Atazanavir Krka - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Atazanavir Krka 150 mg hard capsules

Atazanavir Krka 200 mg hard capsules

Atazanavir Krka 300 mg hard capsules atazanavir

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Atazanavir Krka is and what it is used for

• 2. What you need to know before you take Atazanavir Krka

• 3. How to take Atazanavir Krka

• 4. Possible side effects

• 5. How to store Atazanavir Krka

• 6. Contents of the pack and other information

1. What Atazanavir Krka is and what it is used for

Atazanavir Krka is an antiviral (or antiretroviral) medicine. It is one of a group called protease inhibitors. These medicines control Human Immunodeficiency Virus (HIV) infection by stopping a protein that the HIV needs for its multiplication. They work by reducing the amount of HIV in your body and this in turn, strengthens your immune system. In this way Atazanavir Krka reduces the risk of developing illnesses linked to HIV infection.

Atazanavir Krka capsules may be used by adults and children 6 years of age and older. Your doctor has prescribed Atazanavir Krka for you because you are infected by the HIV that causes Acquired Immunodeficiency Syndrome (AIDS). It is normally used in combination with other anti-HIV medicines. Your doctor will discuss with you which combination of these medicines with Atazanavir Krka is best for you.

2. What you need to know before you take Atazanavir Krka

Do not take Atazanavir Krka

• – if you are allergic to atazanavir or any of the other ingredients of this medicine (listed in

• section 6).

• - if you have moderate to severe liver problems. Your doctor will evaluate how severe

yourliver disease is before deciding whether you can take Atazanavir Krka

• - if you are taking any of these medicines : see also Other medicines and Atazanavir Krka

• – rifampicin (an antibiotic used to treat tuberculosis)

• – astemizole or terfenadine (commonly used to treat allergy symptoms, these medicines may be available without prescription); cisapride (used to treat gastric reflux, sometimes called heartburn); pimozide (used to treat schizophrenia); quinidine or bepridil (used to correct heart rhythm); ergotamine, dihydroergotamine, ergonovine, methylergonovine (used to treat headaches); and alfuzosin (used to treat enlarged prostatic 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 preparation)

• – triazolam and oral (taken by mouth) midazolam (used to help you sleep and/or to relieve anxiety)

• – lomitapide, simvastatin and lovastatin (used to lower blood cholesterol).

• – grazoprevir-containing products, including elbasvir/grazo­previr fixed dose combination

and glecaprevir/pi­brentasvir fixed dose combination (used to treat chronic hepatitis C infection)

Do not take sildenafil with Atazanavir Krka when sildenafil is used for the treatment of pulmonary arterial hypertension. Sildenafil is also used for the treatment of erectile dysfunction. Tell your doctor if you are using sildenafil for the treatment of erectile dysfunction.

Tell your doctor at once if any of these apply to you.

Warnings and precautions

Atazanavir Krka is not a cure for HIV infection. You may continue to develop infections or other illnesses linked to HIV infection. You can still pass on HIV when taking this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your doctor the precautions needed to avoid infecting other people.

Some people will need special care before or while taking Atazanavir Krka. Talk to your doctor or pharmacist before taking Atazanavir Krka and make sure your doctor knows:

• – if you have hepatitis B or C

• – if you develop signs or symptoms of gall stones (pain at the right side of your stomach)

• – if you have type A or B haemophilia

• – if you require haemodialysis

Atazanavir Krka may affect how well your kidneys work.

Kidney stones have been reported in patients taking atazanavir. If you develop signs or symptoms of kidney stones (pain in your side, blood in your urine, pain when you urinate), please inform your doctor immediately.

In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of infection, please inform your doctor immediately. In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness beginning in hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment.

Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

Hyperbilirubinaemia (an increase in the level of bilirubin in the blood) has occurred in patients receiving atazanavir. The signs may be a mild yellowing of the skin or eyes. If you notice any of these symptoms please inform your doctor.

Serious skin rash, including Stevens-Johnson syndrome, has been reported in patients taking atazanavir. If you develop a rash inform your doctor immediately.

If you notice a change in the way your heart beats (heart rhythm changes), please inform your doctor. Children receiving Atazanavir Krka may require their heart to be monitored. Your child's doctor will decide this.

Children

Do not give this medicine to children younger than 3 months of age and weighing less than 5 kg. The use of Atazanavir Krka in children less than 3 months of age and weighing less than 5 kg has not been studied due to the risk of serious complications.

Other medicines and Atazanavir Krka

You must not take Atazanavir Krka with certain medicines. These are listed under Do not take Atazanavir Krka, at the start of Section 2.

There are other medicines that may not mix with Atazanavir Krka. Tell your doctor if you are taking, have recently taken, or might take any other medicines. It is especially important to mention these:

• – other medicines to treat HIV infection (e.g. indinavir, nevirapine and efavirenz)

• – Sofosbuvir/vel­patasvir/voxi­laprevir (used to treat hepatitis C)

• – sildenafil, vardenafil, or tadalafil (used by men to treat impotence (erectile dysfunction))

• – if you are taking an oral contraceptive ("the Pill ") with Atazanavir Krka to prevent pregnancy,

be sure to take it exactly as instructed by your doctor and not miss any doses

• – any medicines used to treat diseases related to the acid in the stomach (e.g. antacids to be taken 1 hour before taking Atazanavir Krka or 2 hours after taking Atazanavir Krka, H2-blockers like famotidine and proton pump inhibitors like omeprazole)

• – medicines to lower blood pressure, to slow heart rate, or to correct heart rhythm (amiodarone, diltiazem, systemic lidocaine, verapamil)

• – atorvastatin, pravastatin, and fluvastatin (used to lower blood cholesterol)

• – salmeterol (used to treat asthma)

• – cyclosporin, tacrolimus, and sirolimus (medicines to decrease the effects of body's immune system)

• – certain antibiotics (rifabutin, clarithromycin)

• – ketoconazole, itraconazole, and voriconazole (antifungals)

• – apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin (anticoagulants, used to reduce the blood clots)

• – carbamazepine, phenytoin, phenobarbital, lamotrigine (antiepileptics)

• – irinotecan (used to treat cancer)

• – sedative agents (e.g. midazolam administered by injection)

• – buprenorphine (used to treat opioid addiction and pain).

Some medicines may interact with ritonavir, a medicine that is taken with Atazanavir Krka. It is important to tell your doctor if you are taking fluticasone or budesonide (given by nose or inhaled to treat allergic symptoms or asthma).

Atazanavir Krka with food and drink

It is important that you take Atazanavir Krka with food (a meal or a substantial snack) as this helps the body absorb the medicine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think that you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Atazanavir, the active substance of Atazanavir Krka, is excreted in human milk. Patients should not breast-feed while taking Atazanavir Krka. It is recommended that women infected with HIV do not breast-feed because the virus might be transmitted through the breast milk.

Driving and using machines

If you feel dizzy or lightheaded, do not drive or use machines and contact your doctor immediately.

Atazanavir Krka contains lactose monohydrate

If you have been told by your doctor that you have an intolerance to some sugars (e.g. lactose), contact your doctor before taking this medicinal product.

3. How to take Atazanavir Krka

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure. This way, you can be sure your medicine is fully effective and you reduce the risk of the virus developing resistance to the treatment.

The recommended adult dose of Atazanavir Krka capsules is 300 mg once daily with 100 mg ritonavir once daily and with food , in combination with other anti-HIV medicines. Your doctor may adjust the dose of Atazanavir Krka according to your anti-HIV therapy.

For children (6 to less than 18 years of age), your child's doctor will decide the right dose based on your child's weight. The dose of Atazanavir Krka capsules for children is calculated by body weight and is taken once daily with food and 100 mg ritonavir as shown below:

Body weight (kg)	Atazanavir Krka Dose once daily (mg)	Ritonavir Dose* once daily (mg)
15 to less than 35	200	100
At least 35	300	100

*Ritonavir capsules, tablets or oral solution may be used.

Other formulations of this medicine may be available for paediatric patients at least 3 months of age and weighing at least 5 kg (see relevant Summary of Product Characteristics for alternative forms). Switching to capsules from other formulations is encouraged as soon as patients are able to consistently swallow capsules.

Take Atazanavir Krka capsules with food (a meal or a substantial snack). Swallow the capsules whole.

Do not open the capsules.

If you take more Atazanavir Krka than you should

Yellowing of the skin and/or eyes (jaundice) and irregular heart beat (QTc prolongation) may occur if you or your child take too much Atazanavir Krka.

If you accidentally take more Atazanavir Krka capsules than your doctor recommended, contact your HIV doctor at once or contact the nearest hospital for advice.

If you forget to take Atazanavir Krka

If you miss a dose, take the missed dose as soon as possible with food and then take your next scheduled dose at its regular time. If it is almost time for your next dose, do not take the missed dose. Wait and take the next dose at its regular time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Atazanavir Krka

Do not stop taking Atazanavir Krka before talking to your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. When treating HIV infection, it is not always easy to identify what side effects are caused by Atazanavir Krka, by the other medicines you are taking, or by the HIV infection itself. Tell your doctor if you notice anything unusual about your health.

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes.

Tell your doctor immediately if you develop any of the following serious side effects:

• – Skin rash, itching that may occasionally be severe has been reported. The rash usually disappears within 2 weeks without any change to your atazanavir treatment. Severe rash may be developed in association with other symptoms which could be serious. Stop taking Atazanavir Krka and talk to your doctor immediately if you develop a severe rash or a rash with flu-like illness symptoms, blisters, fever, mouth sores, muscle or joint pain, swelling in the face, inflammation of the eye which causes redness (conjunctivitis), painful, warm, or red lumps (nodules).

• – Yellowing of your skin or the white part of your eyes caused by high levels of bilirrubin in your blood has been commonly reported. This side effect is usually not dangerous in adults and infants older than 3 months of age; but it might be a symptom of a serious problem. If your skin or the white part of your eyes turns yellow, talk to your doctor immediately.

• – Changes in the way your heart beats (heart rhythm change) may occasionally happen. Talk to your doctor immediately if you get dizzy, lightheaded or if you suddenly faint. These could be symptoms of a serious heart problem.

• – Liver problems may uncommonly happen. Your doctor should do blood tests prior you start Atazanavir Krka and during treatment. If you have liver problems, including hepatitis B or C infection, you may experience a worsening of your liver problems. Talk to your doctor immediately if you get dark (tea-colored) urine, itching, yellowing of your skin or the white part of your eyes, pain around the stomach, pale colored stools or nausea.

• – Gallbladder problems uncommonly happen in people taking atazanavir. Symptoms of gallbladder problems may include pain in the right or middle upper stomach area, nausea, vomiting, fever or yellowing your skin or the white part of your eyes.

• – Atazanavir Krka may affect how well your kidneys work.

• – Kidney stones uncommonly happen in people taking atazanavir. Talk to your doctor immediately if you get symptoms of kidney stones which may include, pain in your low back or low stomach-area, blood in your urine or pain when you urinate.

Other side effects reported for patients treated with atazanavir are the following: Common (may affect up to 1 in 10 people):

• – headache

• – vomiting, diarrhoea, abdominal pain (stomach pain of discomfort), nausea, dyspepsia (indigestion)

• – fatigue (extreme tiredness)

Uncommon (may affect up to 1 in 100 people):

• – peripheral neuropathy (numbness, weakness, tingling or pain in the arms and legs)

• – hypersensitivity (allergic reaction)

• – asthenia (unusual tiredness or weakness)

• – weight decreased, weight gain, anorexia (loss of appetite), appetite increased

• – depression, anxiety, sleep disorder

• – disorientation, amnesia (loss of memory), dizziness, somnolence (sleepiness), abnormal dream – syncope (fainting), hypertension (high blood pressure)

• – dyspnoea (shortness of breath)

• – pancreatitis (inflammation of the pancreas), gastritis (inflammation of the stomach), stomatitis, aphthous (mouth ulcers and cold sores), dysgeusia (impairment of the sense of taste), flatulence (wind), dry mouth, abdominal distension

• – angioedema (severe swelling of the skin and other tissues most often the lips or the eyes)

• – alopecia (unusual hair loss or thinning), pruritus (itching)

• – muscle atrophy (muscle shrinkage), arthralgia (joint pain), myalgia (aching muscles)

• – interstitial nephritis (kidney inflammation), haematuria (blood in the urine), proteinuria (excess protein in the urine), pollakiuria (increased frequency of urination)

• – gynaecomastia (breast enlargement in men)

• – chest pain, malaise (generally feeling unwell), fever

• – insomnia (difficulty sleeping)

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

• – gait disturbance (abnormal manner of walking)

• – oedema (swelling)

• – hepatosplenomegaly (enlargement of the liver and spleen)

• – myopathy (aching muscles, muscle tenderness of weakness, not caused by exercise)

• – kidney pain

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Atazanavir Krka

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 packaging after EXP. The expiry date refers to the last day of that month.

Store below 30°C.

Keep the container tightly closed in order to protect from moisture.

Shelf life after first opening is 2 months, stored below 25°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Atazanavir Krka contains

• – The active substance is atazanavir.

Atazanavir Krka 150 mg hard capsules

Each hard capsule contains 150 mg atazanavir (as sulphate).

Atazanavir Krka 200 mg hard capsules

Each hard capsule contains 200 mg atazanavir (as sulphate).

Atazanavir Krka 300 mg hard capsules

Each hard capsule contains 300 mg atazanavir (as sulphate).

• – The other ingredients are:

What Atazanavir Krka looks like and contents of the pack

Atazanavir Krka 150 mg hard capsules

Hard gelatine capsule (capsule), size no. 1. The body of the capsule is white or almost white colour, the cap of the capsule is brownish-orange colour. The capsule cap is imprinted with black mark A150. The content of the capsule is yellowish-white to yellow-white powder.

Atazanavir Krka 200 mg hard capsules

Hard gelatine capsule (capsule), size no. 0. The body and the cap of the capsule are brownish-orange colour. The capsule cap is imprinted with black mark A200. The content of the capsule is yellowish-white to yellow-white powder.

Atazanavir Krka 300 mg hard capsules

Hard gelatine capsule (capsule), size no. 00. The body of the capsule is white or almost white colour, the cap of the capsule is dark brown colour. The capsule cap is imprinted with white mark A300. The content of the capsule is yellowish-white to yellow-white powder.

Atazanavir Krka 150 mg and 200 mg hard capsules are available in containers containing 60 hard capsules; in a box.

Atazanavir Krka 300 mg hard capsules are available in containers containing 30 hard capsules or 90 (3 × 30) hard capsules; in a box.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

KRKA, d.d., Novo mesto, Smarjeska cesta 6, 8501 Novo mesto, Slovenia

Manufacturers

KRKA, d.d., Novo mesto, Smarjeska cesta 6, 8501 Novo mesto, Slovenia

TAD Pharma GmbH, Heinz-Lohmann-StraBe 5, 27472 Cuxhaven, Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien KRKA Belgium, SA. Tél/Tel: + 32 (0) 487 50 73 62 Et^rapuH KPKA Btnrapua EOOfl Ten.: + 359 (02) 962 34 50 Česká republika KRKA ČR, s.r.o. Tel: + 420 (0) 221 115 150 Danmark KRKA Sverige AB Tlf: + 46 (0)8 643 67 66 (SE)

Lietuva UAB KRKA Lietuva Tel: + 370 5 236 27 40 Luxembourg/Lu­xemburg KRKA Belgium, SA. Tél/Tel: + 32 (0) 487 50 73 62 (BE) Magyarország KRKA Magyarország Kereskedelmi Kft. Tel.: + 36 (1) 355 8490 Malta E. J. Busuttil Ltd. Tel: + 356 21 445 885

Deutschland TAD Pharma GmbH Tel: + 49 (0) 4721 606–0	Nederland KRKA Belgium, SA. Tel: + 32 (0) 487 50 73 62 (BE)
Eesti KRKA, d.d., Novo mesto Eesti filiaal Tel: + 372 (0) 6 671 658	Norge KRKA Sverige AB Tlf: + 46 (0)8 643 67 66 (SE)
Ekkáóa KRKA EAAAS EnE Tni: + 30 2100101613	Österreich KRKA Pharma GmbH, Wien Tel: + 43 (0)1 66 24 300
España KRKA Farmacéutica, S.L. Tel: + 34 911 61 03 80	Polska KRKA-POLSKA Sp. z o.o. Tel.: + 48 (0)22 573 7500
France KRKA France Eurl Tél: + 33 (0)1 57 40 82 25	Portugal KRKA Farmacêutica, Sociedade Unipessoal Lda. Tel: + 351 (0)21 46 43 650
Hrvatska KRKA – FARMA d.o.o. Tel: + 385 1 6312 100	România KRKA Romania S.R.L., Bucharest Tel: + 4 021 310 66 05
Ireland KRKA Pharma Dublin, Ltd. Tel: + 353 1 413 3710	Slovenija KRKA, d.d., Novo mesto Tel: + 386 (0) 1 47 51 100
Ísland LYFIS ehf. Sími: + 354 534 3500	Slovenská republika KRKA Slovensko, s.r.o. Tel: + 421 (0) 2 571 04 501
Italia KRKA Farmaceutici Milano S.r.l. Tel: + 39 02 3300 8841	Suomi/Finland KRKA Finland Oy Puh/Tel: + 358 20 754 5330
Kúnpog KI.PA. (PHARMACAL) LIMITED Tni: + 357 24 651 882	Sverige KRKA Sverige AB Tel: + 46 (0)8 643 67 66 (SE)
Latvija KRKA Latvija SIA Tel: + 371 6 733 86 10	United Kingdom (Northern Ireland) Consilient Health Limited Tel: + 353 (0)1 2057760

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

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