Animal & Veterinary

FDA Provides Important Information to Veterinarians about PACCAL VET-CA1 for Treating Cancer in Dogs


What are the labeled indications for PACCAL VET-CA1?
What does the "CA1" in PACCAL-CA1 mean?
What is the active ingredient in PACCAL VET-CA1 and how does it work?
What adverse reactions are caused by PACCAL VET-CA1?
What should you do if a dog experiences an adverse reaction related to PACCAL VET-CA1?
What are the contraindications for PACCAL VET-CA1?
Are there any human warnings for PACCAL VET-CA1?
Can you use PACCAL VET-CA1 to treat other neoplasias or other diseases?
Important information for your client
What does PACCAL VET-CA1's "designation status" mean?
For more information
Resources for You
References


In February 2014, FDA’s Center for Veterinary Medicine conditionally approved PACCAL VET-CA1, an antineoplastic drug intended to treat dogs with mammary carcinoma or squamous cell carcinoma. Below is a brief reference guide for veterinarians on PACCAL VET-CA1.

What are the labeled indications for PACCAL VET-CA1?

The drug is labeled to treat:

  • Nonresectable stage III, IV, or V mammary carcinoma in dogs that have not received previous chemotherapy or radiotherapy; and
  • Resectable and nonresectable squamous cell carcinoma in dogs that have not received previous chemotherapy or radiotherapy.

The package insert contains detailed instructions on dosage and administration. PACCAL VET-CA1 is given by intravenous (IV) infusion through an IV catheter. Extravasation can cause focal tissue necrosis.

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What does the “CA1” in PACCAL VET-CA1 mean?

The “CA1” means that FDA conditionally approved (CA) the drug and that it’s the first (1) conditionally approved application for this animal drug. As a key provision of the Minor Use and Minor Species Animal Health Act (the MUMS Act) of 2004, conditional approval is one way FDA helps make more drugs available to small populations of animals.

FDA’s conditional approval allows Oasmia Pharmaceutical AB, the manufacturer of PACCAL VET-CA1, to legally market the drug before proving it meets the standard of effectiveness for full approval. The company has shown that, when used according to the label, PACCEL VET-CA1 is safe and has a “reasonable expectation of effectiveness.”

On the labeling for PACCAL VET-CA1, you will see this required statement: "Conditionally approved by FDA pending a full demonstration of effectiveness under application number 141-422.”

PACCAL VET-CA1’s conditional approval is valid for one year. Oasmia Pharmaceutical AB can ask FDA to renew the conditional approval annually for up to four more years, for a total of five years of conditional approval. To receive the renewal from FDA, the company must be actively collecting data to prove the drug meets the effectiveness standard for full approval.

During the conditional approval period, Oasmia Pharmaceutical AB can legally market PACCAL VET-CA1 for the two labeled indications while collecting the remaining effectiveness data. When the company completes the effectiveness requirement, FDA will review the data and, if appropriate, fully approve the drug.

Only drugs for minor species or minor uses in a major species are eligible for conditional approval. Minor species are all animals that are not major species. A minor use in a major species is the use of a drug in one of the seven major species (horses, cattle, pigs, dogs, cats, chickens, and turkeys) for a condition that occurs:

  • Infrequently and in only a small number of animals each year; or
  • In a limited geographic area and in only a small number of animals each year.

PACCAL VET-CA1 was eligible for conditional approval because the Office of Minor Use and Minor Species Animal Drug Development within FDA’s Center for Veterinary Medicine determined that the drug’s two indications fit the “minor use in a major species” category. Both mammary carcinoma and squamous cell carcinoma - within the limitations described on the label - occur infrequently and in a small number of dogs each year (fewer than 70,000 dogs in the U.S. in one year).

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What is the active ingredient in PACCAL VET-CA1 and how does it work?

The active ingredient in PACCAL VET-CA1 is paclitaxel, an antimicrotubule agent that interferes with the dynamic instability of microtubules—the ability of microtubules to switch between phases of growth and shrinkage. Your last cell biology class was likely several years ago, so here’s a brief refresher on the structure and function of microtubules.

Microtubules are long, hollow cylindrical structures found throughout the cytoplasm of eukaryotic cells. They are composed of heterodimers of the globular protein tubulin. These tubulin heterodimers stack head to tail to form linear protofilaments. In general, microtubules consist of 13 protofilaments assembled around a hollow core.

Acting as scaffolds, microtubules maintain cell shape. They also act as conveyer belts inside cells, providing a platform for moving organelles, vesicles, and other cell material. Microtubules form the framework for the mitotic spindle which appears during cell division (mitosis) and is used to separate chromosomes. Microtubule numbers increase during mitosis.

Microtubules undergo continual assembly and disassembly within the cell. In a normal population of microtubules, some are growing and some are shrinking. During the growth phase, tubulin heterodimers attach to the end of the microtubule. During the shrinkage phase, the opposite happens—intact tubulin heterodimers detach from the microtubule.

PACCAL VET-CA1 works by stabilizing microtubules, so they can’t grow and shrink normally. Because microtubules play a central role in mitosis, this abnormal stabilization blocks cells—especially rapidly dividing ones—from completing mitosis, leading to cell death.

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What adverse reactions are caused by PACCAL VET-CA1?

PACCAL VET-CA1 has a low margin of safety. In a field study of 168 dogs with cancer treated with paclitaxel, all dogs experienced at least one adverse reaction and 85 percent experienced a severe reaction. Treatment had to be discontinued in 11 dogs due to adverse reactions, and five dogs died and three were euthanized because of adverse reactions. The most common adverse reactions seen in the field study were:

  • Neutropenia. Paclitaxel can cause severe, transient bone marrow suppression within four to seven days after administration.
  • Gastrointestinal symptoms – vomiting and diarrhea (sometimes bloody). Paclitaxel can cause transient gastrointestinal mucosal cell toxicity.
  • Anorexia
  • Lethargy
  • Alopecia
  • Dehydration
  • Dermatitis

You should closely monitor dogs treated with PACCAL VET-CA1 and provide appropriate supportive care to manage adverse reactions.

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What should you do if a dog experiences an adverse reaction related to PACCAL VET-CA1?

FDA encourages veterinarians to voluntarily report all adverse reactions (also called adverse drug experiences, or ADEs) related to PACCAL VET-CA1. Please see How to Report an Adverse Drug Experience.

Oasmia Pharmaceutical AB is required to submit to FDA all reports of adverse drug experiences that the company receives. FDA reviews the reports to identify potential safety and effectiveness concerns that may not have been apparent at the time of conditional approval. FDA conducts this post-marketing monitoring to make sure that PACCAL VET-CA1 continues to meet the required standard of safety and reasonable expectation of effectiveness established during the conditional approval process.

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What are the contraindications for PACCAL VET-CA1?

You should not use PACCAL VET-CA1 in dogs that have a neutropenia (< 2000 cells/µL) or a concurrent serious infection. You should also not use the drug in dogs that are pregnant, lactating, or intended for breeding because paclitaxel is a teratogen and can affect fertility in both males and females.

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Are there any human warnings for PACCAL VET-CA1?

Yes. People who are sensitive to retinoids should avoid contact with PACCAL VET-CA1. Also, the drug is cytotoxic and can cause birth defects and affect fertility in both men and women. Pregnant or breast-feeding women should not prepare or administer the drug.

Paclitaxel and its metabolites are present in urine, feces, saliva, and vomitus of treated animals. For three days after treatment, people should wear protective gloves when handling and cleaning up after a treated dog.

For a complete description of the Contraindications, Warnings, and Precautions, it’s important to read the package insert.

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Can you use PACCAL VET-CA1 to treat other neoplasias or other diseases?

No. Federal law prohibits extra-label (“off-label”) use of conditionally approved drugs. You can only use PACCAL VET-CA1 for the two labeled indications. To drive this point home, the drug's labeling explicitly states, “It is a violation of Federal Law to use this product other than as directed in the labeling.” This is different for fully approved drugs which, under certain conditions, you can legally prescribe for extra-label uses in animals.

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Important information for your client

PACCAL VET-CA1 has an accompanying Client Information Sheet that you should give your client each time you administer the drug to his or her dog. Written for the dog owner, this sheet summarizes important safety information about the drug and serves as an easy at-home reference guide. It also explains the home care required after a dog is treated with PACCAL VET-CA1. Owners must be careful when handling and cleaning up after their dog for three days after treatment. The Client Information Sheet includes instructions for owners on how to safely clean up after their dog.

The package insert for PACCAL VET-CA1 has a section called “Information for Dog Owners” which may help you in your communication with clients regarding paclitaxel.

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What does PACCAL VET-CA1’s “designation status” mean?

PACCAL VET-CA1’s “designation status” means that the Office of Minor Use and Minor Species Animal Drug Development within FDA’s Center for Veterinary Medicine granted Oasmia Pharmaceutical AB’s request to declare the drug a “designated” animal drug for its two labeled indications. This designation status qualifies the company to receive financial incentives. First, it gives Oasmia Pharmaceutical AB seven years of exclusive marketing rights, beginning on February 27, 2014, the date that FDA conditionally approved PACCAL VET-CA1. During this 7-year period, a different drug company cannot pursue approval or conditional approval of a generic copy or another pioneer (brand name) version of the same drug in the same form for the same intended use. For animal drugs that aren’t designated, the period of marketing exclusivity is three to five years after the date of approval or conditional approval and the exclusivity only protects against generic copies. A different drug company can still pursue approval or conditional approval of another pioneer version during this 3- to 5-year period.

Second, PACCAL VET-CA1’s designation status means Oasmia Pharmaceutical AB and other organizations or individuals working with the company are eligible to receive grants through the federal government. The grant money is used to reduce the cost of conducting studies to support approval of the designated animal drug.

Designation is not the same as approval or conditional approval. It’s simply a status that qualifies a drug company to receive the financial incentives mentioned above. Designation doesn’t mean FDA has approved or conditionally approved the drug. A drug company cannot sell, promote, or advertise a designated drug until it’s approved or, as in the case of PACCAL VET-CA1, conditionally approved.

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For more information

If you have questions or would like more information, please contact CVM’s Education & Outreach Staff at 240-276-9300 or AskCVM@fda.hhs.gov.

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Resources for You

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References

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Page Last Updated: 09/11/2014
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