DOVATO 50 mg/300 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Dovato50mg/300mg film-coated tablets

dolutegravir/lamivudine

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Dovato is and what it is used for
2. What you need to know before you take Dovato
3. How to take Dovato
4. Possible side effects
5. Storage of Dovato
6. Contents of the pack and other information

1. What Dovato is and what it is used for

Dovato is a medicine that contains two active substances used to treat human immunodeficiency virus (HIV) infection: dolutegravir and lamivudine. Dolutegravir belongs to a group of antiretroviral medicines called integrase inhibitors (INI) and lamivudine belongs to a group of antiretroviral medicines called nucleoside analogue reverse transcriptase inhibitors (NRTIs).

Dovato is used to treat HIV infection in adults and adolescents over 12 years of age who weigh at least 40 kg.

Dovato does not cure HIV infection; it keeps the amount of virus in your body at a low level. This helps to keep the number of CD4 cells in your blood at a normal level. CD4 cells are a type of white blood cell that is important in helping your body to fight infection.

Not everyone responds to treatment with Dovato in the same way. Your doctor will monitor the effectiveness of your treatment.

2. What you need to know before you take Dovato

Do not take Dovato

• if you are allergic(hypersensitive) to dolutegravir or lamivudine or any of the other ingredients of this medicine (listed in section 6)
• if you are taking a medicine called fampridine(also known as dalfampridine; used to treat multiple sclerosis).

• If you think any of these apply to you, talk to your doctor.

Warnings and precautions

Some people taking Dovato or other HIV medicines may have a higher risk of serious side effects. You need to know that there is a higher risk:

• if you have moderate or severe liver disease
• if you have ever had liver disease, including hepatitis B or C (if you have hepatitis B, do not stop taking Dovato without your doctor's advice, as this could make the condition worse)
• if you have kidney problems.

• Talk to your doctor before you start taking Dovatoif any of these apply to you. You may need to have extra checks, including blood tests, while you are taking this medicine. For more information, see section 4.

Allergic reactions

Dovato contains dolutegravir. Dolutegravir can cause a serious allergic reaction known as a hypersensitivity reaction. You need to know what important signs and symptoms to look out for while you are taking Dovato.

Read the information“Allergic reactions” in section 4 of this leaflet.

Be aware of important symptoms

Some people taking medicines for HIV infection develop other conditions that can be serious. These include:

• symptoms of infection and inflammation
• pain in the joints, stiffness, and bone problems.

You need to know what important signs and symptoms to look out for while you are taking Dovato.

• Read the information about “Other possible side effects” in section 4of this leaflet.

Children and adolescents

This medicine is not intended for children under 12 years of age and adolescents who weigh less than 40 kg, as it has not been studied in these patients.

Other medicines and Dovato

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

Do not take Dovato with the following medicine:

• fampridine (also known as dalfampridine), used to treat multiple sclerosis.

Some medicines may affect how Dovato works, or increase the chance of side effects. Dovato may also affect how other medicines work.

Tell your doctorif you are taking any of the following medicines:

• metformin, for diabetes
• medicines called antacids, for indigestionand heartburn. Do not take an antacidduring the 6 hours before taking Dovato, or at least 2 hours after taking it (see also section 3, “How to take Dovato”).
• supplements or multivitamins that contain calcium, iron, or magnesium. If you take Dovato with food, you can take supplements or multivitamins that contain calcium, iron, or magnesium at the same time as Dovato. If you do not take Dovato with food, you must not take a supplement or multivitamin that contains calcium, iron, or magnesiumduring the 6 hours before taking Dovato, or at least 2 hours after taking it (see also section 3, “How to take Dovato”).
• emtricitabine, etravirine, efavirenz, nevirapine, or tipranavir/ritonavir, for HIV infection
• medicines (usually liquids) that contain sorbitol and other polyalcohols (such as xylitol, mannitol, lactitol, or maltitol), if taken regularly
• cladribine, used to treat leukaemiaor multiple sclerosis
• rifampicin, for tuberculosis (TB)and other bacterial infections
• phenytoin and phenobarbital, for epilepsy
• oxcarbazepine and carbamazepine, for epilepsyor bipolar disorder
• St John's Wort(Hypericum perforatum), a herbal medicine for depression.

• Tell your doctor or pharmacistif you are taking any of these medicines. Your doctor may decide to adjust your dose or that you need extra checks.

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to have a baby:

• Ask your doctorabout the risks and benefits of taking Dovato.

Tell your doctor immediately if you become pregnant or are planning to become pregnant. Your doctor will review your treatment. Do not stop taking Dovato without your doctor's advice, as this could harm you and your baby.

Breast-feeding

It is not recommendedthat HIV-infected women breast-feed their babies because HIV infection can be passed to the baby through breast milk.

A small amount of the ingredients of Dovato may also pass into breast milk.

If you are breast-feeding or thinking of breast-feeding, you should talk to your doctor as soon as possible.

Driving and using machines

Dovato may make you feel dizzy and may have other effects that reduce your ability to pay attention.

• Do not drive or use machines unless you are sure that you are not affected.

Dovato contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, which is essentially ‘sodium-free’.

3. How to take Dovato

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

• The recommended dose of Dovato is one tablet once a day.

Swallow the tablet with a little water. Dovato can be taken with or without food.

The pack of Dovato in blisters for 30 days; contains four blisters of 7 tablets and one blister of 2 tablets. To help you keep track of taking your medicine over 30 days, the blisters of 7 tablets include the days of the week printed on them and the blister of 2 tablets includes two empty boxes where you can write the day that applies.

Use in adolescents

Adolescents between 12 and 17 years and weighing at least 40 kg can take the adult dose of one tablet once a day.

Antacids

Antacids for indigestion and heartburn can stop Dovato from being absorbed by your body and make it less effective.

Do not take an antacidduring the 6 hours before taking Dovato, or at least 2 hours after taking it.

Other medicines that reduce stomach acid, such as ranitidine and omeprazole, can be taken at the same time as Dovato.

• Ask your doctorfor advice on which acid-reducing medicines you can take with Dovato.

Supplements or multivitamins that contain calcium, iron, or magnesium

Supplements or multivitamins that contain calcium, iron, or magnesium can stop Dovato from being absorbed by your body and make it less effective.

If you take Dovato with food, you can take supplements or multivitamins that contain calcium, iron, or magnesium at the same time as Dovato. If you do not take Dovato with food, you must not take a supplement or multivitamin that contains calcium, iron, or magnesiumduring the 6 hours before taking Dovato, or at least 2 hours after taking it.

• Ask your doctorfor advice on how to take supplements or multivitamins that contain calcium, iron, or magnesium with Dovato.

If you take more Dovato than you should

If you take more Dovato than you should, contact your doctor or pharmacistfor advice. If possible, show them the Dovato pack.

If you forget to take Dovato

If you forget to take a dose, take it as soon as you remember. However, if it is less than 4 hours until your next dose, skip the missed dose and take the next dose at the usual time. Then continue your treatment as before.

• Do not take a double doseto make up for a forgotten dose.

Do not stop taking Dovato without your doctor's advice

Take Dovato until your doctor tells you to stop. Do not stop taking it unless your doctor advises you to. Stopping treatment with Dovato may affect your health and the future effectiveness of the treatment.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them, so it is very important that you comment on any change in your health status to your doctor.

Allergic Reactions

Dovato contains dolutegravir. Dolutegravir can cause a severe allergic reaction known as hypersensitivity reaction.This is a rare reaction (it can affect up to 1 in 100 people) in people taking dolutegravir. If you have any of the following symptoms:

• skin rash
• high temperature (fever)
• lack of energy (fatigue)
• swelling, sometimes of the face or mouth (angioedema), which causes difficulty breathing
• muscle or joint pain.

• Go to a doctor immediately.Your doctor may decide to perform liver, kidney, or blood tests and may indicate that you stop taking Dovato.

Very Common Adverse Effects

These can affect more than 1 in 10people:

• headache
• diarrhea
• nausea.

Common Adverse Effects

These can affect up to 1 in 10people:

• depression (feeling of deep sadness and lack of self-esteem)
• skin rash
• itching (pruritus)
• vomiting
• pain or discomfort in the stomach (abdominal)
• weight gain
• gas (flatulence)
• dizziness
• drowsiness
• difficulty falling asleep (insomnia)
• abnormal dreams
• lack of energy (fatigue)
• hair loss
• anxiety
• joint pain
• muscle pain.

The common adverse effects that may appear in blood tests are:

• increase in liver enzyme levels (aminotransferases)
• increase in muscle enzyme levels (creatine phosphokinase).

Uncommon Adverse Effects

These can affect up to 1 in 100people:

• liver inflammation (hepatitis)
• suicide attempt (especially in patients who have previously had depression or mental health problems)
• suicidal thoughts (especially in patients who have previously had depression or mental health problems)
• anxiety crisis.

The uncommon adverse effects that may appear in blood tests are:

• a decrease in blood cells involved in blood clotting (thrombocytopenia)
• a low red blood cell count (anemia) or low white blood cell count (neutropenia).

Rare Adverse Effects

These can affect up to 1 in 1,000people:

• liver failure (signs may include yellowing of the skin and whites of the eyes or unusually dark urine)
• swelling, sometimes of the face or mouth (angioedema), causing difficulty breathing
• pancreas inflammation (pancreatitis)
• muscle tissue rupture
• suicide (especially in patients who have previously had depression or mental health problems).

• Inform your doctor immediatelyif you experience any mental health problems (see also other mental health problems mentioned above).

The rare adverse effects that may appear in blood tests are:

• increase in bilirubin (liver function test)
• increase in an enzyme called amylase.

Very Rare Adverse Effects

These can affect up to 1 in 10,000people:

• lactic acidosis (excess lactic acid in the blood)
• numbness, tingling sensation in the skin (pinch)
• feeling of weakness in the limbs.

The very rare adverse effects that may appear in blood tests are:

• a failure of the bone marrow to produce new red blood cells (pure red cell aplasia).

Other Possible Adverse Effects

People taking combination treatment for HIV may have other adverse effects.

Symptoms of Infection and Inflammation

People with advanced HIV infection (AIDS) have a weakened immune system and are more likely to develop serious infections (opportunistic infections). Such infections may have developed silently, not being detected by the weakened immune system before treatment began. After starting treatment, the immune system becomes stronger and can fight these infections, which can cause symptoms of infection or inflammation. The symptoms usually include fever, in addition to some of the following:

• headache
• stomach pain
• difficulty breathing.

In rare cases, as the immune system becomes stronger, it can also attack healthy tissues (autoimmune disorders). The symptoms of autoimmune disorders can appear many months after starting to take medications to treat HIV. The symptoms may include:

• palpitations (rapid or irregular heartbeat) or tremors
• hyperactivity (excessive restlessness and movement)
• weakness that starts in the hands and feet and ascends to the trunk of the body.

If you have any symptoms of infectionor if you notice any of the above symptoms:

• Consult your doctor immediately. Do not take other medications for the infection without consulting your doctor first.

Pain in the Joints, Stiffness, and Bone Problems

Some people on combination treatment for HIV develop osteonecrosis. In this condition, parts of the bone tissue are permanently damaged due to reduced blood supply to the bones. People may be more prone to this condition:

Signs of Osteonecrosis Include:

• stiffness in the joints
• discomfort and pain in the joints (especially in the hip, knee, or shoulder)
• difficulty moving.

If you notice any of these symptoms:

• Inform your doctor.

Effects on Weight, Lipids, and Blood Glucose:

During HIV treatment, there may be an increase in weight and lipid and glucose levels in the blood. This is partially related to the recovery of health and lifestyle, and sometimes to the HIV medications themselves. Your doctor will evaluate these changes.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Dovato

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the box and the bottle or blister pack after CAD. The expiration date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be thrown down the drain or into the trash. 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

Dovato Composition

• The active ingredients are dolutegravir and lamivudine. Each tablet contains dolutegravir sodium equivalent to 50 mg of dolutegravir and 300 mg of lamivudine.
• The other ingredients are microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, mannitol (E421), povidone (K29/32), sodium fumarate, hypromellose (E464), macrogol, titanium dioxide (E171).

Product Appearance and Package Contents

The Dovato film-coated tablets are oval, biconvex, white with "SV 137" engraved on one face.

The film-coated tablets are supplied in child-resistant closure bottles or child-resistant blister packs.

Bottle

Each bottle contains 30 film-coated tablets.

Clinical packs containing 90 film-coated tablets (3 bottles of 30 film-coated tablets) are also available.

Blister Pack

Each pack contains 30 film-coated tablets and consists of 4 blister packs with 7 film-coated tablets and 1 blister pack with 2 film-coated tablets. For the 2-tablet blister pack, an empty space is intentionally included in each half of the blister pack.

Clinical packs containing 90 film-coated tablets (3 packs of 30 film-coated tablets, in blister packs) are also available.

Not all pack sizes may be marketed.

Marketing Authorization Holder

ViiV Healthcare BV

Van Asch van Wijckstraat 55H

3811 LP Amersfoort

Netherlands

Manufacturer

Glaxo Wellcome, S.A.

Avda. Extremadura, 3

09400 Aranda de Duero (Burgos)

Spain

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:MM/AAAA

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.