What happens if I overdose Velcade 3.5mg?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.
Proper storage of Velcade 3.5mg:
Velcade 3.5mg is handled and stored by a health care provider. You will not store it at home. Keep all medicines out of the reach of children and away from pets.
Overdose of Velcade 3.5mg in details
There is no known specific antidote for Velcade 3.5mg overdosage. In humans, fatal outcomes following the administration of more than twice the recommended therapeutic dose have been reported, which were associated with the acute onset of symptomatic hypotension (5.2) and thrombocytopenia (5.7). In the event of an overdosage, the patient's vital signs should be monitored and appropriate supportive care given.
Studies in monkeys and dogs showed that intravenous Velcade 3.5mg doses as low as 2 times the recommended clinical dose on a mg/m2 basis were associated with increases in heart rate, decreases in contractility, hypotension, and death. In dog studies, a slight increase in the corrected QT interval was observed at doses resulting in death. In monkeys, doses of 3 mg/m2 and greater (approximately twice the recommended clinical dose) resulted in hypotension starting at 1 hour post-administration, with progression to death in 12 to 14 hours following drug administration.
What should I avoid while taking Velcade 3.5mg?
Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.
This medicine can pass into body fluids (including urine, feces, vomit, semen, vaginal fluid). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Patients and caregivers should wear rubber gloves while cleaning up body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.
Body fluids should not be handled by a woman who is pregnant or who may become pregnant. Use condoms during sexual activity to avoid exposure to body fluids.
This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.
Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.
Avoid becoming dehydrated if you have any vomiting or diarrhea. Symptoms of dehydration include dizziness, dry mouth, fainting, or hot and dry skin. Talk with your doctor about how best to keep yourself hydrated.
Velcade 3.5mg warnings
Peripheral Neuropathy
Velcade 3.5mg treatment causes a peripheral neuropathy that is predominantly sensory; however, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥ Grade 3) during treatment with Velcade 3.5mg. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness.
Patients experiencing new or worsening peripheral neuropathy during Velcade 3.5mg therapy may require a decrease in the dose and/or a less dose-intense schedule. In the Velcade 3.5mg versus dexamethasone phase 3 relapsed multiple myeloma study, improvement in or resolution of peripheral neuropathy was reported in 48% of patients with ≥ Grade 2 peripheral neuropathy following dose adjustment or interruption. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥ Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.
Hypotension
The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 8%. These events are observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and administration of mineralocorticoids and/or sympathomimetics.
Cardiac Toxicity
Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have occurred during Velcade 3.5mg therapy, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart disease should be closely monitored. In the relapsed multiple myeloma study of Velcade 3.5mg versus dexamethasone, the incidence of any treatment-related cardiac disorder was 8% and 5% in the Velcade 3.5mg and dexamethasone groups, respectively. The incidence of adverse reactions suggestive of heart failure (acute pulmonary edema, pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock) was ≤ 1% for each individual reaction in the Velcade 3.5mg group. In the dexamethasone group the incidence was ≤ 1% for cardiac failure and congestive cardiac failure; there were no reported reactions of acute pulmonary edema, pulmonary edema, or cardiogenic shock. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.
Pulmonary Toxicity
Acute Respiratory Distress Syndrome (ARDS) and acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration have occurred in patients receiving Velcade 3.5mg. Some of these events have been fatal.
In a clinical trial, the first two patients given high-dose cytarabine (2g/m2 per day) by continuous infusion with daunorubicin and Velcade 3.5mg for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy.
There have been reports of pulmonary hypertension associated with Velcade 3.5mg administration in the absence of left heart failure or significant pulmonary disease.
In the event of new or worsening cardiopulmonary symptoms, consider interrupting Velcade 3.5mg until a prompt and comprehensive diagnostic evaluation is conducted.
Posterior Reversible Encephalopathy Syndrome (PRES)
Posterior Reversible Encephalopathy Syndrome (PRES; formerly termed Reversible Posterior Leukoencephalopathy Syndrome (RPLS)) has occurred in patients receiving Velcade 3.5mg. PRES is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patients developing PRES, discontinue Velcade 3.5mg. The safety of reinitiating Velcade 3.5mg therapy in patients previously experiencing PRES is not known.
Gastrointestinal Toxicity
Velcade 3.5mg treatment can cause nausea, diarrhea, constipation, and vomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid and electrolyte replacement should be administered to prevent dehydration. Interrupt Velcade 3.5mg for severe symptoms.
Thrombocytopenia/Neutropenia
Velcade 3.5mg is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remain consistent in the studies of multiple myeloma and mantle cell lymphoma, with no evidence of cumulative thrombocytopenia or neutropenia in the treatment regimens studied.
Monitor complete blood counts (CBC) frequently during treatment with Velcade 3.5mg. Measure platelet counts prior to each dose of Velcade 3.5mg. Adjust dose/schedule for thrombocytopenia. Gastrointestinal and intracerebral hemorrhage has occurred during thrombocytopenia in association with Velcade 3.5mg. Support with transfusions and supportive care, according to published guidelines.
In the single-agent, relapsed multiple myeloma study of Velcade 3.5mg versus dexamethasone, the mean platelet count nadir measured was approximately 40% of baseline. The severity of thrombocytopenia related to pretreatment platelet count is shown in Table 6. The incidence of bleeding (≥ Grade 3) was 2% on the Velcade 3.5mg arm and was < 1% in the dexamethasone arm.
| *A baseline platelet count of 50,000/μL was required for study eligibility | |||
| **Data were missing at baseline for 1 patient | |||
Pretreatment Platelet Count* | Number of Patients (N=331)** | Number (%) of Patients with Platelet Count < 10,000/μL | Number (%) of Patients with Platelet Count 10,000 to 25,000/μL |
| ≥ 75,000/μL | 309 | 8 (3%) | 36 (12%) |
| ≥ 50,000/μL to < 75,000/μL | 14 | 2 (14%) | 11 (79%) |
| ≥ 10,000/μL to < 50,000/μL | 7 | 1 (14%) | 5 (71%) |
Tumor Lysis Syndrome
Tumor lysis syndrome has been reported with Velcade 3.5mg therapy. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. Monitor patients closely and take appropriate precautions.
Hepatic Toxicity
Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic reactions include hepatitis, increases in liver enzymes, and hyperbilirubinemia. Interrupt Velcade 3.5mg therapy to assess reversibility. There is limited re-challenge information in these patients.
Embryo-fetal Toxicity
Based on the mechanism of action and findings in animals, Velcade 3.5mg for Injection can cause fetal harm when administered to a pregnant woman. Velcade 3.5mg administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and a decreased number of live fetuses.
Females of reproductive potential should avoid becoming pregnant while being treated with Velcade 3.5mg for Injection. Advise females of reproductive potential that they must use contraception during treatment with Velcade 3.5mg for Injection and for 7 months following cessation of therapy. Advise males with female sexual partners of reproductive potential that they must use contraception during treatment with Velcade 3.5mg for Injection and for 4 months following cessation of therapy. If Velcade 3.5mg for Injection is used during pregnancy or if the patient becomes pregnant during Velcade 3.5mg for Injection treatment, the patient should be apprised of the potential risk to the fetus.
What should I discuss with my healthcare provider before taking Velcade 3.5mg?
You should not use this medication if you are allergic to Velcade 3.5mg, mannitol, or boron.
To make sure Velcade 3.5mg is safe for you, tell your doctor if you have:
-
diabetes;
-
liver disease;
-
kidney disease, or if you are on dialysis;
-
a bleeding or blood clotting disorder;
-
a low level of platelets or white or red blood cells;
-
heart disease, congestive heart failure;
-
lung disease or breathing problems;
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herpes or a history of shingles;
-
high or low blood pressure; or
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nerve problems such as numbness, burning, pain, or tingly feeling.
FDA pregnancy category D. Do not use Velcade 3.5mg if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.
It is not known whether Velcade 3.5mg passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using Velcade 3.5mg. Ask your doctor how long to wait before breast-feeding again.
Velcade 3.5mg precautions
Peripheral Neuropathy
Velcade 3.5mg treatment causes a peripheral neuropathy that is predominantly sensory; however, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥ Grade 3) during treatment with Velcade 3.5mg. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness.
Patients experiencing new or worsening peripheral neuropathy during Velcade 3.5mg therapy may require a decrease in the dose and/or a less dose-intense schedule. In the Velcade 3.5mg versus dexamethasone phase 3 relapsed multiple myeloma study, improvement in or resolution of peripheral neuropathy was reported in 48% of patients with ≥ Grade 2 peripheral neuropathy following dose adjustment or interruption. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥ Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.
Hypotension
The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 8%. These events are observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and administration of mineralocorticoids and/or sympathomimetics.
Cardiac Toxicity
Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have occurred during Velcade 3.5mg therapy, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart disease should be closely monitored. In the relapsed multiple myeloma study of Velcade 3.5mg versus dexamethasone, the incidence of any treatment-related cardiac disorder was 8% and 5% in the Velcade 3.5mg and dexamethasone groups, respectively. The incidence of adverse reactions suggestive of heart failure (acute pulmonary edema, pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock) was ≤ 1% for each individual reaction in the Velcade 3.5mg group. In the dexamethasone group the incidence was ≤ 1% for cardiac failure and congestive cardiac failure; there were no reported reactions of acute pulmonary edema, pulmonary edema, or cardiogenic shock. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.
Pulmonary Toxicity
Acute Respiratory Distress Syndrome (ARDS) and acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration have occurred in patients receiving Velcade 3.5mg. Some of these events have been fatal.
In a clinical trial, the first two patients given high-dose cytarabine (2g/m2 per day) by continuous infusion with daunorubicin and Velcade 3.5mg for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy.
There have been reports of pulmonary hypertension associated with Velcade 3.5mg administration in the absence of left heart failure or significant pulmonary disease.
In the event of new or worsening cardiopulmonary symptoms, consider interrupting Velcade 3.5mg until a prompt and comprehensive diagnostic evaluation is conducted.
Posterior Reversible Encephalopathy Syndrome (PRES)
Posterior Reversible Encephalopathy Syndrome (PRES; formerly termed Reversible Posterior Leukoencephalopathy Syndrome (RPLS)) has occurred in patients receiving Velcade 3.5mg. PRES is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patients developing PRES, discontinue Velcade 3.5mg. The safety of reinitiating Velcade 3.5mg therapy in patients previously experiencing PRES is not known.
Gastrointestinal Toxicity
Velcade 3.5mg treatment can cause nausea, diarrhea, constipation, and vomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid and electrolyte replacement should be administered to prevent dehydration. Interrupt Velcade 3.5mg for severe symptoms.
Thrombocytopenia/Neutropenia
Velcade 3.5mg is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remain consistent in the studies of multiple myeloma and mantle cell lymphoma, with no evidence of cumulative thrombocytopenia or neutropenia in the treatment regimens studied.
Monitor complete blood counts (CBC) frequently during treatment with Velcade 3.5mg. Measure platelet counts prior to each dose of Velcade 3.5mg. Adjust dose/schedule for thrombocytopenia. Gastrointestinal and intracerebral hemorrhage has occurred during thrombocytopenia in association with Velcade 3.5mg. Support with transfusions and supportive care, according to published guidelines.
In the single-agent, relapsed multiple myeloma study of Velcade 3.5mg versus dexamethasone, the mean platelet count nadir measured was approximately 40% of baseline. The severity of thrombocytopenia related to pretreatment platelet count is shown in Table 6. The incidence of bleeding (≥ Grade 3) was 2% on the Velcade 3.5mg arm and was < 1% in the dexamethasone arm.
| *A baseline platelet count of 50,000/μL was required for study eligibility | |||
| **Data were missing at baseline for 1 patient | |||
Pretreatment Platelet Count* | Number of Patients (N=331)** | Number (%) of Patients with Platelet Count < 10,000/μL | Number (%) of Patients with Platelet Count 10,000 to 25,000/μL |
| ≥ 75,000/μL | 309 | 8 (3%) | 36 (12%) |
| ≥ 50,000/μL to < 75,000/μL | 14 | 2 (14%) | 11 (79%) |
| ≥ 10,000/μL to < 50,000/μL | 7 | 1 (14%) | 5 (71%) |
Tumor Lysis Syndrome
Tumor lysis syndrome has been reported with Velcade 3.5mg therapy. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. Monitor patients closely and take appropriate precautions.
Hepatic Toxicity
Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic reactions include hepatitis, increases in liver enzymes, and hyperbilirubinemia. Interrupt Velcade 3.5mg therapy to assess reversibility. There is limited re-challenge information in these patients.
Embryo-fetal Toxicity
Based on the mechanism of action and findings in animals, Velcade 3.5mg for Injection can cause fetal harm when administered to a pregnant woman. Velcade 3.5mg administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and a decreased number of live fetuses.
Females of reproductive potential should avoid becoming pregnant while being treated with Velcade 3.5mg for Injection. Advise females of reproductive potential that they must use contraception during treatment with Velcade 3.5mg for Injection and for 7 months following cessation of therapy. Advise males with female sexual partners of reproductive potential that they must use contraception during treatment with Velcade 3.5mg for Injection and for 4 months following cessation of therapy. If Velcade 3.5mg for Injection is used during pregnancy or if the patient becomes pregnant during Velcade 3.5mg for Injection treatment, the patient should be apprised of the potential risk to the fetus.
What happens if I miss a dose of Velcade 3.5mg?
Call your doctor for instructions if you will miss an appointment for your Velcade 3.5mg injection.
References
- DailyMed. "BORTEZOMIB: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DrugBank. "Bortezomib". http://www.drugbank.ca/drugs/DB00188 (accessed September 17, 2018).
- MeSH. "Antineoplastic Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
