Odystra Film-Coated Tablets

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

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

Do not take ODYSTRA:

• If you are hypersensitive (allergic) to tenofovir disoproxil fumarate, lamivudine, dolutegravir or any of the other ingredients in ODYSTRA 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 ODYSTRA have been established in clinical studies for the treatment of HIV patients. However, safety and efficacy of the fixed drug combination as in ODYSTRA for the treatment of HIV have not been established in clinical studies. ODYSTRA 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: ODYSTRA 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 ODYSTRA 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). You must contact your doctor if you experience joint aches and pain, joint stiffness or difficulty in movement. Talk to your doctor if you suffer from osteoporosis, have a history of bone fracture or if you have problems with your bones. Bone problems (manifesting as persistent or worsening bone pain and sometimes resulting in fractures) may also occur due to damage to kidney tubule cells (see section 4, Possible side effects). Tell your doctor if you have bone pain or fractures. Tenofovir disoproxil may also cause loss of bone mass.
• Liver problems. If you have liver problems including Hepatitis B virus infection.
• Hepatitis B or C. If you have Hepatitis B or C, you are at increased risk for severe and potentially fatal liver adverse reactions.
• Opportunistic infections. Signs and symptoms of inflammation from previous infections may occur soon after anti - HIV treatment such as ODYSTRA 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.
• Pancreas disorders. If you develop abdominal pain, nausea, vomiting, contact your doctor as it could indicate problems with your pancreas.
• Changes in body fat. Changes in body fat develop in some patients taking ODYSTRA. These changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), in the breasts and around the trunk. Loss of fat from the legs, arms and face may also happen. The cause and long - term health effects of these fat changes are not known.
• Depression (including suicidal ideation). Patients should inform their doctor if they notice any symptoms of depression during treatment.

ODYSTRA helps to control (treat) HIV infection but is not a cure. You will need to take it every day. You must not stop taking ODYSTRA without first talking to your doctor. If you are concerned that you may be developing symptoms of a hypersensitivity reaction, call your doctor immediately who will advise whether you must stop taking ODYSTRA. You may continue to develop other infections and other illnesses associated with HIV disease. You should therefore keep in regular contact with your doctor while you are taking ODYSTRA.

Treatment with ODYSTRA has not been shown to reduce the risk of passing HIV infection to others through sexual contact or contaminated blood. If you are sexually active you should continue to use appropriate precautions to prevent this.

To protect other people from becoming infected with HIV:

• a condom must be used when you have oral or penetrative sex;
• blood transfer should be avoided – for example, needles must not be shared.

Children and adolescents:

Do not give this medicine to children under the age of 18 years.

Other medicines and ODYSTRA:

Always tell your health care provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) Do not take ODYSTRA if you are already taking any of the following medicines:

• Other medicines that contain tenofovir disoproxil fumarate, lamivudine, dolutegravir or emtricitabine, either alone, or in other formulations. ODYSTRA should not be used with these medicines because they contain the same or similar active ingredients as ODYSTRA.
• Medicines that contain didanosine. Tenofovir disoproxil fumarate (an ingredient in ODYSTRA) may cause the amount of didanosine in your blood to increase. You may need to be followed more carefully if you are taking ODYSTRA and didanosine together. The dose of didanosine may need to be reduced.
• Adefovir dipivoxil (used for the treatment of chronic hepatitis B).
• Zalcitabine (antiretroviral treatment).
• Trimethoprim, as in co - trimoxazole (an antibiotic), may cause an increase in ODYSTRA plasma levels. If you have no kidney disease, a dosage adjustment is not necessary.
• Rifampicin (antibiotic used to treat several types of bacteria) may decrease the blood levels of dolutegravir.
• Isoniazid (antibiotic used to treat tuberculosis) increased the concentration.
• Polyvalent cation - containing antacids. Recommended to be administered 2 hours before or 6 hours after ODYSTRA.
• Calcium supplements: recommended to be administered 2 hours before or 6 hours after ODYSTRA or taken with food.
• Iron supplements: recommended to be administered 2 hours before or 6 hours after ODYSTRA or taken with food.
• Metformin: co - administered with ODYSTRA may increase plasma levels of insulin.
• Oral contraceptives: ODYSTRA does not change the concentration levels of oral contraceptives.
• Methadone (a pain killer): ODYSTRA does not change the concentration levels of this painkiller.

Some patients who are taking ODYSTRA may continue to experience infections and the use of antibiotics may have to be considered.

ODYSTRA with food and drink: ODYSTRA can be taken without regard to food.

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 ODYSTRA exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure. The usual dose of ODYSTRA is one tablet once a day. ODYSTRA must be taken without regard of food. You can only take ODYSTRA if you are older than 18 years. Your doctor will tell you how long your treatment with ODYSTRA will last.

If you take more ODYSTRA 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 ODYSTRA: If you forget to take a dose of ODYSTRA, 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 ODYSTRA: Do not suddenly stop taking ODYSTRA without consulting with your doctor first. If you have stopped taking ODYSTRA 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 ODYSTRA 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 ODYSTRA and become harder to treat. If you have the impression that the effect of ODYSTRA is too strong or too weak, talk to your doctor or pharmacist.

ODYSTRA can have side effects. Not all side effects reported for ODYSTRA are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking ODYSTRA, please consult your health care provider for advice. If any of the following happens, stop taking ODYSTRA 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 ODYSTRA.
• 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 ODYSTRA (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 ODYSTRA, 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, of 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.

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 ODYSTRA.

• 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).