Cotellic - Cobimetinib uses, dose and side effects

Cotellic is used to treat adult patients with a type of skin cancer called melanoma, which has spread to other parts of the body or cannot be removed by surgery.

It is used in combination with another anti-cancer medicine called vemurafenib.
It can only be given to patients whose cancer has a change ( mutation ) in a protein called “BRAF”. Before starting treatment, your doctor will test if your melanoma has this mutation. This change may have led to the development of melanoma.

How Cotellic works
Cotellic affects a protein called “MEK”, which is important for the growth of cancer cells. When Cotellic is used in combination with vemurafenib (which affects the altered “BRAF” protein ), it further slows down or stops, the growth of your cancer.

What you need to know before taking Cotellic

Do not take Cotellic:

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

If you are not sure, talk to your doctor, pharmacist, or nurse before taking Cotellic.

Warnings and cautions

Talk to your doctor, pharmacist, or nurse before taking Cotellic if you have:

Bleeding

Cotellic can cause severe bleeding, especially in the brain or stomach ( see also Severe bleeding in section 4 ). Contact your doctor immediately if you have any unusual bleeding or any of these symptoms; headache, dizziness, feeling weak, blood in the stool or black stools, and bloody vomiting.

Eye problems

Cotellic can cause eye problems ( see also ” Eye problems “ in section 4 ). Contact your doctor immediately if you experience the following symptoms: blurred vision, distorted vision, loss of vision, or other vision changes during treatment. Your doctor should examine your eyes if you experience any new or worsening problems with your vision while taking Cotellic.

Heart problems

Cotellic may reduce the amount of blood pumped by your heart ( see also ” Heart problems “ in section 4 ). Your doctor should perform tests before and during treatment with Cotellic to check how well your heart can pump blood. Contact your doctor immediately if you have a feeling that your heart is beating, rushing, or beating irregularly, or if you experience dizziness, shortness of breath, fatigue, or swelling in your legs.

Liver problem

Cotellic may increase the level of certain liver enzymes in your blood during treatment. Your doctor will take blood samples to check these levels and how well your liver is working.

Muscle problem

Cotellic can cause elevated levels of creatine phosphokinase, which is an enzyme found primarily in muscle, heart, and brain. This may be a sign of muscle damage ( rhabdomyolysis ) (see also Muscle problems in section 4). Your doctor will take blood samples to check this. Contact your doctor immediately if you get any of these symptoms; muscle pain, muscle spasm, weakness, or dark or red urine.

Diarrhea

Contact your doctor immediately if you get diarrhea. Severe diarrhea can cause loss of body fluid ( dehydration ). Follow your doctor’s instructions for what to do to prevent or treat diarrhea.

Children and young people

Cotellic is not recommended for children and adolescents. The effects of Cotellic in people under 18 years of age are not known.

Other medicines and Cotellic

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

This is because Cotellic may affect the way some other medicines work. Other medicines can also affect the way Cotellic works.

Drug	Purpose of the drug
itraconazole, clarithromycin, erythromycin, telithromycin, voriconazole, rifampicin, posaconazole, fluconazole, miconazole	against certain fungal and bacterial infections
ritonavir, cobicistat, lopinavir, delavirdine, amprenavir, fosamprenavir	against HIV – infection
telaprevir	against hepatitis C
nefazodone	against depression
amiaridon	against irregular heartbeats
diltiazem , verapamil	against high blood pressure
imatinib	against cancer
carbamazepine, phenytoin	against seizures
St. John’s wort	herbal medicine used to treat mild depression

Cotellic with food and drink

Avoid taking Cotellic with grapefruit juice. The reason is that it could increase the amount of Cotellic in the blood.

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Cotellic is not recommended during pregnancy. Although the effects of Cotellic have not been studied in pregnant women, it can lead to permanent damage or malformations in the fetus.
If you become pregnant during treatment with Cotellic or within 3 months of your last dose, contact your doctor immediately.
It is not known if Cotellic passes into breast milk. If you are breast-feeding, your doctor will discuss the benefits and risks of taking Cotellic with you.

Contraceptives
Women of childbearing potential should use two effective methods of contraception, e.g. condom or another barrier method (with spermicide, if available) during treatment and for at least 3 months after treatment has ended. Ask your doctor about the best contraceptive methods for you.

Driving and using machines

Cotellic may affect your ability to drive and use machines. Avoid driving and using machines if you feel that your vision is affected or other problems that may affect your ability, e.g. if you feel dizzy or tired. Contact your doctor if you are unsure.

Cotellic contains lactose and sodium

The tablets contain lactose (a type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains less than 1 mmol (23 mg) sodium per tablet, ie it is essentially ‘sodium-free’.

How to take Cotellic

Always take this medicine exactly as your doctor or pharmacist has told you. Ask your doctor or pharmacist if you are unsure.

How many tablets to take

The recommended dose is 3 tablets once daily (total 60 mg)

Take the tablets every day for 21 days (called a “treatment period”).
After the 21 days, do not take any Cotellic tablets for 7 days. During this 7-day break from Cotellic treatment, you should continue to take vemurafenib according to your doctor’s instructions.
Start your next 21-day treatment period after a 7-day break.
If you experience side effects, your doctor may decide to lower your dose, temporarily or permanently discontinue treatment. Always take Cotellic exactly as your doctor or pharmacist has told you.

How to take your tablets

Swallow the tablets whole with a glass of water
Cotellic can be taken with or without food

If you vomit
If you vomit after taking Cotellic, do not take an extra dose of Cotellic that day. Continue to take Cotellic, as usual, the next day.

If you take more Cotellic then you should

If you take more Cotellic than you should, contact a doctor immediately. Bring the medicine pack and this leaflet.

If you forget to take Cotellic

If there are more than 12 hours left until your next dose, take your dose as soon as you remember.
If there are less than 12 hours left until your next dose, skip the missed dose. Take the next dose at the usual time.
Do not take a double dose to make up for a forgotten dose.

If you stop taking Cotellic

It is important that you continue to take Cotellic for as long as your doctor prescribes it.

If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience side effects, your doctor may decide to lower your dose, temporarily or permanently discontinue treatment.

Also read the package leaflet for vemurafenib, which is used in combination with Cotellic.

Serious side effects are

Contact your doctor immediately if you experience any of the side effects listed below or if they get worse during treatment.

Severe bleeding (common: may affect up to 1 in 10 people)

Cotellic can cause severe bleeding, especially in the brain or stomach. Depending on the bleeding site, symptoms may include:

headache, dizziness, or weakness
bloody vomiting
abdominal pain
red or black stools

Eye (vision) problems (very common: may affect more than 1 user in 10)

Cotellic can cause eye problems. Some of these eye problems can occur due to something called “serous retinopathy” (an accumulation of fluid under the retina of the eye). Symptoms of serious retinopathy include:

Tamsyn
distorted vision
vision loss
all other changes in your vision

Heart problems (common: may affect up to 1 in 10 people)

Cotellic can reduce the amount of blood pumped by your heart. Symptoms of this may include:

feeling dizzy
the feeling of shortness of breath
feeling of tiredness
feeling that your heart is beating, rushing, or beating irregularly
swelling in the legs

Muscle problems ( uncommon: may affect up to 1 in 100 people)

Cotellic may result in the degradation of muscle tissue ( rhabdomyolysis ). Symptoms of this may include:

muscle pain
muscle spasm or weakness
dark or red urine.

Diarrhea (very common: may affect more than 1 user in 10)

Contact your doctor immediately if you get diarrhea. Follow your doctor’s instructions for what to do to prevent or treat diarrhea.

Other side effects are
, tell your doctor, pharmacist, or nurse if you notice any of the following side effects:

Very common: may affect more than 1 user in 10

increased sensitivity to sunlight
rash
nausea
fever
overindulge
increase in liver enzymes (shown in blood tests)
abnormal results of blood tests related to creatine phosphokinase, an enzyme found mainly in the heart, brain, and skeletal muscle
vomiting
skin rash with a flat, discolored, or raised area-like acne.
high blood pressure
anemia (low red blood cell count )
bleeding
abnormal thickening of the skin

Common: may affect up to 1 in 10 users

different types of skin cancer such as basal cell carcinoma, squamous cell carcinoma of the skin, and keratoacanthoma
dehydration, when the body does not have enough fluid
reduced amount of phosphate or sodium (shown in a blood test)
the increased amount of sugar (shown in a blood test)
the increased amount of liver pigment (called “bilirubin”) in the blood. Signs include yellowing of the skin or eyes
inflammation of the lungs that can cause breathing difficulties and can be life-threatening (called “pneumonitis”)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Medical Products Agency. By reporting side effects, you can help increase drug safety information.

5. How to store Cotellic

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The expiration date is the last day of the specified month.
This medicine does not require any special storage instructions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the packaging and other information

Content declaration

The active substance is cobimetinib. Each film-coated tablet contains cobimetinib hemifumarate equivalent to 20 mg cobimetinib.
Other ingredients (see section 2 “Cotellic contains lactose and sodium ):
- lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the tablet core; and
- polyvinyl alcohol, titanium dioxide, macrogol, and talc in the film coating

What the medicine looks like and the contents of the pack

Cotellic film-coated tablets are white and round with “COB” engraved on one side. There is one available pack size: 63 tablets (3 blisters with 21 tablets each).

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG