What to Know About Imbruvica (Ibrutinib)

Imbruvica (ibrutinib) is a tyrosine kinase inhibitor that inhibits the growth and survival of malignant B-lymphocytes (B-cells) and has been FDA-approved for the treatment of marginal zone lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma. It’s also prescribed for a complication following stem cell transplant called chronic graft-versus-host disease, in which the donated cells attack the recipient’s body.

Part of a class of drugs called kinase inhibitors, Imbruvica suppresses immune function by disrupting cellular signaling. This drug, generically known as ibrutinib, is taken as a pill.

Uses

Primarily, Imbruvica is indicated for the following several conditions.

• Mantle cell lymphoma (MCL): MCL, a rare form of non-Hodgkin lymphoma, is a cancer that occurs when B-cells, which are part of the immune system, become malignant. Imbruvica is only indicated after another initial treatment has been attempted.
• Chronic lymphocytic leukemia (CLL): Another blood cancer that arises due to mutations of B-cells, CLL arises gradually and tends to impact older patients.
• Chronic lymphocytic leukemia with 17p deletion: This is an aggressive form of CLL. It’s seen in less than 10% of those diagnosed with CLL. Imbruvica may be prescribed for adults with this condition.
• Waldenström’s macroglobulinemia (WM): This is another form of non-Hodgkin lymphoma that develops from cells located in the bone marrow and can severely hinder immune function.
• Marginal zone lymphoma (MZL): For patients with MZL, another form of non-Hodgkin lymphoma, Imbruvica will be indicated if at least one prior treatment has not yielded the desired results. 
• Chronic graft-versus-host disease: As noted above, this is a complication following transplantation of bone marrow or stem cells, in which the donor’s immune cells attack the host’s tissues. Estimates vary, but this disease is seen in anywhere from 30% to 70% of cases.

Before Taking

As with any prescribed medication, it’s important to understand as much as possible about Imbruvica before taking it. Your healthcare provider and pharmacist will provide you with important information about your prescription. As you start taking this drug, be mindful of how you’re feeling and don’t hesitate to seek help if anything seems awry.  

Precautions and Contraindications

The good news is that there are no contraindications listed for Imbruvica, meaning there are no medical conditions that would prohibit the use of this medication. That said, taking some other drugs may affect how well Imbruvica (see below). Notably, for MCL and MZL, this drug is only prescribed after other treatments have initially been attempted.

As with any prescribed drug, Imbruvica may not be safe to take under certain conditions, including:

• Pregnancy—Taking this drug during pregnancy may potentially harm the developing fetus. This has been observed in animal studies that found high doses of Imbruvica to lead to birth defects. While exact risk has not been established in humans, if you’re expecting, you and your healthcare provider will need to carefully weigh the pros and cons of this therapy.
• Breastfeeding—While the presence of this drug in breast milk has not been established, it’s recommended that you not breastfeed while taking Imbruvica.
• Heart disease—Cardiac events have occurred, particularly in patients with cardiac risk factors, hypertension, acute infections, or with a history of irregular heartbeats. People taking Imbruvica must be monitored periodically for clinical symptoms of irregular heartbeats (e.g., palpitations, light-headedness, syncope, chest pain). An ECG should be performed if symptoms or new-onset dyspnea (serious shortness of breath) develop.
• Pediatric—The health and safety of this drug have not been established for children. Use in this population is not recommended.
• Liver problems—Given the liver’s essential role in cleansing and detoxifying blood, people who have severe liver problems, such as cirrhosis or liver failure, should not be prescribed this drug. Imbruvica should be given at a lower dose for those with mild or moderate liver problems.

It’s essential that you provide as much information as you can about your health status to your healthcare provider.

Other Kinase Inhibitors

Imbruvica is one of a class of drugs called kinase inhibitors. These work by hindering the production of kinase, a protein associated with cancer development and immune reaction.

There are quite a few kinase inhibitors, which are grouped according to their specific mechanism of action. Most notable are type I kinase inhibitors, which function by binding to active forms of kinase, and type II (of which Imbruvica is the first discovered compound), which functions on inactive kinase.

There are a number of kinase inhibitors that may be indicated for cancer treatment. Besides Imbruvica, these include:

• Bosulif (bosutinib)
• Iressa (gefitinib)
• Jakafi (ruxolitinib)
• Sprycel (dasatinib)
• Sutent (sunitinib)
• Tarceva (erlotinib)
• Tykerb (lapatinib)
• Votrient (pazopanib)
• Xalkori (crizotinib)
• Zelboraf (vemurafenib)

Dosage

Your healthcare provider will give you exact instructions regarding how much of this medication should be taken and when. That said, there are general guidelines for use, and these vary significantly based on condition.

• MCL: One dose of 560 milligrams (mg) should be taken once a day until symptoms decrease (or until side effects and toxicity are unbearable).
• CLL and WM: For these conditions, 420 mg once a day is indicated. Sometimes, Imbruvica is combined with other drugs, such as bendamustine, rituximab, or others, to increase efficacy.
• Chronic graft versus host disease: It’s recommended that 420 mg be taken daily for this condition until symptoms have subsided (or until toxicity and side effects become too difficult).

All listed dosages are according to the drug manufacturer and may need to be adjusted for your case. Check your prescription and talk to your healthcare provider to make sure you are taking the right dose for you.

It’s important to note that Imbruvica comes in multiple strengths, from a 70-mg capsule marked "ibr 70" to a 560-mg oblong tablet marked "ibr" on one side and "560" on the other.

How to Take and Store

While your healthcare provider may make some modifications based on your case, typically, Imbruvica should be taken with a glass of water at about the same time every day. If you miss a dose, don’t panic; just take one on the same day as soon as you remember, and then return to your normal schedule.

Should you miss a day, do not attempt to double up or make up for the missing dose. In addition, avoid eating grapefruit (or drinking grapefruit juice) and Seville oranges, since these can interact with this drug and boost its levels in the bloodstream. 

There is no specific protocol for overdosage of Imbruvica, though if you take too much, let your healthcare provider know as they will want to monitor your health. A case has been reported where an excessive dose of 1,680 mg—well over the prescribed daily amount—led to liver problems. Constant monitoring of health while taking this drug is essential.

When it comes to storage of this drug, it’s recommended that you keep your pills at room temperature (68 F to 77 F, or 20 C to 25 C). Be sure, too, that you keep these drugs in a safe place and away from children.

Side Effects

Consistent monitoring is essential for every prescription to succeed. If you’re taking this medication, be sure to let your healthcare provider know if you’re feeling unwell. Stay safe: if you’re feeling severe side effects, seek immediate medical attention.

Common

As with any pharmaceutical drug, use of Imbruvica can lead to a range of side effects. Most commonly, these include:

• Diarrhea
• Tiredness
• Muscle and bone pain
• Rash
• Bruising
• Mouth sores (stomatitis)
• Muscle spasms
• Nausea
• Pneumonia

Severe

In rarer cases, more severe side effects crop up. They include the following.

Hemorrhage

Though relatively rare, severe bleeding events—occurring in up to 6% of cases—have been reported with administration of this drug. Notably, use has been tied to intracranial hemorrhage (bleeding in the brain), gastrointestinal bleeding, blood in the urine (hematuria), and post-operative hemorrhage (excessive bleeding during and after surgery).

Less severe bleeding cases occur in 39% those who take Imbruvica and are characterized by the presence of red welts or dots on the skin (petechiae) or easier bruising.

Infection

Use of this drug has also been tied to certain viral, fungal, or bacterial infections in 21% of patients.

Among these, progressive multifocal leukoencephalopathy, a viral infection that attacks the brain’s white matter, is particularly concerning. In addition, a severe, fungal lung infection called Pneumocystis jirovecii pneumonia may also arise.

Cytopenias

Cytopenia is a term for when one or more of your blood cell types are lower than they should be. Of particular concern are reduced white blood cell levels, as with neutropenia or anemia, in which the body doesn’t get enough oxygen due to a lack of healthy red blood cells.  

Atrial Fibrillation

Taking Imbruvica raises the risk of irregular heart beats in conditions such as atrial fibrillation and atrial flutter. This is especially a risk in cases where patients have had previous heart problems, high blood pressure, or those with a history of this condition.

Hypertension

High blood pressure occurs in about 19% of Imbruvica users. Other medications may be needed to help manage this.

Second Primary Malignancies

Some other diseases and cancers can occur as you’re taking this drug. These issues occur in an estimated 10% of cases, with non-melanoma skin cancer being the most common of these.

Tumor Lysis Syndrome

A rarer condition seen in those who take Imbruvica is tumor lysis syndrome, in which tumors release their cells into the bloodstream, leading to a number of symptoms, including nausea, muscle cramping, vomiting, diarrhea, and fatigue, among others.

Embryo-Fetal Toxicity

Research on animals has unearthed the potential for Imbruvica to cause harm to a developing fetus. Healthcare providers carefully assess the relative advantages and risks of taking this drug during pregnancy and will let you know of any risks.

Warnings and Interactions

Largely, Imbruvica is able to coexist with other drugs and substances. That said, when prescribed alongside a class of drugs called CYP3A inhibitors, dosages may need to be reduced. This includes a number of prescribed medications, such as:

• Clarithromycin (e.g., Biaxin)
• Diltiazem (e.g., Cardizem, Tiazac)
• Erythromycin (e.g., Erythrocin)
• Ritonavir (e.g., Norvir)
• Itraconazole (e.g., Sporanox, Tolsura)
• Verapamil (e.g., Verelan, Calan SR)
• Ketoconazole (e.g., Xolegel, Extina)
• Voriconazole (e.g., Vfend)
• Posaconazole (e.g., Noxafil)

In addition, some other medications, foods, herbs, and supplements have been found to influence CYP3A inhibition, which may influence the function of Imbruvica. These include:

• Goldenseal
• Phenobarbital
• Phenytoin (e.g., Phenytek, Dilantin)
• Rifampin (e.g., Rifadin)
• St. John’s wort

It’s always important to tell your healthcare provider about all the medications, supplements, and vitamins you’re currently taking. While some of these pose only minor interaction risks, others may be contraindicated for use. You and your healthcare provider will need to carefully weigh the pros and cons of treatment and any additional therapies in your case.