Zepzelca

Zepzelca is used to treat small-cell lung cancer (SCLC) in adults as maintenance therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage disease that has not progressed. It is administered as an intravenous infusion every 21 days.

Zepzelca (lurbinectedin) gained FDA approval on June 15, 2020. There is no generic.

Zepzelca is FDA-approved for:

• Extensive-stage SCLC as maintenance treatment in adults whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin, and etoposide. Used in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs.

Zepzelca is given by an intravenous (IV) infusion into a vein over 60 minutes.

• Zepzelca is usually given every 21 days.
• Before each treatment, you may receive medicines to help prevent nausea and vomiting or make it less severe.

Your healthcare provider will decide how long you will continue treatment.

Your healthcare provider may do certain tests during your treatment to check you for side effects and to see how well you respond to the treatment.

Before receiving Zepzelca, tell your healthcare provider about all of your medical conditions, including if you:

• have liver or kidney problems
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

For females who can become pregnant, Zepzelca can harm your unborn baby.

• Your healthcare provider should do a pregnancy test before you start treatment.
• You should use effective birth control (contraception) during treatment with and for 7 months after your last dose.
• Tell your healthcare provider right away if you become pregnant or think that you are pregnant during treatment.

Males with female partners who can become pregnant should use effective birth control during treatment with and for 4 months after their last dose.

Breastfeeding

It is not known if Zepzelca passes into your breastmilk. Do not breastfeed during treatment, and for 2 weeks after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment.

Common Side Effects

The most common side effects of Zepzelca when given alone are:

• Tiredness
• Low white and red blood cell counts
• Increased kidney function blood test (creatinine)
• Increased liver function blood tests
• Increased blood sugar (glucose)
• Nausea
• Decreased appetite
• Muscle and joint (musculoskeletal) pain
• Low level of albumin in the blood
• Constipation
• Trouble breathing
• Low levels of sodium and magnesium in the blood
• Vomiting
• Cough
• Diarrhea.

The most common side effects of Zepzelca when given with atezolizumab are:

• Low white and red blood cell counts
• Nausea
• Tiredness or weakness
• Increased liver enzymes in the blood
• Low levels of sodium and calcium in the blood
• Increased kidney function blood test (creatinine)
• Muscle and joint (musculoskeletal) pain
• Decreased appetite
• Diarrhea.

Serious Side Effects and Warnings

Zepzelca can cause the following serious side effects.

Low Blood Cell Counts

Low blood counts, including low neutrophil counts (neutropenia) and low platelet counts (thrombocytopenia), are common with Zepzelca and can also be severe. Some people with low white blood cell counts may get a fever or an infection throughout their body (sepsis), which can cause death. Your healthcare provider should do blood tests before you receive each treatment to check your blood cell counts. Tell your healthcare provider right away if you develop:

• Fever or any other signs of infection
• Unusual bruising or bleeding
• Tiredness
• Pale colored skin.

Liver problems

Increased liver function tests are common with Zepzelca, and can also be severe. Your healthcare provider should do blood tests to check your liver function before you start and during treatment. Tell your healthcare provider right away if you develop symptoms of liver problems, including:

• Loss of appetite
• Nausea or vomiting
• Pain on the right side of your stomach area (abdomen).

Skin Damage at or Near The Infusion Site

Zepzelca can cause damage and death of tissue cells if it leaks into the tissues around your infusion site. You may need to have surgery to remove any dead tissue. Tell your healthcare provider right away if you see any fluid leaking at or around the catheter during your infusion, or if you notice any redness, swelling, itching, or discomfort at the infusion site at any time.

Severe Muscle Problems (Rhabdomyolysis)

Treatment with Zepzelca may increase the level of an enzyme in your blood called creatine phosphokinase (CPK). Your healthcare provider should do blood tests to check your CPK levels before you start and during treatmentwith Zepzelca. Tell your healthcare provider if you have severe muscle pain or weakness.

Notes:

Your healthcare provider may temporarily stop treatment, lower your dose, or permanently stop Zepzelca if you develop low blood cell counts or liver problems during treatment.

These are not all of the possible side effects of Zepzelca. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Zepzelca (lurbinectedin) works by binding to specific parts of cancer cell DNA, causing the DNA structure to bend and become damaged. This damage triggers a chain reaction that disrupts how the DNA functions, interfering with cell processes like growth and repair. Eventually, these disruptions cause the cancer cells to die.

Additionally, Zepzelca affects certain immune cells called macrophages that can support tumor growth, helping to reduce their presence in tumors.

Zepzelca (lurbinectedin) belongs to the drug class called alkylating agents. Lurbinectedin is an analog of the marine compound ET-736 isolated from the sea squirt Ecteinacidia turbinata.

Dose of Zepzelca for SCLC

• 3.2 mg/m2 intravenously every 21 days.
• Continue until disease progression or unacceptable toxicity occurs.

Avoid eating or drinking grapefruit, Seville oranges, or products that contain grapefruit juice andSeville oranges during treatment with Zepzelca.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain other medicines may affect how Zepzelca works. Especially tell your healthcare provider if you take:

• Strong or moderate CYP3A inhibitors such as ketoconazole, itraconazole, ritonavir, cobicistat, clarithromycin, or grapefruit juice
• Strong CYP3A inducers, such as rifampin, phenytoin, carbamazepine, or St. John's Wort.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Active ingredient: lurbinectedinInactive ingredients: sucrose, lactic acid, and sodium hydroxide.

Supplied as a 4 mg lyophilized powder in a single-dose vial.

Zepzelca is distributed by Jazz Pharmaceuticals, Inc, under license from PharmaMar, S.A.