Lorlatinib

Lorlatinib is a prescription medication used for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). 

• Lorlatinib is available under the following different brand names: Lorbrena 

Common side effects of Lorlatinib include:

• Fluid retention (edema),
• Numbness and tingling of the extremities,
• Cognitive effects (problems with memory or attention),
• Shortness of breath,
• Fatigue,
• Weight gain,
• Joint pain,
• Mood effects (aggression, agitation, anxiety, depression, euphoria, irritability, mania, mood swings, personality changes, stress, suicidal ideation),
• Diarrhea,
• Headache,
• Cough,
• Nausea,
• Muscle pain,
• Dizziness,
• Vision problems,
• Skin rash,
• Constipation,
• Back pain,
• Pain in extremities,
• Vomiting,
• Speech problems,
• Fever,
• Upper respiratory tract infection, and
• Sleep problems.

Serious side effects of Lorlatinib include:

• Swelling in the 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

Rare side effects of Lorlatinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 25 mg
• 100 mg

Non-small Cell Lung Cancer

Adult dosage

• 100 mg orally once a day with or without food

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Lorlatinib has severe interactions with at least 27 other drugs.
• Lorlatinib has serious interactions with at least 137 other drugs.
• Lorlatinib has moderate interactions with at least 169 other drugs.
• Lorlatinib has minor interactions with the following drug:
  • Ruxolitinib topical

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.\

Contraindications

• Coadministration with strong CYP3A inducers due to the potential for serious hepatotoxicity 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Lorlatinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lorlatinib?”

Cautions

• Increased serum cholesterol and triglycerides may occur; initiate or increase the dose of lipid-lowering agents in patients with hyperlipidemia; monitor serum cholesterol and triglycerides; withhold and resume at the same dose for the first occurrence; resume at the same or a reduced dose for recurrence based on the severity
• PR interval prolongation and AV block reported; monitor ECG before initiating treatment and periodically thereafter; withhold and resume at a reduced dose or at the same dose in patients who undergo pacemaker placement; permanently discontinue for recurrence in patients without a pacemaker
• Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur; promptly investigate for ILD/pneumonitis in any patient who presents with worsening respiratory symptoms indicative of ILD/pneumonitis (.g, dyspnea, cough, and fever); immediately withhold drug in patients with suspected ILD/pneumonitis; permanently discontinue therapy for treatment-related ILD/pneumonitis of any severity
• Hypertension was reported; median time to onset was 6.4 months (1 day to 2.8 years), and 2.3% of patients temporarily discontinued for hypertension; control blood pressure before initiating; monitor blood pressure after 2 weeks and at least monthly thereafter during treatment; withhold and resume at reduced dose or permanently discontinue the drug based on the severity
• Hyperglycemia can occur; the median time to onset of hyperglycemia was 4.8 months (1 day to 2.9 years), and 0.8% of patients temporarily discontinued for hyperglycemia; assess fasting serum glucose before initiating and monitor periodically thereafter; withhold and resume at reduced dose or permanently discontinue based on the severity
• Fetal harm may occur
• Risk of serious hepatotoxicity with concomitant use of strong CYP3A inducers
• Serious hepatotoxicity occurred in healthy patients who received a single dose of lorlatinib with multiple daily doses of rifampin (a strong CYP3A4 inducer)
• ALT or AST elevations occurred within 3 days and returned to within normal limits after a median of 15 days; the median time to recovery for Grades above 3 was 18 days and for Grade 2 was 7 days
• CNS effects
  • A broad spectrum of CNS effects may occur
  • These include seizures, psychotic effects, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep
  • The median time to the first onset of any CNS effect was 1.4 months (1 day to 3.4 years)
  • Withhold and resume at the same dose or a reduced dose or permanently discontinue based on the severity
• Drug interactions overview
  • CYP3A4 substrate; moderate CYP3A4 inducer and CYP2B6 inducer
    • Inhibitor of P-GP and organic cation transporter (OCT)1, organic anion transporter (OAT)3, multidrug and toxin extrusion (MATE)1, and intestinal breast cancer resistance protein (BCRP)
  • CYP3A4 inducers
    • Strong and moderate CYP3A inducers decrease lorlatinib plasma concentrations
    • Coadministration with strong CYP3A4 inducers is contraindicated and avoid use with moderate CYP3A4 inducers
  • CYP3A4 inhibitors
    • Avoid coadministration
    • Strong CYP3A inhibitors increased lorlatinib plasma concentrations
  • CYP3A substrates
    • Coadministration with certain CYP3A substrates decreases the concentration of CYP3A substrates, which may reduce the efficacy of these substrates
    • Avoid use with CYP3A substrates with narrow therapeutic index; if coadministration is unavoidable, increase the dose of CYP3A substrate by prescribing information
  • Fluconazole
    • Avoid coadministration
    • Fluconazole may increase lorlatinib plasma concentrations and the risk of adverse reactions

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, embryo-fetal harm may occur when administered to a pregnant woman
• No available data on use in pregnant women
• Advise pregnant women of the potential risk to the fetus
• Verify pregnancy status in females of reproductive potential before initiating treatment
• Contraception
  • Female patients of reproductive potential: Use effective nonhormonal contraception during treatment and for at least 6 months after the final dose, because lorlatinib can render hormonal contraceptives ineffective
  • Males: Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose
• Infertility
  • Based on animal studies, male fertility may transiently be impaired
• Lactation
  • No data on the presence of lorlatinib or its metabolites in either human or animal milk or its effects on the breastfed infant or milk production
  • Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment and for 7 days after the final dose