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Cabozantinib

Medically reviewed by Drugs.com. Last updated on Apr 30, 2020.

Pronunciation

(ka boe ZAN ti nib)

Index Terms

  • BMS-907351
  • Cabozantinib (S)-malate
  • Cabozantinib s-Malate
  • Cabozantinib-s-malate
  • XL184

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

Brand Names: U.S.

  • Cabometyx
  • Cometriq (100 MG Daily Dose)
  • Cometriq (140 MG Daily Dose)
  • Cometriq (60 MG Daily Dose)

Pharmacologic Category

  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
  • Antineoplastic Agent, Vascular Endothelial Growth Factor (VEGF) Inhibitor

Pharmacology

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).

Distribution

Vd: ~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

Special Populations: Hepatic Function Impairment

Cabozantinib exposure was increased by 81% in subjects with mild impairment (Child-Pugh class A) and by 63% in subjects with moderate impairment (Child-Pugh class B), compared to subjects 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.

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 therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for surgery: Withhold cabozantinib treatment for at least 3 weeks prior to scheduled surgery (including dental surgery). Do not administer cabozantinib for at least 2 weeks after major surgery and until adequate wound healing.

Dosing: Adjustment for Toxicity

Cabometyx:

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

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 once daily. If previously receiving 100 mg daily, resume therapy at 60 mg once daily. If previously receiving 60 mg daily, resume at 60 mg once daily if tolerated; otherwise, discontinue therapy.

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

Cabometyx and Cometriq:

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.

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

Permanently discontinue for:

Gastrointestinal perforation or grade 4 fistula formation

Hemorrhage (severe)

Hypertension (severe, that cannot be controlled with antihypertensive therapy) or hypertensive crisis

Nephrotic syndrome

Reversible posterior leukoencephalopathy syndrome

Thromboembolic events (acute MI or arterial or venous thromboembolic events that require medical intervention)

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. Do not substitute cabozantinib tablets and capsules.

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

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

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

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 Cabozantinib. 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, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Cabozantinib. 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, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. 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

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

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. 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%)

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

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

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

Genitourinary: Proteinuria (2% to 12%)

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

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

Nervous system: Dizziness (11% to 14%), fatigue (41% to 56%), headache (11% to 18%), mouth pain (36%), voice disorder (19% to 20%)

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

Renal: Increased serum creatinine (58%)

Respiratory: Cough (18%), dyspnea (12% to 19%)

1% to 10%:

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

Dermatologic: Dermal ulcer (grades 3/4: 3%), hyperkeratosis (7%)

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

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

Hematologic & oncologic: Hemorrhage (grade ≥3: 3% to 5%), increased hemoglobin (8%)

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

Neuromuscular & skeletal: Back pain (grades 3/4: 4%), musculoskeletal chest pain (9%), 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 tracheoesophageal fistula), wound healing impairment (2%)

<1%:

Gastrointestinal: Pancreatitis

Genitourinary: Nephrotic syndrome

Hepatic: Cholestatic hepatitis

Nervous system: Reversible posterior leukoencephalopathy syndrome, seizure

Frequency not defined: Cardiovascular: Hypertensive crisis

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic toxicity: Palmar-plantar erythrodysesthesia syndrome occurred in one-half of patients; grade 3 events were reported. May require treatment interruption, dosage reduction, and/or discontinuation.

• GI toxicity: Diarrhea has been commonly observed in cabozantinib-treated patients; grade 3 and 4 diarrhea has occurred. Withhold cabozantinib for grade 4 diarrhea, grade 3 diarrhea that cannot be managed with standard antidiarrheal therapy, or for intolerable grade 2 diarrhea; may resume at a reduced dose upon improvement to grade 1. Cabozantinib is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea/vomiting (Hesketh 2017). GI perforations and fistulas (including fatal cases) have been reported with cabozantinib. Tracheal/esophageal fistulas were also noted; some cases were fatal. Monitor for signs/symptoms of perforations and fistulas, including abscess and sepsis. Discontinue for GI perforation or grade 4 fistula formation.

• Hemorrhage: Severe and fatal hemorrhages have occurred with cabozantinib, including grade 3 or higher events. Discontinue cabozantinib for grade 3 or 4 hemorrhage. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

• Hypertension: Cabozantinib may increase the risk of treatment-emergent hypertension. Stage 1 and 2 hypertension were commonly seen in cabozantinib-treated patients; grade 3 and 4 hypertension has been reported. Do not initiate cabozantinib in patients with uncontrolled hypertension. Monitor blood pressure regularly; withhold cabozantinib for hypertension that is uncontrolled despite appropriate medical management. When blood pressure is controlled, resume cabozantinib at a reduced dose. Discontinue cabozantinib for severe hypertension (that cannot be controlled with antihypertensive therapy) or hypertensive crisis.

• 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 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold cabozantinib until complete resolution if ONJ develops.

• Proteinuria: Proteinuria occurred in some patients receiving cabozantinib; 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), a syndrome of subcortical vasogenic edema (based on MRI findings), may occur with cabozantinib. Evaluate for RPLS in patients who present with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue cabozantinib in patients who develop RPLS.

• Thromboembolic events: Cabozantinib is associated with an increased risk of thrombotic events. Venous thromboembolism (including pulmonary embolism) and arterial thromboembolism have been observed in cabozantinib-treated patients. Fatal thromboembolic events have occurred. Discontinue cabozantinib in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

• Wound healing impairment: Cabozantinib inhibits vascular endothelial growth factor receptors 1, 2, and 3; wound healing complications have been reported with therapy. Withhold cabozantinib for at least 3 weeks prior to elective surgery (including dental surgery). Do not administer cabozantinib for at least 2 weeks after major surgery and until after adequate wound healing. The safety of resuming cabozantinib after resolution of wound healing complications has not been established.

Disease-related concerns:

• Hepatic impairment: Cabozantinib exposure is increased in patients with mild to moderate 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.

Dosage form specific issues:

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

Monitoring Parameters

Monitor renal function, liver function, CBC with differential and platelets, serum electrolytes; pregnancy test (prior to treatment in females of reproductive potential); blood pressure (regularly during therapy); monitor for GI perforations, fistulas, signs/symptoms of bleeding/hemorrhage, 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.

Reproductive Considerations

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.

Pregnancy Considerations

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

Patient Education

What is this drug used for?

• It is used to treat cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Loss of strength and energy

• Abdominal pain

• Hair loss

• Mouth irritation

• Weight loss

• Diarrhea

• Nausea

• Vomiting

• Change in taste

• Constipation

• Lack of appetite

• Skin changes to hard and thick

• Hair discoloration

• Joint pain

• Muscle spasms

• Anxiety

• Change in voice

• Dry skin

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• 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

• Low thyroid level like constipation; trouble 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

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Posterior reversible encephalopathy syndrome like confusion, not alert, vision changes, seizures, or severe headache

• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, tachycardia, increased thirst, seizures, loss of strength and energy, lack of appetite, unable to pass urine or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting

• Sweating a lot

• Abnormal gait

• Severe headache

• Severe dizziness

• Passing out

• Vision changes

• Shortness of breath

• Cough

• Gagging

• Choking

• Skin wound healing impairment

• Jaw pain

• Mouth sores

• Redness or irritation of hands or soles of feet

• Swelling in the arms or legs

• Burning or numbness feeling

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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