EVOTAZ 300 MG/150 MG FILM-COATED TABLETS

2. What you need to know before you take EVOTAZ

Do not take EVOTAZ

• if you are allergicto atazanavir, cobicistat or any of the other ingredients of this medicine (listed in section 6)
• if you have moderate to severe liver problems
• if you are taking any of these medicines: see also Taking EVOTAZ with other medicines
• rifampicin (an antibiotic used to treat tuberculosis)
• carbamazepine, phenobarbital and phenytoin (antiepileptics used to prevent seizures)
• astemizole or terfenadine (frequently used to treat allergic symptoms, these medicines may be available without a prescription); cisapride (used to treat stomach reflux, sometimes called heartburn); pimozide (used to treat schizophrenia); amiodarone, dronedarone, quinidine, lidocaine (injectable) or bepridil (used to correct heart rhythm); ergotamine, dihydroergotamine, ergonovine, ergometrine and methylergonovine (used to treat headaches); and alfuzosin (used to treat enlarged prostate)
• quetiapine (used to treat schizophrenia, bipolar disorder and major depressive disorder); lurasidone (used to treat schizophrenia)
• medicines containing St. John's Wort (Hypericum perforatum, a medicinal plant)
• triazolam and oral midazolam (used to induce sleep and/or relieve anxiety)
• simvastatin, lovastatin and lomitapide (used to lower blood cholesterol)
• avanafil (used to treat erectile dysfunction)
• colchicine (used to treat gout), if you have kidney and/or liver problems
• dabigatran and ticagrelor (used to prevent and reduce blood clots)
• products containing grazoprevir, including the fixed-dose combination of elbasvir/grazoprevir, and the fixed-dose combination of glecaprevir/pibrentasvir (used to treat chronic hepatitis C infection)

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 using sildenafil to treat erectile dysfunction.

Tell your doctor immediately if you are in any of these situations.

Warnings and precautions

Some people will need special monitoring before or during treatment with EVOTAZ. Talk to 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 tell your doctor:

• if you have liver problems
• if you develop signs or symptoms of gallstones (pain in your right side). Gallstones have been reported in patients treated with atazanavir, a component of EVOTAZ
• if you have haemophilia type A or B. You may experience increased bleeding.
• if you have kidney problems or need to undergo haemodialysis. 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 the urine, pain when urinating), please inform your doctor immediately
• if you are taking oral contraceptives ("the pill") to prevent pregnancy. If you are currently using an oral contraceptive or 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, signs and symptoms of inflammation of previous infections may appear soon after starting anti-HIV 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 any apparent symptoms. If you notice 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 notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up towards the trunk of the body, palpitations, tremors or hyperactivity, please inform your doctor immediately to receive the 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 many 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. The symptoms of osteonecrosis are stiffness in the joints, pain and discomfort (especially in the hips, knees and shoulders) and difficulty moving. If you notice any of these symptoms, please inform your doctor.

Hyperbilirubinemia (increased bilirubin levels in the blood) has occurred in patients receiving EVOTAZ. The signs may be a slightly yellowish tint to the skin or eyes. If you notice any of these symptoms, please inform your doctor.

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

EVOTAZ may affect the way your kidneys work.

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

Children

Do not give this medicine to childrenunder 12 years of age or weighing less than 35kgas the use of EVOTAZ has not been studied in this population.

Other medicines and EVOTAZ

Do not take EVOTAZ with certain medicines.These are listed under the heading Do not take EVOTAZ, at the beginning of section 2.

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

• medicines containing 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 hepatitis C)
• sildenafil, vardenafil and tadalafil (used by men to treat impotence [erectile dysfunction])
• if you are taking an oral contraceptive ("the pill"). You should use an additional or different method of contraception (e.g. condom).
• certain medicines used to treat diseases related to stomach acid ("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 blood cholesterol)
• 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 type 2 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, chlordiazepoxide, diazepam, estazolam, flurazepam and zolpidem (used to treat nervous system disorders)
• buprenorphine (used to treat opioid addiction and pain)

It is especially important that you tell 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 disease, inflammatory eye, joint and muscle conditions, and other inflammatory conditions. If alternative medicines cannot be used, their use should only be done after a clinical assessment and with close monitoring by your doctor to assess the adverse effects of corticosteroids.

Pregnancy and breast-feeding

EVOTAZ should not be used during pregnancy, because 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 not known if cobicistat, the other component of EVOTAZ, passes into breast milk, but it has been shown to pass into breast milk in animals. Patients must not breast-feed while taking EVOTAZ.

It is not recommendedthat HIV-positive women breast-feed their babies because HIV infection can be transmitted to the baby through breast milk.

If you are breast-feeding or thinking of breast-feeding, you must consultyour doctor as soon as possible.

Driving and using machines

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

3. How to take EVOTAZ

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor again. This way, you can be sure that the treatment is fully effective and reduces the risk of HIV developing resistance to the treatment.

The recommended dose of EVOTAZ in adults and adolescents (12 years of age and older, weighing at least 35 kg) is one tablet once daily, taken by mouth and with food, in combination with other anti-HIV medicines. 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 has recommended, contact your doctor immediately or go to the nearest hospital for advice.

If you forget to take EVOTAZ

If you forget a dose of EVOTAZ during 12 hours or less, 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 the time you should have taken EVOTAZ, do not take the missed dose. Wait and take the next dose at the usual time. Do not take a double dose. It is important that you do not miss any dose of EVOTAZ or your other anti-HIV medicines.

If you stop taking EVOTAZ

Do not stop taking EVOTAZ without consulting your doctor.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Inform your doctor of any change you notice in your state of health.

The following adverse effects may occur while taking EVOTAZ

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

• yellowish discoloration of the skin or the white part of your eyes
• nausea

Common (may affect up to 1 in 10 people)

• increase in bilirubin levels in the blood
• vomiting, diarrhea, stomach pain or discomfort, indigestion, bloated or distended abdomen (belly), 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 (torsades de pointes)
• allergic reaction (hypersensitivity)
• liver inflammation
• pancreas inflammation, stomach inflammation
• allergic reactions including rash, elevated temperature, increased liver enzyme levels in blood tests, increased levels of a type of white blood cell (eosinophilia) and/or increased lymph node size (see section 2)
• severe swelling of the skin and other tissues, usually the lips or eyes
• fainting, high blood pressure
• chest pain, usually feeling unwell, fever
• difficulty breathing
• kidney stone formation, kidney inflammation, blood in the urine, excess protein in the urine, increased frequency of urination, chronic kidney disease (how well your kidneys are working)
• gallstones
• muscle contraction, joint pain, muscle pain
• breast enlargement 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 including severe skin rash, elevated temperature, and increased lymph node size (Stevens-Johnson syndrome, see section 2)
• rapid or irregular heartbeat (prolonged QTc interval)
• increase in liver and spleen size
• gallbladder inflammation
• kidney pain
• swelling
• visible fluid accumulation under the skin, skin rash, blood vessel enlargement
• abnormal gait
• muscle pain, loss of muscle tone or muscle weakness not caused by exercise

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

Reporting of Adverse Effects

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

5. Storage of EVOTAZ

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

Do not use this medicine after the expiration date stated on the label and carton after EXP. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of EVOTAZ

• The active ingredients are atazanavir and cobicistat. Each film-coated tablet contains 300 mg of atazanavir (as sulfate) and 150 mg of cobicistat.
• The other ingredients 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), red iron oxide (E172)

Appearance and Package Contents of the Product

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

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

Not all package sizes may be marketed in your country.

Date of Last Revision of this Leaflet:

Other Sources of Information

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