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Injection Site Reactions

Medically reviewed by C.H. Weaver M.D. Medical Editor 8/2018

There are two types of injection site reactions: a local allergic reaction called a flare reaction, and a more severe reaction characterized by damage to the tissue due to extravasation. Extravasation is leakage of a small amount of drug from the blood vessel where it was injected. Symptoms for both reactions typically include redness, tenderness, warmth, and itching, but the consequences of extravasation are more severe and may include pain, blistering, and severe skin damage. Because extravasation can cause severe tissue damage, great care is taken to prevent it from occurring. One common approach is to administer drugs that may cause tissue damage into a larger blood vessel in the torso, rather than a smaller one in the arm. Depending on the cause, injection site reactions may be treated with warm compresses, ice, possibly an antidote for certain drugs that have extravasated, and in extreme cases, plastic surgery.

  • What is an injection site reaction?
  • Which drugs can extravasate and cause injection site reaction?
  • Which drugs can cause a flare reaction?
  • What are the symptoms of injection site reaction?
  • How can extravasation be prevented?
  • How are injection site reactions treated?

What is an injection site reaction

There are two types of injection site reactions. One is a local allergic reaction, also called a flare reaction, and is caused by drugs that are irritants. The other type of reaction is more severe and is caused by extravasation, which is the leakage of a small amount of chemotherapy from the blood vessel at the site of injection. Extravasation of highly corrosive chemotherapy drugs, called vesicants, can cause damage to the tissue surrounding the injection site.

Which drugs can extravasate and cause tissue damage

The chemotherapy drugs that may extravasate and cause tissue damage are called vesicants. These include:

  • Daunorubicin (Cerubidine®)
  • Doxorubicin (Adriamycin®, Rubex®)
  • Epirubicin (Ellence®)
  • Idarubicin (Idamycin®)
  • Mechlorethamine (Mustargen®)
  • Mitomycin (Mutamycin®)
  • Mitoxantrone (Novantrone®)
  • Paclitaxel (Taxol®, Onxal™)
  • Streptozocin (Zanosar®)
  • Teniposide (Vumon®)
  • Vinblastine (Velban®)
  • Vincristine (Oncovin®, Vincasar®)
  • Vinorelbine (Navelbine®)

Which drugs can cause a flare reaction

Any drug can be an irritant and cause a flare reaction. However, some are more likely than others. The irritants that commonly cause a flare reaction in cancer patients are:

  • Carmustine (BCNU)®
  • Cladribine (Leustatin®)
  • Dacarbazine (DTIC-Dome®)
  • Dolesatrone (Anzemet®)
  • Fulvestrant (Faslodex®)
  • Pamidronate (Aredia®)
  • Pegfilgrastim (Neulasta®)
  • Plicamycin (Mithracin®)
  • Vinorelbine (Navelbine®)

What are the symptoms of an injection site reaction

Symptoms of a flare reaction include:

  • Tenderness
  • Warmth
  • Redness along the vein or at the site of the injection
  • Itching
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A more severe reaction that is caused by extravasation may initially have the same signs as a flare reaction, but will worsen to include:

  • Pain at the site of the injection
  • Blistering
  • Severe skin damage

These symptoms may occur immediately or may be delayed 6-12 hours after administration of the drug. Notify your doctor immediately if you have any symptoms of an injection site reaction, and especially if you have pain at the site of the injection.

How can extravasation be prevented

Extravasation can lead to severe side effect; so if your treatment includes a vesicant, preventive steps may be taken. For example, your healthcare provider may install a tunnel catheter, which is a tube that is inserted into the superior vena cava, the major blood vessel that returns blood to the heart. This reduces the risk of extravasation by allowing the delivery of drugs into a larger vessel, rather than through a small vessel in your arm or other extremity.

How are injection site reactions treated

Treatment for injection site reaction depends on which drug is involved and how severe the reaction is.

Hot compresses: These are used for treatment of reactions due to vinca alkaloid drugs, which include vincristine (Oncovin®), vinblastine (Velban®) or vinorelbine (Navelbine®).

Ice: Treatment of a reaction from drugs other than the vinca alkaloids may be treated with ice or cold compresses, especially if it is only mild redness or discomfort.

Antidote: Various antidotes are available to treat reactions due to extravasation, depending on the type of drug and how much has leaked into the tissue.

Plastic surgery: Severe tissue damage due to extravasation may require plastic surgery.