Dovilamir Film-Coated Tablets

DOVILAMIR is a triple combination therapy used to treat Human Immunodeficiency Virus - 1 (HIV - 1) infected adults over 18 years of age.

Do not take DOVILAMIR:

• if you are hypersensitive (allergic) to dolutegravir, lamivudine or tenofovir disoproxil fumarate, or any of the other ingredients of DOVILAMIR (listed in section 6).
• If you have uncontrolled kidney failure.
• If you have moderate or severe liver disease.
• If you are pregnant or breastfeeding your baby.
• If you plan on becoming pregnant.
• If you are a woman of child bearing age and are not using effective contraceptives to prevent falling pregnant.
• If you are also taking medication for irregular heart beat containing dofetilide and pilsicainide.
• If you are taking metformin for the treatment of diabetes.
• If you are taking medication for the treatment of hepatitis B containing adefovir dipivoxil.
• If you are taking another antiretroviral medicine containing didanosine.
• If you are younger than 18 years of age.

Warnings and precautions

Tell your doctor:

• If you have abnormal metabolic processes, such as, increased cholesterol, glucose or lactate in the blood or are resistant to insulin. Your doctor may perform regular blood tests to confirm normal metabolic processes.
• If you develop changes in body fat, which may be caused by combination antiretroviral medicines, such as DOVILAMIR. These changes may include increased fat in the upper back and neck areas (“buffalo hump”), breast, and around the main part of your body (trunk). Loss of fat from the legs, arms and face may also happen.
• If you show any symptoms of infection while you are taking DOVILAMIR. Patients with advanced HIV infection (AIDS) have weak immune systems and are more likely to develop serious infections (opportunistic infections). When these patients start with the treatment, they may find that old hidden infections (such as tuberculosis) flare up, causing signs and symptoms of inflammation (such as localised swelling, area appears red and hot, painful).
• If you experience joint aches and pain, joint stiffness or difficulty in movement or bone fractures, you may suffer from a condition called osteonecrosis for which you may need treatment.
• If you show symptoms such as nausea, vomiting, abdominal pain, non-specific general feeling of being ill, loss of appetite, weight loss, rapid and/or deep breathing, or muscle weakness, you may be experiencing a condition called lactic acidosis (build-up of lactic acid in the body) (see "Possible side effects").
• If you are female, very overweight (obese), or have been using medicines for the treatment of HIV for a long time, as you may be more likely to get lactic acidosis.
• If your child experiences symptoms of poor growth, loss of muscle coordination, muscle weakness, visual problems, hearing problems, learning disabilities, heart disease, liver disease, kidney disease, gastrointestinal disorders, respiratory disorders, nervous system problems (brain, spine and nerves), loss of voluntary body functions (such as breathing, bladder function, heartbeat and digestive processes) and dementia (loss of memory), as these symptoms can be a sign of mitochondrial (part of the cell that creates energy) disorder. These findings should be considered for any child exposed to treatment, before being born.
• If you experience severe pain in the stomach, nausea or vomiting, as these can be symptoms of pancreatitis (swelling of the pancreas) (see "Possible side effects").
• If you suffer from kidney problems.
• If you have had bone problems in the past, your doctor may need to do tests to check your bone mineral density or may prescribe medicines to help improve your bone mineral density.
• If you suffer from liver disease, including hepatitis B or C infections, as the use of DOVILAMIR can cause deadly, unfavourable liver symptoms. Your doctor will monitor your liver enzymes through tests, as DOVILAMIR can cause liver toxicity.
• If you show signs of liver injury (yellowing of the skin and whites of the eyes, feeling generally weak or tired, loss of weight, nausea, vomiting).
• If you develop a rash, or show any general signs of allergy (rash, accompanied by fever, general feeling of being ill, tiredness, muscle or joint aches, sores, oral scrapes, eye infection, facial swelling, a serious liver infection or swelling of the skin.

Special care should be taken with DOVILAMIR: DOVILAMIR does not reduce the risk of passing HIV on to other people through sexual contact or blood contamination. Therefore, it is important to continue to take appropriate precautions to prevent passing HIV on to others. Even if you are receiving treatment for HIV, you are still at risk of contracting other infections and other complications of the HIV infection. Therefore, you should remain under close observation by your doctor.

Children and adolescents

DOVILAMIR should not be used in children under the age of 18 years, as safety has not been established.

Other medicines and DOVILAMIR

Always tell your healthcare provider if you are taking any other medicine (this includes all complementary or traditional medicines).

Do not share medicines prescribed for you with any other person. Always take DOVILAMIR exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The usual dose for DOVILAMIR is one film-coated tablet taken orally, once daily, with or without food. Film-coated tablets must be swallowed whole with water and must not be crushed or chewed. DOVILAMIR should only be used by adults and should not be taken by patients younger than 18 years of age.

If you take more DOVILAMIR 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 DOVILAMIR

Do not take a double dose to make up for forgotten individual doses and take your dose as soon as you remember to.

If you stop taking DOVILAMIR

Your doctor will tell you how long your treatment with DOVILAMIR will last. Do not stop treatment early because this may worsen your condition and make your body resistant to the medicine.

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

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

• Swelling of the hands, feet ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing.
• Rash or itching.
• Fainting.

These are all very serious side effects. If you have them, you may have had a serious allergic reaction to DOVILAMIR. 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.

• IRS (Immune reconstitution syndrome): People with advanced HIV infection (AIDS) have weak immune systems and are more likely to develop serious infections (opportunistic infections). When these people start treatment, they may find that old, hidden infections flare up, causing signs and symptoms of inflammation. These symptoms are probably caused by the body’s immune system becoming stronger, so that the body starts to fight these infections. 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 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 seek necessary treatment.
• Swelling (inflammation) of the liver (hepatitis), that may include the following symptoms:

• Fatigue (tiredness).
• Nausea and vomiting.
• Stomach pain or discomfort, especially in the area of your liver on your right side beneath your lower ribs.
• Clay-coloured bowel movements.
• Loss of appetite.
• Fever.
• Dark urine.
• Joint pain.
• Yellowing of the skin and eyes (jaundice).

• Neutropenia (an abnormal low concentration of white blood cells). Symptoms include:

• Fever.
• Painful swallowing.
• Pain of the gums.
• Skin abscesses.
• Painful ears.

• Anaemia (when you have a low red blood cell count). Symptoms include:

• Tiredness.
• Unusually rapid heartbeat.
• Shortness of breath.
• Difficulty concentrating.
• Dizziness.
• Pale skin.
• Leg cramps.
• Sleeplessness.

• If you have a blood clotting problem, symptoms include:

• Serious bleeding.
• Purple, red or brown bruises.

• Red blood cell aplasia (decreased number of red blood cells). Symptoms include:

• Tiredness.
• Lethargy (feeling without any energy).
• Getting tired quickly when doing exercise.
• Pale skin.

• Patients who take DOVILAMIR can develop a serious condition called lactic acidosis/hyperlactataemia (build-up of acid in the blood). Symptoms include:

• 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 light-headed.
• You have a fast or irregular heartbeat.

• Lipodystrophy – abnormal distribution or loss of body fat in certain areas such as:

• Increased waist or breast size.
• Fat accumulation around neck, jaw or upper back (referred to as “moon face” or “buffalo hump”).
• Loss of fat under the skin, most visibly on the face (especially cheeks), arms and legs.
• Prominent leg veins due to loss of fat under the skin.

• Pancreatitis (swelling of the pancreas). Symptoms include:

• Stomach pain.
• Nausea and vomiting.
• Abnormal urine tests.

• Rhabdomyolysis (breakdown of muscle fibres that leads to the release of muscle fibre contents into the bloodstream). Symptoms include:

• Abnormal urine colour (dark, red, or cola coloured).
• Decreased urine production.
• General weakness.
• Muscle stiffness or pain (myalgia).
• Muscle tenderness.
• Weakness of the affected muscles.

• Kidney damage or failure that includes the following symptoms:

• Decreased urination.
• Fluid retention (swelling of the legs, ankles or feet).
• Weakness and shortness of breath.

• Confusion.
• Abnormal heart rhythm.
• Loss of appetite.
• High blood pressure.

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:

• Sleeplessness.
• Headaches, dizziness.
• Abnormal dreams.
• Nausea, vomiting, diarrhoea.
• Upper abdominal pain or cramps.
• Loss of appetite, indigestion.
• Rash, itching.
• Hair loss.
• Muscle disorders, painful joints and muscles.
• Tiredness, feeling of discomfort, fever, lack of energy.
• Increase in liver enzymes in the blood (ALT & AST) (seen in a blood test).
• Passing a lot of urine and feeling thirsty (nephrogenic diabetes insipidus).

Less frequent side effects:

• Increase in an enzyme called amylase in the blood (seen in a blood test).
• Decrease in bone density, bone fractures.
• Flatulence or wind.

The following side effects have also been reported (frequency not known):

• Anxiety.
• Increase in weight.
• High blood sugar – you may experience increased thirst and a dry mouth, needing to pee frequently, tiredness, blurred vision.
• Tingly feelings in the skin (pins and needles) burning or stabbing pain, weakness, usually in back, foot, hands, thigh or face.
• Worsening of hepatitis B infection symptoms, such as fever, fatigue, abdominal pain after treatment with DOVILAMIR is stopped.
• Hives (urticaria).
• Rapid swelling under the skin (puffiness).
• Decreased phosphate in your blood (seen in a blood test).
• Low levels of potassium in the blood (seen in a blood test).
• Feeling breathless (dyspnoea).
• Muscle weakness (myopathy).

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 “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of DOVILAMIR.

Store at or below 30 °C in the original container. Keep the container tightly closed. Do not remove desiccant. After first opening, store at or below 25 °C in the original container and use within 180 days after first opening. STORE ALL MEDICINES OUT OF REACH AND SIGHT OF CHILDREN. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).