REYATAZ 300 mg HARD CAPSULES

2. What you need to know before taking REYATAZ

Do not take REYATAZ

• 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 REYATAZ
• if you are taking any of these medicines:see also Other medicines and REYATAZ
• rifampicin (an antibiotic used to treat tuberculosis)
• astemizole or terfenadine (used to treat allergic symptoms, these medicines may be available without a prescription); cisapride (used to treat gastroesophageal 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 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)
• lomitapide, simvastatin, and lovastatin (used to lower blood cholesterol)
• medicines 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)
• apalutamide (used to treat prostate cancer)

Do not take sildenafil with REYATAZ 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.

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

Warnings and precautions

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

Some people will need special monitoring before or during treatment with REYATAZ. Consult your doctor or pharmacist before starting to take REYATAZ 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 A or B
• if you need to undergo hemodialysis

REYATAZ may affect the way your kidneys work.

There have been reports of kidney stones in patients treated with REYATAZ. 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 shortly 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 immunodepression, and high body mass index. The symptoms of osteonecrosis are 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 REYATAZ. The signs may be a slightly yellowish tone of the skin or eyes. If you notice any of these symptoms, please inform your doctor.

Severe skin rash, including Stevens-Johnson syndrome, has been reported in patients treated with REYATAZ. 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 taking REYATAZ 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 REYATAZ 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 REYATAZ

Do not take REYATAZ with certain medicines.These are listed under the heading "Do not take REYATAZ" at the beginning of Section 2.

There are other medicines that should not be taken with REYATAZ. Inform your doctor if you are taking, have recently taken, or may need to take any other medicine. 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 REYATAZ, to avoid pregnancy, make sure to take it exactly as your doctor has indicated and do not miss any doses
• certain medicines used to treat diseases related to stomach acid (e.g., antacids that should be administered 1 hour before taking REYATAZ or 2 hours after taking REYATAZ, H2 blockers such as famotidine, and proton pump inhibitors such as omeprazol)
• 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, warfarin, clopidogrel, prasugrel, and ticagrelor (used to reduce blood clots)
• carbamazepine, phenytoin, phenobarbital, and lamotrigine (antiepileptics)
• encorafenib, ivosidenib, and irinotecan (used to treat cancer)
• elagolix (gonadotropin-releasing hormone receptor antagonists, used to treat severe endometriosis pain)
• fostamatinib (used to treat chronic immune thrombocytopenia)
• sedative agents (e.g., midazolam administered by injection)
• buprenorphine (used to treat opioid addiction and pain)
• corticosteroids (all routes of administration; including dexamethasone)

Some medicines may interact with ritonavir, a medicine that is administered with REYATAZ. It is important that you inform your doctor if you are using an inhaled or nasal corticosteroid (administered nasally), including fluticasone or budesonide (administered to treat allergic symptoms or asthma).

Taking REYATAZ with food and drinks

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

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Atazanavir, the active ingredient of REYATAZ, is excreted in breast milk. Patients should not breastfeed while taking REYATAZ.

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

If you are breastfeeding or plan to breastfeed, 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.

REYATAZ contains lactose.

If your doctor has told you that you have an intolerance to certain sugars (e.g., lactose), consult with them before taking this medicine.

3. How to take REYATAZ

Follow the instructions for taking this medicine exactly as indicated 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 the treatment.

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

For children (from 6 to less than 18years of age), your doctor will decide the correct dose based on your child's weight.The dose of REYATAZ 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.

REYATAZ is also available as an oral powder for use in children aged at least 3 months and weighing at least 5 kg. It is recommended to switch from REYATAZ oral powder to REYATAZ capsules as soon as patients are able to swallow the capsules properly.

When switching between the oral powder and capsules, a dose change may be necessary. Your doctor will decide the correct dose based on your child's weight.

There are no dosage recommendations for REYATAZ in pediatric patients under 3 months of age.

Take REYATAZ capsules with food(a meal or snack). Swallow the capsules whole. Do not open the capsules.

If you take more REYATAZ than you should

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

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

If you forget to take REYATAZ

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 REYATAZ

Do not stop taking REYATAZ before consulting your doctor.

If you have any other 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 all people suffer from them. During the treatment of HIV infection, it is not always easy to identify the adverse effects caused by REYATAZ, 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 REYATAZ. Severe rash associated with other symptoms that can be severe may develop. Discontinue treatment with REYATAZ and inform your doctor immediately if you develop a severe rash or a rash with symptoms similar to 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 could be a symptom of a serious problem. If your skin or the white part of your eyes turns yellow, inform your doctor immediately.
• Changes in the way your heart beats (changes in heart rhythm) can occasionally 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 REYATAZ 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 color), you have itching, your skin or the white part of your eyes turns yellow, you have pain around the stomach, pale stools, or nausea.
• Bile duct problems can occur infrequently in people taking REYATAZ. Symptoms of bile duct 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.
• REYATAZ may affect the way your kidneys work.
• Kidney stones can occur infrequently in people taking REYATAZ. 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 when urinating.

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

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

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

Infrequent (may affect up to 1 in 100 patients):

• peripheral neuropathy (numbness, weakness, tingling, or pain in the arms and legs)
• hypersensitivity (allergic reaction)
• asthenia (unusual 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 (breathing difficulties)
• pancreatitis (inflammation of the pancreas), gastritis (inflammation of the stomach), stomatitis (mouth ulcers and cold sores), dysgeusia (alteration 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 thinning), 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, malaise (feeling generally unwell), fever
• insomnia (difficulty sleeping)

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

• gait disturbance (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 nurse, even if it is a possible adverse effect that does not appear 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 REYATAZ

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

Do not use this medicine after the expiration date that appears on the label, carton, or blister. The expiration date is the last day of the month indicated.

Do not store above 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 REYATAZ

• The active substance is atazanavir. Each capsule contains 300 mg of atazanavir (as sulfate).
• The other ingredients are crospovidone, lactose monohydrate, and magnesium stearate. The capsule shell and printing ink contain gelatin, shellac, ammonium hydroxide, simethicone, red iron oxide, black iron oxide, yellow iron oxide, propylene glycol, indigo carmine (E132), and titanium dioxide (E171).

Appearance and Package Contents of the Product

Each REYATAZ 300 mg capsule contains 300 mg of atazanavir.

The REYATAZ 300 mg capsule is a opaque red and blue capsule printed with white ink on one half "BMS 300 mg" and on the other "3622".

REYATAZ 300 mg hard capsules are presented in bottles containing 30 capsules. Each carton contains one or three bottles with 30 hard capsules.

REYATAZ 300 mg hard capsules are also presented in blister strips packaged in cartons containing 30 capsules.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

CATALENT ANAGNI S.R.L.

Loc. Fontana del Ceraso snc

Strada Provinciale 12 Casilina, 41

03012 Anagni (FR)

Italy

Swords Laboratories Unlimited Company T/A Bristol-Myers Squibb Pharmaceutical Operations, External Manufacturing

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

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.