Voraxaze Side Effects, Safety, Health Benefits, & Effectiveness

FDA allows drug that rids toxic levels of cancer remedy: The United States Food and Drug Administration on Jan. 17 approved a drug to reduce dangerous levels of a specified chemotherapy medication in cancer patients with failing kidneys. The drug, called Voraxaze (glucarpidase), helps eliminate the chemotherapy agent methotrexate in patients whose kidneys have been distressed by treatment with high doses of the chemotherapy drug.

Methotrexate is a commonly used cancer chemotherapy used to treat breast, bone and lung cancer and leukemia. In much lower doses, it is used to treat rheumatoid arthritis and other autoimmune diseases. Normally eliminated from the body by the kidneys, methotrexate can be harmful if it builds up in the body.

The new drug, Voraxaze, rapidly reduces methotrexate levels, as it is an enzyme that breaks the chemotherapy drug down into a form the body can eliminate. Voraxaze is administered intravenously or directly into a patient’s vein.





“Prolonged exposure to high levels of methotrexate can result in kidney and liver damage, severe mouth sores, damage to the lining of the intestine, skin rashes, and death due to low blood counts,” said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. Patients receiving high doses of methotrexate may develop kidney failure, Dr. Pazdur said in a press release.

“Voraxaze is an important new treatment option for cancer patients aimed at preventing these toxicities associated with sustained high levels of methotrexate,” he added.

The FDA granted Voraxaze orphan drug status—reserved for rare diseases or conditions that affect a very small portion of the population. The orphan designation comes with seven years of marketing exclusivity before a rival medicine can be approved. This is meant as incentive for companies to develop such special and needed drugs.

The drug is made and marketed by British specialty drug maker BTG International Inc.

According to the study used to support FDA approval, on average, patients taking Voraxaze eliminated 95 percent of the methotrexate in their system.

The study considered treatment with Voraxaze a success if the methotrexate level fell below a critical level within 15 minutes and stayed there for eight days. Ten of the 22 patients achieved this standard, the FDA said. While not all patients experienced this result, Voraxaze eliminated 95 percent of the methotrexate in all patients.

The safety of Voraxaze was also tested in a separate clinical study evaluating 290 patients who were experiencing problems clearing methotrexate from their blood.

The most common side effects observed in greater than one percent of patients in the clinical study were low blood pressure, headache, nausea, vomiting, flushing and paraesthesia or abnormal sensation.

The FDA is tasked to protect public health in the U.S. by assuring the safety, effectiveness and security of human and veterinary drugs, vaccines and other biological products for human use, as well as medical devices.





An agency of the U.S. Department of Health and Human Services, it is also responsible for the safety and security of the country’s food supply, cosmetics, dietary supplements and products that give off electronic radiation. Regulating tobacco products also falls within its jurisdiction.

Side effects of Voraxaze noted
A recently approved drug that rids the body of the toxic side effects of a cancer chemotherapy medication has, in turn, a number of side effects itself.

The medicine, called Voraxaze (glucarpidase), helps get rid of the chemotherapy agent methotrexate in cancer patients who suffer from failing kidneys resulting from being treated with high doses of the chemotherapy drug.

Voraxaze was approved by the United States Food and Drug Administration on Jan. 17 to reduce dangerous levels of the chemotherapy medication in cancer patients with failing kidneys.

Methotrexate is a cancer chemotherapy commonly used to treat breast, bone and lung cancer and leukemia. In much lower doses, it is used to treat rheumatoid arthritis and other autoimmune diseases. Normally, it’s eliminated from the body by the kidneys, but it can build up in the body and cause harm.

Voraxaze rapidly reduces methotrexate levels because it’s an enzyme that breaks the chemotherapy drug down into a form the body can eliminate. It’s administered intravenously or directly into a patient’s vein.

In a press release on the FDA’s website, Dr. Richard Pazdur notes: “prolonged exposure to high levels of methotrexate can result in kidney and liver damage, severe mouth sores, damage to the lining of the intestine, skin rashes, and death due to low blood counts.” Dr. Pazdur is the director of the Office of Hematology and Oncology Products at the FDA’s Center for Drug Evaluation and Research.

Patients receiving high doses of methotrexate may develop kidney failure, Dr. Pazdur says. “Voraxaze is an important new treatment option for cancer patients aimed at preventing these toxicities associated with sustained high levels of methotrexate,” he adds.

But Dr. Richard Pazdur warns patients that the new drug Voraxaze also has side effects. Most are mild. Commonly observed side effects, found in at most one or two in every 100 patients in the clinical study used for FDA approval, were:

• Paresthesias (2%)
• Flushing (2%)
• Nausea/vomiting (2%)
• Headache (1%)
• Hypotension (1%)





Less common side effects found in less than one percent of patients:
• Blurred vision
• Diarrhea
• Hypersensitivity
• Hypertension
• Rash
• Throat irritation/throat tightness
• Tremor

The FDA granted Voraxaze orphan drug status—reserved for rare diseases or conditions that affect a very small portion of the population. Drug makers granted this designation have an exclusive period of seven years of marketing before a rival medicine is allowed in the market. This is an incentive mechanism for companies to develop medications that are special or needed.

British specialty drug maker BTG International Inc. makes and markets Voraxaze.

The study used to support FDA approval showed that, on average, people taking Voraxaze eliminated 95 percent of the methotrexate in their system.

According to the FDA, the study considered treatment with Voraxaze a success if their bodies’ methotrexate level fell below a critical level within 15 minutes and stayed there for eight days.

Of the 22 patients in the trial, 10 achieved this standard — and while not all patients experienced this result, Voraxaze eliminated 95 percent of the methotrexate in all patients.

The safety of Voraxaze was also tested in a separate clinical study evaluating 290 patients who were experiencing problems clearing methotrexate from their blood.

In a advisory published on the cancer.gov website, the FDA advised healthcare providers to ensure that:

1. Methotrexate concentrations within 48 hours following administration of Voraxaze can only be reliably measured by a chromatographic method due to interference from metabolites (4-deoxy-4-amino-N10-methylpteroic acid (DAMPA)).

2. Measuring methotrexate concentrations, using immunoassays, within 48 hours of the administration of Voraxaze can overestimate the methotrexate concentration.





3. Leucovorin should not be administered within 2 hours before or after a Voraxaze dose because leucovorin is a substrate for Voraxaze.

4. The recommended dose and schedule for Voraxaze is as a single intravenous injection of 50 units/kg.

The FDA is tasked to protect public health in the U.S. by assuring the safety, effectiveness and security of human and veterinary drugs, vaccines and other biological products for human use, as well as medical devices.

An agency of the U.S. Department of Health and Human Services, it’s also responsible for the safety and security of the country’s food supply, cosmetics, dietary supplements and products that give off electronic radiation. Regulating tobacco products also falls within its jurisdiction.