Regorafenib

What is Regorafenib?

• Regorafenib (Stivarga) is a kinase inhibitor used for the treatment of Metastatic colorectal cancer, metastatic gastrointestinal stromal tumor, Hepatocellular carcinoma.

Regorafenib

Regorafenib2DACS

What are the uses of this medicine?

This medicine is used to treat people with:

• colon or rectal cancer that has spread to other parts of the body and for which they have received previous treatment with certain chemotherapy medicines
• a rare stomach, bowel, or esophagus cancer called GIST (gastrointestinal stromal tumors) that cannot be treated with surgery or that has spread to other parts of the body and for which they have received previous treatment with certain medicines
• a type of liver cancer called hepatocellular carcinoma (HCC) in people who have been previously treated with sorafenib

How does this medicine work?

• Regorafenib (re goe raf’ e nib) is an orally available, small molecule, multi-specific kinase inhibitor with activity against vascular endothelial growth factors (VEGF) receptors -1, -2 and -3, as well as against the receptor for platelet derived growth factor (PDGF) and several RAF kinases, c-Kit and TIE2.
• Inhibition of these kinases decreases angiogenesis, which plays an important role in the growth and spread of several forms of solid tumors.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Avoid concomitant use of Stivarga with strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John’s Wort).
• Avoid concomitant use of Stivarga with strong CYP3A4 inhibitors (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole).
• Monitor patients closely for signs and symptoms of exposure related toxicity to the BCRP substrate (e.g. methotrexate, fluvastatin, atorvastatin).

Is this medicine FDA approved?

• FDA approved this drug in the year of 2013.

How should this medicine be used?

Recommended Dosage:

• The recommended dose is 160 mg Stivarga (four 40 mg tablets) taken orally once daily for the first 21 days of each 28-day cycle. Continue treatment until disease progression or unacceptable toxicity.

Administration

• Take Stivarga exactly as your healthcare provider tells you.
• You will usually take Stivarga 1 time a day for 21 days (3 weeks) and then stop for 7 days (1 week). This is 1 cycle of treatment. Repeat this cycle for as long as your healthcare provider tells you to.
• Swallow Stivarga tablets whole with water following a low-fat meal.
• Take Stivarga at the same time each day following a low-fat meal that contains less than 600 calories and less than 30% fat.
• If you miss a dose, take it as soon as you remember on that day. Do not take two doses on the same day to make up for a missed dose.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 40 mg

This medicine is available in fallowing brand namesː

• Stivarga

What side effects can this medication cause?

The most common side effects of this medicine include:

• pain, including stomach-area (abdomen)
• tiredness, weakness, fatigue
• frequent or loose bowel movements (diarrhea)
• decreased appetite
• infection
• voice changes or hoarseness
• increase in certain liver function test
• fever
• swelling, pain and redness of the lining in your mouth, throat, stomach and bowel (mucositis)
• weight loss

Stivarga can cause serious side effects including:

• Liver problems
• Infection
• severe bleeding
• a tear in your stomach or intestinal wall (bowel perforation)
• a skin problem called hand-foot skin reaction and severe skin rash
• high blood pressure
• decreased blood flow to the heart and heart attack
• a condition called Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
• risk of wound healing problems

What special precautions should I follow?

• Avoid drinking grapefruit juice and taking St. John’s Wort during treatment with Stivarga. These can affect the way Stivarga works.
• Severe drug-induced liver injury with fatal outcome occurred in Stivarga-treated patients in clinical trials. Monitor liver function tests. Withhold and then reduce or discontinue Stivarga based on severity and duration.
• Stivarga caused an increased risk of infections. Withhold Stivarga in patients with worsening or severe infections.
• Stivarga caused an increased incidence of hemorrhage. Permanently discontinue Stivarga for severe or life-threatening hemorrhage.
• In randomized, placebo-controlled trials, adverse skin reactions occurred. Withhold and then reduce or discontinue Stivarga depending on severity and persistence of dermatologic toxicity.
• Gastrointestinal perforation occurred patients treated with Stivarga. Discontinue Stivarga.
• Stivarga caused an increased incidence of hypertension. Temporarily or permanently withhold Stivarga for severe or uncontrolled hypertension.
• Stivarga increased the incidence of myocardial ischemia and infarction. Withhold Stivarga for new or acute cardiac ischemia/infarction and resume only after resolution of acute ischemic events.
• Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in one of 4800 Stivarga-treated patients. Discontinue Stivarga.
• Impaired wound healing complications can occur in patients who receive drugs that inhibit the VEGF signaling pathway. Withhold for at least 2 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of Stivarga after resolution of wound healing complications has not been established.
• Stivarga Can cause fetal harm. Advise women of potential risk to a fetus and to use effective contraception during treatment and for 2 months after the final dose. Advise males to use effective contraception for 2 months after the final dose.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• dermatological events
• dysphonia
• diarrhea
• mucosal inflammation
• dry mouth
• decreased appetite
• hypertension
• fatigue

Management of overdosage:

• There is no known antidote for Stivarga overdose. In the event of suspected overdose, interrupt Stivarga, institute supportive care, and observe until clinical stabilization.

Can this medicine be used in pregnancy?

• Based on animal studies and its mechanism of action, Stivarga can cause fetal harm when administered to a pregnant woman.
• There are no available data on Stivarga use in pregnant women.

Can this medicine be used in children?

• The safety and efficacy of Stivarga in pediatric patients less than 18 years of age have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: regorafenib
• Inactive ingredients: cellulose microcrystalline, croscarmellose sodium, magnesium stearate, povidone and colloidal silicon dioxide.

Film coat: ferric oxide red, ferric oxide yellow, lecithin (soy), polyethylene glycol 3350, polyvinyl alcohol, talc and titanium dioxide.

Who manufactures and distributes this medicine?

• Manufactured for Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ USA.

What should I know about storage and disposal of this medication?

• Store Stivarga tablets at room temperature between 68° F to 77° F (20° C to 25°C).
• Keep Stivarga in the bottle that it comes in. Do not put Stivarga tablets in a daily or weekly pill box.
• The Stivarga bottle contains a desiccant to help keep your medicine dry. Keep the desiccant in the bottle.
• Keep the bottle of Stivarga tightly closed.
• Safely throw away (discard) any unused Stivarga tablets after 7 weeks of opening the bottle.
• Keep Stivarga and all medicines out of the reach of children.

• Dailymed label info on Regorafenib
• FDA Regorafenib

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