Avastin Archives - Retina Specialist | Fairfax, Virginia

Avastin is Safe | Study Shows No Link to Infection

Avastin is Safe As reported this week in Jama Ophthalmology , the chance of contracting endophthalmitis from Avastin is no different than with the case of Lucentis.

Both are equally safe.

Several outbreaks of endophthalmitis (infection inside the eye) have occurred over the past few years questioning the safety of Avastin vs. the practices of compounding pharmacies.

What are Compounding Pharmacies?

A compounding pharmacy is NOT Walgreen’s, CVS or Rite Aid.

Compounding pharmacies can make, or “compound.” individualized specialty medications. In the case of Avastin, a compounding pharmacy will purchase large amounts of Avastin and divide them into smaller doses for use by retina specialists.

Both a compounding pharmacy and a pharmaceutical company are responsible for packaging and distributing drugs using approved sterile techniques.

Avastin is Repackaged

Avastin is only supplied in massive doses from the manufacturer. As Avastin is an FDA approved anti-VEGF treatment for certain types of cancer, it is distributed only for chemotherapy treatments. Genentech, the manufacturer, does not sell the smaller doses used for intravitreal injections (IVT).

Compounding pharmacies purchase the Avastin and re-package the drug in smaller doses for sale to the ophthalmologists.

Lucentis is Directly Shipped

In contrast, Lucentis is sold directly from Genentech to the practicing retina specialist. As Lucentis is FDA approved for eye treatments, the Lucentis is manufactured, packaged and shipped directly to the ophthalmologist.

In 2011, an outbreak of endophthalmitis caused concern over the practices of compounding pharmacies. Similar suspicions developed in 2012 over an outbreak of fungal meningitis – caused by contaminated steroid injections, but processed at a compounding pharmacy.

In 2013, the FDA released the Compounding Quality Act offering guidelines to reduce the chance of endophthalmitis.

Study Shows Avastin is Safe

The retrospective study just published in Jama Ophthalmology compared the rates of endophthalmitis between Avastin and Lucentis from 2005 to 2012, in essence, studying the two drugs BEFORE the Compounding Quality Act was created.

The authors found that there was no statistical differences in the rates of infection! In other words, Avastin itself, does not cause infection.

What Does this Mean?

Historically, the threat of blinding infection (endophthalmitis) is the biggest concern with administering intravitreal injections (IVT). It doesn’t matter if we are injecting Avastin, Lucentis, Ozurdex, etc.

In 2011, 12 cases of endophthalmitis were reported to have occurred in Florida. Though all the injections emanated from the same compounding pharmacy, it questioned whether it was the Avastin versus the pharmacy itself.

Similar concerns were noted in cases of endophthalmitis from a compounding pharmacy in Tennessee. Finally, an outbreak of meningitis, causing many fatalities, was linked to contamination from a single compounding pharmacy.

This study should alleviate concerns over use of Avastin causing blindness from endophthalmitis. Concerns over the cause of endophthalmitis are limited to the practices of the compounding pharmacies and not to the actual drugs.

Patients should find relief as Avastin continues to provide excellent treatment results from diseases such as macular degeneration and diabetic retinopathy.

Diabetic Macular Edema Treated with Ozurdex, Randall Wong, M.D., Retina Specialist, Fairfax, Virginia 22031

Ozurdex Improves Vision in Diabetic Patient | Treatment for DME

Ozurdex to treat diabetic macular edema improved my patient’s vision in just 3 months! AB first came to my office in November 2014. He was complaining of blurry vision (in fact, he was legally blind).

AB was diagnosed with Type 1 (Insulin Dependent Diabetes Mellitus) 8 years ago. He did not have regular eye exams.

Legally Blind

His vision in both eyes, with correction, was 20/400 at his initial visit with me in November (2014). He had significant diabetic macular edema (also known as DME or CSME) causing the loss of vision. He barely has cataracts.

Standard fluorescein angiography was performed. The OCT’s from November are included below.

Treatment for Diabetic Macular Edema

I felt it best to treat him with a combination of Avastin and then Ozurdex. Intraocular injections of Avastin were given to each eye followed by Ozurdex two weeks later.

Before Treatment with Ozurdex

Diabetic Macular Edema Improved with Ozurdex, Randall Wong, M.D., Retina Specialist, Fairfax, Virginia 22031

Right

Left

After Treatment with Ozurdex

Right

Diabetic Macular Edema After Ozurdex, Randall Wong, M.D., Retina Specialist, Fairfax, Virginia 22030

Left

What Does This Mean?

This is a remarkable case where there has been significant and rapid restoration of vision. This case also reminds me of the many options we now have for treating diabetic macular edema….not just laser.

In this case, I preferred a combination of Avastin and Ozurdex because of the significant amount of macular edema and the dramatic loss of vision of both eyes.

I am pleasantly surprised by both the rapidity of improvement and the amount of vision improvement!

The Avastin may or may not be needed, but in my experience starts the improvement faster. The Ozurdex will continue to treat the macular edema for up to four months. This has the potential of reducing the number of office visits to a minimum.

The diabetic macular edema could return at any time. I’ll need to monitor AB for any signs of recurrence. If the swelling does recur, he may need additional injections.

Eylea Best for Diabetic Macular Edema | Treatment for DME

Eylea Best for Diabetic Macular Edema, Randall Wong, M.D. Retina Speciailst, Northern Virginia, 22030 Eylea, Lucentis and Avastin were compared head to head for the treatment of diabetic macular edema. For certain patients with this common complication of diabetic retinopathy, Eylea was superior.

Common Complication of Diabetic Retinopathy

The common complication of diabetic retinopathy is diabetic macular edema (aka DME, CSME). The normal blood vessels of the retina leak blood and fluid into the retinal tissue. When the fluid accumulates in the macula (the functional center of the retina), vision decreases.

Treatment for diabetic macular edema includes laser treatment, intraocular steroid injections, Ozurdex and the use of anti-VEGF drugs.

Anti-VEGF drugs include: Eylea (aflibercept), Lucentis (ranibizumab) and Avastin (bevacizumab). Both Eylea and Lucentis are FDA approved for the treatment of DME, whereas all three are used routinely by retina specialists and are considered “standard of care.”

Protocol T | Comparative Study of Anti-VEGF Drugs

A study comparing the 3 drugs has never been completed. This NIH-funded study, called Protocol T, is the first to compare these similar treatments for diabetic macular edema.

The study involved 660 patients randomized to receive one of the three drugs. The study lasted one year with the results published recently in the New England Journal of Medicine.

Results of “Protocol T”

The results indicate that all 3 anti-VEGF medications are effective treatments for DME. Those patients with moderate or worse vision treated with Eylea, however, improved more than similar patients treated with Lucentis or Avastin.

Moderate vision loss was defined as 20/50 or worse.

To restate the findings; patients with 20/50 vision or worse had better vision improvement if given Eylea.

For patients with less severe vision loss, the 3 drugs seem to be equally effective.

What Does This Mean?

It is estimated that 75% of the patients receiving treatment for DME have vision better than 20/50. This comparison indicates the 3 are equally effective.

I personally prefer Avastin over the other two drugs, because, until now, there was no evidence any particular drug was better, but Avastin is significantly cheaper.

We purchase Avastin for about $50 per injection. Eylea may cost about $1950 and Lucentis $1200.

We finally have evidence giving us clinical evidence as to when to use which drug.

In these days of cost containment, it’s now clear that Avastin, Lucentis or Eylea are equally effective for most patients. But now, based upon price, Avastin may be the clear “winner” for most patients.

Avastin Injection Recall

Avastin injections, used for wet ARMD, are again linked to eye infections. At least five patients have developed intraocular eye infections after receiving Avastin injections distributed by the same compounding pharmacy located in Augusta, Georgia. A voluntary recall of all sterile products from Clinical Specialities, Inc., has been issued. Most of their drugs are distributed to Georgia, Louisiana, South Carolina, Tennessee and Indiana.

Intraocular infections, called endophthalmitis, can lead to blindness. These are infections which occur in the inside of the eye compared to external infections such as pink eye. Clinical Specialties, Inc., is the compounding pharmacy where the injections were repackaged.

Does Avastin Cause Eye Infections

Avastin itself is safe and does not cause eye infections. Avastin is used “off label” to treat wet macular degeneration. The parent company, Genentech, does not manufacture nor distribute Avastin specifically for eye treatments.

Genentech manufactures Avastin for chemotherapy for treatment of various cancers including colon cancer. It does make a very similar drug, called Lucentis, for the treatment of wet ARMD. Lucentis is FDA approved for the eye, whereas, Avastin is not FDA approved.

Genentech, a pharmaceutical company, must adhere to strict FDA regulations as to the manufacturing process required for synthesizing and distributing their products. The manufacturing process must adhere to FDA rules to ensure the drugs to not contain bacteria, molds, viruses or contaminants.

Bacteria and molds are the biggest concern when manufacturing and could cause infection.

What is a Compounding Pharmacy?

A compounding pharmacy mixes or modifies drugs based upon a specific prescription written by a doctor. For instance, if a patient requires a flavor added, needs a pill changed to a liquid, has an allergy to a component of the drug, etc., these changes can be made at a compounding pharmacy.

A compounding pharmacy does NOT manufacture medicine, they may remix or repackage medicines. Compounding pharmacies are not governed by the FDA.

Nowadays, very few compounding pharmacies exist. CVS, Walgreens, Rite Aid, Costco, etc. are retail pharmacies, not compounding pharmacies. Avastin is, however, standard of care in many areas of the United States for the treatment of wet ARMD. I use Avastin for my patients.

Repackaging Avastin

Avastin is FDA approved, and sold for chemotherapy treatment for certain cancers. Chemotherapy requires larger volumes compared to the small 0.1 cc’s doses needed for eye treatment. (1.0 cc is about 1/30 of a fluid ounce. I use less than a tenth of 1.0 cc for injection!).

Avastin is purchased by a compounding pharmacy in larger quantities for cancer chemotherapy…as the drugs were intended and FDA approved. The compounding pharmacy, receives the Avastin from Genentech, and then repackages the drug for use in my office (for example).

What Does This Mean?

The problem is not the Avastin. The problem is that the compounding pharmacy is not regulated by the FDA. There is no governing agency to impose regulations for sterility and impose penalties for substandard conditions.

For now, make sure your doctor is not using product from Clinical Sciences, Inc. Avastin from other sources should be safe.

Randy

Retina Specialist
Ophthalmologist
Fairfax, Virginia

Treatment for Proliferative Diabetic Retinopathy

VEGF causes proliferative diabetic retinopathy Patients with proliferative diabetic retinopathy can be treated with laser photocoagulation and/or Avastin. Proliferative diabetic retinopathy, or PDR, is a specific stage of diabetic retinopathy which may lead to blindness if left untreated.

While most patients (if not all) develop some degree of diabetic retinopathy, most patients will not progress to the proliferative stage.

“Proliferative” Means Growth of Abnormal Blood Vessels

Diabetes is a disease which affects blood vessels. The retina may lose blood supply resulting in “retinal ischemia,” a condition where insufficient oxygen gets to the tissues (“angina” is another ischemic condition, chest pain develops due to lack of oxygen).

In response to chronic ischemia (poor oxygenation), the eye secretes VEGF (vascular endothelial growth factor). VEGF acts as a fertilizer to grow abnormal vessels somewhere in the eye. These abnormal vessels are called neovascularization.

Neovascular tissue may cause a diabetic retinal detachment or neovascular glaucoma. Either can blind.

Treatments Neutralize VEGF

Avastin, a common anti-VEGF, when used in the eye, can treat wet macular degeneration and macular edema. Over the last few years, Avastin has also been used to chemically treat PDR.

Avastin works by chemically neutralizing VEGF circulating in the eye.

Laser treatment, called pan-retinal photocoagulation (PRP), indirectly reduces VEGF by killing retinal cells. By reducing the number of retinal cells (we don’t really need them for vision by the way), the overall demand for oxygen is reduced. At some point, the reduced oxygen supply becomes adequate and VEGF is no longer produced.

Avastin is Only Temporary Treatment

Avastin, in my opinion and experience, is a quick and immediate treatment for PDR. It needs to be repeated as it does not fix the actual problem…the ischemia.

I have found that repeating the injections every 90 days or so can keep the neovascularization under control.

PRP, the laser photocoagulation, is a more permanent therapy as it remedies the actual problem…it cures the relative ischemia. Ischemia is inadequate supply of blood flow/oxygen. While the laser does not improve supply, it reduces demand and cures the oxygen problem.

What Does this Mean?

I don’t really know how long laser treatment takes to work on patients. There are several reasons why PRP is not immediately effective; severity of disease, amount of laser, etc.

Avastin works almost immediately and usually within 24-48 hours. It gives me a great clue as to the likely success of the eventual PRP.

I can often “stop” the disease with the Avastin and perform the more curative treatment at a later date.

Fake Avastin Hits United States…Again

Fake Avastin Hits U.S. Markets Another fake shipment of Avastin was discovered in late March. The first episode occurred in early February. In both instances, the bogus drug was purchased from a manufacturer in Turkey, then distributed eventually to the U.S. by a string of suppliers.

The brand name “Altuzan” is used for the drug manufactured in Turkey. Apparently the packaging of “Altuzan” contains only Turkish language, but the bogus anti-VEGF drugs were packaged with markings in English.

Avastin, an anti-cancer drug, is a popular treatment for wet macular macular degeneration. Annual sales of Avastin are reported to be abou $6 billion.

Altuzan Not Approved in the U.S.

Despite containing the same active ingredient, bevacizumab, foreign manufactured Altuzan is not approved for sale in the United States. Medical offices in the United States, however, purchased the drug priced 25% lower than the Avastin available in the U.S.

Only Avastin, manufactured in the United States, is approved for use in the United States.

Roche Makes Avastin

Roche makes “bevacizumab” (generic name) outside the United States. Within the U.S., Genentech, owned by Roche, makes and distributes the drug.

Most of the time the drug is sold in quantities intended for chemotherapy. Avastin is primarily an anti-cancer drug FDA approved for the treatment of a variety of cancers; colon, lung, kidney and brain cancer (glioblastoma multiforme).

In the ophthalmic world, Avastin is commonly used as an intravitreal injection for the treatment of wet ARMD.

Compounding pharmacies purchase the drug directly from the manufacturer. Once received, the pharmacy will then divide the allotment into smaller doses used for eye injections.

My local compounding pharmacy packages the Avastin in small, ready-to-use, syringes. My patients pick up the drug on the way to the office or have it delivered. The syringe is pre-loaded with just the right amount of drug to be injected.

What Does This Mean?

There are so many possible topics discuss, but I just don’t know enough about drug regulations and distributions, etc. to have a meaningful conversation. I am pretty ignorant about this.

The real question is…

Are you safe? I don’t think we know. Moreover, what about the patients receiving this to treat their cancer?

There are apparently no mechanisms to ensure the safety and reliability of drugs as they change hands from manufacturers to suppliers as the drugs are distributed. Obviously, we certainly need them.

By simply changing the packaging, vials of useless water, makes it all the way into your doctors’ offices! Seems an impossibility in this era. Seems too simple.

Sadly, this scenario is not unique, but rampant in poorer countries and especially where medical supplies are scarce. For most developed countries, we only assume this is not a bigger problem.

For now, the best I can do is assume that our pharmacy is as trustworthy as I once thought our system to be.

Avastin Does Not Cause Infection

One of the most feared complications of eye injections is blindness. This infection is called endophthalmitis. Last week the FDA issued an alert the 12 cases of endophthalmitis were caused by the injections.

The cause of the infections is NOT Avastin. There is nothing wrong with the drug itself.

Avastin Must Be RePackaged

Upon further investigation, a common denominator was a single pharmacy and, possibly, a single lot of tainted syringes.

Avastin is not FDA approved for injection into the eye, but it is standard of care. Also, Genentech manufactures Avastin and its close cousin, Lucentis. Lucentis is FDA approved for the treatment of wet macular degeneration.

Thus, in order for physicians like me, to get Avastin, a larger dose of Avastin is ordered. Once received the “repackaging” of the ARMD drug involves breaking up the larger dose (usually used for chemotherapy) into many more smaller doses for the eye. The doses are commonly broken up and placed in small syringes ready for injection.

“Repackaging” sounds kind of haphazard, but it’s not. A licensed pharmacist will distribute the Avastin in smaller allotments under strict sterile conditions. There are specific protocols for such “repackaging.”

Compounding Pharmacies Routinely Divide Drugs

Apparently, in one particular pharmacy, either the protocol was breached and/or the sterile laboratory conditions were not maintained and they shipped out a few contaminated syringes. Unfortunately, this caused 12 individuals loss of vision or blindness.

Fortunately, there was a plausible explanation and widespread panic was avoided.

Avastin, itself, is safe. The mechanisms used to deliver the drug to your doctor’s office are proven safe, too. Realize that over 2 million injections have been given.

What Does this Mean? Normally, informed consent is obtained prior to the delivery of an injection. We inform the patient that there is a risk of infection that could lead to blindness. That risk is estimated to be about 1:1000 to 1:2000 (approximates the risk of cataract surgery).

The source of the infection is thought to be the bacteria that reside on your eyelashes and the surface of the eye, not the actual substance injected nor the container in which it was shipped.

In the end, this was a very rare and unfortunate event for the 12 patients, their families and their doctors. The culprit; however, was not Avastin.

FDA Delays Decision on VEGF Trap Eye

VEGF Trap-Eye was not approved by the FDA for the treatment of wet macular degeneration. The parent company, Regeneron, was hopeful to gain FDA approval last week, but the FDA delayed its decision until November of this year.

VEGF Trap-Eye Treats Wet Macular Degeneration

VEGF Trap-Eye, or aflibercept, is another anti-VEGF drug formulated to treat wet macular degeneration.

Like its competitors, aflibercept is designed to neutralize the effects of the Vascular Endothelial Growth Factor a key component in the pathway of wet macular degeneration. It, too, will be administered as an injection into the eye as are Lucentis and Avastin.

If you recall, Lucentis is FDA approved for wet macular degeneration. Avastin is not FDA approved, but is commonly used by retinal specialists, hence, it has become the standard of care.

Fewer Injections into the Eye

Unlike its competitors, aflibercept may be injected less frequently than its competitor, Lucentis. Instead of monthly injections, VEGF Trap-Eye may be injected every 2 months!

What Does this Mean? There is a potential new drug near FDA approval for the treatment of wet macular degeneration.

Assuming that Eylea (the proposed trade name) is just as effective as Lucentis, there are two particular advantages to the new drug: cost and frequency of administration.

Eylea will be the third drug to be used for wet ARMD, but only the second that is FDA approved (Lucentis is FDA approved, but Avastin is used “off label”). It is conceivable that that Eylea will be priced between the two drugs…

Fewer injections means fewer office visits, fewer complications and this means….cost savings (thus an argument to increase the price compared to Lucentis!).

Personally, I think there is room for a drug that doesn’t have to be given monthly. There are substantial savings to realize; costs in terms of office visits, costs of injections and the intangible costs…the costs involved to have a family member or friend accompany the patient…

FDA Upholds Denial of Avastin

Avastin is no longer FDA approved for breast cancer. This decision was upheld at a hearing last week. Eye patients, however, need not worry.

The Food and Drug Administration had removed its approval for Avastin for the treatment of breast cancer last December. A hearing last week (June, 2011) allowed Genentech and the drugs’ supporters, to voice their concerns about the removal of the drug.

While the FDA has removed its approval for one type of cancer, the drug is not being removed from the market.

The FDA argues that bevacizumab (generic name) is not effective in treating breast cancer patients and, so, reversed its original decision. The counter argument claims that Avastin is effective, though in a minority of patients.

This anti-VEGF drug has become effective treatment for wet macular degeneration. Avastin, used for the treatment of a variety of cancers, has become the standard of care and is used my most retinal specialists for their patients.

Avastin Not Effective for Breast Cancer

The initial data indicated that bevacizumab, when given along with another drug, stymied the progression of the disease for 5-6 months compared to the other drug alone. Avastin was given quick approval for breast cancer.

Since then, re-investigation could not duplicate the results, yet the incidence of GI bleeding complications were notable. There was no evidence showing improved lifespan either.

The FDA upheld the decision.

What Does This Mean?

Removing an FDA approval only means that insurance companies are likely not to reimburse doctors and hospitals for the treatment. While treatment can theoretically still be performed, it would require that patients pay for it out-of-pocket. Thus, it is cost prohibitive in most cases.

Regardless of the FDA hearing, eye patients do not need to worry. Though the drug may no longer be available for patients with breast cancer, the drug will still be on the market for other treatments.

We should be able to continue using it as a first line treatment for wet macular degeneration. Avastin may have lost its FDA approval for the treatment of breast cancer, but this is different than a drug being removed from the market.

(By the way, I have wondered why the FDA could not have compromised, in that, as long as existing patients accept the risks, treatment could continue. Why not remove the FDA approval from this point forward?)

Two Lasers for Diabetic Retinopathy

Laser Treatment for Diabetic Retinopathy

There are two different laser treatments to treat diabetic retinopathy. One laser treatment is used to treat diabetic macular edema, the most common “complication” of diabetic retinopathy. The second laser treatment is used to treat proliferative diabetic retinopathy (aka PDR), yet far fewer people develop this potentially blinding stage of the disease.

Same Laser Used for Both Treatments

Macular edema is treated with “focal” laser treatment. The laser is used to treat/burn/cauterize those areas of blood vessels that are leaking near the macula. The treatment is focused to treat certain specific areas, hence “focal” laser.

Proliferative diabetic retinopathy (PDR) is treated with “scatter” or “pan-retinal” photocoagulation (PRP). The peripheral retina is “scattered” with laser burns.

Some Patients Need Both Laser Treatments

The timing of the treatment can be crucial. Treating the PDR (proliferative diabetic retinopathy) before the macular swelling is controlled, or treated, can lead to progressive loss of vision because the PRP (used to treat PDR) can worse the macular edema.

I prefer treating and controlling the macular swelling first, before treating the neovascular disease (PDR). Depending upon the situation, however, I don’t always have this luxury as sometimes the PDR is so advanced that we can not wait.

Remember, the neovascularization can cause blindness.

What Does This Mean? In most cases, patients need only one or the other treatment. Macular edema is treated with focal laser and PDR is treated with PRP. In the unlikely situation where patients need both…

When possible, I’ll treat the macular edema with focal and wait several weeks, or months, to treat with scatter laser. I don’t want the macular edema to worsen.

Macular fluid causes decreased vision (patients can tell). Worsening macular edema means lousy vision….and anxious patients.

Avastin, however, has improved my ability to treat those patients with both macular and proliferative disease. Avastin (or Lucentis) allows me to treat both the PDR and macular edema…it buys me time!

Tag Archives: Avastin

What are Compounding Pharmacies?

Avastin is Repackaged

Lucentis is Directly Shipped

Study Shows Avastin is Safe

Legally Blind

Treatment for Diabetic Macular Edema

Before Treatment with Ozurdex

After Treatment with Ozurdex

Common Complication of Diabetic Retinopathy

Protocol T | Comparative Study of Anti-VEGF Drugs

Results of “Protocol T”

Does Avastin Cause Eye Infections

What is a Compounding Pharmacy?

Repackaging Avastin

“Proliferative” Means Growth of Abnormal Blood Vessels

Treatments Neutralize VEGF

Avastin is Only Temporary Treatment

Altuzan Not Approved in the U.S.

Roche Makes Avastin

Avastin Must Be RePackaged

Compounding Pharmacies Routinely Divide Drugs

VEGF Trap-Eye Treats Wet Macular Degeneration

Fewer Injections into the Eye

Avastin Not Effective for Breast Cancer

Same Laser Used for Both Treatments

Some Patients Need Both Laser Treatments

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