Imatinib Side Effects

Diagnosis and Management of Common Symptoms

Obligatory—This is not medical advice

Imatinib is the most commonly prescribed medication in my clinic. This medication has been approved now for 22 years and remains the standard of care for first-line treatment of multiple cancers, for which, prior to its creation, there was no treatment.¹ Although imatinib helps many patients live longer and feel better, it is not without its side effects. Most will experience at least one side effect. It is part of our duty as a medical oncologist to minimize the impact of our medications on the daily lives of our patients. With this in mind, let us review what can be done for a few of the more common toxicities.

Imatinib Molecular Structure. https://commons.wikimedia.org/wiki/File:Imatinib2DACS.svg

Fluid Retention and Edema

Edema is present in approximately 77% of patients. 9% of patients had severe edema, that is, grade 3 or higher. This can be as simple as swelling of the lower limbs that is mild and only noticeable by at trained healthcare professional. On the other hand, fluid retention can contribute to effusions, which can be life-threatening. While these are less common with imatinib, it should be recognized that they are possible complications of the medicine and prompt evaluation should ensue if there is clinical concern. For the sake of this post, we’ll focus more so on the lower grade adverse events patients experience and how to improve them. These can cause cumulative distress.

The management of edema varies and depends on its severity. For severe periorbital edema, treatment holds, and if it recurs, dose reduction may be considered after adequate discussion. Diuretics, or ‘water pills, ’ can be attempted, but their success is often limited. Compression stockings can be helpful in treating lower extremity swelling. I usually recommend that stockings with at least 20 mmHg pressure above the knee be applied daily. There are multiple brands.

Mild topical corticosteroids have been used to treat periorbital edema. Care must be taken to avoid exposing the mucous membranes or eyes to steroids.²

For each of the following, if very servere, there should be consideration of dose adjustment or drug holiday after ample review with an oncologist.

1. Lower extremity edema:

   1. Compression stockings (20 millimeters mercury (mmHg) or more

   2. Increased mobility

   3. Possible consideration of low dose diuretics under physician oversight

2. Periorbital edema:

   1. Cold eye compresses

   2. Careful application of weak topical corticosteroids (hydrocortisone)

   3. Low dose diuretics

   4. Referral to opthalmology

Myalgias (muscle cramps)

Myalgias are often referred to by patients as muscle cramps or spasms. They can be very painful and disruptive to sleep if they occur at night. Multiple supplements have been tried, and there are some theories as to the mechanism, but ultimately no strict guidelines for evaluation and management have been made. As with before, discuss the following with your oncologist prior to starting. Tonic water is frequently given and is actually in the NCCN guidelines. It is thought to function by giving a low amount of quinine.³ There is a possible biologic reason for why supplementation with calcium, magnesium, or other electrolytes can assist in this problem, as imatinib has been observed to alter bone and mineral metabolism.⁴

1. Myalgias

   1. Tonic water

      1. 50% Tonic water, 50% gatorade (or juice or pedialyte per preference)

      2. Consume after dinner, or approximately 2 hours prior to bed time

   2. Calcium and Magnesium Supplementation

      1. Calcium Carbonate 1 gram daily in 1-3 divided doses

      2. Magnesium Chloride (slowmag or magdelay)

   3. Stretching

   4. Exercise

   5. Appropriate sleep/rest

   6. Adequate hydration

Neutropenia (low absolute neutrophil count)

The immune system is complicated, but painting with a broad brush, having a lower neutrophil count can make patients susceptible to bacterial and fungal infections. This can be a very serious consequence of treatment, although most patients remain asymptomatic and do well.

The FDA label for imatinib requires frequent monitoring of white blood cell count after starting treatment. If neutropenia recurs, the dose is reduced at the time of reinitiation. Growth factors can also be used for this purpose. In most situations when I encounter neutropenia, it is mild and resolves with a temporary dose hold.

Neutropenia:

1. If the neutrophil count is less than 1000 per microliter, it is recommended to hold imatinib until ANC is greater than 1.5k/uL

   1. 1st time: resume at prior dose

   2. >=2nd occurrence: dose reduction

2. Growth factors can be considered, although this is only done in exceptional cases⁵

Final Thoughts

I usually counsel my patients that they will have at least one side effect from imatinib. We conquer these side effects by frequent reassessment, communication, and adjustment. There must be a consistent dialog with the oncologist. Most of my patients find their side effects to be very manageable, however, and continue to take imatinib with infrequent need for holds or reductions. Many sarcoma oncologists and hematologists will share that they have patients who have been on imatinib for decades.

1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021588s024lbl.pdf

2. https://ashpublications.org/blood/article/120/7/1390/30736/How-I-treat-newly-diagnosed-chronic-phase-CML

3. https://www.nccn.org/

4. https://www.nejm.org/doi/full/10.1056/NEJMoa051140

5. https://pubmed.ncbi.nlm.nih.gov/15197801/