Evotaz 300 mg/150 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

EVOTAZ 300mg/150mg film-coated tablets

atazanavir/cobicistat

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What EVOTAZ is and what it is used for
2. What you need to know before taking EVOTAZ
3. How to take EVOTAZ
4. Possible side effects
5. How to store EVOTAZ
6. Contents of the pack and other information

1. What EVOTAZ is and what it is used for

EVOTAZ contains two active substances:

• Atazanavir, an antiviral (or antiretroviral) medicine. It belongs to a group of medicines called protease inhibitors. These medicines control human immunodeficiency virus (HIV) infection by blocking the production of a protein that HIV needs to multiply. They work by reducing the amount of HIV in your body, thereby strengthening your immune system. In this way, atazanavir reduces the risk of developing diseases associated with HIV infection.
• Cobicistat, a booster (pharmacokinetic enhancer) that helps improve the effects of atazanavir. Cobicistat does not directly treat HIV infection, but increases the levels of atazanavir in the blood. It does this by delaying the breakdown of atazanavir, allowing it to remain in the body for a longer period.

EVOTAZ may be used by adults and adolescents (aged 12 years 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 medicines to help control your HIV infection. Your doctor will determine the best combination of these medicines to use with EVOTAZ.

2. What you need to know before taking EVOTAZ

Do not take EVOTAZ

• if you are allergic to 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 the following medicines: see also Taking EVOTAZ with other medicines

• rifampicin (an antibiotic used to treat tuberculosis)

• carbamazepine, phenobarbital, and phenytoin (used to prevent seizures)

• apalutamide, encorafenib, ivosidenib (used to treat cancer)

• astemizole or terfenadine (commonly used to treat allergic symptoms; these medicines may be available without a prescription); cisapride (used to treat gastric reflux, sometimes called heartburn); pimozide (used to treat schizophrenia); amiodarone, dronedarone, quinidine, lidocaine (injected), or bepridil (used to correct heart rhythm); ergotamine, dihydroergotamine, ergonovine, ergometrine, and methylergonovine (used to treat headaches); and alfuzosin (used to treat enlarged prostate gland)

• 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 herbal remedy)

• triazolam and oral midazolam (taken by mouth) (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 taking sildenafil for the treatment of erectile dysfunction.

Inform 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 illnesses associated with HIV infection.

Make sure to inform your doctor:

• if you have liver problems
• if you develop signs or symptoms of gallstones (pain on 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 require 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 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 (AIDS) and a history of opportunistic infections, signs and symptoms of inflammation from previous infections may appear shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, allowing the body to fight infections that were present but without apparent symptoms. If you notice any signs of infection, please inform your doctor immediately. In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you start taking medicines for your HIV infection. Autoimmune disorders may appear many months after treatment has started. If you notice any signs of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up toward the trunk, palpitations, tremors, or hyperactivity, please inform your doctor immediately for appropriate treatment.

Some patients receiving combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Numerous risk factors for developing this condition include duration of combination antiretroviral therapy, corticosteroid use, 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 (increased bilirubin levels in the blood) has occurred in patients receiving EVOTAZ. Signs may include a slightly yellowish tint to 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 how your kidneys function.

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

Children

Do not give this medicine to children under 12 years of age or who weigh less than 35 kg, as the use of EVOTAZ has not been studied in this population.

Other medicines and EVOTAZ

You must 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 together or that may require a change in dosing when taken with EVOTAZ. Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicine. It is especially important to mention the use of the following:

• medicines containing ritonavir or cobicistat (booster 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 type of contraception (e.g., condom).
• some medicines used to treat acid-related stomach conditions ("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)
• cyclosporine, tacrolimus, and sirolimus (medicines to reduce the body's immune system activity)
• 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 (administered by injection), buspirone, clorazepate, diazepam, estazolam, flurazepam, and zolpidem (used to treat disorders of the nervous system)
• buprenorphine (used to treat opioid addiction and pain)
• elagolix (used to treat endometriosis pain)
• fostamatinib (used to treat low platelet count in adults)

It is especially important that you tell your doctor if you are taking corticosteroids, including dexamethasone, betamethasone, budesonide, fluticasone, mometasone, prednisone, and triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory eye, joint, and muscle conditions, and other inflammatory disorders. If alternative medicines cannot be used, corticosteroids should only be used after a clinical evaluation and under close medical supervision to monitor for corticosteroid-related adverse effects.

Pregnancy and breastfeeding

EVOTAZ should not be used during pregnancy, as drug levels 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 shown to pass into milk in animals. Patients should not breastfeed while taking EVOTAZ.

Breastfeeding is not recommended for women living with HIV because HIV infection can be transmitted to the baby through breast milk.

If you are breastfeeding or planning to breastfeed, you must consult your doctor as soon as possible.

Driving and using machines

Some patients have reported dizziness during treatment with atazanavir or cobicistat, the active substances in EVOTAZ. If you feel dizzy or lightheaded, do not drive, operate tools, or machinery, and contact your doctor immediately.

3. How to take EVOTAZ

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, 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 daily taken by mouth and with food, in combination with other anti-HIV medicines. The tablets have an unpleasant taste; therefore, swallow the tablet whole. Do not crush or chew the tablets. This will help ensure that you receive the full dose.

If you take more EVOTAZ than you should

If you accidentally take more EVOTAZ than your doctor has prescribed, contact your doctor immediately or go to the nearest hospital for advice.

If you forget to take EVOTAZ

If you miss a dose of EVOTAZ by 12 hours or less, take it immediately with food, and then take your next scheduled dose at the usual time. If you miss a dose and more than 12 hours have passed since you were supposed to take 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 important not to miss any doses of EVOTAZ or of your other anti-HIV medicines.

If you stop taking EVOTAZ

Do not stop treatment with EVOTAZ without first consulting your doctor.

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

4. Possible adverse effects

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

The following adverse effects may occur while taking EVOTAZ

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

• yellowing of the skin or of the white part of the 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 tiredness
• 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
• inflammation of the pancreas, inflammation of the stomach
• allergic reactions including rash, elevated temperature, increased liver enzyme levels in blood tests, increase in a type of white blood cells [eosinophilia] and/or enlarged lymph nodes (see section 2)
• severe swelling of the skin and other tissues, usually lips or eyes
• fainting, high blood pressure
• chest pain, generally 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 your kidneys work)
• gallstones
• muscle cramps, joint pain, muscle pain
• breast enlargement in men
• depression, anxiety, sleep disturbances
• unusual tiredness or weakness
• loss of appetite, weight loss, weight gain
• disorientation, memory loss
• numbness, weakness, tingling or pain in arms and legs
• mouth ulcers and cold sores
• rash, abnormal hair loss or thinning, itching

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

• allergic reactions including severe skin rash, high temperature, and enlarged lymph nodes (Stevens-Johnson syndrome, see section 2)
• fast or irregular heartbeat (prolongation of QTc interval)
• enlargement of the liver and spleen
• inflammation of the gallbladder
• kidney pain
• swelling
• visible fluid accumulation under the skin, skin rash, blood vessel dilation
• 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 in blood glucose and lipid levels. This is partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medicines themselves. Your doctor will monitor 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 help provide more information on the safety of this medicine.

5. Storage of EVOTAZ

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the label and on the carton, following EXP. The expiry date refers to the last day of the month indicated.

Do not store above 30 °C.

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

6. Contents of the container and other information

Composition of EVOTAZ

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

Tablet core – 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 methylcellulose, E464), titanium dioxide (E171), talc (E553b), triacetin (E1518), iron oxide red (E172)

Appearance of the product and contents of the container

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

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

Only certain pack sizes may be marketed in your country.

Date of the most recent review of this leaflet:

Other sources of information

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