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Nipent
Overview
What is Nipent?
NIPENT (pentostatin for injection) is supplied as a sterile, apyrogenic, lyophilized powder in single-dose vials for intravenous administration. Each vial contains 10 mg of pentostatin and 50 mg of Mannitol, USP. The pH of the final product is maintained between 7.0 and 8.5 by addition of sodium hydroxide or hydrochloric acid.
Pentostatin, also known as 2'-deoxycoformycin (DCF), is a potent inhibitor of the enzyme adenosine deaminase and is isolated from fermentation cultures of . Pentostatin is known chemically as (R)-3-(2-deoxy-ß-D-erythropentofuranosyl)3,6,7,8 tetrahydroimidazo[4,5d][1,3]diazepin-8-ol with a molecular formula of CHNO and a molecular weight of 268.27. The molecular structure of pentostatin is:
Pentostatin is a white to off-white solid, freely soluble in distilled water.
What does Nipent look like?
What are the available doses of Nipent?
Sorry No records found.
What should I talk to my health care provider before I take Nipent?
Sorry No records found
How should I use Nipent?
NIPENT is indicated as single-agent treatment for both untreated and alpha-interferon-refractory hairy cell leukemia patients with active disease as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.
It is recommended that patients receive hydration with 500 to 1,000 mL of 5% Dextrose in 0.5 Normal Saline or equivalent before NIPENT administration. An additional 500 mL of 5% Dextrose or equivalent should be administered after NIPENT is given.
The recommended dosage of NIPENT for the treatment of hairy cell leukemia is 4 mg/m every other week. NIPENT may be administered intravenously by bolus injection or diluted in a larger volume and given over 20 to 30 minutes (See ).
Higher doses are not recommended.
No extravasation injuries were reported in clinical studies.
The optimal duration of treatment has not been determined. In the absence of major toxicity and with observed continuing improvement, the patient should be treated until a complete response has been achieved. Although not established as required, the administration of two additional doses has been recommended following the achievement of a complete response.
All patients receiving NIPENT at 6 months should be assessed for response to treatment. If the patient has not achieved a complete or partial response, treatment with NIPENT should be discontinued.
If the patient has achieved a partial response, NIPENT treatment should be continued in an effort to achieve a complete response. At any time thereafter that a complete response is achieved, two additional doses of NIPENT are recommended. NIPENT treatment should then be stopped. If the best response to treatment at the end of 12 months is a partial response, it is recommended that treatment with NIPENT be stopped.
Withholding or discontinuation of individual doses may be needed when severe adverse reactions occur. Drug treatment should be withheld in patients with severe rash, and withheld or discontinued in patients showing evidence of nervous system toxicity.
NIPENT treatment should be withheld in patients with active infection occurring during the treatment but may be resumed when the infection is controlled.
Patients who have elevated serum creatinine should have their dose withheld and a creatinine clearance determined. There are insufficient data to recommend a starting or a subsequent dose for patients with impaired renal function (creatinine clearance <60 mL/min).
Patients with impaired renal function should be treated only when the potential benefit justifies the potential risk. Two patients with impaired renal function (creatinine clearances 50 to 60 mL/min) achieved complete response without unusual adverse events when treated with 2 mg/m.
No dosage reduction is recommended at the start of therapy with NIPENT in patients with anemia, neutropenia, or thrombocytopenia. In addition, dosage reductions are not recommended during treatment in patients with anemia and thrombocytopenia if patients can be otherwise supported hematologically. NIPENT should be temporarily withheld if the absolute neutrophil count falls during treatment below 200 cells/mm in a patient who had an initial neutrophil count greater than 500 cells/mm and may be resumed when the count returns to predose levels.
Preparation of Intravenous Solution
Stability
NIPENT vials are stable at refrigerated storage temperature 2° to 8° C (36° to 46°F) for the period stated on the package. Vials reconstituted or reconstituted and further diluted as directed may be stored at room temperature and ambient light but should be used within 8 hours because NIPENT contains no preservatives.
What interacts with Nipent?
NIPENT is contraindicated in patients who have demonstrated hypersensitivity to NIPENT.
What are the warnings of Nipent?
See
Patients with hairy cell leukemia may experience myelosuppression primarily during the first few courses of treatment. Patients with infections prior to NIPENT treatment have in some cases developed worsening of their condition leading to death, whereas others have achieved complete response. Patients with infection should be treated only when the potential benefit of treatment justifies the potential risk to the patient. Efforts should be made to control the infection before treatment is initiated or resumed.
In patients with progressive hairy cell leukemia, the initial courses of NIPENT treatment were associated with worsening of neutropenia. Therefore, frequent monitoring of complete blood counts during this time is necessary. If severe neutropenia continues beyond the initial cycles, patients should be evaluated for disease status, including a bone marrow examination.
Elevations in liver function tests occurred during treatment with NIPENT and were generally reversible.
Renal toxicity was observed at higher doses in early studies; however, in patients treated at the recommended dose, elevations in serum creatinine were usually minor and reversible. There were some patients who began treatment with normal renal function who had evidence of mild to moderate toxicity at a final assessment (See ).
Rashes, occasionally severe, were commonly reported and may worsen with continued treatment. Withholding of treatment may be required (See ).
Acute pulmonary edema and hypotension, leading to death, have been reported in the literature in patients treated with pentostatin in combination with carmustine, etoposide and high dose cyclophosphamide as part of the ablative regimen for bone marrow transplant.
Pregnancy
Pentostatin can cause fetal harm when administered to a pregnant woman. Pentostatin was administered intravenously at doses of 0, 0.01, 0.1, or 0.75 mg/kg/day (0, 0.06, 0.6, and 4.5 mg/m) to pregnant rats on days 6 through 15 of gestation. Drug-related maternal toxicity occurred at doses of 0.1 and 0.75 mg/kg/day (0.6 and 4.5 mg/m). Teratogenic effects were observed at 0.75 mg/kg/day (4.5 mg/m) manifested by increased incidence of various skeletal malformations. In a dose range-finding study, pentostatin was administered intravenously to rats at doses of 0, 0.05, 0.1, 0.5, 0.75, or 1 mg/kg/day (0, 0.3, 0.6, 3, 4.5, 6 mg/m), on days 6 through 15 of gestation. Fetal malformations that were observed were an omphalocele at 0.05 mg/kg (0.3 mg/m), gastroschisis at 0.75 mg/kg and 1 mg/kg (4.5 and 6 mg/m), and a flexure defect of the hindlimbs at 0.75 mg/kg (4.5 mg/m). Pentostatin was also shown to be teratogenic in mice when administered as a single 2 mg/kg (6 mg/m) intraperitoneal injection on day 7 of gestation. Pentostatin was not teratogenic in rabbits when administered intravenously on days 6 through 18 of gestation at doses of 0, 0.005, 0.01, or 0.02 mg/kg/day (0, 0.015, 0.03, or 0.06 mg/m); however maternal toxicity, abortions, early deliveries, and deaths occurred in all drug-treated groups. There are no adequate and well-controlled studies in pregnant women. If NIPENT is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential receiving NIPENT should be advised to avoid becoming pregnant.
What are the precautions of Nipent?
General
Therapy with NIPENT requires regular patient observation and monitoring of hematologic parameters and blood chemistry values. If severe adverse reactions occur, the drug should be withheld (see ), and appropriate corrective measures should be taken according to the clinical judgment of the physician.
NIPENT treatment should be withheld or discontinued in patients showing evidence of nervous system toxicity.
Information for Patients
Patients should be advised of the signs and symptoms of adverse events associated with NIPENT therapy (See ).
Laboratory Tests
Prior to initiating therapy with NIPENT, renal function should be assessed with a serum creatinine and/or a creatinine clearance assay (See and ). Complete blood counts and serum creatinine should be performed before each dose of NIPENT and at other appropriate periods during therapy (see ). Severe neutropenia has been observed following the early courses of treatment with NIPENT and therefore frequent monitoring of complete blood counts is recommended during this time. If hematologic parameters do not improve with subsequent courses, patients should be evaluated for disease status, including a bone marrow examination. Periodic monitoring of the peripheral blood for hairy cells should be performed to assess the response to treatment.
In addition, bone marrow aspirates and biopsies may be required at 2 to 3 month intervals to assess the response to treatment.
Drug Interactions
Allopurinol and NIPENT are both associated with skin rashes. Based on clinical studies in 25 refractory patients who received both NIPENT and allopurinol, the combined use of NIPENT and allopurinol did not appear to produce a higher incidence of skin rashes than observed with NIPENT alone. There has been a report of one patient who received both drugs and experienced a hypersensitivity vasculitis that resulted in death. It was unclear whether this adverse event and subsequent death resulted from the drug combination.
Biochemical studies have demonstrated that pentostatin enhances the effects of vidarabine, a purine nucleoside with antiviral activity. The combined use of vidarabine and NIPENT may result in an increase in adverse reactions associated with each drug. The therapeutic benefit of the drug combination has not been established.
The combined use of NIPENT and fludarabine phosphate is not recommended because it may be associated with an increased risk of fatal pulmonary toxicity (see ).
Acute pulmonary edema and hypotension, leading to death, have been reported in the literature in patients treated with pentostatin in combination with carmustine, etoposide and high dose cyclophosphamide as part of the ablative regimen for bone marrow transplant.
Carcinogenesis, Mutagenesis, Impairment of Fertility
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Pregnancy
(See )
Nursing Mothers
It is not known whether NIPENT is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from pentostatin, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of NIPENT to the mother.
Pediatric Use
Safety and effectiveness in children or adolescents have not been established.
What are the side effects of Nipent?
Most patients treated for hairy cell leukemia in the five NCI-sponsored Phase 2 studies and the Phase 3 SWOG study experienced an adverse event. The following table lists the most frequently occurring adverse events in patients treated with NIPENT (both frontline and IFN-refractory patients) compared with IFN (frontline only), regardless of drug association. The drug association of some adverse events is uncertain as they may be associated with the disease itself (eg, infection, hematologic suppression), but other events, such as the gastrointestinal symptoms, rashes, and abnormal liver function tests, can in many cases be attributed to the drug. Most adverse events that were assessed for severity were either mild or moderate, and diminished in frequency with continued therapy.
The total incidence for all types of infections is considerably higher for both treatment groups in the SWOG 8691 study than is listed in the table above. An intent-to-treat analysis of infections found that 38% of patients treated with NIPENT and 34% of patients treated with IFN averaged 2.4 and 1.9 documented infections during treatment, respectively. The following table lists the different types of infections that were reported as adverse events during the initial phase of the SWOG study. There were no apparent differences in the types of infection between the 2 treatment groups, with the possible exception of herpes zoster which was reported more frequently for NIPENT (8%) than for IFN (1%).
The drug relatedness of the adverse events listed below cannot be excluded. The following adverse events occurred in 3% to 10% of NIPENT-treated patients in the initial phase of the SWOG study:
Body as a Whole
Cardiovascular System
Digestive System
Hemic and Lymphatic System
Laboratory Deviations
Musculoskeletal System
Nervous System
Psychobiologic Function
Respiratory System
Skin & Appendages
The remaining adverse events which occurred in less than 3% of NIPENT-treated patients during the initial phase of the SWOG study:
Body as a Whole
Cardiovascular System
Digestive System
Hemic and Lymphatic System
Laboratory Deviations
Musculoskeletal System
Nervous System
Psychobiologic Function
Respiratory System
Skin and Appendages
Special Senses
Urogenital System
One patient with hairy cell leukemia treated with NIPENT during another clinical study developed unilateral uveitis with vision loss.
Nineteen (5%) patients withdrew from the Phase 3 SWOG 8691 study because of adverse events; 9 during initial NIPENT treatment, 4 during NIPENT crossover, 5 during initial IFN treatment, and 1 during both initial IFN treatment and NIPENT crossover. In the Phase 2 studies in IFN-refractory hairy cell leukemia, 11% of patients withdrew from treatment with NIPENT due to an adverse event.
| NR = Not Reported Occurring in more than 10% of patients, in any group, regardless of drug association Includes only nausea with vomiting These figures represent only unspecified infections. Refer to infection table. Elevated liver enzymes and liver disorder for SWOG | |||
| Percent of Patients | |||
| All Adverse Events | |||
| Nausea and/or Vomiting | 63 | 22 | 53 |
| Fever | 46 | 59 | 42 |
| Rash | 43 | 30 | 26 |
| Fatigue | 42 | 55 | 29 |
| Leukopenia | 22 | 15 | 60 |
| Pruritus | 21 | 6 | 10 |
| Coughing/Increased Cough | 20 | 15 | 17 |
| Myalgia | 19 | 36 | 11 |
| Chills | 19 | 34 | 11 |
| Headache | 17 | 29 | 13 |
| Diarrhea | 17 | 17 | 15 |
| Abdominal Pain | 16 | 15 | 4 |
| Anorexia | 13 | 10 | 16 |
| Upper Respiratory Infection | 13 | 8 | 16 |
| Asthenia | 12 | 13 | 10 |
| Stomatitis | 12 | 7 | 5 |
| Rhinitis | 11 | 15 | 10 |
| Dyspnea | 11 | 13 | 8 |
| Anemia | 8 | 5 | 35 |
| Pain | 8 | 19 | 20 |
| Pharyngitis | 8 | 11 | 10 |
| Sweating/Increased Sweating | 8 | 21 | 10 |
| Viral Infection | 8 | 17 | NR |
| Infection | 7 | 2 | 36 |
| Arthralgia | 6 | 14 | 3 |
| Thrombocytopenia | 6 | 6 | 32 |
| Skin Disorder | 4 | 5 | 17 |
| Allergic Reaction | 2 | 1 | 11 |
| Hepatic Disorder/Elevated Liver Function Tests | 2 | 2 | 19 |
| Neurologic Disorder, CNS/CNS Toxicity | 1 | NR | 11 |
| Lung Disorder/Disease | NR | 1 | 12 |
| Nausea | NR | NR | 22 |
| Genitourinary Disorder | NR | NR | 15 |
| Percent of Patients | |||
| Type of Infection | |||
| Upper Respiratory Infection | 13 | 8 | |
| Rhinitis | 11 | 15 | |
| Herpes Zoster | 8 | 1 | |
| Pharyngitis | 8 | 11 | |
| Viral Infection | 8 | 17 | |
| Infection (Unspecified) | 7 | 2 | |
| Sinusitis | 6 | 4 | |
| Cellulitis | 6 | 3 | |
| Bacterial Infection | 5 | 4 | |
| Pneumonia | 5 | 7 | |
| Conjunctivitis | 4 | 2 | |
| Furunculosis | 4 | <1 | |
| Herpes Simplex | 4 | 1 | |
| Bronchitis | 3 | 2 | |
| Sepsis | 3 | 2 | |
| Urinary Tract Infection | 3 | 3 | |
| Abscess, Skin | 2 | 4 | |
| Moniliasis, Oral | 2 | <1 | |
| Mycotic Infection, Skin | <1 | 3 | |
| Osteomyelitis | 1 | 0 |
What should I look out for while using Nipent?
NIPENT is contraindicated in patients who have demonstrated hypersensitivity to NIPENT.
See
Patients with hairy cell leukemia may experience myelosuppression primarily during the first few courses of treatment. Patients with infections prior to NIPENT treatment have in some cases developed worsening of their condition leading to death, whereas others have achieved complete response. Patients with infection should be treated only when the potential benefit of treatment justifies the potential risk to the patient. Efforts should be made to control the infection before treatment is initiated or resumed.
In patients with progressive hairy cell leukemia, the initial courses of NIPENT treatment were associated with worsening of neutropenia. Therefore, frequent monitoring of complete blood counts during this time is necessary. If severe neutropenia continues beyond the initial cycles, patients should be evaluated for disease status, including a bone marrow examination.
Elevations in liver function tests occurred during treatment with NIPENT and were generally reversible.
Renal toxicity was observed at higher doses in early studies; however, in patients treated at the recommended dose, elevations in serum creatinine were usually minor and reversible. There were some patients who began treatment with normal renal function who had evidence of mild to moderate toxicity at a final assessment (See ).
Rashes, occasionally severe, were commonly reported and may worsen with continued treatment. Withholding of treatment may be required (See ).
Acute pulmonary edema and hypotension, leading to death, have been reported in the literature in patients treated with pentostatin in combination with carmustine, etoposide and high dose cyclophosphamide as part of the ablative regimen for bone marrow transplant.
Pregnancy
Pentostatin can cause fetal harm when administered to a pregnant woman. Pentostatin was administered intravenously at doses of 0, 0.01, 0.1, or 0.75 mg/kg/day (0, 0.06, 0.6, and 4.5 mg/m) to pregnant rats on days 6 through 15 of gestation. Drug-related maternal toxicity occurred at doses of 0.1 and 0.75 mg/kg/day (0.6 and 4.5 mg/m). Teratogenic effects were observed at 0.75 mg/kg/day (4.5 mg/m) manifested by increased incidence of various skeletal malformations. In a dose range-finding study, pentostatin was administered intravenously to rats at doses of 0, 0.05, 0.1, 0.5, 0.75, or 1 mg/kg/day (0, 0.3, 0.6, 3, 4.5, 6 mg/m), on days 6 through 15 of gestation. Fetal malformations that were observed were an omphalocele at 0.05 mg/kg (0.3 mg/m), gastroschisis at 0.75 mg/kg and 1 mg/kg (4.5 and 6 mg/m), and a flexure defect of the hindlimbs at 0.75 mg/kg (4.5 mg/m). Pentostatin was also shown to be teratogenic in mice when administered as a single 2 mg/kg (6 mg/m) intraperitoneal injection on day 7 of gestation. Pentostatin was not teratogenic in rabbits when administered intravenously on days 6 through 18 of gestation at doses of 0, 0.005, 0.01, or 0.02 mg/kg/day (0, 0.015, 0.03, or 0.06 mg/m); however maternal toxicity, abortions, early deliveries, and deaths occurred in all drug-treated groups. There are no adequate and well-controlled studies in pregnant women. If NIPENT is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential receiving NIPENT should be advised to avoid becoming pregnant.
What might happen if I take too much Nipent?
No specific antidote for NIPENT overdose is known. NIPENT administered at higher doses (20- 50 mg/m in divided doses over 5 days) than recommended was associated with deaths due to severe renal, hepatic, pulmonary, and CNS toxicity. In case of overdose, management would include general supportive measures through any period of toxicity that occurs.
How should I store and handle Nipent?
Storage and HandlingStore in a dry place at 77°F (25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature]. Keep out of the reach of children. Storage and HandlingStore in a dry place at 77°F (25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature]. Keep out of the reach of children. Storage and HandlingStore in a dry place at 77°F (25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature]. Keep out of the reach of children. NIPENT (pentostatin for injection) is supplied as a sterile lyophilized white to off-white powder in single-dose vials containing 10 mg of pentostatin. The vials are packed in individual cartons. Storage: Store NIPENT vials under refrigerated storage conditions 2° to 8° C (36° to 46°F).NIPENT (pentostatin for injection) is supplied as a sterile lyophilized white to off-white powder in single-dose vials containing 10 mg of pentostatin. The vials are packed in individual cartons. Storage: Store NIPENT vials under refrigerated storage conditions 2° to 8° C (36° to 46°F).
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Mechanism of Action
Pentostatin is a potent transition state inhibitor of the enzyme adenosine deaminase (ADA). The greatest activity of ADA is found in cells of the lymphoid system with T-cells having higher activity than B-cells, and T-cell malignancies having higher ADA activity than B-cell malignancies. Pentostatin inhibition of ADA, particularly in the presence of adenosine or deoxyadenosine, leads to cytotoxicity, and this is believed to be due to elevated intracellular levels of dATP which can block DNA synthesis through inhibition of ribonucleotide reductase. Pentostatin can also inhibit RNA synthesis as well as cause increased DNA damage. In addition to elevated dATP, these mechanisms may also contribute to the overall cytotoxic effect of pentostatin. The precise mechanism of pentostatin's antitumor effect, however, in hairy cell leukemia is not known.
Pharmacokinetics/Drug Metabolism
A tissue distribution and whole-body autoradiography study in the rat revealed that radioactivity concentrations were highest in the kidneys with very little central nervous system penetration.
In man, following a single dose of 4 mg/m of pentostatin infused over 5 minutes, the distribution half-life was 11 minutes, the mean terminal half-life was 5.7 hours, the mean plasma clearance was 68 mL/min/m, and approximately 90% of the dose was excreted in the urine as unchanged pentostatin and/or metabolites as measured by adenosine deaminase inhibitory activity. The plasma protein binding of pentostatin is low, approximately 4%.
A positive correlation was observed between pentostatin clearance and creatinine clearance (CrCl) in patients with creatinine clearance values ranging from 60 mL/min to 130 mL/min. Pentostatin half-life in patients with renal impairment (CrCl <50 mL/min, n=2) was 18 hours, which was much longer than that observed in patients with normal renal function (CrCl >60 mL/min, n=14), about 6 hours.
Non-Clinical Toxicology
NIPENT is contraindicated in patients who have demonstrated hypersensitivity to NIPENT.See
Patients with hairy cell leukemia may experience myelosuppression primarily during the first few courses of treatment. Patients with infections prior to NIPENT treatment have in some cases developed worsening of their condition leading to death, whereas others have achieved complete response. Patients with infection should be treated only when the potential benefit of treatment justifies the potential risk to the patient. Efforts should be made to control the infection before treatment is initiated or resumed.
In patients with progressive hairy cell leukemia, the initial courses of NIPENT treatment were associated with worsening of neutropenia. Therefore, frequent monitoring of complete blood counts during this time is necessary. If severe neutropenia continues beyond the initial cycles, patients should be evaluated for disease status, including a bone marrow examination.
Elevations in liver function tests occurred during treatment with NIPENT and were generally reversible.
Renal toxicity was observed at higher doses in early studies; however, in patients treated at the recommended dose, elevations in serum creatinine were usually minor and reversible. There were some patients who began treatment with normal renal function who had evidence of mild to moderate toxicity at a final assessment (See ).
Rashes, occasionally severe, were commonly reported and may worsen with continued treatment. Withholding of treatment may be required (See ).
Acute pulmonary edema and hypotension, leading to death, have been reported in the literature in patients treated with pentostatin in combination with carmustine, etoposide and high dose cyclophosphamide as part of the ablative regimen for bone marrow transplant.
Pregnancy
Pentostatin can cause fetal harm when administered to a pregnant woman. Pentostatin was administered intravenously at doses of 0, 0.01, 0.1, or 0.75 mg/kg/day (0, 0.06, 0.6, and 4.5 mg/m) to pregnant rats on days 6 through 15 of gestation. Drug-related maternal toxicity occurred at doses of 0.1 and 0.75 mg/kg/day (0.6 and 4.5 mg/m). Teratogenic effects were observed at 0.75 mg/kg/day (4.5 mg/m) manifested by increased incidence of various skeletal malformations. In a dose range-finding study, pentostatin was administered intravenously to rats at doses of 0, 0.05, 0.1, 0.5, 0.75, or 1 mg/kg/day (0, 0.3, 0.6, 3, 4.5, 6 mg/m), on days 6 through 15 of gestation. Fetal malformations that were observed were an omphalocele at 0.05 mg/kg (0.3 mg/m), gastroschisis at 0.75 mg/kg and 1 mg/kg (4.5 and 6 mg/m), and a flexure defect of the hindlimbs at 0.75 mg/kg (4.5 mg/m). Pentostatin was also shown to be teratogenic in mice when administered as a single 2 mg/kg (6 mg/m) intraperitoneal injection on day 7 of gestation. Pentostatin was not teratogenic in rabbits when administered intravenously on days 6 through 18 of gestation at doses of 0, 0.005, 0.01, or 0.02 mg/kg/day (0, 0.015, 0.03, or 0.06 mg/m); however maternal toxicity, abortions, early deliveries, and deaths occurred in all drug-treated groups. There are no adequate and well-controlled studies in pregnant women. If NIPENT is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential receiving NIPENT should be advised to avoid becoming pregnant.
Allopurinol and NIPENT are both associated with skin rashes. Based on clinical studies in 25 refractory patients who received both NIPENT and allopurinol, the combined use of NIPENT and allopurinol did not appear to produce a higher incidence of skin rashes than observed with NIPENT alone. There has been a report of one patient who received both drugs and experienced a hypersensitivity vasculitis that resulted in death. It was unclear whether this adverse event and subsequent death resulted from the drug combination.
Biochemical studies have demonstrated that pentostatin enhances the effects of vidarabine, a purine nucleoside with antiviral activity. The combined use of vidarabine and NIPENT may result in an increase in adverse reactions associated with each drug. The therapeutic benefit of the drug combination has not been established.
The combined use of NIPENT and fludarabine phosphate is not recommended because it may be associated with an increased risk of fatal pulmonary toxicity (see ).
Acute pulmonary edema and hypotension, leading to death, have been reported in the literature in patients treated with pentostatin in combination with carmustine, etoposide and high dose cyclophosphamide as part of the ablative regimen for bone marrow transplant.
Therapy with NIPENT requires regular patient observation and monitoring of hematologic parameters and blood chemistry values. If severe adverse reactions occur, the drug should be withheld (see ), and appropriate corrective measures should be taken according to the clinical judgment of the physician.
NIPENT treatment should be withheld or discontinued in patients showing evidence of nervous system toxicity.
Most patients treated for hairy cell leukemia in the five NCI-sponsored Phase 2 studies and the Phase 3 SWOG study experienced an adverse event. The following table lists the most frequently occurring adverse events in patients treated with NIPENT (both frontline and IFN-refractory patients) compared with IFN (frontline only), regardless of drug association. The drug association of some adverse events is uncertain as they may be associated with the disease itself (eg, infection, hematologic suppression), but other events, such as the gastrointestinal symptoms, rashes, and abnormal liver function tests, can in many cases be attributed to the drug. Most adverse events that were assessed for severity were either mild or moderate, and diminished in frequency with continued therapy.
The total incidence for all types of infections is considerably higher for both treatment groups in the SWOG 8691 study than is listed in the table above. An intent-to-treat analysis of infections found that 38% of patients treated with NIPENT and 34% of patients treated with IFN averaged 2.4 and 1.9 documented infections during treatment, respectively. The following table lists the different types of infections that were reported as adverse events during the initial phase of the SWOG study. There were no apparent differences in the types of infection between the 2 treatment groups, with the possible exception of herpes zoster which was reported more frequently for NIPENT (8%) than for IFN (1%).
The drug relatedness of the adverse events listed below cannot be excluded. The following adverse events occurred in 3% to 10% of NIPENT-treated patients in the initial phase of the SWOG study:
Body as a Whole
Cardiovascular System
Digestive System
Hemic and Lymphatic System
Laboratory Deviations
Musculoskeletal System
Nervous System
Psychobiologic Function
Respiratory System
Skin & Appendages
The remaining adverse events which occurred in less than 3% of NIPENT-treated patients during the initial phase of the SWOG study:
Body as a Whole
Cardiovascular System
Digestive System
Hemic and Lymphatic System
Laboratory Deviations
Musculoskeletal System
Nervous System
Psychobiologic Function
Respiratory System
Skin and Appendages
Special Senses
Urogenital System
One patient with hairy cell leukemia treated with NIPENT during another clinical study developed unilateral uveitis with vision loss.
Nineteen (5%) patients withdrew from the Phase 3 SWOG 8691 study because of adverse events; 9 during initial NIPENT treatment, 4 during NIPENT crossover, 5 during initial IFN treatment, and 1 during both initial IFN treatment and NIPENT crossover. In the Phase 2 studies in IFN-refractory hairy cell leukemia, 11% of patients withdrew from treatment with NIPENT due to an adverse event.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
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