Trastuzumab and Hyaluronidase

Dosage Forms

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

Solution, Subcutaneous [preservative free]:

Herceptin Hylecta: Trastuzumab 600 mg and hyaluronidase-oysk 10,000 units per 5 mL (5 mL)

Pharmacology

Mechanism of Action

Trastuzumab is a monoclonal antibody which binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2); it mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells which overexpress HER-2 protein.

Hyaluronidase increases the dispersion and absorption rate of subcutaneous trastuzumab-containing products by increasing permeability of subcutaneous tissue through temporary depolymerization of hyaluronan; at the recommended doses, hyaluronidase acts transiently and locally; permeability of the subcutaneous tissue is restored within 24 to 48 hours.

Pharmacokinetics/Pharmacodynamics

Distribution

Trastuzumab: SubQ: 2.9 L

Excretion

Trastuzumab: SubQ: In most patients, trastuzumab is estimated to reach concentrations of <1 mcg/mL by 7 months following the last trastuzumab/hyaluronidase dose.

Clearance: Linear: Trastuzumab: SubQ: 0.11 L/day

Time to Peak

Trastuzumab: SubQ: ~3 days (Jackisch 2015)

Use in Specific Populations

Special Populations Note

Body weight: While not clinically relevant, body weight demonstrated a statistically significant influence on pharmacokinetics. The mean steady state AUC of trastuzumab was ~80% higher after trastuzumab/hyaluronidase (compared to IV trastuzumab) in patients <51 kg. The AUC was 20% lower after trastuzumab/hyaluronidase (compared to IV trastuzumab) in patients >90 kg.

Use: Labeled Indications

Breast cancer, adjuvant treatment: Adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature) in adults with breast cancer, as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; as a single agent following multi-modality anthracycline-based therapy.

Breast cancer, metastatic: First-line treatment of HER2-overexpressing metastatic breast cancer (in combination with paclitaxel) in adults; single agent treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.

Limitations of use: Select patients for trastuzumab treatment based on an approved companion diagnostic test for tumor specimen for HER2 overexpression or HER2 gene amplification.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosage and Administration

Dosing: Adult

Note: Do not substitute trastuzumab/hyaluronidase with IV trastuzumab products (eg, conventional trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan). No loading dose is required for trastuzumab/hyaluronidase.

Breast cancer, adjuvant treatment, HER2+: SubQ: Trastuzumab 600 mg/hyaluronidase 10,000 units once every 3 weeks for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. Administer in combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or in combination with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline based therapy.

Breast cancer, metastatic, HER2+: SubQ: Trastuzumab 600 mg/hyaluronidase 10,000 units once every 3 weeks (in combination with paclitaxel or as a single agent following one or more chemotherapy regimens for metastatic disease) until disease progression or unacceptable toxicity.

Missed doses: If one dose is missed, administer the missed dose as soon as possible. The interval between subsequent trastuzumab/hyaluronidase doses should not be <3 weeks.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Cardiomyopathy:

≥16% absolute left ventricular ejection fraction (LVEF) decrease from pretreatment values or LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from pretreatment values: Withhold trastuzumab/hyaluronidase dosing for at least 4 weeks. If LVEF returns to normal limits and the absolute decrease from baseline is ≤15% within 4 to 8 weeks, may resume trastuzumab/hyaluronidase.

Persistent (>8 weeks) LVEF decline or if trastuzumab/hyaluronidase dosing is withheld on >3 occasions for cardiomyopathy: Permanently discontinue trastuzumab/hyaluronidase.

Hypersensitivity:

Grade 1 or 2 hypersensitivity (reversible): Consider premedication with an analgesic, antipyretic, or an antihistamine prior to subsequent trastuzumab/hyaluronidase doses.

Anaphylaxis or severe hypersensitivity reactions: Permanently discontinue trastuzumab/hyaluronidase.

Reconstitution

Check vial labels to ensure appropriate product is being reconstituted (trastuzumab/hyaluronidase and ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, or conventional trastuzumab are different products and are NOT interchangeable).

Using a transfer needle, withdraw solution from vial into a syringe; replace transfer needle with a syringe closing cap. To avoid clogging the needle, attach the needle to the syringe immediately prior to administration and adjust volume to 5 mL. Trastuzumab/hyaluronidase is compatible with syringes made with polypropylene and polycarbonate and with stainless steel transfer and injection needles.

Administration

SubQ: Administer subcutaneously over 2 to 5 minutes. For subcutaneous use only. Doses should be administered by a health care professional. Alternate the injection site between the left and right thigh. Administer new injections on healthy skin at least 2.5 cm from the previous site; do not administer into areas where the skin is red, bruised, tender, or hard, or areas where there are moles or scars. Do not administer other subcutaneous medications at the same sites as trastuzumab/hyaluronidase. To avoid clogging the needle, attach the injection needle to the syringe immediately prior to administration followed by volume adjustment to 5 mL.

Check label to ensure appropriate product is being administered; trastuzumab/hyaluronidase, conventional trastuzumab products, ado-trastuzumab emtansine, and fam-trastuzumab deruxtecan are different products and are NOT interchangeable.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Store in the original carton to protect from light. Do not shake. Once vial is removed from the refrigerator, trastuzumab/hyaluronidase must be administered within 4 hours and should not be kept above 30°C (86°F). If syringe prepared for administration is not used immediately, store the syringe refrigerated at 2°C to 8°C (36°F to 46°F) (do not freeze) for up to 24 hours and subsequently at room temperature at 20°C to 25°C (68°F to 77°F) for up to 4 hours. Protect from light. Do not shake.

Drug Interactions

Alpha-/Beta-Agonists: Hyaluronidase may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Exceptions: EPINEPHrine (Nasal); EPINEPHrine (Oral Inhalation); Isometheptene; Pseudoephedrine. Consider therapy modification

Anthracyclines: Trastuzumab may enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Consider therapy modification

Antihistamines: May diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Corticosteroids: May diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Exceptions: Beclomethasone (Nasal); Budesonide (Nasal); Ciclesonide (Nasal); Desonide; DexAMETHasone (Ophthalmic); Difluprednate; Flunisolide (Nasal); Fluocinolone (Ophthalmic); Fluticasone (Nasal); Hydrocortisone (Ophthalmic); Loteprednol; Mometasone (Nasal); PrednisoLONE (Ophthalmic); Triamcinolone (Nasal); Triamcinolone (Ophthalmic). Consider therapy modification

DOPamine: Hyaluronidase may enhance the adverse/toxic effect of DOPamine. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of dopamine. Use of hyaluronidase for other purposes in patients receiving dopamine may be considered as clinically indicated. Consider therapy modification

Estrogen Derivatives: May diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving estrogens (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Immunosuppressants: Trastuzumab may enhance the neutropenic effect of Immunosuppressants. Exceptions: Cytarabine (Liposomal). Monitor therapy

Local Anesthetics: Hyaluronidase may enhance the adverse/toxic effect of Local Anesthetics. Exceptions: Benzocaine; Benzydamine; Cocaine (Topical); Dibucaine; Dyclonine; Ethyl Chloride; Hexylresorcinol; Lidocaine (Ophthalmic); Lidocaine (Topical); Pramoxine; Proparacaine; Tetracaine (Ophthalmic); Tetracaine (Topical). Monitor therapy

PACLitaxel (Conventional): Trastuzumab may decrease the serum concentration of PACLitaxel (Conventional). PACLitaxel (Conventional) may increase the serum concentration of Trastuzumab. Monitor therapy

Phenylephrine (Systemic): Hyaluronidase may enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Avoid combination

Salicylates: May diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving salicylates (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Adverse Reactions

Note: Incidences reported may be with concomitant chemotherapy.

>10%:

Cardiovascular: Edema (12% to 14%), flushing (12% to 14%)

Central nervous system: Fatigue (21% to 46%), peripheral neuropathy (14% to 20%; grade ≥3: <1%), headache (13% to 17%), peripheral sensory neuropathy (11%)

Dermatologic: Alopecia (9% to 63%), skin rash (10% to 26%), nail disease (10% to 14%)

Gastrointestinal: Nausea (15% to 49%), diarrhea (21% to 34%), vomiting (7% to 23%), stomatitis (6% to 21%; grade ≥3: <1%), decreased appetite (20%), abdominal pain (10% to 14%), constipation (9% to 14%), dyspepsia (11%)

Hematologic & oncologic: Neutropenia (6% to 44%; grade ≥3: 4% to 30%), anemia (8% to 12%; grade ≥3: <1%), leukopenia (1% to 11%; grade ≥3: 1% to 5%)

Immunologic: Antibody development (16% to 21%; neutralizing: 6%)

Local: Injection site reaction (10% to 20%), incisional pain (11%)

Neuromuscular & skeletal: Asthenia (12% to 25%), arthralgia (18% to 21%), myalgia (14% to 21%), limb pain (10% to 11%), back pain (8% to 11%)

Respiratory: Upper respiratory tract infection (10% to 24%), cough (11% to 12%), dyspnea (7% to 11%)

Miscellaneous: Radiation injury (skin: 14%), fever (11% to 13%)

1% to 10%:

Cardiovascular: Hypertension (2% to 8%), cardiac arrhythmia (5%), reduced ejection fraction (5%), left ventricular dysfunction (3%), palpitations (2%), tachycardia (2%), cardiac failure (1%)

Central nervous system: Dizziness (6% to 10%), pain (5% to 8%), insomnia (7%), paresthesia (6%)

Dermatologic: Skin discoloration (9%), erythema of skin (7% to 9%), pruritus (6% to 9%), cellulitis (grade ≥3: 1%)

Endocrine & metabolic: Hot flash (10%), menstrual disease (grade ≥3%: 2%), amenorrhea (grade ≥3: 1%)

Gastrointestinal: Dysgeusia (10%)

Genitourinary: Urinary tract infection (6% to 4%)

Hematologic & oncologic: Febrile neutropenia (2% to 6%; grade ≥3: 2% to 6%), granulocytopenia (grade ≥3: 1%)

Hepatic: Abnormal hepatic function tests (6%)

Hypersensitivity: Hypersensitivity reaction (7% to 9%), anaphylaxis (4%)

Infection: Viral infection (5%)

Local: Erythema at injection site (7%), pain at injection site (6%)

Neuromuscular & skeletal: Musculoskeletal pain (7% to 8%), ostealgia (6%)

Respiratory: Epistaxis (6%), nasal discomfort (≤6%), rhinitis (≤6%)

<1%, postmarketing, and/or case reports: Acute respiratory distress syndrome, cardiomyopathy, decreased left ventricular ejection fraction, discomfort at injection site, drug-induced hypersensitivity reaction, hypoxia, interstitial pneumonitis, noncardiogenic pulmonary edema, pleural effusion, pulmonary fibrosis, pulmonary infiltrates, pulmonary toxicity, respiratory insufficiency

Warnings/Precautions

Concerns related to adverse effects:

• Cardiomyopathy: [US Boxed Warning]: Trastuzumab/hyaluronidase administration can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab/hyaluronidase with anthracycline-containing chemotherapy regimens. Evaluate left ventricular function in all patients prior to and during treatment with trastuzumab/hyaluronidase. Discontinue trastuzumab/hyaluronidase treatment in patients receiving adjuvant therapy and withhold trastuzumab/hyaluronidase in patients with metastatic disease for clinically significant decrease in left ventricular function. Trastuzumab/hyaluronidase may cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Trastuzumab/hyaluronidase may also result in an asymptomatic decline in left ventricular ejection fraction (LVEF). Other cardiac adverse effects associated with trastuzumab/hyaluronidase include tachycardia, palpitations, and heart failure. Among patients receiving trastuzumab (as a single agent or in combination with chemotherapy), there is a 4- to 6-fold increase in the incidence of symptomatic myocardial dysfunction, compared to patients not receiving trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an anthracycline. The incidence of symptomatic myocardial dysfunction for trastuzumab/hyaluronidase and intravenous trastuzumab was similar in clinical trials. Withhold trastuzumab/hyaluronidase for ≥16% absolute decrease in LVEF from pretreatment values or an LVEF value below institutional limits of normal and ≥10% absolute decrease in LVEF (from pretreatment values). The safety of continuing or resuming trastuzumab/hyaluronidase with trastuzumab-induced left ventricular cardiac dysfunction has not been studied. Patients who receive anthracycline after stopping trastuzumab/hyaluronidase may also be at increased risk of cardiac dysfunction. Conduct thorough cardiac assessment, including history, physical examination, and LVEF assessment (by echocardiogram or MUGA scan). LVEF should be assessed at baseline (immediately prior to trastuzumab/hyaluronidase initiation), every 3 months during and upon completion of trastuzumab/hyaluronidase therapy, every 4 weeks if trastuzumab/hyaluronidase is withheld for significant left ventricular cardiac dysfunction, and every 6 months for at least 2 years following completion of trastuzumab/hyaluronidase when used as a component of adjuvant therapy.

ASCO has developed guidelines for prevention and monitoring of cardiac dysfunction in adult survivors of cancer (ASCO [Armenian 2017]). According to the guidelines, the risk of cardiac dysfunction related to trastuzumab is increased with the following:

- Trastuzumab alone AND any of the following risk factors: Multiple cardiovascular risk factors (≥2 risk factors), including smoking, hypertension, diabetes, dyslipidemia, and obesity (during or after completion of therapy), or older age (≥60 years of age) at cancer treatment, or compromised cardiac function (eg, borderline low LVEF [50% to 55%], history of myocardial infarction, moderate or higher valvular heart disease) before or during treatment.

- Treatment with lower-dose anthracycline (eg, doxorubicin <250 mg/m², epirubicin <600 mg/m²) followed by trastuzumab (sequential therapy)

The ASCO guidelines recommend a comprehensive assessment in patients with cancer that includes a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking. An echocardiogram should be obtained prior to initiating potentially cardiotoxic therapies. Modifiable risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) should be actively managed before initiating potentially cardiotoxic therapies. In patients who develop signs/symptoms of cardiac dysfunction during therapy, in addition to the above LVEF monitoring recommendations, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized. Serum cardiac biomarkers are recommended, along with referral to a cardiologist if indicated. Routine echocardiographic surveillance may be utilized in patients with metastatic breast cancer receiving trastuzumab indefinitely.

• Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis, have been reported with trastuzumab/hyaluronidase. Patients with dyspnea at rest due to complications of advanced malignancy and/or comorbidities may be at increased risk of a severe or fatal adverse reaction. Grades 3 or 4 reactions have occurred (rare); permanent discontinuation due to hypersensitivity or anaphylaxis was required in a small number of patients. Serious and fatal reactions have been reported following treatment with IV trastuzumab products. Monitor for systemic hypersensitivity reactions, particularly with the initial dose. Permanently discontinue trastuzumab/hyaluronidase in patients who experience anaphylaxis or severe hypersensitivity reactions. Medications to treat anaphylaxis or hypersensitivity and emergency equipment should be available for immediate use. Consider premedication with an analgesic, antipyretic, or an antihistamine prior to subsequent trastuzumab/hyaluronidase doses in patients who experienced a reversible grade 1 or 2 hypersensitivity reaction.
• Pulmonary toxicity: [US Boxed Warning]: Trastuzumab/hyaluronidase administration can result in serious and fatal pulmonary toxicity. Symptoms usually occur during or within 24 hours of trastuzumab/hyaluronidase administration. Discontinue trastuzumab/hyaluronidase for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Monitor patients until symptoms completely resolve. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Patients with symptomatic intrinsic lung disease or extensive pulmonary tumor involvement, resulting in dyspnea at rest, appear to have more severe pulmonary toxicity.

Concurrent drug therapy issues:

• Chemotherapy: Trastuzumab/hyaluronidase may increase the incidence of neutropenia when used in combination with myelosuppressive chemotherapy. The incidences of grades 3 and 4 neutropenia and febrile neutropenia were higher in patients receiving trastuzumab (compared to those who received chemotherapy alone).
• 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:

• Pregnancy: [US Boxed Warning]: Exposure to trastuzumab/hyaluronidase during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.

Dosage form specific issues:

• Do not interchange: Trastuzumab/hyaluronidase and conventional trastuzumab products, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan are not interchangeable. Verify product label prior to reconstitution and administration to prevent medication errors. Dosing and treatment schedules differ between trastuzumab/hyaluronidase and conventional trastuzumab (Herceptin or trastuzumab biosimilars), ado-trastuzumab emtansine (Kadcyla), or fam-trastuzumab deruxtecan (Enhertu).

Other warnings/precautions:

• HER2 expression: Establish human epidermal growth receptor 2 (HER2) status prior to treatment with an approved test, either HER2 protein overexpression by validated immunohistochemistry assay or gene amplification by fluorescence in situ hybridization assay. Tests appropriate for breast cancer should be used to assess HER2 status. Unreliable results may occur from improper assay performance, such as use of suboptimally fixed tissue, failure to utilize specified reagents or to include appropriate controls for assay validation, or incorrectly following specific assay instructions. Information regarding HER2 diagnostic testing may be found at http://www.fda.gov/CompanionDiagnostics.

Monitoring Parameters

Assess for human epidermal growth receptor 2 (HER2) overexpression and HER2 gene amplification by validated immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methodology (pretherapy) specific for breast cancer. Pregnancy test (prior to treatment in women of reproductive potential). Assess left ventricular ejection fraction (LVEF) at baseline, every 3 months during treatment, upon therapy completion and if component of adjuvant therapy, every 6 months for at least 2 years; if treatment is withheld for significant LVEF dysfunction, monitor LVEF at 4-week intervals. Monitor for signs/symptoms of cardiomyopathy, hypersensitivity, and/or pulmonary toxicity.

Additional cardiovascular monitoring (ASCO [Armenian 2017]): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking. In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized; obtain serum cardiac biomarkers. Routine echocardiographic surveillance may be utilized in patients with metastatic breast cancer receiving trastuzumab indefinitely.

Pregnancy

Pregnancy Considerations

[US Boxed Warning]: Exposure to trastuzumab/hyaluronidase during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception. Adverse fetal events may occur with exposure during pregnancy or if exposure occurs within 7 months prior to conception.

Evaluate pregnancy status of females of reproductive potential prior to the initiation of therapy. Females of reproductive potential should use effective contraception during treatment and for at least 7 months after the last trastuzumab/hyaluronidase dose.

Also refer to individual monographs for additional information.

If exposure to trastuzumab/hyaluronidase occurs during pregnancy, or if a patient becomes pregnant during or within 7 months after treatment, report exposure to Genentech Adverse Events at 1-888-835-2555.

Patient Education

What is this drug used for?

• It is used to treat breast cancer.

Frequently reported side effects of this drug

• Hair loss
• Lack of appetite
• Abdominal pain
• Change in taste
• Bone pain
• Joint pain
• Muscle pain
• Back pain
• Painful extremities
• Trouble sleeping
• Mouth irritation
• Mouth sores
• Injection site irritation
• Flushing
• Common cold symptoms
• Nail changes
• Skin discoloration
• Constipation
• Diarrhea
• Vomiting
• Nausea

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

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out
• Severe pulmonary disorder like lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse
• Infection
• Severe headache
• Dizziness
• Passing out
• Vision changes
• Severe loss of strength and energy
• Burning or numbness feeling
• Depression
• 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.