Stribild 150 mg/150 mg/200 mg/245 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Stribild 150 mg/150 mg/200 mg/245 mg film-coated tablets

elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Stribild is and what it is used for

Stribild contains four active substances:

• elvitegravir, an antiretroviral medicine known as an integrase inhibitor
• cobicistat, a booster (pharmacokinetic enhancer) of elvitegravir's effects
• emtricitabine, an antiretroviral medicine known as a nucleoside reverse transcriptase inhibitor (NRTI)
• tenofovir disoproxil, an antiretroviral medicine known as a nucleotide reverse transcriptase inhibitor

Stribild is a single-tablet regimen for the treatment of human immunodeficiency virus (HIV) infection in adults.

Stribild is also used to treat HIV-1 infected adolescents aged 12 to 18 years who weigh at least 35 kg and who have been treated with other HIV medicines that caused them side effects.

Stribild reduces the amount of HIV in the body. This improves the immune system and reduces the risk of developing illnesses associated with HIV infection.

2. What you need to know before taking Stribild

Do not take Stribild

• If you are allergic to elvitegravir, cobicistat, emtricitabine, tenofovir, tenofovir disoproxil, or any of the other ingredients of this medicine (listed in section 6 of this leaflet).
• If you have previously stopped treatment with a medicine containing tenofovir disoproxil on the advice of your doctor due to kidney problems.
• If you are taking any of the following medicines:
  • alfuzosin (used to treat an enlarged prostate)
  • amiodarone, quinidine (used to correct irregular heartbeats)
  • dabigatran (used to prevent and treat blood clots)
  • carbamazepine, phenobarbital, phenytoin (used to prevent seizures)
  • rifampicin (used to prevent and treat tuberculosis and other infections)
  • dihydroergotamine, ergotamine, ergometrine (used to treat migraines)
  • cisapride (used to relieve certain stomach problems)
  • St John’s wort (Hypericum perforatum, a herbal remedy used for depression and anxiety) or products containing it
  • lovastatin, simvastatin (used to lower blood cholesterol)
  • pimozide, lurasidone (used to treat abnormal thoughts or feelings)
  • sildenafil (used to treat pulmonary arterial hypertension, a lung disease that makes breathing difficult)
  • midazolam taken orally, triazolam (used to help sleep and/or relieve anxiety)

? If you are in any of these situations, you must not take Stribild and should consult your doctor immediately.

Warnings and precautions

You must remain under your doctor's supervision while taking Stribild.

While taking this medicine, you can still transmit HIV to others, although effective antiviral treatment reduces the risk. Ask your doctor what precautions are necessary to avoid infecting other people. This medicine is not a cure for HIV infection. While you are taking Stribild, you may still develop infections or other illnesses associated with HIV infection.

Talk to your doctor before starting Stribild if:

• You have kidney problems, have had kidney problems in the past, or if blood tests have shown kidney problems. Your doctor will carefully consider whether Stribild is appropriate for you.

Stribild can affect the kidneys. Before starting treatment, your doctor will arrange for blood tests to check kidney function. Your doctor will also arrange for regular blood tests during treatment to monitor your kidneys.

Stribild is generally not taken together with other medicines that may harm the kidneys (see section "Taking Stribild with other medicines"). If this is unavoidable, your doctor will monitor your kidney function more frequently.

• You have liver problems or a history of liver disease, including hepatitis.

Patients with liver disease, including chronic hepatitis B or C, who are treated with antiretrovirals, have an increased risk of severe and potentially life-threatening liver complications. If you have hepatitis B infection, your doctor will carefully consider the best treatment regimen for you.

If you have hepatitis B infection, liver problems may worsen after stopping Stribild. It is important that you do not stop taking Stribild without first talking to your doctor: see section 3, Do not stop treatment with Stribild.

• You are over 65 years of age. Stribild has not been studied in patients over 65 years of age. If you are older than this and have been prescribed Stribild, your doctor will monitor you closely.

? If you are in any of these situations, consult your doctor before starting Stribild.

While taking Stribild

Once you start taking Stribild, be alert for:

• Any signs of inflammation or infection
• Bone problems

? If you notice any of these symptoms, inform your doctor immediately.

Children and adolescents

Do not give this medicine to children under 12 years of age. The use of Stribild has not been studied in children under 12 years of age who weigh less than 35 kg.

Other medicines and Stribild

There are some medicines that must never be taken with Stribild.

These have already been mentioned in the section "Do not take Stribild if you are taking any of the following medicines."

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines. Stribild may interact with other medicines. As a result, blood levels of Stribild or other medicines may be affected. This could prevent your medicines from working properly or worsen their possible side effects. In some cases, your doctor may need to adjust the dose or monitor your blood levels.

It is especially important that you consult your doctor if you are taking any of the following medicines:

• Any other medicine containing:

  • tenofovir disoproxil
  • tenofovir alafenamide
  • lamivudine
  • adefovir dipivoxil

• Medicines that may harm the kidneys, such as:

  • aminoglycosides (such as streptomycin, neomycin, and gentamicin), vancomycin (for bacterial infections)
  • foscarnet, ganciclovir, cidofovir (for viral infections)
  • amphotericin B, pentamidine (for fungal infections)
  • interleukin-2, also known as aldesleukin (for treating cancer)
  • non-steroidal anti-inflammatory drugs (NSAIDs, for relieving bone or muscle pain)

It is also important to consult your doctor if you are taking any of the following types of medicines:

• Antifungals, used to treat fungal infections, such as:
  • ketoconazole, itraconazole, voriconazole, fluconazole, and posaconazole
• Antivirals, used to treat hepatitis C virus infection:
  • ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir
• Antibiotics, used to treat bacterial infections including tuberculosis, containing:
  • rifabutin, clarithromycin, or telithromycin
• Antidepressants, used to treat depression:
  • medicines containing trazodone or escitalopram
• Sedatives and hypnotics, used to treat anxiety:
  • buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, and zolpidem
• Immunosuppressants, used to control the body's immune response after transplantation, such as:
  • cyclosporine, sirolimus, and tacrolimus
• Corticosteroids, including:
  • betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone.

These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory eye conditions, joint and muscle conditions, and other inflammatory disorders.

If no alternatives are available, they should only be used after clinical evaluation and with close monitoring by your doctor to assess corticosteroid side effects.

• Medicines used to treat diabetes:
  • metformin
• Oral contraceptive pill, used to prevent pregnancy
• Medicines for erectile dysfunction, used to treat impotence, such as:
  • sildenafil, tadalafil, and vardenafil
• Medicines for the heart, such as:
  • digoxin, disopyramide, flecainide, lidocaine, mexiletine, propafenone, metoprolol, timolol, amlodipine, diltiazem, felodipine, nicardipine, nifedipine, and verapamil
• Medicines used to treat pulmonary arterial hypertension:
  • bosentan
• Anticoagulants, used to prevent and treat blood clots, such as:
  • warfarin, edoxaban, apixaban, and rivaroxaban
• Bronchodilators, used to treat asthma and other lung-related problems:
  • salmeterol
• Medicines to lower cholesterol, such as:
  • rosuvastatin, atorvastatin, pravastatin, fluvastatin, and pitavastatin
• Medicines used to treat gout:
  • colchicine
• Antacids, used to treat heartburn or acid reflux, such as:
  • aluminium/magnesium hydroxide

? If you are taking an antacid or a multivitamin supplement, take it at least 4 hours before or at least 4 hours after taking Stribild.

? Inform your doctor if you are taking these or any other medicines. Do not stop your treatment without consulting your doctor.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, talk to your doctor or pharmacist before using this medicine.

• Inform your doctor immediately if you become pregnant, think you may be pregnant, or plan to become pregnant. Pregnant women should not take Stribild. The amount of this medicine in the blood may decrease during pregnancy, which could cause it to stop working properly.
• Use an effective method of contraception while taking Stribild.

Do not breast-feed while being treated with Stribild. This is because some of the active substances in this medicine pass into breast milk. If you are a woman with HIV infection, you are advised not to breast-feed in order to avoid transmitting the virus to your child through breast milk.

Driving and using machines

Stribild may cause dizziness, fatigue, and insomnia. If you experience these during treatment with Stribild, do not drive or operate tools or machinery.

Stribild contains lactose

If your doctor has told you that you have an intolerance to certain sugars, talk to him before taking this medicine.

3. How to take Stribild

Follow exactly the instructions for using this medicine as given by your doctor. If you are unsure, consult your doctor or pharmacist again.

Recommended dose for adults and adolescents aged 12 to 18 years weighing at least 35 kg:

• One tablet daily by mouth, taken with food. Do not chew, crush, or split the tablet.

Always take the dose prescribed by your doctor. This is to ensure that your medicine remains fully effective and to reduce the risk of developing treatment resistance. Do not change your dose unless your doctor tells you to do so.

If you are taking an antacid such as aluminium/magnesium hydroxide or a multivitamin supplement, take it at least 4 hours before or at least 4 hours after taking Stribild.

If you take more Stribild than you should

If you accidentally take more than the recommended dose of Stribild, you may be at increased risk of experiencing possible adverse effects with this medicine (see section 4, Possible side effects).

Contact your doctor or go to the nearest emergency room immediately. Take the medicine bottle with you so you can easily describe what you have taken.

If you forget to take Stribild

It is important not to miss a dose of Stribild.

If you miss a dose:

• and you realize within 18 hours of the time you usually take Stribild, take the tablet as soon as possible. Always take the tablet with food. Then take your next dose at the usual time.
• and you realize 18 hours or more after the time you usually take Stribild, do not take the missed dose. Wait and take the next dose with food at the usual time.

If you vomit within 1 hour after taking Stribild, take another tablet with food.

Do not stop treatment with Stribild

Do not stop treatment with Stribild without first talking to your doctor. Stopping Stribild may seriously affect your response to future treatments. If Stribild is stopped for any reason, consult your doctor before restarting treatment with Stribild.

When you notice that you are running low on Stribild, contact your doctor or pharmacist to get more. This is very important, as the amount of virus may start to increase if the medicine is interrupted, even for a short period of time. This could make the disease more difficult to treat.

If you have HIV and hepatitis B infection, it is especially important not to stop your treatment with Stribild without first talking to your doctor. You may need to have blood tests for several months after stopping treatment. In some patients with advanced liver disease or cirrhosis, stopping treatment is not recommended, as this may cause a worsening of hepatitis, a condition that could be potentially fatal.

? Contact your doctor immediately about any new or unusual symptoms after stopping your treatment, particularly symptoms you associate with hepatitis B virus infection (such as yellowing of the skin or whites of the eyes, dark brown urine, pale stools, loss of appetite for several days, nausea or vomiting, or stomach pain).

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

4. Possible adverse effects

During HIV treatment, there may be an increase in weight and in blood glucose and lipid levels. This may be partly due to improved health, lifestyle factors, and, in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will monitor these changes.

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. When treating HIV infection, it is not always possible to determine whether certain unwanted effects are due to Stribild, to other medicines being taken at the same time, or to the HIV disease itself.

Serious possible adverse effects: inform a doctor immediately

• Lactic acidosis (excess lactic acid in the blood) is a rare but potentially life-threatening side effect of some HIV medicines. Lactic acidosis occurs more frequently in women, especially those who are overweight, and in people with liver disease. The following may be signs of lactic acidosis:
  • rapid, deep breathing
  • tiredness or drowsiness
  • nausea and vomiting
  • stomach pain

? If you think you may have lactic acidosis, inform your doctor immediately.

• Any sign of inflammation or infection. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections (infections that occur in people with a weakened immune system), signs and symptoms of inflammation from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without obvious symptoms. In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks the body's healthy tissues) may also occur after starting treatment for HIV infection. Autoimmune disorders may occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving toward the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive necessary treatment.

? If you notice any signs of inflammation or infection, inform your doctor immediately.

Very common adverse effects

(may affect more than 1 in 10 patients treated)

• diarrhoea
• vomiting
• nausea
• weakness
• headache, dizziness
• rash

Blood tests may also show:

• decreased blood phosphate levels
• increased blood creatine kinase levels, which may cause muscle pain and weakness

Common adverse effects

(may affect up to 1 in 10 patients treated)

• loss of appetite
• difficulty sleeping (insomnia), abnormal dreams
• pain, stomach ache
• digestive problems with discomfort after meals (dyspepsia)
• feeling bloated
• constipation, gas (flatulence)
• rashes (including red spots or pimples, sometimes with blisters and skin swelling), which may be allergic reactions, itching, changes in skin colour such as darkening of the skin in patches
• other allergic reactions
• tiredness

Blood tests may also show:

• low white blood cell count (which may make you more prone to infections)
• increased blood sugar, fatty acids (triglycerides), and bilirubin levels
• liver and pancreas problems
• increased blood creatinine levels

Uncommon adverse effects

(may affect up to 1 in 100 patients treated)

• suicidal thoughts and suicide attempts (in patients who have previously had depression or mental health problems), depression
• back pain due to kidney problems, including kidney failure. Your doctor may perform blood tests to check whether your kidneys are functioning properly
• damage to renal tubule cells
• swelling of the face, lips, tongue, or throat
• abdominal (stomach) pain caused by inflammation of the pancreas (pancreatitis)
• muscle rupture, muscle pain, muscle weakness

Blood tests may also show:

• anaemia (low red blood cell count)
• decreased blood potassium levels
• changes in urine

Rare adverse effects

(may affect up to 1 in 1,000 patients treated)

• lactic acidosis (see Serious possible adverse effects: inform a doctor immediately)
• yellowing of the skin or eyes, itching, or abdominal (stomach) pain caused by liver inflammation (hepatitis)
• fatty liver
• kidney inflammation (nephritis)
• increased urine volume and feeling thirsty (nephrogenic diabetes insipidus)
• weakening of the bones (with bone pain and sometimes leading to fractures)

Muscle rupture, weakening of the bones (with bone pain and sometimes leading to fractures), muscle pain, muscle weakness, and decreased blood potassium or phosphate levels may occur due to damage to renal tubule cells.

? If you consider any of the adverse effects you experience to be severe, inform your doctor.

Other effects that may occur during HIV treatment

The frequency of the following adverse effects is unknown (cannot be estimated from available data).

• Bone problems. Some patients treated with combination antiretroviral medicines such as Stribild may develop a bone disease called osteonecrosis (death of bone tissue due to loss of blood supply to the bone). Taking this type of medicine for a prolonged time, taking corticosteroids, drinking alcohol, having a very weak immune system, and being overweight may be some of the many risk factors for developing this disease. Signs of osteonecrosis include:
  • joint stiffness
  • joint discomfort and pain (especially in the hip, knee, and shoulder)
  • difficulty moving

Other effects in children

• Children who were given emtricitabine very commonly experienced skin colour changes, including
  • dark spots on the skin
• Children frequently experienced low red blood cell count (anaemia)
  • this may cause the child to feel tired or short of breath

? If you notice any of these symptoms, inform your doctor.

? If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if they are possible adverse effects not mentioned in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Stribild

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and carton after EXP. The expiry date is the last day of the month indicated.

Store in the original packaging to protect from moisture. Keep the bottle tightly closed.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Stribild

The active substances are: elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil. Each Stribild film-coated tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg of tenofovir disoproxil fumarate or 136 mg of tenofovir).

The other components are

Tablet core:

Croscarmellose sodium, hydroxypropylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, silicon dioxide, sodium lauryl sulfate.

Film coating:

Indigo carmine aluminium lake (E132), macrogol 3350 (E1521), polyvinyl alcohol (partially hydrolysed) (E1203), talc (E553B), titanium dioxide (E171), yellow iron oxide (E172).

Appearance of the product and contents of the pack

Stribild film-coated tablets are green, capsule-shaped tablets, marked on one side with “GSI” and on the other side with the number “1” within a square box. Stribild is available in bottles of 30 tablets (with a silica gel desiccant which should be kept in the bottle to help protect the tablets). The silica gel desiccant is contained in a separate sachet or container and must not be swallowed.

This medicine is available in packs containing 1 bottle of 30 film-coated tablets and packs of 90 (3 bottles of 30) film-coated tablets. Only some pack sizes may be marketed.

Marketing Authorisation Holder

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Manufacturer

Gilead Sciences Ireland UC

IDA Business & Technology Park

Carrigtohill

County Cork

Ireland

For further information regarding this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the last revision of this leaflet: <{MM/YYYY}> <{month YYYY}>.

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