fludarabine

High Alert

B-cell chronic lymphocytic leukemia (CLL) (in combination with cyclophosphamide and rituximab).
B-cell CLL in patients who have not responded to or whose disease has progressed during treatment with ≥1 regimen containing an alkylating agent (as monotherapy).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to fludarabine, mannitol, or sodium hydroxide;
Severe renal impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Moderate renal impairment (↓ dose);
Bone marrow depression;
OB: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema

Derm: rash

EENT: hearing loss, sinusitis, visual disturbances

Endo: gonadal suppression

GI: diarrhea, nausea, vomiting, anorexia, esophagitis, GI BLEEDING, mucositis, stomatitis

GU: dysuria, hematuria, urinary tract infection

Hemat: anemia, neutropenia, thrombocytopenia, HEMOLYTIC ANEMIA, IDIOPATHIC THROMBOCYTOPENIC PURPURA, TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE

MS: myalgia

Neuro: fatigue, agitation, COMA, confusion, headache, malaise, peripheral neuropathy, SEIZURES, weakness

Resp: cough, pneumonia, dyspnea, PULMONARY HYPERSENSITIVITY

Misc: fever, tumor lysis syndrome

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow suppression with other antineoplastics or radiation therapy.
Pentostatin may ↑ risk of potentially fatal pulmonary toxicity; concurrent use not recommended.
May ↓ antibody response to or ↑ risk of adverse reactions to live vaccines; avoid concurrent use.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 50 mg/vial
Solution for injection: 25 mg/mL

Route/Dosage ⬆ ⬇

In Combination With Cyclophosphamide and Rituximab

IV (Adults ): 25 mg/m² once daily for 1st 3 days (Days 1–3) of each 28-day cycle for 6 cycles or until disease progression or unacceptable toxicity.

Renal Impairment

IV (Adults ): CCr 50–79 mL/min: 25 mg/m² once daily for 1st 3 days (Days 1–3) of each 28-day cycle for 6 cycles or until disease progression or unacceptable toxicity. CCr 30–49 mL/min: 15 mg/m² once daily for 1st 3 days (Days 1–3) of each 28-day cycle for 6 cycles or until disease progression or unacceptable toxicity.

As Monotherapy

IV (Adults ): 25 mg/m² daily for 5 days; repeat course every 28 days.

Renal Impairment

IV (Adults ): CCr 50–79 mL/min: 25 mg/m² once daily for 1st 3 days (Days 1–3) of each 28-day cycle for 6 cycles or until disease progression or unacceptable toxicity. CCr 30–49 mL/min: 15 mg/m² once daily for 1st 3 days (Days 1–3) of each 28-day cycle for 6 cycles or until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

~~Fludara,~~ ~~Oforta~~

Action ⬆ ⬇

Converted intracellularly to an active phosphorylated metabolite that inhibits DNA synthesis.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: antimetabolites

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Following administration, rapidly converted to an active metabolite (2-fluoro-ara-A), which, when phosphorylated intracellularly, exerts antineoplastic activity; 40% of initial active metabolite excreted unchanged by the kidneys.

Half-Life: 20 hr (for initial active metabolite).

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	7 wk‡	13–16 days	unknown

‡Median time to response.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of fludarabine.
Emphasize the need for periodic lab tests to monitor for side effects.
Caution patient to avoid crowds and persons with known infections. Health care provider should be informed immediately if symptoms of infection (chills, cough, or burning pain on urination) occur.
Instruct patient to report unusual bleeding. Advise patient of thrombocytopenia precautions (use soft toothbrush and electric razor; avoid contact sports and other situations in which injury might occur). Do not drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate GI bleeding.
Instruct patient to inspect oral mucosa for redness and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Consult health care provider if pain interferes with eating. Stomatitis pain treatment may require opioid analgesics.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: May cause fetal harm; advise women of reproductive potential to use effective contraception during therapy and for ≥6 mo after last dose. Advise patient to avoid breastfeeding during therapy and 1 wk after last dose Advise men with female partners of reproductive potential to use effective contraception during therapy and for 3 mo after last dose. May cause male infertility.

Pronunciation ⬆ ⬇

Code ⬆

NDC Code

0480- Teva Pharmaceuticals, Inc.
- 0480-9772- Fludarabine Phosphate
  - 0480-9772-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (0480-9772-01) / 2 mL in 1 VIAL, SINGLE-DOSE

0527- Lannett Company, Inc.
- 0527-1242- Fludarabine Phosphate
  - 0527-1242-02- 1 VIAL, SINGLE-DOSE in 1 CARTON (0527-1242-02) / 2 mL in 1 VIAL, SINGLE-DOSE

25021- Sagent Pharmaceuticals
- 25021-242- Fludarabine Phosphate
  - 25021-242-02- 1 VIAL in 1 CARTON (25021-242-02) / 2 mL in 1 VIAL

33656- Chongqing Biocare Pharmaceutical Ltd.
- 33656-0015-
  - 33656-0015-1- 1 g in 1 POUCH (33656-0015-1)

45963- Actavis Pharma, Inc.
- 45963-609- Fludarabine phosphate
  - 45963-609-55- 1 VIAL, GLASS in 1 CARTON (45963-609-55) / 2 mL in 1 VIAL, GLASS

51916- Wuhan Biocause Pharmaceutical Development Co., Ltd
- 51916-310-
  - 51916-310-01- 100 g in 1 BOTTLE, GLASS (51916-310-01)

53183- Sicor S.r.l.
- 53183-7841-
  - 53183-7841-1- 1 kg in 1 CARTON (53183-7841-1)

58623- Zhejiang Hisun Pharmaceutical Co., Ltd.
- 58623-0043-
  58623-0043-1- 1 kg in 1 DRUM (58623-0043-1)

59923- Areva Pharmaceuticals
- 59923-604- Fludarabine Phosphate
  59923-604-02- 1 VIAL, SINGLE-DOSE in 1 CARTON (59923-604-02) / 2 mL in 1 VIAL, SINGLE-DOSE

63323- Fresenius Kabi USA, LLC
- 63323-192- Fludarabine
  - 63323-192-02- 1 VIAL in 1 BOX (63323-192-02) / 2 mL in 1 VIAL

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Indications ⬇