Manifestations of Varitrinox (arsenic trioxide) overdosage include convulsions, muscle weakness and confusion.
ManagementIf symptoms of Varitrinox (arsenic trioxide) overdosage develop, the injection should be immediately discontinued and chelation therapy should be considered.
A conventional protocol for acute arsenic intoxication includes dimercaprol administered at a dose of 3 mg/kg intramuscularly every 4 hours until immediate life-threatening toxicity has subsided. Thereafter, penicillamine at a dose of 250 mg orally, up to a maximum frequency of four times per day (≤ 1 g per day), may be given.
Varitrinox is contraindicated in patients who are hypersensitive to arsenic.
The following serious adverse reactions are described elsewhere in the labeling.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Safety information was available for 52 patients with relapsed or refractory APL who participated in clinical trials of Varitrinox. Forty patients in the Phase 2 study received the recommended dose of 0.15 mg/kg of which 28 completed both induction and consolidation treatment cycles. An additional 12 patients with relapsed or refractory APL received doses generally similar to the recommended dose. Most patients experienced some drug-related toxicity, most commonly leukocytosis, gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, and dizziness. These adverse effects have not been observed to be permanent or irreversible nor do they usually require interruption of therapy.
Serious adverse events (SAEs), Grade 3/4 according to version 2 of the NCI Common Toxicity Criteria, were common. Those SAEs attributed to Varitrinox in the Phase 2 study of 40 patients with refractory or relapsed APL included APL differentiation syndrome (n=3), hyperleukocytosis (n=3), QTc interval ≥ 500 msec (n=16, 1 with torsade de pointes), atrial dysrhythmias (n=2), and hyperglycemia (n=2).
Table 1 describes the adverse events that were observed in patients, between the ages of 5-73 years, treated for APL with Varitrinox at the recommended dose at a rate of 5% or more. Similar adverse event profiles were seen in the other patient populations who received Varitrinox.
Table 1 : Adverse Events (Any Grade) Occurring in ≥ 5% of 40 Patients with APL Who Received Varitrinox (arsenic trioxide) Injection at a Dose of 0.15 mg/kg/day
| System organ class Adverse event | All Adverse Events, Any Grade | Grade 3/4 Events | ||
| n | % | n | % | |
| General disorders and administration site conditions | ||||
| Fatigue | 25 | 63 | 2 | 5 |
| Pyrexia (fever) | 25 | 63 | 2 | 5 |
| Edema - non-specific | 16 | 40 | ||
| Rigors | 15 | 38 | ||
| Chest pain | 10 | 25 | 2 | 5 |
| Injection site pain | 8 | 20 | ||
| Pain - non-specific | 6 | 15 | 1 | 3 |
| Injection site erythema | 5 | 13 | ||
| Injection site edema | 4 | 10 | ||
| Weakness | 4 | 10 | 2 | 5 |
| Hemorrhage | 3 | 8 | ||
| Weight gain | 5 | 13 | ||
| Weight loss | 3 | 8 | ||
| Drug hypersensitivity | 2 | 5 | 1 | 3 |
| Gastrointestinal disorders | ||||
| Nausea | 30 | 75 | ||
| Anorexia | 9 | 23 | ||
| Appetite decreased | 6 | 15 | ||
| Diarrhea | 21 | 53 | ||
| Vomiting | 23 | 58 | ||
| Abdominal pain (lower & upper) | 23 | 58 | 4 | 10 |
| Sore throat | 14 | 35 | ||
| Constipation | 11 | 28 | 1 | 3 |
| Loose stools | 4 | 10 | ||
| Dyspepsia | 4 | 10 | ||
| Oral blistering | 3 | 8 | ||
| Fecal incontinence | 3 | 8 | ||
| Gastrointestinal hemorrhage | 3 | 8 | ||
| Dry mouth | 3 | 8 | ||
| Abdominal tenderness | 3 | 8 | ||
| Diarrhea hemorrhagic | 3 | 8 | ||
| Abdominal distension | 3 | 8 | ||
| Metabolism and nutrition disorders | ||||
| Hypokalemia | 20 | 50 | 5 | 13 |
| Hypomagnesemia | 18 | 45 | 5 | 13 |
| Hyperglycemia | 18 | 45 | 5 | 13 |
| ALT increased | 8 | 20 | 2 | 5 |
| Hyperkalemia | 7 | 18 | 2 | 5 |
| AST increased | 5 | 13 | 1 | 3 |
| Hypocalcemia | 4 | 10 | ||
| Hypoglycemia | 3 | 8 | ||
| Acidosis | 2 | 5 | ||
| Nervous system disorders | ||||
| Headache | 24 | 60 | 1 | 3 |
| Insomnia | 17 | 43 | 1 | 3 |
| Paresthesia | 13 | 33 | 2 | 5 |
| Dizziness (excluding vertigo) | 9 | 23 | ||
| Tremor | 5 | 13 | ||
| Convulsion | 3 | 8 | 2 | 5 |
| Somnolence | 3 | 8 | ||
| Coma | 2 | 5 | 2 | 5 |
| Respiratory | ||||
| Cough | 26 | 65 | ||
| Dyspnea | 21 | 53 | 4 | 10 |
| Epistaxis | 10 | 25 | ||
| Hypoxia | 9 | 23 | 4 | 10 |
| Pleural effusion | 8 | 20 | 1 | 3 |
| Post nasal drip | 5 | 13 | ||
| Wheezing | 5 | 13 | ||
| Decreased breath sounds | 4 | 10 | ||
| Crepitations | 4 | 10 | ||
| Rales | 4 | 10 | ||
| Hemoptysis | 3 | 8 | ||
| T achypnea | 3 | 8 | ||
| Rhonchi | 3 | 8 | ||
| Skin & subcutaneous tissue disorders | ||||
| Dermatitis | 17 | 43 | ||
| Pruritus | 13 | 33 | 1 | 3 |
| Ecchymosis | 8 | 20 | ||
| Dry skin | 6 | 15 | ||
| Erythema - non-specific | 5 | 13 | ||
| Increased sweating | 5 | 13 | ||
| Facial edema | 3 | 8 | ||
| Night sweats | 3 | 8 | ||
| Petechiae | 3 | 8 | ||
| Hyperpigmentation | 3 | 8 | ||
| Non-specific skin lesions | 3 | 8 | ||
| Urticaria | 3 | 8 | ||
| Local exfoliation | 2 | 5 | ||
| Eyelid edema | 2 | 5 | ||
| Cardiac disorders | ||||
| T achycardia | 22 | 55 | ||
| ECG QT corrected interval prolonged > 500 msec | 16 | 40 | ||
| Palpitations | 4 | 10 | ||
| ECG abnormal other than QT interval prolongation | 3 | 8 | ||
| Infections and infestations | ||||
| Sinusitis | 8 | 20 | ||
| Herpes simplex | 5 | 13 | ||
| Upper respiratory tract infection | 5 | 13 | 1 | 3 |
| Bacterial infection - non-specific | 3 | 8 | 1 | 3 |
| Herpes zoster | 3 | 8 | ||
| Nasopharyngitis | 2 | 5 | ||
| Oral candidiasis | 2 | 5 | ||
| Sepsis | 2 | 5 | 2 | 5 |
| Musculoskeletal, connective tissue and bone disorders | ||||
| Arthralgia | 13 | 33 | 3 | 8 |
| Myalgia | 10 | 25 | 2 | 5 |
| Bone pain | 9 | 23 | 4 | 10 |
| Back pain | 7 | 18 | 1 | 3 |
| Neck pain | 5 | 13 | ||
| Pain in limb | 5 | 13 | 2 | 5 |
| Hematologic disorders | ||||
| Leukocytosis | 20 | 50 | 1 | 3 |
| Anemia | 8 | 20 | 2 | 5 |
| Thrombocytopenia | 7 | 18 | 5 | 13 |
| Febrile neutropenia | 5 | 13 | 3 | 8 |
| Neutropenia | 4 | 10 | 4 | 10 |
| Disseminated intravascular coagulation | 3 | 8 | 3 | 8 |
| Lymphadenopathy | 3 | 8 | ||
| Vascular disorders | ||||
| Hypotension | 10 | 25 | 2 | 5 |
| Flushing | 4 | 10 | ||
| Hypertension | 4 | 10 | ||
| Pallor | 4 | 10 | ||
| Psychiatric disorders | ||||
| Anxiety | 12 | 30 | ||
| Depression | 8 | 20 | ||
| Agitation | 2 | 5 | ||
| Confusion | 2 | 5 | ||
| Ocular disorders | ||||
| Eye irritation | 4 | 10 | ||
| Blurred vision | 4 | 10 | ||
| Dry eye | 3 | 8 | ||
| Painful red eye | 2 | 5 | ||
| Renal and urinary disorders | ||||
| Renal failure | 3 | 8 | 1 | 3 |
| Renal impairment. | 3 | 8 | ||
| Oliguria | 2 | 5 | ||
| Incontinence | 2 | 5 | ||
| Reproductive system disorders | ||||
| Vaginal hemorrhage | 5 | 13 | ||
| Intermenstrual bleeding | 3 | 8 | ||
| Ear disorders | ||||
| Earache | 3 | 8 | ||
| Tinnitus | 2 | 5 | ||
The following additional adverse events were reported as related to Varitrinox treatment in 13 pediatric patients (defined as ages 4 through 20): gastrointestinal (dysphagia, mucosal inflammation/stomatitis, oropharyngeal pain, caecitis), metabolic and nutrition disorders (hyponatremia, hypoalbuminemia, hypophosphatemia, and lipase increased), cardiac failure congestive, respiratory (acute respiratory distress syndrome, lung infiltration, pneumonitis, pulmonary edema, respiratory distress, capillary leak syndrome), neuralgia, and enuresis. Pulmonary edema (n=1) and caecitis (n=1) were considered serious reactions.
Postmarketing ExperienceThe following reactions have been reported from clinical trials and/or worldwide postmarketing surveillance. Because they are reported from a population of unknown size, precise estimates of frequency cannot be made.
Cardiacdis Orders : ventricular extrasystoles in association with QT prolongation, and ventricular tachycardia in association with QT prolongation.
Nervous System Disorders : peripheral neuropathy
Hematologic Disorders : pancytopenia
Investigations: gamma-glutamyltransferase increased
Respiratory, Thoracic, And Mediastinal Disorders : A differentiation syndrome, like retinoic acid syndrome, has been reported with the use of Varitrinox for the treatment of malignancies other than APL.
Varitrinox is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
A dedicated QTc study was not performed with Varitrinox. However, in a single arm trial of Varitrinox (0.15 mg/kg daily), 16 of 40 patients (40%) had a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after Varitrinox infusion, and then returned towards baseline by the end of 8 weeks after Varitrinox infusion.
The inorganic, lyophilized form of arsenic trioxide, when placed into solution, immediately forms the hydrolysis product arsenious acid (AsIII). AsIII is the pharmacologically active species of arsenic trioxide. Monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) are the main pentavalent metabolites formed during metabolism, in addition to arsenic acid (AsV) a product of As oxidation. The pharmacokinetics of arsenical species ([AsIII], [AsV], [MMAV], [DMAV]) were determined in 6 APL patients following once daily doses of 0.15 mg/kg for 5 days per week. Over the total single dose range of 7 to 32 mg (administered as 0.15 mg/kg), systemic exposure (AUC) appears to be linear. Peak plasma concentrations of arsenious acid (AsIII), the primary active arsenical species were reached at the end of infusion (2 hours). Plasma concentration of As declined in a biphasic manner with a mean elimination half-life of 10 to 14 hours and is characterized by an initial rapid distribution phase followed by a slower terminal elimination phase. The daily exposure to AsIII (mean AUC0-24) was 194 ng·hr/mL (n=5) on Day 1 of Cycle 1 and 332 ng·hr/mL (n=6) on Day 25 of Cycle 1, which represents an approximate 2-fold accumulation. The primary pentavalent metabolites, MMAV and DMAV, are slow to appear in plasma (approximately 10-24 hours after first administration of arsenic trioxide), but, due to their longer half-life, accumulate more upon multiple dosing than does AsIII. The mean estimated terminal elimination half-lives of the metabolites MMAV and DMAV are 32 hours and 72 hours, respectively. Approximate accumulation ranged from 1.4- to 8-fold following multiple dosing as compared to single dose administration. AsV is present in plasma only at relatively low levels.
DistributionThe volume of distribution (Vss ) for AsIII is large (mean 562 L, N=10) indicating that AsIII is widely distributed throughout body tissues. Vss is also dependent on body weight and increases as body weight increases.
MetabolismMuch of the AsIII is distributed to the tissues where it is methylated to the less cytotoxic metabolites, monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) by methyltransferases primarily in the liver. The metabolism of arsenic trioxide also involves oxidation of AsIII to AsV, which may occur in numerous tissues via enzymatic or nonenzymatic processes. AsV is present in plasma only at relatively low levels following administration of arsenic trioxide.
ExcretionApproximately 15% of the administered Varitrinox dose is excreted in the urine as unchanged AsIII. The methylated metabolites of AsIII (MMAV, DMAV) are primarily excreted in the urine. The total clearance of AsIII is 49 L/h and the renal clearance is 9 L/h. Clearance is not dependent on body weight or dose administered over the range of 7-32 mg.
Renal ImpairmentThe effect of renal impairment on the pharmacokinetics of AsIII, AsV, and the pentavalent metabolites MMAV and DMAV was evaluated in 20 patients with advanced malignancies. Patients were classified as having normal renal function (creatinine clearance [CrCl] > 80 mL/min, n=6), mild renal impairment (CrCl 50-80 mL/min, n=5), moderate renal impairment (CrCl 30-49 mL/min, n=6), or severe renal impairment (CrCl < 30 mL/min, n=3). Following twice weekly administration of 0.15 mg/kg over a 2- hour infusion, the mean AUC0-∞ for AsIII was comparable among the normal, mild and moderate renal impairment groups. However, in the severe renal impairment group, the mean AUC0-∞ for AsIII was approximately 48% higher than that in the normal group.
Systemic exposure to MMAV and DMAV tended to be larger in patients with renal impairment; however, the clinical consequences of this increased exposure are not known. AsV plasma levels were generally below the limit of assay quantitation in patients with impaired renal function. The use of arsenic trioxide in patients on dialysis has not been studied.
Hepatic ImpairmentThe effect of pharmacokinetics of AsIII, AsV, and the pentavalent metabolites MMAV and DMAV was evaluated following administration of 0.25-0.50 mg/kg of arsenic trioxide in patients with hepatocellular carcinoma. Patients were classified as having normal hepatic function (n=4), mild hepatic impairment (Child-Pugh class A, n=12), moderate hepatic impairment (Child-Pugh class B, n=3), or severe hepatic impairment (Child-Pugh class C, n=1). No clear trend toward an increase in systemic exposure to AsIII, AsV, MMAV or DMAV was observed with decreasing level of hepatic function as assessed by dose-normalized (per mg dose) AUC in the mild and moderate hepatic impairment groups. However, the one patient with severe hepatic impairment had mean dose-normalized AUC0-24 and Cmax values 40% and 70% higher, respectively, than those patients with normal hepatic function. The mean dose-normalized trough plasma levels for both MMAV and DMAV in this severely hepatically impaired patient were 2.2-fold and 4.7-fold higher, respectively, than those in the patients with normal hepatic function.
Pediatric PatientsFollowing IV administration of 0.15 mg/kg/day of arsenic trioxide in 10 APL patients (median age = 13.5 years, range 4-20 years), the daily exposure to AsIII (mean AUC0-24h) was 317 ng·hr/mL on Day 1 of Cycle 1.
Included as part of the PRECAUTIONS section.
PRECAUTIONS APL Differentiation SyndromeNine of 40 patients with APL treated with Varitrinox, at a dose of 0.15 mg/kg, experienced the APL differentiation syndrome. High-dose steroids have been administered at the first suspicion of the APL differentiation syndrome and appear to mitigate signs and symptoms. At the first signs that could suggest the syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg intravenously BID) should be immediately initiated, irrespective of the leukocyte count, and continued for at least 3 days or longer until signs and symptoms have abated. The majority of patients do not require termination of Varitrinox therapy during treatment of the APL differentiation syndrome.
Cardiac Conduction Abnormalities : Torsade de Pointes, Complete Heart Block, And QT ProlongationTorsade de pointes and complete heart block have been reported. QT/QTc prolongation can occur. Sixteen of 40 patients (40%) had at least one ECG tracing with a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after Varitrinox infusion, and then returned towards baseline by the end of 8 weeks after Varitrinox infusion.
Prior to initiating therapy with Varitrinox, a 12-lead ECG should be performed and serum electrolytes (potassium, calcium, and magnesium) and creatinine should be assessed. Preexisting electrolyte abnormalities should be corrected and, if possible, drugs that are known to prolong the QT interval should be discontinued. If it is not possible to discontinue the interacting drug, perform cardiac monitoring frequently.
Monitor ECG weekly, and more frequently for clinically unstable patients.
For QTc greater than 500 msec, complete corrective measures and reassess the QTc with serial ECGs prior to initiating Varitrinox. During Varitrinox therapy, maintain potassium concentrations above 4 mEq/L and magnesium concentrations above 1.8 mg/dL. Reassess patients who reach an absolute QT interval value > 500 msec and immediately correct concomitant risk factors, if any, while the risk/benefit of continuing versus suspending Varitrinox therapy should be considered. There are no data on the effect of Varitrinox on the QTc interval during the infusion.
The risk may be increased when Varitrinox is coadministered with medications that can lead to electrolyte abnormalities (such as diuretics or amphotericin B).
CarcinogenesisThe active ingredient of Varitrinox, arsenic trioxide, is a human carcinogen. Monitor patients for the development of second primary malignancies.
Embryo-Fetal ToxicityVaritrinox can cause fetal harm when administered to a pregnant woman. Arsenic trioxide was embryolethal and teratogenic in rats when administered on gestation day 9 at a dose approximately 10 times the recommended human daily dose on a mg/m² basis. A related trivalent arsenic, sodium arsenite, produced teratogenicity when administered during gestation in mice at a dose approximately 5 times the projected human dose on a mg/m² basis and in hamsters at an intravenous dose approximately equivalent to the projected human daily dose on a mg/m² basis. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and after treatment with Varitrinox.
Laboratory TestsThe patient's electrolyte and glucose levels, as well as hepatic, renal, hematologic and coagulation profiles should be monitored at least twice weekly, and more frequently for clinically unstable patients during the induction phase and at least weekly during the consolidation phase.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of FertilityCarcinogenicity studies have not been conducted with Varitrinox by intravenous administration.
Arsenic trioxide and trivalent arsenite salts have not been demonstrated to be mutagenic to bacteria, yeast or mammalian cells. Arsenite salts are clastogenic in vitro (human fibroblast, human lymphocytes, Chinese hamster ovary cells, Chinese hamster V79 lung cells). Trivalent arsenic produced an increase in the incidence of chromosome aberrations and micronuclei in bone marrow cells of mice.
The effect of arsenic on fertility has not been adequately studied.
Use In Specific Populations Pregnancy Risk SummaryVaritrinox can cause fetal harm when administered to a pregnant woman. Arsenic trioxide was embryolethal and teratogenic in rats when administered on gestation day 9 at a dose approximately 10 times the recommended human daily dose on a mg/m² basis. A related trivalent arsenic, sodium arsenite, produced teratogenicity when administered during gestation in mice at a dose approximately 5 times the projected human dose on a mg/m² basis and in hamsters at an intravenous dose approximately equivalent to the projected human daily dose on a mg/m² basis. There are no studies in pregnant women using Varitrinox. Advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
DataHuman Data
One patient who became pregnant while receiving arsenic trioxide had a miscarriage.
Animal Data
Studies in pregnant mice, rats, hamsters, and primates have shown that inorganic arsenicals cross the placental barrier when given orally or by injection. An increase in resorptions, neural-tube defects, anophthalmia and microphthalmia were observed in rats administered 10 mg/kg of arsenic trioxide on gestation day 9 (approximately 10 times the recommended human daily dose on a mg/m² basis). Similar findings occurred in mice administered a 10 mg/kg dose of a related trivalent arsenic, sodium arsenite (approximately 5 times the projected human dose on a mg/m² basis), on gestation days 6, 7, 8 or 9. Intravenous injection of 2 mg/kg sodium arsenite (approximately equivalent to the projected human daily dose on a mg/m² basis) on gestation day 7 (the lowest dose tested) resulted in neural-tube defects in hamsters.
LactationArsenic is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Varitrinox, discontinue breastfeeding during treatment with Varitrinox.
Females And Males Of Reproductive Potential ContraceptionFemales
Varitrinox can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during and after treatment with Varitrinox.
Males
Males with female sexual partners of reproductive potential should use effective contraception during and after treatment with Varitrinox.
Pediatric UseThere are limited clinical data on the pediatric use of Varitrinox. Of 5 patients below the age of 18 years (age range: 5 to 16 years) treated with Varitrinox, at the recommended dose of 0.15 mg/kg/day, 3 achieved a complete response.
In an additional study, the toxicity profile observed in 13 pediatric patients with APL between the ages of 4 and 20 receiving Varitrinox at 0.15 mg/kg/day was similar to that observed in adult patients. No children less than 4 years of age were enrolled in the trial due to the rarity of APL in this age group.
Geriatric UseClinical trials of Varitrinox (arsenic trioxide) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Monitor elderly patients closely, reflecting the greater frequency of decreased hepatic and renal function, concomitant disease or other drug therapy in this population.
Patients With Renal ImpairmentExposure of arsenic trioxide may be higher in patients with severe renal impairment. Patients with severe renal impairment (creatinine clearance less than 30 mL/min) should be monitored for toxicity when these patients are treated with Varitrinox, and a dose reduction may be warranted.
The use of Varitrinox in patients on dialysis has not been studied.
Patients With Hepatic ImpairmentSince limited data are available across all hepatic impairment groups, caution is advised in the use of Varitrinox in patients with hepatic impairment. Monitor patients with severe hepatic impairment (Child-Pugh Class C) who are treated with Varitrinox for toxicity.
Administer Varitrinox intravenously at a dose of 0.15 mg/kg daily until Sections or subsections omitted from the full prescribing information are not listed. bone marrow remission. Do not exceed 60 doses for induction.
Consolidation Treatment ScheduleBegin consolidation treatment 3 to 6 weeks after completion of induction therapy. Administer Varitrinox intravenously at a dose of 0.15 mg/kg daily for 25 doses over a period up to 5 weeks.
Dose Adjustment For Non-Hematologic Adverse ReactionsIf a severe non-hematologic adverse reaction occurs (such as neurologic or dermatologic toxicity), consider delaying Varitrinox infusion until the event has resolved (≤ Grade 1).
Instructions For Preparation And Intravenous Administration AdministrationAdminister Varitrinox intravenously over 1-2 hours. The infusion duration may be extended up to 4 hours if acute vasomotor reactions are observed. A central venous catheter is not required.
The Varitrinox vial is single-dose and does not contain any preservatives. Unused portions of each vial should be discarded properly. Do not mix Varitrinox with other medications.
ReconstitutionDilute Varitrinox with 100 to 250 mL 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP, using proper aseptic technique, immediately after withdrawal from the vial. Do not save any unused portions for later administration.
Safe Handling ProceduresVaritrinox is a cytotoxic drug. Follow applicable special handling and disposal procedures.
StabilityAfter dilution, Varitrinox is chemically and physically stable when stored for 24 hours at room temperature and 48 hours when refrigerated.
