Clolar

Name: Clolar

Clolar Overview

Clolar is a prescription medication used to treat acute lymphoblastic leukemia, or ALL. Clolar belongs to a group of drugs called purine nucleoside antimetabolites. These work by killing existing cancer cells and limiting the development of new cancer cells.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects include nausea, vomiting, and diarrhea.

Clolar Drug Class

Clolar is part of the drug class:

  • Purine analogues

Clolar Dosage

This medication is available in an injectable form to be dosed by a healthcare professional.

The recommended dose of 52 mg/m2 as an intravenous (into the vein) infusion over 2 hours daily for 5 days in a row.

Cycles are repeated following recovery or return to baseline function (approximately every 2 to 6 weeks). The dosage is based on body surface area (BSA).

How is clofarabine given?

Clofarabine is injected into a vein through an IV. A healthcare provider will give you this injection.

Clofarabine is usually given daily for 5 days in a row during one or more 1-month treatment cycles. Your doctor will determine how many treatment cycles you will receive and how often.

You may receive other medications to help prevent certain side effects of clofarabine.

Clofarabine can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your kidney or liver function may also need to be tested. Your cancer treatments may be delayed based on the results of these tests.

What should I avoid while receiving clofarabine?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Cautions for Clolar

Contraindications

  • No known contraindications to use of clofarabine;1 use with caution in patients with known hypersensitivity to the drug or any ingredient in the formulation.8

Warnings/Precautions

Warnings

Administer only under supervision of clinicians qualified in use of cytotoxic therapy.1

Hematologic Effects and Infectious Complications

Anticipate bone marrow suppression (usually reversible and dose dependent) with use.1

Severe bone marrow suppression (neutropenia, anemia, thrombocytopenia) reported.1

Increased risk of developing infectious complications, including severe sepsis and opportunistic infections.1

Tumor Lysis Syndrome

Monitor for signs and symptoms of tumor lysis syndrome.1

Use appropriate measures (e.g., hydration, allopurinol) to prevent hyperuricemia.1

Systemic Inflammatory Response Syndrome (SIRS)/Capillary Leak Syndrome

Signs and symptoms of cytokine release (i.e., tachypnea, tachycardia, hypotension, pulmonary edema) reported.1

Rapid onset of respiratory distress, hypotension, capillary leak (e.g., pleural and pericardial effusions), and multiorgan failure reported.1

Monitor closely and intervene early by discontinuance of the drug and supportive measures (e.g., corticosteroids, diuretics, and/or albumin).1

Development of SIRS or capillary leak syndrome may be fatal.1 (See Dosage under Dosage and Administration.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals.1

Avoid pregnancy during therapy.1 If used during pregnancy, apprise of potential fetal hazard.1

General Precautions

Adequate Patient Monitoring

Perform CBC, including platelet counts at regular intervals; more frequently in patients who develop cytopenias.1

Monitor hepatic and renal function prior to therapy and throughout the 5 days of clofarabine administration.1

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)1

Lactation

Not known whether clofarabine or its metabolites are distributed into milk.1

Discontinue nursing because of potential risk to nursing infants.1

Pediatric Use

Safety and efficacy established for treatment of relapsed or refractory ALL in patients 1–21 years of age.1

Evaluated in a limited number of children with refractory acute myeloid leukemia (AML)†.2 4 5 6 7

Adult Use

Safety and efficacy not established in adults >21 years of age.1

Dosage of 40 mg/m2 (given by IV infusion over 1–2 hours) daily for 5 days every 28 days was used in a phase II clinical trial in adults with relapsed or refractory hematologic malignancies.1 2 6

Hepatic Impairment

[64] Not studied in patients with hepatic impairment; use with caution.1

[64] If increases in bilirubin concentrations occur, withhold drug until hepatic function returns to baseline.1 Dosage adjustment may be considered.1

Renal Impairment

Not studied in patients with renal impairment; use with caution.1

If substantial increases in serum creatinine concentrations occur, withhold drug until renal function returns to baseline.1 Dosage adjustment may be considered.1

Common Adverse Effects

Nausea, vomiting, diarrhea, anemia, leukopenia, thrombocytopenia, neutropenia (including febrile neutropenia), infections.1

Uses For Clolar

Clofarabine injection is used to treat acute lymphoblastic leukemia (ALL), a cancer of the white blood cells, in patients who have already used at least 2 other cancer medicines.

Clofarabine is an antineoplastic (cancer) medicine. It interferes with the growth of cancer cells, which are eventually destroyed by the body. Since the growth of normal cells may also be affected by clofarabine, other unwanted effects can occur. Before you begin treatment, talk to your doctor about the benefits of this medicine as well as the possible risks of using it.

This medicine is to be given only by or under the immediate supervision of your doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Feeling confused.
  • Feeling very tired or weak.
  • Chest pain or pressure.
  • Mood changes.
  • Pale skin.
  • Redness or irritation of the palms of hands or soles of feet.
  • Very bad belly pain.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

Indications and Usage for Clolar

Clolar® (clofarabine) Injection is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Clolar.

Clolar Description

Clolar (clofarabine) Injection contains clofarabine, a purine nucleoside metabolic inhibitor. Clolar (1 mg/mL) is supplied in a 20 mL, single-dose vial. The 20 mL vial contains 20 mg clofarabine formulated in 20 mL unbuffered normal saline (comprised of Water for Injection, USP, and Sodium Chloride, USP). The pH range of the solution is 4.5 to 7.5. The solution is sterile, clear and practically colorless, and is preservative-free.

What should I avoid while receiving Clolar?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Clofarabine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

What other drugs will affect Clolar?

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Clolar, especially blood pressure medication.

Clolar can harm your liver or kidneys. This effect is increased when you also use other medicines harmful to the liver or kidneys. During your 5-day treatment with Clolar, you may need to avoid using certain medications. Many other drugs (including some over-the-counter medicines) can be harmful to the liver or kidneys, such as:

  • leflunomide, methotrexate, teriflunomide;

  • an antibiotic, antifungal medicine, antiviral medicine, sulfa drug, or tuberculosis medicine;

  • birth control pills or hormone replacement therapy;

  • gout or arthritis medications (including gold injections);

  • HIV/AIDS medications;

  • injectable osteoporosis medicine;

  • medication to prevent organ transplant rejection;

  • medicines to treat a bowel disorder;

  • medicines to treat mental illness;

  • other cancer medications;

  • cholesterol-lowering medications - Crestor, Lipitor, Pravachol, Simcor, Vytorin, Zocor, and others;

  • pain or arthritis medicines - acetaminophen (Tylenol), ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others; or

  • seizure medication - carbamazepine, phenytoin, and others.

This list is not complete. Other drugs may interact with clofarabine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

For Healthcare Professionals

Applies to clofarabine: intravenous solution

Gastrointestinal

Gastrointestinal side effects including vomiting (83%), nausea (75%), diarrhea (53%), abdominal pain (36%), anorexia (31%), constipation (21%), gingival bleeding (15%), sore throat (14%), and decreased appetite (11%) have been reported. Postmarketing reports have included gastrointestinal hemorrhage some with fatalities.[Ref]

Other

A total of 85% of patients experienced at least one infection after clofarabine (the active ingredient contained in Clolar) treatment, including fungal, viral, and bacterial infections.[Ref]

Other side effects have included infections and infestations such as sepsis (15%), staphylococcal infection (13%), oral candidiasis (13%), herpes simplex (11%), cellulitis (11%), bacteremia (10%), and pneumonia (10%).

Several cases of capillary leak syndrome have been reported. (Signs and symptoms of cytokine release have included tachypnea, tachycardia, hypotension, and pulmonary edema.) Several patients developed rapid onset of respiratory distress, hypotension, capillary leak (pleural and pericardial effusions), and multi-organ failure.[Ref]

Hematologic

Hematologic side effects including febrile neutropenia (57%), neutropenia (10%), transfusion reactions (10%) and bone marrow failure have been reported.[Ref]

Dermatologic

Dermatologic side effects including pruritus (47%), dermatitis (41%), petechiae (29%), erythema (18%), palmar-plantar erythrodysesthesia syndrome (13%), contusion (11%), and dry skin (10%) have been reported. Occurrences of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients who were receiving or had recently been treated with clofarabine (the active ingredient contained in Clolar) and other medications (e.g. allopurinol or antibiotics) known to cause these syndromes.[Ref]

Nervous system

Nervous system side effects including headache (46%), dizziness (16%), somnolence (10%), and tremor (10%) have been reported.[Ref]

Hepatic

Veno-occlusive disease has been reported in patients that received conditioning regimens that included busulfan, melphalan, and/or the combination of cyclophosphamide and total body irradiation.

Elevations of AST and ALT were transient and typically of less that 2 weeks duration.[Ref]

Hepatic side effects including jaundice (15%), hepatomegaly (15%), and veno-occlusive disease have been reported. Grade 3 or 4 elevated ALT (44%), grade 3 or 4 elevated AST (38%), and grade 3 or 4 elevated bilirubin (15%) have also been reported.[Ref]

General

General side effects including pyrexia (41%), rigors (38%), fatigue (36%), edema (20%), pain (19%), mucosal inflammation (18%), lethargy (11%), decreased weight (10%) and systemic inflammatory response syndrome (SIRS) have been reported.[Ref]

Cardiovascular

Cardiovascular side effects including pericardial effusion (35%), tachycardia (34%), left ventricular systolic dysfunction (27%), hypertension (3%), flushing (2%), and hypotension (1%) have been reported.[Ref]

Respiratory

Respiratory side effects including epistaxis (31%), cough (19%), respiratory distress (14%), dyspnea (13%), and pleural effusion (10%) have been reported.[Ref]

Musculoskeletal

Musculoskeletal side effects including pain in limb (29%), myalgia (14%), back pain (13%), and arthralgia (11%) have been reported.[Ref]

Psychiatric

Psychiatric side effects have been reported including anxiety (22%), depression (11%), and irritability (11%).[Ref]

Genitourinary

Genitourinary side effects including hematuria (17%) have been reported.[Ref]

Local

Local side effects including injection site pain (14%) have been reported.[Ref]

Renal

Renal side effects including grade 3 or 4 elevated creatinine (6%) have been reported.[Ref]

Oncologic

Oncologic side effects have included clastogenic activity in the in vitro mammalian cell chromosome aberration assay (CHO cells) and in the in vivo rat micronucleus assay.[Ref]

Some side effects of Clolar may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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