Clofarabine (Intravenous)

Administered as an injection, Clofarabine is a chemotherapy drug that works by killing cancer cells and preventing them from multiplying.

Overview

Clofarabine is a prescription-only medication that is used to treat patients with acute lymphoblastic leukemia where the patient has already tried at least two other similar treatments. The drug is administered as an injection via the intravenous route.

This medication is part of a family of drugs called antineoplastic (cancer) medicines. It works by interrupting the production of cancer cells, enabling them to be killed by the body. Unfortunately, antineoplastic medicines like clofarabine cannot distinguish between cancerous cells and normal healthy cells. Therefore, taking the medicine can also affect the growth rate of normal cells, leading to various unwanted side effects and health complications. It will also leave the patient vulnerable to the impact of infections.

This is a chemotherapy drug, and therefore the side effects can be severe in some cases. However, there may be other drugs that you can take to help alleviate some of the side effects, of minimize the discomfort while you complete the course.

Clofarabine is a very strong treatment, which is why it is only usually used when patients have already tried other medications to treat and control their conditions. Before taking a course of Clofarabine, patients should speak to their doctor about the likely impact of Clofarabine on the body, and whether there are any more suitable options available.

Acute lymphoblastic leukemia is a particularly aggressive form of cancer that interferes with white blood cells. The disease is likely to progress very quickly and aggressively. Therefore, it will require immediate treatment upon its detection. Although ALL is a very rare condition, it can affect anyone - and is just as common in children as it is in adults. It is the most common type of leukemia to impact children, with the vast majority of cases of the disease being detected in patients under the age of 15. The most common age for developing the condition is between two and five years old.

Clofarabine is only to be administered by and under the supervision of a trained medical professional. It is also known by the brand name Clolar, in the United States.

Type of medicine

  • Solution, to be administered via an injection

Conditions treated

  • Acute lymphoblastic leukemia (ALL)

Side effects

Unfortunately, as Clofarabine destroys healthy cells as well as cancerous cells, there are some very severe side effects that can take place in patients. Patients should be closely monitored throughout their entire treatment course in case the side effects become too severe for the body to cope with. Not all patients will experience all of the reported side effects below, but some are fairly common.

The drug is not intended as a long-term treatment, and side effects should subside once the treatment has stopped. However, when taking this medication, patients should be prepared to deal with and manage side effects, and also take extra precautions to protect themselves from contracting an infection. When the body's blood cells are attacked, this can cause the immune system to weaken, leaving the body very vulnerable and unable to fight off simple viral infections such as common colds and the flu. When taking a drug like Clofarabine, the patient should stay in a sterile environment, avoid going out and avoid being around others that may have an infection - no matter how small.

Common side effects (present in at least 30 percent of patients) include:

  • Decrease in the number of white blood cells
  • Decrease in neutrophils (a type of white blood cell)
  • Decrease in lymphocytes (another type of white blood cell)
  • Fever
  • Vomiting and nausea, particularly at the time of administration
  • Low count of platelets
  • Diarrhea
  • Headache
  • Infections, such as bacterial, viral and fungal)
  • Increased level of creatinine
  • Increased level of bilirubin
  • Itching in various areas of the body
  • Elevated liver enzymes
  • Anemia
  • Pain in the limbs
  • Chills and shivers
  • Extreme tiredness, and need to sleep or rest more often
  • Increased heart rate
  • Pain in the abdomen
  • Skin rashes
  • Lack of appetite

The following side effects are less common, occurring in between ten and 29 percent of clofarabine:

  • Lower blood pressure
  • Small areas of bleeding beneath the skin, with the appearance of small purple or red spots
  • Pain in the joints or muscles
  • Hot flushing
  • Nose bleeds
  • Mucosal inflammation
  • Urine that contains traces of blood
  • Swelling in any part of the body, especially in the hands or feet
  • Rapid or severe weight gain
  • Bleeding from the gums
  • Hand-foot syndrome
  • Anxiety and confusion
  • Difficulty in catching your breath
  • Redness in the skin
  • Irritability
  • Fluid build-up around the lungs
  • Pain in the back - particularly the lower back or sides
  • Feeling of weakness, in the muscles or the joints
  • Drowsiness or sleepiness
  • High blood pressure
  • Pneumonia
  • Herpes
  • Infections in the blood (sepsis)

If patients experience any of the following side effects as a result of taking clofarabine, they should contact a doctor immediately, or head to an emergency room:

  • Fever of at least 100.4 degrees Fahrenheit
  • Chills accompanying the fever (this indicates that the patient may have picked up an infection)
  • Wheezing or tightness in the chest
  • Itching
  • Severe cough
  • Change in skin color, particularly to a grey or blue shade
  • Seizures
  • Swelling of the lips, face tongue or throat

Other side effects that patients should report to a doctor are below. Although these are not considered to be an emergency, they will require medical intervention to prevent them from becoming more serious:

  • Unusual bleeding
  • Jaundice (yellow eyes or skin)
  • Tarry stools, or dark stools
  • Blood in the urine or stools
  • Unusual bruising
  • Inability to pass urine
  • Vomiting more regularly than four times per 24 hour period
  • Diarrhea episodes that have taken place more than four times per 24 hour period
  • Sores in the mouth, such as ulcers, swelling or redness
  • Severe headache
  • Change in mental state e.g. losing the ability to think clearly or rationally
  • Skin rash or severe skin irritation
  • A severe sore throat
  • Pain in the ears or sinuses
  • Wounds that will not heal
  • Itching or pain of the anus area

Dosage

At each application, you should consume at least two to three quarts of fluid, such as water. This will help your body to cope with the medication by diluting it, making you pass more urine and lessening the impact on the kidneys.

The usual dosage for both adults and children over the age of one year is 52 mg/m2 by intravenous injection over two hours. The administration should happen daily for five days in a row.

Your treatment cycle will be repeated after either your recovery or after your return to basic organ function. This repeat will take place around every two to six weeks, depending on your individual needs. Any following cycles should start within 14 days from the first day of the previous treatment cycle. In order to administer subsequent treatment cycles, the ANC level must be 750 / mm3 or above.

Major drug interactions

Before prescribing a course of Clofarabine, the doctor will very carefully assess the health history of the patient, as well as his or her responses to other similar cancer drugs. There are various other medications that can react with Clofarabine when taken at the same time, so if the patient is taking any of these, they may need to stop before Clofarabine can be administered. There are more than 600 drugs that have been found to have some form of reaction with Clofarabine, of which 59 of these have a major interaction. Major drug interactions should be avoided at all times, as the side effects of taking these together will be too severe for the body to cope with. Patients should not take any of the following medications when on a course of Clofarabine:

  • adalimumab
  • BCG
  • certolizumab
  • cidofovir
  • clozapine
  • deferiprone
  • diatrizoate
  • diatrizoate / iodipamide
  • efavirenz / emtricitabine / tenofovir
  • emtricitabine / lopinavir / ritonavir / tenofovir
  • emtricitabine / nelfinavir / tenofovir
  • etanercept
  • fingolimod
  • golimumab
  • infliximab
  • influenza virus vaccine, h1n1, live
  • influenza virus vaccine, live, trivalent
  • iodamide
  • iodipamide
  • iodixanol
  • iohexol
  • iopamidol
  • iopromide
  • iothalamate
  • ioversol
  • ioxaglate
  • ioxilan
  • leflunomide
  • lomitapide
  • measles virus vaccine
  • measles virus vaccine / mumps virus vaccine / rubella virus vaccine
  • measles virus vaccine / mumps virus vaccine / rubella virus vaccine / varicella virus vaccine
  • measles virus vaccine / rubella virus vaccine
  • metrizamide
  • mipomersen
  • mumps virus vaccine
  • mumps virus vaccine / rubella virus vaccine
  • natalizumab
  • poliovirus vaccine, live, trivalent
  • rotavirus vaccine
  • rubella virus vaccine
  • samarium sm 153 lexidronam
  • smallpox vaccine
  • talimogene laherparepvec
  • teriflunomide
  • thalidomide
  • tofacitinib
  • typhoid vaccine, live
  • varicella virus vaccine
  • yellow fever vaccine
  • zoster vaccine live

Warnings

Vaccinations

Do not take any form of vaccination while you are taking clofarabine. You should consult your doctor if for any reason you think you may need an immunization.

Pregnancy and conception

This medication is not usually suitable for administration on pregnant women, unless the health benefit is seen to outweigh the risk to an unborn fetus. You should notify your doctor if you or pregnant or think you may be pregnant while you are taking the drug. The drug has been given a category D warning for use during pregnancy, meaning that there is a potential risk of harm to the fetus.

You should also not attempt to conceive a child while taking this medication - this advice applies to both men and women. If you would like to conceive a child after your treatment has finished, you should speak to your doctor for advice, as there may be an initial period afterwards where it is still not safe to become pregnant.

Infections

When taking clofarabine, you should take extra precautions to protect yourself against picking up an infection. Your body will be more vulnerable to catching an infection and less effective at fighting it during a treatment course of chemotherapy. You can help to protect yourself by washing your hands regularly and finishing with an anti-bacterial gel. Use an electric razor when you shave instead of a harsher manual razor, and use a soft toothbrush to prevent bleeding through the gums.

You should also avoid any activity that could cause you injury, such as sports or manual labor. Also, stay away from crowds as other people could be carrying infections. Likewise, if anyone you know has a common cold or flu, stay away from them until you and they are sure that the infection has passed. You can also help to prevent mouth sores by rinsing your mouth up to three times per day with baking soda or salt. Also, use a soft toothbrush and take care not to bite the inside of your mouth when eating food.

Do not go out in the sun, and always wear a sunblock when you are outdoors.

Disease interactions

You may not be a suitable candidate for taking clofaramide if you suffer from various other health conditions or diseases. This is because certain diseases can cause an interaction with the drug, either causing it to create severe side effects, or impacting on the drug's ability to work. The conditions that interact with clofaraide are:

  • Anemia
  • Bleeding issues or conditions such as hemorrhage
  • Infections, such as bacterial, viral or fungal
  • Liver disease
  • Low white blood cell count
  • Low platelet count
  • Kidney disease

Alcohol

When taking a medication such as clofarabine, patients should refrain from consuming alcohol. Alcohol can interfere with the effectiveness of the drug, or can leave you open to heightened side effects such as nausea, vomiting, headache, dizziness and lack of judgement.

Storage

Clofarabine will be supplied as concentrate, which a doctor will then mix into an injectable solution. Vials that contain clofarabine should be kept at a temperature of 25 degrees centigrade, but may remain effective at temperatures ranging from 15 to 30 degrees centigrade.

Only diluted, the solution must be injected into the patient immediately.

Summary

There have been many medical studies into the effectiveness and safety of clorfarabine in patients ranging from pediatric to geriatric. The drug has in general been found to be very effective; however, it does carry the risk of increased likelihood of treatment-related mortality. Because of this risk, the drug is usually only used if the condition has become particularly aggressive, and when at least two other treatment methods have failed to work. If the patient does not respond to other medications, the benefits to health and potential prolonging of life can outweigh the risks of treatment-related deaths.

Clofaramide also has a strong likelihood of the patient experiencing unpleasant side effects and an increased risk of contracting an infection. During a treatment course of clofaramide, the patient will be particularly vulnerable to picking up an infection. Due to the potency of the drug, the immune system may become too risk to fight the infection, resulting in risk of death. Patients that are undergoing a course of clofaramide should therefore be very closely monitored at all times. This is particularly important in pediatric patients that may not be able to communicate the severity or acute details of their symptoms. It is advisable that the child is kept in the hospital throughout the treatment if possible.

The cure rate for acute lymphoblastic leukemia remains relatively low, at 40 percent. Around half of those that are initially cured of the condition relapse. However, clofaramide can offer hope of eradicating the condition, and is considered to be one of the most aggressive drugs that can be prescribed to treat the condition.

Before prescribing a course of clofaramide, it is very important that the doctor explains to the patient all of the health risks surrounding the drug, and that the patient explains his or her full medical history. Due to the potency of the drug, it may not be compatible with all patients, or there may need to be some changes to existing medications before a course of clafaramide can begin. The drug is intended as a short-term treatment.