Cabozantinib

Dosage Forms

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

Kit, Oral:

Cometriq (100 MG Daily Dose): Capsules: 100 mg daily-dose: 80 mg (7s) and 20 mg (7s)

Cometriq (140 MG Daily Dose): Capsules: 140 mg daily-dose: 80 mg (7s) and 20 mg (21s)

Cometriq (60 MG Daily Dose): Capsules: 60 mg daily-dose: 20 mg (21s)

Tablet, Oral:

Cabometyx: 20 mg, 40 mg, 60 mg

Pharmacology

Mechanism of Action

Cabozantinib is a potent inhibitor of proinvasive receptor tyrosine kinases (RTKs), including AXL, FLT-3, KIT, MER, MET, RET, ROS1, TIE-2, TRKB, TYRO3, and VEGFR-1, -2, and -3; induces apoptosis of cancer cells and suppresses tumor growth, metastasis, and angiogenesis (Yakes 2011).

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: ~349 L (Cometriq); ~319 L (Cabometyx)

Metabolism

Hepatic via CYP3A4

Excretion

Feces (~54%; 43% as unchanged drug); urine (~27%)

Time to Peak

2 to 5 hours (Cometriq); 3 to 4 hours (Cabometyx)

Half-Life Elimination

~55 hours (Cometriq); ~99 hours (Cabometyx)

Protein Binding

≥99.7% to plasma proteins

Use in Specific Populations

Special Populations: Hepatic Function Impairment

Cabozantinib exposure was increased by 63% in patients with moderate hepatic impairment compared to patients with normal liver function.

Use: Labeled Indications

Hepatocellular carcinoma, advanced (Cabometyx): Treatment of hepatocellular carcinoma (HCC) in patients who have previously been treated with sorafenib

Renal cell carcinoma, advanced (Cabometyx): Treatment of advanced renal cell carcinoma (RCC)

Thyroid cancer, medullary (Cometriq): Treatment of progressive, metastatic medullary thyroid cancer (MTC)

Contraindications

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

Canadian labeling: Hypersensitivity to cabozantinib or any component of the formulation.

Dosage and Administration

Dosing: Adult

Note: Do not substitute cabozantinib tablets and capsules. Cabozantinib is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea/vomiting (Hesketh 2017).

Hepatocellular carcinoma, advanced: Cabometyx: Oral: 60 mg once daily until disease progression or unacceptable toxicity (Abou-Alfa 2018); do not exceed 80 mg daily

Renal cell carcinoma, advanced: Cabometyx: Oral: 60 mg once daily, continue as long as benefiting clinically or until unacceptable toxicity (Choueiri 2015; Choueiri 2017); do not exceed 80 mg daily

Thyroid cancer, medullary, metastatic: Cometriq: Oral: 140 mg once daily until disease progression or unacceptable toxicity (Schlumberger 2017); do not exceed 180 mg daily

Missed doses: Do not take a missed dose within 12 hours of the next dose.

Dosage adjustment for concomitant CYP3A4 inhibitors/inducers:

Strong CYP3A4 inhibitors:

Cabometyx: Reduce the daily dose of cabozantinib by 20 mg (from 60 mg to 40 mg daily or from 40 mg to 20 mg daily). If the strong inhibitor is discontinued, allow ~2 to 3 days to elapse prior to adjusting the cabozantinib dose upwards to the dose used prior to the initiation of the strong inhibitor.

Cometriq: Avoid concomitant use; if concomitant use is required, reduce the daily dose of cabozantinib by 40 mg (ie, from 140 mg to 100 mg daily or from 100 mg to 60 mg daily). If the strong inhibitor is discontinued, allow ~2 to 3 days to elapse prior to adjusting the cabozantinib dose upwards to the dose used prior to the initiation of the strong inhibitor.

Strong CYP3A4 inducers:

Cabometyx: Increase the daily dose of cabozantinib by 20 mg (from 60 mg to 80 mg daily or from 40 mg to 60 mg daily) as tolerated; do not exceed 80 mg/day. If the strong inducer is discontinued, allow ~2 to 3 days to elapse prior to reducing the cabozantinib dose to the dose used prior to the initiation of the strong inducer.

Cometriq: Avoid concomitant use; if concomitant use is required, increase the daily dose of cabozantinib by 40 mg (ie, from 140 mg to 180 mg daily or from 100 mg to 140 mg daily); do not exceed 180 mg/day. If the strong inducer is discontinued, allow ~2 to 3 days to elapse prior to reducing the cabozantinib dose to the dose used prior to the initiation of the strong inducer.

Dosage adjustment for surgery: Withhold treatment for at least 28 days prior to scheduled surgery (including dental surgery). Resume therapy based on clinical judgment of adequate wound healing.

Dosing: Adjustment for Toxicity

Cabometyx:

Grade 3 or 4 adverse reactions or intolerable grade 2 adverse reactions: Withhold therapy. Upon return to baseline or improvement to grade 1, resume therapy with a reduction in dose. If previously receiving 60 mg daily, resume therapy at 40 mg daily. If previously receiving 40 mg daily, resume therapy at 20 mg daily. If previously receiving 20 mg daily, resume at 20 mg daily if tolerated; if not tolerated, discontinue therapy.

Diarrhea (intolerable grade 2, grade 3 that cannot be managed with standard antidiarrheal therapy, or grade 4): Withhold therapy. Upon improvement to grade 1, resume at a reduced dose.

Hypertension (inadequately controlled with medical management): Withhold therapy. When controlled, resume at a reduced dose.

Osteonecrosis of the jaw: Withhold therapy until complete resolution.

Palmar-plantar erythrodysesthesia (Grade 3 or intolerable grade 2): Withhold therapy. Upon improvement to grade 1, resume at a reduced dose.

Permanently discontinue for:

Development of gastrointestinal perforation or unmanageable fistula

Hypertensive crisis or severe uncontrolled hypertension despite optimal therapy

Nephrotic syndrome

Reversible posterior leukoencephalopathy syndrome (RPLS)

Serious thromboembolic event (eg, MI or cerebral infarction)

Severe hemorrhage

Cometriq:

Hematologic: Withhold therapy for grade 4 hematologic adverse reactions. Upon return to baseline or improvement to grade 1, reduce the dose to 100 mg daily. If previously receiving 100 mg daily, resume therapy at 60 mg daily. If previously receiving 60 mg daily, resume at 60 mg daily if tolerated; otherwise, discontinue therapy.

Other toxicity: Withhold therapy for grade 3 or higher nonhematologic toxicity or intolerable grade 2 toxicity. Upon return to baseline or improvement to grade 1, reduce the dose to 100 mg daily. If previously receiving 100 mg daily, resume therapy at 60 mg daily. If previously receiving 60 mg daily, resume at 60 mg daily if tolerated; otherwise, discontinue therapy.

Hypertension (inadequately controlled with medical management): Withhold therapy. When controlled, resume at a reduced dose.

Palmar-plantar erythrodysesthesia (Grade 3 or intolerable grade 2): Withhold therapy. Upon improvement to grade 1, resume at a reduced dose.

Permanently discontinue for:

Malignant hypertension, hypertensive crisis, persistent uncontrolled hypertension despite optimal therapy

Nephrotic syndrome

Osteonecrosis of the jaw

Reversible posterior leukoencephalopathy syndrome (RPLS)

Serious arterial thromboembolic event (eg, MI or cerebral infarction)

Severe hemorrhage

Visceral perforation or fistula formation

Administration

Oral: Administer on an empty stomach (1 hour before or 2 hours after eating). Note: The prescribing information (for Cometriq) describes when to give food with respect to cabozantinib; no food should be consumed for at least 2 hours before or for at least 1 hour after the cabozantinib dose. Swallow whole; do not open capsules or crush tablets.

Cabozantinib is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea/vomiting (Hesketh 2017).

Dietary Considerations

Avoid grapefruit and grapefruit juice throughout therapy.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F).

Drug Interactions

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Bisphosphonate Derivatives: Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. 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

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

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

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Grapefruit Juice: May increase the serum concentration of Cabozantinib. 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

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

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

MRP2 Inhibitors: May increase the serum concentration of Cabozantinib. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Rifabutin: May decrease the serum concentration of Cabozantinib. Monitor therapy

Rifapentine: May decrease the serum concentration of Cabozantinib. Monitor therapy

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

St John's Wort: May decrease the serum concentration of Cabozantinib. Avoid combination

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Hypertension (30% to 61%)

Central nervous system: Fatigue (41% to 56%), mouth pain (36%), voice disorder (19%), headache (11% to 18%), dizziness (11% to 14%)

Dermatologic: Palmar-plantar erythrodysesthesia (42% to 50%), hair discoloration (34%), skin rash (19% to 23%), xeroderma (11% to 19%), alopecia (16%), erythema (11%)

Endocrine & metabolic: Increased lactate dehydrogenase (84%), increased serum triglycerides (53%), hypocalcemia (8% to 52%), hypoalbuminemia (36% to 51%), hypophosphatemia (25% to 48%), weight loss (17% to 48%), hyperglycemia (37%), hypomagnesemia (19% to 31%), hyponatremia (10% to 30%), increased gamma-glutamyl transferase (27%), hypokalemia (18% to 23%), hypothyroidism (8% to 21%)

Gastrointestinal: Diarrhea (54% to 74%), stomatitis (13% to 51%; grades 3/4: 2% to 5%), nausea (31% to 50%), decreased appetite (46% to 48%), dysgeusia (12% to 34%), vomiting (24% to 32%), constipation (25% to 27%), abdominal pain (23% to 27%), mucositis (14% to 19%), increased serum amylase (16%), dysphagia (13%), dyspepsia (10% to 12%)

Genitourinary: Proteinuria (2% to 12%)

Hematologic & oncologic: Lymphocytopenia (25% to 53%; grades 3/4: 1% to 16%), neutropenia (31% to 43%; 35%; grades 3/4: 2% to 7%), leukopenia (35%), thrombocytopenia (25% to 35%; grades 3/4: 1%), anemia (17% to 31%; grades 3/4: 1% to 5%)

Hepatic: Increased serum aspartate aminotransferase (73% to 86%), increased serum alanine aminotransferase (68% to 86%), increased serum alkaline phosphatase (35% to 52%), hyperbilirubinemia (25%)

Neuromuscular & skeletal: Asthenia (19% to 22%), arthralgia (11% to 14%), limb pain (9% to 14%), muscle spasm (8% to 13%)

Renal: Increased serum creatinine (58%)

Respiratory: Dyspnea (12% to 19%), cough (18%)

1% to 10%:

Cardiovascular: Hypotension (7%), venous thromboembolism (6% to 7%), syncope (grades 3/4: 5%), pulmonary embolism (4%), arterial thromboembolism (1% to 2%), vascular disease (grades 3/4: 1%)

Central nervous system: Anxiety (9%), paresthesia (7%), peripheral sensory neuropathy (7%), pain (grades 3/4: 5%), peripheral neuropathy (5%), depression (grades 3/4: 4%), confusion (grades 3/4: 1%)

Dermatologic: Hyperkeratosis (7%), dermal ulcer (grades 3/4: 3%)

Endocrine & metabolic: Dehydration (7%), hyperkalemia (grades 3/4: 1%)

Gastrointestinal: Hemorrhoids (9%), gastrointestinal hemorrhage (3%), gastrointestinal perforation (1% to 3%), gastrointestinal fistula (1%)

Hematologic & oncologic: Increased hemoglobin (8%), hemorrhage (grade ≥3: 5%)

Neuromuscular & skeletal: Musculoskeletal chest pain (9%), back pain (grades 3/4: 4%), ostealgia (grades 3/4: 3%), osteonecrosis of the jaw (≤1%)

Renal: Acute renal failure (grades 3/4: 4%)

Respiratory: Pulmonary infection (grades 3/4: 4%)

Miscellaneous: Fistula (nongastrointestinal: 4%; includes tracheal/esophageal), wound healing impairment (≤2%)

<1%, postmarketing, and/or case reports: Cholestatic hepatitis, hypertensive crisis, nephrotic syndrome, pancreatitis, reversible posterior leukoencephalopathy syndrome, seizure

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic toxicity: Palmar-plantar erythrodysesthesia syndrome (PPES) was commonly observed in clinical trials; severe PPES (≥ grade 3) also occurred. May require treatment interruption, dosage reduction, and/or discontinuation.
• GI toxicity: Diarrhea was commonly observed in cabozantinib-treated patients in clinical trials. May require therapy interruption and/or dosage reduction. Cabozantinib is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea/vomiting (Hesketh 2017). [US Boxed Warning]: Cometriq: Serious GI perforations and fistulas have been reported when used for medullary thyroid cancer; discontinue for GI perforation or fistula formation. May be fatal. Tracheal/esophageal fistulas were also noted; some cases were fatal. GI fistula/perforation (including fatal perforations) were also reported in patients treated with cabozantinib. Monitor for signs/symptoms of perforations and fistulas, including abscess and sepsis. May require therapy discontinuation.
• Hemorrhage: [US Boxed Warning]: Cometriq: Serious and occasionally fatal hemorrhage (including hemoptysis and gastrointestinal) has occurred with cabozantinib when used for medullary thyroid cancer. Monitor for signs/symptoms of bleeding and do not administer to patients with severe hemorrhage or a recent history of hemorrhage or hemoptysis. Severe hemorrhage has also been reported in patients with renal cell cancer and hepatocellular carcinoma, including grade 3 or higher events. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena. Discontinue for grade 3 or 4 hemorrhagic events.
• Hypertension: Treatment emergent hypertension was commonly seen in clinical trials (including grade 3 or higher toxicity and hypertensive crisis). Do not initiate cabozantinib in patients with uncontrolled hypertension. Monitor blood pressure prior to therapy initiation and regularly thereafter; withhold for hypertension that is uncontrolled with appropriate medical management. May require cabozantinib dosage reduction and/or therapy discontinuation.
• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ) occurred rarely; manifestations may include jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain or slow healing of the mouth or jaw after dental surgery. Oral examinations should be performed prior to and periodically throughout therapy. Patients should maintain proper oral hygiene practices. If possible, withhold therapy for at least 28 days prior to scheduled invasive dental procedures. Withhold cabozantinib until complete resolution if ONJ develops.
• Proteinuria: Proteinuria occurred in patients receiving cabozantinib in clinical trials; nephrotic syndrome was also reported (rare). Monitor urine protein regularly and discontinue therapy if nephrotic syndrome develops.
• Reversible posterior leukoencephalopathy syndrome: Reversible posterior leukoencephalopathy syndrome (RPLS) has occurred with cabozantinib. Monitor for signs/symptoms of RPLS (seizures, headache, visual disturbances, confusion or altered mental function); if diagnosis confirmed, discontinue therapy.
• Thromboembolic events: An increased incidence of thrombotic events (venous thromboembolism, including pulmonary embolism and arterial thromboembolism), including fatal events, was seen in cabozantinib-treated patients in clinical trials; discontinue therapy in patients who develop an acute myocardial infarction, cerebral infarction, or other clinically significant arterial or venous thromboembolic event that requires medical intervention.
• Wound healing impairment: Cabozantinib inhibits vascular endothelial growth factor receptors 1, 2, and 3; wound complications have been reported with therapy. Hold treatment at least 28 days prior to scheduled surgery (including dental surgery); resume based on judgment of adequate wound healing post surgery. Withhold treatment in patients with dehiscence or other wound healing complications requiring intervention.

Disease-related concerns:

• Hepatic impairment: Cabozantinib exposure is increased in patients with hepatic impairment. Reduced initial doses are recommended for patients with mild or moderate impairment (product dependent); use is not recommended in patients with severe 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.

Dosage form specific issues:

• Formulations: Cabozantinib is available in tablets (Cabometyx) and capsules (Cometriq) which are NOT interchangeable; do NOT substitute.

Monitoring Parameters

Renal function, liver function, CBC with differential and platelets, serum electrolytes; pregnancy test (prior to treatment in females of reproductive potential); blood pressure (prior to initiation and regularly during therapy); monitor for perforations, fistulas, signs/symptoms of bleeding, palmar-plantar erythrodysesthesia syndrome (PPES), reversible posterior leukoencephalopathy syndrome (RPLS), proteinuria (regularly during therapy), osteonecrosis of the jaw (perform oral examination prior to initiation and periodically during therapy), wound healing complications, diarrhea, stomatitis. Monitor adherence.

Pregnancy

Pregnancy Considerations

Based on its mechanism of action and data from animal reproduction studies, adverse effects on pregnancy may be expected.

Evaluate pregnancy status in females of reproductive potential prior to initiating therapy. Females of reproductive potential should use effective contraception during therapy and for 4 months after the last cabozantinib dose.

Patient Education

What is this drug used for?

• It is used to treat cancer.

Frequently reported side effects of this drug

• Hair loss
• Weight loss
• Change in taste
• Constipation
• Lack of appetite
• Hair loss
• Hair discoloration
• Joint pain
• Muscle spasms
• Anxiety
• Altered voice
• Dry skin

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 bleeding or persistent bleeding.
• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting.
• Low thyroid level like constipation; difficulty handling heat or cold; memory problems; mood changes; or burning, numbness, or tingling feeling.
• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood.
• Posterior reversible encephalopathy syndrome like confusion, not alert, vision changes, seizures, or severe headache.
• Sweating a lot
• Abnormal gait
• Severe headache
• Severe dizziness
• Passing out
• Vision changes
• Cough
• Gagging
• Choking
• Severe loss of strength and energy healing impairment
• Jaw pain
• Severe mouth irritation
• Mouth sores
• Unable to pass urine
• Change in amount of urine passed
• Redness or irritation of hands or soles of feet
• Swelling in the arms or legs
• Burning or numbness feeling
• 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.