means pain in the spine, muscles, discs, joints, or nerves of the back. সহজ বাংলা: পিঠ/কোমরের ব্যথা।" data-rx-term="back pain" data-rx-definition="Back pain means pain in the spine, muscles, discs, joints, or nerves of the back. সহজ বাংলা: পিঠ/কোমরের ব্যথা।">back pain
- diarrhea
- constipation
- nausea
- vomiting
- tiredness
- headache
- vision changes
- rash or itching
- swelling in your arms, legs, hands and feet
- difficulty breathing
- shortness of breath, cough, or fever
- numbness and tingling feeling in your joints or arms and legs
- difficulty thinking or confusion
- seizures
- seeing things or hearing voices that do not exist
- changes in mood, feeling sad or anxious
- problems with speech
- difficulty falling asleep or staying asleep
- unusual dreams or nightmares
- headache, dizziness, blurred vision, feeling faint, chest pain, or shortness of breath
- feeling more hungry or thirsty than usual, increased urination, extreme tiredness, weakness, confusion, or breath that smells fruity
More common
- Actions that are out of control
- aggression
- agitation
- anxiety
- black, tarry stools
- bleeding gums
- blood in the urine or stools
- blurred vision or other changes in vision
- body aches or pain
- burning, crawling, itching, numbness, prickling, “pins and needles”, tingling, or painful sensations
- changes in behavior
- chills
- cough
- defects in intelligence, short-term memory, learning ability, and attention
- difficult or labored breathing
- difficulty in breathing
- discouragement
- dizziness
- dry mouth
- ear congestion
- false or unusual sense of well-being
- feeling sad or empty
- fever
- flushed, dry skin
- fruit-like breath odor
- headache
- hoarseness
- increased hunger
- increased thirst
- increased urination
- irritability
- lack of appetite
- loss of interest or pleasure
- loss of voice
- lower back or side pain
- nausea
- nervousness
- painful or difficult urination
- pale skin
- pinpoint red spots on the skin
- pounding in the ears
- runny or stuffy nose
- seeing, hearing, or feeling things that are not there
- skin rash
- slow or fast heartbeat
- sneezing
- sore throat
- stomach pain
- sweating
- swelling
- talking, feeling, and acting with excitement
- thoughts of killing oneself
- tightness in the chest
- trouble concentrating
- trouble sleeping
- trouble breathing
- unexplained weight loss
- unsteadiness or awkwardness
- unusual bleeding or bruising
- unusual tiredness or weakness
- vomiting
- weakness in the arms, hands, legs, or feet
Rare
- Abnormal dreams
- back pain
- constipation
- difficulty in moving
- difficulty in speaking
- drowsiness
- joint pain
- muscle aches, cramps, pains, or stiffness
- pain in the arms or legs
- sleep talking
- swollen joints
Drug Interaction
| DRUG | INTERACTION |
|---|---|
| Abametapir | The serum concentration of Lorlatinib can be increased when it is combined with Abametapir. |
| Abatacept | The metabolism of Lorlatinib can be increased when combined with Abatacept. |
| Abemaciclib | The serum concentration of Abemaciclib can be decreased when it is combined with Lorlatinib. |
| Acalabrutinib | The metabolism of Acalabrutinib can be increased when combined with Lorlatinib. |
| Acenocoumarol | The metabolism of Acenocoumarol can be increased when combined with Lorlatinib. |
| Adalimumab | The metabolism of Lorlatinib can be increased when combined with Adalimumab. |
| Afatinib | The serum concentration of Afatinib can be decreased when it is combined with Lorlatinib. |
| Albendazole | The metabolism of Albendazole can be increased when combined with Lorlatinib. |
| Alectinib | The metabolism of Alectinib can be increased when combined with Lorlatinib. |
| Alfentanil | The metabolism of Lorlatinib can be decreased when combined with Alfentanil. |
| Alpelisib | The metabolism of Alpelisib can be increased when combined with Lorlatinib. |
| Alprazolam | The metabolism of Lorlatinib can be decreased when combined with Alprazolam. |
| Ambrisentan | The metabolism of Lorlatinib can be decreased when combined with Ambrisentan. |
| Aminophylline | The metabolism of Aminophylline can be increased when combined with Lorlatinib. |
| Amiodarone | The metabolism of Lorlatinib can be decreased when combined with Amiodarone. |
| Amitriptyline | The metabolism of Lorlatinib can be decreased when combined with Amitriptyline. |
| Amlodipine | The metabolism of Amlodipine can be increased when combined with Lorlatinib. |
| Amprenavir | The metabolism of Lorlatinib can be decreased when combined with Amprenavir. |
| Anakinra | The metabolism of Lorlatinib can be increased when combined with Anakinra. |
| Apalutamide | The metabolism of Lorlatinib can be increased when combined with Apalutamide. |
| Apixaban | The metabolism of Lorlatinib can be decreased when combined with Apixaban. |
| Apomorphine | The metabolism of Lorlatinib can be decreased when combined with Apomorphine. |
| Apremilast | The metabolism of Lorlatinib can be increased when combined with Apremilast. |
| Aprepitant | The metabolism of Lorlatinib can be decreased when combined with Aprepitant. |
| Aripiprazole | The metabolism of Aripiprazole can be increased when combined with Lorlatinib. |
| Aripiprazole l | The metabolism of Aripiprazole lauroxil can be increased when combined with Lorlatinib. |
| Armodafinil | The metabolism of Lorlatinib can be increased when combined with Armodafinil. |
| Artemether | The metabolism of Lorlatinib can be decreased when combined with Artemether. |
| Articaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Articaine. |
| Astemizole | The metabolism of Astemizole can be increased when combined with Lorlatinib. |
| Asunaprevir | The metabolism of Lorlatinib can be decreased when combined with Asunaprevir. |
| Atazanavir | The metabolism of Lorlatinib can be decreased when combined with Atazanavir. |
| Atorvastatin | The metabolism of Lorlatinib can be decreased when combined with Atorvastatin. |
| Avanafil | The serum concentration of Avanafil can be increased when it is combined with Lorlatinib. |
| Axitinib | The serum concentration of Axitinib can be decreased when it is combined with Lorlatinib. |
| Azelastine | The metabolism of Lorlatinib can be decreased when combined with Azelastine. |
| Azithromycin | The metabolism of Azithromycin can be increased when combined with Lorlatinib. |
| Beclomethasone | The metabolism of Lorlatinib can be increased when combined with Beclomethasone dipropionate. |
| Bendamustine | The serum concentration of Bendamustine can be decreased when it is combined with Lorlatinib. |
| Benzocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Benzocaine. |
| Benzyl alcohol | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Benzyl alcohol. |
| Berotralstat | The serum concentration of Berotralstat can be decreased when it is combined with Lorlatinib. |
| Betamethasone | The metabolism of Lorlatinib can be increased when combined with Betamethasone. |
| Betamethasone | The metabolism of Lorlatinib can be increased when combined with Betamethasone phosphate. |
| Bicalutamide | The metabolism of Bicalutamide can be increased when combined with Lorlatinib. |
| Bimekizumab | The metabolism of Lorlatinib can be increased when combined with Bimekizumab. |
| Binimetinib | The serum concentration of Binimetinib can be decreased when it is combined with Lorlatinib. |
| Boceprevir | The metabolism of Lorlatinib can be decreased when combined with Boceprevir. |
| Bortezomib | The serum concentration of Bortezomib can be decreased when it is combined with Lorlatinib. |
| Bosutinib | The serum concentration of Bosutinib can be decreased when it is combined with Lorlatinib. |
| Brentuximab vedotin | The serum concentration of Brentuximab vedotin can be decreased when it is combined with Lorlatinib. |
| Brigatinib | The metabolism of Brigatinib can be increased when combined with Lorlatinib. |
| Budesonide | The metabolism of Lorlatinib can be increased when combined with Budesonide. |
| Bupivacaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Bupivacaine. |
| Buprenorphine | The metabolism of Lorlatinib can be decreased when combined with Buprenorphine. |
| Buspirone | The metabolism of Lorlatinib can be decreased when combined with Buspirone. |
| Busulfan | The metabolism of Busulfan can be increased when combined with Lorlatinib. |
| Butacaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Butacaine. |
| Butamben | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Butamben. |
| Cabazitaxel | The serum concentration of Cabazitaxel can be decreased when it is combined with Lorlatinib. |
| Cabergoline | The serum concentration of Cabergoline can be decreased when it is combined with Lorlatinib. |
| Canakinumab | The metabolism of Lorlatinib can be increased when combined with Canakinumab. |
| Cannabidiol | The metabolism of Lorlatinib can be decreased when combined with Cannabidiol. |
| Capmatinib | The serum concentration of Capmatinib can be decreased when it is combined with Lorlatinib. |
| Capsaicin | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Capsaicin. |
| Carbamazepine | The metabolism of Carbamazepine can be increased when combined with Lorlatinib. |
| Carfilzomib | The serum concentration of Carfilzomib can be decreased when it is combined with Lorlatinib. |
| Cenobamate | The serum concentration of Lorlatinib can be decreased when it is combined with Cenobamate. |
| Cephalexin | The metabolism of Cephalexin can be increased when combined with Lorlatinib. |
| Ceritinib | The serum concentration of Ceritinib can be decreased when it is combined with Lorlatinib. |
| Cerivastatin | The metabolism of Lorlatinib can be decreased when combined with Cerivastatin. |
| Certolizumab pegol | The metabolism of Lorlatinib can be increased when combined with Certolizumab pegol. |
| Chloramphenicol | The metabolism of Lorlatinib can be decreased when combined with Chloramphenicol. |
| Chloroprocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Chloroprocaine. |
| Chloroquine | The metabolism of Lorlatinib can be decreased when combined with Chloroquine. |
| Chlorpheniramine | The metabolism of Lorlatinib can be decreased when combined with Chlorpheniramine. |
| Chlorpromazine | The metabolism of Chlorpromazine can be increased when combined with Lorlatinib. |
| Cilostazol | The metabolism of Lorlatinib can be decreased when combined with Cilostazol. |
| Cimetidine | The metabolism of Lorlatinib can be decreased when combined with Cimetidine. |
| Cinchocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Cinchocaine. |
| Ciprofloxacin | The metabolism of Lorlatinib can be decreased when combined with Ciprofloxacin. |
| Cisapride | The metabolism of Cisapride can be increased when combined with Lorlatinib. |
| Clarithromycin | The metabolism of Lorlatinib can be decreased when combined with Clarithromycin. |
| Clindamycin | The metabolism of Clindamycin can be increased when combined with Lorlatinib. |
| Clobetasol propi | The metabolism of Lorlatinib can be increased when combined with Clobetasol propionate. |
| Clofazimine | The metabolism of Lorlatinib can be decreased when combined with Clofazimine. |
| Clomipramine | The metabolism of Clomipramine can be increased when combined with Lorlatinib. |
| Clonazepam | The metabolism of Clonazepam can be increased when combined with Lorlatinib. |
| Clonidine | The metabolism of Clonidine can be increased when combined with Lorlatinib. |
| Clopidogrel | The metabolism of Lorlatinib can be decreased when combined with Clopidogrel. |
| Clozapine | The serum concentration of Clozapine can be decreased when it is combined with Lorlatinib. |
| Cobicistat | The metabolism of Lorlatinib can be decreased when combined with Cobicistat. |
| Cobimetinib | The serum concentration of Cobimetinib can be decreased when it is combined with Lorlatinib. |
| Cocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Cocaine. |
| Conivaptan | The metabolism of Lorlatinib can be decreased when combined with Conivaptan. |
| Copanlisib | The serum concentration of Copanlisib can be decreased when it is combined with Lorlatinib. |
| Cortisone acetate | The metabolism of Lorlatinib can be increased when combined with Cortisone acetate. |
| Crizotinib | The serum concentration of Crizotinib can be decreased when it is combined with Lorlatinib. |
| Curcumin | The metabolism of Lorlatinib can be decreased when combined with Curcumin. |
| Cyclophosphamide | The metabolism of Cyclophosphamide can be increased when combined with Lorlatinib. |
| Cyclosporine | The serum concentration of Cyclosporine can be decreased when it is combined with Lorlatinib. |
| Cyproterone acet | The metabolism of Cyproterone acetate can be increased when combined with Lorlatinib. |
| Dabigatran ete | The serum concentration of Dabigatran etexilate can be decreased when it is combined with Lorlatinib. |
| Dabrafenib | The serum concentration of Lorlatinib can be decreased when it is combined with Dabrafenib. |
| Daclatasvir | The metabolism of Lorlatinib can be decreased when combined with Daclatasvir. |
| Dacomitinib | The serum concentration of Dacomitinib can be decreased when it is combined with Lorlatinib. |
| Dactinomycin | The serum concentration of Dactinomycin can be decreased when it is combined with Lorlatinib. |
| Danazol | The metabolism of Lorlatinib can be decreased when combined with Danazol. |
| Dapsone | The metabolism of Lorlatinib can be decreased when combined with Dapsone. |
| Darbepoetin alfa | The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Lorlatinib. |
| Darunavir | The metabolism of Lorlatinib can be decreased when combined with Darunavir. |
| Dasatinib | The serum concentration of Dasatinib can be decreased when it is combined with Lorlatinib. |
| Daunorubicin | The metabolism of Lorlatinib can be increased when combined with Daunorubicin. |
| Deferasirox | The metabolism of Lorlatinib can be decreased when combined with Deferasirox. |
| Delavirdine | The metabolism of Lorlatinib can be decreased when combined with Delavirdine. |
| Desogestrel | The metabolism of Desogestrel can be increased when combined with Lorlatinib. |
| Desvenlafaxine | The metabolism of Lorlatinib can be decreased when combined with Desvenlafaxine. |
| Deutetrabenazine | The metabolism of Deutetrabenazine can be decreased when combined with Lorlatinib. |
| Dexamethasone | The metabolism of Lorlatinib can be increased when combined with Dexamethasone. |
| Dexamethasone | The metabolism of Lorlatinib can be increased when combined with Dexamethasone acetate. |
| Dextromethorphan | The metabolism of Lorlatinib can be decreased when combined with Dextromethorphan. |
| Diazepam | The metabolism of Lorlatinib can be decreased when combined with Diazepam. |
| Dienogest | The metabolism of Dienogest can be increased when combined with Lorlatinib. |
| Diethylstilbestrol | The metabolism of Diethylstilbestrol can be increased when combined with Lorlatinib. |
| Difluocortolone | The metabolism of Lorlatinib can be increased when combined with Difluocortolone. |
| Digitoxin | The serum concentration of Digitoxin can be decreased when it is combined with Lorlatinib. |
| Digoxin | Lorlatinib may increase the excretion rate of Digoxin which could result in a lower serum level and potentially a reduction in efficacy. |
| Dihydroergocornine | The metabolism of Dihydroergocornine can be increased when combined with Lorlatinib. |
| Dihydroergocristine | The metabolism of Dihydroergocristine can be increased when combined with Lorlatinib. |
| Dihydroergotamine | The metabolism of Dihydroergotamine can be increased when combined with Lorlatinib. |
| Diltiazem | The metabolism of Lorlatinib can be decreased when combined with Diltiazem. |
| Diphenhydramine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Diphenhydramine. |
| Disulfiram | The metabolism of Lorlatinib can be decreased when combined with Disulfiram. |
| Docetaxel | The metabolism of Docetaxel can be increased when combined with Lorlatinib. |
| Dofetilide | The metabolism of Dofetilide can be increased when combined with Lorlatinib. |
| Domperidone | The metabolism of Lorlatinib can be decreased when combined with Domperidone. |
| Doravirine | The metabolism of Doravirine can be decreased when combined with Lorlatinib. |
| Doxazosin | The metabolism of Doxazosin can be increased when combined with Lorlatinib. |
| Doxorubicin | The serum concentration of Doxorubicin can be decreased when it is combined with Lorlatinib. |
| Dronedarone | The metabolism of Dronedarone can be increased when combined with Lorlatinib. |
| Drospirenone | The metabolism of Drospirenone can be increased when combined with Lorlatinib. |
| Dutasteride | The metabolism of Lorlatinib can be decreased when combined with Dutasteride. |
| Duvelisib | The metabolism of Duvelisib can be increased when combined with Lorlatinib. |
| Dyclonine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Dyclonine. |
| Ebastine | The metabolism of Ebastine can be increased when combined with Lorlatinib. |
| Efavirenz | The metabolism of Lorlatinib can be decreased when combined with Efavirenz. |
| Elbasvir | The metabolism of Lorlatinib can be decreased when combined with Elbasvir. |
| Elexacaftor | The metabolism of Elexacaftor can be increased when combined with Lorlatinib. |
| Eltrombopag | The metabolism of Lorlatinib can be decreased when combined with Eltrombopag. |
| Elvitegravir | The metabolism of Lorlatinib can be decreased when combined with Elvitegravir. |
| Emapalumab | The metabolism of Lorlatinib can be increased when combined with Emapalumab. |
| Enasidenib | The metabolism of Enasidenib can be increased when combined with Lorlatinib. |
| Entrectinib | The metabolism of Entrectinib can be increased when combined with Lorlatinib. |
| Enzalutamide | The serum concentration of Lorlatinib can be decreased when it is combined with Enzalutamide. |
| Eplerenone | The metabolism of Lorlatinib can be decreased when combined with Eplerenone. |
| Erdafitinib | The metabolism of Erdafitinib can be increased when combined with Lorlatinib. |
| Ergotamine | The metabolism of Lorlatinib can be decreased when combined with Ergotamine. |
| Erlotinib | The serum concentration of Erlotinib can be decreased when it is combined with Lorlatinib. |
| Erythromycin | The metabolism of Lorlatinib can be decreased when combined with Erythromycin. |
| Erythropoietin | The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Lorlatinib. |
| Estetrol | The metabolism of Estetrol can be increased when combined with Lorlatinib. |
| Estradiol | The metabolism of Estradiol can be increased when combined with Lorlatinib. |
| Estradiol acetate | The metabolism of Estradiol acetate can be decreased when combined with Lorlatinib. |
| Estradiol benzoate | The metabolism of Estradiol benzoate can be increased when combined with Lorlatinib. |
| Estradiol cypionate | The metabolism of Estradiol cypionate can be increased when combined with Lorlatinib. |
| Estradiol dienant | The metabolism of Estradiol dienanthate can be decreased when combined with Lorlatinib. |
| Estradiol valerate | The metabolism of Estradiol valerate can be increased when combined with Lorlatinib. |
| Estrone sulfate | The metabolism of Estrone sulfate can be increased when combined with Lorlatinib. |
| Eszopiclone | The serum concentration of Eszopiclone can be decreased when it is combined with Lorlatinib. |
| Etanercept | The metabolism of Lorlatinib can be increased when combined with Etanercept. |
| Ethinylestradiol | The metabolism of Ethinylestradiol can be increased when combined with Lorlatinib. |
| Ethyl chloride | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Ethyl chloride. |
| Ethynodiol diac | The metabolism of Ethynodiol diacetate can be increased when combined with Lorlatinib. |
| Etidocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Etidocaine. |
| Etonogestrel | The metabolism of Etonogestrel can be increased when combined with Lorlatinib. |
| Etoposide | The serum concentration of Etoposide can be decreased when it is combined with Lorlatinib. |
| Everolimus | The serum concentration of Everolimus can be decreased when it is combined with Lorlatinib. |
| Felodipine | The metabolism of Lorlatinib can be decreased when combined with Felodipine. |
| Fenofibrate | The metabolism of Fenofibrate can be increased when combined with Lorlatinib. |
| Fexinidazole | The metabolism of Fexinidazole can be decreased when combined with Lorlatinib. |
| Finasteride | The metabolism of Lorlatinib can be decreased when combined with Finasteride. |
| Fluconazole | The metabolism of Lorlatinib can be decreased when combined with Fluconazole. |
| Flunitrazepam | The metabolism of Lorlatinib can be decreased when combined with Flunitrazepam. |
| Fluocinonide | The metabolism of Lorlatinib can be increased when combined with Fluocinonide. |
| Fluocortolone | The metabolism of Lorlatinib can be increased when combined with Fluocortolone. |
| Flutamide | The metabolism of Lorlatinib can be decreased when combined with Flutamide. |
| Fluticasone | The metabolism of Lorlatinib can be decreased when combined with Fluticasone. |
| Fluticasone fu | The metabolism of Lorlatinib can be decreased when combined with Fluticasone furoate. |
| Fluticasone prop | The metabolism of Lorlatinib can be decreased when combined with Fluticasone propionate. |
| Fluvastatin | The metabolism of Lorlatinib can be decreased when combined with Fluvastatin. |
| Fluvoxamine | The metabolism of Lorlatinib can be decreased when combined with Fluvoxamine. |
| Fosaprepitant | The metabolism of Fosaprepitant can be increased when combined with Lorlatinib. |
| Fosnetupitant | The metabolism of Lorlatinib can be decreased when combined with Fosnetupitant. |
| Fosphenytoin | The metabolism of Fosphenytoin can be increased when combined with Lorlatinib. |
| Fusidic acid | The metabolism of Lorlatinib can be decreased when combined with Fusidic acid. |
| Futibatinib | The serum concentration of Futibatinib can be decreased when it is combined with Lorlatinib. |
| Gefitinib | The metabolism of Lorlatinib can be decreased when combined with Gefitinib. |
| Gemcitabine | The serum concentration of Gemcitabine can be decreased when it is combined with Lorlatinib. |
| Gemfibrozil | The metabolism of Lorlatinib can be decreased when combined with Gemfibrozil. |
| Gestrinone | The metabolism of Gestrinone can be increased when combined with Lorlatinib. |
| Gilteritinib | The metabolism of Gilteritinib can be increased when combined with Lorlatinib. |
| Glyburide | The metabolism of Lorlatinib can be decreased when combined with Glyburide. |
| Golimumab | The metabolism of Lorlatinib can be increased when combined with Golimumab. |
| Halofantrine | The metabolism of Lorlatinib can be decreased when combined with Halofantrine. |
| Haloperidol | The serum concentration of Haloperidol can be increased when it is combined with Lorlatinib. |
| Hydrocortisone | The metabolism of Lorlatinib can be decreased when combined with Hydrocortisone. |
| Hydrocortisone a | The metabolism of Hydrocortisone acetate can be decreased when combined with Lorlatinib. |
| Hydrocortisone bu | The metabolism of Hydrocortisone butyrate can be decreased when combined with Lorlatinib. |
| Hydrocortisone c | The metabolism of Hydrocortisone cypionate can be decreased when combined with Lorlatinib. |
| Hydrocortisone ph | The metabolism of Hydrocortisone phosphate can be decreased when combined with Lorlatinib. |
| Hydroxyprogeste | The metabolism of Hydroxyprogesterone caproate can be increased when combined with Lorlatinib. |
| Hydroxyzine | The metabolism of Lorlatinib can be decreased when combined with Hydroxyzine. |
| Ibrutinib | The metabolism of Lorlatinib can be decreased when combined with Ibrutinib. |
| Idelalisib | The metabolism of Idelalisib can be increased when combined with Lorlatinib. |
| Ifosfamide | The metabolism of Ifosfamide can be increased when combined with Lorlatinib. |
| Iloperidone | The metabolism of Lorlatinib can be decreased when combined with Iloperidone. |
| Imatinib | The metabolism of Lorlatinib can be decreased when combined with Imatinib. |
| Imipramine | The serum concentration of Imipramine can be decreased when it is combined with Lorlatinib. |
| Indinavir | The metabolism of Lorlatinib can be decreased when combined with Indinavir. |
| Infigratinib | The metabolism of Infigratinib can be increased when combined with Lorlatinib. |
| Infliximab | The metabolism of Lorlatinib can be increased when combined with Infliximab. |
| Inotuzumab | The serum concentration of Inotuzumab ozogamicin can be decreased when it is combined with Lorlatinib. |
| Irinotecan | The metabolism of Irinotecan can be increased when combined with Lorlatinib. |
| Isavuconazole | The metabolism of Lorlatinib can be decreased when combined with Isavuconazole. |
| Isavuconazonium | The metabolism of Lorlatinib can be decreased when combined with Isavuconazonium. |
| Isoniazid | The metabolism of Lorlatinib can be decreased when combined with Isoniazid. |
| Isradipine | The metabolism of Lorlatinib can be decreased when combined with Isradipine. |
| Istradefylline | The metabolism of Lorlatinib can be decreased when combined with Istradefylline. |
| Itraconazole | The metabolism of Lorlatinib can be decreased when combined with Itraconazole. |
| Ivacaftor | The metabolism of Lorlatinib can be decreased when combined with Ivacaftor. |
| Ivosidenib | The metabolism of Lorlatinib can be increased when combined with Ivosidenib. |
| Ixabepilone | The metabolism of Ixabepilone can be increased when combined with Lorlatinib. |
| Ixazomib | The metabolism of Ixazomib can be increased when combined with Lorlatinib. |
| Ketoconazole | The metabolism of Lorlatinib can be decreased when combined with Ketoconazole. |
| Lacosamide | The metabolism of Lacosamide can be increased when combined with Lorlatinib. |
| Lapatinib | The metabolism of Lorlatinib can be decreased when combined with Lapatinib. |
| Ledipasvir | The serum concentration of Ledipasvir can be decreased when it is combined with Lorlatinib. |
| Lefamulin | Lorlatinib may increase the excretion rate of Lefamulin which could result in a lower serum level and potentially a reduction in efficacy. |
| Lemborexant | The serum concentration of Lemborexant can be decreased when it is combined with Lorlatinib. |
| Lercanidipine | The metabolism of Lorlatinib can be decreased when combined with Lercanidipine. |
| Letermovir | The metabolism of Lorlatinib can be decreased when combined with Letermovir. |
| Levacetylmet | The metabolism of Levacetylmethadol can be increased when combined with Lorlatinib. |
| Levamlodipine | The metabolism of Lorlatinib can be decreased when combined with Levamlodipine. |
| Levobupivacaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Levobupivacaine. |
| Levoketoconazole | The metabolism of Lorlatinib can be decreased when combined with Levoketoconazole. |
| Levomilnacipran | The metabolism of Levomilnacipran can be increased when combined with Lorlatinib. |
| Levonorgestrel | The metabolism of Levonorgestrel can be increased when combined with Lorlatinib. |
| Lidocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Lidocaine. |
| Linagliptin | The serum concentration of Linagliptin can be decreased when it is combined with Lorlatinib. |
| Lomitapide | The metabolism of Lomitapide can be increased when combined with Lorlatinib. |
| Lonafarnib | The metabolism of Lorlatinib can be decreased when combined with Lonafarnib. |
| Lopinavir | The metabolism of Lorlatinib can be decreased when combined with Lopinavir. |
| Lovastatin | The metabolism of Lorlatinib can be decreased when combined with Lovastatin. |
| Lumacaftor | The metabolism of Lorlatinib can be increased when combined with Lumacaftor. |
| Lumateperone | The serum concentration of Lumateperone can be decreased when it is combined with Lorlatinib. |
| Lynestrenol | The metabolism of Lynestrenol can be increased when combined with Lorlatinib. |
| Mavacamten | The serum concentration of Lorlatinib can be decreased when it is combined with Mavacamten. |
| Medroxyprog | The metabolism of Medroxyprogesterone acetate can be increased when combined with Lorlatinib. |
| Megestrol ac | The metabolism of Megestrol acetate can be increased when combined with Lorlatinib. |
| Meloxicam | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Meloxicam. |
| Meperidine | The metabolism of Meperidine can be increased when combined with Lorlatinib. |
| Mepivacaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Mepivacaine. |
| Meprednisone | The metabolism of Lorlatinib can be increased when combined with Meprednisone. |
| Mestranol | The metabolism of Mestranol can be increased when combined with Lorlatinib. |
| Methimazole | The metabolism of Lorlatinib can be decreased when combined with Methimazole. |
| Methotrexate | The metabolism of Methotrexate can be increased when combined with Lorlatinib. |
| Methoxy po | The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Lorlatinib. |
| Methylene blue | The metabolism of Lorlatinib can be decreased when combined with Methylene blue. |
| Methylprednisone | The metabolism of Methylprednisone can be increased when combined with Lorlatinib. |
| Methysergide | The metabolism of Methysergide can be increased when combined with Lorlatinib. |
| Metreleptin | The metabolism of Lorlatinib can be increased when combined with Metreleptin. |
| Metronidazole | The metabolism of Lorlatinib can be decreased when combined with Metronidazole. |
| Miconazole | The metabolism of Lorlatinib can be decreased when combined with Miconazole. |
| Midazolam | The metabolism of Lorlatinib can be decreased when combined with Midazolam. |
| Midostaurin | The metabolism of Lorlatinib can be decreased when combined with Midostaurin. |
| Mifepristone | The metabolism of Mifepristone can be increased when combined with Lorlatinib. |
| Milnacipran | The metabolism of Milnacipran can be increased when combined with Lorlatinib. |
| Mitotane | The metabolism of Lorlatinib can be increased when combined with Mitotane. |
| Mobocertinib | The metabolism of Mobocertinib can be decreased when combined with Lorlatinib. |
| Modafinil | The metabolism of Lorlatinib can be increased when combined with Modafinil. |
| Mometasone fu | The metabolism of Lorlatinib can be increased when combined with Mometasone furoate. |
| Mycophenolate | The metabolism of Lorlatinib can be decreased when combined with Mycophenolate mofetil. |
| Nateglinide | The metabolism of Lorlatinib can be decreased when combined with Nateglinide. |
| Nefazodone | The metabolism of Lorlatinib can be decreased when combined with Nefazodone. |
| Nelfinavir | The metabolism of Lorlatinib can be decreased when combined with Nelfinavir. |
| Neratinib | The metabolism of Neratinib can be increased when combined with Lorlatinib. |
| Netupitant | The metabolism of Lorlatinib can be decreased when combined with Netupitant. |
| Nevirapine | The metabolism of Lorlatinib can be decreased when combined with Nevirapine. |
| Nicardipine | The metabolism of Lorlatinib can be decreased when combined with Nicardipine. |
| Nifedipine | The metabolism of Lorlatinib can be decreased when combined with Nifedipine. |
| Nilotinib | The metabolism of Lorlatinib can be decreased when combined with Nilotinib. |
| Nilvadipine | The metabolism of Lorlatinib can be decreased when combined with Nilvadipine. |
| Nintedanib | The metabolism of Nintedanib can be increased when combined with Lorlatinib. |
| Nisoldipine | The metabolism of Lorlatinib can be decreased when combined with Nisoldipine. |
| Nitrendipine | The metabolism of Lorlatinib can be decreased when combined with Nitrendipine. |
| Nomegestrol | The metabolism of Nomegestrol can be increased when combined with Lorlatinib. |
| Nomegestrol acetate | The metabolism of Nomegestrol acetate can be increased when combined with Lorlatinib. |
| Norelgestromin | The metabolism of Norelgestromin can be increased when combined with Lorlatinib. |
| Norethisterone | The metabolism of Norethisterone can be increased when combined with Lorlatinib. |
| Norethynodrel | The metabolism of Norethynodrel can be increased when combined with Lorlatinib. |
| Norgestimate | The metabolism of Norgestimate can be increased when combined with Lorlatinib. |
| Norgestrel | The metabolism of Norgestrel can be increased when combined with Lorlatinib. |
| Nortriptyline | The serum concentration of Nortriptyline can be decreased when it is combined with Lorlatinib. |
| Olaparib | The metabolism of Olaparib can be increased when combined with Lorlatinib. |
| Oliceridine | The serum concentration of Oliceridine can be decreased when it is combined with Lorlatinib. |
| Ondansetron | The metabolism of Lorlatinib can be decreased when combined with Ondansetron. |
| Osilodrostat | The metabolism of Lorlatinib can be decreased when combined with Osilodrostat. |
| Osimertinib | The serum concentration of Osimertinib can be decreased when it is combined with Lorlatinib. |
| Oxcarbazepine | The metabolism of Lorlatinib can be increased when combined with Oxcarbazepine. |
| Oxetacaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Oxetacaine. |
| Oxybuprocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Oxybuprocaine. |
| Oxybutynin | The metabolism of Lorlatinib can be decreased when combined with Oxybutynin. |
| Oxycodone | The metabolism of Lorlatinib can be decreased when combined with Oxycodone. |
| Paclitaxel | The metabolism of Paclitaxel can be increased when combined with Lorlatinib. |
| Palbociclib | The metabolism of Palbociclib can be increased when combined with Lorlatinib. |
| Paliperidone | The serum concentration of Paliperidone can be decreased when it is combined with Lorlatinib. |
| Panobinostat | The serum concentration of Panobinostat can be decreased when it is combined with Lorlatinib. |
| Paritaprevir | The metabolism of Lorlatinib can be decreased when combined with Paritaprevir. |
| Pazopanib | The serum concentration of Pazopanib can be decreased when it is combined with Lorlatinib. |
| Peginesatide | The risk or severity of Thrombosis can be increased when Peginesatide is combined with Lorlatinib. |
| Pentamidine | The metabolism of Lorlatinib can be decreased when combined with Pentamidine. |
| Pentobarbital | The metabolism of Lorlatinib can be increased when combined with Pentobarbital. |
| Perampanel | The metabolism of Perampanel can be increased when combined with Lorlatinib. |
| Pexidartinib | The metabolism of Pexidartinib can be increased when combined with Lorlatinib. |
| Phenobarbital | The metabolism of Lorlatinib can be increased when combined with Phenobarbital. |
| Phenol | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Phenol. |
| Phenprocoumon | The metabolism of Phenprocoumon can be increased when combined with Lorlatinib. |
| Phenytoin | The metabolism of Lorlatinib can be increased when combined with Phenytoin. |
| Pimavanserin | The metabolism of Pimavanserin can be increased when combined with Lorlatinib. |
| Pimozide | The metabolism of Pimozide can be increased when combined with Lorlatinib. |
| Pitolisant | The serum concentration of Lorlatinib can be decreased when it is combined with Pitolisant. |
| Pomalidomide | The serum concentration of Pomalidomide can be decreased when it is combined with Lorlatinib. |
| Ponatinib | The metabolism of Ponatinib can be increased when combined with Lorlatinib. |
| Ponesimod | The metabolism of Lorlatinib can be decreased when combined with Ponesimod. |
| Posaconazole | The metabolism of Lorlatinib can be decreased when combined with Posaconazole. |
| Pralsetinib | The metabolism of Lorlatinib can be decreased when combined with Pralsetinib. |
| Pramocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Pramocaine. |
| Praziquantel | The metabolism of Lorlatinib can be decreased when combined with Praziquantel. |
| Prednisolone p | The metabolism of Lorlatinib can be increased when combined with Prednisolone phosphate. |
| Prednisone aceta | The metabolism of Lorlatinib can be increased when combined with Prednisone acetate. |
| Pretomanid | The metabolism of Pretomanid can be increased when combined with Lorlatinib. |
| Prilocaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Prilocaine. |
| Primaquine | The metabolism of Lorlatinib can be decreased when combined with Primaquine. |
| Primidone | The metabolism of Lorlatinib can be increased when combined with Primidone. |
| Procaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Procaine. |
| Progesterone | The metabolism of Progesterone can be increased when combined with Lorlatinib. |
| Proparacaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Proparacaine. |
| Propoxycaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Propoxycaine. |
| Propranolol | The metabolism of Lorlatinib can be decreased when combined with Propranolol. |
| Quetiapine | The metabolism of Lorlatinib can be decreased when combined with Quetiapine. |
| Quinidine | The serum concentration of Quinidine can be decreased when it is combined with Lorlatinib. |
| Quinine | The metabolism of Lorlatinib can be decreased when combined with Quinine. |
| Ranolazine | The metabolism of Ranolazine can be increased when combined with Lorlatinib. |
| Regorafenib | The serum concentration of Regorafenib can be decreased when it is combined with Lorlatinib. |
| Relugolix | The serum concentration of Relugolix can be decreased when it is combined with Lorlatinib. |
| Reserpine | The metabolism of Lorlatinib can be increased when combined with Reserpine. |
| Retapamulin | The metabolism of Retapamulin can be increased when combined with Lorlatinib. |
| Ribociclib | The metabolism of Lorlatinib can be decreased when combined with Ribociclib. |
| Rifampicin | The metabolism of Lorlatinib can be increased when combined with Rifampicin. |
| Rifamycin | The metabolism of Lorlatinib can be increased when combined with Rifamycin. |
| Rifapentine | The metabolism of Lorlatinib can be increased when combined with Rifapentine. |
| Rilonacept | The metabolism of Lorlatinib can be increased when combined with Rilonacept. |
| Rilpivirine | The serum concentration of Rilpivirine can be decreased when it is combined with Lorlatinib. |
| Rimegepant | The metabolism of Rimegepant can be increased when combined with Lorlatinib. |
| Risperidone | The metabolism of Lorlatinib can be decreased when combined with Risperidone. |
| Ritonavir | The serum concentration of Lorlatinib can be increased when it is combined with Ritonavir. |
| Rivaroxaban | The metabolism of Lorlatinib can be decreased when combined with Rivaroxaban. |
| Roflumilast | The metabolism of Roflumilast can be increased when combined with Lorlatinib. |
| Romidepsin | The serum concentration of Romidepsin can be decreased when it is combined with Lorlatinib. |
| Ropivacaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Ropivacaine. |
| Rosuvastatin | The metabolism of Rosuvastatin can be increased when combined with Lorlatinib. |
| Rucaparib | The metabolism of Lorlatinib can be decreased when combined with Rucaparib. |
| Ruxolitinib | The metabolism of Ruxolitinib can be increased when combined with Lorlatinib. |
| Salmeterol | The metabolism of Lorlatinib can be decreased when combined with Salmeterol. |
| Saquinavir | The metabolism of Lorlatinib can be decreased when combined with Saquinavir. |
| Satralizumab | The serum concentration of Lorlatinib can be decreased when it is combined with Satralizumab. |
| Saxagliptin | The metabolism of Lorlatinib can be decreased when combined with Saxagliptin. |
| Secukinumab | The metabolism of Lorlatinib can be increased when combined with Secukinumab. |
| Segesterone acetate | The metabolism of Segesterone acetate can be increased when combined with Lorlatinib. |
| Selpercatinib | The serum concentration of Selpercatinib can be decreased when it is combined with Lorlatinib. |
| Selumetinib | The metabolism of Lorlatinib can be decreased when combined with Selumetinib. |
| Sildenafil | The metabolism of Lorlatinib can be decreased when combined with Sildenafil. |
| Siltuximab | The metabolism of Lorlatinib can be increased when combined with Siltuximab. |
| Simeprevir | The metabolism of Lorlatinib can be decreased when combined with Simeprevir. |
| Simvastatin | The metabolism of Lorlatinib can be decreased when combined with Simvastatin. |
| Siponimod | The metabolism of Siponimod can be increased when combined with Lorlatinib. |
| Sirolimus | The serum concentration of Sirolimus can be decreased when it is combined with Lorlatinib. |
| Sofosbuvir | The serum concentration of Sofosbuvir can be decreased when it is combined with Lorlatinib. |
| Somatrogon | The metabolism of Lorlatinib can be increased when combined with Somatrogon. |
| Sonidegib | The metabolism of Sonidegib can be increased when combined with Lorlatinib. |
| Sorafenib | The metabolism of Sorafenib can be increased when combined with Lorlatinib. |
| Sotorasib | The serum concentration of Lorlatinib can be decreased when it is combined with Sotorasib. |
| St. John’s Wort | The metabolism of Lorlatinib can be increased when combined with St. John’s Wort. |
| Stiripentol | The metabolism of Lorlatinib can be decreased when combined with Stiripentol. |
| Sunitinib | The metabolism of Sunitinib can be increased when combined with Lorlatinib. |
| Suvorexant | The metabolism of Suvorexant can be increased when combined with Lorlatinib. |
| Tacrolimus | The metabolism of Tacrolimus can be increased when combined with Lorlatinib. |
| Tadalafil | The metabolism of Lorlatinib can be decreased when combined with Tadalafil. |
| Talazoparib | The serum concentration of Talazoparib can be decreased when it is combined with Lorlatinib. |
| Tamoxifen | The metabolism of Tamoxifen can be increased when combined with Lorlatinib. |
| Tasimelteon | The metabolism of Tasimelteon can be increased when combined with Lorlatinib. |
| Tazemetostat | The metabolism of Tazemetostat can be increased when combined with Lorlatinib. |
| Tegafur | The metabolism of Tegafur can be decreased when combined with Lorlatinib. |
| Telaprevir | The metabolism of Lorlatinib can be decreased when combined with Telaprevir. |
| Telithromycin | The metabolism of Lorlatinib can be decreased when combined with Telithromycin. |
| Telotristat ethyl | The serum concentration of Lorlatinib can be decreased when it is combined with Telotristat ethyl. |
| Temsirolimus | The serum concentration of Temsirolimus can be decreased when it is combined with Lorlatinib. |
| Teniposide | The metabolism of Teniposide can be increased when combined with Lorlatinib. |
| Tenofovir alafen | The serum concentration of Tenofovir alafenamide can be decreased when it is combined with Lorlatinib. |
| Terfenadine | The metabolism of Lorlatinib can be decreased when combined with Terfenadine. |
| Testosterone | The metabolism of Lorlatinib can be decreased when combined with Testosterone. |
| Testosterone cyp | The metabolism of Testosterone cypionate can be decreased when combined with Lorlatinib. |
| Testosterone en | The metabolism of Testosterone enanthate can be increased when combined with Lorlatinib. |
| Tetracaine | The risk or severity of methemoglobinemia can be increased when Lorlatinib is combined with Tetracaine. |
| Tezacaftor | The metabolism of Lorlatinib can be decreased when combined with Tezacaftor. |
| Thalidomide | The metabolism of Lorlatinib can be increased when combined with Thalidomide. |
| Theophylline | The metabolism of Theophylline can be increased when combined with Lorlatinib. |
| Thiotepa | The metabolism of Thiotepa can be increased when combined with Lorlatinib. |
| Ticagrelor | The metabolism of Lorlatinib can be decreased when combined with Ticagrelor. |
| Tipranavir | The metabolism of Lorlatinib can be decreased when combined with Tipranavir. |
| Tivozanib | The metabolism of Tivozanib can be increased when combined with Lorlatinib. |
| Tocilizumab | The metabolism of Lorlatinib can be increased when combined with Tocilizumab. |
| Tolvaptan | The serum concentration of Tolvaptan can be decreased when it is combined with Lorlatinib. |
| Topotecan | The serum concentration of Topotecan can be decreased when it is combined with Lorlatinib. |
| Trabectedin | The metabolism of Trabectedin can be increased when combined with Lorlatinib. |
| Tramadol | The metabolism of Tramadol can be increased when combined with Lorlatinib. |
| Trastuzumab emtan | The serum concentration of Trastuzumab emtansine can be decreased when it is combined with Lorlatinib. |
| Trazodone | The metabolism of Lorlatinib can be decreased when combined with Trazodone. |
| Tretinoin | The metabolism of Lorlatinib can be decreased when combined with Tretinoin. |
| Triamcinolone | The metabolism of Lorlatinib can be increased when combined with Triamcinolone. |
| Triazolam | The metabolism of Lorlatinib can be decreased when combined with Triazolam. |
| Trimipramine | The serum concentration of Trimipramine can be decreased when it is combined with Lorlatinib. |
| Troglitazone | The metabolism of Lorlatinib can be decreased when combined with Troglitazone. |
| Troleandomycin | The metabolism of Lorlatinib can be decreased when combined with Troleandomycin. |
| Tucatinib | The metabolism of Tucatinib can be decreased when combined with Lorlatinib. |
| Udenafil | The metabolism of Lorlatinib can be decreased when combined with Udenafil. |
| Ulipristal | The metabolism of Ulipristal can be increased when combined with Lorlatinib. |
| Valbenazine | The metabolism of Lorlatinib can be decreased when combined with Valbenazine. |
| Vandetanib | The metabolism of Vandetanib can be increased when combined with Lorlatinib. |
| Vardenafil | The metabolism of Lorlatinib can be decreased when combined with Vardenafil. |
| Vemurafenib | The serum concentration of Vemurafenib can be decreased when it is combined with Lorlatinib. |
| Venetoclax | The serum concentration of Venetoclax can be decreased when it is combined with Lorlatinib. |
| Verapamil | The metabolism of Lorlatinib can be decreased when combined with Verapamil. |
| Viloxazine | The metabolism of Lorlatinib can be decreased when combined with Viloxazine. |
| Vinblastine | The serum concentration of Vinblastine can be decreased when it is combined with Lorlatinib. |
| Vincristine | The serum concentration of Vincristine can be decreased when it is combined with Lorlatinib. |
| Vindesine | The metabolism of Vindesine can be increased when combined with Lorlatinib. |
| Vinflunine | The serum concentration of Vinflunine can be decreased when it is combined with Lorlatinib. |
| Vinorelbine | The metabolism of Vinorelbine can be increased when combined with Lorlatinib. |
| Vonoprazan | The metabolism of Lorlatinib can be decreased when combined with Vonoprazan. |
| Vorapaxar | The metabolism of Vorapaxar can be increased when combined with Lorlatinib. |
| Voriconazole | The metabolism of Lorlatinib can be decreased when combined with Voriconazole. |
| Vortioxetine | The metabolism of Lorlatinib can be decreased when combined with Vortioxetine. |
| Warfarin | The metabolism of Warfarin can be increased when combined with Lorlatinib. |
| Zaleplon | The metabolism of Lorlatinib can be decreased when combined with Zaleplon. |
| Zanubrutinib | The metabolism of Zanubrutinib can be increased when combined with Lorlatinib. |
| Zimelidine | The metabolism of Lorlatinib can be decreased when combined with Zimelidine. |
| Ziprasidone | The metabolism of Lorlatinib can be decreased when combined with Ziprasidone. |
| Zolpidem | The metabolism of Zolpidem can be increased when combined with Lorlatinib. |
| Zonisamide | The metabolism of Lorlatinib can be decreased when combined with Zonisamide. |
| Zuclopenthixol | The metabolism of Zuclopenthixol can be increased when combined with Lorlatinib. |
Pregnancy and Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], LORBRENA can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on LORBRENA use in pregnant women. Administration of lorlatinib to pregnant rats and rabbits by oral gavage during the period of organogenesis resulted in malformations, increased post-implantation loss, and abortion at maternal exposures that were equal to or less than the human exposure at the recommended dose of
100 mg once daily based on AUC (see Data). Advise a pregnant woman of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.
Lactation
There are no data on the presence of lorlatinib or its metabolites in either human or animal milk or its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.
Why is this medication prescribed?
Lorlatinib is used to treat a certain type of non-small cell lung cancer (NSCLC) in adults that has spread to other parts of the body. Lorlatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.
How should this medicine be used?
Lorlatinib comes as a tablet to take by mouth. It is usually taken with or without food once daily. Take lorlatinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take lorlatinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
If you vomit after taking the medication, do not take another dose. Continue your regular dosing schedule.
Swallow the tablets whole; do not split, chew, or crush them. Do not take tablets that are already broken or cracked.
Your doctor may decrease your dose or temporarily or permanently stop your treatment depending on if you experience any side effects. Be sure to tell your doctor how you are feeling during your treatment with lorlatinib. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient. This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking lorlatinib,
- tell your doctor and pharmacist if you are allergic to lorlatinib, any other medications, or any of the ingredients in lorlatinib tablets. Ask your pharmacist for a list of the ingredients.
- tell your doctor if you are taking carbamazepine (Epitol, Equetro, Carbatrol, Tegretol, Teril), efavirenz (Sustiva, in Atripla), nevirapine (Viramune), phenobarbital, phenytoin (Dilantin, Phenytek), pioglitazone (Actos, in Actoplus, Duetact), rifabutin (Mycobutin), rifampin (Rifadin, Rimactane, in Rifamate, Rifater), or St. John’s wort. Your doctor will probably tell you not to take lorlatinib if you are taking one or more of these medications.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: alprazolam (Xanax); calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Dilacor, Tiazac), felodipine (Plendil), nifedipine (Adalat, Procardia), nisoldipine (Sular), and verapamil (Calan, Covera); certain medications to treat high cholesterol such as atorvastatin (Lipitor) and lovastatin (Mevacor); clarithromycin (Biaxin, in Prevpac); cyclosporine (Gengraf, Neoral, Sandimmune); diazepam (Valium); erythromycin (E.E.S, Erytab, Eryped); certain medications to treat HIV including atazanavir (Reyataz, in Evotaz), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, in Kaletra, in Technivie), or saquinavir (Invirase); fluconazole; itraconazole (Onmel, Sporanox); ketoconazole; midazolam; nefazodone; oral contraceptives (birth control pills); quinidine (in Nuedexta); sildenafil (Revatio, Viagra); sirolimus (Rapamune); tacrolimus (Prograf); tadalafil (Adcirca, Cialis); trazodone; triazolam (Halcion); or vardenafil (Levitra, Staxyn). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with lorlatinib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you have or have ever had high blood pressure, an irregular heartbeat, diabetes or high blood sugar levels, depression, seizures, high levels of cholesterol and other fatty substances in the blood, or kidney or lung disease.
- tell your doctor if you are pregnant, plan to become pregnant, or plan to father a child. Lorlatinib may interfere with the action of hormonal contraceptives (birth control pills, patches, rings, implants, or injections), so you should not use these as your only method of birth control during your treatment. You must use a non-hormonal birth control such as a barrier method (device that blocks sperm from entering the uterus such as a condom or a diaphragm). Ask your doctor to help you choose a method of birth control that will work for you. If you are female, you will need to take a pregnancy test before you start treatment and should use non-hormonal birth control to prevent pregnancy during your treatment and for 6 months after your final dose. If you are male, you and your female partner should use birth control during your treatment and for 3 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you or your partner become pregnant while taking lorlatinib, call your doctor immediately. Lorlatinib may harm the fetus.
- tell your doctor if you are breast-feeding. You should not breast-feed while you are taking lorlatinib and for 7 days after your final dose.
- you should know that this medication may temporarily decrease fertility in men. Talk to your doctor about the risks of taking lorlatinib.
What special dietary instructions should I follow?
Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medication.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is within 4 hours of the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
