Ranega Film-Coated Tablets

Each film - coated tablet contains the active substances: Lamivudine Tenofovir disoproxil fumarate Dolutegravir sodium equivalent to dolutegravir RANEGA belongs to a group of medicines, known as antiretrovirals. Combination antiretroviral medicines, such as RANEGA, are used in the treatment of HIV - 1 (human immunodeficiency virus - 1) infection in adults aged 18 years and older.

RANEGA does not cure or prevent HIV infection, however, it helps to keep HIV from reproducing and appears to slow down the destruction of the immune system. RANEGA will not keep you from spreading HIV to other people. Appropriate precautions must continue to be used.

Do not take RANEGA:

• If you are hypersensitive (allergic) to tenofovir disoproxil fumarate, lamivudine, dolutegravir or any of the other ingredients in RANEGA tablets.
• If you have or had kidney problems
• If you are a woman of child - bearing age and not using effective contraceptives.
• If you are pregnant or planning to become pregnant or breastfeeding.
• If you are taking any other tenofovir - containing or other lamivudine - containing, or emtricitabine - containing, or dolutegravir containing medicines.
• If you are taking a medicine called adefovir dipivoxil (used for the treatment of chronic hepatitis B).
• If you are taking a medicine called dofetilide and pilsicainide (used for the treatment of abnormal heartbeat – cardiac dysrhythmias).
• If you are taking a medicine called didanosine (used for the treatment of HIV infection).
• If you are younger than 18 years of age.
• If you have moderate to severe liver failure.

Warnings and precautions:

Safety and efficacy of the individual active ingredients in various antiretroviral combination regimens with similar dosages as contained in RANEGA have been established in clinical studies for the treatment of HIV patients. However, safety and efficacy of the fixed drug combination as in RANEGA for the treatment of HIV have not been established in clinical studies.

RANEGA will not keep you from spreading HIV to other people. Appropriate precautions must continue to be used:

• If you are a female, overweight or have been taking nucleoside - containing medicines for a long time, as you are more likely to get lactic acidosis (build - up of lactic acid in the body) (see information about lactic acidosis under 4. Possible side effects).
• High cholesterol: If you have been told you have high cholesterol (certain bad fats that are too high in the blood), you could be at risk of getting heart disease or having a heart attack.
• Increase blood sugar levels: RANEGA may contribute to your sugar levels increasing, this may also cause insulin resistance where the insulin levels in your pancreas have a poor response to insulin.
• Increased blood lactate levels: high blood lactate levels in combination with lactic acidosis may be caused by an imbalance of oxygen that is being delivered to the tissues in your body.
• Kidney problems. Before starting treatment, your doctor may order blood tests to assess your kidney function and may advise you to take RANEGA tablets less often. Do not reduce the prescribed dose unless your doctor has told you to do so. Your doctor may also order blood tests during treatment to monitor how your kidneys work.
• Bone problems. Some people taking combination medicines for HIV develop a condition called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone).

Do not share medicines prescribed for you with any other person. Treatment should be prescribed and initiated by a doctor experienced in the management of HIV infection. Always take RANEGA exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure.

The usual dose of RANEGA is one tablet once a day. RANEGA must be taken without regard of food. You can only take RANEGA if you are older than 18 years. Your doctor will tell you how long your treatment with RANEGA will last.

If you take more RANEGA than you should: In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre.

If you forget to take RANEGA: If you forget to take a dose of RANEGA, take it as soon as you remember unless it is nearly time for your next dose and then continue as before. Do not take a double dose to make up for missed individual doses.

If you stop taking RANEGA: Do not suddenly stop taking RANEGA without consulting with your doctor first. If you have stopped taking RANEGA 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. You should not stop treatment unless your doctor instructs you to. When your RANEGA supply starts to run low, get more from your healthcare provider or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to the ingredients in RANEGA and become harder to treat. If you have the impression that the effect of RANEGA is too strong or too weak, talk to your doctor or pharmacist.

RANEGA can have side effects. Not all side effects reported for RANEGA are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking RANEGA, please consult your health care provider for advice.

If any of the following happens, stop taking RANEGA and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Sudden swelling of hands, face, lips, mouth, tongue and throat or mucous membranes with difficulty breathing and/or itching and rash. These are all very serious side effects. If you have them, you may have had a serious allergic reaction to RANEGA.
• Serious liver problems (hepatitis) with liver enlargement (hepatomegaly) and fat in the liver (steatosis). The following are signs of the liver problems:

• Yellow discolouration of the skin and the white part of your eyeballs
• Darkening of your urine
• Your bowel movements turn lighter in colour
• You feel sick to your stomach (nausea)
• You have stomach pain

You may need urgent medical attention or hospitalisation.

LACTIC ACIDOSIS:

Some people who have taken medicines like RANEGA (nucleoside analogues) have developed a serious condition called lactic acidosis (build - up of acid in the blood). Lactic acidosis can be a medical emergency and may need to be treated in the hospital. Call your doctor immediately if you get the following signs or symptoms of lactic acidosis:

• You feel very weak or tired
• You have unusual (not normal) muscle pain
• You have trouble breathing
• You have stomach pain with nausea and vomiting
• You feel cold, especially in your arms and legs
• You feel dizzy or lightheaded
• You have a fast or irregular heartbeat

This side effect can cause inflammation of the pancreas, liver and kidney failure, and has occasionally been fatal. Lactic acidosis also occurs more often in women, particularly if they are overweight. If you have liver disease, you may also be more at risk of getting this condition. While you are being treated with RANEGA, your doctor will monitor you closely for any signs that you may be developing lactic acidosis. Tell your doctor if you notice any of the following:

• Frequent: Headache
• Difficulty in sleeping (insomnia)
• Nausea, vomiting
• Upper abdominal pain
• Diarrhoea, flatulence
• Rash, itching
• Hair loss
• Joint pain (arthralgia)
• Muscles become weak, painful and may even cause paralysis (Muscle disorder)
• Feeling tired, weak (fatigue)
• Feeling of bodily discomfort (malaise)
• Fever
• Loss of bone mass

• Less Frequent: Depression
• Neutropenia (low white blood cell count)
• Anaemia (low red blood cell count)
• Increased bruising or bleeding (thrombocytopenia)
• Increases in enzymes produced by the liver
• Allergic reaction (hypersensitivity)
• Immune system begins to recover (immune reconstitution syndrome)
• Abdominal pain or discomfort
• Hepatitis (disease of the liver)
• Bone marrow stops making red blood cells (pure red cell aplasia)
• Redistribution/ accumulation of body fat
• Abnormal sensation of tingling, numbness or burning (paraesthesia)
• Peripheral neuropathy (when the nerves carrying messages to and from the brain are damaged)
• Inflammation of the pancreas, which causes severe pain in the abdomen and back
• Abnormal muscle breakdown which can lead to kidney problems
• Bones are more porous than they should be (osteopenia)
• Fractures
• Abnormally low levels of phosphate in the blood (hypophosphataemia)
• Shortness of breath (dyspnoea)
• Chronic kidney disease, or kidney failure (renal insufficiency)
• Nose and throat infection
• Nasal discharge and congestion
• Increased blood sugar levels
• Feeling depressed
• Cough
• Loss of appetite

If you notice any side effects not mentioned in this leaflet, please inform the medical practitioner or pharmacist.

• STORE ALL MEDICINES OUT OF REACH OF CHILDREN.

• Store at or below 30 °C. Store in the original container. Do not remove from the carton until required for use. Bottles must be kept tightly closed.

• Do not store in a bathroom.

• 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).