Pentostatin (Nipent) is a purine analog - an anti-metabolite. It is used in the treatment of certain blood cancers.

Indications of Pentostatin:

• Hairy cell leukemia:

  • It is prescribed as monotherapy for untreated and interferon-refractory hairy cell leukemia in patients with active disease.

• Off Label Use of Pentostatin in Adults:

  • Treatment of Acute graft-versus-host disease;
  • Treatment of steroid-refractory chronic graft-versus-host disease;
  • Chronic lymphocytic leukemia;
  • Cutaneous T-cell lymphomas, mycosis fungoides/Sezary syndrome;
  • Refractory T-cell prolymphocytic leukemia

Pentostatin dose in adults:

Pentostatin dose in the treatment of Hairy cell leukemia:

•  4 mg/m² intravenous every 2 weeks.

Note:

The optimal duration has not been determined; in the absence of unacceptable toxicity, may continue until complete response is achieved or until 2 doses after complete response. Discontinue after 6 months if partial or complete response is not achieved.

Pentostatin dose in the treatment of steroid-refractory acute graft-versus-host disease (GVHD):

• Initial therapy: 1.5 mg/m² intravenous days 1 to 3 and days 15 to 17 (in combination with corticosteroids).

• Steroid-refractory disease:

  • 5 mg/m intravenous daily for 3 days; may repeat after 2 weeks if needed.

Treatment dose of steroid-refractory chronic graft-versus-host disease (off-label):

• 4 mg/m² intravenous once every 2 weeks; discontinue after 6 months for a sustained objective response, or continue every 2 to 4 weeks for up to 12 months if still improving or 4 mg/m² once every 2 weeks for 3 months.

Pentostatin dose in the treatment of Chronic lymphocytic leukemia (off-label):

• Previously treated:

  • 4 mg/m² intravenous once every 3 weeks (in combination with cyclophosphamide and rituximab) for 6 cycles.

• Previously untreated:

  • 2 mg/m² intravenous once every 3 weeks (in combination with cyclophosphamide and rituximab) for 6 cycles.

Pentostatin dose in the treatment of cutaneous T-cell lymphoma, mycosis fungoides/Sezary syndrome (off-label):

• 4 mg/m² intravenous once weekly for 3 weeks, then every 2 weeks for 6 weeks, then once monthly for a maximum of 6 months.

Pentostatin dose in the treatment of refractory T-cell prolymphocytic leukemia (off-label):

• 4 mg/m² intravenous once weekly for 4 weeks then every 2 weeks until optimum response is achieved or 4 mg/m² once weekly for 4 weeks then every 2 weeks (in combination with alemtuzumab) until complete or best response or up to a total of 14 doses.

Pentostatin dose in children:

Pentostatin dose in steroid-refractory chronic graft-versus-host disease:

• Infant, Children, and Adolescents:

  • Initial: 4 mg/m² intravenous once every 2 weeks;
  • after 6 months of therapy, discontinue for sustained objective response, or continue same dose every 2 to 4 weeks for up to 12 months if still improving  or 4 mg/m once every 2 weeks for 3 months.

• Dosing adjustment for toxicity:

  • Infants, Children, and Adolescents:

    • ANC 500 to 1,000/mm³: 

      • 25% dose reduction.

    • ANC <500/mm³, platelets <20,000/mm³, or neutropenic fever:

      • 50% dose reduction.

    • Severe Infection:

      • Interrupt treatment until infection is controlled.

    • Rash:

      • Severe rashes may require treatment interruption or discontinuation based on experience in adult patients.

    • Other severe adverse reactions:

      • Withhold treatment or discontinue based on experience in adult patients.

Pregnancy Risk Category: D

• Studies on animal reproduction revealed that there were adverse events.
• During treatment, it is important to avoid pregnancy.

Use of pentostatin while breastfeeding

• It is not known if pentostatin is excreted in breast milk.
• Pentostatin can cause serious adverse reactions when it is given to infants. The decision to stop nursing should be made based on the mother's needs.

Pentostatin Dose adjustment in renal disease:

• The manufacturer's labeling does not include any dosage adjustments. However, two CrCl patients with CrCl 50-60 mL/minute responded to treatment with 2 mg/m.
• To prevent renal toxicities, do not take serum creatinine above normal and test creatinine clearance. These adjustments are also recommended:

  • CrCl 46 to 60 mL/minute:

    • Administer 70% of the dose.

  • CrCl 31 to 45 mL/minute:

    • Administer 60% of dose.

  • CrCl <30 mL/minute:

    • Consider use of alternative drug.

• Alternate recommendations: 

  • CrCl ≥60 mL/minute:

    • Administer 4 mg/m²/dose.

  • CrCl 40 to 59 mL/minute:

    • Administer 3 mg/m² /dose.

  • CrCl 20 to 39 mL/minute:

    • Administer 2 mg/m² /dose.

• For GVHD treatment:

  • CrCl 30 to 50 mL/minute:

    • 50% dose reduction.

  • CrCl <30 mL/minute/1.73 m²:

    • Withhold dose.

• For previously treated CLL:

  • Serum creatinine >2 mg/dL or 20% above patient’s baseline:

    • Withhold treatment until serum creatinine ≤2 mg/dL or returns to baseline, or until CrCl ≥50 mL/minute.

Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Common Side Effects of Pentostatin (Nipent):

• Central Nervous System:

  • Fatigue
  • Pain
  • Chills
  • Headache
  • Central Nervous System Toxicity

• Dermatologic:

  • Skin Rash
  • Pruritus
  • Skin Changes

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea
  • Anorexia
  • Abdominal Pain
  • Stomatitis

• Hematologic & Oncologic:

  • Leukopenia
  • Anemia
  • Thrombocytopenia
  • Bone Marrow Depression

• Hepatic:

  • Increased Serum Transaminases

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Myalgia
  • Weakness

• Respiratory:

  • Cough
  • Upper Respiratory Tract Infection
  • Rhinitis
  • Dyspnea

• Miscellaneous:

  • Fever

Rare Side Effects Of Pentostatin:

• Cardiovascular:

  • Chest Pain
  • Facial Edema
  • Hypotension
  • Peripheral Edema
  • Angina Pectoris
  • Atrioventricular Block
  • Bradycardia
  • Cardiac Arrhythmia
  • Cardiac Failure
  • Deep Vein Thrombophlebitis
  • Hypertension
  • Localized Phlebitis
  • Pericardial Effusion
  • Sinoatrial Arrest
  • Syncope
  • Tachycardia
  • Vasculitis
  • Ventricular Premature Contractions

• Central Nervous System:

  • Anxiety
  • Confusion
  • Depression
  • Dizziness
  • Drowsiness
  • Insomnia
  • Nervousness
  • Paresthesia
  • Abnormal Dreams
  • Abnormality In Thinking
  • Amnesia
  • Ataxia
  • Dysarthria
  • Emotional Lability
  • Encephalitis
  • Hallucination
  • Hostility
  • Meningism
  • Neuralgia
  • Neuritis
  • Neuropathy
  • Paralysis
  • Psychoneurosis
  • Seizure
  • Twitching
  • Vertigo

• Dermatologic:

  • Diaphoresis
  • Cellulitis
  • Furunculosis
  • Xeroderma
  • Urticaria
  • Acne Vulgaris
  • Alopecia
  • Eczema
  • Skin Photosensitivity

• Endocrine & Metabolic:

  • Amenorrhea
  • Decreased Libido
  • Hypercalcemia
  • Hyponatremia
  • Gout
  • Loss Of Libido

• Gastrointestinal:

  • Dyspepsia
  • Flatulence
  • Gingivitis
  • Constipation
  • Dysgeusia
  • Dysphagia
  • Glossitis
  • Intestinal Obstruction
  • Oral Candidiasis

• Genitourinary:

  • Urinary Tract Infection
  • Impotence

• Hematologic & Oncologic:

  • Agranulocytosis
  • Hemorrhage
  • Acute Leukemia
  • Aplastic Anemia
  • Hemolytic Anemia
  • Petechia

• Infection:

  • Herpes Zoster
  • Viral Infection
  • Bacterial Infection
  • Herpes Simplex Infection
  • Sepsis
  • Abscess

• Neuromuscular & Skeletal:

  • Arthralgia
  • Arthritis
  • Hyperkinesia
  • Osteomyelitis

• Ophthalmic:

  • Conjunctivitis
  • Amblyopia
  • Lacrimal Dysfunction
  • Nonreactive Pupils
  • Photophobia
  • Retinopathy
  • Visual Disturbance
  • Watery Eyes
  • Xerophthalmia

• Otic:

  • Deafness
  • Labyrinthitis
  • Otalgia
  • Tinnitus

• Renal:

  • Increased Serum Creatinine
  • Nephrolithiasis
  • Renal Disease
  • Renal Failure
  • Renal Function Abnormality
  • Renal Insufficiency

• Respiratory:

  • Pharyngitis
  • Sinusitis
  • Pneumonia
  • Asthma
  • Bronchitis
  • Bronchospasm
  • Flu-Like Symptoms
  • Laryngeal Edema
  • Pulmonary Embolism

Contraindications to Pentostatin (Nipent):

Hypersensitivity to pentostatin and any component of the formulation

Warnings and precautions

• Suppression of bone marrow
  • Pentostatin can cause myelosuppression, most often neutropenia when treated early.
  • For persistent neutropenia, it is important to determine the status of your disease.
  • During treatment, it is important to monitor blood counts.
• CNS toxicity: [U.S.Boxed Warnings]
  • Pentostatin in higher doses can cause severe CNS toxicities.
  • In this case, you should not seek treatment.
• Hepatotoxicity: [U.S.Boxed Warnings]
  • Pentostatin can cause liver toxicities, including elevated liver function tests and severe liver toxicities if taken in a higher dose.
• Pulmonary toxicities: [U.S.Boxed Warnings]
  • High doses can lead to severe pulmonary toxicities.
  • Combining fludarabine therapy with fludarabine can lead to fatal pulmonary toxicities.
• Rash:
  • It can cause severe rashes that are treated with discontinuation or interruption of treatment.
• Renal toxicities: [U.S.Boxed Warnings]
  • High doses can cause severe renal toxicities, as well as elevated serum creatinine.
  • Elevated serum creatinine should not be treated. Creatinine clearance should also be monitored.
  • You may need to adjust your dosage or stop taking the therapy..
• Infections
  • Pentostatin can exacerbate pre-existing infections so it is important to treat any infection before you start therapy.
  • Active infections should be treated temporarily during treatment.
• Renal impairment
  • Pentostatin's terminal half-life is extended in patients with renal dysfunction (CrCl >60 mL/minute). Therefore, dosage adjustments are necessary.

Pentostatin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• CBC with differential
• peripheral blood smears (periodically for hairy cells and to assess treatment response)
• Liver function tests
• Renal function tests
• Serum uric acid
• Bone marrow evaluation
• Signs/symptoms of pulmonary and CNS toxicity.

How to administer Pentostatin (Nipent)?

Pentostatin can be given as bolus infusion or intravenous infusion over half an hour with 500 to 1,000 mL fluid hydration before infusion and 500 mL after infusion.

Mechanism of action of Pentostatin (Nipent):

• Pentostatin, a purine antimetabolite, prevents the deamination from adenosine into inosine. It also inhibits adenosine desminase.
• Deoxyadenosine 5’triphosphate (dAdo), and purine metabolism (dAdo), can cause a reduction in purine metabolism, which results in cell death and DNA synthesis being blocked.

Protein binding:

• 4%

Half-life elimination:

• Terminal: 6 hours Renal impairment (CrCl <50 mL/minute): 18 hours (range: 11 to 23 hours).

Excretion:

• Urine (50% to 96%) within 24 hours (30% to 90% as unchanged drug)
• Clearance: Adults: 68 mL/minute/m (mean)

International Brands of Pentostatin:

• Nipent

Pentostatin Brand Names in Pakistan:

No Brands Available in Pakistan.