Boxed Warning
Experienced physician:
Teniposide is a cytotoxic drug. Administer under the supervision of a qualified health care provider experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.
Bone marrow suppression:
Severe myelosuppression with resulting infection or bleeding may occur.
Hypersensitivity reactions:
Hypersensitivity reactions, including anaphylaxis-like symptoms, may occur with initial dosing or with repeated exposure to teniposide. Epinephrine, with or without corticosteroids and antihistamines, has been employed to alleviate hypersensitivity reaction symptoms.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 10 mg/mL (5 mL)
Pharmacology
Mechanism of Action
Teniposide does not inhibit microtubular assembly; it has been shown to delay transit of cells through the S phase and arrest cells in late S or early G2 phase, preventing cells from entering mitosis. Teniposide is a topoisomerase II inhibitor, and appears to cause DNA strand breaks by inhibition of strand-passing and DNA ligase action.
Pharmacokinetics/Pharmacodynamics
Distribution
Vdss: Children: 3 to 11 L/m2; Adults: 8 to 44 L/m2; mainly into liver, kidneys, small intestine, and adrenals; limited distribution into CSF <1%
Metabolism
Extensively hepatic
Excretion
Urine (44%, 4% to 12% as unchanged drug); feces (≤10%)
Clearance: Renal: 10% of total body clearance
Half-Life Elimination
Children: 5 hours
Protein Binding
>99%; primarily albumin
Use in Specific Populations
Special Populations: Hepatic Function Impairment
There appears to be an association between an increase in serum alkaline phosphatase or gamma glutamyl-transpeptidase and a decrease in plasma clearance of teniposide.
Use: Labeled Indications
Acute lymphoblastic leukemia, refractory: Treatment of refractory childhood acute lymphoblastic leukemia (ALL) in combination with other chemotherapy
Use: Off Label
Acute lymphoblastic leukemiab
Data from a clinical trial in patients with acute lymphoblastic leukemia (ALL) supports the use of teniposide as consolidation therapy in adults with ALL, in combination with other chemotherapy agents Linker 1991.
Contraindications
Hypersensitivity to teniposide, polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), or any component of the formulation
Dosage and Administration
Dosing: Adult
Note: Patients with Down syndrome and leukemia may be more sensitive to the myelosuppressive effects; administer the first course at half the usual dose and adjust dose in subsequent cycles upward based on degree of toxicities (myelosuppression and mucositis) in the previous course(s).
Acute lymphoblastic leukemia (ALL) consolidation treatment (off-label use; combination chemotherapy): IV: 165 mg/m2/dose days 1, 4, 8, and 11 of alternating consolidation cycles (Linker 1991)
Dosing: Pediatric
Note: Patients with Down syndrome may be more sensitive to the myelosuppressive effects; administer the first course at half the usual dose and adjust dose in subsequent cycles upward based on degree of toxicities (myelosuppression and mucositis) in the previous course(s).
Acute lymphoblastic leukemia (ALL; combination therapy): Note: Although FDA approved, teniposide is generally no longer used due to improved toxicity and efficacy profiles with other combination regimens used in the treatment of ALL (Salzer 2010):
Infants ≥6 months, Children, and Adolescents: Regimens may vary: IV: 165 mg/m2 twice weekly for 8 to 9 doses or 250 mg/m2 weekly for 4 to 8 weeks
Neuroblastoma; high-risk: Limited data available: Children and Adolescents : IV: 100 mg/m2/dose administered 48 hours after completion of a 6-hour cisplatin infusion dose every 3 weeks (McWilliams 1995)
Reconstitution
Precipitation may occur at any concentration. Teniposide must be diluted with either D5W or NS solutions to a final concentration of 0.1, 0.2, 0.4, or 1 mg/mL. Solutions should be prepared in non-DEHP-containing containers such as glass or polyolefin containers. The use of polyvinyl chloride (PVC) containers is not recommended. Because precipitation may occur at any concentration, the manufacturer recommends administrating as soon as possible after preparation. Teniposide contains N,N-dimethylacetamide, which may be incompatible with some closed system transfer devices (CSTDs); the plastic components of some CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]). Refer to the specific CSTD device manufacturer for compatibility data.
Administration
IV: Administer over at least 30 to 60 minutes; do not administer by rapid IV injection. Administer through non-DEHP-containing administration sets. Incompatible with heparin; flush infusion line with D5W or NS before and after infusion. Precipitation may occur at any concentration; administer as soon as possible after preparation; inspect solution prior to administration. Observe patient continuously for at least the first 60 minutes after the start of the infusion, observe frequently thereafter. Stop infusion for signs of anaphylaxis (may require treatment with epinephrine, corticosteroids, antihistamines, pressors, or volume expanders); discontinue for clinically significant hypotension during infusion; if infusion is restarted after being withheld for hypotension, reinitiate at a slower infusion rate.
Teniposide contains N, N-dimethylacetamide, which may be incompatible with some closed system transfer devices (CSTDs); the plastic components of some CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]). Refer to the specific CSTD device manufacturer for compatibility data.
Storage
Store ampuls in refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light. Solutions diluted for infusion in D5W or NS to a concentration of 0.1, 0.2, or 0.4 mg/mL are stable at room temperature for up to 24 hours after preparation; solutions diluted to 1 mg/mL should be used within 4 hours of preparation. Because precipitation may occur at any concentration, the manufacturer recommends administrating as soon as possible after preparation. Use appropriate precautions for handling and disposal. Do not refrigerate solutions prepared for infusion.
Drug Interactions
Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Barbiturates: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification
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
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
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
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
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
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
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
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosphenytoin: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with phenytoin and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination
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
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Phenytoin: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with phenytoin and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification
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
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
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
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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
VinCRIStine: Teniposide may enhance the neurotoxic effect of VinCRIStine. Monitor therapy
VinCRIStine (Liposomal): Teniposide may enhance the neurotoxic effect of VinCRIStine (Liposomal). Monitor therapy
Adverse Reactions
>10%:
Gastrointestinal: Mucositis (76%), diarrhea (33%), nausea and vomiting (29%; mild to moderate)
Hematologic & oncologic: Neutropenia (95%), leukopenia (89%), anemia (88%), thrombocytopenia (85%), bone marrow depression (75%)
Infection: Infection (12%)
1% to 10%:
Cardiovascular: Hypotension (2%; may be intractable; associated with rapid [<30 minutes] infusions)
Dermatologic: Alopecia (9%; usually reversible), skin rash (3%)
Hematologic & oncologic: Hemorrhage (5%)
Hypersensitivity: Hypersensitivity reaction (5%; includes bronchospasm, chills, dyspnea, fever, flushing, hypertension, hypotension, tachycardia, or urticaria)
Miscellaneous: Fever (3%)
<1%, postmarketing, and/or case reports: Cardiac arrhythmia, central nervous system depression, confusion, fluid and electrolyte disturbance, headache, hepatic insufficiency, metabolic acidosis, neuropathy (severe), neurotoxicity, renal insufficiency, thrombophlebitis, weakness
Warnings/Precautions
Concerns related to adverse effects:
- Bone marrow suppression: [US Boxed Warning]: Severe myelosuppression resulting in infection or bleeding may occur; may be dose-limiting; monitor blood counts during and after treatment.
- Extravasation: Teniposide is considered an irritant (Pérez Fidalgo, 2012). For IV use only; ensure proper catheter/needle position prior to infusion; monitor infusion site; may cause local tissue necrosis and/or thrombophlebitis if extravasation occurs.
- Hypersensitivity: [US Boxed Warning]: Hypersensitivity reactions, including anaphylaxis-like reactions, have been reported; may occur with initial dosing or with repeated exposure to teniposide. Epinephrine, with or without corticosteroids and antihistamines, has been employed to alleviate hypersensitivity reaction symptoms. Hypersensitivity reactions may include bronchospasm, dyspnea, hypertension, hypotension, tachycardia, flushing, chills, fever, or urticaria. Monitor closely during infusion (observe continuously for first 60 minutes, frequently thereafter). Stop infusion for signs of anaphylaxis; immediate treatment for anaphylactic reaction should be available during administration (may require treatment with epinephrine, corticosteroids, antihistamines, pressors, or volume expanders). Patients experiencing prior hypersensitivity are at risk for recurrence; re-treat only if the potential benefit outweighs the risk of hypersensitivity; premedication (with corticosteroids and antihistamines) is recommended for re-treatment.
- Hypotension: Hypotension may occur with rapid infusion; infuse slowly over at least 30 to 60 minutes; discontinue for clinically significant hypotension. If infusion is restarted after being withheld for hypotension, reinitiate at a slower infusion rate.
- Toxicity with high doses: Acute CNS depression, hypotension and metabolic acidosis have been reported; these events occurred in patients who received high-dose teniposide (investigation protocol) and were premedicated with antiemetics, which along with the alcohol content of teniposide, may have contributed to the CNS depression.
Disease-related concerns:
- Hepatic impairment: Use with caution; may require dosage reduction in patients with significant impairment.
- Renal impairment: Use with caution; may require dosage reduction in patients with significant impairment.
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.
Special populations:
- Down syndrome: Patients with Down syndrome and leukemia may be more sensitive to the myelosuppressive effects; reduced initial doses are recommended.
- Hypoalbuminemia: Since teniposide is highly bound to plasma proteins, carefully monitor patients with hypoalbuminemia.
Dosage form specific issues:
- Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.
- Dehydrated alcohol: Product contains about 43% alcohol.
- Polyoxyl 35/polyoxyethylated castor oil: Contains polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), which is associated with hypersensitivity reactions.
Other warnings/precautions:
- Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.
Monitoring Parameters
CBC with differential and platelet count, renal and hepatic function tests; blood pressure; monitor for hypersensitivity reaction (observe continuously for first 60 minutes of infusion, frequently thereafter)
Pregnancy
Pregnancy Risk Factor
D
Pregnancy Considerations
Adverse effects were observed in animal reproduction studies. May cause fetal harm if administered during pregnancy. Females of reproductive potential should avoid becoming pregnant during teniposide treatment.
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 mouth irritation, mouth sores, nausea, vomiting, diarrhea, loss of strength and energy, or hair loss. Have patient report immediately to prescriber signs of infection, 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 lactic acidosis (fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), fast heartbeat, abnormal heartbeat, severe headache, severe dizziness, passing out, vision changes, flushing, severe injection site redness, burning, pain, edema, or irritation, or confusion (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.