Lorlatinib

Lorlatinib
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Uma Maveli[2]

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Black Box Warning

WARNING: SERIOUS CENTRAL NERVOUS SYSTEM EFFECTS See full prescribing information for complete Boxed Warning. Broad-spectrum of Central Nervous system side effects with the use of Lorlatinib Seizures, Hallucinations, changes in mood, sleep, mental health are all examples of the side effects Reduce the dosage of Lorlatinib depending on the severity of the side effect For patients requiring first time reduction, give them 75 mg daily through mouth For patients requiring second time reduction, give them 50 mg daily through mouth

Overview

Lorlatinib is a Antineoplastic Agents that is FDA approved for the treatment of The treatment of patients with lung cancer

• Should not be given to patients experiencing life threatening episodes
• In other words, Revefenacin should not be used as a rescue drug
• Discontinue the drug if patients appears to suffer from paradoxical bronchospasm or hypersensitivity reactions. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Edema, Peripheral Neuropathy, Cognitive Effects, Dyspnea (shortness of breath), fatigue, weight gain, arthralgia, mood effects, diarrhea.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Lorlatinib is indicated for:

• The treatment of patients with anaplastic lymphoma kinase- aggressive, wide-spread lung cancer
• It is indicated for with:
  • Crizonitib and another ALK inhibitor, or Alectinib, the first therapy for metastatic disease, or Ceritinib as the first ALK inhibitor for this type of disease

Limitations of Use

• Revefenacin delivered via jet nebulizer can result in "longer administration time, variability in residual volume and particle size, daily cleaning requirements, limited portability, and need for device assembly"
  • The benefits may outweigh this because some patients are required to use nebulizers

Recommended Vaccination and Prophylaxis

Recommended Weight-Based Dosage Regimen - OCPD

Recommended Weight-Based Dosage Regimen - aHUS

Dosing Considerations

• Some dose reductions if the patients have adverse reactions include:
  • Swallow Lorlatinib orally in a recommended dosage of 75 mg once daily
  • If there is need for more reduction, take Lorlatinib 50 mg once daily orally

Preparation of Lorlatinib

Administration of Lorlatinib

• It is recommended that the patient take 100 mg of Lorlatinib, no matter if they have or have not eaten
• The tablets are meant to be swallowed whole: it is unacceptable to chew, break, split tablets because it will not have the same effect and it could be dangerous
  • Make sure to not to take them if they are broken, cracked, not in packaging etc
• It is important that the patient takes the medication the same time each day
  • The patient may take the forgotten dose if it is more that 4 hours from their next dose
  • It is really important that they do not take multiple doses at once

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Lorlatinib Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.

Non–Guideline-Supported Use

There is limited information regarding Lorlatinib Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Lorlatinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Lorlatinib Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.

Non–Guideline-Supported Use

There is limited information regarding Lorlatinib Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.

Contraindications

• It is crucial to withhold ingesting Lorlatinib for three plasma half lives for patients taking strong CYP3A inducers
• Mixing them together could lead to serious hepatotoxicity or chemical-driven liver damage

Warnings

WARNING: SERIOUS CENTRAL NERVOUS SYSTEM EFFECTS See full prescribing information for complete Boxed Warning. Broad-spectrum of Central Nervous system side effects with the use of Lorlatinib Seizures, Hallucinations, changes in mood, sleep, mental health are all examples of the side effects Reduce the dosage of Lorlatinib depending on the severity of the side effect For patients requiring first time reduction, give them 75 mg daily through mouth For patients requiring second time reduction, give them 50 mg daily through mouth

Serious Central Nervous System Effects

• Seizures, Hallucinations, changes in mood, sleep, mental health are all examples of the side effects
• Reduce the dosage of Lorlatinib depending on the severity of the side effect
• For patients requiring first time reduction, give them 75 mg daily through mouth
• For patients requiring second time reduction, give them 50 mg daily through mouth
• About 54% of patients acquiring this drug may experience Central Nervous system side effects listed above

Hyperlipidemia

• Patients will be monitored for the first 1-2 months ingesting Lorbrena, and followed up on after the initial period
• Patients may experience an increase in serum cholesterol and triglycerides
• About 7% of patients in the Study B7461001 required to discontinue the drug for a short period of time, and another 3% of the patients required a dose reduction
• In the same study, 80% of the patients required to instigate lipid-lowering medications because they were not responding to reduction and temporary pause
  • This may have required a period of adjustment for 21 days to get accustomed to the lipid-lowering medications

Monitoring Disease Manifestations after ULTOMIRIS Discontinuation

Infusion Reactions

Adverse Reactions

Clinical Trials Experience

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Atypical Hemolytic Uremic Syndrome (aHUS)

Immunogenicity

Postmarketing Experience

There is limited information regarding Yupelri Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Yupelri Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There are no available data on Revefencain use in pregnant women to inform a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lorlatinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lorlatinib during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Revefenacin with respect to nursing.

Pediatric Use

There is no FDA guidance on the use of Lorlatinib in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Lorlatinib in geriatric settings.

Gender

There is no FDA guidance on the use of Lorlatinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lorlatinib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Lorlatinib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Lorlatinib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lorlatinib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Revefenacin in patients who are immunocompromised.

Administration and Monitoring

Administration

• After intravenous administration of revefenacin, the reported volume of distribution is 218 L which suggests an extensive distribution to the tissues

Monitoring

There is limited information regarding Lorlatinib Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Lorlatinib and IV administrations.

Overdosage

Common signs and symptoms of overdosage of Revefenacin:

• nausea, vomiting, dizziness, lightheadedness, blurred vision, increased intraocular pressure, obstipation and difficulties in voiding
• If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Lorlatinib
Systematic (IUPAC) name
?
Identifiers
CAS number	1803171-55-2
ATC code	?
PubChem	?
Chemical data
Formula	?
Mol. mass	55768.94 Da
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Mechanism of Action

There is limited information regarding Lorlatinib Mechanism of Action in the drug label.

Structure

There is limited information regarding Ultomiris Structure in the drug label.

Pharmacodynamics

There is limited information regarding Lorlatinib Pharmacodynamics in the drug label.

Pharmacokinetics

Distribution

Elimination

Specific Populations

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Clinical Studies

Anaplastic Lymphoma Kinase(COPD)

ALK Study 301 [ALXN1210-PNH-301; NCT02946463]

ALK Study 302 [ALXN1210-PNH-302; NCT03056040]

Study in Adult Patients with Anaplastic Lymphoma Kinase [ALXN1210-aHUS-311; NCT02949128]

Study in Pediatric Patients with Anaplastic Lymphoma Kinase[ALXN1210-aHUS-312; NCT03131219]

• There is limited information regarding Lorlatinib Studies in Pediatric Patients

How Supplied

• It is supplied in a child-resistant vial that contains 25 or 100 mg worth of tablets. There will be 30 tablets in the bottle. Some of the inactive ingredients in the tablet include microcrystalline cellulose, sodium starch glycolate, and magnesium stearate.
  • The 25 mg bottles will contain tablets that appear as 8mm round, tan-colored, film-coated, and has 25 on one side and LLN on the other side
  • The 100 mg bottles will contain tablets that appear as 8.5 by 17 mm round, lavender-colored, film-coated, contains Pfizer on on side, and 100 and LLn on the other

Storage

• Lorbrena is stored in a temperature of 20-25 degrees Celsius (68-77 degrees Fahrenheit)
• It is allowed to be exposed to temperatures from 15-30 degrees Celsius for some time

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

Hepatotoxicity

• Patients should be aware that utilizing Lobrena concurrent to CYP3A inducers can lead to serious cases of hepatotoxicity
• Patients should check with a doctor to confirm the compatibility of certain medications with Lobrena

Other Infections

Discontinuation

• Patients who express Paradoxical Bronchospasm, which means breathing or wheezing will worsen, should discontinue Revefenacin and initiate therapy with another agent

Infusion reactions

• There is limited information on Lobrena infusion reactions

Precautions with Alcohol

Alcohol-Lorlatinib interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

Lorbrena

Look-Alike Drug Names

There is limited information regarding Lorlatinib Look-Alike Drug Names in the drug label.

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.