Avastin® and Hypertension

I recently received this question:

My mother (age 76) recently had intraocular Avastin injection for wet ARMD in one eye About a week later, she had PDT followed by a steroid injection. The following day, she experienced severe HTN, requiring 2 days of hospitalization! I'm trying to find out how likely it was that the Avastin was the culprit.She did have pre-existing HTN, usually well-controlled except for during medical appts ("white coat HTN"). Sadly, no one at the ophth office took her BP before or after her injection!

The questions now are, "can she safely take Avastin in the future if her ARMD requires further treatment?" "Would switching to Lucentis be any safer, in respect to HTN?"She is mostly concerned about her eyesight. I'm more concerned about losing her to a stroke.

My response:

Hypertension is the main side-effect of Avastin® when it’s given for the treatment of colon cancer. For colon cancer the dose is 5milligrams (mg) per kilogram of weight. Someone who weighs 70 kilograms, (154 pounds), would get 350 mg intravenously. The intraocular dose for AMD is 1.25mg which is two hundred and eight times less than the intravenous dose. Doctors in Europe often inject 2.5 mg or twice the usual dose in the United States. Because the dose is so much less, we have thought it was very safe. Avastin has been given hundreds of thousands of times without reported side-effects but then doctors might not be anxious to publicize that they had a complication.

BUT- We know that Avastin injected into one eye can cause an effect in the other eye meaning that it must get into the bloodstream.1 We also know that Avastin and Lucentis can be detected in the bloodstream after either of them are injected into the eye. There have been recent concerns of an increased risk of stroke in a preliminary analysis of patients who received Lucentis®. (blog March 1, 2007)

Did the Avastin cause the high blood pressure in your mother? I don’t know but it is suspicious. We don’t know what her blood pressure was before the injection since it was never measured. Maybe it was already high and the Avastin tipped it over the edge. We also don’t know if the right amount of Avastin was injected into the eye. Could the pharmacy have diluted it incorrectly? It’s unlikely that the doctor injected too much because the increased volume would have caused elevated intraocular pressure and pain.

So what should you and she do now? I wouldn’t get another dose of Avastin. Lucentis may be a better option since its systemic half-life is much shorter. Of course Lucentis is smaller so more may get out of the eye in the first place and Lucentis binds VEGF more tightly than Avastin which may increase its systemic risk. Frankly I’m not too thrilled about Lucentis either.

I’m hoping that your mother doesn’t need any more treatment. She has received triple therapy with the Avastin, PDT, and steroid. Often only one round of this triple therapy is enough to cause resolution of the new blood vessels. If the vessels leak again, PDT with steroids alone may be a good option. PDT with steroids doesn’t have quite as good visual results as Avastin or Lucentis but they’re close. If your mother has already lost vision, the final results may not be different with PDT and steroids alone compared to combining them with Avastin or Lucentis. Plus she also has the other eye. My mentor, Dr. Robert C. Watzke, once said to me, “There are things worse than blindness.” He meant that I should weigh the risk of an operation to the chance of its success. I might tell your mother that, “There are things worse than losing maybe one more line of vision with a safe treatment.”

References:

1. Avery RL, Pearlman J, Pieramici, DJ, Castellarin AA, et al.” Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy.” Ophthalmology. 2006 Oct;113(10):1695.e1-15.