Lorlatinib | Lorbrena

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side effects
tests to perform
Dosing Guidelines
Additional resources

Timeline of Lorlatinib side effects:

A timeline of side effects associated with lorlatinib over the first 7 months of treatment, including hyperlipidemia, CNS effects, edema, hyperglycaemia, hepatotoxicity, fatigue, weight gain, peripheral neuropathy, and hypertension.

Other Lorlatinib side effects:

Tests to perform before starting treatment:

Vial of blood and magnifying glass examining it.

    • pancreatic enzyme test: elevated lipase and amylase

    • serum cholesterol and triglyceride levels for hyperlipidemia

    • fasting serum glucose for hyperglycemia

    • liver function tests: ALT, AST, and bilirubin levels

Illustration of a human brain showing the cerebrum, cerebellum, and brainstem.

  • Evaluate CNS or include neurological exam to establish a baseline.

    Lorlatinib can cause CNS effects including:

    • seizures

    • psychotic effects

    • changes in cognitive function

    • changes in mood (including suicidal ideation)

    • changes in speech

    • changes in mental status

    • changes in sleep

Blood pressure cuff used to measure blood pressure

  • Monitor ECG and blood pressure at the start of treatment. Particularly in patients with predisposing conditions to cardiac events.

    Advise patients to report symptoms of high blood pressure including:

    • headaches

    • dizziness

    • blurred vision

    • chest pain

    • shortness of breath

    • swelling

Bathroom scale with blue platform and gray border.

  • Establish what a healthy baseline weight for the patient is. This may be a weight prior to cancer diagnosis.

    Advise patients to report any rapid or large increases in weight.

A medical monitoring schedule chart showing weekly blood tests and other tests over two months, with key monitoring points at weeks 2, 4, and 8, including blood lipid and pressure tests, and monitoring for cognitive, mood, or speech changes.

Tests to perform during treatment:

General dose guidelines:

Illustration of a medication bottle labeled 100mg, 1x/day.

  • Recommended starting dose: 100mg orally 1x/day.

    Can be taken with or without food (avoid grapefruit products- CYP3A inhibitor, and St. John’s wort- CYP3A inducer).

    Medication should be taken at the same time each day.

    Tablets should be swallowed whole, do not use if compromised (broken, cracked, etc.).

A medication bottle labeled 75mg 1x/day, with a pink arrow pointing to it, marked '1st reduction' indicating a decreased dosage.

  • First reduction: 75mg 1x/day

    Confirm condition does not fall under specific dose reductions.

A medication bottle labeled 50mg 1x/day, with a pink arrow pointing to it, marked '2nd reduction' indicating a decreased dosage.

  • Second reduction: 50mg 1x/day

    Confirm condition does not fall under specific dose reductions.

A red circle with a diagonal line through it, indicating a prohibition or 'no' symbol.

  • Discontinue if patient cannot tolerate 50mg 1x/day.

Specific dose guidelines:

Cartoon illustration of a pink and a brown capsule pills with expressive eyes and open mouths, fighting each other.

  • Strong CYP3A inhibitors:

    Avoid if possible (potential for serious hepatotoxicity).

    If unavoidable, reduce to 75mg 1x/day.

    If CYP3A inhibitor is discontinued, resume prior dose after a washout period of 3-5 half lives of the CYP3A inhibitor.

    Fluconazole:

    Avoid if possible.

    If unavoidable, reduce starting dose to 75mg 1x/day.

    CYP3A inducers:

    Discontinue STRONG CYP3A inducers for 3 plasma half-lives before starting lorlatinib.

    Avoid use of STRONG CYP3A inducers (reduce lorlatinib plasma concentrations).

    If unavoidable, increase starting dose of lorlatinib to 125mg 1x/day.

Digital illustration of a human liver in shades of brown on a plain white background.

  • No formal studies have been conducted.

    For mild hepatic impairment no dose adjustment is recommended.

    For moderate-severe hepatic impairment limited information is available.

Digital illustration of two human kidneys with ureters.

  • For mild-moderate impairment no adjustment is recommended.

    For severe renal impairments reduce dose to 75mg 1x/day.

    Not recommended for patients requiring hemodialysis.

Cross-section of a blood vessel with fat building up to indicate hyperlipidemia which can cause arteries to become blocked.

  • If mild to moderate: introduce or modify lipid lowering therapy and continue lorlatinib at same dose.

    If severe: introduce or increase the dose of, or change to a new lipid lowering therapy. Withhold lorlatinib until recovery to a mild-moderate level. If severe levels recur, reduce lorlatinib by 1 dose level.

Illustration of a human brain showing the cerebrum, cerebellum, and brainstem.

  • If mild: continue at the same dose or withhold dose until recovery to baseline then resume at the same dose or reduce by 1 dose level.

    If moderate or severe: withhold dose until toxicity is less than or equal to mild level. Then reduce lorlatinib by 1 dose level.

    If life threatening or urgent intervention is indicated permanently discontinue lorlatinib.

Illustration of human lungs, showing bronchial tubes and lobes.

  • If ILD or pneumonitis is suspected, withhold dose during investigation.

    If ILD or pneumonitis is confirmed, permanently discontinue.

A pink heart with a dial gauge indicating high blood pressure.

  • If grade 3: withhold lorlatinib until recovered to grade 1 or less.

    • If grade 3 recurs withhold lorlatinib until recovery to grade 1 or less and reduce dose

    • If hypertension cannot be managed permanently discontinue

    If grade 4: withhold lorlatinib until recovery to grade 1 or less then resume reduced dose or permanently discontinue

    • If grade 4 recurs permanently discontinue

Blood droplet with two sugar cubes next to it to indicate hyperglycemia.

  • If grade 3 or 4: withhold lorlatinib until hyperglycemia is controlled then resume at reduced dose.

    If control isn’t achieved discontinue use.

Pink heart with a medical heartbeat line across it

  • First degree AV block:

    • If asymptomatic, continue at same dose.

    • If symptomatic, withhold dose. If symptoms resolve continue at same or reduce 1 dose level.

    Second degree AV block:

    • If asymptomatic, withhold lorlatinib until ECG is checked. If ECG does not show second degree block resume or reduce 1 dose level.

    • If symptomatic, withhold lorlatinib. If symptoms and second degree block resolve or become asymptomatic first degree AV block, resume or reduce one dose level.

    Complete AV block:

    • Withhold dose.

    • If pacemaker is placed full dose may be resumed.

    • If no pacemaker is placed resume at 1 reduced dose level only when symptoms resolve and PR interval is less than 200 msec.

Lorlatinib Monograph

Additional resources:

Dose reductions are common and don’t compromise treatment

People who needed to reduce their dose of lorlatinib early still had similar results to those who did not have their dose reduced early. Both groups lived without their cancer getting worse (including brain metastases), or new tumors spreading to the brain.

Fewer people who took lorlatinib had tumors that spread to the brain, or had brain tumors that got worse compared to those who took crizotinib.

Know what to expect regarding lorlatinib side effects

Side effects of lorlatinib can be managed with dose modification and supportive care. Open communication between healthcare providers and patients is important to educate patients on how to respond to common side effects.

Side effects unique to lorlatinib include high rates of hyperlipidemia and CNS effects.

A pragmatic guide for management of adverse events associated with lorlatinib

Lorlatinib has very strong CNS/brain metastases activity

Lorlatinib also has a 2.8% cumulative incidence risk of CNS disease progression at 12 months compared to 9.4% with alectinib.

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