MitoMYcin (Systemic)

Dosage Forms

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

Solution Reconstituted, Intravenous:

Mutamycin: 5 mg (1 ea); 20 mg (1 ea); 40 mg (1 ea)

Generic: 5 mg (1 ea); 20 mg (1 ea); 40 mg (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 5 mg (1 ea); 20 mg (1 ea); 40 mg (1 ea)

Pharmacology

Mechanism of Action

Mitomycin alkylates DNA to produce DNA cross-linking (primarily with guanine and cytosine pairs) and inhibits DNA and RNA synthesis. Mitomycin is not cell cycle specific but has its maximum effect against cells in late G and early S phases (Perry 2012).

Pharmacokinetics/Pharmacodynamics

Metabolism

Primarily hepatic

Excretion

Feces (primarily [Perry 2012]); Urine (~10% as unchanged drug)

Half-Life Elimination

17 minutes (30 mg dose)

Use: Labeled Indications

Gastric cancer: Treatment of disseminated adenocarcinoma of the stomach (in combination with other chemotherapy agents) and as palliative treatment when other modalities have failed.

Pancreatic cancer: Treatment of disseminated adenocarcinoma of the pancreas (in combination with other chemotherapy agents) and as palliative treatment when other modalities have failed.

Limitations of use: Not recommended for single-agent primary therapy or to replace appropriate surgery and/or radiotherapy in the treatment of these conditions.

Use: Off Label

Anal cancera

Data from a multicenter, phase III, randomized, controlled study support the use of mitomycin (in combination with fluorouracil and radiation therapy) in the treatment of anal cancer Ajani 2008. Data from another randomized, phase III study also support the use of mitomycin (in combination with fluorouracil and radiation therapy) in the treatment of anal cancer Flam 1996. Data from a large phase III study (including long term follow up) and from a smaller phase III study comparing radiation therapy alone to radiation therapy plus fluorouracil and mitomycin also support the use of mitomycin for the treatment of anal cancer Bartelink 1997, Northover 2010, UKCCCR 1996. Additional data from retrospective studies support the use of mitomycin in combination with capecitabine and radiation therapy Meulendijks 2014, Thind 2014.

Bladder cancerayes

Data from a multicenter phase III trial in muscle invasive bladder cancer support the use of systemic mitomycin (in combination with concurrent radiation and fluorouracil) for the treatment of this condition James 2012. Additionally, data from phase III and IV trials support the use of intravesicular mitomycin in the management of nonmuscle invasive bladder cancer Au 2001, Friedrich 2007, O'Brien 2013.

Based on the American Urological Association (AUA)/Society of Urologic Oncology (SUO) guideline for the diagnosis and treatment of nonmuscle invasive bladder cancer: (stages Ta, T1 and Tis): 2016, mitomycin administered intravesicularly for the treatment of low or intermediate risk nonmuscle invasive bladder cancer is effective and recommended in the management of this condition Chang 2016

Based on the AUA/American Society of Clinical Oncology/American Society for Radiation Oncology/SUO guideline on the treatment of nonmetastatic muscle-invasive bladder cancer, mitomycin (in combination with fluorouracil and external beam radiation therapy) is recommended as a component of multimodal bladder preservation therapy in the treatment of nonmetastatic muscle-invasive bladder cancer Chang 2017.

Cervical cancer, recurrent or metastaticc

Data from a small phase II trial suggest that mitomycin (in combination with cisplatin) may be an option for management of recurrent or metastatic cervical cancer Wagenaar 2001.

Esophageal cancer, advancedb

Data from a randomized phase III trial suggest that mitomycin (in combination with cisplatin and fluorouracil; MCF regimen) may be an effective regimen in the treatment of advanced esophageal cancer Ross 2002.

Hepatocellular carcinoma (chemoembolization)c

Data from a retrospective study support the use of mitomycin as a component of conventional transcatheter arterial chemoembolization (TACE) for the treatment hepatocellular carcinoma Yamada 2019. Another retrospective study in patients with unresectable hepatocellular carcinoma supports the use of mitomycin as a component of conventional TACE Vogl 2012. A retrospective review performed across 2 institutions (with 2 years of follow-up data) also suggests the utility of mitomycin as a component of TACE Morse 2012.

Vulvar cancer, advancedc

Data from a small prospective phase II trial support the use of mitomycin (in combination with fluorouracil and radiation) for the treatment of locally advanced or recurrent vulvar carcinoma Landoni 1996.

Contraindications

Hypersensitivity to mitomycin or any component of the formulation; thrombocytopenia; coagulation disorders, or other increased bleeding tendency

Dosage and Administration

Dosing: Adult

Anal carcinoma (off-label use): IV: 10 mg/m² as an IV bolus on days 1 and 29 (maximum: 20 mg/dose) in combination with fluorouracil and radiation therapy (Ajani 2008; Flam 1996) or 12 mg/m² on day 1 only in combination with fluorouracil and radiation therapy (Northover 2010; UKCCCR 1996) or 15 mg/m² on day 1 only in combination with fluorouracil and radiation therapy (Bartelink 1997) or 10 mg/m² on day 1 (maximum dose: 15 mg) in combination with capecitabine and radiation therapy (Meulendijks 2014) or 12 mg/m² on day 1 (maximum dose: 20 mg) in combination with capecitabine and radiation therapy (Thind 2014)

Bladder cancer (off-label use):

Muscle invasive: IV: 12 mg/m² on day 1 (in combination with fluorouracil and radiation) (James 2012)

Nonmuscle invasive (off-label route): Intravesicular instillation:

Low risk of recurrence (uncomplicated): 40 mg as a single dose postoperatively; retain in bladder for 1 to 2 hours (Hall 2007; O'Brien 2013)

Increased risk of recurrence: 20 mg weekly for 6 weeks, followed by 20 mg monthly for 3 years; retain in bladder for 1 to 2 hours (Friedrich 2007) or 40 mg weekly for 6 weeks (with urine alkalinization and decreased urine volume to increase drug concentration); retain in bladder for 2 hours (Au 2001)

Cervical cancer, recurrent or metastatic (off-label use; based on limited data): IV: 6 mg/m² on day 1 once every 4 weeks (in combination with cisplatin) for a minimum of 2 cycles (preferably 9 cycles) (Wagenaar 2001)

Esophageal cancer, advanced (off-label use): IV: 7 mg/m² (maximum dose: 14 mg) once every 6 weeks for 4 cycles (in combination with cisplatin and fluorouracil) (Ross 2002)

Gastric cancer: IV: 20 mg/m² once every 6 to 8 weeks

Off-label dosing: IV: 7 mg/m² (maximum dose: 14 mg) once every 6 weeks for 4 cycles (in combination with cisplatin and fluorouracil) (Ross 2002)

Hepatocellular cancer, chemoembolization (off-label use): Conventional transcatheter arterial chemoembolization (cTACE): Intra-arterial: 10 mg as a single dose via intra-arterial injection; based on clinical judgement, may repeat at 6 to 8 week intervals (Yamada 2019) or 8 mg/m² as a single dose via intra-arterial injection every 4 weeks for at least 2 doses (Vogl 2012). Refer to protocol and institutional policies for additional dosing/administration details.

Pancreatic cancer: IV: 20 mg/m² once every 6 to 8 weeks

Vulvar cancer, advanced (off-label use; based on limited data): IV: 15 mg/m² on day 1 every 14 days for 2 cycles (in combination with concomitant radiation and fluorouracil) (Landoni 1996)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Leukocytes 2,000 to <3,000/mm³: Hold therapy until leukocyte count ≥4,000/mm³; reduce to 70% of prior dose in subsequent cycles

Leukocytes <2,000/mm³: Hold therapy until leukocyte count ≥4,000/mm³; reduce to 50% of prior dose in subsequent cycles

Platelets 25,000 to <75,000/mm³: Hold therapy until platelets ≥100,000/mm³; reduce to 70% of prior dose in subsequent cycles

Platelets <25,000/mm³: Hold therapy until platelets ≥100,000 mm³; reduce to 50% of prior dose in subsequent cycles

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).

Reconstitution

Reconstitute powder with SWFI to a concentration of 0.5 mg/mL; shake to dissolve. If powder does not dissolve immediately, allow to stand at room temperature until dispersion. May further dilute in NS or sodium lactate to 20 to 40 mcg/mL.

Intravesicular preparation (off-label route): For bladder instillation, mix 20 to 40 mg mitomycin in 20 to 40 mL of normal saline or sterile water for injection (final concentration 1 to 2 mg/mL) (Au 2001; Hall 2007; O’Brien 2013).

Administration

IV: Administer by slow IV push/bolus via a freely-running saline infusion. Consider using a central venous catheter.

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate dimethyl sulfate (DMSO) antidote. Apply dry cold compress for 20 minutes 4 times/day for 1 to 2 days (Pérez Fidalgo 2012).

DMSO: Apply topically to a region covering twice the affected area every 8 hours for 7 days; begin within 10 minutes of extravasation; do not cover with a dressing (Perez Fidalgo 2012).

Intravesicular (off-label route): Instill into bladder and retain for 1 to 2 hours (Au 2001; Friedrich 2007; Hall 2007; O’Brien 2013); rotate patient every 15 to 30 minutes

Intra-arterial: Transcatheter arterial chemoembolization (TACE; off-label use): For conventional TACE, mitomycin was administered with lipiodol and contrast media followed by particle embolization with an embolic agent (Yamada 2019) or followed by starch microspheres for vessel occlusion (Vogl 2012). IV antibiotics were administered prior to the procedure and embolic material was injected through the catheter until hemostasis was achieved (Morse 2012). Refer to protocol and institutional policies for additional administration details.

Storage

Store intact vials at 25°C (77°F); avoid exposure to temperatures >40°C (104°F). Reconstituted solution is stable for 7 days at room temperature and 14 days when refrigerated. Protect reconstituted solution from light. Solutions further diluted for infusion (concentration 20 to 40 mcg/mL) are stable for 12 hours at room temperature when diluted in NS and 24 hours at room temperature when diluted in sodium lactate.

Drug Interactions

Antineoplastic Agents (Vinca Alkaloids): May enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased. 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

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

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

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

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

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

Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

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

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

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

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. 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

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

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%:

Gastrointestinal: Anorexia (14%), nausea (14%), vomiting (14%)

Hematologic & oncologic: Bone marrow depression (64%; onset: 4 weeks; recovery: 8 to 10 weeks), hemolytic-uremic syndrome (HUS; ≤15%), thrombotic thrombocytopenic purpura (TTP; ≤15%)

Miscellaneous: Fever (14%)

1% to 10%:

Dermatologic: Alopecia (4%)

Gastrointestinal: Mucous membrane disease (toxicity: 4%), stomatitis (4%)

Renal: Increased serum creatinine (2%)

<1%, postmarketing, and/or case reports: Adult respiratory distress syndrome (ARDS), bladder spasm (intravesical administration), cardiac failure, dyspnea, extravasation reactions, fibrosis (bladder; intravesical administration), hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease), interstitial fibrosis, malaise, nonproductive cough, pulmonary infiltrates, renal failure (irreversible), skin rash, weakness

Warnings/Precautions

Concerns related to adverse effects:

• Bladder fibrosis/contraction: Bladder fibrosis/contraction has been reported with intravesical administration (unlabeled administration route).
• Bone marrow suppression: [US Boxed Warning]: Bone marrow suppression (thrombocytopenia and leukopenia) is common and may be severe and/or contribute to infections. WBC and platelet nadir usually occurs at 4 weeks, although may occur at up to 8 weeks; recovery occurs within 10 weeks. Fatalities due to sepsis have been reported; monitor for infections. Myelosuppression is dose-limiting, delayed in onset, and cumulative; therefore, monitor blood counts closely during and for at least 8 weeks following treatment; treatment delay or dosage adjustment may be required for significant thrombocytopenia (platelets <100,000/mm³) or leukopenia (WBC<4,000/mm³) or a progressive decline in either value.
• Extravasation: Mitomycin is a potent vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. May cause necrosis and tissue sloughing; delayed erythema and/or ulceration have been reported.
• Heart failure: In a scientific statement from the American Heart Association, mitomycin has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).
• Hemolytic-uremic syndrome: [US Boxed Warning]: Hemolytic-uremic syndrome (HUS) has been reported (incidence not defined); condition usually involves microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (≤100,000/mm³), and irreversible renal failure (serum creatinine ≥1.6 mg/dL). HUS may occur at any time (either with single agent or combination therapy), is generally associated with single doses ≥60 mg, and HUS symptoms may be exacerbated by blood transfusion. Other less common effects may include pulmonary edema, neurologic abnormalities, and hypertension. A high mortality from HUS has been reported.
• Pulmonary toxicity: Cases of acute respiratory distress syndrome (ARDS) have been reported in patients receiving mitomycin in combination with other chemotherapy who were maintained at FIO₂ concentrations >50% perioperatively; use caution to provide only enough oxygen to maintain adequate arterial saturation and avoid overhydration. Pulmonary toxicity has also been reported as dyspnea with nonproductive cough and appearance of pulmonary infiltrates on radiograph; discontinue therapy if pulmonary toxicity occurs and other potential etiologies have been ruled out.

Disease-related concerns:

• Renal impairment: Do not administer if serum creatinine is >1.7 mg/dL; monitor for renal toxicity.

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.
• Vinca alkaloids: Shortness of breath and bronchospasm have been reported in patients receiving vinca alkaloids in combination with mitomycin or who received mitomycin previously; this acute respiratory distress has occurred within minutes to hours following the vinca alkaloid; may be managed with bronchodilators, steroids and/or oxygen.

Other warnings/precautions:

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.

Monitoring Parameters

Monitor CBC with differential (repeatedly during therapy and for ≥8 weeks following therapy); serum creatinine; pulmonary function tests; monitor for signs/symptoms of HUS; monitor infusion site.

Pregnancy

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat stomach cancer.
• It is used to treat pancreatic cancer.
• If you have been given this drug for some other reason, talk with your doctor about the benefits and risks. Talk with your doctor if you have questions or concerns about using this drug.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Mouth irritation
• Mouth sores
• Hair loss
• Lack of appetite

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Bleeding like 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.
• Hemolytic-uremic syndrome like unable to pass urine; loss of strength and energy; signs of bleeding or bruising; fever; or swelling of the face, hands, feet, or body.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Severe dizziness
• Passing out
• Yellow skin
• Pale skin
• Severe loss of strength and energy
• Shortness of breath
• Cough
• Excessive weight gain
• Swelling of arms or legs
• Severe injection site redness, pain, swelling, or irritation
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.