DRUGS & SUPPLEMENTS

Batinel

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Batinel uses


INDICATIONS AND USAGE

Batinel is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). Batinel is not indicated in the treatment of patients with primary progressive multiple sclerosis.

The clinical patterns of multiple sclerosis in the studies were characterized as follows: secondary progressive and progressive relapsing disease were characterized by gradual increasing disability with or without superimposed clinical relapses, and worsening relapsing-remitting disease was characterized by clinical relapses resulting in a step-wise worsening of disability.

Batinel in combination with corticosteroids is indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer.

Batinel in combination with other approved drug(s) is indicated in the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.

CONTRAINDICATIONS

Batinel is contraindicated in patients who have demonstrated prior hypersensitivity to it.

WARNINGS

WHEN Batinel IS USED IN HIGH DOSES SUCH AS INDICATED FOR THE TREATMENT OF LEUKEMIA, SEVERE MYELOSUPPRESSION WILL OCCUR. THEREFORE, IT IS RECOMMENDED THAT Batinel BE ADMINISTERED ONLY BY PHYSICIANS EXPERIENCED IN THE CHEMOTHERAPY OF THIS DISEASE. LABORATORY AND SUPPORTIVE SERVICES MUST BE AVAILABLE FOR HEMATOLOGIC AND CHEMISTRY MONITORING AND ADJUNCTIVE THERAPIES, INCLUDING ANTIBIOTICS.

BLOOD AND BLOOD PRODUCTS MUST BE AVAILABLE TO SUPPORT PATIENTS DURING THE EXPECTED PERIOD OF MEDULLARY HYPOPLASIA AND SEVERE MYELOSUPPRESSION. PARTICULAR CARE SHOULD BE GIVEN TO ASSURING FULL HEMATOLOGIC RECOVERY BEFORE UNDERTAKING CONSOLIDATION THERAPY (IF THIS TREATMENT IS USED) AND PATIENTS SHOULD BE MONITORED CLOSELY DURING THIS PHASE. Batinel ADMINISTERED AT ANY DOSE CAN CAUSE MYELOSUPPRESSION.

CONTAINS SODIUM METABISULFITE, A SULFITE THAT MAY CAUSE ALLERGIC-TYPE REACTIONS INCLUDING ANAPHYLACTIC SYMPTOMS AND LIFE-THREATENING OR LESS SEVERE ASTHMATIC EPISODES IN CERTAIN SUSCEPTIBLE PEOPLE. THE OVERALL PREVALENCE OF SULFITE SENSITIVITY IN THE GENERAL POPULATION IS UNKNOWN AND PROBABLY LOW. SULFITE SENSITIVITY IS SEEN MORE FREQUENTLY IN ASTHMATIC THAN IN NONASTHMATIC PEOPLE.

General

Patients with preexisting myelosuppression as the result of prior drug therapy should not receive Batinel unless it is felt that the possible benefit from such treatment warrants the risk of further medullary suppression.

The safety of Batinel Injection, USP (concentrate) in patients with hepatic insufficiency is not established (see CLINICAL PHARMACOLOGY ).

Safety for use by routes other than intravenous administration has not been established.

Batinel is not indicated for subcutaneous, intramuscular, or intra-arterial injection. There have been reports of local/regional neuropathy, some irreversible, following intra-arterial injection.

Batinel must not be given by intrathecal injection. There have been reports of neuropathy and neurotoxicity, both central and peripheral, following intrathecal injection. These reports have included seizures leading to coma and severe neurologic sequelae, and paralysis with bowel and bladder dysfunction.

Topoisomerase II inhibitors, including Batinel, have been associated with the development of secondary acute myeloid leukemia and myelosuppression.

Cardiac Effects

Because of the possible danger of cardiac effects in patients previously treated with daunorubicin or doxorubicin, the benefit-to-risk ratio of Batinel therapy in such patients should be determined before starting therapy.

Functional cardiac changes including decreases in left ventricular ejection fraction and irreversible congestive heart failure can occur with Batinel. Cardiac toxicity may be more common in patients with prior treatment with anthracyclines, prior mediastinal radiotherapy, or with preexisting cardiovascular disease. Such patients should have regular cardiac monitoring of LVEF from the initiation of therapy. Cancer patients who received cumulative doses of 140 mg/m2 either alone or in combination with other chemotherapeutic agents had a cumulative 2.6% probability of clinical congestive heart failure. In comparative oncology trials, the overall cumulative probability rate of moderate or severe decreases in LVEF at this dose was 13%.

Multiple Sclerosis

Changes in cardiac function may occur in patients with multiple sclerosis treated with Batinel. In one controlled trial (Study 1, see CLINICAL TRIALS, Multiple Sclerosis ), two patients (2%) of 127 receiving Batinel, one receiving a 5 mg/m2 dose and the other receiving the 12 mg/m2 dose, had LVEF values that decreased to below 50%. An additional patient receiving 12 mg/m2, who did not have LVEF measured, had a decrease in another echocardiographic measurement of ventricular function (fractional shortening) that led to discontinuation from the trial (see ADVERSE REACTIONS, Multiple Sclerosis ). There were no reports of congestive heart failure in either controlled trial.

MS patients should be assessed for cardiac signs and symptoms by history, physical examination, ECG, and quantitative LVEF evaluation using appropriate methodology (ex. Echocardiogram, MUGA, MRI, etc.) prior to the start of Batinel therapy. MS patients with a baseline LVEF below the lower limit of normal should not be treated with Batinel. Subsequent LVEF and ECG evaluations are recommended if signs or symptoms of congestive heart failure develop and prior to every dose administered to MS patients. Batinel should not be administered to MS patients who experience a reduction in LVEF to below the lower limit of normal, to those who experience a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of 140 mg/m2. MS patients should have yearly quantitative LVEF evaluation after stopping Batinel to monitor for late-occurring cardiotoxicity.

Leukemia

Acute congestive heart failure may occasionally occur in patients treated with Batinel for ANLL. In first-line comparative trials of Batinel + cytarabine vs daunorubicin + cytarabine in adult patients with previously untreated ANLL, therapy was associated with congestive heart failure in 6.5% of patients on each arm. A causal relationship between drug therapy and cardiac effects is difficult to establish in this setting since myocardial function is frequently depressed by the anemia, fever and infection, and hemorrhage that often accompany the underlying disease.

Hormone-Refractory Prostate Cancer

Functional cardiac changes such as decreases in LVEF and congestive heart failure may occur in patients with hormone-refractory prostate cancer treated with Batinel. In a randomized comparative trial of Batinel plus low-dose prednisone vs low-dose prednisone, 7 of 128 patients treated with Batinel had a cardiac event defined as any decrease in LVEF below the normal range, congestive heart failure (n = 3), or myocardial ischemia. Two patients had a prior history of cardiac disease. The total Batinel dose administered to patients with cardiac effects ranged from > 48 to 212 mg/m2.

Among 112 patients evaluable for safety on the Batinel + hydrocortisone arm of the CALGB trial, 18 patients (19%) had a reduction in cardiac function, 5 patients (5%) had cardiac ischemia, and 2 patients (2%) experienced pulmonary edema. The range of total Batinel doses administered to these patients is not available.

Pregnancy

Batinel may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant. Batinel is considered a potential human teratogen because of its mechanism of action and the developmental effects demonstrated by related agents. Treatment of pregnant rats during the organogenesis period of gestation was associated with fetal growth retardation at doses ≥0.1 mg/kg/day (0.01 times the recommended human dose on a mg/m2 basis). When pregnant rabbits were treated during organogenesis, an increased incidence of premature delivery was observed at doses ≥0.1 mg/kg/day (0.01 times the recommended human dose on a mg/m2 basis). No teratogenic effects were observed in these studies, but the maximum doses tested were well below the recommended human dose (0.02 and 0.05 times in rats and rabbits, respectively, on a mg/m2 basis). There are no adequate and well-controlled studies in pregnant women. Women with multiple sclerosis who are biologically capable of becoming pregnant should have a pregnancy test prior to each dose, and the results should be known prior to administration of the drug. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus.

Secondary Leukemia

Batinel therapy increases the risk of developing secondary leukemia in patients with cancer and in patients with multiple sclerosis.

In a study of patients with prostate cancer, acute myeloid leukemia occurred in 1% (5/487) of mitoxantrone-treated patients versus no cases in the control group (0/496) not receiving Batinel at 4.7 years followup.

In a prospective, open-label, tolerability and safety monitoring study of Batinel treated MS patients followed for up to five years (median of 2.8 years), leukemia occurred in 0.6% (3/509) of patients. Publications describe leukemia risk of 0.25% to 2.8% in cohorts of patients with MS treated with Batinel and followed for varying periods of time. This leukemia risk exceeds the risk of leukemia in the general population. The most commonly reported types were acute promyelocytic leukemia and acute myelocytic leukemia.

In 1774 patients with breast cancer who received Batinel concomitantly with other cytotoxic agents and radiotherapy, the cumulative risk of developing treatment-related acute myeloid leukemia was estimated as 1.1% and 1.6% at 5 and 10 years, respectively. The second largest report involved 449 patients with breast cancer treated with Batinel, usually in combination with radiotherapy and/or other cytotoxic agents. In this study, the cumulative probability of developing secondary leukemia was estimated to be 2.2% at 4 years.

Secondary acute myeloid leukemia has also been reported in cancer patients treated with anthracyclines. Batinel is an anthracenedione, a related drug. The occurrence of secondary leukemia is more common when anthracyclines are given in combination with DNA-damaging antineoplastic agents, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated.

Symptoms of acute leukemia may include excessive bruising, bleeding, and recurrent infections.

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PRECAUTIONS

General

Therapy with Batinel should be accompanied by close and frequent monitoring of hematologic and chemical laboratory parameters, as well as frequent patient observation.

Systemic infections should be treated concomitantly with or just prior to commencing therapy with Batinel.

Information for Patients

Inform patients of the availability of a Medication Guide and instruct them to read the Medication Guide prior to initiating treatment with Batinel and prior to each infusion. Review the Batinel Medication Guide with every patient prior to initiation of treatment and periodically during treatment. Instruct patients that Batinel should be taken only as prescribed.

Advise patients that Batinel can cause myelosuppression and inform patients of the signs and symptoms of myelosuppression. Advise patients that Batinel can cause congestive heart failure that may lead to death even in people who have never had heart problems before, and inform patients of the signs and symptoms of congestive heart failure. Advise patients receiving Batinel to treat multiple sclerosis that they should receive cardiac monitoring prior to each Batinel dose and yearly after stopping Batinel.

Batinel may impart a blue-green color to the urine for 24 hours after administration, and patients should be advised to expect this during therapy. Bluish discoloration of the sclera may also occur.

Laboratory Tests

A complete blood count, including platelets, should be obtained prior to each course of Batinel and in the event that signs and symptoms of infection develop. Liver function tests should also be performed prior to each course of therapy. Batinel therapy in multiple sclerosis patients with abnormal liver function tests is not recommended because Batinel clearance is reduced by hepatic impairment and no laboratory measurement can predict drug clearance and dose adjustments.

In leukemia treatment, hyperuricemia may occur as a result of rapid lysis of tumor cells by Batinel. Serum uric acid levels should be monitored and hypouricemic therapy instituted prior to the initiation of antileukemic therapy.

Women with multiple sclerosis who are biologically capable of becoming pregnant, even if they are using birth control, should have a pregnancy test, and the results should be known, before receiving each dose of Batinel (see WARNINGS, Pregnancy ).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Intravenous treatment of rats and mice, once every 21 days for 24 months, with Batinel resulted in an increased incidence of fibroma and external auditory canal tumors in rats at a dose of 0.03 mg/kg, and hepatocellular adenoma in male mice at a dose of 0.1 mg/kg (0.03 fold the recommended human dose, on a mg/m2 basis). Intravenous treatment of rats, once every 21 days for 12 months with Batinel resulted in an increased incidence of external auditory canal tumors in rats at a dose of 0.3 mg/kg (0.15 fold the recommended human dose, on a mg/m2 basis).

Mutagenesis

Batinel was clastogenic in the in vivo rat bone marrow assay. Batinel was also clastogenic in two in vitro assays; it induced DNA damage in primary rat hepatocytes and sister chromatid exchanges in Chinese hamster ovary cells. Batinel was mutagenic in bacterial and mammalian test systems (Ames/Salmonella and E. coli and L5178Y TK+/-mouse lymphoma).

Drug Interactions

Batinel and its metabolites are excreted in bile and urine, but it is not known whether the metabolic or excretory pathways are saturable, may be inhibited or induced, or if Batinel and its metabolites undergo enterohepatic circulation. To date, post-marketing experience has not revealed any significant drug interactions in patients who have received Batinel for treatment of cancer. Information on drug interactions in patients with multiple sclerosis is limited.

Following concurrent administration of Batinel with corticosteroids, no evidence of drug interactions has been observed.

Special Populations

Hepatic Impairment

Patients with multiple sclerosis who have hepatic impairment should ordinarily not be treated with Batinel. Batinel should be administered with caution to other patients with hepatic impairment. In patients with severe hepatic impairment, the AUC is more than three times greater than the value observed in patients with normal hepatic function.

Pregnancy

Pregnancy Category D

.

Nursing Mothers

Batinel is excreted in human milk and significant concentrations (18 ng/mL) have been reported for 28 days after the last administration. Because of the potential for serious adverse reactions in infants from Batinel, breast feeding should be discontinued before starting treatment.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Multiple Sclerosis

Clinical studies of Batinel did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Hormone-Refractory Prostate Cancer

One hundred forty-six patients aged 65 and over and 52 younger patients have been treated with Batinel in controlled clinical studies. These studies did not include sufficient numbers of younger patients to determine whether they respond differently from older patients. However, greater sensitivity of some older individuals cannot be ruled out.

Acute Nonlymphocytic Leukemia

Although definitive studies with Batinel have not been performed in geriatric patients with ANLL, toxicity may be more frequent in the elderly. Elderly patients are more likely to have age-related comorbidities due to disease or disease therapy.

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ADVERSE REACTIONS

Multiple Sclerosis

Batinel has been administered to 149 patients with multiple sclerosis in two randomized clinical trials, including 21 patients who received Batinel in combination with corticosteroids.

In Study 1, the proportion of patients who discontinued treatment due to an adverse event was 9.7% in the 12 mg/m2 Batinel arm (leukopenia, depression, decreased LV function, bone pain and emesis, renal failure, and one discontinuation to prevent future complications from repeated urinary tract infections) compared to 3.1% (n = 2) in the placebo arm (hepatitis and myocardial infarction). The following clinical adverse experiences were significantly more frequent in the Batinel groups: nausea, alopecia, urinary tract infection, and menstrual disorders, including amenorrhea.

Table 4a summarizes clinical adverse events of all intensities occurring in ≥5% of patients in either dose group of Batinel and that were numerically greater on drug than on placebo in Study 1. The majority of these events were of mild to moderate intensity, and nausea was the only adverse event that occurred with severe intensity in more than one patient (three patients [5%] in the 12 mg/m2 group). Of note, alopecia consisted of mild hair thinning.

Two of the 127 patients treated with Batinel in Study 1 had decreased LVEF to below 50% at some point during the 2 years of treatment. An additional patient receiving 12 mg/m2 did not have LVEF measured, but had another echocardiographic measure of ventricular function (fractional shortening) that led to discontinuation from the study.

Percent of Patients
Preferred Term Placebo (N = 64) 5 mg/m2

Batinel (N = 65)

12 mg/m2

Batinel (N = 62)

Nausea 20 55 76
Alopecia 31 38 61
Menstrual disorderPercentage of female patients. 26 51 61
Amenorrhea 3 28 43
Upper respiratory tract infection 52 51 53
Urinary tract infection 13 29 32
Stomatitis 8 15 19
Arrhythmia 8 6 18
Diarrhea 11 25 16
Urine abnormal 6 5 11
ECG abnormal 3 5 11
Constipation 6 14 10
Back pain 5 6 8
Sinusitis 2 3 6
Headache 5 6 6

The proportion of patients experiencing any infection during Study 1 was 67% for the placebo group, 85% for the 5 mg/m2 group, and 81% for the 12 mg/m2 group. However, few of these infections required hospitalization: one placebo patient (tonsillitis), three 5 mg/m2 patients (enteritis, urinary tract infection, viral infection), and four 12 mg/m2 patients (tonsillitis, urinary tract infection [two], endometritis).

Table 4b summarizes laboratory abnormalities that occurred in ≥ 5% of patients in either Batinel dose group, and that were numerically more frequent than in the placebo group.

Percent of Patients
Event Placebo (N = 64) 5 mg/m2

Batinel (N = 65)

12 mg/m2

Batinel (N = 62)

Leukopenia< 4000 cells/mm3 0 9 19
Gamma-GT increased 3 3 15
SGOT increased 8 9 8
Granulocytopenia< 2000 cells/mm3 2 6 6
Anemia 2 9 6
SGPT increased 3 6 5

There was no difference among treatment groups in the incidence or severity of hemorrhagic events.

In Study 2, Batinel was administered once a month. Clinical adverse events most frequently reported in the Batinel group included amenorrhea (53% of female patients), alopecia (33% of patients), nausea (29% of patients), and asthenia (24% of patients). Tables 5a and 5b respectively summarize adverse events and laboratory abnormalities occurring in > 5% of patients in the Batinel group and numerically more frequent than in the control group.

Percent of Patients
Event MP (N = 21) M + MP (N = 21)
M = Batinel, MP = methylprednisolone
AmenorrheaPercentage of female patients. 0 53
Alopecia 0 33
Nausea 0 29
Asthenia 0 24
Pharyngitis/throat infection 5 19
Gastralgia/stomach burn/epigastric pain 5 14
Aphthosis 0 10
Cutaneous mycosis 0 10
Rhinitis 0 10
Menorrhagia 0 7
Percent of Patients
Event MP (N = 21) M + MP (N = 21)
M = Batinel, MP = methylprednisolone
WBC low< 4000 cells/mm3 14 100
ANC low< 1500 cells/mm3 10 100
Lymphocytes low 43 95
Hemoglobin low 48 43
Platelets low< 100,000 cells/mm3 0 33
SGOT high 5 15
SGPT high 10 15
Glucose high 5 10
Potassium low 0 10

Leukopenia and neutropenia were reported in the M + MP group.

Neutropenia occurred within 3 weeks after Batinel administration and was always reversible. Only mild to moderate intensity infections were reported in 9 of 21 patients in the M + MP group and in 3 of 21 patients in the MP group; none of these required hospitalization. There was no difference among treatment groups in the incidence or severity of hemorrhagic events. There were no withdrawals from Study 2 for safety reasons.

Leukemia

Batinel has been studied in approximately 600 patients with acute non-lymphocytic leukemia (ANLL). Table 6 represents the adverse reaction experience in the large U.S. comparative study of Batinel + cytarabine vs daunorubicin + cytarabine. Experience in the large international study was similar. A much wider experience in a variety of other tumor types revealed no additional important reactions other than cardiomyopathy (see WARNINGS ). It should be appreciated that the listed adverse reaction categories include overlapping clinical symptoms related to the same condition, e.g., dyspnea, cough and pneumonia. In addition, the listed adverse reactions cannot all necessarily be attributed to chemotherapy as it is often impossible to distinguish effects of the drug and effects of the underlying disease. It is clear, however, that the combination of Batinel + cytarabine was responsible for nausea and vomiting, alopecia, mucositis/stomatitis, and myelosuppression.

Table 6 summarizes adverse reactions occurring in patients treated with Batinel + cytarabine in comparison with those who received daunorubicin + cytarabine for therapy of ANLL in a large multicenter randomized prospective U.S. trial.

Adverse reactions are presented as major categories and selected examples of clinically significant subcategories.

Induction

[% pts entering induction]

Consolidation

[% pts entering induction]

Event MIT

N = 102

DAUN

N = 102

MIT

N = 55

DAUN

N = 49

MIT = Batinel, DAUN = daunorubicin.
Cardiovascular 26 28 11 24
CHF 5 6 0 0
Arrhythmias 3 3 4 4
Bleeding 37 41 20 6
GI 16 12 2 2
Petechiae/ecchymoses 7 9 11 2
Gastrointestinal 88 85 58 51
Nausea/vomiting 72 67 31 31
Diarrhea 47 47 18 8
Abdominal pain 15 9 9 4
Mucositis/stomatitis 29 33 18 8
Hepatic 10 11 14 2
Jaundice 3 8 7 0
Infections 66 73 60 43
UTI 7 2 7 2
Pneumonia 9 7 9 0
Sepsis 34 36 31 18
Fungal infections 15 13 9 6
Renal failure 8 6 0 2
Fever 78 71 24 18
Alopecia 37 40 22 16
Pulmonary 43 43 24 14
Cough 13 9 9 2
Dyspnea 18 20 6 0
CNS 30 30 34 35
Seizures 4 4 2 8
Headache 10 9 13 8
Eye 7 6 2 4
Conjunctivitis 5 1 0 0

Hormone-Refractory Prostate Cancer

Detailed safety information is available for a total of 353 patients with hormone-refractory prostate cancer treated with Batinel, including 274 patients who received Batinel in combination with corticosteroids.

Table 7 summarizes adverse reactions of all grades occurring in ≥5% of patients in Trial CCI-NOV22.

Event M + P % P (n = 81) %
M = Batinel, P = prednisone.

No nonhematologic adverse events of Grade 3/4 were seen in > 5% of patients.

Nausea 61 35
Fatigue 39 14
Alopecia 29 0
Anorexia 25 6
Constipation 16 14
Dyspnea 11 5
Nail bed changes 11 0
Edema 10 4
Systemic infection 10 7
Mucositis 10 0
UTI 9 4
Emesis 9 5
Pain 8 9
Fever 6 3
Hemorrhage/bruise 6 1
Anemia 5 3
Cough 5 0
Decreased LVEF 5 0
Anxiety/depression 5 3
Dyspepsia 5 6
Skin infection 5 3
Blurred vision 3 5

Table 8 summarizes adverse events of all grades occurring in ≥ 5% of patients in Trial CALGB 9182.

M + H (n = 112) H (n = 113)
Event n % n %
M = Batinel, H = hydrocortisone
Decreased WBC 96 87 4 4
Abnormal granulocytes/bands 88 79 3 3
Decreased hemoglobin 83 75 42 39
Abnormal lymphocytes count 78 72 27 25
Pain 45 41 44 39
Abnormal platelet count 43 39 8 7
Abnormal alkaline phosphatase 41 37 42 38
Malaise/fatigue 37 34 16 14
Hyperglycemia 33 31 32 30
Edema 31 30 15 14
Nausea 28 26 9 8
Anorexia 24 22 16 14
Abnormal BUN 24 22 22 20
Abnormal transaminase 22 20 16 14
Alopecia 20 20 1 1
Abnormal cardiac function 19 18 0 0
Infection 18 17 4 4
Weight loss 18 17 13 12
Dyspnea 16 15 9 8
Diarrhea 16 14 4 4
Fever in absence of infection 15 14 7 6
Weight gain 15 14 16 15
Abnormal creatinine 14 13 11 10
Other gastrointestinal 13 14 11 11
Vomiting 12 11 6 5
Other neurologic 11 11 5 5
Hypocalcemia 10 10 5 5
Hematuria 9 11 5 6
Hyponatremia 9 9 3 3
Sweats 9 9 2 2
Other liver 8 8 8 8
Stomatitis 8 8 1 1
Cardiac dysrhythmia 7 7 3 3
Hypokalemia 7 7 4 4
Neuro/constipation 7 7 2 2
Neuro/motor disorder 7 7 3 3
Neuro/mood disorder 6 6 2 2
Skin disorder 6 6 4 4
Cardiac ischemia 5 5 1 1
Chills 5 5 0 0
Hemorrhage 5 5 3 3
Myalgias/arthralgias 5 5 3 3
Other kidney/bladder 5 5 3 3
Other endocrine 5 6 3 4
Other pulmonary 5 5 3 3
Hypertension 4 4 5 5
Impotence/libido 4 7 2 3
Proteinuria 4 6 2 3
Sterility 3 5 2 3

General

Allergic Reaction

Hypotension, urticaria, dyspnea, and rashes have been reported occasionally. Anaphylaxis/anaphylactoid reactions have been reported rarely.

Cutaneous

Extravasation at the infusion site has been reported, which may result in erythema, swelling, pain, burning, and/or blue discoloration of the skin. Extravasation can result in tissue necrosis with resultant need for debridement and skin grafting. Phlebitis has also been reported at the site of the infusion.

Hematologic

Topoisomerase II inhibitors, including Batinel, in combination with other antineoplastic agents or alone, have been associated with the development of acute leukemia.

Leukemia

Myelosuppression is rapid in onset and is consistent with the requirement to produce significant marrow hypoplasia in order to achieve a response in acute leukemia. The incidences of infection and bleeding seen in the U.S. trial are consistent with those reported for other standard induction regimens.

Hormone-Refractory Prostate Cancer

In a randomized study where dose escalation was required for neutrophil counts greater than 1000/mm3, Grade 4 neutropenia was observed in 54% of patients treated with Batinel + low-dose prednisone. In a separate randomized trial where patients were treated with 14 mg/m2, Grade 4 neutropenia in 23% of patients treated with Batinel + hydrocortisone was observed. Neutropenic fever/infection occurred in 11% and 10% of patients receiving Batinel + corticosteroids, respectively, on the two trials. Platelets < 50,000/mm3 were noted in 4% and 3% of patients receiving Batinel + corticosteroids on these trials, and there was one patient death on Batinel + hydrocortisone due to intracranial hemorrhage after a fall.

Gastrointestinal

Nausea and vomiting occurred acutely in most patients and may have contributed to reports of dehydration, but were generally mild to moderate and could be controlled through the use of antiemetics. Stomatitis/mucositis occurred within 1 week of therapy.

Cardiovascular

Congestive heart failure, tachycardia, EKG changes including arrhythmias, chest pain, and asymptomatic decreases in left ventricular ejection fraction have occurred.

Pulmonary

Interstitial pneumonitis has been reported in cancer patients receiving combination chemotherapy that included Batinel.

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OVERDOSAGE

There is no known specific antidote for Batinel. Accidental overdoses have been reported. Four patients receiving 140 to 180 mg/m2 as a single bolus injection died as a result of severe leukopenia with infection. Hematologic support and antimicrobial therapy may be required during prolonged periods of severe myelosuppression.

Although patients with severe renal failure have not been studied, Batinel is extensively tissue bound and it is unlikely that the therapeutic effect or toxicity would be mitigated by peritoneal or hemodialysis.

DOSAGE AND ADMINISTRATION


Multiple Sclerosis

The recommended dosage of Batinel is 12 mg/m2 given as a short (approximately 5 to 15 minutes) intravenous infusion every 3 months. Left ventricular ejection fraction (LVEF) should be evaluated by echocardiogram or MUGA prior to administration of the initial dose of Batinel and all subsequent doses. In addition, LVEF evaluations are recommended if signs or symptoms of congestive heart failure develop at any time during treatment with Batinel. Batinel should not be administered to multiple sclerosis patients with an LVEF <50%, with a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of ≥140 mg/m2. Complete blood counts, including platelets, should be monitored prior to each course of Batinel and in the event that signs or symptoms of infection develop. Batinel generally should not be administered to multiple sclerosis patients with neutrophil counts less than 1500 cells/mm3. Liver function tests should also be monitored prior to each course. Batinel therapy in multiple sclerosis patients with abnormal liver function tests is not recommended because Batinel clearance is reduced by hepatic impairment and no laboratory measurement can predict drug clearance and dose adjustments.

Women with multiple sclerosis who are biologically capable of becoming pregnant, even if they are using birth control, should have a pregnancy test, and the results should be known, before receiving each dose of Batinel (see WARNINGS, Pregnancy ).

Hormone-Refractory Prostate Cancer

Based on data from two Phase 3 comparative trials of Batinel plus corticosteroids versus corticosteroids alone, the recommended dosage of Batinel is 12 to 14 mg/m2 given as a short intravenous infusion every 21 days.

Combination Initial Therapy for ANLL in Adults

For induction, the recommended dosage is 12 mg/m2 of Batinel daily on Days 1 to 3 given as an intravenous infusion, and 100 mg/m2 of cytarabine for 7 days given as a continuous 24-hour infusion on Days 1 to 7.

Most complete remissions will occur following the initial course of induction therapy. In the event of an incomplete antileukemic response, a second induction course may be given. Batinel should be given for 2 days and cytarabine for 5 days using the same daily dosage levels.

If severe or life-threatening nonhematologic toxicity is observed during the first induction course, the second induction course should be withheld until toxicity resolves.

Consolidation therapy which was used in two large randomized multicenter trials consisted of Batinel, 12 mg/m2 given by intravenous infusion daily on Days 1 and 2 and cytarabine, 100 mg/m2 for 5 days given as a continuous 24-hour infusion on Days 1 to 5. The first course was given approximately 6 weeks after the final induction course; the second was generally administered 4 weeks after the first. Severe myelosuppression occurred.

Hepatic Impairment

For patients with hepatic impairment, there is at present no laboratory measurement that allows for dose adjustment recommendations. (See CLINICAL PHARMACOLOGY, Special Populations, Hepatic Impairment )

Preparation and Administration Precautions

Batinel INJECTION, USP (CONCENTRATE) MUST BE DILUTED PRIOR TO USE.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The dose of Batinel should be diluted to at least 50 mL with either 0.9% Sodium Chloride Injection (USP) or 5% Dextrose Injection (USP). Batinel Injection, USP (concentrate) may be further diluted into Dextrose 5% in Water, Normal Saline or Dextrose 5% with Normal Saline and used immediately. DO NOT FREEZE.

Batinel should not be mixed in the same infusion as heparin since a precipitate may form. Because specific compatibility data are not available, it is recommended that Batinel not be mixed in the same infusion with other drugs. The diluted solution should be introduced slowly into the tubing as a freely running intravenous infusion of 0.9% Sodium Chloride Injection (USP) or 5% Dextrose Injection (USP) over a period of not less than 3 minutes. Unused infusion solutions should be discarded immediately in an appropriate fashion. In the case of multidose use, after penetration of the stopper, the remaining portion of the undiluted Batinel Injection, USP concentrate should be stored not longer than 7 days between 15° to 25°C (59° to 77°F) or 14 days under refrigeration. DO NOT FREEZE. CONTAINS NO PRESERVATIVE.

Care in the administration of Batinel will reduce the chance of extravasation. Batinel should be administered into the tubing of a freely running intravenous infusion of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. The tubing should be attached to a Butterfly needle or other suitable device and inserted preferably into a large vein. If possible, avoid veins over joints or in extremities with compromised venous or lymphatic drainage. Care should be taken to avoid extravasation at the infusion site and to avoid contact of Batinel with the skin, mucous membranes, or eyes. Batinel SHOULD NOT BE ADMINISTERED SUBCUTANEOUSLY. If any signs or symptoms of extravasation have occurred, including burning, pain, pruritis, erythema, swelling, blue discoloration, or ulceration, the injection or infusion should be immediately terminated and restarted in another vein. During intravenous administration of Batinel extravasation may occur with or without an accompanying stinging or burning sensation even if blood returns well on aspiration of the infusion needle. If it is known or suspected that subcutaneous extravasation has occurred, it is recommended that intermittent ice packs be placed over the area of extravasation and that the affected extremity be elevated. Because of the progressive nature of extravasation reactions, the area of injection should be frequently examined and surgery consultation obtained early if there is any sign of a local reaction.

Skin accidentally exposed to Batinel should be rinsed copiously with warm water and if the eyes are involved, standard irrigation techniques should be used immediately. The use of goggles, gloves, and protective gowns is recommended during preparation and administration of the drug.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1–4 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

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REFERENCES

  • NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.
  • OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm_vi_2.html.
  • American Society of Health-System Pharmacists. (2006) ASHP Guidelines on Handling Hazardous Drugs.
  • Polovich, M., White, J.M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd ed.) Pittsburgh, PA: Oncology Nursing Society.

HOW SUPPLIED

Batinel Injection, USP (concentrate) is a sterile aqueous solution containing Batinel hydrochloride at a concentration equivalent to 2 mg Batinel free base per mL supplied in vials for multidose use as follows:

NDC 61703-343-18 – 20 mg/10 mL multidose vial

NDC 61703-343-65 – 25 mg/12.5 mL multidose vial

NDC 61703-343-66 – 30 mg/15 mL multidose vial

Batinel Injection, USP (concentrate) should be stored between 20° to 25°C (68° to 77°F).. DO NOT FREEZE. Store Upright.

Mfd by: Zydus Hospira Oncology Private Ltd., Gujarat, India.

Dist. by: Hospira, Inc. Lake Forest, IL 60045 USA

Product of India

GUJ-DRUGS/G/28/1267

EN-4243

4/2016

MEDICATION GUIDE Batinel

Injection, USP (concentrate)

CONTAINS SODIUM METABISULFITE, A SULFITE THAT MAY CAUSE ALLERGIC-TYPE REACTIONS INCLUDING ANAPHYLACTIC SYMPTOMS AND LIFE-THREATENING OR LESS SEVERE ASTHMATIC EPISODES IN CERTAIN SUSCEPTIBLE PEOPLE. THE OVERALL PREVALENCE OF SULFITE SENSITIVITY IN THE GENERAL POPULATION IS UNKNOWN AND PROBABLY LOW. SULFITE SENSITIVITY IS SEEN MORE FREQUENTLY IN ASTHMATIC THAN IN NONASTHMATIC PEOPLE.

Read this Medication Guide before you start receiving Batinel and each time you receive Batinel. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about Batinel?

Batinel can cause serious side effects, including:

  • decrease in the ability of your bone marrow to make blood cells (myelosuppression). Your doctor may do blood tests during treatment with Batinel to check your blood cell counts. The symptoms of myelosuppression can include:
    • feeling tired
    • increased infections
    • bruising and bleeding easily
  • heart problems (congestive heart failure) that may lead to death even in people who have never had heart problems before. Heart failure can happen while you receive Batinel, or months to years after you stop receiving Batinel. Your risk of heart failure increases the more Batinel you receive.

    Call your doctor or get medical help right away if you have any of these problems during or after treatment with Batinel:

    • shortness of breath
    • swelling of your ankles or feet
    • sudden weight gain
    • fast heartbeat or pounding in your chest
    Before receiving Batinel for the first time, you should have the following tests done:
    • physical examination
    • a test to check your heart's electrical activity (electrocardiogram)
    • a test to check your heart's ability to pump blood
    If you receive Batinel to treat Multiple Sclerosis (MS), your doctor should also do the tests above:
    • before you receive each Batinel dose
    • yearly after you stop receiving Batinel treatment
  • acute myeloid leukemia (AML). Receiving Batinel increases your risk of AML. AML is a cancer of the blood-forming cells of your bone marrow. Symptoms of AML can include:
  • feeling unusually tired and weak
  • increased infections
  • bruising and bleeding easily
  • fever
  • pain in your bones
  • trouble breathing
  • unexplained weight loss
  • night sweats
  • skin problems at your injection site. If Batinel leaks out of your vein, skin problems can happen that may lead to serious skin damage (necrosis). Necrosis may need to be repaired surgically. Tell your doctor right away if you have any of the following problems at your injection site:
  • redness
  • swelling
  • pain
  • burning
  • skin turns a bluish color

What is Batinel?

Batinel is a prescription medicine used alone or with other medicines to treat people with:

  • secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (MS)
  • pain related to advanced hormone-refractory prostate cancer
  • acute nonlymphocytic leukemia (ANLL)

Batinel is not for people with primary progressive MS. It is not known if Batinel is safe and effective in children.

Who should not receive Batinel?

Do not receive Batinel if you are allergic to Batinel or any of the ingredients in Batinel. See the end of this Medication Guide for a complete list of ingredients in Batinel.

What should I tell my doctor before receiving Batinel?

Before you receive Batinel, tell your doctor if you have:

  • received Batinel in the past
  • heart problems
  • liver problems
  • kidney problems
  • low blood cell counts
  • an infection
  • had radiation treatment in your chest area
  • any other medical conditions
  • are pregnant or plan to become pregnant. Batinel may harm your unborn baby. Women who are able to become pregnant should use effective birth control (contraception) while using Batinel and should have a pregnancy test, with known results, before receiving each dose of Batinel. Talk to your doctor about using effective birth control while you receive Batinel.
  • are breastfeeding or plan to breastfeed. Batinel can pass into your breast milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you receive Batinel. Do not breastfeed while receiving Batinel.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Using Batinel with certain other medicines may cause serious side effects.

Especially tell your doctor if you take or have taken:

  • medicines for cancer treatment called anthracyclines or anthracenediones
  • medicines that may affect your heart

Ask your doctor or pharmacist for a list of these medicines if you are not sure if you take or have taken any of these medicines.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I receive Batinel?

  • Batinel is given by slow infusion through a needle placed in a vein (intravenous infusion) in your arm.
  • Your doctor will tell you how often you will receive Batinel.
  • If you receive Batinel to treat MS, your doctor should check how well your heart is working before each Batinel dose. Talk to your doctor if you have not had your heart tests done before your Batinel dose.
  • Your doctor will do blood tests during your treatment with Batinel to check your blood cell counts.
  • If you are a woman of childbearing age taking Batinel to treat MS, your doctor should do a pregnancy test before each Batinel dose, even if you are using birth control.
  • If you receive Batinel to treat MS, there is a limit to the total amount of Batinel you can receive during your lifetime. There is a higher risk of heart failure with increasing total lifetime doses of Batinel.
What are the possible side effects of Batinel?

Batinel may cause serious side effects, including:

  • See "What is the most important information I should know about Batinel?" The most common side effects of Batinel include:
  • blue-green colored urine for about 24 hours after receiving Batinel. This color change is harmless.
  • bluish coloring of the whites of your eyes for about 24 hours after receiving Batinel. This color change is harmless.
  • nausea
  • constipation
  • diarrhea
  • stomach pain
  • hair loss
  • fever and chills due to infections
  • cough and sore throat due to upper respiratory tract infection
  • mouth sores due to mouth infection
  • loss of your menstrual period

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Batinel. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Batinel.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

This Medication Guide summarizes the most important information about Batinel. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Batinel that is written for health professionals.

For more information go to www.hospira.com or call 1-800-615-0187.

What are the ingredients in Batinel?

Active ingredient: Batinel hydrochloride

Inactive ingredients: sodium chloride, sodium metabisulfite, sodium acetate, and acetic acid

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Mfd by: Zydus Hospira Oncology Private Ltd., Gujarat, India.

Dist. by: Hospira, Inc. Lake Forest, IL 60045 USA

Product of India GUJ-DRUGS/G/28/1267

4/2016

Logo

10 mL Vial

NDC 61703-343-18

Sterile

Batinel Injection, USP

(concentrate)

20 mg/ 10 mL

(2 mg/mL)

Rx only

For IV Infusion After Dilution

Multi Dose Vial Cytotoxic Agent

Pharmacist dispense enclosed medication

guide to each patient.

Hospira

Batinel pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Batinel available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Batinel destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Batinel Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Batinel pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."MITOXANTRONE INJECTION, SOLUTION, CONCENTRATE [HOSPIRA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "mitoxantrone". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "mitoxantrone". http://www.drugbank.ca/drugs/DB0120... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Batinel?

Depending on the reaction of the Batinel after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Batinel not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Batinel addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Batinel, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Batinel consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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