ATAZANAVIR KRKA 300 mg HARD CAPSULES

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

Do not take Atazanavir Krka

• if you are allergicto 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 assess the severity of your liver disease before deciding if 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 (used frequently 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); quinidine or bepridil (used to correct heart rhythm); ergotamine, dihydroergotamine, ergonovine, 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 in the treatment of schizophrenia)
• medicines that contain St. John's Wort (Hypericum perforatum, a medicinal plant)
• triazolam and midazolam oral (given by mouth) (used to induce sleep and/or relieve anxiety)
• lomitapide, simvastatin, and lovastatin (used to lower blood cholesterol)
• medicines that contain 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 Atazanavir Krka 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

Atazanavir Krka is not a cure for HIV infection.You may continue to develop infections or other illnesses associated with HIV infection.

Some people will need special monitoring before or during treatment with Atazanavir Krka. Consult your doctor or pharmacist before starting Atazanavir Krka and make sure to inform your doctor:

• if you have hepatitis B or C
• if you develop signs or symptoms of gallstones (pain in the right side of your stomach)
• if you have hemophilia type A or B
• if you need to undergo hemodialysis

Atazanavir Krka may affect how your kidneys work.

There have been reports of kidney stones in patients treated with atazanavir. If you experience signs or symptoms of kidney stones (side pain, blood in the urine, pain when urinating), please inform your doctor immediately.

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 infections that were present without 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 start 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 to 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 (elevated bilirubin levels in the blood) has occurred in patients receiving atazanavir. The signs may be a slightly yellowish tint to the skin or eyes. If you notice any of these symptoms, please inform your doctor.

Severe skin rash, including Stevens-Johnson syndrome, has been observed in patients treated with atazanavir. Inform your doctor immediately if you develop a rash.

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

Children

Do not give this medicine to childrenunder 3 months of age and weighing less than 5 kg.

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

Other medicines and Atazanavir Krka

Do not take Atazanavir Krka with certain medicines.These are listed under the heading Do not take Atazanavir Krka, at the beginning of Section 2.

There are other medicines that should not be taken with Atazanavir Krka. Inform your doctor 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:

• other medicines for the treatment of 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, make sure to take it exactly as your doctor has told you and do not miss any dose
• certain medicines used to treat diseases related to stomach acid (e.g., antacids that should be administered 1 hour before taking Atazanavir Krka or 2 hours after taking Atazanavir Krka, H2 blockers such as famotidine, and proton pump inhibitors such as omeprazole)

• medicines to lower blood pressure, slow heart rate, or correct heart rhythm (amiodarone, diltiazem, systemic lidocaine, verapamil)
• atorvastatin, pravastatin, and fluvastatin (used to lower blood cholesterol)
• salmeterol (used to treat asthma)
• cyclosporine, tacrolimus, and sirolimus (medicines to reduce the effects of the body's immune system)
• certain antibiotics (rifabutin, clarithromycin)
• ketoconazole, itraconazole, and voriconazole (antifungals)
• apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin (anticoagulants, used to reduce blood clots)
• warfarin (anticoagulant, used to reduce 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 given with Atazanavir Krka. It is important that you inform your doctor if you are using fluticasone or budesonide (administered by nasal or inhalation route, for the treatment of allergic symptoms or asthma).

Taking Atazanavir Krka with food and drinks

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

Pregnancy and breastfeeding

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

Atazanavir Krka, the active substance of atazanavir, is excreted in breast milk. Patients must not breastfeed while taking Atazanavir Krka.

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

If you are breastfeeding or thinking of breastfeeding, you must consultyour doctor as soon as possible.

Driving and using machines

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

Atazanavir Krka contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Atazanavir Krka

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

The recommended dose of Atazanavir Krka capsules for adults is 300 mg together with 100 mg of ritonavir once a day and with food,in combination with other anti-HIV medicines. Your doctor may adjust the dose of Atazanavir Krka according to your anti-HIV treatment.

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

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

This medicine is available in other formulations for children from at least 3 months of age and at least 5 kg of weight (see Summary of Product Characteristics for alternative forms). It is recommended to switch from other formulations to capsules as soon as patients are able to swallow the capsules properly.

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

Do not open the capsules.

If you take more Atazanavir Krka than you should

If you or your child take too much Atazanavir Krka, the skin and/or eyes may turn yellow (jaundice) and irregular heartbeats (prolonged QTc) may occur.

If you or your child have accidentally taken more Atazanavir Krka capsules than your doctor recommended, contact your doctor immediately or go to the nearest hospital for consultation.

If you forget to take Atazanavir Krka

If you have missed a dose, take it as soon as possible with some food and then take the next scheduled dose at the usual time. If it is almost time for the next dose, do not take the missed dose. Wait and take the next dose at the usual time. Do not take a double dose to make up for missed doses.

If you stop taking Atazanavir Krka

Do not stop taking Atazanavir Krka before 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. During the treatment of HIV infection, it is not always easy to identify the adverse effects caused by Atazanavir Krka, by any other medicine you are taking, or by the HIV infection itself. Inform your doctor of any change you notice in your state of health.

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

Inform your doctor immediately if you develop any of the following serious adverse effects:

• Skin rash, itching that can occasionally be severe has been reported. The rash usually disappears within 2 weeks without changing your treatment with atazanavir. Severe rash associated with other symptoms that can be serious may develop. Discontinue treatment with Atazanavir Krka and inform your doctor immediately if you develop a severe rash or a rash with symptoms similar to the flu, blisters, fever, mouth sores, muscle or joint pain, swelling in the face, eye inflammation that causes redness (conjunctivitis), painful, hot, or red lumps (nodules).
• Yellowing of the skin or the white part of the eyes caused by high bilirubin levels in the blood has been frequently reported. This adverse effect is usually not dangerous in adults and children over 3 months of age; but it can be a symptom of a serious problem. If your skin or the white part of your eyes turns yellow, inform your doctor immediately.
• Occasionally, changes in the way your heart beats (changes in heart rhythm) can occur. Inform your doctor immediately if you feel dizzy, faint, or if you suddenly faint. These can be symptoms of a serious heart problem.
• Liver problems can occur infrequently. Your doctor must perform blood tests before starting treatment with Atazanavir Krka and during treatment.
• • If you have liver problems, including hepatitis B or C infection, you may experience worsening of your liver problems. Inform your doctor immediately if your urine turns dark (tea-colored), you have itching, your skin or the white part of your eyes turns yellow, you have pain around the stomach, pale stools, or nausea.

• Infrequently, problems in the gallbladder can occur in people taking Atazanavir Krka. Symptoms of gallbladder problems may include pain in the right or upper middle part of the stomach, nausea, vomiting, fever, or yellowing of the skin or the white part of the eyes.
• Atazanavir Krka may affect the way your kidneys function.
• Infrequently, kidney stones can occur in people taking atazanavir. Inform your doctor immediately if you have symptoms of kidney stones, which may include pain in the lower back or lower stomach, blood in the urine, or pain while urinating.

Other adverse effects reported in patients treated with atazanavir are the following:

Frequent (may affect up to 1 in 10 people):

• headache
• vomiting, diarrhea, abdominal pain (stomach discomfort), nausea, dyspepsia (indigestion)
• fatigue (extreme tiredness)

• Infrequent (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 or excessive tiredness or weakness)
• weight loss, weight gain, anorexia (loss of appetite), increased appetite
• depression, anxiety, sleep disturbance
• disorientation, amnesia (memory loss), dizziness, somnolence (drowsiness), abnormal dreams
• syncope (fainting), hypertension (high blood pressure)
• dyspnea (difficulty breathing)
• pancreatitis (inflammation of the pancreas), gastritis (inflammation of the stomach), aphthous stomatitis (mouth ulcers and cold sores), dysgeusia (altered sense of taste), flatulence (gas), dry mouth, abdominal distension
• angioedema (severe swelling of the skin and other tissues, usually the lips or eyes)
• alopecia (abnormal hair loss or weakening), pruritus (itching)
• muscle atrophy (muscle contraction), arthralgia (joint pain), myalgia (muscle pain)
• interstitial nephritis (inflammation of the kidney), hematuria (blood in the urine), proteinuria (excess protein in the urine), polyuria (increased frequency of urination)
• gynecomastia (breast enlargement in men)
• chest pain, discomfort (feeling unwell), fever
• insomnia (difficulty sleeping)

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

• altered gait (abnormal walking)
• edema (swelling)
• hepatosplenomegaly (enlargement of the liver and spleen)
• myopathy (muscle pain, muscle weakness, loss of muscle tone not caused by exercise)
• kidney pain

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 that is 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 Atazanavir Krka

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

Do not use this medicine after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Store below 30°C.

Keep the container tightly closed to protect it from moisture.

Shelf life after opening: 2 months, stored below 25°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 Atazanavir Krka

• The active ingredient is atazanavir

Atazanavir Krka 150 mg hard capsules EFG

Each hard capsule contains 150 mg of atazanavir (as sulfate).

Atazanavir Krka 200 mg hard capsules EFG

Each hard capsule contains 200 mg of atazanavir (as sulfate).

Atazanavir Krka 300 mg hard capsules EFG

Each hard capsule contains 300 mg of atazanavir (as sulfate).

• The other ingredients are:

Capsule content: lactose monohydrate, crospovidone (type A), magnesium stearate. See section 2 "Atazanavir Krka contains lactose monohydrate".

Atazanavir Krka 150 mg hard capsules EFG:

Body:titanium dioxide (E171) and gelatin.

Cap:titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), gelatin, and ink (gum lac, black iron oxide (E172), potassium hydroxide).

Atazanavir Krka 200 mg hard capsules EFG:

Body: titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and gelatin.

Cap:titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), gelatin, and ink (gum lac, black iron oxide (E172), potassium hydroxide).

Atazanavir Krka 300 mg hard capsules EFG:

Body:titanium dioxide (E171) and gelatin.

Cap: titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172), gelatin, and ink (gum lac, titanium dioxide (E171), and potassium hydroxide).

Appearance of the Product and Package Contents

Atazanavir Krka 150 mg hard capsules EFG

Hard gelatin capsule (capsule), size 1. The body of the capsule is white or almost white, and the cap is brown-orange. The cap of the capsule is printed with a black mark A150. The content of the capsule is a white-yellowish to yellowish-white powder.

Atazanavir Krka 200 mg hard capsules EFG

Hard gelatin capsule (capsule), size 0. The body and cap of the capsule are brown-orange. The cap of the capsule is printed with a black mark A200. The content of the capsule is a white-yellowish to yellowish-white powder.

Atazanavir Krka 300 mg hard capsules EFG

Hard gelatin capsule (capsule), size 00. The body of the capsule is white or almost white, and the cap of the capsule is dark brown. The cap of the capsule is printed with a white mark A300. The content of the capsule is a white-yellowish to yellowish-white powder.

Atazanavir Krka 150 mg and 200 mg hard capsules are available in packs of 60 hard capsules per box.

Atazanavir Krka 300 mg hard capsules are available in packs of 30 hard capsules or 90 (3x30) hard capsules per box.

Not all pack sizes may be marketed.

Marketing Authorization Holder

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

Manufacturer

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

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

You can obtain more information about this medicine by contacting the local representative of the marketing authorization holder.

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/.