Applies to bortezomib: powder for solution, solution.

Serious side effects of Bortezomib

Along with its needed effects, bortezomib may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking bortezomib:

More common

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• chills
• confusion
• cough
• cough producing mucus
• decreased urination
• difficult or labored breathing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• ear congestion
• fainting
• fever
• headache
• increase in heart rate
• loss of voice
• lower back or side pain
• nerve pain
• painful blisters on the trunk of the body
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• rapid breathing
• runny nose
• sneezing
• sore throat
• stuffy nose
• sunken eyes
• sweating
• swollen glands
• thirst
• tightness in the chest
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• weakness in the arms, hands, legs, or feet
• wrinkled skin

Less common

• Dilated neck veins
• general feeling of discomfort or illness
• increased sensitivity to pain
• increased sensitivity to touch
• irregular breathing
• irregular heartbeat
• swelling of the face, fingers, feet, or lower legs
• thickening of bronchial secretions
• tingling in the hands and feet
• weight gain

Incidence not known

• Agitation
• back pain
• blistering, peeling, or loosening of the skin
• bloating
• bruising
• change in consciousness
• coughing or vomiting blood
• dark urine
• deafness
• deep or fast breathing with dizziness, numbness to feet, hands, and around the mouth
• diarrhea
• drowsiness
• fast heartbeat
• general tiredness and weakness
• irritability
• itching
• light-colored stools
• loss of consciousness
• pain in the stomach, side, or abdomen, possibly radiating to the back
• persistent bleeding or oozing from puncture sites, mouth, or nose
• pounding, slow heartbeat
• rectal bleeding
• red skin lesions, often with a purple center
• red, irritated eyes
• restlessness
• seeing, hearing, or feeling things that are not there
• seizures
• shaking
• stiff neck
• stomach pain and tenderness
• trouble sleeping
• upper right stomach pain
• yellow eyes or skin

Other side effects of Bortezomib

Some side effects of bortezomib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Belching
• bone pain
• difficulty having a bowel movement
• difficulty with moving
• feeling unusually cold or shivering
• hair loss or thinning of hair
• heartburn
• indigestion
• joint pain or swelling
• loss of appetite
• loss of taste
• mental depression
• muscle cramps
• muscle pain or stiffness
• nausea
• pain in the arms or legs
• rash
• stomach discomfort, upset, or pain
• vomiting
• weight loss

For Healthcare Professionals

Applies to bortezomib: injectable powder for injection, intravenous injection, intravenous powder for injection, intravenous solution.

Gastrointestinal

Grade 3 gastrointestinal events were reported to have occurred in 18% of patients and Grade 4 events were reported in 1%. Gastrointestinal events were considered to be serious in 11% of patients.^[Ref]

Very common (10% or more): Nausea (up to 64%), diarrhea (up to 51%), constipation (up to 43%), decreased appetite (up to 43%), vomiting (up to 36%), dyspepsia (up to 13%)

Frequency not reported: Ascites, dysphagia, fecal impaction, hemorrhagic gastritis, gastrointestinal hemorrhage, hematemesis, paralytic ileus, large intestinal obstruction, paralytic intestinal obstruction, small intestinal obstruction, large intestinal perforation, stomatitis, melena, gastroenteritis, hemorrhagic duodenitis, peritonitis, oral mucosal petechiae, gastroesophageal reflux, acute pancreatitis^[Ref]

Hematologic

Very common (10% or more): Thrombocytopenia (34%), neutropenia (27%), anemia (23%), leukopenia (20%), lymphopenia (23%)

Uncommon (0.1% to 1%): Lymphadenopathy, febrile neutropenia, pancytopenia, hemolytic anemia, thrombocytopenia purpura

Frequency not reported: Disseminated intravascular coagulation, subdural hematoma, pancytopenia, hemolytic anemia, thrombocytopenia purpura^[Ref]

Thrombocytopenia was characterized by a dose related decrease in platelet count during the dosing period (days 1 through 11) with a return to the baseline platelet count during the rest period (days 12 through 21) of each treatment cycle. Thrombocytopenia was grade 3 or 4 for 24% and 5% of patients, respectively.

Grade 3 or 4 neutropenia have been reported to have occurred in 9% and 3% of treated patients, respectively.^[Ref]

Nervous system

Very common (10% or more): Peripheral neuropathy (39%), paresthesia and dysesthesia (23%), headache (22%), dizziness (17%), dysgeusia (13%), anxiety (10%)

Common (1% to 10%): Peripheral sensory neuropathy, tremor

Uncommon (0.1% to 1%): Cerebrovascular accident, convulsion, syncope, disturbance in attention, increased activity, ageusia, somnolence, migraine, jerky movements, postural dizziness, sciatica, post herpetic neuralgia, cognitive disorder, mononeuropathy, paresis, restless leg syndrome, speech disorder, intracranial hemorrhage, paraplegia, subarachnoid hemorrhage

Postmarketing reports: Autonomic neuropathy, encephalopathy^[Ref]

Bortezomib treatment causes a peripheral neuropathy that is predominantly sensory. However, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with preexisting symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy during treatment with bortezomib. 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 may require change in the dose and schedule of bortezomib.

Following dose adjustments, improvement in or resolution of peripheral neuropathy has been reported in 51% of patients with peripheral neuropathy greater than or equal to grade 2 in the relapsed multiple myeloma study. Improvement in or resolution of peripheral neuropathy has been reported in 73% of patients who discontinued due to grade 2 neuropathy or who had greater than or equal to 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.^[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (26%), pain in limb (26%), bone pain (14%), myalgia (14%), muscle cramps (14%), back pain (13%)

Common (1% to 10%): Peripheral swelling, muscle weakness, musculoskeletal pain

Uncommon (0.1% to 1%): Joint stiffness, buttock pain, joint swelling, muscle spasms, muscle twitching, sensation of heaviness, muscle stiffness, swelling, pain in jaw^[Ref]

Cardiovascular

Most reports of hypotension (including orthostatic hypotension) were grade 1 or 2 in severity. Grade 3 hypotension was reported to have occurred in 3% and Grade 4 hypotension was reported in less than 1% of patients.^[Ref]

Very common (10% or more): Hypotension (13%)

Frequency not reported: Aggravated atrial fibrillation, atrial flutter, cardiac amyloidosis, cardiac arrest, congestive cardiac failure, hypertension, myocardial ischemia, myocardial infarction, pericardial effusion, pulmonary edema, angina pectoris, bradycardia, sinus arrest, complete atrioventricular block, pericarditis, Torsades de pointes, decreased left ventricular ejection fraction, ventricular tachycardia^[Ref]

Respiratory

Very common (10% or more): Dyspnea (22%), cough (20%), upper respiratory tract infection (18%), cough (17%), lower respiratory tract/lung infection (15%), nasopharyngitis (14%), pneumonia (12%)

Common (1% to 10%): Epistaxis, dyspnea on exertion, rhinorrhea, bronchitis, sinusitis

Uncommon (0.1% to 1%): Nasal congestion, wheezing, pleural effusion, hoarseness, chest wall pain, hypoxia, pulmonary congestion, rhinitis, asthma, hyperventilation, orthopnea, sinus pain, throat tightness, productive cough, respiratory alkalosis, respiratory arrest, tachypnea, pneumococcal, bronchopneumonia, pleural infection, pulmonary edema

Frequency not reported: Acute respiratory distress syndrome, acute diffuse infiltrative pulmonary disease, atelectasis, exacerbated chronic obstructive airways disease, hemoptysis, pulmonary hypertension, pulmonary alveolar hemorrhage^[Ref]

Dermatologic

Very common (10% or more): Rash (18%), herpes zoster (12%)

Very rare (less than 0.01%): Erythematous plaques or nodules on the trunk, generalized morbilliform erythema with ulcerations and fever, cutaneous vasculitis, histiocytoid Sweet Syndrome

Frequency not reported: Toxic epidermal necrolysis, leukocytoclastic vasculitis, pruritus, urticaria, facial edema^[Ref]

Other

Very common (10% or more): Asthenic conditions (fatigue, malaise, and weakness) (65%), pyrexia (36%), headache (28%), insomnia (27%), dizziness (excluding vertigo) (21%), dehydration (18%), anxiety (14%), fatigue (15%), dysgeusia (13%), rigors (12%)

Common (1% to 10%): Pyrexia

Frequency not reported: Impaired hearing, aspergillosis, bacteremia, herpes viral infection, listeriosis, septic shock, toxoplasmosis, oral candidiasis, tumor lysis syndrome, vertigo^[Ref]

Ocular

Very common (10% or more): Blurred vision (11%)

Common (1% to 10%): Eye pain

Uncommon (0.1% to 1%): Dry eye, conjunctivitis, eye discharge, abnormal vision, eye hemorrhage, photophobia, eye irritation, increased lacrimation, conjunctival hyperemia, blepharitis, eye swelling

Rare (less than 0.1%): Ophthalmic herpes

Frequency not reported: Conjunctival infection, irritation, diplopia

Postmarketing reports: Optic neuropathy, blindness^[Ref]

Hypersensitivity

Very rare (less than 0.01%): Stevens-Johnson Syndrome

Frequency not reported: Anaphylactic reaction, drug hypersensitivity, immune complex mediated hypersensitivity^[Ref]

Hepatic

Rare (less than 0.1%): Acute liver failure (in patients receiving multiple concomitant medications and with serious underlying medical conditions)

Frequency not reported: Hyperbilirubinemia, cholestasis, hepatic hemorrhage, hepatitis, portal vein thrombosis, asymptomatic increases in liver enzymes^[Ref]

Metabolic

Very common (10% or more): Anorexia (34 to 43%), dehydration (18%)

Common (1% to 10%): Hyper- or hypocalcemia, hypokalemia, decreased weight, increased blood lactate dehydrogenase

Uncommon (0.1% to 1%): Hypoglycemia, hyperkalemia, hyperuricemia, hyper or hyponatremia, hypomagnesemia, hypophosphatemia, decreased blood bicarbonate levels, increased blood alkaline phosphatase, urea, blood amylase, and C-reactive protein, increased appetite and weight, cachexia, vitamin B12 deficiency, tumor lysis syndrome^[Ref]

Psychiatric

Very common (10% or more): Peripheral neuropathies (50%), insomnia (18 to 27%), neuralgia (23%), anxiety (14%)

Common (1% to 10%): Agitation, confusion, depression

Uncommon (0.1% to 1%): Delirium, restlessness, mood swings, mental status changes, sleep disorder, irritability, hallucinations, abnormal dreams

Frequency not reported: Agitation, confusion, psychotic disorder, mental status change, suicidal ideation^[Ref]

Renal

Very common (10% or more): Acute and chronic renal impairment, dysuria

Uncommon (0.1% to 1%): Increased blood creatinine

Frequency not reported: Renal calculus, renal colic, hematuria, proteinuria, difficulty in micturition or micturition urgency, oliguria, bilateral hydronephrosis, bladder spasm, urinary tract infection, hemorrhagic cystitis, proliferative glomerular nephritis^[Ref]

Local

Uncommon (0.1% to 1%): Injection site erythema, catheter related infection, catheter related complication, post procedural pain, post procedural hemorrhage, burns^[Ref]

Immunologic

Frequency not reported: Angioedema, laryngeal edema^[Ref]

Endocrine

Uncommon (0.1% to 1%): Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Genitourinary

Uncommon (0.1% to 1%): Testicular pain, erectile dysfunction