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Mercaptopurine

Pronunciation

Pronunciation

(mer kap toe PURE een)

Index Terms

  • 6-Mercaptopurine (error-prone abbreviation)
  • 6-MP (error-prone abbreviation)
  • Purinethol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Suspension, Oral:

Purixan: 2000 mg/100 mL (100 mL) [contains aspartame, methylparaben, propylparaben]

Tablet, Oral:

Purinethol: 50 mg [DSC] [scored]

Generic: 50 mg

Brand Names: U.S.

  • Purinethol [DSC]
  • Purixan

Pharmacologic Category

  • Antineoplastic Agent, Antimetabolite
  • Antineoplastic Agent, Antimetabolite (Purine Analog)
  • Immunosuppressant Agent

Pharmacology

Mercaptopurine is a purine antagonist which inhibits DNA and RNA synthesis; acts as false metabolite and is incorporated into DNA and RNA, eventually inhibiting their synthesis; specific for the S phase of the cell cycle

Absorption

Variable and incomplete (~50% of a dose is absorbed); Cmax of suspension is 34% higher than the tablet

Distribution

Vd > total body water; CNS penetration is poor

Metabolism

Hepatic and via GI mucosa; hepatically via xanthine oxidase and methylation via TPMT to sulfate conjugates, 6-thiouric acid, and other inactive compounds; first-pass effect

Excretion

Urine (46% as mercaptopurine and metabolites)

Time to Peak

Serum: Within 2 hours

Half-Life Elimination

Children: 21 minutes; Adults: 47 minutes

Protein Binding

~19%

Special Populations: Renal Function Impairment

Might result in slower elimination of parent drug and metabolites, and a greater cumulative effect.

Use: Labeled Indications

Acute lymphoblastic leukemia: Treatment of acute lymphoblastic leukemia (ALL), as part of a combination chemotherapy regimen

Use: Unlabeled

Steroid-sparing agent for corticosteroid-dependent Crohn disease (CD) and ulcerative colitis (UC); maintenance of remission in CD; fistulizing Crohn disease; maintenance treatment in acute promyelocytic leukemia (APL); treatment component for non Hodgkin lymphoma (NHL), treatment of autoimmune hepatitis

Contraindications

Hypersensitivity to mercaptopurine or any component of the formulation; patients whose disease showed prior resistance to mercaptopurine

Dosing: Adult

Note: Patients with minimal or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe toxicity at conventional mercaptopurine doses and generally require dose reduction; consider TPMT gene polymorphism testing in patients who experience severe bone marrow suppression (homozygous deficient patients may require up to a 90% dosage reduction; heterozygous patients usually tolerate recommended doses, although some may require dosage reduction).

Acute lymphoblastic leukemia (ALL): Maintenance: Oral: 1.5 to 2.5 mg/kg once daily (50 to 75 mg/m2 once daily); continue based on blood counts or

Off-label ALL dosing (combination chemotherapy; refer to specific reference for combinations):

Early intensification (two 4-week courses): 60 mg/m2/day days 1 to 14 (Larson 1995; Larson 1998)

Interim maintenance (12-week course): 60 mg/m2/day days 1 to 70 (Larson 1995; Larson 1998)

Maintenance (prolonged): 50 mg 3 times/day for 2 years (Kantarjian 2000) or 60 mg/m2/day for 2 years from diagnosis (Larson 1995; Larson 1998)

Acute promyelocytic leukemia (APL) maintenance (off-label use): 60 mg/m2/day for 1 year (in combination with tretinoin and methotrexate) (Powell 2010)

Crohn disease, remission maintenance or reduction of steroid use (off-label use): Oral: 1 to 1.5 mg/kg/day (Lichtenstein 2009)

Lymphoblastic lymphoma (off-label use): Maintenance (prolonged): 50 mg 3 times daily for 2 years (Kantarjian 2000; Thomas 2004)

Ulcerative colitis (off-label use): Oral:

Initial: 50 mg once daily; titrate dose up if clinical remission not achieved or down if leukopenia occurs (Lobel 2004) or

Initial: 50 mg (25 mg if heterozygous for TPMT activity) once daily; titrate up to goal of 1.5 mg/kg (0.75 mg/kg if heterozygous for TPMT activity) if WBC >4,000/mm3 (and at least 50% of baseline) and LFTs and amylase are stable (Siegel 2005) or

Maintenance: 1 to 1.5 mg/kg/day (Carter 2004) or

Remission maintenance: 1.5 mg/kg/day (Danese 2011)

Dosage adjustment with concurrent allopurinol: Reduce mercaptopurine dosage to 25% to 33% of the usual dose.

Dosing: Geriatric

Due to renal decline with age, initiate treatment at the low end of recommended dose range.

Dosing: Pediatric

Note: Patients with minimal or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe toxicity at conventional mercaptopurine doses and generally require dose reduction; consider TPMT gene polymorphism testing in patients who experience severe bone marrow suppression (homozygous deficient patients may require up to a 90% dosage reduction; heterozygous patients usually tolerate recommended doses, although some may require dosage reduction).

Acute lymphoblastic leukemia (ALL): Maintenance: Oral: 1.5 to 2.5 mg/kg once daily (50 to 75 mg/m2 once daily); continue based on blood counts or

Off-label ALL dosing (combination chemotherapy; refer to specific reference for combinations): Adolescents ≥15 years:

Consolidation phase: 60 mg/m2/day days 0 to 27 days (5-week course) (Stock 2008) or 60 mg/m2/day days 0 to 13 and days 28 to 41 (9-week course) (Stock 2008)

Early intensification (two 4-week courses): 60 mg/m2/day days 1 to 14 (Larson 1995; Larson 1998; Stock 2008)

Interim maintenance: 60 mg/m2/day days 0-41 (8-week course) (Stock 2008) or 60 mg/m2/day days 1 to 70 (12-week course) (Larson 1995; Larson 1998; Stock 2008)

Maintenance (prolonged): 50 mg 3 times/day for 2 years (Kantarjian 2000) or 60 mg/m2/day for 2 years from diagnosis (Larson 1995; Larson 1998; Stock 2008) or 75 mg/m2/day for 2 years (girls) or 3 years (boys) from first interim maintenance (Stock 2008)

Acute promyelocytic leukemia (APL) maintenance (off-label use): Oral: Adolescents ≥15 years: 60 mg/m2/day for 1 year (in combination with tretinoin and methotrexate) (Powell 2010)

Autoimmune hepatitis (off-label use): Oral: 1.5 mg/kg/day (in combination with prednisone) (Manns 2010)

Crohn disease, remission maintenance (off-label use): Doses range from 1 to 1.5 mg/kg/day (Grossman 2008; Markowitz 2000); children ≤6 years may require higher doses to achieve clinical improvement (Grossman 2008).

Lymphoblastic lymphoma (off-label use): Adolescents ≥15 years: Maintenance (prolonged): 50 mg 3 times daily for 2 years (Kantarjian 2000; Thomas 2004) or 60 mg/m2/day for 2 years from diagnosis (Stock 2008) or 75 mg/m2/day for 2 years (girls) or 3 years (boys) from first interim maintenance (Stock 2008)

Ulcerative colitis, remission maintenance (off-label use): Doses range from 1 to 1.5 mg/kg/day (Grossman 2008; Sandhu 2010); children ≤6 years may require higher doses to achieve clinical improvement (Grossman 2008); additional trials may be necessary to further define the role of mercaptopurine in pediatric patients with this condition.

Dosage adjustment with concurrent allopurinol: Reduce mercaptopurine dosage to 25% to 33% of the usual dose.

Dosing: Renal Impairment

The manufacturer's labeling recommends starting with reduced doses (starting at the low end of the dosing range) or increasing the dosing interval to every 36 to 48 hours in patients with renal impairment to avoid accumulation; however, no specific dosage adjustment is provided. The following adjustments have also been recommended (Aronoff 2007): Children:

CrCl ≤50 mL/minute/1.73 m2: Administer every 48 hours

Hemodialysis: Administer every 48 hours

Continuous ambulatory peritoneal dialysis (CAPD): Administer every 48 hours

Continuous renal replacement therapy (CRRT): Administer every 48 hours

Dosing: Hepatic Impairment

The manufacturer’s labeling recommends considering a reduced dose (starting at the low end of the dosing range) with close monitoring for toxicity dose in patients with baseline hepatic impairment; however, no specific dosage adjustment is provided.

Dosing: Adjustment for Toxicity

Adjust dosage for excessive hematologic toxicity.

Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Suspension: Wear disposable gloves when handling. Measure dose with an oral dosing syringe to assure proper dose is administered. Oral syringe provided by the manufacturer is intended to be reused, wash with warm soapy water and rinse well (hold syringe under water and move plunger several times to ensure inside of syringe is clean); allow to dry completely.

Extemporaneously Prepared

Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). When manipulating tablets, NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye protection as well as ventilated engineering controls are recommended (NIOSH 2014).

A 50 mg/mL oral suspension may be prepared in a vertical flow hood with tablets and a mixture of sterile water for injection (SWFI), simple syrup, and cherry syrup. Crush thirty 50 mg tablets in a mortar and reduce to a fine powder. Add ~5 mL SWFI and mix to a uniform paste; then add ~10 mL simple syrup; mix while continuing to add cherry syrup to make a final volume of 30 mL; transfer to a calibrated bottle. Label "shake well" and "caution chemotherapy". Stable for 35 days at room temperature.

Aliabadi HM, Romanick M, Desai, S, et al, “Effect of Buffer and Antioxidant on Stability of a Mercaptopurine Suspension,” Am J Health Syst Pharm 2008, 65(5):441-7. 18281736

Administration

Administer preferably on an empty stomach (1 hour before or 2 hours after meals)

ALL treatment in children (Schmiegelow 1997): Administration in the evening has demonstration superior outcome; administration with food did not significantly affect outcome.

Suspension: Shake well for at least 30 seconds to ensure suspension is mixed thoroughly (suspension is viscous). Measure dose with an oral dosing syringe (a 1 mL and a 5 mL oral dosing syringe are supplied by the manufacturer) to assure proper dose is administered. Patients and caregivers should be trained on appropriate measuring and administration, handling, storage, disposal, cleanup of accidental spills, and proper cleaning of oral dosing syringe. Use within 6 weeks after opening.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Avoid exposure to crushed or broken tablets; if it is necessary to manipulate the tablets (eg, to prepare an oral solution), it is recommended to double glove, wear a protective gown, and prepare in a controlled device. Disposable gloves should be worn when handling tablets or suspension for administration; health care providers should also wear a protective gown (NIOSH 2014).

Storage

Tablets: Store at 15°C to 25°C (59°F to 77°F). Store in a dry place.

Suspension: Store at 15°C to 25°C (59°F to 77°F). Do not store above 25°C (77°F). Store in a dry place. Use within 6 weeks after opening.

Drug Interactions

5-ASA Derivatives: May decrease the metabolism of Thiopurine Analogs. Monitor therapy

Allopurinol: May increase the serum concentration of Mercaptopurine. Allopurinol may also promote formation of active thioguanine nucleotides. Management: Reduce the mercaptopurine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. US labeling for mercaptopurine oral suspension (Purixan brand) recommends avoiding allopurinol. Consider therapy modification

AzaTHIOprine: May enhance the myelosuppressive effect of Mercaptopurine. Avoid combination

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

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. Avoid combination

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

DOXOrubicin (Conventional): May enhance the hepatotoxic effect of Mercaptopurine. Monitor therapy

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

Febuxostat: May increase the serum concentration of Mercaptopurine. Avoid combination

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

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. Consider therapy modification

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

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

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

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

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Sulfamethoxazole: May enhance the myelosuppressive effect of Mercaptopurine. Monitor therapy

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

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. Avoid combination

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

Trimethoprim: May enhance the myelosuppressive effect of Mercaptopurine. Monitor therapy

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): Mercaptopurine may enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Mercaptopurine may diminish the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

TPMT testing: Recent transfusions may result in a misinterpretation of the actual TPMT activity. Concomitant drugs may influence TPMT activity in the blood.

Adverse Reactions

Frequency not always defined.

Central nervous system: Malaise (5% to 20%), drug fever

Dermatologic: Skin rash (5% to 20%), hyperpigmentation (<5%), urticaria (<5%), alopecia

Endocrine & metabolic: Hyperuricemia (<5%)

Gastrointestinal: Anorexia (5% to 20%), diarrhea (5% to 20%), nausea (5% to 20%; minimal), vomiting (5% to 20%; minimal), oral lesion (<5%), pancreatitis (<5%), cholestasis, mucositis, sprue-like symptoms, stomach pain, ulcerative bowel lesion

Genitourinary: Oligospermia, renal toxicity, uricosuria

Hematologic & oncologic: Bone marrow depression (>20%; onset 7-10 days; nadir 14 days; recovery: 21 days), anemia, granulocytopenia, hemorrhage, hepatosplenic T-cell lymphomas, leukopenia, lymphocytopenia, metastases, neutropenia, thrombocytopenia

Hepatic: Hyperbilirubinemia (<5%), increased serum transaminases (<5%), ascites, hepatic encephalopathy, hepatic fibrosis, hepatic injury, hepatic necrosis, hepatomegaly, hepatotoxicity, intrahepatic cholestasis, jaundice, toxic hepatitis

Immunologic: Immunosuppression

Infection: Infection

Respiratory: Pulmonary fibrosis

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Dose-related leukopenia, thrombocytopenia, and anemia are common; however, may be indicative of disease progression. Hematologic toxicity may be delayed. Bone marrow may appear hypoplastic (could also appear normal). Monitor blood counts; dose may require adjusting for severe neutropenia or thrombocytopenia. Monitor for bleeding (due to thrombocytopenia) or infection (due to neutropenia). Profound severe or repeated hematologic toxicity may be indicative of thiopurine methyltransferase (TPMT) deficiency (see “Thiopurine methyltransferase deficiency” below).

• Hepatotoxicity: Hepatotoxicity has been reported, including jaundice, ascites, hepatic necrosis (may be fatal), intrahepatic cholestasis, parenchymal cell necrosis, and/or hepatic encephalopathy; may be due to direct hepatic cell damage or hypersensitivity. While hepatotoxicity or hepatic injury may occur at any dose, dosages exceeding the recommended dose are associated with a higher incidence. Signs of jaundice generally appear early in treatment, after ~1 to 2 months (range: 1 week to 8 years) and may resolve following discontinuation; recurrence with rechallenge has been noted. Monitor liver function tests, including transaminases, alkaline phosphatase, and bilirubin weekly with treatment initiation, then monthly thereafter (monitor more frequently if used in combination with other hepatotoxic drugs or in patients with preexisting hepatic impairment). Consider a reduced dose in patients with baseline hepatic impairment; monitor closely for toxicity. Withhold treatment for clinical signs of jaundice (hepatomegaly, anorexia, tenderness), deterioration in liver function tests, toxic hepatitis, or biliary stasis until hepatotoxicity is ruled out.

• Immunosuppression: Mercaptopurine is immunosuppressive; immune responses to infections may be impaired and the risk for infection is increased. Common signs of infection, such as fever and leukocytosis may not occur; lethargy and confusion may be more prominent signs of infection.

• Secondary malignancy: Immunosuppressive agents, including mercaptopurine, are associated with the development of lymphoma and other malignancies. In an analysis of T-cell lymphomas associated with TNF blockers (with or without thiopurines) for the treatment of rheumatoid arthritis, Crohn disease, ulcerative colitis, or ankylosing spondylitis (off-label uses for thiopurines), an increase in the incidence of T-cell lymphomas, most commonly mycosis fungoides/Sézary syndrome and hepatosplenic T-cell lymphoma (HSTCL) was reported (Deepak 2013). HSTCL is a rare white blood cell cancer that is usually fatal. Most HSTCL cases occurred in patients treated with a combination of TNF blockers and thiopurines, although cases of HSTCL also occurred in patients receiving azathioprine or mercaptopurine monotherapy.

Disease-related concerns:

• Renal impairment: Consider dosage modification in patients with renal impairment. Some renal adverse effects may be minimized with hydration and prophylactic antihyperuricemic therapy.

NUDT15 genetic variation: A germline variant in nucleoside diphophate-linked moiety X-type motif 15 (NUDT15) is strongly correlated with mercaptopurine intolerance in children receiving treatment for acute lymphoblastic leukemia (ALL). A genome-wide association study was performed in two prospective clinical childhood ALL trials, and showed that patients homozygous for the TT genotype were extremely sensitive to mercaptopurine, and achieved an average dose intensity of only 8.3%. The NUDT15 genetic variant is most common in East Asian and Hispanic patients. In patients homozygous for either TPMT or NUDT15 (or heterozygous for both), mercaptopurine dose reductions of ≥50% were required in 100% of patients (Yang 2015).

• Thiopurine methyltransferase deficiency: Patients with homozygous genetic defect of thiopurine methyltransferase (TPMT) are more sensitive to myelosuppressive effects; generally associated with rapid myelosuppression. Significant mercaptopurine dose reductions will be necessary (possibly with continued concomitant chemotherapy at normal doses). Patients who are heterozygous for TPMT defects will have intermediate activity; may have increased toxicity (primarily myelosuppression) although will generally tolerate normal mercaptopurine doses. Consider TPMT testing for severe toxicities/excessive myelosuppression.

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. Because azathioprine is metabolized to mercaptopurine, concomitant use with azathioprine may result in a significant increase in hematologic toxicity and profound myelosuppression; avoid concurrent use. Hematologic toxicity may be exacerbated by other medications which inhibit TPMT (eg, mesalamine, olsalazine, sulfasalazine) or by other myelosuppressive drugs.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Other warnings/precautions:

• Error-prone terms: To avoid potentially serious dosage errors, the terms “6-mercaptopurine” or “6-MP” should be avoided; use of these terms has been associated with six-fold overdosages.

• Vaccines: Immune response to vaccines may be diminished. Live virus vaccines impose a risk for infection.

Monitoring Parameters

CBC with differential (weekly initially, although clinical status may require increased frequency), bone marrow exam (to evaluate marrow status), liver function tests (transaminases, alkaline phosphatase, and bilirubin; weekly initially, then monthly; monitor more frequently if on concomitant hepatotoxic agents or in patients with pre-existing hepatic impairment), renal function, urinalysis; consider TPMT genotyping to identify TPMT defect (if severe hematologic toxicity occurs)

For use as immunomodulatory therapy in CD or UC, monitor CBC with differential weekly for 1 month, then biweekly for 1 month, followed by monitoring every 1 to 2 months throughout the course of therapy. LFTs should be assessed every 3 months. Monitor for signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss).

Pregnancy Risk Factor

D

Pregnancy Considerations

May cause fetal harm if administered during pregnancy. Case reports of fetal loss have been noted with mercaptopurine administration during the first trimester; adverse effects have also been noted with second and third trimester use. Women of child bearing potential should avoid becoming pregnant during 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 lack of appetite. 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 bleeding that is very bad or that will not stop), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe diarrhea, severe nausea, severe vomiting, skin discoloration, redness or white patches in mouth or throat, severe loss of strength and energy, shortness of breath, severe abdominal pain, or skin growths (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 healthcare 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.

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