cladribine

KLAD-ri-been

Therapeutic Classification: antineoplastics

Pharmacologic Classification: antimetabolites

High Alert

IV: Active hairy cell leukemia manifested as anemia, leukopenia, thrombocytopenia, or clinical symptoms.
PO: Relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease in patients who have had an inadequate response to or have not tolerated other medications indicated for the treatment of MS.

Inhibits DNA synthesis.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.
Reduction in MS relapse rate and disability progression.

Absorption: IV administration results in complete bioavailability. 40% absorbed following oral administration.

Distribution: Extensively distributed to body tissues; penetrates into cerebrospinal fluid.

Metabolism/Excretion: Prodrug; activated via phosphorylation in lymphocytes to an active metabolite, Cd-ATP. 29% excreted by the kidneys as unchanged drug.

Half-Life: 24 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown
PO	unknown	30 min	unknown

Contraindicated in:

Hypersensitivity;
Current malignancy (oral);
HIV (oral);
Active tuberculosis (oral);
Active hepatitis (oral);
Active infection (oral);
Diluent contains benzyl alcohol and should be avoided in patients with known intolerance (IV);
Moderate to severe renal impairment (oral);
Moderate to severe hepatic impairment (oral);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infection (IV);
↓bone marrow reserve;
Hepatic or renal impairment (IV);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

CV: edema, HF, hypertension, tachycardia

Derm: rash, alopecia, erythema, petechiae, pruritus, STEVENS-JOHNSON SYNDROME, sweating, TOXIC EPIDERMAL NECROLYSIS

EENT: epistaxis

GI: anorexia, diarrhea, nausea, vomiting, abdominal pain, constipation, HEPATOTOXICITY

Hemat: anemia, lymphopenia, neutropenia, thrombocytopenia

Local: injection site reactions, phlebitis, thrombosis

MS: arthralgia, myalgia

Neuro: fatigue, headache, depression, dizziness, insomnia, malaise, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML), SEIZURES, weakness

Resp: abnormal breath sounds, cough, dyspnea

Misc: fever, hypersensitivity reactions (including angioedema), infection, chills, MALIGNANCY

Drug-drug:

Additive bone marrow depression may occur with other antineoplastics or radiation therapy.
Cilostazol, cyclosporine, dipyridamole, eltrombopag, nifedipine, nimodipine, ritonavir, and sulindac may ↑ levels and risk of toxicity; avoid concurrent use.
Corticosteroids and rifampin may ↓ levels and effectiveness; avoid concurrent use.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Hairy Cell Leukemia

IV (Adults ): 0.09 mg/kg/day for 7 days.

Multiple Sclerosis

PO (Adults ≥110 kg): 1st treatment course (Year 1): 1st cycle: 100 mg (10 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 100 mg (10 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 100 mg (10 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 100 mg (10 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.
PO (Adults 100–<110 kg): 1st treatment course (Year 1): 1st cycle: 100 mg (10 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 90 mg (9 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 100 mg (10 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 90 mg (9 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.
PO (Adults 90–<100 kg): 1st treatment course (Year 1): 1st cycle: 90 mg (9 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 80 mg (8 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 90 mg (9 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 80 mg (8 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.
PO (Adults 80–<90 kg): 1st treatment course (Year 1): 1st cycle: 80 mg (8 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 70 mg (7 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 80 mg (8 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 70 mg (7 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.
PO (Adults 70–<80 kg): 1st treatment course (Year 1): 1st cycle: 70 mg (7 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 70 mg (7 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 70 mg (7 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 70 mg (7 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.
PO (Adults 60–<70 kg): 1st treatment course (Year 1): 1st cycle: 60 mg (6 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 60 mg (6 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 60 mg (6 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 60 mg (6 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.
PO (Adults 50–<60 kg): 1st treatment course (Year 1): 1st cycle: 50 mg (5 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 50 mg (5 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 50 mg (5 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 50 mg (5 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.
PO (Adults 40–<50 kg): 1st treatment course (Year 1): 1st cycle: 40 mg (4 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 1st treatment course/1st cycle): 40 mg (4 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd treatment course (Year 2): 1st cycle (to be started ≥43 wk after last dose of 1st treatment course/2nd cycle): 40 mg (4 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days. 2nd cycle (to be started 23–27 days after last dose of 2nd treatment course/1st cycle): 40 mg (4 tablets) administered as 1–2 tablets once daily for 4–5 consecutive days.

(Generic available)

Tablets: 10 mg
Solution for injection: 1 mg/mL

Monitor for bone marrow depression. Assess for fever, chills, sore throat, and signs of infection. Monitor platelet count throughout therapy. Assess for bleeding (bleeding gums; bruising; petechiae; test stool, urine, and emesis for blood). Avoid administering IM injections and taking rectal temperatures. Apply pressure to venipuncture site for 10 min. Anemia may occur. Monitor for ↑ fatigue and dyspnea.
Monitor IV site for phlebitis.
Monitor intake and output. Development of uric acid nephropathy in patients with leukemia and lymphoma may be prevented with adequate oral hydration and allopurinol, if needed.
Screen for TB, HIV, and hepatitis B and C before 1st and 2nd courses of therapy.
Screen for herpes virus antibodies before starting therapy. Vaccinate patients who are antibody negative 4–6 wk before starting therapy. Patients who are seropositive to varicella zoster virus are recommended to be vaccinated with zoster vaccine recombinant. Patients may be administered zoster vaccine recombinant at any time prior to or during the year 1 or year 2 of therapy. These patients may also be administered the vaccine if their lymphocyte counts are ≤ 500 cells/microliter.
Assess vaccination status before starting therapy. Do not begin therapy until infection has been treated. Administer live-attenuated or live vaccines ≥4–6 wk prior to starting, due to risk of active vaccine infection. Avoid vaccination with live-attenuated or live vaccines during and after therapy while the white blood cell counts are not within normal limits.
Obtain baseline (within 3 mo) MRI to monitor for PML before starting therapy. Assess for signs of PML (hemiparesis, apathy, confusion, cognitive deficiencies, ataxia) periodically during therapy. Hold therapy and determine cause.

Lab Test Considerations:

Verify negative pregnancy test before starting each course of therapy.Monitor CD4 T-lymphocyte count and CD8 T-lymphocyte count before initiation of therapy and periodically during and after therapy. Cladribine causes prolonged depression of CD4 and CD8 lymphocyte subset counts, with recovery taking at least 6–12 mo.
- Monitor CBC with differential, lymphocyte, and platelet counts before 1st and 2nd course, 2 and 6 mo after start of treatment in each course, and periodically during therapy. Lymphocytes must be within normal limits before starting first course of therapy and at least 800 cells/microliter before starting second course of therapy. May delay the second course of therapy for up to 6 mo to allow for recovery of lymphocytes to >800 cells/microliter. If recovery takes >6 mo, patient should not receive further therapy. If lymphocyte count at month 2 is <200 cells/m³, monitor monthly until month 6. If during the first 2 wk after therapy, platelet counts, ANC, and hemoglobin decrease, transfusions of platelets and red blood cells may be required. Platelet count, ANC, and hemoglobin usually return to normal levels by day 12, wk 5, and wk 8, respectively.
- Monitor AST, ALT, alkaline phosphatase, and total bilirubin before each treatment cycle and course. If signs and symptoms of hepatic impairment (unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, dark urine) occur, hold therapy and obtain serum transaminases and total bilirubin promptly. .
- Monitor renal function before and periodically during therapy. May cause nephrotoxicity, resulting in ↑ serum creatinine, anuria, and acidosis.
- Monitor serum uric acid concentrations before and periodically during therapy, especially in patients with high tumor burden. May cause ↑ serum and uric acid concentrations. May require alkalinization of the urine.

Toxicity and Overdose:

May cause irreversible neurologic toxicity, resulting in motor weakness progressing to paraparesis or quadriparesis with high doses. If symptoms occur, discontinue cladribine. There is no known antidote.

PO: Administer tablets without regard to food ≥3 hr before or after other medications. DNC: Swallow tablets whole; do not crush, break, or chew. Tablet is uncoated and must be swallowed immediately once removed from the blister. If a tablet is left on a surface, or if a broken or fragmented tablet is released from the blister, the area must be thoroughly washed with water. The patient’s hands must be dry when handling the tablets and washed thoroughly afterward. Avoid prolonged contact with skin.
Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.

IV Administration:

Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
Diluent: Add the daily dose to 500 mL of 0.9% NaCl for injection. Recommend using a 0.22 micron hydrophilic syringe filter prior to adding to infusion bag. Solution is stable for 24 hr at room temperature or 8 days if refrigerated.
- May also be prepared as a 7-day solution. Dilute to a total volume of 100 mL in a CADD medication cassette reservoir using bacteriostatic 0.9% NaCl solution. Filter diluent and cladribine with a 0.22 micron hydrophilic filter prior to adding to cassette/reservoir.
Rate: Administer as a continuous infusion over 24 hr.

Instruct patient to take cladribine as directed. Take missed dose as soon as remembered on same day. If not until next day, extend the days of the cycle. If 2 doses are missed, extend the cycle by 2 days. Do not take 2 doses on the same day.
Instruct patient to notify health care professional promptly in the event of fever; sore throat; signs of infection (fever; loss of appetite; aching, painful muscles; burning, tingling, numbness, or itchiness of the skin in affected area; headache; skin blotches, blistered rash and severe pain; feeling unwell); bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; unusual swelling; joint pain; shortness of breath; or confusion. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to be especially careful to avoid falls. Patients should also be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs because these may precipitate GI hemorrhage.
Advise patient to notify health care professional if signs and symptoms of cardiac failure (shortness of breath, rapid or irregular heartbeat, swelling), PML (weakness on 1 side of body, changes in vision, loss of coordination in arms and legs, changes in thinking or memory, decreased strength, confusion, problems with balance, changes in personality), liver problems (nausea, loss of appetite, vomiting, yellow skin or whites of eyes, stomach pain, dark urine, tiredness), or allergic reaction (rash; swelling or itching of face, lips, tongue, or throat; trouble breathing) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
Instruct patient not to receive any vaccinations without advice of health care professional.
Inform patients that cladribine may increase their risk of malignancies. Instruct patients to follow standard cancer-screening guidelines.
Rep: May cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during and for 6 mo after last dose. Advise females to avoid breastfeeding for 10 days after last dose.

Improvement in hematologic status in patients with leukemia.
Reduced frequency of relapse and slowed progression of disability in patients with MS.

Mavenclad

NDC Code

0143- Hikma Pharmaceuticals USA Inc.
- 0143-9871- Cladribine
  - 0143-9871-01- 1 VIAL in 1 BOX, UNIT-DOSE (0143-9871-01) > 10 mL in 1 VIAL

44087- EMD Serono, Inc.
- 44087-4000- Mavenclad
  - 44087-4000-0- 5 BLISTER PACK in 1 CARTON (44087-4000-0) > 2 TABLET in 1 BLISTER PACK

44087- EMD Serono, Inc.
- 44087-4000- Mavenclad
  - 44087-4000-4- 4 BLISTER PACK in 1 CARTON (44087-4000-4) > 1 TABLET in 1 BLISTER PACK

44087- EMD Serono, Inc.
- 44087-4000- Mavenclad
  - 44087-4000-5- 5 BLISTER PACK in 1 CARTON (44087-4000-5) > 1 TABLET in 1 BLISTER PACK

44087- EMD Serono, Inc.
- 44087-4000- Mavenclad
  - 44087-4000-6- 6 BLISTER PACK in 1 CARTON (44087-4000-6) > 1 TABLET in 1 BLISTER PACK

44087- EMD Serono, Inc.
- 44087-4000- Mavenclad
  - 44087-4000-7- 7 BLISTER PACK in 1 CARTON (44087-4000-7) > 1 TABLET in 1 BLISTER PACK

44087- EMD Serono, Inc.
- 44087-4000- Mavenclad
  - 44087-4000-8- 8 BLISTER PACK in 1 CARTON (44087-4000-8) > 1 TABLET in 1 BLISTER PACK

44087- EMD Serono, Inc.
- 44087-4000- Mavenclad
  - 44087-4000-9- 9 BLISTER PACK in 1 CARTON (44087-4000-9) > 1 TABLET in 1 BLISTER PACK

63323- Fresenius Kabi USA, LLC
- 63323-140- Cladribine
  - 63323-140-10- 1 VIAL, SINGLE-DOSE in 1 CARTON (63323-140-10) > 10 mL in 1 VIAL, SINGLE-DOSE

67457- Mylan Institutional LLC
- 67457-450- Cladribine
  - 67457-450-10- 1 VIAL in 1 CARTON (67457-450-10) > 10 mL in 1 VIAL

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