Lorbrexen 100 (Lorlatinib)

Introduction & Overview

Lorbrexen 100 mg is an updated formulation of Lorlatinib, a 3rd generation ALK inhibitor for treatment of ALK positive non-small cell lung cancer(NSCLC). It was developed in response to resistance against earlier ALK therapy and offers better central nervous system penetration as well as improved effectiveness against metastatic disease.

This treatment is mainly given to patients whose tumor has grown after earlier ALK-targeted therapies. By specifically blocking ALK and ROS1 tyrosine kinases, Lorbrexen 100 mg helps stop the signals that support tumor growth giving patients a more targeted and individualized way of care.

It is trusted by oncologists for reliable performance in clinical practice. 

Manufactured by Everest Pharmaceuticals, it becomes a critical step to improve quality of life and outcomes for patients facing complex challenges of lung cancer within a precision oncology strategy.

How It Works

Lorbrexen 100 mg acts by selectively inhibiting the abnormal ALK and ROS1 proteins which usually drive the growth of cancer cells in ALK-positive non-small cell lung cancer. These genetic mutations cause uncontrolled division of cells, especially in patients with the advanced or metastatic condition of lung cancer.

It is a third-generation ALK inhibitor, and it’s active ingredient has been designed to be able to cross the blood-brain barrier, thus being highly effective against brain metastases, the most common complication in patients with ALK-positive NSCLC.

By blocking major signaling routes, It helps slow the progression of tumors and reduce the spread of cancer while enhancing better outcomes for patients. Its precise targeting offers less off-target assault compared to conventional chemotherapy, thus placing it as a major player in modern personalized cancer therapy.

Approved Indications

Lorbrexen 100 mg is recommended for treating adult patients with ALK-positive metastatic NSCLC. It has been specifically approved to be used in the individuals whose disease has progressed after one or more treatments with ALK inhibitors such as crizotinib, alectinib, or ceritinib. 

This treatment will likely help more in patients having a central nervous system condition as it shows better activity against metastases in the brain.

It provides specific care for controlling ALK-rearranged NSCLC, aiding in the delay of disease growth and better quality of life in late-stage cases. It must be given by a cancer doctor who knows targeted lung cancer treatments and based on proven ALK mutation status.

Pharmacological Details

Lorbrexen 100 mg is a powerful third-generation kinase inhibitor with activity against ALK and ROS1, as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK kinases. Lorlatinib 100 mg as lorlatinib is the active ingredient of Lorbrexen effectively inhibits those kinase mutations that lead to ALK resistance, including the G1202R and I1171T mutations. Potent in vitro against a wide variety of ALK mutants, it showed promising activity in vivo in mouse models bearing I1171T- and G1202R-driven tumors. 

Such mutations are the most frequent ones observed in lorlatinib-treated tumors. In mice bearing EML4-ALK-driven tumors, including intracranial tumors, the activity of lorlatinib was particularly striking, showing dose-dependent antitumor efficacy in all models with a strong inhibition of ALK phosphorylation that also resulted in prolonged survival.

Dosage and Administration

Lorbrexen 100 mg should be administered orally at the recommended dose of 100 mg once daily, with or without food. The tablet should be swallowed whole and should not be chewed, crushed or divided. Treatment should be continued until disease progression or unacceptable toxicity, as determined by the treating physician.

Missed dose: If a dose is missed, it should be taken as soon as possible on the same day. If a whole day is missed, the next dose should be taken at the scheduled time the following day. Two doses should not be taken at once.

Monitoring: Routine assessment of lipid levels, liver function and neurological status is recommended during treatment.

Potential Drug Interactions

Enzyme and Transporter Interactions  

CYP3A4/5 Induction

Lorbrexen 100 mg has been established to involve CYP3A4/5 enzymes which are essential in the metabolism of a lot of drugs. In the study, Lorbrexen reduced the concentration of mndazolam, a known substrate of CYP3A, in plasma, indicating a moderate inductive effect. Therefore, medicines that are dependent on CYP3A4/5 for metabolism may be compromised when administered with this medication. Such medicines include alfentanil, ciclosporin, ergotamine, fentanyl, hormonal contraceptives (specific), pimozide, quinidine, sirolimus, and tacrolimus. Dosage forms that contain these drugs should not be co-administered with Lorbrexen.

Other CYP Enzymes:

In addition to the above, it may reduce the plasma levels of substrates for CYP2B6 (example, bupropion, efavirenz) because it induces this enzyme. Though the clinical relevance is not clearly established, it may inhibit CYP2C9. Its effect on CYP1A2 is weak, if any at all.

UGT Pathways:

Based on laboratory data, it may inhibit UGT1A1, an enzyme involved in metabolism and clearance of bilirubin. Until more definitive data are collected, this theoretical interaction should be considered in the risk-benefit analysis during clinical decision-making.

Transporter Proteins: 

Lorbrexen 100 mg can stop very key drug movers which are P-glycoprotein (P-gp), BCRP, OATP1B1, OATP1B3, OCT1, MATE1, and OAT3. These proteins affect drugs getting into the cells and leaving the cells, mostly in the gut, liver, and kidneys. Blocking them could change how some drugs are taken up, worked on, or removed.

Contraindications

Contraindications

• Do not take the drug if you are allergic to lorlatinib or any of the ingredients in it. An allergic reaction may cause a rash, itching, swelling, severe dizziness, or trouble breathing.
• Avoid concomitant use of strong CYP3A4/5 inducers with this drug. Inducers could be rifampin, carbamazepine, phenytoin, enzalutamide, or St John’s wort. These drugs drastically reduce the level of Lorbrexen in the blood with the potential to make the medicine less effective and cause raising of liver enzyme levels.
• Category X : Contraindicated in pregnancy, possible fetal harm. 
• Applies to isotretinoin: oral capsule Along with its needed effects, isotretinoin (the active ingredient contained in Claravis) may cause some unwanted effects.

It is not known if Lorbrexen 100 mg is found in breast milk. Because many drugs are

Side Effects

• Hyperlipidaemia: Raised levels of serum cholesterol and of serum triglycerides are often seen. They are usually self-limiting, occurring within the first few months of treatment, and may require the use of lipid lowering drugs.
• Central Nervous System: Cognitive changes, mood changes, speech issue, and memory loss may occur in patients. These reactions may necessitate dose adjustment or discontinuation.
• Cardiovascular Effects: The PR interval has been prolonged and complete atrioventricular block has occurred. Frequent ECG follow-up is recommended, particularly in those with predisposing factors.
• LVEF Patients have experienced reduced cardiac output. Patients with known cardiac risk need to be watched.
• Elevation of Pancreatic Enzymes: Elevations of lipase and amylase have been reported. While frequently asymptomatic, pancreatitis should be considered, especially in the setting of elevated triglycerides.
• Pneumonitis/Interstitial Lung Disease: Interstitial lung disease (ILD)/pneumonitis can occur. Patients should be evaluated immediately in the presence of new or worsening cough, dyspnoea, and fever, and treatment should be temporarily interrupted if necessary.

Precautions and Safety Warnings

Hyperlipidaemia

It has been linked to increased serum cholesterol and triglycerides. Commonly, there is severe hypercholesterolemia at a median of 201 days (range: 42–518), and hypertriglyceridemia at 127 days (range: 15–358). Test lipid levels before beginning treatment and at 2, 4, and 8 weeks after starting therapy. Then, continue monitoring on a regular schedule. Start or adjust the dosage for agents that lower lipids as necessary.

Central Nervous System Attack

Patients being administered Lorbrexen 100 mg should be alive to the possibility of CNS-related adverse reactions, such as cognitive dysfunction, affect lability, and at times verbal disturbances. Which may call for adjustment or even discontinuation of the dose based on intensity.

Atrioventricular (AV) Block

There have been reports of AV block and PR interval prolongation. Patients with second- or third-degree AV block, unless paced, were excluded from the clinical trials. An ECG check is recommended before the initiation of Lorbrexen, and then monthly, particularly in this population with cardiac risk.

Left Ventricular Ejection Fraction (LVEF) Decrease

Reductions in the left ventricular ejection fraction have been observed in patients that have been treated with the drug in question. Although a casual relationship has not been established, risk factors should prompt consideration for cardiac monitoring. An LVEF measurement should be taken before the initiation of treatment to serve as a baseline of cardiac signs and periodically during treatment.

Elevated Lipase and Amylase

Onset elevations in serum lipase and/or amylase levels have been seen with a median of 70 days (range 7-696) and 41 days (range 7-489). Check pancreatic enzymes at baseline and from time to time. Keep the patients in the high-risk category for pancreatitis, especially in the presence of hypertriglyceridemia.

Interstitial Lung Disease (ILD)/Pneumonitis

Fatal interstitial lung disease (ILD)/pneumonitis has occurred. Any new or worsening respiratory symptoms (cough, dyspnea, fever) must be evaluated immediately. Use of this medication should be stopped and may not be restarted based on how bad the reaction is.

Fertility and Pregnancy

There should be impairment of male fertility by this medication. There should be contraception of effective nature in male patients for 14 weeks after the treatment. In female patients, non-hormonal contraception should be used during the treatment and for 35 days after, as the efficacy of hormonal contraceptives can be reduced by Lorbrexen. No pregnant partners should not be protected with condom use. Before the initiation of therapy, fertility preservation should be considered.

Dietary Sodium

Each 25 mg or 100 mg tablet of Lorbrexen contains less than 1 mmol (23 mg) sodium. It is essentially “sodium-free” and suitable for patients on low-sodium diets.

Pharmacokinetics

Lorbrexen 100 mg is primarily metabolized by CYP3A4 and UGT1A4, with minor contributions from CYP2C8, CYP2C19, CYP3A5, and UGT1A3.

CYP3A4/5 Inducers

A strong inductor, rifampin, reduces Lorbrexen plasma levels to a large extent (by 85% in AUC, and by 76% in Cmax) and can be accompanied by elevated liver enzymes; therefore, co-administration is contraindicated. Whenever possible, moderate inducers should not be used as their use would also carry a similar risk regarding reduced efficacy.

CYP3A4/5 Inhibitors

Potent inhibitors increase Lorbrexen exposure. Co-administration should be avoided. If co-administration is necessary, the dose of Lorbrexen should be adjusted. Grapefruit and its products should be avoided as they may increase plasma 

Special Population Considerations

• Geriatric (65 years and older): As there is insufficient information available for recommending a dose for patients greater than 65 years of age, no dosage recommendation can be made in this population.
• Renal Dosage adjustment not necessary in patients with normal renal function and mild to moderate renal impairment (ClCr >30mL/min) according to a population pharmacokinetic analysis. There is very limited data on the use of this medication in Patients with severe (ClCr: <30 mL/min) renal impairment. Therefore, It is not recommended in patients with moderate to severe renal insufficiency.
• Hepatic Function Impairment: No dosage adjustments is necessary in patients with mild hepatic function impairment. There is no data for this medication in subjects with moderate and severe hepatic impairment. Lorbrexen 100 mg is therefore contraindicated in patients with moderate and severe hepatic impairment.
• Paediatric population Safety and efficacy of the medication in children aged below 18 have not been established. No data are available.

Overdose Management

Contact your medical provider immediately if there is an overdose of Lorbrexen 100mg (Lorlatinib). Provided that there is no particular antidote available, care should be supportive and aligned with the symptoms presented by the patient. As given, all other cases have to be monitored as to their vital signs, cardiac vital activity on top of their neurological condition. If the overdose is recent and clinically appropriate, activated charcoal may be used for gastric decontamination. As with all medications, it should be kept out of reach of children for the purpose of preventing accidental or deliberate overdose, stored securely, and be used according to the prescription issued.

Storage Guidelines

Store below 30°C (86°F) in a dry place, away from moisture and direct sunlight.

Keep the tablets in their original packaging to protect them from light and humidity.

Do not refrigerate or freeze this medication.

Keep out of reach of children and pets.

Do not use Lorbrexen 100 mg after the expiry date mentioned on the pack.

Dispose of unused or expired medication properly, as per local regulations or your pharmacist’s advice.

About the Manufacturer – Everest Pharmaceuticals

Everest Pharmaceuticals Ltd. is a reputable Bangladeshi company known for producing high-quality generic medicines. As the manufacturer of Lorbrexen 100 mg, Everest follows international standards to ensure safety, efficacy, and affordability, making advanced cancer treatments more accessible worldwide.

Supplied by Onus Pharma – Global Access, Local Care

Lorbrexen 100 mg is proudly supplied by Onus Pharma, a trusted name in providing access to high-quality oncology medications worldwide. Guided by our motto – Global Access, Local Care – we ensure timely delivery and personalized support to meet the needs of patients and healthcare providers across the globe.

Benefits at a Glance

• Lorbrexen 100 mg (Lorlatinib) is an targeted medicine for the treatment of ALK-positive non-small cell lung cancer (NSCLC). It has a number of distinct advantages:
• Targeted Treatment: Uniquely formulated to suppress ALK and ROS1 gene mutations, working to slow or stop the growth of cancer cells.
• Works on resistant disease: Useful for patients who have had prior ALK inhibitors OR are intolerant to them.
• Brain Penetration: Demonstrates strong activity against brain metastases due to its ability to cross the blood-brain barrier.

• Oral Convenience: Taken as a once-daily oral tablet, improving ease of use and adherence.

• Improved Survival: Shown to prolong progression-free survival and improve response rates in clinical studies.

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