Dinutuximab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Unituxin: 17.5 mg/5 mL (5 mL)

Pharmacology

Mechanism of Action

Dinutuximab binds to the disialoganglioside GD2, which is highly expressed in neuroblastoma, most melanomas, and other tumors, as well as on normal tissues such as neurons, skin melanocytes, and peripheral sensory nerve fibers (Yu 2010). By binding to cell surface GD2, dinutuximab induces cell lysis (of GD2-expressing cells) through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Pharmacokinetics/Pharmacodynamics

Distribution

Pediatric patients (age: 3.9 ± 1.9 years): V_dss: 5.4 L

Excretion

Clearance: Pediatric patients (age: 3.9 ± 1.9 years): 0.21 L/day; increased with body size

Half-Life Elimination

Terminal: 10 days

Use: Labeled Indications

Neuroblastoma: Treatment of high-risk neuroblastoma (in combination with granulocyte-macrophage colony-stimulating factor [GM-CSF; sargramostim], interleukin-2 [IL-2; aldesleukin] and 13-cis-retinoic acid [RA; isotretinoin]) in pediatric patients who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Contraindications

History of anaphylaxis to dinutuximab

Dosage and Administration

Dosing: Pediatric

Note: Intravenous hydration and premedication with analgesics, antihistamines, and antipyretics is required prior to administration. Ensure adequate hematologic, respiratory, hepatic, and renal function prior to each cycle of therapy.

Neuroblastoma, high-risk: Infants, Children, and Adolescents: IV: 17.5 mg/m²/day for 4 consecutive days for a maximum of 5 cycles (in combination with GM-CSF [sargramostim], IL-2 [aldesleukin] and 13-cis-retinoic acid [isotretinoin]). Infuse on days 4, 5, 6, and 7 during cycles 1, 3, and 5 (cycles 1, 3, and 5 are 24 days in duration); infuse on days 8, 9, 10, and 11 during cycles 2 and 4 (cycles 2 and 4 are 32 days in duration). In the reported trials, the youngest patient was 11 months of age.

Premedications:

IV hydration: NS: IV: 10 mL/kg; infuse over 1 hour just prior to each dinutuximab infusion

Antihistamine: Diphenhydramine: IV: 0.5 to 1 mg/kg/dose; maximum dose: 50 mg/dose; administer over 10 to 15 minutes starting 20 minutes prior to dinutuximab infusion and every 4 to 6 hours as tolerated during the infusion

Antiemetics: Dinutuximab is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting

Antipyretics:

Acetaminophen: Oral: 10 to 15 mg/kg/dose; administer 20 minutes prior to each infusion and every 4 to 6 hours as needed for fever and pain; maximum dose: 650 mg/dose

Ibuprofen: Oral: 5 to 10 mg/kg/dose every 6 hours as needed for control of persistent fever or pain; maximum dose: 400 mg/dose

Analgesics: Morphine: IV: 50 mcg/kg; administer immediately prior to dinutuximab infusion initiation; continue as a morphine drip at a rate of 20 to 50 mcg/kg/hour during and for 2 hours following completion of dinutuximab infusion. May administer additional morphine doses of 25 to 50 mcg/kg IV as needed up to once every 2 hours followed by an increase in the drip rate in clinically stable patients. Consider conversion to fentanyl or hydromorphone if morphine is not tolerated; if pain is inadequately controlled with opioids, consider adjunct therapy with gabapentin or lidocaine.

Dosing adjustment for toxicity: Infants, Children, and Adolescents:

Anaphylaxis, grade 3 or 4: Permanently discontinue therapy.

Capillary leak syndrome:

Moderate to severe, but not life-threatening: Immediately interrupt infusion; upon resolution, resume infusion at 50% of the previous rate

Life-threatening: Discontinue infusion for the current cycle; in subsequent cycles, infuse at 50% of the previous rate. If life-threatening capillary leak syndrome recurs, permanently discontinue therapy.

Hemolytic uremic syndrome: Permanently discontinue therapy and administer supportive management.

Hyponatremia, grade 4 (despite appropriate fluid management): Permanently discontinue therapy.

Hypotension (symptomatic hypotension, systolic blood pressure [SBP] less than lower limit of normal for age, or SBP decreased by more than 15% compared to baseline): Interrupt infusion; upon resolution, resume infusion at 50% of the previous rate. If blood pressure remains stable for ≥2 hours, gradually increase infusion rate as tolerated up to a maximum rate of 1.75 mg/m²/hour.

Infection (systemic)/sepsis, severe: Discontinue therapy until infection resolves; may resume therapy with subsequent cycles.

Infusion-related reaction:

Mild to moderate reaction (eg, transient rash, fever, rigors, and localized urticaria that respond promptly to symptomatic treatment): Reduce infusion rate by 50%; monitor closely. Upon resolution, gradually increase infusion rate up to a maximum of 1.75 mg/m²/hour.

Severe or prolonged reaction (eg, mild bronchospasm without other symptoms, angioedema that does not affect the airway): Immediately interrupt infusion; if symptoms resolve rapidly, resume infusion at 50% of the previous rate and monitor closely. If reaction recurs, discontinue therapy until the following day. If symptoms resolve and further treatment is warranted, premedicate with IV hydrocortisone 1 mg/kg (maximum dose: 50 mg/dose) and infuse at a rate of 0.875 mg/m²/hour in an intensive care unit. If reaction recurs again, permanently discontinue therapy.

Life-threatening reaction: Permanently discontinue therapy and administer supportive management.

Neuropathy:

Grade 4 sensory neuropathy or grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks: Permanently discontinue therapy.

Grade 2 or higher peripheral motor neuropathy: Permanently discontinue therapy.

Ocular neurological disorders (eg, blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, and/or papilledema): Discontinue infusion until symptom resolution; upon resolution, reduce dose by 50%. If reaction recurs, or if reaction is accompanied by visual impairment (eg, subtotal or total vision loss), permanently discontinue therapy.

Pain, severe (grade 3): Decrease the infusion rate to 0.875 mg/m²/hour. If pain is not adequately controlled despite rate reduction and use of maximum supportive measures, permanently discontinue therapy.

Reversible posterior leukoencephalopathy syndrome: Permanently discontinue therapy.

Serum sickness, grade 3 or 4: Permanently discontinue therapy.

Transverse myelitis: Permanently discontinue therapy.

Urinary retention (persistent after opioid discontinuation): Permanently discontinue therapy.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Keep the vial in the outer carton to protect from light. Solutions diluted for infusion in NS should be stored at 2°C to 8°C (36°F to 46°F). Initiate infusion within 4 hours of preparation. Discard diluted solution 24 hours after preparation.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

>10%:

Cardiovascular: Hypotension (60%), capillary leak syndrome (40%), tachycardia (19%), edema (17%), hypertension (14%)

Central nervous system: Pain (85%), peripheral neuropathy (13%; grades 3/4: 6%)

Dermatologic: Urticaria (37%)

Endocrine & metabolic: Hyponatremia (58%), hypokalemia (43%), hypoalbuminemia (33%), hypocalcemia (27%), hypophosphatemia (20%), hyperglycemia (18%), hypertriglyceridemia (16%), hypomagnesemia (12%)

Gastrointestinal: Increased serum ALT (56%), vomiting (46%), diarrhea (43%), increased serum AST (28%), decreased appetite (15%)

Genitourinary: Proteinuria (16%)

Hematologic & oncologic: Thrombocytopenia (66%; grades 3/4: 39%), lymphocytopenia (62%; grades 3/4: 51%), anemia (51%; grades 3/4: 34%), neutropenia (39%; grades 3/4: 34%), hemorrhage (17%; grades 3/4: 6%)

Hypersensitivity: Severe infusion-related reaction (26%)

Infection: Sepsis (18%), infection (device-related: 16%), bacteremia (grades 3/4: 13%)

Renal: Increased serum creatinine (15%)

Respiratory: Hypoxia (24%)

Miscellaneous: Fever (72%), infusion-related reaction (60%)

1% to 10%

Central nervous system: Peripheral sensory neuropathy (9%; grade 3: 1%), peripheral motor neuropathy (grade 3: 1%)

Dermatologic: Anaphylaxis (1%)

Endocrine & metabolic: Weight gain (10%)

Gastrointestinal: Nausea (10%)

Hematologic & oncologic: Febrile neutropenia (grades 3/4: 4%), hemolytic-uremic syndrome (2%)

Ophthalmic: Blurred vision (2%)

Frequency not defined: Ophthalmic: Blepharoptosis, optic nerve damage, papilledema, photophobia

<1%, postmarketing, and/or case reports: Diplopia, fixation of pupils, mydriasis, reversible posterior leukoencephalopathy syndrome, transverse myelitis, urinary retention (prolonged)

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Severe (grade 3 or 4) anemia, neutropenia, thrombocytopenia, and neutropenic fever were observed in dinutuximab-treated patients. Monitor complete blood counts closely during treatment.
• Capillary leak syndrome: Severe capillary leak syndrome was reported in close to one-fourth of patients receiving dinutuximab. Immediately interrupt infusion if capillary leak syndrome develops; infusion rate reduction and/or therapy discontinuation may be necessary. Initiate appropriate management in patients with symptomatic or severe capillary leak syndrome.
• Electrolyte abnormalities: Electrolyte abnormalities (such as hyponatremia, hypokalemia, and hypocalcemia) were reported in at least one-fourth of patients who received dinutuximab, including grade 3 or 4 events. In a study of a related anti-GD2 antibody, syndrome of inappropriate antidiuretic hormone secretion (SIADH) resulting in severe hyponatremia was reported. Monitor electrolytes closely during therapy.
• Gastrointestinal toxicity: Dinutuximab is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.
• Hemolytic uremic syndrome: Hemolytic uremic syndrome (without documented infection) resulted in renal insufficiency, electrolyte abnormalities, anemia, and hypertension in a small number of patients. Atypical hemolytic uremic syndrome recurred in one patient upon rechallenge. Permanently discontinue if hemolytic uremic syndrome develops; manage supportively.
• Hypotension: Severe hypotension occurred more frequently in patients receiving dinutuximab. Intravenous hydration is required prior to each infusion; closely monitor blood pressure during infusion. May require therapy interruption or discontinuation; initiate appropriate medical management in patients with a systolic blood pressure (SBP) less than lower limit of normal for age, or SBP that is decreased by more than 15% compared to baseline.
• Infection: Severe (grade 3 or 4) bacteremia was reported more frequently in dinutuximab-treated patients, and required intravenous antibiotics or other urgent interventions. Sepsis was also observed in patients receiving dinutuximab. Monitor closely for signs/symptoms of systemic infection; may require therapy interruption until resolution of infection.
• Infusion reaction: [US Boxed Warning]: Serious and potentially life-threatening infusion reactions occurred in approximately one-fourth of patients treated with dinutuximab. Administer required prehydration and premedication, including antihistamines, prior to each dinutuximab infusion. Monitor patients closely for signs and symptoms of an infusion reaction during and for at least 4 hours following completion of each dinutuximab infusion. Immediately interrupt dinutuximab for severe infusion reactions and permanently discontinue dinutuximab for anaphylaxis. Infusion reactions typically occurred during infusion or within 24 hours of completion and may include facial and upper airway edema, dyspnea, bronchospasm, stridor, urticaria, and hypotension. Infusion reactions may require blood pressure support, bronchodilator therapy, corticosteroids, infusion rate interruption and/or reduction, or permanent therapy discontinuation. Infusion should be in a facility with cardiopulmonary medication/equipment available.
• Neurotoxicity: [US Boxed Warning]: Dinutuximab causes serious neurologic adverse reactions including severe neuropathic pain and peripheral neuropathy; severe neuropathic pain occurs in the majority of patients. Administer intravenous opioids prior to, during, and for 2 hours following completion of the dinutuximab infusion. In clinical studies of patients with high-risk neuroblastoma, grade 3 peripheral sensory neuropathy occurred in 2% to 9% of patients. In clinical studies of dinutuximab and related GD2-binding antibodies, severe motor neuropathy has occurred. Resolution of motor neuropathy did not occur in all cases. Discontinue dinutuximab for severe unresponsive pain, severe sensory neuropathy, or moderate to severe peripheral motor neuropathy. Discontinue permanently for grade 2 or higher peripheral motor neuropathy, grade 3 sensory neuropathy that interferes with activities of daily living for more than 2 weeks, or grade 4 sensory neuropathy. In patients who experienced peripheral sensory neuropathy of any grade, the median duration was 9 days (range: 3 to 163 days).
• Ocular toxicity: Neurological ocular toxicity such as blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, and papilledema were reported in clinical trials. In patients who experienced complete resolution of ocular toxicity, the median duration of toxicity was 4 days (range: 0 to 221 days). May require therapy interruption, dosage reduction, and/or treatment discontinuation.
• Pain: Most patients experienced pain; severe pain was observed in over 50% of patients treated with dinutuximab; pain may occur despite analgesic/opioid therapy. Pain typically occurred during infusion and included abdominal, generalized, extremity, or back pain, neuralgia, musculoskeletal chest pain, and arthralgia. Premedication with analgesics, including opioids, is required prior to each dose, during the infusion, and for 2 hours following the infusion. Severe pain may require reduction of the infusion rate or therapy discontinuation.
• Reversible posterior leukoencephalopathy syndrome: Reversible posterior leukoencephalopathy syndrome (RPLS) has been reported. Symptoms of RPLS include severe headache, hypertension, visual changes, seizures or lethargy. Begin appropriate management and discontinue dinutuximab in patients with RPLS signs/symptoms.
• Transverse myelitis: Transverse myelitis has occurred in patients receiving dinutuximab; signs/symptoms (weakness, paresthesia, sensory loss or incontinence) should be evaluated promptly. Discontinue permanently in patients who develop transverse myelitis.
• Urinary retention: Prolonged urinary retention that persists for weeks to months after opioid discontinuation has occurred in patients receiving dinutuximab; discontinue permanently if urinary retention does not resolve following opioid discontinuation.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

CBC with differential, serum electrolytes, renal function, blood pressure; monitor for signs/symptoms of infusion reactions (during and for at least 4 hours after infusion), pain, peripheral neuropathy, capillary leak syndrome, infection/sepsis, hemolytic uremic syndrome, ocular toxicity, urinary retention, transverse myelitis, and/or reversible posterior leukoencephalopathy syndrome.

Pregnancy

Pregnancy Considerations

Dinutuximab is a monoclonal antibody (IgG₁). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009). Based on the mechanism of action, dinutuximab may cause fetal harm.

Women of reproductive potential should use effective contraception during therapy and for 2 months after the last dose.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea, lack of appetite, nausea, vomiting, or weight gain. Have patient report immediately to prescriber signs of infusion reaction (chills, dizziness, passing out, fever, itching, swelling in your throat, or difficulty breathing), severe pain, burning or numbness feeling, muscle weakness, difficult urination, leaking of urine, bowel incontinence, signs of capillary leak syndrome (abnormal heartbeat; chest pain; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; unable to pass urine or change in amount of urine passed; or blood in the urine), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit), signs of infection, blurred vision, blindness, vision changes, change in pupil size, sensitivity to lights, dizziness, passing out, fast heartbeat, severe loss of strength and energy, pale skin, edema, signs of posterior reversible encephalopathy syndrome (confusion, not alert, vision changes, seizures, or severe headache), or signs of Hemolytic-uremic syndrome (unable to pass urine; loss of strength and energy; signs of bleeding or bruising; fever; or swelling of the face, hands, feet, or body) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.