Pentostatin is a synthetic purine nucleoside antimetabolite. It is indicated for the treatment of hairy-cell leukemia in patients with active disease that is previously untreated or refractory to alpha-interferon therapy. Using a dose that is higher than the FDA-approved dosage is not recommended due to the potential for severe renal, hepatic, pulmonary, and nervous system toxicity. Additionally, the use of pentostatin in combination with fludarabine resulted in severe or fatal pulmonary toxicity in patients with refractory chronic lymphocytic leukemia; therefore, the use of pentostatin and fludarabine is not recommended.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-Treat spills and waste with 5% sodium hypochlorite solution prior to disposal.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Pentostatin may be administered as an intravenous (IV) bolus injection or (after dilution) as an IV infusion.
-Prehydrate with 500 to 1,000 mL of IV fluids (e.g., 5% Dextrose and 0.45% Sodium Chloride injection) prior to the pentostatin infusion; give an additional 500 mL of IV fluids after the dose.
Reconstitution:
-Add 5 mL of sterile water for injection to the 10-mg lyophilized powder vial for a final vial concentration of 2 mg/mL.
-Mix contents thoroughly until complete powder dissolution occurs.
-Storage after reconstitution: use or further dilute and use within 8 hours after reconstitution; discard unused portion of the vial.
IV Injection:
-Withdraw the calculated dose from the reconstituted vial into a syringe.
-Inject as an IV bolus.
IV Infusion:
-Further dilute the calculated dose in 5% Dextrose injection or 0.9% Sodium Chloride injection to a final admixture concentration between 0.18 and 0.33 mg/mL.
-Infuse IV over 20 to 30 minutes.
Allergic reaction was reported in 2% of previously untreated patients with hairy cell leukemia (HCL) (n = 180) who received pentostatin in a multicenter, comparative, phase III study. Additionally, allergic reaction occurred in 11% of patients with interferon-refractory HCL who received pentostatin in 2 noncomparative, phase II studies (n = 197).
Flu-like symptoms and hangover effect each occurred in less than 3% of previously untreated patients with hairy cell leukemia who received pentostatin (n = 180) in a multicenter, comparative, phase III study.
Hematologic toxicity has been reported with pentostatin therapy. Monitor complete blood counts prior to each dose and frequently during initial cycles of pentostatin. Perform a bone marrow evaluation if severe neutropenia persists beyond the initial cycles of therapy. Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase 3 study and in patients with interferon (INF)-refractory HCL in 2 noncomparative, phase 2 studies (n = 197). Hematologic toxicity reported in these studies include anemia (previously untreated, 8%; INF-refractory, 35%), leukopenia (previously untreated, 22%; INF-refractory, 60%), and thrombocytopenia (previously untreated, 6%; INF-refractory, 32%). Additionally, agranulocytosis occurred in 3% to 10% of previously untreated patients and acute leukemia (new primary malignancy/neoplasm), hemolytic anemia, and aplastic anemia each occurred in less than 3% of previously untreated patients in the phase 3 study. Febrile neutropenia, hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura (TTP), and autoimmune thrombocytopenia were reported in postmarketing surveillance of pentostatin.
Infection occurred in 38% of previously untreated patients with hairy cell leukemia (HCL) (n = 180) who received pentostatin in a multicenter, comparative, phase III study. Infectious events reported in this study were upper respiratory infection (13%), rhinitis (11%), herpes zoster (8%), pharyngitis (8%), viral infection (8%), infection (unspecified) (7%), sinusitis (6%), cellulitis (6%), bacterial infection (5%), pneumonia (5%), conjunctivitis (4%), furunculosis (4%), herpes simplex infection (4%), bronchitis (3%), sepsis (3%), urinary tract infection (3%), skin abscess (2%), oral moniliasis (2%), skin mycotic infection (< 1%), and osteomyelitis (1%). Fatalities have been reported in patients who had an infection prior to pentostatin therapy. Withhold pentostatin in patients with an active infection that occurs during treatment; pentostatin may be resumed when the infection is controlled.
Dermatologic toxicity has been reported with pentostatin therapy. Withhold pentostatin in patients who experience a severe rash. Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase 3 study and in patients with interferon (INF)-refractory HCL in 2 noncomparative, phase 2studies (n = 197). Dermatologic adverse events reported in these studies include rash (previously untreated, 43%; INF-refractory, 26%), pruritus (previously untreated, 21%; INF-refractory, 10%), sweating/hyperhidrosis (previously untreated, 8%; INF-refractory, 10%), and skin disorder (previously untreated, 4%; INF-refractory, 17%). Additionally, xerosis and urticaria each occurred in 3% to 10% of previously untreated patients and acne vulgaris, alopecia, eczema, petechiae, and photosensitivity each occurred in less than 3% of previously untreated patients in the phase 3 study. Exfoliative dermatitis was reported in postmarketing surveillance of pentostatin. A maculopapular rash with erythema occurs in up to 67% of patients.
Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase III study and in patients with interferon (INF)-refractory HCL in 2 noncomparative, phase II studies (n = 197). Nervous system adverse events reported in these studies include headache (previously untreated, 19%; INF-refractory, 11%) and neurologic disorder/central nervous system (CNS) toxicity (previously untreated, 1%; INF-refractory, 11%). Additionally, confusion, dizziness, insomnia, paresthesias, and somnolence/drowsiness each occurred in 3% to 10% of previously untreated patients and amnesia, ataxia, seizures, abnormal dreams, dysarthria, encephalitis, hyperkinesis, meningism, neuralgia, neuritis, neuropathy, muscle paralysis, syncope, twitching, and vertigo each occurred in less than 3% of previously untreated patients who received pentostatin in the phase III study. Severe CNS toxicity/neurotoxicity was reported with higher than recommended pentostatin doses (20 to 50 mg/m2 in divided doses over 5 days) in phase I studies. Withhold or discontinue pentostatin in patients showing evidence of nervous system toxicity.
Amblyopia, xerophthalmia, lacrimation disorder, nonreactive eye, photophobia, retinopathy, abnormal vision (visual impairment), and watery eyes each occurred in less than 3% of previously untreated patients with hairy cell leukemia (HCL) who received pentostatin (n = 180) in a multicenter, comparative, phase III study. Unilateral uveitis with vision loss has been reported with pentostatin use in 1 patient with HCL in another clinical study.
Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase III study and in patients with interferon (INF)-refractory HCL in 2 noncomparative, phase II studies (n = 197). Gastrointestinal (GI) adverse events reported in these studies include nausea/vomiting (previously untreated, 63%; INF-refractory, 53%), diarrhea (previously untreated, 17%; INF-refractory, 15%), abdominal pain (previously untreated, 16%; INF-refractory, 4%), anorexia (previously untreated, 13%; INF-refractory, 16%), and stomatitis (previously untreated, 12%; INF-refractory, 5%). Nausea alone was reported in 22% of patients with interferon-refractory HCL. Additionally, dyspepsia, flatulence, and gingivitis each occurred in 3% to 10% of previously untreated patients and constipation, dysphagia, glossitis, and ileus occurred in less than 3% of previously untreated patients in the phase III study.
In a multicenter, comparative, phase III study in previously untreated patients with hairy cell leukemia who received pentostatin (n = 180), chest pain (unspecified) and hypotension each occurred in 3% to 10% of patients and angina pectoris, arrhythmias, AV block, bradycardia, ventricular extrasystoles, cardiac arrest, heart failure, hypertension, pericardial effusion, phlebitis, pulmonary embolism, sinus arrest, sinus tachycardia, deep thrombo-phlebitis, and vasculitis each occurred in less than 3% of patients. Acute pulmonary edema and hypotension have been reported in patients who received pentostatin in combination with carmustine, etoposide, and high-dose cyclophosphamide as part of the ablative regimen for bone marrow transplant; some cases were fatal.
Genitourinary disorder occurred in 15% of patients with interferon-refractory hairy cell leukemia (HCL) who received pentostatin in 2 noncomparative, phase II studies (n = 197). In a multicenter, comparative, phase III study in previously untreated patients with HCL who received pentostatin (n = 180), elevated creatinine levels occurred in 3% to 10% of patients and amenorrhea, breast lump, impotence (erectile dysfunction), abnormal kidney function, nephropathy, renal failure (unspecified), renal insufficiency, and nephrolithiasis each occurred in less than 3% of patients. Severe nephrotoxicity was reported with higher than recommended pentostatin doses (20 to 50 mg/m2 in divided doses over 5 days) in phase I studies. At the recommended dosage, elevations in serum creatinine concentrations were usually minor and reversible. Determine renal function with a serum creatinine and/or a creatinine clearance assay before pentostatin initiation. Assess serum creatinine before each pentostatin dose and at other appropriate periods during therapy. Withhold pentostatin in patients who have elevated serum creatinine concentrations; determine a creatinine clearance. There are insufficient data to recommend a starting or a subsequent dose for patients with a creatinine clearance < 60 ml/minute. Only treat patients with impaired renal function when the potential benefit justifies the potential risk. Two patients with creatinine clearances of 50 to 60 mL/minute achieved a complete response without unusual adverse events when treated with 2 mg/m2.
Hearing loss, earache (otalgia), labyrinthitis, and tinnitus each occurred in less than 3% of previously untreated patients with hairy cell leukemia who received pentostatin (n = 180) in a multicenter, comparative, phase III study.
Face edema and peripheral edema each occurred in 3% to 10% of previously untreated patients with hairy cell leukemia who received pentostatin (n = 180) in a multicenter, comparative, phase III study.
Liver disorder/elevated hepatic enzymes occurred in 2% of previously untreated patients with hairy cell leukemia (HCL) who received pentostatin (n = 180) in a multicenter, comparative, phase III study. Additionally, Liver disorder/elevated hepatic enzymes occurred in 19% of patients with interferon-refractory HCL who received pentostatin in 2 noncomparative, phase II studies (n = 197). Severe hepatotoxicity was reported with higher than recommended pentostatin doses (20 to 50 mg/m2 in divided doses over 5 days) in phase I studies.
Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase 3 study and in patients with interferon (INF)-refractory HCL in 2 noncomparative, phase 2 studies (n = 197). Respiratory system adverse events reported in these studies include cough (previously untreated, 20%; INF-refractory, 17%), upper respiratory infection (previously untreated, 13%; INF-refractory, 16%), and dyspnea (previously untreated, 11%; INF-refractory, 8%). Lung disorder/disease was reported in 12% of patients with interferon-refractory HCL. Additionally, asthma occurred in 3% to 10% of previously untreated patients and bronchospasm and laryngeal edema each occurred in less than 3% of previously untreated patients in the phase 3 study. Severe pulmonary toxicity was reported with higher than recommended pentostatin doses (20 to 50 mg/m2 in divided doses over 5 days) in phase 1 studies. Severe or fatal pulmonary toxicity occurred in 4 of 6 patients with refractory chronic lymphocytic leukemia who received recommended doses of pentostatin in combination with fludarabine; therefore, the use of pentostatin plus fludarabine is not recommended. Acute respiratory failure was reported in postmarketing surveillance of pentostatin.
Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase III study and in patients with interferon-refractory HCL in 2 noncomparative, phase II studies (n = 197). Adverse events reported in these studies include fever (previously untreated, 46%; INF-refractory, 42%) and chills (previously untreated, 19%; INF-refractory, 11%).
Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase III study and in patients with interferon (INF)-refractory HCL in 2 noncomparative, phase II studies (n = 197). Musculoskeletal adverse events reported in these studies include myalgia (previously untreated, 19%; INF-refractory, 11%) and arthralgia (previously untreated, 6%; INF-refractory, 3%). Additionally, arthritis occurred in less than 3% of previously untreated patients who received pentostatin in the phase III study.
Gout occurred in less than 3% of previously untreated patients with hairy cell leukemia who received pentostatin in multicenter, comparative, phase III study.
Pentostatin has been studied in previously untreated patients with hairy cell leukemia (HCL) (n = 180) in a multicenter, comparative, phase III study and in patients with interferon (INF)-refractory HCL in 2 noncomparative, phase II studies (n = 197). Adverse events reported in these studies include fatigue (previously untreated, 42%; INF-refractory, 29%) and asthenia (previously untreated, 12%; INF-refractory, 10%).
Bleeding occurred in 3% to 10% of previously untreated patients with hairy cell leukemia who received pentostatin (n = 180) in a multicenter, comparative, phase III study.
In a multicenter, comparative, phase III study in previously untreated patients with hairy cell leukemia who received pentostatin (n = 180), anxiety, depression, and nervousness each occurred in 3% to 10% of patients and libido decrease, emotional lability, hallucinations, hostility, neurosis, and abnormal thinking each occurred in less than 3% of patients.
Hypercalcemia and hyponatremia each occurred in less than 3% of previously untreated patients with hairy cell leukemia who received pentostatin (n = 180) in a multicenter, comparative, phase III study.
Dysgeusia occurred in less than 3% of previously untreated patients with hairy cell leukemia (HCL) who received pentostatin (n = 180) in a multicenter, comparative, phase III study.
Pentostatin administration requires an experienced clinician who is qualified and knowledgeable in the use of cancer chemotherapeutic agents. The use of higher than the FDA-approved dosage is not recommended; severe nephrotoxicity, hepatotoxicity, pulmonary toxicity, and neurotoxicity occurred with pentostatin 20 to 50 mg/m2 administered in divided doses over 5 days in a phase 1 study. Therapy interruption or discontinuation may be necessary in patients who experience severe nervous system toxicity.
Pentostatin in combination with fludarabine resulted in severe or fatal pulmonary toxicity in 4 of 6 patients with refractory chronic lymphocytic leukemia; therefore, use with fludarabine is not recommended.
Pentostatin use is contraindicated in patients who have had a hypersensitivity reaction with pentostatin therapy. Serious rash has been reported; an interruption in pentostatin therapy may be necessary in patients who develop a severe or worsening rash.
Severe bone marrow suppression (e.g., anemia, neutropenia, thrombocytopenia) and infection have been reported with pentostatin therapy; some cases were fatal. Evaluate patients for and treat infections prior to starting or continuing pentostatin. Obtain complete blood cell counts prior to each dose and then frequently during therapy as appropriate. Interrupt therapy if the absolute neutrophil count (ANC) is less than 200 cells/mm3 during therapy in patients who had an initial ANC greater than 500 cells/mm3; resume pentostatin therapy when the ANC returns to pre-dose levels. Evaluate patients for disease status and response to treatment; bone marrow aspirates and biopsies may be obtained at 2- to 3-month intervals.
Use pentostatin with caution in patients with renal impairment; data is insufficient to recommend a starting or a subsequent dose in patients with a creatinine clearance (CrCl) less than 60 mL/min. Evaluate renal function (e.g., serum creatinine level, CrCl) prior to each pentostatin dose and then during therapy as appropriate.
Pentostatin may cause fetal harm if administered during pregnancy; therefore, females of reproductive potential should avoid becoming pregnant during therapy. Women should be informed of the potential risk to the fetus if pregnancy does occur. In animal studies, doses equivalent to a human clinical dose on a mg/m2 basis caused maternal toxicity and fetal teratogenicity manifested by increased incidence of various skeletal malformations, early delivery, spontaneous abortions, and fetal death.
Infertility studies using pentostatin have not been conducted in humans; however, in a 5-day intravenous toxicity study in canines, mild seminiferous tubular degeneration was observed at doses of 1 mg/kg and 4 mg/kg. The possible adverse effects on fertility in humans have not been determined.
It is not known whether pentostatin is excreted into human breast milk. The potential for serious adverse effects on the infant indicate that breast-feeding should be discontinued during pentostatin therapy or discontinue the drug, taking into account the importance of pentostatin to the mother.
For the treatment of hairy-cell leukemia:
NOTE: Pentostatin has been designated as an orphan drug by the FDA for the treatment of hairy-cell leukemia.
-for the treatment of hairy-cell leukemia in patients with active disease that is previously untreated or refractory to alpha-interferon therapy:
Intravenous dosage:
Adults: 4 mg/m2 IV once every other week; higher doses are not recommended. Continue treatment for 2 doses after the achievement of a complete response (CR). Discontinue pentostatin in patients who do not achieve a CR or partial response (PR) after 6 months of therapy or at the end of 12 months of therapy if the best response is a PR. Prehydrate with 500 to 1,000 mL of IV fluids (e.g., 5% Dextrose and 0.45% Sodium Chloride injection) prior to the pentostatin infusion; give an additional 500 mL of IV fluids after the dose. Therapy interruption or discontinuation may be necessary in patients who experience severe toxicity. Clinical trials with pentostatin in hairy-cell leukemia resulted in a CR of 83% and a PR of 15%. Overall survival was higher than 98% at 9 years for patients achieving CR. The survival at 5 years for PR plateaued at higher than 80%. With a median follow-up of 9.3 years, the 5- and 10-year relapse-free survival rates were 85% and 67%, respectively. The mortality rate and incidence of subsequent malignancies were not higher than expected than the general population.
For the treatment of chronic lymphocytic leukemia (CLL)*, in combination with cyclophosphamide and rituximab:
NOTE: Pentostatin was designated an orphan drug by the FDA for this indication
Intravenous dosage:
Adults: 2 mg/m2 or 4 mg/m2 IV on day 1 in combination with cyclophosphamide (600 mg/m2 IV on day 1) and rituximab (375 mg/m2 IV on day 1) repeated every 21 days for 6 or 8 cycles has been studied in clinical trials. The first cycle rituximab administration varied in these studies with 1 study giving rituximab 100 mg/m2 on day 1 and 375 mg/m2 on days 3 and 5 on cycle 1 and another study administering rituximab 100 mg/m2 on day 8 and 275 mg/m2 on day 9 on cycle 1. Patients received prophylactic antibiotic and/or antiviral therapy in these studies.
For stem cell transplant preparation* prior to allogeneic stem cell transplantation, in combination with extracorporeal photopheresis and reduced dose total body irradiation:
Intravenous dosage:
Adults: 4 mg/m2/day continuous IV infusion on days -5 and -4, preceded by extracorporeal photopheresis on days -7 and -6, and followed by reduced intensity total body irradiation on days -3 and -2. All patients received cyclosporin starting on day -1 and methotrexate on days +1 and +3 to prevent graft-versus-host disease.
For the treatment of graft-versus-host disease (GVHD)*:
-for the treatment of acute GVHD*:
Intravenous dosage:
Adults: 1.5 mg/m2/dose IV once daily for 3 days; may repeat cycle every 2 weeks as indicated. Guidelines suggest pentostatin as a third-line treatment option for steroid-refractory acute GVHD.
Children and Adolescents: 1.5 mg/m2/dose IV once daily for 3 days; may repeat cycle every 2 weeks as indicated. Guidelines suggest pentostatin as a third-line treatment option for steroid-refractory acute GVHD.
-for the treatment of chronic GVHD*:
Intravenous dosage:
Adults: 4 mg/m2/dose IV every 2 weeks for 12 doses. In persons still showing improvement at 6 months, may continue pentostatin every 3 to 4 weeks until therapeutic plateau. Guidelines suggest pentostatin as a second-line treatment option for refractory chronic GVHD.
Children and Adolescents: 4 mg/m2/dose IV every 2 weeks for 12 doses. In persons still showing improvement at 6 months, may continue pentostatin every 3 to 4 weeks until therapeutic plateau. Guidelines suggest pentostatin as a second-line treatment option for refractory chronic GVHD.
For graft-versus-host disease (GVHD) prophylaxis*:
Intravenous dosage:
Adults: 1.5 mg/m2 IV on days +8, +15, +22, and +30 after transplantation. Doses were adjusted for decreased renal function (serum creatinine 1.5 to 2 g/dL: reduce dose by 75%; serum creatinine level higher than 2 g/dL: withhold). In addition to pentostatin, tacrolimus was given IV on day -2 to achieve target levels between 5 and 15 ng/mL, and methotrexate 5 mg/m2 IV was given on days +1, +3, and +6.
For the treatment of advanced cutaneous T-cell lymphoma (CTCL)*, including mycosis fungoides* and Sezary syndrome*:
NOTE: Pentostatin has been designated an orphan drug by the FDA for the treatment of cutaneous T cell lymphoma and peripheral T cell lymphoma.
Intravenous dosage:
Adults: 4 mg/m2 IV weekly for 3 or 4 weeks as induction therapy has been evaluated in nonrandomized clinical trials. Treatment was continued with pentostatin 4 mg/m2 IV every 2 weeks until maximal response in 1 study and with pentostatin 4 mg/m2 IV every 2 weeks for 6 weeks followed by maintenance therapy with pentostatin 4 mg/m2 IV monthly in another study. Pentostatin 2.8, 3.75, or 5 mg/m2/day (median dose of 3.75 mg/m2) IV for 3 days repeated every 3 weeks (median of 2 cycles; range, 1 to 12 cycles) was evaluated in another nonrandomized trial. Patients were started at the 5 mg/m2 dose (age 60 years and older and patients with significant medical problems started at 3.75 mg/m2) and were lowered to 3.75 mg/m2 (-1 dose level) or 2.8 mg/m2 (-2 dose levels) based on severity of toxicity. Supportive measures such as hydration; allopurinol; and prophylactic antibacterial, antifungal, and/or antiviral were used in clinical studies.
Maximum Dosage Limits:
-Adults
4 mg/m2 IV once every other week.
-Geriatric
4 mg/m2 IV once every other week.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Creatinine clearance (CrCl) of 60 mL/min or greater: No dosage adjustment needed.
CrCl less than 60 mL/min: Data is insufficient to recommend a starting or a subsequent dose. Two patients with impaired renal function (CrCl of 50 to 60 mL/min) who received a reduced pentostatin dose (2 mg/m2) achieved a complete response without experiencing unusual adverse events.
*non-FDA-approved indication
Abciximab: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Acetaminophen; Ibuprofen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Albuterol; Budesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Anagrelide: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Aspirin, ASA; Dipyridamole: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Azelastine; Fluticasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Basiliximab: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
Beclomethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Betamethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide; Formoterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chikungunya Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciclesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cilostazol: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Clopidogrel: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Corticosteroids: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cyclophosphamide: (Moderate) Monitor for signs and symptoms of cardiac dysfunction if coadministration of cyclophosphamide with pentostatin is necessary as there is an increased risk of cardiotoxicity.
Cyclosporine: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as immunosuppressives may result in additive effects. A dosage reduction of the antineoplastic may be indicated when used in combination with other myelosuppressive chemotherapy.
Deflazacort: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dexamethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Diclofenac: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Dipyridamole: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Eptifibatide: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Etodolac: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fenoprofen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fludarabine: (Contraindicated) The combined use of pentostatin and fludarabine phosphate is not recommended because it may be associated with an increased risk of fatal pulmonary toxicity. A boxed warning about this potentially fatal interaction exists in the product label. In a clinical investigation in patients with refractory chronic lymphocytic leukemia using pentostatin at the recommended dose in combination with fludarabine phosphate, 4 of 6 patients entered in the study had severe or fatal pulmonary toxicity.
Fludrocortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Flunisolide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Flurbiprofen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fluticasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Salmeterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Vilanterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Formoterol; Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Hydrocortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Ibuprofen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Famotidine: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Indomethacin: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ketoprofen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Methylprednisolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Nabumetone: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Olopatadine; Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Oxaprozin: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Piroxicam: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Platelet Inhibitors: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Prasugrel: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Prednisolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Prednisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Ropeginterferon alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sulindac: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Ticagrelor: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Tirofiban: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Tolmetin: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Triamcinolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Vigabatrin: (Major) Vigabatrin should not be used with pentostatin, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Vorapaxar: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Pentostatin is a potent transition state inhibitor of the enzyme adenosine deaminase (ADA), which acts as a regulator on intracellular adenosine levels. Following inhibition, an increase in intracellular deoxyadenosine triphosphate (dATP) results in apoptosis of B and T cells. dATP is an allosteric inhibitor of ribonucleotide reductase. The ultimate effect on inhibition of ribonucleotide reductase and depletion of other deoxynucleotides affects DNA and RNA synthesis. This inhibition results in the arrest of cells in the G1 or S phase of the cell cycle and subsequent cell dysfunction and death. Pentostatin also decreases levels of nicotinamide, leading to depletion of nicotinamide adenine dinucleotide. Death of lymphocytes can be partly attributed to a reduction of this important vitamin. T lymphocytes have a much higher level of adenosine deaminase than B lymphocytes. This difference explains the increased susceptibility of T lymphocytes to the cytotoxic effects of pentostatin. Higher doses of pentostatin are required for cells containing greater amounts of adenosine deaminase. Other observed pharmacologic actions include inhibition of RNA transcription, production of DNA strand breaks, and incorporation of pentostatin triphosphate in DNA.
Resistance mechanisms via p53 pathways are under investigation. The TP53 gene is mutated and/or deleted in approximately 10% to 15% of patients with CLL while 15% to 20% of patients exhibit a mutation in the gene encoding ATM (ataxia telangiectasia mutated), a kinase regulating p53. Such mutations result in impaired accumulation of p53 and thereby resistance to killing. Drug resistance also arises from low cellular capacity for purine analogue phosphorylation. The clinical response to purine analogues also appears to correlate with the expression of Bcl-2 proteins. Strategies for overcoming purine analogue resistance include the following: combine purine analogue with monoclonal antibodies, combine with Bcl-2 antisense oligonucleotide, or reestablishment of p53 function via insertion of peptides corresponding to the C-terminus of wild-type p53.
Pentostatin is administered intravenously.
Plasma protein binding is only 4%. Pentostatin has limited penetration of the blood/brain barrier. Concentrations of pentostatin in cerebrospinal fluid reach 10-12% of those in plasma 2-4 hours after IV administration. CSF half-life is > 11 hours. Pentostatin undergoes little metabolism. Excretion is 90% renal, mainly as unchanged drug. The mean terminal half-life is 5.7 hours (range of 2.6-15 hours). Mean total clearance is independent of dosage, but correlates with creatinine clearance as 90% of the drug is excreted unchanged in urine.
-Route-Specific Pharmacokinetics
Intravenous Route
Mean plasma concentrations of pentostatin are proportional to the dose. Distribution half-life has been recorded at 11 minutes following a dose of 4 mg/m2 infused over 5 minutes.
-Special Populations
Renal Impairment
There is a positive correlation between pentostatin clearance and renal function in patients with creatine clearance (CrCl) ranging from 60-130 ml/min with a half-life of 6 hours. For patients with CrCl < 50 ml/min, the half-life is 18 hours. Patients with elevated serum creatinine should have their dose withheld and a CrCl determined. There are insufficient data to recommend a starting or subsequent dose for patients with impaired renal function. In a study comparing the pharmacokinetics of pentostatin in patients with renal insufficiency to those with normal renal function, the mean plasma clearance in the normal renal function (NRF) patients was 114 ml/min compared to 72 ml/min in impaired renal function (IRF) patients. The mean half life was 5.35 hours (NRF) compared to 7.16 hours (IRF). This study revealed that CrCl predicts total pentostatin plasma clearance but not pentostatin renal clearance. Pentostatin total plasma clearance and renal clearance were lower in patients with impaired renal function.