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Indications & Uses
Lorbrexen is indicated for:
Pharmacology
Lorlatinib is a kinase inhibitor. In laboratory (in vitro) tests it was active against ALK and ROS1, and also against TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2 and ACK. It also showed in vitro activity against many mutant forms of the ALK enzyme, including some mutations found in tumors when the disease progressed on crizotinib and other ALK inhibitors.
In mice with tumors implanted under the skin, carrying EML4 fusions with either ALK variant 1 or ALK mutations, lorlatinib produced antitumor activity. These mutations included G1202R and 11171T, both found in tumors when the disease progressed on ALK inhibitors. Mice with EML4-ALK-driven tumor cell lines implanted intracranially also showed antitumor activity and longer survival. Across the in vivo models, the antitumor effect depended on the dose and went along with inhibition of ALK phosphorylation.
Dosage Reference
Reference Information Only
Dosages shown are general references from official sources. Always consult your doctor or pharmacist for personalized dosing.
Adults:
The recommended dose of Lorlatinib is 100 mg taken by mouth once daily. Treatment can continue as long as the patient is getting clinical benefit from it without unacceptable toxicity.
If a dose is missed, the patient should take it as soon as they remember. The one exception is when it is less than 4 hours before the next dose, and then the missed dose should be skipped. Patients should not take 2 doses at the same time to make up for a missed dose.
Dosing interruption or dose reduction may be required, depending on individual safety and tolerability. The dose reduction levels for Lorlatinib are as follows:
First dose reduction: 75 mg taken orally once daily.
Second dose reduction: 50 mg taken orally once daily.
If the patient is unable to tolerate the 50 mg dose taken orally once daily, Lorlatinib should be stopped permanently.
Side Effects
The side effects reported most often with Lorlatinib were hypercholesterolaemia (84.4%), hypertriglyceridaemia (67.1%), oedema (54.6%), peripheral neuropathy (47.8%), cognitive effects (28.8%), fatigue (28.1%), weight increased (26.4%) and mood effects (22.7%). In 23.4% of patients taking Lorlatinib, the dose had to be reduced because of side effects. Oedema and peripheral neuropathy were the most common reasons for these reductions. Treatment was stopped permanently because of side effects in 3.1% of patients, and cognitive effects were the most frequent cause of this.
Cautions & Contraindications
Warnings & Precautions
Hyperlipidaemia Lorlatinib has been linked with rises in serum cholesterol and triglycerides. A severe rise in cholesterol shows up after a median of 201 days (range: 42 to 518 days), and a severe rise in triglycerides after a median of 127 days (range: 15 to 358 days). Serum cholesterol and triglycerides should be checked before Lorlatinib is started, then 2, 4 and 8 weeks after starting, and regularly after that. If indicated, start a lipid-lowering medicine or increase its dose. Central nervous system effects Patients taking Lorlatinib have shown central nervous system (CNS) effects, including changes in cognitive function, mood or speech. Patients who develop these effects may need a dose change or may need to stop the medicine. Atrioventricular block The studies of Lorlatinib left out patients with second-degree or third-degree AV block (unless paced) and any AV block with a PR interval above 220 msec. PR interval prolongation and AV block have been reported in patients on Lorlatinib. An electrocardiogram (ECG) should be checked before starting Lorlatinib and every month after that, especially in patients with conditions that make a clinically significant cardiac event more likely. Patients who develop AV block may need a dose change. Left ventricular ejection fraction decrease A decrease in left ventricular ejection fraction (LVEF) has been reported in patients on Lorlatinib who had a baseline LVEF assessment and at least one follow-up assessment. The clinical study data available can't show whether Lorlatinib causes changes in cardiac contractility. In patients with cardiac risk factors, and in those with conditions that can affect LVEF, cardiac monitoring should be considered, including LVEF assessment at baseline and during treatment. The same applies to patients who develop relevant cardiac signs or symptoms during treatment. Lipase and amylase increase Lipase and/or amylase levels have gone up in patients taking Lorlatinib. The median time to a rise in serum lipase is 70 days (range: 7 to 696 days), and for amylase it is 41 days (range: 7 to 489 days). Pancreatitis risk should be considered in these patients, because of the accompanying hypertriglyceridemia and/or a possible mechanism of the medicine itself. Lipase and amylase should be monitored before Lorlatinib treatment begins and regularly afterwards as clinically indicated. Interstitial lung disease/Pneumonitis Severe or life-threatening lung reactions consistent with ILD/pneumonitis have occurred with Lorlatinib. Any patient whose breathing symptoms get worse in a way that suggests ILD/pneumonitis (e.g. dyspnoea, cough and fever) should be evaluated promptly. Depending on severity, Lorlatinib should be withheld and/or stopped permanently. Drug-drug interactions In a study in healthy volunteers, Lorlatinib taken with rifampin, a strong CYP3A4/5 inducer, was linked with higher alanine aminotransferase (ALT) and aspartate aminotransferase (AST), with no rise in total bilirubin or alkaline phosphatase. Using a strong CYP3A4/5 inducer together with Lorlatinib is contraindicated. Moderate CYP3A4/5 inducers should be avoided if possible, as they may also lower Lorlatinib plasma concentrations. Lorlatinib should not be given at the same time as CYP3A4/5 substrates with narrow therapeutic indices, including but not limited to alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, hormonal contraceptives, pimozide, quinidine, sirolimus and tacrolimus, because Lorlatinib may reduce the concentration of these medicines. Fertility and pregnancy Male patients with female partners of childbearing potential must use effective contraception, including a condom, during treatment with Lorlatinib and for at least 14 weeks after the last dose. Male patients with pregnant partners must use condoms. Male fertility may be compromised during treatment, so men should seek advice on effective fertility preservation before starting. Women of childbearing potential should be advised to avoid becoming pregnant while on Lorlatinib. Female patients need a highly effective non-hormonal method of contraception during treatment, because Lorlatinib can make hormonal contraceptives ineffective. If a hormonal method can't be avoided, a condom must be used together with it. Effective contraception must be continued for at least 35 days after therapy ends. It is not known whether Lorlatinib affects female fertility. Dietary sodium This medicine contains less than 1 mmol sodium (23 mg) per 25 mg or 100 mg tablet. Patients on low sodium diets should be told that Lorlatinib is essentially "sodium-free". Pharmacokinetic interactions In vitro data show that Lorlatinib is mainly metabolised by CYP3A4 and uridine diphosphate-glucuronosyltransferase (UGT)1A4, with minor contributions from CYP2C8, CYP2C19, CYP3A5 and UGT1A3. CYP3A4/5 inducers Rifampin, a strong inducer of CYP3A4/5, was given at oral doses of 600 mg once daily for 12 days. In healthy volunteers who took a single 100 mg oral dose of Lorlatinib, this cut the mean Lorlatinib area under curve (AUC) by 85% and Cmax by 76%, and increases in AST and ALT were also seen. Giving Lorlatinib with strong CYP3A4/5 inducers (e.g. rifampicin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort) may lower Lorlatinib plasma concentrations. Using a strong CYP3A4/5 inducer with Lorlatinib is contraindicated. Moderate CYP3A4/5 inducers should be avoided if possible, as they may also lower Lorlatinib plasma concentrations. CYP3A4/5 inhibitors Itraconazole, a strong inhibitor of CYP3A4/5, was given at oral doses of 200 mg once daily for 5 days. In healthy volunteers who took a single 100 mg oral dose of Lorlatinib, it raised the mean Lorlatinib AUC by 42% and Cmax by 24%. Giving Lorlatinib with strong CYP3A4/5 inhibitors (e.g. boceprevir, cobicistat, itraconazole, ketoconazole, posaconazole, troleandomycin, voriconazole, ritonavir, paritaprevir in combination with ritonavir and ombitasvir and/or dasabuvir, and ritonavir in combination with either elvitegravir, indinavir, lopinavir or tipranavir) may raise Lorlatinib plasma concentrations. Grapefruit products may also raise Lorlatinib plasma concentrations and should be avoided. An alternative medicine with less potential to inhibit CYP3A4/5 should be considered. If a strong CYP3A4/5 inhibitor must be given at the same time, a lower dose of Lorlatinib is recommended.
Contraindications
Don't use Lorlatinib if you are hypersensitive to it. It must also not be taken together with strong CYP3A4/5 inducers.
Pregnancy & Breastfeeding
Women who could become pregnant should be advised to avoid pregnancy while taking Lorlatinib. Female patients need a highly effective non-hormonal method of contraception during treatment, because Lorlatinib can make hormonal contraceptives ineffective. If a hormonal method can't be avoided, a condom must be used together with it. Effective contraception must continue for at least 35 days after therapy is completed. Male patients with female partners who could become pregnant must use effective contraception, including a condom, during treatment and for at least 14 weeks after the final dose. Male patients with pregnant partners must use condoms. Studies in animals have shown embryo-fetal toxicity, and there are no data on the use of Lorlatinib in pregnant women. It may cause fetal harm when given to a pregnant woman, so it is not recommended during pregnancy, or for women of childbearing potential who are not using contraception. It is not known whether Lorlatinib and its metabolites pass into human milk, and a risk to newborns and infants can't be excluded. The medicine should not be used during breastfeeding. Breastfeeding should be stopped during treatment and for 7 days after the final dose. Based on non-clinical safety findings, male fertility may be compromised during treatment. It is not known whether Lorlatinib affects female fertility. Men should seek advice on effective fertility preservation before treatment.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Use in Special Populations
Elderly (≥65 years): There is limited data on Lorlatinib in this age group, so no dose recommendation can be made for patients aged 65 years and older.
Renal impairment: A population pharmacokinetic analysis shows no dose adjustment is needed for patients with normal kidney function or mild to moderate renal impairment (ClCr: >30mL/min). Information on Lorlatinib in severe renal impairment (ClCr: <30 mL/min) is very limited, so it is not recommended for these patients.
Hepatic impairment: No dose adjustment is recommended for mild hepatic impairment. There is no information on the medicine in moderate or severe hepatic impairment, so it is not recommended for patients with moderate to severe impairment.
Pediatric population: The safety and efficacy of Lorlatinib in patients below 18 years have not been established, and no data are available.
Overdose
If someone takes too much Lorlatinib, the treatment is general supportive care. The medicine affects the PR interval on the ECG, and the effect grows with the dose, so ECG monitoring is recommended. There is no antidote for Lorlatinib.
⚠️ In an emergency call 999 or go to the nearest hospital emergency department.
Storage
Keep Lorlatinib below 30°C. Protect it from moisture and light. Store it where children can't see or reach it.
Drug Interactions
Common questions about Lorbrexen 100 mg
What is Lorbrexen 100 mg Tablet?
Lorbrexen 100 mg Tablet is a medicine that contains Lorlatinib. It is made by Everest Pharmaceuticals Ltd. It belongs to the Cytotoxic Chemotherapy group of medicines.
What is Lorbrexen used for?
Lorbrexen is used for: Cancer.
What are the side effects of Lorbrexen?
The side effects reported most often with Lorlatinib were hypercholesterolaemia (84.4%), hypertriglyceridaemia (67.1%), oedema (54.6%), peripheral neuropathy (47.8%), cognitive effects (28.8%), fatigue (28.1%), weight increased (26.4%) and mood effects (22.7%). In 23.4% of patients taking Lorlatinib, the dose had to be reduced because of side effects.
Can I take Lorbrexen during pregnancy or while breastfeeding?
Women who could become pregnant should be advised to avoid pregnancy while taking Lorlatinib. Female patients need a highly effective non-hormonal method of contraception during treatment, because Lorlatinib can make hormonal contraceptives ineffective. Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
What happens if I take too much Lorbrexen?
If someone takes too much Lorlatinib, the treatment is general supportive care. The medicine affects the PR interval on the ECG, and the effect grows with the dose, so ECG monitoring is recommended. In an emergency call 999 or go to the nearest hospital emergency department.
How should I store Lorbrexen?
Keep Lorlatinib below 30°C. Protect it from moisture and light.
Can I take other medicines with Lorbrexen?
Some medicines can interact with Lorlatinib, for example: Fentanyl, Tacrolimus, Cyclosporine, Midazolam, Efavirenz, Bupropion Hydrochloride. Tell your doctor or pharmacist about every medicine you take.
Is there a cheaper medicine with the same ingredient?
Lorbrexen is already among the lowest-priced brands of Lorlatinib at this strength.
Do I need a prescription for Lorbrexen?
Lorbrexen is a prescription (Rx) medicine. Take it as your doctor advises.