Brukinsa

Brukinsa (zanubrutinib) is a targeted cancer medicine used to treat several types of blood cancer in adults, including mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL). It comes as a capsule or tablet taken by mouth once or twice a day.

Brukinsa belongs to a group of medicines called BTK inhibitors. It works by blocking an enzyme called Bruton's tyrosine kinase (BTK), which the abnormal white blood cells (B cells) behind these cancers need to grow and survive. Blocking BTK slows the growth and spread of these cancer cells.

Brukinsa first received FDA approval on November 14, 2019. It was designed to block BTK more selectively than some older BTK inhibitors, which is intended to reduce effects on other parts of the body. There is no generic version of Brukinsa available.

Brukinsa is FDA-approved to treat the following blood cancers in adults:

• Mantle cell lymphoma (MCL) in people who have had at least one prior treatment. This use was granted accelerated approval based on response rate, and continued approval may depend on confirming the benefit in further trials.
• Waldenstrom's macroglobulinemia (WM).
• Relapsed or refractory marginal zone lymphoma (MZL) in people who have had at least one anti-CD20-based treatment. This use was granted accelerated approval based on response rate, and continued approval may depend on confirming the benefit in further trials.
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more prior lines of treatment. This use was granted accelerated approval based on response rate and durability of response, and continued approval may depend on confirming the benefit in further trials.

It is not known whether Brukinsa is safe and effective in children.

Take Brukinsa exactly as directed. Do not change your dose or stop taking it unless your provider tells you to. Your provider may lower your dose, pause treatment, or stop it if certain side effects develop.

• Take Brukinsa with or without food.
• Swallow capsules whole with a glass of water. Do not open, break, or chew capsules.
• Swallow tablets whole with water. Do not chew or crush them. Tablets can be split in half only if your provider tells you to.
• If you miss a dose, take it as soon as you remember on the same day, then return to your normal schedule the next day. Do not take two doses in one day.

Brukinsa has no contraindications listed in its FDA label, but it is not right for everyone. Before you start, tell your healthcare provider about all your medical conditions, including if you:

• Have bleeding problems
• Have had recent surgery or plan to have surgery or a dental procedure (your provider may pause Brukinsa around the procedure)
• Have an infection or are at increased risk of infection
• Have or have had heart rhythm problems
• Have high blood pressure
• Have liver problems, including a history of hepatitis B infection
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed

Tell your provider about all the medicines you take, since some can raise or lower Brukinsa levels.

Pregnancy

Brukinsa can harm an unborn baby. If you can become pregnant, your provider may do a pregnancy test before you start. Do not become pregnant during treatment, and use effective birth control during treatment and for at least 1 week after the last dose. Men with partners who can become pregnant should also use effective birth control during treatment and for at least 1 week after the last dose.

Breastfeeding

It is not known if Brukinsa passes into breast milk. Because of the risk of serious side effects in a breastfed baby, do not breastfeed during treatment and for 2 weeks after your last dose.

Common side effects

The most common side effects of Brukinsa, including laboratory abnormalities seen in 30% or more of people, are:

• Low neutrophil count (a type of white blood cell)
• Low platelet count
• Upper respiratory tract infection, such as a cold
• Bleeding or bruising (hemorrhage)
• Muscle, bone, or joint pain (musculoskeletal pain)

Serious side effects and warnings

Get emergency medical help if you have signs of an allergic reaction to Brukinsa, such as hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Brukinsa may cause serious side effects, including:

• Bleeding problems (hemorrhage). Bleeding is common and can be serious or life-threatening. The risk may be higher if you also take a blood thinner. Tell your provider about signs of bleeding, such as black or tarry stools, pink or brown urine, coughing or vomiting blood (or material that looks like coffee grounds), severe or uncontrolled bleeding, increased bruising, dizziness, weakness, confusion, a change in speech, or a long-lasting headache.
• Infections. Serious and sometimes fatal infections can occur. Tell your provider right away if you have a fever, chills, or flu-like symptoms.
• Low blood cell counts. Brukinsa can lower white blood cells, platelets, and red blood cells. Your provider will do blood tests during treatment.
• Second primary cancers. New cancers, including skin cancers, have happened during treatment. Use sun protection outdoors, and your provider will check you for new cancers.
• Heart rhythm problems. Serious and sometimes fatal irregular heartbeats (such as atrial fibrillation, atrial flutter, and ventricular arrhythmias) can occur. Tell your provider if you have a fast or irregular heartbeat, lightheadedness, fainting, shortness of breath, or chest discomfort.
• Liver problems. Serious, sometimes life-threatening liver injury can occur. Your provider will check your liver with blood tests before and during treatment. Get help right away for stomach pain, dark urine, or yellowing of the skin or eyes.

Brukinsa may harm an unborn baby. This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

In these blood cancers, abnormal B cells (a type of white blood cell) multiply out of control. These cells rely on an enzyme called Bruton's tyrosine kinase (BTK) to receive the signals that keep them growing and alive. Zanubrutinib attaches to BTK and blocks it, which interrupts those signals and helps slow the growth and spread of the cancer cells. Because Brukinsa was designed to bind BTK more precisely, it is intended to have fewer effects on other enzymes in the body, though side effects can still occur.

Brukinsa's approvals are based on clinical trials that measured how many people had their cancer shrink or disappear (the overall response rate) and how long those responses lasted. In chronic lymphocytic leukemia, Brukinsa has also been compared directly with an older BTK inhibitor.

• In ALPINE, a head-to-head trial in adults with relapsed or refractory CLL/SLL, Brukinsa produced a response in about 80% of people, compared with about 73% for ibrutinib (Imbruvica). People taking Brukinsa also went longer without their cancer worsening (longer progression-free survival).
• For mantle cell lymphoma, marginal zone lymphoma, and follicular lymphoma, Brukinsa was approved under the FDA's accelerated approval pathway based on response rates. These approvals may be continued only if later trials confirm the clinical benefit.

How well Brukinsa works depends on the specific cancer, previous treatments, and individual factors. Your cancer care team can explain what the results mean for your situation.

Usual adult dose for MCL, WM, MZL, CLL, SLL, and FL: 160 mg by mouth twice daily, or 320 mg by mouth once daily, with or without food, until the disease progresses or side effects become unacceptable.

Severe liver disease: the dose is reduced to 80 mg twice daily. No change is needed for mild or moderate liver impairment.

Drug interaction adjustments: the dose is reduced to 80 mg once daily with a strong CYP3A inhibitor, or 80 mg twice daily with a moderate CYP3A inhibitor. Strong and moderate CYP3A inducers should be avoided; if a moderate inducer cannot be avoided, the dose is increased to 320 mg twice daily.

What happens if I miss a dose?

Take the missed dose on the same day you remember it, then take your next dose at the regular time. Do not take two doses in one day.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Brukinsa is broken down by a liver enzyme called CYP3A, so medicines and foods that affect this enzyme can change your Brukinsa levels and the risk of side effects. Tell your provider about all medicines you take, especially:

• Moderate to strong CYP3A inhibitors, such as clarithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, ritonavir, erythromycin, verapamil, or grapefruit juice. Your Brukinsa dose may need to be lowered.
• Moderate to strong CYP3A inducers, such as rifampin, carbamazepine, phenobarbital, phenytoin, and certain glucocorticoids. These should generally be avoided.

Tell your provider about all prescription and over-the-counter medicines, vitamins, and herbal supplements you take. This list is not complete, and other drugs may interact with zanubrutinib.

Store Brukinsa in its original container at room temperature, 68°F to 77°F (20°C to 25°C). Brief exposure to temperatures between 59°F and 86°F (15°C and 30°C) is allowed. Keep this and all medicines out of the reach of children.

Active ingredient: zanubrutinib.

Inactive ingredients (capsule): silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, gelatin, titanium dioxide, and ferrosoferric oxide.

Inactive ingredients (tablet): colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate. The film coating contains FD&C Blue No. 1, FD&C Blue No. 2, hypromellose, titanium dioxide, and triacetin.

Available as 80 mg capsules and 160 mg tablets.