Pentostatin is a medication used in the treatment of certain types of cancer and immune system disorders. It belongs to a class of drugs known as purine analogs, and it works by interfering with the growth and reproduction of abnormal cells in the body.

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:

The usual dose is 4 mg for every square meter of a person's body area, given into a vein every 2 weeks.

When to stop? If everything goes well without bad side effects:

• Keep giving it until the cancer is completely gone.
• After the cancer is gone, give 2 more doses and then stop.

If the cancer isn't mostly or completely gone after 6 months, stop the medicine.

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

Starting Treatment:

• Give 1.5 mg for every square meter of the person's body area into a vein.
• Do this on days 1, 2, 3, then again on days 15, 16, 17.
• This is combined with other drugs called corticosteroids.

For those where steroids didn't work:

• Give 1.5 mg for every square meter of the person's body area into a vein.
• Do this daily for 3 days.
• If the disease isn't better after 2 weeks, you can do the 3-day treatment again.

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

Usual Dose:

• Give 4 mg for every square meter of the person's body size into a vein.
• Do this once every 2 weeks.

Stopping or Continuing the Treatment:

• If there's a good response after 6 months, stop the medicine.
• If the condition is getting better but hasn't fully improved, continue the dose once every 2 to 4 weeks. You can do this for up to 12 months.

Another Treatment Plan:

• Alternatively, some suggest giving 4 mg for every square meter of the person's body size into a vein once every 2 weeks, but only for 3 months.

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

For patients who've had treatment before:

• Dose: 4 mg for every square meter of the person's body size, given into a vein.
• Frequency: Once every 3 weeks.
• Duration: Do this for 6 cycles (rounds).
• Note: This is given together with two other drugs, cyclophosphamide and rituximab.

For patients who've never had treatment:

• Dose: 2 mg for every square meter of the person's body size, given into a vein.
• Frequency: Once every 3 weeks.
• Duration: Do this for 6 cycles (rounds).
• Note: This is also given together with cyclophosphamide and rituximab.

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

Start:

• Dose: 4 mg for every square meter of the person's body size, given into a vein.
• Frequency: Once a week.
• Duration: Do this weekly for 3 weeks.

Next Phase:

• Keep the dose the same.
• Frequency: Once every 2 weeks.
• Duration: Do this for 6 weeks.

Final Phase:

• Keep the dose the same.
• Frequency: Once a month.
• Duration: Continue monthly up to a maximum of 6 months.

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

First Treatment Plan (Mercieca, 1994):

• Dose: 4 mg for each square meter of the person's body size, given into a vein.
• Frequency: Once a week.
• Duration: Do this weekly for 4 weeks.
• After this: Continue the same dose every 2 weeks until the best possible result is seen.

Second Treatment Plan (Ravandi, 2009):

• Dose: 4 mg for each square meter of the person's body size, given into a vein.
• Frequency: Once a week.
• Duration: Do this weekly for 4 weeks.
• After this: Combine with another drug called alemtuzumab and continue the same dose every 2 weeks. Continue until the patient achieves the best response or a total of 14 doses are given.

Pentostatin dose in children:

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

Infants, children, and teenagers when regular steroid treatments aren't working:

Usual Dose:

• Dose: 4 mg for every square meter of the young person's body size, given into a vein.
• Frequency: Once every 2 weeks.

Stopping or Continuing the Treatment:

• If there's a good response after 6 months, stop the medicine.
• If things are getting better but haven't fully improved, continue giving the same dose. This can be once every 2 to 4 weeks, for up to a year.

Another Treatment Plan:

• Another option is to give the 4 mg dose (based on body size) once every 2 weeks, but only for 3 months.

Dosing adjustment for toxicity:

For children and adolescents when using Pentostatin to treat graft-versus-host disease (GVHD):

• If Absolute Neutrophil Count (ANC) is between 500 to 1,000/mm³:
  • Reduce the Pentostatin dose by 25%.
• If ANC is less than 500/mm³, or platelet count is less than 20,000/mm³, or if the patient has neutropenic fever (a fever due to low white blood cell count):
  • Reduce the Pentostatin dose by 50%.
• If the patient has a severe infection:
  • Stop Pentostatin treatment until the infection is under control.
• If the patient develops a severe rash:
  • Severe rashes may require a pause or discontinuation of Pentostatin treatment based on the experience with adult patients.
• For other severe adverse reactions:
  • Depending on the severity and type of adverse reaction, Pentostatin treatment may need to be temporarily withheld or discontinued. This decision is often based on the experience with adult patients.

These adjustments are made to manage any side effects or complications that may arise during the course of treatment.

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

• We don't know if Pentostatin gets into breast milk.
• Because it might harm a breastfeeding baby, mothers need to choose either to stop taking Pentostatin or to stop breastfeeding.
• This choice should consider how important the medicine is for the mother's health.

Pentostatin Dose adjustment in renal disease:

• Manufacturer's Labeling:
  • The manufacturer doesn't provide specific dosage adjustments based on kidney function.
  • Two patients with a moderate decrease in kidney function (CrCl 50 to 60 mL/minute) responded well to a reduced dose of 2 mg/m².
• Kintzel, 1995 Recommendations:
  • If the creatinine clearance (CrCl) is between 46 to 60 mL/minute, give 70% of the usual dose.
  • If the CrCl is between 31 to 45 mL/minute, give 60% of the usual dose.
  • If the CrCl is less than 30 mL/minute, consider using a different drug.
• Lathia, 2002 Recommendations:
  • If the CrCl is 60 mL/minute or higher, administer the usual dose of 4 mg/m².
  • If the CrCl is between 40 to 59 mL/minute, administer 3 mg/m².
  • If the CrCl is between 20 to 39 mL/minute, administer 2 mg/m².
• Alousi, 2009; Jacobsohn, 2009; Poi, 2013 (for GVHD treatment):
  • If the CrCl is between 30 to 50 mL/minute per 1.73 m², reduce the dose by 50%.
  • If the CrCl is less than 30 mL/minute per 1.73 m², withhold the dose.
• Lamanna, 2006 (for previously treated CLL):
  • If the serum creatinine is greater than 2 mg/dL or 20% higher than the patient's baseline, withhold treatment until the serum creatinine is less than or equal to 2 mg/dL, returns to baseline, or the CrCl is at least 50 mL/minute.

Pentostatin 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):

If someone is allergic to Pentostatin or any ingredient in the medicine, they shouldn't take it.

Warnings and precautions

Suppression of bone marrow

• Bone marrow can get weaker, mostly at the start of treatment.
• This can lead to a low number of white blood cells, especially when treating hairy cell leukemia.
• If there's a big drop in white blood cells and it doesn't get better after the first few treatments, check to see how the disease is doing.
• Always keep an eye on blood counts during treatment, especially at the beginning.

CNS toxicity: [U.S.Boxed Warnings]

• Taking too much of this medication can harm your brain and nerves.
• Follow the recommended dose and don't take more.
• If you experience problems with your brain or nerves, stop taking the medication.

Hepatotoxicity: [U.S.Boxed Warnings]

• Using more than the recommended dose of this medication can harm your liver.
• Stick to the suggested amount.
• It might also make your liver function tests show abnormal results, but this is usually temporary and goes back to normal.

Pulmonary toxicities: [U.S.Boxed Warnings]

• Using too much of this medication can harm your lungs.
• Stick to the recommended dose and don't use it at the same time as fludarabine, as this can lead to serious or deadly lung problems.

Rash:

• Serious rashes can develop, and they may get worse if you keep taking the medication.
• You might need to stop or pause the treatment if this happens.

Renal toxicities: [U.S.Boxed Warnings]

• Using more than the recommended dose of this medication can harm your kidneys.
• Stick to the suggested amount.
• If your blood test shows elevated creatinine levels while taking the recommended dose, it's usually not a big problem and can be reversed.
• However, if your creatinine levels rise significantly, you might need to stop the treatment, adjust the dose, or even discontinue it.

Infections

• If you have an infection before starting this treatment, it's best to treat and clear the infection first, if possible.
• Using this medication with existing infections can make them worse.
• If you get a new infection while on pentostatin treatment, your healthcare provider may temporarily stop the treatment until the infection is under control.
• This medication should only be used in patients with infections if the potential benefits outweigh the risks.

Renal impairment

• If you have kidney issues with a creatinine clearance (CrCl) less than 60 mL/minute, be careful when using this medication.
• It stays in your body longer when your kidneys aren't working well.

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:

• Before each dose:
  • CBC (Complete Blood Count) with differential and platelet count
  • More often at the start of treatment
• Periodic peripheral blood smears to check for hairy cells and assess treatment response

Liver and Kidney Function

• Check liver function regularly
• Measure serum uric acid levels
• Monitor renal function with serum creatinine
• Evaluate creatinine clearance at the beginning
• Recheck serum creatinine before each dose

Bone Marrow Evaluation

• Periodically assess bone marrow for any changes

Watch for Toxicity Signs

• Keep an eye out for symptoms of lung (pulmonary) and brain (CNS) toxicity

How to administer Pentostatin (Nipent)?

• Give as an IV (intravenous) infusion
• Administer over 20 to 30 minutes or as a quick bolus (rapid injection)
• Before the infusion, hydrate with 500 to 1,000 mL of fluids
• After the infusion, provide an additional 500 mL of fluids

Mechanism of action of Pentostatin (Nipent):

• Pentostatin is a medication that interferes with a process in cells.
• It blocks an enzyme called adenosine deaminase.
• By doing this, it stops adenosine from turning into inosine.
• This causes deoxyadenosine (dAdo) and deoxyadenosine 5′-triphosphate (dATP) to build up in cells.
• The increase in these substances reduces the cell's ability to make purines, which are essential for DNA production.
• With purine metabolism disrupted, cells can't make DNA properly, and this can lead to cell death.

Distribution

• Volume of distribution (V): About 20 liters per square meter of body surface area (L/m²).

Protein Binding

• Approximately 4% of the medication is bound to proteins in the blood.

Half-life

• Terminal Half-life: Approximately 6 hours.
• In individuals with kidney problems (CrCl <50 mL/minute): The half-life is extended to around 18 hours, with a range between 11 to 23 hours.

Excretion

• Most of the drug is eliminated through urine, typically within 24 hours.
• A significant portion (30% to 90%) is excreted unchanged in the urine.

Clearance

• In adults, the mean clearance rate is about 68 mL per minute per square meter of body surface area (m²).

International Brands of Pentostatin:

• Nipent

Pentostatin Brand Names in Pakistan:

Not available.