Lorlatinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of lorlatinib.
Drugs List
Therapeutic Indications
Uses
Anaplastic lymphoma kinase (ALK)+ve advanced non-small cell lung cancer
Monotherapy for adults with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) in patients not previously treated with ALK inhibitor or in patients treated with an ALK inhibitor previously but disease has progressed.
Dosage
Adults
100mg once daily.
Patients with Renal Impairment
Severe Renal Impairment: Starting dose 75mg once daily.
Additional Dosage Information
Dose reductions
First dose reduction: 75mg once daily.
Second dose reduction: 50mg once daily.
Dose modifications
Hypercholesterolaemia or hypertriglyceridaemia
Mild or moderate hypercholesterolaemia or hypertriglyceridaemia: Introduce or modify lipid-lowering therapy in accordance with respective prescribing information; continue lorlatinib at same dose.
Severe hypercholesterolaemia or hypertriglyceridaemia: Introduce the use of lipid-lowering therapy; if currently on lipid-lowering therapy, increase the dose of this therapy in accordance with respective prescribing information; or change to a new lipid-lowering therapy. Continue lorlatinib at the same dose without interruption.
Life-threatening hypercholesterolaemia or hypertriglyceridaemia: Introduce the use of lipid-lowering therapy or increase the dose of this therapy in accordance with respective prescribing information or change to a new lipid-lowering therapy. Withhold lorlatinib until recovery of hypercholesterolaemia or hypertriglyceridaemia to moderate or mild severity grade. Re-challenge at same lorlatinib dose while maximising lipid-lowering therapy in accordance with respective prescribing information.
Recurring severe hypercholesterolaemia or hypertriglyceridaemia: Reduce lorlatinib by 1 dose level.
Central nervous system effects (changes in cognition, mood or speech)
Grade 2 or Grade 3: Withhold dose until toxicity is less than or equal to Grade 1. Then resume lorlatinib at 1 reduced dose level.
Grade 4: Permanently discontinue lorlatinib.
Lipase/Amylase increase
Grade 3 or Grade 4: Withhold lorlatinib until lipase or amylase returns to baseline. Then resume lorlatinib at 1 reduced dose level.
Interstitial lung disease (ILD)/Pneumonitis
Grade 1 or Grade 2: Withhold lorlatinib until symptoms have returned to baseline and consider initiating corticosteroids. Resume lorlatinib at 1 reduced dose level. Permanently discontinue lorlatinib if ILD/pneumonitis recurs or fails to recover after 6 weeks of lorlatinib hold and steroid treatment.
Grade 3 or Grade 4: Permanently discontinue lorlatinib.
PR interval prolongation/Atrioventricular (AV) block
First degree AV block (asymptomatic): Continue lorlatinib at the same dose without interruption. Consider effects of concomitant medicinal products, and assess and correct electrolyte imbalance that may prolong PR interval. Monitor ECG/symptoms potentially related to AV block closely.
First degree AV block (symptomatic): Withhold lorlatinib. Consider effects of concomitant medicinal products, and assess and correct electrolyte imbalance that may prolong PR interval. Monitor ECG/symptoms potentially related to AV block closely. If symptoms resolve, resume lorlatinib at 1 reduced dose level.
Second degree AV block (asymptomatic): Withhold lorlatinib. Consider effects of concomitant medicinal products, and assess and correct electrolyte imbalance that may prolong PR interval. Monitor ECG/symptoms potentially related to AV block closely. If subsequent ECG does not show second degree AV block, resume lorlatinib at 1 reduced dose level.
Second degree AV block (symptomatic): Withhold lorlatinib. Consider effects of concomitant medicinal products, and assess and correct electrolyte imbalance that may prolong PR interval. Refer for cardiac observation and monitoring. Consider pacemaker placement if symptomatic AV block persists. If symptoms and the second degree AV block resolve or if patients revert to asymptomatic first degree AV block, resume lorlatinib at 1 reduced dose level.
Complete AV block: Withhold lorlatinib. Consider effects of concomitant medicinal products, and assess and correct electrolyte imbalance that may prolong PR interval. Refer for cardiac observation and monitoring. Pacemaker placement may be indicated for severe symptoms associated with AV block. If AV block does not resolve, placement of a permanent pacemaker may be considered. If pacemaker placed, resume lorlatinib at full dose. If no pacemaker placed, resume lorlatinib at 1 reduced dose level only when symptoms resolve and PR interval is less than 200 milliseconds.
Hypertension
Grade 3: Withhold lorlatinib until hypertension has recovered to Grade 1 or less, then resume lorlatinib at the same dose. If Grade 3 hypertension recurs, withhold lorlatinib until recovery to Grade 1 or less, and resume at a reduced dose. If hypertension control cannot be achieved with optimal medical management permanently discontinue lorlatinib.
Grade 4: Withhold lorlatinib until recovery to Grade 1 or less, and resume at a reduced dose or permanently discontinue lorlatinib. If Grade 4 hypertension recurs, permanently discontinue lorlatinib.
Hyperglycaemia
Grade 3 or Grade 4: Withhold lorlatinib until hyperglycaemia is adequately controlled, then resume lorlatinib at the next lower dose. If adequate hyperglycaemic control cannot be reached with optimal medical management, permanently discontinue lorlatinib.
Other adverse reactions
Grade 1 or Grade 2: Consider no dose modification or reduce by 1 dose level, as clinically indicated.
Greater than or equal to Grade 3: Withhold lorlatinib until symptoms resolve to less than or equal to Grade 2 or baseline. Then resume lorlatinib at 1 reduced dose level.
Contraindications
Children under 18 years
Patients over 65 years
Breastfeeding
Galactosaemia
Moderate hepatic impairment
Pregnancy
Precautions and Warnings
Predisposition to cardiac failure
Glucose-galactose malabsorption syndrome
Lactose intolerance
Severe renal impairment
Advise patient condom barrier must be used if female partner is pregnant
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor ECG before initiating and at least monthly thereafter
Monitor fasting serum glucose prior to and periodically during treatment
Monitor serum amylase and lipase before and regularly during treatment
Consider monitoring LVEF in patients who develop cardiac signs/symptoms
Monitor blood pressure regularly
Monitor cholesterol and triglyceride levels
Monitor for signs and symptoms of interstitial lung disease
Monitor for signs and symptoms of pneumonitis
Perform eye tests in any patient with vision change/ophthalmologic symptoms
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report new visual problems and symptoms
Reduce dose if severe hypercholesterolaemia or hypertriglyceridaemia recur
Consider disc'g treatment when medical management of hyperglycaemia failed
Consider interrupting/reducing dose if AV block occurs
Discontinue if persistent hypertension unresponsive to therapy occurs
Discontinue if recurrent grade 1 or 2 pneumonitis or ILD occurs
Discontinue or reduce dose if CNS toxicity occurs
Discontinue treatment if grade 3 or greater pneumonitis occurs
Interrupt if life-threatening hypercholesterolaemia/hypertriglyceridaemia
Suspend treatment if grade 3 or greater adverse reaction occurs
Suspend treatment if grade 3 or greater elevations in lipase or amylase
Suspend treatment if grade 3 or greater hyperglycaemia occurs
Suspend/reduce dose if grade 1 or 2 pneumonitis or ILD occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Advise patient to avoid Seville (sour) orange products
Male: May cause infertility
Female: Barrier or non-hormonal contraception advised during treatment
Female: Contraception required during and at least 35 days after treatment
Female: Non-hormonal contraception required during and after treatment
Male: Contraception required during and for 14 weeks after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Pregnancy and Lactation
Pregnancy
Lorlatinib is contraindicated during pregnancy.
The manufacturer recommends that lorlatinib is not used during pregnancy. Animal studies have shown embryo-foetal toxicity. At the time of writing there are no data from the use of lorlatinib in pregnant women, a risk of foetal harm when administered to pregnant women cannot be excluded.
Lactation
Breastfeeding is contraindicated during pregnancy and for 7 days after the final dose.
The manufacturer recommends that lorlatinib should not be used during breastfeeding and for 7 days after the final dose. It is unknown whether lorlatinib is excreted in breast milk and therefore a risk to newborns/infants cannot be excluded.
Side Effects
Aggression
Agitation
Amnesia
Anaemia
Anxiety
Arthralgia
Asthenia
Attention disturbances
Auditory hallucinations
Blurred vision
Burning sensation
Changes in mood
Cognitive impairment
Confusion
Constipation
Delirium
Dementia
Depressed mood
Depression
Dermatitis acneiform
Diarrhoea
Diplopia
Disorientation
Dysaesthesia
Dysarthria
Elevated amylase levels
Elevated serum lipase
Euphoria
Fatigue
Floaters
Formication
Gait abnormality
Generalised oedema
Hallucinations
Headache
Hyperactivity
Hypercholesterolaemia
Hypertriglyceridaemia
Hypoaesthesia
Impaired memory
Impaired vision
Impairment of mental skills
Increase in plasma cholesterol
Increase in plasma triglyceride concentration
Interstitial lung disease
Irritability
Lability of affect
Maculopapular rash
Mania
Muscle weakness
Musculoskeletal pain
Myalgia
Nausea
Neuralgia
Neurotoxicity
Oedema
Pancreatitis
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Peripheral sensory neuropathy
Personality change
Photophobia
Photopsia
Pneumonitis
Prolongation of PR interval
Pruritic rash
Psychosis
Rash
Reduced visual acuity
Seizures
Sensory disturbances
Slow speech
Speech disturbances
Swelling
Visual hallucinations
Weight gain
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2022
Reference Sources
Summary of Product Characteristics: Lorviqua 25mg and 100mg tablets. Pfizer Ltd. Revised September 2021.
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