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Axitinib

Medically reviewed by Drugs.com. Last updated on Jul 10, 2020.

Pronunciation

(ax I ti nib)

Index Terms

  • AG-013736

Dosage Forms

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

Tablet, Oral:

Inlyta: 1 mg, 5 mg

Brand Names: U.S.

  • Inlyta

Pharmacologic Category

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

Pharmacology

Axitinib is a selective second-generation tyrosine kinase inhibitor which blocks angiogenesis and tumor growth by inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3).

Absorption

Rapid (Rugo 2005)

Distribution

Vd: 160 L

Metabolism

Hepatic; primarily via CYP3A4/5 and to a lesser extend via CYP1A2, CYP2C19 and UGT1A1

Excretion

Feces (~41%; 12% as unchanged drug); urine (~23%; as metabolites)

Time to Peak

2.5 to 4 hours

Half-Life Elimination

2.5 to 6.1 hours

Protein Binding

>99%; to albumin (primarily) and to alpha1 acid glycoprotein (AAG)

Special Populations: Hepatic Function Impairment

Systemic exposure was higher in subjects with moderate impairment (Child-Pugh class B).

Use: Labeled Indications

Renal cell carcinoma, advanced:

First-line treatment (in combination with avelumab or pembrolizumab) of advanced renal cell carcinoma.

Treatment (as a single-agent) of advanced renal cell carcinoma after failure of 1 prior systemic therapy.

Off Label Uses

Thyroid cancer (differentiated, advanced)

Data from a multi-center phase II study in patients with advanced differentiated (papillary, follicular, or Hurthle) thyroid cancer supports the use of axitinib in the management of I131-refractory disease or in patients who could not receive I131 [Cohen 2014]. Data from another multi-center phase II study in advanced thyroid cancer also supports the use of axitinib in the management of I131-refractory disease [Locati 2014].

Contraindications

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

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

Dosing: Adult

Note: Axitinib dose increases may be considered if dose is tolerated (no adverse events above grade 2, BP is normal, and no antihypertensive use); temporary interruption and/or dose reduction may be required due to adverse reactions. Temporarily withhold axitinib at least 2 days prior to elective surgery; do not administer axitinib for at least 2 weeks following major surgery and until adequate wound healing.

Renal cell carcinoma, advanced, first-line combination therapy:

In combination with avelumab: Initial: 5 mg twice daily, every 12 hours; if tolerated for 2 weeks or longer, may increase to 7 mg twice daily and then 10 mg twice daily, or reduce to 3 mg twice daily and then 2 mg twice daily based on adverse events; continue until disease progression or unacceptable toxicity (Motzer 2019).

In combination with pembrolizumab: Initial: 5 mg twice daily, every 12 hours; after 6 weeks (or longer), if tolerated, may increase to 7 mg twice daily and then may further increase to 10 mg twice daily, or reduce to 3 mg twice daily and then 2 mg twice daily based on adverse events; continue until disease progression or unacceptable toxicity (Rini 2019).

Renal cell carcinoma, advanced, second-line single-agent therapy: Oral: Initial: 5 mg twice daily, approximately every 12 hours; if tolerated for at least 2 consecutive weeks, may increase to 7 mg twice daily and then 10 mg twice daily, or reduce to 3 mg twice daily and then 2 mg twice daily based on adverse events (Motzer 2013; Rini 2011).

Thyroid cancer, differentiated, advanced (off-label use): Oral: Initial: 5 mg twice daily on an empty stomach; increase or decrease dose in 20% increments based on response or toxicity; continue until disease progression or unacceptable toxicity (Cohen 2014) or Initial: 5 mg twice daily with food; if tolerated for 2 consecutive weeks, may increase to 7 mg twice daily, and then to 10 mg twice daily (unless receiving antihypertensive medication or BP >150/90 mm Hg); for grade 3 or higher toxicity, interrupt therapy and/or reduce dose to 3 mg twice daily, if further dose reduction necessary, reduce to 2 mg twice daily; continue until disease progression or unacceptable toxicity (Locati 2014).

Missed doses: If a dose is missed or vomited, do not make up; resume dosing with the next scheduled dose.

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

Dosing: Geriatric

Refer to adult dosing. No adjustment necessary.

Dosing: Adjustment for Toxicity

Adverse events: May require temporary interruption, axitinib dose decreases (reduce dose from 5 mg twice daily to 3 mg twice daily; further reduce to 2 mg twice daily) or axitinib discontinuation. Refer to avelumab and pembrolizumab monographs for information on toxicity management.

Cardiac events: Discontinue axitinib for grade 3 or 4 cardiovascular events.

Hypertension: Treat with standard antihypertensive therapy.

Persistent hypertension: May require axitinib dose reduction.

Severe, persistent (despite antihypertensives and dose reduction), or evidence of hypertensive crisis: Discontinue axitinib treatment.

Hemorrhage: Any bleeding requiring medical intervention: Temporarily interrupt axitinib treatment.

Proteinuria (moderate to severe): Reduce dose or temporarily interrupt axitinib treatment.

Reversible posterior leukoencephalopathy syndrome: Discontinue axitinib.

Extemporaneously Prepared

For patients unable to swallow tablets whole, a suspension may be prepared for nasogastric tube administration (for doses of 2 to 10 mg). Place a 20 mL tightly capped amber syringe in a small drinking glass, with the open end of the syringe pointing up. Place the appropriate axitinib dose in the open syringe barrel; add 15 mL of USP grade water (do not use tap water or bottled water) to the syringe. Allow at least 10 minutes to dissolve the tablets; avoid direct light. Place the plunger of the syringe into the barrel, invert the syringe so the tip is pointing upward and remove the cap. Expel excess air; replace the cap until ready for use (keep syringe tip facing up). Prior to administration, gently invert the syringe several times to ensure a uniform suspension. Flush the nasogastric feeding tube with 15 mL of USP grade water before administration. After administering the dose, draw up 10 mL of USP grade water (into the same syringe which contained the dose) and flush the feeding tube; repeat this step 5 additional times to ensure the entire dose has been administered. Lastly, flush the feeding tube with a separate syringe containing 15 mL of USP grade water. Administer within 15 minutes of preparation.

Borst DL, Arruda LS, MacLean E, Pithavala YK, Morgado JE. Common questions regarding clinical use of axitinib in advanced renal cell carcinoma. Am J Health Syst Pharm. 2014;71(13):1092-1096.

Administration

Oral: Swallow tablet(s) whole with a full glass of water. May administer with or without food. A suspension may be prepared for NG administration (refer to Extemporaneously Prepared information).

Dietary Considerations

Avoid grapefruit and grapefruit juice.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 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

Artesunate: Axitinib may increase serum concentrations of the active metabolite(s) of Artesunate. Monitor therapy

Avelumab: Axitinib may enhance the cardiotoxic effect of Avelumab. Axitinib may enhance the hepatotoxic effect of Avelumab. 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 Axitinib. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Axitinib. Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Axitinib. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. 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

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 Axitinib. 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

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

Pembrolizumab: Axitinib may enhance the hepatotoxic effect of Pembrolizumab. 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 Axitinib. 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 (40%)

Dermatologic: Palmar-plantar erythrodysesthesia (27%), skin rash (13%)

Endocrine & metabolic: Decreased serum bicarbonate (44%), hyperglycemia (28%), hyperkalemia (15%), hypernatremia (17%), hypoalbuminemia (15%), hypocalcemia (39%), hypoglycemia (11%), hyponatremia (13%), hypophosphatemia (13%), hypothyroidism (19%), weight loss (25%)

Gastrointestinal: Abdominal pain (14%), constipation (20%), decreased appetite (34%), diarrhea (55%), dysgeusia (11%), increased serum amylase (25%), increased serum lipase (3% to 27%), mucosal swelling (15%), nausea (32%), stomatitis (15%; grades 3/4: 1%), vomiting (24%)

Genitourinary: Proteinuria (11%)

Hematologic & oncologic: Decreased absolute lymphocyte count (33%; grades 3/4: 3%), decreased platelet count (15%; grades 3/4: <1%), decreased white blood cell count (11%), hemorrhage (16%; grades 3/4: 1%)

Hepatic: Increased serum alanine aminotransferase (22%), increased serum alkaline phosphatase (30%), increased serum aspartate aminotransferase (20%)

Nervous system: Fatigue (39%), headache (14%), voice disorder (31%)

Neuromuscular & skeletal: Arthralgia (15%), asthenia (21%), limb pain (13%)

Renal: Increased serum creatinine (55%)

Respiratory: Cough (15%), dyspnea (15%)

1% to 10%:

Cardiovascular: Arterial thrombosis (2%), cardiac failure (2%), deep vein thrombosis (1%), pulmonary embolism (2%), retinal thrombosis (≤1%), transient ischemic attacks (1%), venous thrombosis (3%)

Dermatologic: Alopecia (4%), erythema of skin (2%), pruritus (7%), xeroderma (10%)

Endocrine & metabolic: Dehydration (6%), hypercalcemia (6%), hyperthyroidism (1%)

Gastrointestinal: Dyspepsia (10%), gastrointestinal fistula (1%), gastrointestinal perforation (≤1%), glossalgia (3%), hemorrhoids (4%), upper abdominal pain (8%)

Genitourinary: Hematuria (3%)

Hematologic & oncologic: Anemia (4%), increased hemoglobin (9%), polycythemia (1%), rectal hemorrhage (2%)

Nervous system: Dizziness (9%)

Neuromuscular & skeletal: Myalgia (7%)

Ophthalmic: Retinal vein occlusion (≤1%)

Otic: Tinnitus (3%)

Respiratory: Epistaxis (6%), hemoptysis (2%)

<1%:

Cardiovascular: Cerebrovascular accident, hypertensive crisis

Nervous system: Reversible posterior leukoencephalopathy syndrome

Frequency not defined:

Cardiovascular: Acute myocardial infarction

Gastrointestinal: Gastrointestinal hemorrhage, melena

Nervous system: Cerebral hemorrhage

Ophthalmic: Retinal artery occlusion

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac events: Cardiac failure, including fatal events, has been observed rarely with axitinib monotherapy. Monitor for signs/symptoms of cardiac failure throughout therapy; management may require permanent axitinib discontinuation. Axitinib in combination with avelumab may result in severe and fatal cardiovascular events. Major adverse cardiovascular events (MACE) occurred more frequently in advanced renal cell carcinoma patients receiving the combination of axitinib plus avelumab versus those treated with sunitinib in a clinical trial. Events included grade 3 or 4 myocardial infarction, grade 3 or 4 heart failure, and death due to cardiac events. The median time to MACE onset was ~4 months (range: 2 days to 24.5 months). Monitor for signs and symptoms of cardiovascular events and optimize management of cardiovascular risk factors such as hypertension, diabetes, and dyslipidemia. Consider baseline and periodic left ventricular ejection fraction evaluations. Discontinue axitinib and avelumab for grade 3 or 4 cardiovascular events.

• GI events: GI perforation and fistulas (including a fatality) have been reported. Monitor for signs/symptoms throughout treatment.

• Hemorrhage: Hemorrhagic events (cerebral hemorrhage, GI hemorrhage, hematuria, hemoptysis, and melena) have been reported (with some fatalities). Temporarily interrupt treatment with any hemorrhage requiring medical intervention.

• Hepatotoxicity: AST and/or ALT elevations have occurred with single-agent axitinib or when used as a part of combination therapy (with avelumab or pembrolizumab), including grade 3 and 4 events. Higher than expected grade 3 and 4 transaminase elevations may occur when axitinib is used as part of combination therapy. The median time to onset of elevated ALT (in patients receiving combination therapy with pembrolizumab) was ~3 months (range: 7 days to ~20 months); close to 60% of these patients received systemic corticosteroids. In patients receiving combination therapy with avelumab or pembrolizumab who developed ALT ≥3 times ULN, ALT resolved to ≤ grade 1 in over 90% of patients. When rechallenged with axitinib either as monotherapy or combination therapy, over 50% of patients had no recurrence of ALT >3 times ULN. Monitor ALT, AST, and bilirubin prior to axitinib initiation and as clinically necessary during treatment; consider more frequent monitoring when axitinib is used as a part of combination therapy. Withhold axitinib and avelumab for grade 2 hepatotoxicity and permanently discontinue the combination for grade 3 or 4 toxicity. Withhold axitinib and pembrolizumab for elevated liver enzymes. Administer systemic corticosteroids as necessary for hepatotoxicity. Systemic exposure of axitinib is increased in patients with moderate impairment (Child-Pugh class B); dose reductions are recommended. Axitinib has not been studied in patients with severe impairment (Child-Pugh class C).

• Hypertension: May cause hypertension; the median onset is within the first month, and has been observed as early as 4 days after treatment initiation. Hypertensive crisis has been reported. BP should be well-controlled prior to treatment initiation. Monitor BP and treat with standard antihypertensive therapy. Persistent hypertension (despite antihypertensive therapy) may require dose reduction; discontinue if severe and persistent despite concomitant antihypertensives (or dose reduction), or with evidence of hypertensive crisis. Monitor for hypotension if on antihypertensive therapy and axitinib is withheld or discontinued.

• Proteinuria: Proteinuria is associated with axitinib use. Monitor for proteinuria at baseline and periodically throughout therapy. If moderate or severe proteinuria occurs, reduce dose or temporarily withhold treatment.

• Reversible posterior leukoencephalopathy syndrome: Cases of reversible posterior leukoencephalopathy syndrome (RPLS) have been reported. Symptoms of RPLS include confusion, headache, hypertension (mild to severe), lethargy, seizure, blindness, and/or other vision or neurologic disturbances. MRI is necessary to confirm RPLS diagnosis. Discontinue axitinib if RPLS is confirmed. The safety of reinitiating axitinib in patients previously experiencing RPLS is unknown.

• Thrombotic events: Arterial thrombotic events (cerebrovascular accident, MI, retinal artery occlusion, and transient ischemic attack), with fatalities, have been reported. Venous thrombotic events, including pulmonary embolism, deep vein thrombosis, retinal vein occlusion and retinal vein thrombosis, have been observed (with some fatalities). Use with caution in patients with a history of or risks for arterial or venous thrombotic events; axitinib has not been studied in patients within 12 months of an arterial thrombotic event or within 6 months of a venous thrombotic event.

• Thyroid dysfunction: Hypothyroidism occurs commonly with tyrosine kinase inhibitors, including axitinib. Hyperthyroidism has also been reported. Monitor thyroid function at baseline and periodically throughout therapy. Thyroid disorders should be treated according to standard practice to achieve/maintain euthyroid state.

• Wound healing complications: Vascular endothelial growth factor receptor inhibitors are associated with impaired wound healing; therefore, axitinib may affect wound healing. Withhold axitinib treatment for ≥2 days prior to elective surgery; do not administer axitinib for ≥2 weeks following major surgery and until adequate wound healing. The safety of resuming axitinib treatment after resolution of wound healing complications has not been established.

Disease-related concerns:

• Brain metastases: Axitinib has not been studied in patients with evidence of untreated brain metastases; use is not recommended.

• GI bleeding: Axitinib has not been studied in patients with recent active GI bleeding; use is not recommended.

Monitoring Parameters

Hepatic function (ALT, AST, and bilirubin; baseline and periodic), thyroid function (baseline and periodic), urinalysis (for proteinuria; baseline and periodically); consider baseline and periodic evaluations of left ventricular ejection fraction; BP; evaluate pregnancy status prior to therapy (in females of reproductive potential). Monitor for signs/symptoms of RPLS, GI bleeding/perforation/fistula, signs/symptoms of major adverse cardiovascular events (MACE). Monitor adherence.

Thyroid function testing recommendations (Hamnvik 2011):

Preexisting levothyroxine therapy: Obtain baseline TSH levels, then monitor every 4 weeks until levels and levothyroxine dose are stable, then monitor every 2 months.

Without preexisting thyroid hormone replacement: TSH at baseline, then monthly for 4 months, then every 2 to 3 months.

Reproductive Considerations

Females of reproductive potential should have a pregnancy test prior to therapy; effective contraception should be used during axitinib therapy and for 1 week after the final axitinib dose.

Males with female partners of reproductive potential should also use effective contraception during axitinib therapy and for 1 week after the final axitinib dose.

Pregnancy Considerations

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

Patient Education

What is this drug used for?

• It is used to treat kidney cancer.

• It may be given to you for other reasons. Talk with the doctor.

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:

• Stomach pain

• Heartburn

• Change in taste

• Feeling tired or weak

• Painful extremities

• Diarrhea

• Upset stomach

• Throwing up

• Weight loss

• Not hungry

• Mouth irritation

• Mouth sores

• Muscle pain

• Constipation

• Joint pain

• Cough

• 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:

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

• Bleeding like throwing up blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• High blood sugar like confusion, feeling tired, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Low blood sugar like dizziness, headache, feeling tired, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating

• Liver problems like dark urine, feeling tired, not hungry, upset stomach, stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Thyroid problems like change in weight without trying, anxiety, agitation, feeling very weak, hair thinning, depression, neck swelling, trouble focusing, inability handling heat or cold, menstrual changes, tremors, or sweating

• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, fast heartbeat, increased thirst, seizures, loss of strength and energy, not hungry, unable to pass urine or change in amount of urine passed, dry mouth, dry eyes, or upset stomach or throwing up

• 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

• 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 headache

• Severe dizziness

• Passing out

• Vision changes

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

• Redness or irritation of the palms or soles of feet

• Sore throat

• Chills

• Change in voice

• 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.