Stivarga – Regorafenib uses, dose and side effects

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40 mg film-coated tablets
regorafenib

What Stivarga is and what it is used for

Stivarga contains the active substance regorafenib. It is a drug used to treat cancer by inhibiting the growth and spread of cancer cells and cutting off the blood supply that causes the cancer cells to grow.

Stivarga is used for the treatment of:

  • colon or rectal cancer that has spread to other parts of the body in adult patients who have received other treatment or cannot be treated with other medicines (fluoropyrimidine-based chemotherapy, a VEGF inhibitor treatment, or an anti-EGFR treatment)
  • gastrointestinal stromal cell tumors ( GIST ), a type of cancer of the stomach and intestine, which has spread to other parts of the body or cannot be treated surgically, in adult patients who have previously been treated with other cancer medicines (imatinib and sunitinib)
  • liver cancer in adult patients who have previously been treated with another cancer medicine (sorafenib).

If you have any questions about how Stivarga works or why you have been prescribed this medicine, talk to your doctor.

What you need to know before taking Stivarga

Do not take Stivarga

– if you are allergic to regorafenib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking Stivarga.

Be especially careful with Stivarga

  • if you have liver problems, e.g. Gilbert’s syndrome, with signs such as yellowish discoloration of the skin and whites of the eyes, dark-colored urine, and confusion and/or disorientation. Treatment with Stivarga may lead to a greater risk of liver problems. Before and during treatment with Stivarga, the doctor takes blood samples to check liver function. If you have a severe hepatic impairment, you should not be treated with Stivarga as there are no data on the use of Stivarga in patients with severe hepatic impairment
  • if you get an infection with symptoms such as high fever, severe cough with or without increased mucus production, very sore throat, shortness of breath, burning sensation/pain when urinating, abnormal vaginal discharge or irritation, redness, swelling and/or pain in any part of the body, your doctor may temporarily pause the treatment.
  • if you have or have had bleeding problems and if you are taking warfarin, phenprocoumon, or another medicine that thins the blood to prevent blood clots. Treatment with Stivarga may lead to a greater risk of bleeding. Before you start taking Stivarga, your doctor may decide to take blood tests. Stivarga can cause severe bleeding in the digestive system, such as the stomach, throat, rectum, large intestine, or small intestine, or in the lungs, kidneys, mouth, vagina, and/or brain. See a doctor immediately if you experience any of the following symptoms: blood in the stool or black stool, blood in the urine, stomach pain, coughing up blood, or vomiting blood
  • if you get severe stomach or intestinal problems ( gastrointestinal perforation or fistula ), your doctor must decide to stop treatment with Stivarga. Seek medical help immediately if you experience the following symptoms: severe stomach pain or stomach pain that does not go away, vomiting blood, red or black stools
  • if you get chest pain or have heart problems. Before you start taking Stivarga and during treatment, your doctor will check how well your heart is working. See a doctor immediately if you experience the following symptoms as they may be a sign of a heart attack or reduced blood flow to the heart: discomfort or pain in the chest that may radiate to the shoulders, arms, back, neck, teeth, jaw or stomach and may come and walking, shortness of breath, sudden sweating with cold, clammy skin, dizziness or fainting
  • if you develop a severe or persistent headache, visual disturbances, seizure or altered mental status (such as confusion, loss of memory or disorientation), contact your doctor immediately
  • if you have high blood pressure. Stivarga can increase blood pressure et and the doctor will check your blood pressure before and during treatment and may give you a medicine to treat high blood pressure
  • if you have or have had an aneurysm (enlargement and weakening of the vessel wall) or a rupture in a vessel wall.
  • if you have recently undergone or are about to undergo an operation. Stivarga can affect wound healing and treatment may need to be interrupted until the wound is healed
  • if you get skin problems. Stivarga can cause redness, pain, swelling, or blistering on the palms of the hands or soles of the feet. If you notice any changes, contact your doctor. The doctor may recommend that you use creams and/or insoles and gloves to treat the symptoms. If you experience this side effect, the doctor may change the dose or stop the treatment until the condition improves.

Before taking Stivarga, tell the doctor if any of the above apply to you. You may need treatment and more tests may need to be done (see also section 4 “Possible side effects”).

Children and young people

There is no relevant use of Stivarga for children and adolescents for colorectal indication cancer with spread to other parts of the body.

Safety and efficacy in children and adolescents for the indication of gastrointestinal stromal cell tumors ( GIST ) have not been established. No data is available.

There is no relevant use of Stivarga for children and adolescents for the indication of liver cancer.

Other medicines and Stivarga

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This also applies to over-the-counter medicines and products such as vitamins, dietary supplements, and herbal preparations. Some medicines can affect the effect of Stivarga or Stivarga can affect how other medicines work and lead to serious side effects. In particular, you should tell the doctor if you are taking anything from the list below or any other medicine:

Ask your doctor or pharmacist for advice before taking any medicine.

Taking Stivarga with food and drink

Avoid drinking grapefruit juice while being treated with Stivarga. It can affect the mechanism of action of Stivarga.

Pregnancy, breastfeeding, and fertility

Tell your doctor if you think you are pregnant, may be pregnant, or plan to become pregnant as Stivarga should not be used during pregnancy unless necessary. The doctor will discuss the possible risks of taking Stivarga during pregnancy with you.

Avoid becoming pregnant while being treated with Stivarga as this medicine may harm the fetus.

Both fertile women and men must use an effective contraceptive method during treatment and at least eight weeks after the end of treatment.

You must not breastfeed your child while you are being treated with Stivarga because this medicine can affect the child’s growth and development. Tell the doctor if you are breastfeeding or plan to breastfeed.

Stivarga can reduce fertility in both men and women. Consult a doctor before taking Stivarga.

Driving ability and use of machinery

It is not known whether Stivarga affects the ability to drive and use machines. Do not drive or operate machinery if you experience any treatment-related symptoms that affect your ability to concentrate and react.

Important information about some ingredients in Stivarga

This medicine contains 56.06 mg of sodium (the main ingredient in common/table salt) per daily dose (4 tablets). This corresponds to 3% of the maximum recommended daily intake of sodium for adults.

This medicine contains 1.68 mg of lecithin (produced from soy) per daily dose

(4 tablets).

How to take Stivarga

Always take Stivarga as directed by your doctor. Ask your doctor or pharmacist if you are unsure.

The recommended daily dose for adults is 4 tablets of Stivarga á 40 mg (160 mg regorafenib). The doctor can change the dose. Take that dose of Stivarga prescribed by the doctor.

The doctor usually asks you to take Stivarga for 3 weeks and then take a break for 1 week. This corresponds to one treatment cycle.

Take Stivarga at the same time every day after a light (low-fat) meal. Swallow the tablet whole with water after a light meal containing less than 30% fat. An example of a light (low-fat) meal is 1 portion of cereal (about 30 g), 1 glass of low-fat milk, 1 slice of toast with marmalade, 1 glass of apple juice, and 1 cup of coffee or tea (520 calories, 2 g of fat). You should not take Stivarga together with grapefruit juice (see also the section “Taking Stivarga with food and drink”).

If you vomit after taking regorafenib, you should not take any extra tablets and you should inform the doctor.

The doctor may need to reduce the dose or decide that you must interrupt or stop the treatment permanently if necessary. You should normally take Stivarga as long as you benefit from the treatment and do not suffer from unacceptable side effects.

No dose adjustment is necessary if you have mildly impaired liver function. If you have mild or moderate liver dysfunction while you are being treated with Stivarga, your doctor should check you carefully. If you have severely impaired liver function, you should not be treated with Stivarga as there is no information on the use of Stivarga in patients with severely impaired liver function.

No dose adjustment is necessary if you have mild, moderate, or severe renal impairment.

If you have taken too much Stivarga

Contact your doctor immediately if you have taken more than the prescribed dose. You may need treatment and the doctor may ask you to stop taking Stivarga.

Taking too much Stivarga can make some side effects more likely or more serious, especially:

  • skin reactions (rash, blisters, redness, pain, swelling, itching, or scaling of the skin)
  • voice changes or hoarseness ( dysphonia )
  • frequent or loose bowel movements ( diarrhea )
  • mouth ulcers ( mucosal inflammation )
  • dry mouth
  • decreased appetite
  • high blood pressure ( hypertension )
  • excessive tiredness ( exhaustion ).

If you forget to take Stivarga

If you have forgotten a dose, take it on the same day as soon as you remember. Do not take two doses of Stivarga on the same day to make up for a missed dose the day before. Tell the doctor that you have forgotten a dose.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. This medicine may also affect the results of some blood tests.

The most serious side effects, for which a fatal outcome has been observed, are:

  • serious liver problems (including liver failure), bleeding, perforation of the gastrointestinal tract, and infection.

Tell your doctor immediately if you experience any of the following symptoms:

Liver problems

Treatment with Stivarga may lead to a greater risk of serious liver problems. Seek medical attention immediately if you experience the following symptoms:

  • yellowish discoloration of the skin and the whites of the eyes
  • dark colored urine
  • confusion and/or disorientation.

These can be signs of serious liver damage.

Bleeding

Stivarga can lead to severe bleeding in the digestive system, e.g. in the stomach, throat, rectum, or intestines, or in the lungs, kidneys, mouth, vagina, and/or brain. Seek medical attention immediately if you experience the following symptoms:

Severe gastrointestinal problems ( gastrointestinal perforation or fistula )

Seek medical attention immediately if you experience the following symptoms:

– severe stomach pain or stomach pain that does not go away

vomiting blood

– red or black stools.

These can be signs of serious stomach or intestinal problems.

infection

Treatment with Stivarga may lead to a higher risk of infection, especially in the urinary tract, nose, throat, and lungs. Treatment with Stivarga can also lead to a higher risk of fungal infections in the mucous membrane, on the skin, or in the body. Contact a doctor immediately if you experience the following symptoms:

  • high fever
  • severe cough with or without increased mucus production
  • very sore throat
  • shortness of breath
  • burning sensation/pain when urinating
  • abnormal vaginal discharge or irritation
  • redness, swelling, and/or pain in any part of the body.

This may be a sign of an infection.

Other side effects of Stivarga are listed by frequency:

Very common side effects ( may affect more than 1 in 10 users)

  • reduced number of blood platelets which may be characterized by bruising or bleeding more easily ( thrombocytopenia )
  • reduced number of red blood cells ( anemia )decreased appetite and decreased food intake
  • high blood pressure ( hypertension )
  • voice changes or hoarseness ( dysphonia )
  • frequent or loose bowel movements ( diarrhea )
  • pain in the mouth or dry mouth, pain in the tongue, mouth ulcers ( stomatitis and/or mucositis )
  • nausea
  • vomiting
  • high levels of bilirubin in the blood, a substance produced by the liver ( hyperbilirubinemia )
  • changes in liver enzymes that may indicate that something is wrong with the liver ( increase in transaminases )
  • redness, pain, blisters, and swelling of the palms of the hands or soles of the feet ( hand-foot-skin reaction )
  • rash
  • weakness ( asthenia ) and excessive tiredness ( fatigue )
  • pain (including abdominal pain and back pain)
  • constipation
  • fever
  • weight loss

Common side effects ( may affect up to 1 in 10 users)

  • decreased number of white blood cells ( leukopenia )
  • decreased activity of the thyroid glandhypothyroidism )
  • low levels of potassium, phosphate, calciumsodium, or magnesium in the blood ( hypokalemia, hypophosphatemia, hypocalcemia, hyponatremia, and hypomagnesemia )
  • high level of uric acid in the blood ( hyperuricemia )
  • loss of body fluids (dehydration)
  • headache
  • tremors _ _
  • nerve disease that can cause changes in sensory sensations, e.g. numbness, tingling, weakness, or painperipheral neuropathy )
  • taste disturbancesdry mouth
  • heartburngastroesophageal reflux )infection or irritation of the stomach or intestines ( gastroenteritis )
  • hair lossalopecia )
  • dry skin
  • scaly skin rash ( exfoliative rash )
  • sudden, involuntary muscle contractions ( muscle spasms )
  • protein in the urine ( proteinuria )
  • high levels of other enzymes involved in digestion ( increase in amylase and lipase )
  • abnormal clotting of the blood ( abnormal INR value )

Uncommon side effects ( may affect up to 1 in 100 users)

  • signs/symptoms of an allergic reaction which may include a widespread severe rash, nausea, fever, shortness of breath, jaundice, changes in chemicals produced by the liver ( hypersensitivity reaction )heart attack, chest painmyocardial infarction and ischemia )
  • severe increase in blood pressure et leading to headache, confusion, blurred vision, nausea, vomiting, and convulsions ( hypertensive crisis )
  • inflammation of the pancreas manifests itself as pain in the stomach, nausea, vomiting, and feverpancreatitis )
  • nail disease (changes on the nails such as furrows and/or splitting)
  • multiple skin rashes ( erythema multiforme )

Rare side effects ( may affect up to 1 in 1,000 users)

  • certain types of skin cancerkeratoacanthoma/squamous cancer )
  • headache, confusion, seizures, and loss of vision with or without high blood pressure (posterior reversible encephalopathy syndrome/PRES)
  • serious reactions in the skin and/or mucous membranes which may consist of painful blisters and fever with extensive skin shedding (Stevens-Johnson syndrome and toxic epidermal necrolysis ).

No known frequency

  • an enlargement and weakening of a vessel wall or a rupture in a vessel wall ( aneurysms and arterial dissections ).

How Stivarga should be stored

Keep this medicine out of the sight and reach of children.

Use before the expiry date which is stated on the carton and can label after EXP. The expiration date is the last day of the specified month.

Store in the original packaging. Moisture sensitive.

Close the jar well.

Once the can has been opened, the medicine must be thrown away after 7 weeks.

Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.

Contents of the packaging and other information

Contents declaration

– The active substance is regorafenib. Each film-coated tablet contains 40 mg of regorafenib.

– Other ingredients are microcrystalline cellulose, croscarmellose sodium, magnesium stearate, povidone (K-25) and colloidal anhydrous silica, red iron oxide (E172), yellow iron oxide (E172), lecithin (produced from soy), macrogol 3350, polyvinyl alcohol (partially hydrolyzed), talc and titanium dioxide (E171) (see also section “Important information about some ingredients in Stivarga”).

Appearance and package sizes of the medicine

Stivarga 40 mg tablets are pale pink and oval, marked with “BAYER” on one side and “40” on the other side.

Each jar contains 28 film-coated tablets.

Stivarga 40 mg tablets are available in packs containing 1 jar or 3 jars.

Not all pack sizes may be marketed.

Leave the desiccant in the jar. The desiccant is a moisture-absorbing material in a small container that protects the tablets from moisture.

Marketing Authorisation Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser Wilhelm Allee

51368 Leverkusen

Germany

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