Zatonav Film-Coated Tablets

ZATONAV is a combination antiviral (or antiretroviral) medicine, used in combination with other antiretroviral medicines for the treatment of HIV infection. It is one of a group called protease inhibitors. These medicines control Human Immunodeficiency Virus (HIV) infection by blocking HIV protease, an enzyme that the HIV virus 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 ZATONAV reduces the risk of developing illnesses linked to HIV infection. Your doctor has prescribed ZATONAV to you to treat your Human Immunodeficiency Virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Do not take ZATONAV:

• If you are hypersensitive (allergic) to atazanavir, ritonavir or to any of the ingredients of ZATONAV (listed in section 6).
• If you are taking any other medicines containing ritonavir or atazanavir.
• If you have a liver disorder.
• If you are pregnant or breastfeeding your baby.
• If you are elderly (age 65 years or more), as safety and efficacy have not been established.
• If you are currently taking any of the following medicines:

• Amiodarone, encainide, flecainide, propafenone, quinidine, bepridil and digoxin (for treatment of irregular heartbeats and/or heart failure);
• Astemizole (used to treat allergy symptoms);
• Cisapride (used to treat gastric reflux, or heartburn);
• Alfuzosin (for enlarged prostate gland);
• Rifampicin (an antibiotic used to treat/prevent certain infections such as tuberculosis);
• Blonanserin (used to treat schizophrenia – a chronic brain disorder that affects a person’s ability to think, act and behave appropriately);
• Ergotamine, dihydroergotamine, ergovonine, methylergovine (used to treat migraines and headaches);
• Fusidic acid (an antibiotic);
• Lovastatin and simvastatin (used for lowering cholesterol);
• Pimozide and clozapine (used to treat certain mental conditions);
• Irinotecan (for treatment of cancer);
• Indinavir (used in the treatment of HIV infection);
• St John’s Wort (Hypericum perforatum) (a herbal remedy used for depression and anxiety);
• Midazolam taken by mouth or parenterally, triazolam, (used to help you sleep and/or to relieve anxiety);
• Voriconazole (used to treat fungal infections);
• Sildenafil if you suffer from a lung disease called pulmonary arterial hypertension that makes breathing difficult. Patients without this disease may use sildenafil for impotence (erectile dysfunction) under their doctor’s supervision;
• Omeprazole (used to treat acid in the stomach).

If you are taking any of these medicines, tell your doctor immediately. Taking these medicines with ZATONAV could cause serious side effects or stop these medicines from working properly.

Warnings and precautions

Take special care with ZATONAV:

• If you are taking ZATONAV you may still develop infections or other illnesses associated with HIV disease and AIDS. It is therefore important that you remain under the supervision of your doctor while taking ZATONAV.
• If you have or had a history of liver disorders, as patients with a history of liver disease, including chronic hepatitis B or C, are at increased risk of severe and potentially fatal liver side effects. Your doctor will carefully consider the best treatment for you and may conduct blood tests to monitor your liver function.
• If you have haemophilia type A and B, as ZATONAV might increase the risk of bleeding.
• Combination antiretroviral therapy (including ZATONAV) may change your body shape, by changing the way body fat is distributed. You may lose fat from your legs, arms and face; gain fat around the tummy (abdomen) and internal organs; get larger breasts or fatty lumps on the back of the neck (“buffalo hump”).
• If you have or have had diabetes, as increased blood sugars has been reported in patients receiving ZATONAV. If you experience thirst, frequent urination, blurred vision or weight loss, this may indicate raised sugar levels in the blood.
• If you have bone problems, including previous bone breaks (fractures).
• Some patients with HIV taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone. 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, tell your doctor.
• If you experience symptoms of dizziness, light-headedness, fainting or sensation of abnormal heartbeats. ZATONAV may cause changes in your heart rhythm and the electrical activity of your heart. These changes may be seen on an ECG (electrocardiogram).
• If you have advanced HIV infection 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. Common examples of opportunistic infections are tuberculosis (cough that does not go away, weight loss, sweating a lot at night), pneumocystis jiroveci pneumonia (rapid breathing, shortness of breath), atypical mycobacterial infection (progressively severe diarrhoea, stomach pain, nausea and vomiting), cytomegalovirus retinitis (unclear vision, blind spot, specks in your vision) and cryptococcal meningitis (headache, mental changes including confusion, sensitivity to light, nausea, vomiting).
• 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 antiretroviral 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 the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to get the necessary treatment.
• You may develop the following symptoms due to the active ingredient ritonavir: hives, skin eruptions, difficulty breathing, painless swelling under the skin. In rare cases you may develop a serious allergic reaction or a rare, serious disorder of the skin and mucous membranes called Stevens-Johnson syndrome. You may develop the following symptoms due to the active ingredient atazanavir: mild to moderate flat or raised red bumps/eruptions on the skin within the first 3 weeks of therapy. In some cases you may develop: the rare, serious disorder of the skin and mucous membranes called Stevens-Johnson syndrome, a skin disorder characterised by bull's-eye-shaped lesions or toxic skin eruptions which include Drug Rash, Eosinophilia, and Systemic Symptoms (DRESS) syndrome (symptoms included skin rash, fever, enlargement of lymph nodes).
• Some patients taking ZATONAV may develop serious problems with their pancreas (pancreatitis), which, if not treated, could result in death. Tell your doctor as soon as possible if you experience nausea, vomiting, or severe abdominal pain. These may be signs of may be signs of inflammation of the pancreas.
• If you are taking medicines called corticosteroids (medicines used to treat inflammation and allergies including fluticasone) in your nose or inhaled, you may develop a disease called Cushing’s syndrome (when your body has too much of the cortisol hormone in your body).
• If you are taking medicine for the inability to get and keep an erection firm enough for sex or high blood pressure, called sildenafil, tadalafil or vardenafil, please tell your doctor. You may develop low blood pressure or a prolonged erection when used in combination with ZATONAV.
• If you are taking the herbal product called St. John’s Wort, please inform your doctor as it may lower the effect of ZATONAV.
• If you are taking a class of medicines to treat high cholesterol, called statins (such as simvastatin, lovastatin, atorvastatin and rosuvastatin) as your doctor may want to change these medicines.
• Hyperbilirubinemia (an increase in the level of bilirubin in the blood) has occurred in patients receiving ZATONAV. The signs may be a mild yellowing of the skin or eyes. If you notice any of these symptoms please inform your doctor.
• Your doctor will perform blood and urine tests before and during your treatment with ZATONAV to monitor your liver function and blood lipids (fats).
• You may develop gallstones during your treatment with ZATONAV, which may result in hospitalisation and management. Your doctor may temporarily stop or discontinue your treatment.
• Kidney stones have been reported in patients taking ZATONAV. 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.
• If you have any type of kidney disease, please inform your doctor. Your doctor may monitor your kidney function regularly, as you may develop kidney disease.
• Safety and efficacy of ZATONAV in the elderly have not been established.
• ZATONAV will not cure or prevent HIV infection or AIDS, however, it helps keep HIV from reproducing and appears to slow down the destruction of the immune system. ZATONAV will not keep you from spreading HIV to other people.

Do not share medicines prescribed for you with any other person. Always take ZATONAV exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. Adults: The recommended dose of ZATONAV is one tablet once daily taken with food. The ZATONAV tablets should be swallowed whole. Your doctor will tell you how long your treatment with ZATONAV will last. Do not suddenly stop taking ZATONAV without consulting with your doctor first. If you have the impression that the effect of ZATONAV is too strong or too weak, talk to the doctor or pharmacist.

If you take more ZATONAV than you should:

In the event of overdosage, speak to a doctor or pharmacist. If neither is available, contact the nearest hospital or poison control centre for help.

If you forget to take ZATONAV:

If you forget to take a dose of ZATONAV, take it as soon as you remember and then continue as before. Do not take a double dose to make up for missed individual doses.

Effects when treatment with ZATONAV is stopped:

If you have stopped taking ZATONAV for any reason, especially if you think you are having side effects, or for another illness, it is important that you contact your doctor before restarting. In some cases your doctor will ask you to restart ZATONAV under direct medical supervision or where medical care can be easily accessed by yourself or others. If your doctor thinks that there is a possibility your symptoms were related to a hypersensitivity reaction, you may be told not to take ZATONAV or any other medicine containing atazanavir and ritonavir ever again.

ZATONAV can have side effects. Not all side effects reported for ZATONAV are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking ZATONAV, please consult your health care provider for advice. If any of the following happens, stop taking ZATONAV and tell your doctor immediately or go to the casualty department at your nearest hospital:

• A life-threatening allergic reaction referred to as anaphylaxis. Symptoms include, but are not limited to, fast or irregular breathing, puffiness or swelling around the face, shortness of breath, a sudden severe decrease in blood pressure, abdominal pain and cramping, anxiety, confusion, cough, diarrhoea, difficulty in swallowing, fainting, light-headedness, dizziness, hives, itchiness, wheezing and blocked nose.
• Severe skin rash, or
• If you experience any one or more symptoms affecting at least TWO organ systems (e.g. Shortness of breath (respiratory system) and diarrhoea (gastrointestinal system), stop taking ZATONAV and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Respiratory - shortness of breath, sore throat or cough, swelling of the face, tongue or throat and difficulty with breathing.
• Gastrointestinal - nausea or vomiting or diarrhoea or abdominal (stomach) pain.
• Musculoskeletal - severe tiredness or aches and pains or generally feeling ill.

These are all very serious side effects. If you have them, you may have had a serious reaction to ZATONAV. You may need urgent medical attention or hospitalisation. Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• If your heart beats harder (increased intensity), or you experience other disorders such as an increase in your heart rate, an irregular heartbeat or a heart attack.
• Low blood pressure.
• Fever.
• Headache.

These are all serious side effects. You may need urgent medical attention. Tell your doctor if you notice any of the following:

Frequent side effects:

• Headache; dizziness.
• Vomiting; diarrhoea; abdominal pain; nausea; indigestion.
• Yellowing of the skin and white part of the eyes indicating liver inflammation (jaundice).
• Rash; itching.
• Accumulation or loss of body fat (body changes due to fat redistribution).
• Loss of appetite; weight loss.
• Anxiety.
• Numbness, tingling, a burning sensation or weakness of hands and feet.
• Fainting; swelling of feet and lower legs.
• Bad taste in the mouth; loss of taste; prickling sensation around or near the mouth.
• Swelling of the face.
• Widening of the blood vessel.
• Cough or hoarseness.
• Mouth ulcers, dry mouth; sore throat.
• Inflammation of the pancreas; inflammation of the stomach; enlarged abdomen (excessive amount of air or gas in the stomach); bloated feeling.
• Eczema and stevens-johnson syndrome: an extremely severe skin reaction with ulcers or blisters on the skin; acne; dry skin and other skin disorders; inflammation of the hair follicles; severe tiredness; chest pain; feeling of bodily discomfort (malaise) and weakness; fever or chills.

Less frequent side effects:

• Weight gain; increased appetite; excess of watery fluid collecting in the tissues of the body.
• Depression; disorientation; sleep disorders; confusion.
• Abnormal dreams; forgetfulness; feeling nervous; emotional instability.
• Exaggerated feeling of physical and mental well-being; seeing or hearing things that are not there.
• Abnormal thinking; sleepiness.
• Enlargement of the liver and spleen; formation of gallstones; stop of the flow of bile; inflammation of the gallbladder.
• Hair loss (alopecia).
• Anaemia (a low red blood cell count), that can leave you feeling tired and lethargic; blood under the skin.
• A rash of round, red weals on the skin which itch intensely.
• Increased sensitivity of the skin to sunlight; psoriasis; dandruff.
• Kidney pain and other kidney disorders; blood in the urine; protein in the urine; frequent passing of urine; difficulty in passing urine; kidney stones.
• Kidney failure; passing excessive urine at night.
• Acute kidney disorders as well as failure.
• Impotence; breast enlargement in men; penis disorder; decreased sexual drive.
• Disease of the lymph nodes; dehydration.
• Diabetes (body cannot remove sugar from the blood normally).
• Deficiency of vitamins in the diet; general ill health and malnutrition.
• Swelling of feet and lower legs.
• Feeling agitated, personality disorder.
• Breathing difficulties; lung disorders.
• An abnormal sensation such as prickling or burning; increased sensitivity or abnormal feeling to touch; abnormal sensation in arms or legs.
• Seizure (fits); speech disorder; incoordination; nerve pain.
• Disturbance of nervous system; paralysis; abnormal sense of smell.
• Trembling; bleeding.
• Abnormal vision; blurred vision; double vision; eye pain; inflammation of parts of the eye and the eyelid; abnormal intolerance of light.
• Hearing disorder; increased wax in the ear; ringing in the ears, sensation of movement.
• Severe tummy pain (possible inflammation of your pancreas).
• Runny nose; bleeding nose; hiccup; sweating.
• Breakdown of muscle tissue and muscle disorders.
• Back pain; joint disorders; neck pain or stiffness; twitching.
• Muscle pain, cramps or weakness.
• Abnormal laboratory test results (this will be discussed with you by your doctor).

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of ZATONAV.

Store all medicines out of reach of children. Store at or below 30 ºC. Store the tablets in the original container. Do not remove from the carton until required for use. Keep the bottle tightly closed. Do not store in bathrooms. Do not use after the expiry date stated on the label. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).