Label: information for the user

EVOTAZ 300mg/150mg film-coated tablets

atazanavir/cobicistat

Read this label carefully before starting to take this medicine, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this label. See section4.

EVOTAZ contains two active ingredients:

• atazanavir, an antiviral (or antiretroviral) medication.Pertaining to a group of medications known asprotease inhibitors. These medications control the infection caused by the human immunodeficiency virus (HIV) by blocking the production of a protein that HIV needs to multiply. They act by reducing the amount of HIV in the body and thereby strengthen the immune system. In this way, atazanavir reduces the risk of developing diseases associated with HIV infection.
• cobicistat, a booster (pharmacokinetic enhancer) to help improve the effects of atazanavir. Cobicistat does not directly treat HIV infection, but rather potentiates the levels of atazanavir in the blood. It does this by delaying the degradation of atazanavir, causing it to remain in the body for a longer period.

EVOTAZ may be used by adults and adolescents (12 years of age and older, weighing at least 35 kg) who are infected with HIV, the virus that causes acquired immunodeficiency syndrome (AIDS). It is used in combination with other anti-HIV medications to help control HIV infection. Your doctor will determine the best combination of these medications with EVOTAZ for you.

Do not take EVOTAZ

• if you are allergicto atazanavir, cobicistat, or any of the other ingredients in this medicine (listed in section6)
• if you have moderate to severe liver problems
• if you are taking any of these medicines: see alsoTaking EVOTAZ with other medicines
• rifampicin (an antibiotic used to treat tuberculosis)
• carbamazepine, phenobarbital, and phenytoin (anti-epileptic medicines used to prevent seizures)
• astemizole or terfenadine (often used to treat allergic symptoms, these medicines may be available over the counter); cisapride (used to treat gastroesophageal reflux, sometimes called heartburn); pimozide (used to treat schizophrenia); amiodarone, dronedarone, quinidine, lidocaine (injectable) or bepridil (used to correct irregular heart rhythms); ergotamine, dihydroergotamine, ergonovine, ergometrine, and methylergonovine (used to treat headaches); and alfuzosin (used to treat an enlarged prostate)
• quetiapine (used to treat schizophrenia, bipolar disorder, and major depressive disorder); lurasidone (used to treat schizophrenia)
• medicines that contain St. John's Wort (Hypericum perforatum, a medicinal plant)
• triazolam and midazolam oral (taken by mouth) (used to induce sleep and/or relieve anxiety)
• simvastatin, lovastatin, and lomitapide (used to lower cholesterol in the blood)
• avanafil (used to treat erectile dysfunction)
• colchicine (used to treat gout), if you have kidney problems and/or liver problems
• dabigatran and ticagrelor (used to prevent and reduce blood clots)
• products that contain grazoprevir, including the fixed-dose combination of elbasvir/grazoprevir, and the fixed-dose combination of glecaprevir/pibrentasvir (used to treat chronic hepatitisC)

Do not take sildenafil with EVOTAZ when sildenafil is used to treat pulmonary arterial hypertension. Sildenafil is also used to treat erectile dysfunction. Inform your doctor if you are taking sildenafil for erectile dysfunction.

Inform your doctor immediately if you experience any of the following:

Warnings and precautions

Some people may need special monitoring before or during treatment with EVOTAZ. Consult your doctor or pharmacist before starting EVOTAZ.

EVOTAZ is not a cure for HIV infection.You may continue to develop infections or other diseases associated with HIV infection.

Make sure to inform your doctor:

• if you have liver problems
• if you develop signs or symptoms of gallstones (pain in your right side). Cases of gallstones have been reported in patients treated with atazanavir, a component of EVOTAZ
• if you have hemophilia typeA orB. You may experience increased bleeding.
• if you have kidney problems and/or need to undergo hemodialysis. Cases of kidney stones have been reported in patients treated with atazanavir, a component of EVOTAZ. If you experience signs or symptoms of kidney stones (side pain, blood in urine, painful urination), please inform your doctor immediately
• if you are taking oral contraceptives("the pill")to prevent pregnancy. If you are currently taking oral contraceptives or a contraceptive patch to prevent pregnancy, you should use an additional or different method of contraception (e.g., condom)

In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections, symptoms of previous infections may appear shortly after starting antiretroviral treatment. It is believed that these symptoms are due to an improvement in the body's immune response, allowing it to fight off infections that were present without apparent symptoms. If you experience any symptoms of infection, please inform your doctor immediately. In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also appear after you have started taking medicines to treat your HIV infection. Autoimmune disorders may appear many months after starting treatment. If you experience any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and ascending to the trunk of the body, palpitations, tremors, or hyperactivity, please inform your doctor immediately to receive necessary treatment.

Some patients receiving combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). Among the numerous risk factors for developing this disease are the duration of combination antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immunosuppression, and high body mass index. Symptoms of osteonecrosis include joint stiffness, pain, and discomfort (especially in the hip, knee, and shoulder) and difficulty moving. If you notice any of these symptoms, please inform your doctor.

Hyperbilirubinemia (elevated bilirubin levels in the blood) has been reported in patients receiving EVOTAZ. Symptoms may include a slightly yellowish tone of the skin or eyes. If you notice any of these symptoms, please inform your doctor.

Patients treated with EVOTAZ may develop severe skin rash, including Stevens-Johnson syndrome. Inform your doctor immediately if you develop a rash.

EVOTAZ may affect kidney function.

If you notice a change in the way your heart beats (changes in heart rhythm), please inform your doctor.

Children

Do not administer this medicine to childrenunder 12years of ageor weighing less than 35kgas it has not been studied in this population.

Other medicines and EVOTAZ

You should not take EVOTAZ with certain medicines.These are listed under the title Do not take EVOTAZ at the beginning of section2.

There are other medicines that cannot be taken together or that may require a change in their administration when taken with EVOTAZ. Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine. It is especially important to mention the use of the following:

• medicines that contain ritonavir or cobicistat (boosting agents)
• other medicines for the treatment of HIV infection (e.g., indinavir, didanosine, tenofovir disoproxil, tenofovir alafenamide, efavirenz, etravirine, nevirapine, and maraviroc)
• sofosbuvir/velpatasvir/voxilaprevir (used to treat hepatitisC)
• sildenafil, vardenafil, and tadalafil (used by men to treat erectile dysfunction)
• if you are taking oral contraceptives ("the pill"). You should use an additional or different method of contraception (e.g., condom)
• some medicines used to treat acid-related stomach diseases ("heartburn") (e.g., antacids, H2 blockers such as famotidine, and proton pump inhibitors such as omeprazole)
• disopyramide, flecainide, mexiletine, propafenone, digoxin, bosentan, amlodipine, felodipine, nicardipine, nifedipine, verapamil, diltiazem, metoprolol, and timolol (medicines to lower blood pressure, slow heart rate, or correct heart rhythm)
• atorvastatin, pravastatin, fluvastatin, pitavastatin, and rosuvastatin (used to lower cholesterol in the blood)
• salmeterol (used to treat asthma)
• ciclosporin, tacrolimus, and sirolimus (medicines to reduce the effects of the body's immune system)
• certain antibiotics (rifabutin, clarithromycin)
• ketoconazole, itraconazole, voriconazole, and fluconazole (antifungals)
• metformin (used to treat type2 diabetes)
• warfarin, apixaban, edoxaban, clopidogrel, and rivaroxaban (used to reduce blood clots)
• irinotecan, dasatinib, nilotinib, vinblastine, and vincristine (used to treat cancer)
• trazodone (used to treat depression)
• perphenazine, risperidone, thioridazine, midazolam (given by injection), buspirone, clorazepate, diazepam, estazolam, flurazepam, and zolpidem (used to treat nervous system disorders)
• buprenorphine (used to treat opioid addiction and pain)

It is especially important to inform your doctor if you are taking: corticosteroids, including dexamethasone, betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, eye, joint, and muscle inflammatory diseases, and other inflammatory diseases. If alternative medicines cannot be used, their use should only be made after a clinical evaluation and with close monitoring by your doctor to evaluate the adverse effects of corticosteroids.

Pregnancy and breastfeeding

EVOTAZ should not be used during pregnancy, as the levels of the medicine in your blood may be lower during pregnancy and may not be high enough to control HIV. Your doctor may prescribe different medicines if you become pregnant while taking EVOTAZ.

Atazanavir, a component of EVOTAZ, passes into breast milk. It is unknown whether cobicistat, the other component of EVOTAZ, passes into breast milk, but it has been seen to pass into breast milk in animals. Patients should not breastfeed while taking EVOTAZ.

It is not recommendedthat women with HIV infection breastfeed as the infection can be transmitted to the baby through breast milk.

If you are breastfeeding or plan to breastfeed, you shouldconsult withyour doctoras soon as possible.

Driving and using machines

Some patients have reported dizziness during treatment with atazanavir or cobicistat, active ingredients of EVOTAZ. If you feel dizzy or disoriented, do not drive, operate any tools or machines, and contact your doctor immediately.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again. This way, you can be sure that the treatment is completely effective and reduces the risk of the HIV developing resistance to treatment.

The recommended dose of EVOTAZ in adults and adolescents (12 years and older, weighing at least 35 kg) is one tablet taken by mouth daily with food, in combination with other anti-HIV medications. The tablets have an unpleasant taste, so swallow the tablet whole; do not crush or chew the tablets. This will help ensure that you take the full dose.

If you take more EVOTAZ than you should

If you have accidentally taken more EVOTAZ than your doctor recommended, contact your doctor immediately or visit the nearest hospital for consultation.

If you forget to take EVOTAZ

If you forget a dose of EVOTAZ within 12 hours, take it immediately with food and then take the next scheduled dose at the usual time. If you forget a dose and more than 12 hours have passed since you should have taken EVOTAZ, do not take the missed dose. Wait and take the next dose at the usual time. Do not double the next dose. It is essential that you do not forget any dose of EVOTAZ or your other anti-HIV medications.

If you interrupt treatment with EVOTAZ

Do not stop treatment with EVOTAZ without consulting your doctor.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Inform your doctor of any change you notice in your health status.

The following side effects may occur while taking EVOTAZ

Very common (may affect more than 1 in 10 people)

• Yellowing of the skin or the white part of your eyes
• Nausea

Common (may affect up to 1 in 10 people)

• Increased levels of bilirubin in the blood
• Vomiting, diarrhea, stomach pain or discomfort, indigestion, bloated or distended abdomen, gas (flatulence)
• Headache, dizziness
• Extreme fatigue
• Increased appetite, altered sense of taste, dry mouth
• Difficulty sleeping, abnormal dreams, numbness
• Skin rash

Uncommon (may affect up to 1 in 100 people)

• Potentially life-threatening irregular heartbeat (torsade de pointes)
• Allergic reaction (hypersensitivity)
• Liver inflammation
• Pancreatitis, stomach inflammation
• Allergic reactions that include rash, high temperature, increased levels of liver enzymes in blood tests, increased eosinophils, and/or enlarged lymph nodes (see section 2)
• Severe skin swelling and other tissues, usually the lips or eyes
• Fainting, high blood pressure
• Chest pain, usually feeling unwell, fever
• Difficulty breathing
• Stone formation in the kidney, kidney inflammation, blood in the urine, excess protein in the urine, increased frequency of urination, chronic kidney disease (how your kidneys function)
• Bile stones
• Muscle contraction, joint pain, muscle pain
• Enlarged breasts in men
• Depression, anxiety, sleep disturbance
• Unusual fatigue or weakness
• Loss of appetite, weight loss, weight gain
• Disorientation, memory loss
• Numbness, weakness, tingling or pain in the arms and legs
• Mouth ulcers and cold sores
• Rash, abnormal hair loss or weakening, itching

Rare (may affect up to 1 in 1,000 people)

• Allergic reactions that include severe skin rash, high temperature, and enlarged lymph nodes (Stevens-Johnson syndrome, see section 2)
• Fast or irregular heartbeat (prolonged QTc interval)
• Enlarged liver and spleen
• Bile duct inflammation
• Kidney pain
• Swelling
• Visible accumulation of fluid under the skin, skin rash, dilated blood vessels
• Abnormal gait
• Muscle pain, loss of muscle tone or weakness not caused by exercise

During HIV treatment, there may be an increase in weight and blood glucose and lipid levels. This is partly related to recovery of health and lifestyle, and in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will evaluate these changes.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and on the box after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of EVOTAZ

• The active ingredients are atazanavir and cobicistat. Each film-coated tablet contains 300mg of atazanavir (as sulfate) and 150mg of cobicistat.
• The other components are:

Core of the tablet‑microcrystalline cellulose (E460(i)), sodium croscarmellose (E468), sodium starch glycolate, crospovidone (E1202), stearic acid (E570), magnesium stearate (E470b), hydroxypropyl cellulose (E463), silica (E551)

Film coating‑hypromellose (hydroxypropyl methyl cellulose, E464), titanium dioxide (E171), talc (E553b), triacetin (E1518), iron oxide red (E172)

Appearance of the product and contents of the package

The film-coated tablets of EVOTAZ are pink, oval, biconvex,, with approximate dimensions of 19mm x 10.4mm, marked with "3641" on one face and smooth on the other face of the tablet.

EVOTAZfilm-coated tablets are presented in bottles of 30tablets. The following package sizes are available: packages containing 1bottle of 30film-coated tablets and packages containing 90(3bottles of30) film-coated tablets.

Only some package sizes may be marketed in your country.

Last revision date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.