Lorviqua (Lorlatinib)

What Is Lorviqua and What Is It Used For?

Lorviqua (lorlatinib) is a targeted cancer medicine used to treat adults with advanced ALK-positive non-small cell lung cancer (NSCLC). It belongs to a class of drugs called ALK tyrosine kinase inhibitors and works by blocking the abnormal ALK protein that drives cancer cell growth.

Lorviqua contains the active substance lorlatinib, a potent third-generation inhibitor of the enzyme anaplastic lymphoma kinase (ALK). ALK is a type of tyrosine kinase, a protein that normally plays a role in cell signaling and growth. In some patients with non-small cell lung cancer, a chromosomal rearrangement creates an abnormal fusion of the ALK gene with another gene, producing a constitutively active ALK protein. This continuously active protein drives uncontrolled cell division and cancer growth. Lorviqua works by binding to and blocking this abnormal ALK protein, cutting off the signal that tells cancer cells to grow and divide.

Non-small cell lung cancer accounts for approximately 80–85% of all lung cancers worldwide, according to the World Health Organization. Among NSCLC patients, roughly 3–7% carry ALK gene rearrangements. These patients tend to be younger than the typical lung cancer population, are often non-smokers or light smokers, and typically present with adenocarcinoma histology. While ALK-positive NSCLC represents a relatively small subset of lung cancer, the availability of targeted ALK inhibitors has dramatically improved outcomes for these patients.

Lorviqua is classified as a third-generation ALK inhibitor. The development of ALK inhibitors has progressed through multiple generations: first-generation (crizotinib), second-generation (ceritinib, alectinib, brigatinib), and third-generation (lorlatinib). Each successive generation was designed to overcome resistance mutations that can develop during treatment with earlier-generation inhibitors and to improve penetration into the central nervous system (CNS).

Approved Indications

Lorviqua may be prescribed in the following clinical situations:

• First-line treatment: For adult patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor. The landmark CROWN study demonstrated significant improvements in progression-free survival compared to crizotinib in the first-line setting
• After alectinib or ceritinib: For patients whose cancer has progressed after treatment with alectinib or ceritinib as the first ALK-targeted therapy
• After crizotinib and another ALK inhibitor: For patients who were previously treated with crizotinib followed by at least one other ALK inhibitor and whose disease has progressed

How Lorviqua Works

Lorlatinib inhibits ALK through a highly selective mechanism. It binds to the ATP-binding site of the ALK kinase domain, preventing the enzyme from phosphorylating its downstream substrates. This blocks the intracellular signaling cascades that promote cancer cell survival, proliferation, and migration. Lorlatinib also inhibits ROS1, another tyrosine kinase that can drive certain cancers.

A critical advantage of lorlatinib is its ability to penetrate the blood-brain barrier. Brain metastases are a significant clinical challenge in ALK-positive NSCLC, occurring in approximately 20–40% of patients at initial diagnosis and up to 50–60% over the course of the disease. Earlier-generation ALK inhibitors have limited CNS penetration, which often leads to brain progression even when systemic disease is controlled. Lorlatinib was specifically designed with physicochemical properties that allow efficient crossing of the blood-brain barrier, resulting in meaningful concentrations in the cerebrospinal fluid.

In the pivotal CROWN study (NCT03052608), treatment-naive patients with advanced ALK-positive NSCLC who received lorlatinib demonstrated a hazard ratio of 0.27 for progression-free survival compared to crizotinib, indicating a 73% reduction in the risk of disease progression or death. Notably, the intracranial objective response rate in patients with measurable brain metastases was 82%, underscoring lorlatinib's exceptional CNS activity. Updated data from the CROWN study showed that at 5 years, 60% of patients in the lorlatinib group remained progression-free.

What Should You Know Before Taking Lorviqua?

Before starting Lorviqua, your doctor will assess your cholesterol levels, heart function, liver function, blood sugar, and mental health status. You must not take Lorviqua with certain medications including rifampicin, carbamazepine, phenytoin, enzalutamide, mitotane, or St. John's wort. Special precautions apply during pregnancy and breastfeeding.

Lorviqua is a powerful targeted therapy that requires careful patient assessment before and during treatment. Your healthcare team will conduct thorough baseline evaluations and ongoing monitoring to identify and manage potential complications. Understanding contraindications, warnings, and drug interactions is essential for safe and effective therapy.

Contraindications

You must not take Lorviqua if:

• You are allergic to lorlatinib or any of the other ingredients in the tablets (including lactose monohydrate, microcrystalline cellulose, calcium hydrogen phosphate, sodium starch glycolate, or magnesium stearate)
• You are taking any of the following medications, which are strong CYP3A inducers:
  • Rifampicin – used to treat tuberculosis
  • Carbamazepine or phenytoin – used to treat epilepsy
  • Enzalutamide – used to treat prostate cancer
  • Mitotane – used to treat adrenal gland cancer
  • St. John's wort (Hypericum perforatum) – an herbal remedy for depression

These medications dramatically reduce the blood levels of lorlatinib, potentially making the treatment ineffective. The combination is strictly prohibited, not merely cautioned against.

Warnings and Precautions

Talk to your doctor before taking Lorviqua if you have any of the following conditions or concerns:

• High cholesterol or triglycerides: Lorlatinib frequently causes significant elevations in blood lipids. Your doctor will check your fasting lipid panel before starting treatment and at regular intervals. Lipid-lowering medications (statins) may be needed during therapy
• Elevated pancreatic enzymes: If you have high levels of amylase or lipase, or a history of pancreatitis, close monitoring is required. Lorlatinib can further increase these enzyme levels
• Heart problems: If you have heart failure, slow heart rate (bradycardia), or if your electrocardiogram (ECG) shows prolonged PR interval or atrioventricular (AV) block, inform your doctor. Lorlatinib can cause or worsen these cardiac conduction abnormalities
• Lung disease: If you have cough, chest pain, shortness of breath, or a history of pneumonitis (non-infectious lung inflammation), tell your doctor. Lorlatinib can, in rare cases, cause interstitial lung disease
• High blood pressure: Lorlatinib may raise blood pressure. Regular monitoring and antihypertensive treatment may be necessary
• High blood sugar: Lorlatinib can increase blood glucose levels. Patients with diabetes or prediabetes require particularly careful monitoring

Pregnancy and Breastfeeding

Lorviqua can harm an unborn baby and must not be taken during pregnancy. Important fertility and contraception information includes:

• Women of childbearing potential: You must use highly effective non-hormonal contraception during treatment and for at least 5 weeks after the last dose. Lorlatinib may reduce the effectiveness of hormonal contraceptives (such as birth control pills), so hormonal methods alone are not considered sufficient. If a hormonal method is used, it must be combined with a barrier method (such as a condom)
• Male patients: You must use condoms during treatment and for at least 14 weeks after the last dose if there is any possibility of your partner becoming pregnant
• Breastfeeding: Do not breastfeed during treatment with Lorviqua and for at least 7 days after the last dose, as it is unknown whether lorlatinib passes into breast milk
• Fertility: Lorlatinib may impair male fertility. Discuss fertility preservation options with your doctor before starting treatment

Children and Adolescents

Lorviqua is not approved for use in children and adolescents under 18 years of age. Safety and efficacy have not been established in this population.

Driving and Operating Machinery

Use particular caution when driving or operating machinery during treatment with Lorviqua. Given its potential effects on the central nervous system, including cognitive changes, mood alterations, and speech difficulties, your ability to drive safely or operate complex equipment may be impaired. Discuss this with your doctor, especially if you experience any CNS side effects.

How Does Lorviqua Interact with Other Drugs?

Lorviqua has several important drug interactions. It must not be combined with strong CYP3A inducers. Strong CYP3A inhibitors can increase lorlatinib levels and may require dose adjustments. Additionally, lorlatinib itself is a moderate CYP3A inducer, which can reduce the effectiveness of other medications metabolized by this enzyme pathway.

Drug interactions are a critical consideration for patients taking Lorviqua. Lorlatinib is primarily metabolized by the liver enzymes CYP3A4 and UGT1A4. Medications that affect these enzymes can significantly alter lorlatinib blood levels, either reducing its effectiveness or increasing the risk of side effects. Furthermore, lorlatinib itself is a moderate inducer of CYP3A4, meaning it can accelerate the breakdown of other medications metabolized by this pathway.

Always tell your doctor, pharmacist, or nurse about all medications you are taking, including prescription drugs, over-the-counter medicines, herbal remedies, and supplements. This is essential for managing potential interactions safely.

Major Interactions (Contraindicated)

The following medications must never be taken with Lorviqua:

Important Interactions Requiring Caution

The following medications require careful monitoring or dose adjustments when taken with Lorviqua. Inform your doctor if you are taking any of these:

Food and Beverage Interactions

Do not consume grapefruit or grapefruit juice while taking Lorviqua. Grapefruit inhibits the CYP3A4 enzyme in the gut wall, which can increase the absorption and blood levels of lorlatinib, potentially leading to increased side effects. Other citrus fruits such as Seville oranges (bitter oranges) may have a similar effect and should also be avoided. Regular oranges, lemons, and limes are generally considered safe.

What Is the Correct Dosage of Lorviqua?

The recommended dose of Lorviqua is 100 mg taken orally once daily. Tablets should be swallowed whole, with or without food, at approximately the same time each day. Your doctor may adjust the dose based on side effects or tolerance.

Lorviqua should always be taken exactly as prescribed by your doctor. Do not change your dose or stop taking the medication without consulting your healthcare team. Consistent adherence to the prescribed schedule is important for maintaining therapeutic drug levels and maximizing treatment efficacy.

Adults

Your doctor may reduce the dose in steps if you experience significant side effects. The standard dose reduction levels are:

If a dose of 50 mg once daily is not tolerated, your doctor may decide to discontinue Lorviqua permanently.

Children

Lorviqua is not approved for use in children or adolescents under 18 years of age. The safety and effectiveness of lorlatinib in pediatric patients have not been established.

Elderly

No dose adjustment is required based on age alone. In clinical trials, patients over 65 years of age were included and received the same starting dose as younger adults. However, elderly patients may be more susceptible to certain side effects, particularly CNS effects and cardiac conduction abnormalities, and may require closer monitoring.

Missed Dose

If you miss a dose of Lorviqua, what to do depends on when you remember:

• If the next dose is 4 hours or more away: Take the missed dose as soon as you remember, then take the next dose at the usual time
• If the next dose is less than 4 hours away: Skip the missed dose entirely and take the next dose at the usual time
• Do not take a double dose to make up for a missed one

If You Vomit After Taking Lorviqua

If you vomit after taking a dose of Lorviqua, do not take an additional dose. Simply take your next scheduled dose at the usual time. Do not try to make up for the lost dose.

Overdose

If you accidentally take more Lorviqua than prescribed, contact your doctor, pharmacist, or emergency department immediately. You may require medical attention. Take the medicine packaging with you so the healthcare team knows exactly what was taken.

What Tests and Monitoring Are Required During Treatment?

During treatment with Lorviqua, your doctor will regularly monitor your blood lipids (cholesterol and triglycerides), pancreatic enzymes (amylase and lipase), liver function, blood glucose, blood pressure, and heart rhythm. Additional monitoring for CNS effects is also important.

Regular monitoring is essential throughout treatment with Lorviqua to detect and manage potential side effects early. Your healthcare team will establish a monitoring schedule tailored to your individual needs. Understanding what tests are required helps you stay engaged in your own care and report any concerns promptly.

Baseline Tests (Before Starting Treatment)

Before you begin Lorviqua, your doctor will typically order the following assessments:

• Fasting lipid panel: To measure baseline cholesterol and triglyceride levels
• Pancreatic enzymes: Amylase and lipase levels
• Liver function tests: Including ALT, AST, bilirubin, and alkaline phosphatase
• Fasting blood glucose or HbA1c: To assess blood sugar control
• Electrocardiogram (ECG): To evaluate heart rhythm and conduction intervals, particularly the PR interval
• Blood pressure measurement
• Complete blood count: To check for anemia and other blood cell abnormalities
• Cognitive and mood assessment: A baseline neurological and psychological evaluation

Ongoing Monitoring

During treatment, these tests are repeated at regular intervals, typically every 1–3 months or as clinically indicated. More frequent monitoring may be needed during dose adjustments or if abnormalities are detected. Always attend your scheduled blood tests and clinic appointments, even if you are feeling well.

What Are the Side Effects of Lorviqua?

Like all medicines, Lorviqua can cause side effects. The most common include elevated cholesterol and triglycerides, edema (swelling), vision problems, peripheral neuropathy, and CNS effects such as mood changes and cognitive difficulties. Some side effects are serious and require immediate medical attention.

Understanding the potential side effects of Lorviqua helps you recognize symptoms early and seek appropriate medical care. Not everyone will experience side effects, and many can be effectively managed with dose adjustments or supportive medications. Always discuss any new or worsening symptoms with your healthcare team.

Managing Common Side Effects

Many of the common side effects of Lorviqua can be effectively managed:

• High cholesterol/triglycerides: Often managed with statin medications or other lipid-lowering drugs. Dietary modifications may also help
• Edema: Leg elevation, compression stockings, and in some cases diuretics may be recommended
• Peripheral neuropathy: Report early symptoms to your doctor. Dose reduction may be necessary. Avoid alcohol and ensure adequate vitamin B12 intake
• High blood pressure: Antihypertensive medications may be started or adjusted as needed. Regular home blood pressure monitoring is helpful
• CNS effects: Report any mood, cognitive, or speech changes immediately. These are often dose-dependent and may improve with dose reduction

Reporting Side Effects

Reporting suspected side effects after a medicine has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report adverse reactions to their national regulatory authority (such as the EMA in Europe or the FDA in the United States).

How Should You Store Lorviqua?

Store Lorviqua at room temperature, in its original packaging, out of the reach of children. No special storage temperature is required. Do not use the medicine after the expiry date printed on the packaging.

Proper storage helps ensure that Lorviqua remains safe and effective throughout its shelf life. Follow these storage guidelines carefully:

• Keep out of sight and reach of children at all times
• No special storage conditions are required – store at room temperature
• Check the expiry date printed on the blister pack and carton after "EXP." The expiry date refers to the last day of the stated month. Do not use the medicine after this date
• Keep in original packaging – do not remove tablets from blister packs until you are ready to take them
• Do not use if the packaging appears damaged or tampered with
• Disposal: Do not dispose of medicines in wastewater or household waste. Return unused medications to your pharmacy for safe disposal. This helps protect the environment

What Does Lorviqua Contain?

The active ingredient is lorlatinib. Lorviqua is available as 25 mg (light pink, round) and 100 mg (dark pink, oval) film-coated tablets manufactured by Pfizer.

Each Lorviqua tablet contains the following components:

Active Substance

• Lorviqua 25 mg tablets: Each film-coated tablet contains 25 mg of lorlatinib
• Lorviqua 100 mg tablets: Each film-coated tablet contains 100 mg of lorlatinib

Other Ingredients

• Tablet core: Microcrystalline cellulose, calcium hydrogen phosphate, sodium starch glycolate, magnesium stearate
• Film coating: Hypromellose, lactose monohydrate, macrogol, triacetin, titanium dioxide (E171), black iron oxide (E172), and red iron oxide (E172)

Appearance and Pack Sizes

• 25 mg tablets: Round, light pink film-coated tablets with "Pfizer" on one side and "25" and "LLN" on the other. Packaged in blisters of 10 tablets, in packs of 90 tablets (9 blisters)
• 100 mg tablets: Oval, dark pink film-coated tablets with "Pfizer" on one side and "LLN 100" on the other. Packaged in blisters of 10 tablets, in packs of 30 tablets (3 blisters)

Not all pack sizes may be marketed in your country. The marketing authorization holder is Pfizer Europe MA EEIG, Brussels, Belgium. The manufacturer is Pfizer Manufacturing Deutschland GmbH, Freiburg im Breisgau, Germany.

Frequently Asked Questions About Lorviqua