STRIBILD 150mg/150mg/200mg/245mg FILM-COATED TABLETS

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

1. What is Stribild and what is it used for

Stribild contains four active substances:

• elvitegravir, an antiretroviral medicine known as an integrase inhibitor
• cobicistat, a booster (pharmacokinetic enhancer) of the effects of elvitegravir
• emtricitabine, an antiretroviral medicine known as a nucleoside analogue reverse transcriptase inhibitor (NRTI)
• tenofovir disoproxil, an antiretroviral medicine known as a nucleotide analogue 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 adolescents aged 12 to 18 years who weigh at least 35 kg and are infected with HIV-1, who have been previously treated with other HIV medicines that have caused side effects.

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

2. What you need to know before you take 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).
• If you have previously stopped treatment with a medicine that contains tenofovir disoproxil on the advice of your doctor, after you had problems with your kidneys.
• If you are taking any of the following medicines:
  • alfuzosin (used to treat 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 that contain it
  • lovastatin, simvastatin (used to lower cholesterol in the blood)
  • pimozide, lurasidone (used to treat abnormal thoughts or feelings)
  • sildenafil (used to treat pulmonary arterial hypertension, a disease of the lung that makes it difficult to breathe)
  • midazolam given by mouth, triazolam (used to help you sleep and/or relieve anxiety)

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

Warnings and precautions

You must remain under the supervision of your doctor while taking Stribild.

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

Consult your doctor before starting Stribild:

• If you have kidney problems, or have had kidney problems, or if blood tests have shown kidney problems. Your doctor will carefully consider whether you should be treated with Stribild.

Stribild can affect your kidneys. Before starting treatment, your doctor will ask you to have blood tests to check your kidney function. Your doctor will also ask you to have blood tests during treatment to monitor your kidneys.

Stribild is not normally taken with other medicines that can harm your kidneys (see Taking Stribild with other medicines). If this is unavoidable, your doctor will monitor your kidney function more closely.

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

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

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

• If you are over 65 years old. Stribild has not been studied in patients over 65 years old. If you are over this age 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 aware of:

• any signs of inflammation or infection
• bone problems

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

Children and adolescents

Do not give this medicine to childrenunder 12 years of age. 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 should never be taken with Stribild.

These were mentioned earlier, in the section “Do not take Stribild if you are taking one of these 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, the levels of Stribild or other medicines in your blood may be affected. This may stop your medicines from working properly or may increase the risk of side effects. In some cases, your doctor may need to adjust the dose or check the levels of the medicines in your blood.

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

• any other medicine that contains:
  • tenofovir disoproxil
  • tenofovir alafenamide
  • lamivudine
  • adefovir dipivoxil

• medicines that can harm your 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 cancer treatment)
  • non-steroidal anti-inflammatory drugs (NSAIDs, for relieving bone or muscle pain)

It is also important that you consult your doctorif 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 infection:
  • ledipasvir/sofosbuvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir
• antibiotics, used to treat bacterial infections, including tuberculosis, that contain:
  • rifabutin, clarithromycin or telithromycin
• antidepressants, used to treat depression:
  • medicines that contain trazodone or escitalopram
• sedatives and hypnotics, used to treat anxiety:
  • buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam and zolpidem
• immunosuppressants, used to control the immune response of the body after a transplant, such as:
  • cyclosporin, sirolimus and tacrolimus
• corticosteroids, including:
  • betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone

These medicines are used to treat allergies, asthma, inflammatory diseases of the intestine, inflammatory diseases of the eyes, joints and muscles, and other inflammatory diseases.

If alternatives cannot be used, they should only be used after a clinical evaluation and with close monitoring by your doctor to assess the adverse effects of corticosteroids.

• medicines used to treat diabetes:
  • metformin
• oral contraceptive, 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 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 Stribild.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

• Tell your doctor immediately if you become pregnant, think you may be pregnant or are planning to have a baby. Women who are pregnant should not take Stribild. The amount of this medicine in your blood may decrease during pregnancy, which may stop it from working properly.
• Use an effective method of contraception while taking Stribild.

Do not breast-feed while taking Stribild.This is because some of the active substances in this medicine pass into breast milk. If you are a woman with HIV, it is recommended that you do not breast-feed your baby to avoid passing the virus to your baby through your breast milk.

Driving and using machines

Stribild may cause dizziness, tiredness and insomnia. If you are affected, do not drive or use tools or machines.

Stribild contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Stribild

Follow the instructions for taking this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

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

• One tablet a day by mouth, with food. Do not chew, crush or divide the tablet.

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

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

If you take more Stribild than you should

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

Consult your doctor or go to the nearest emergency department immediately. Take the pack of tablets with you so that you can easily describe what you have taken.

If you forget to take Stribild

It is important that you do not miss a dose of Stribild.

If you forget a dose:

• and you notice within 18 hours of the time you normally take Stribild, you must take the tablet as soon as possible. Take the tablet with food. Then take the next dose as usual.
• and you notice 18 hours or more after the time you normally 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 of taking Stribild,take another tablet with food.

Do not stop taking Stribild

Do not stop taking Stribild without talking to your doctor first.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 see that you have little Stribild left,go to your doctor or pharmacist to get more. This is very important, because the amount of virus may start to increase if the medicine is stopped, even for a short time. It may then become more difficult to treat your disease.

If you have HIV and hepatitis B infection,it is especially important not to stop your treatment with Stribild without talking to your doctor first. You may need to have blood tests for several months after stopping treatment. In some patients with advanced liver disease or cirrhosis, it is not recommended to stop treatment as this may cause your hepatitis to get worse, which can be life-threatening.

Talk to your doctor immediatelyabout new or unusual symptoms after stopping your treatment, particularly symptoms that you associate with hepatitis B infection (such as yellowing of the skin or the white of the eyes, dark-coloured urine, pale-coloured stools, loss of appetite for several days, nausea or vomiting, or pain in the stomach area).

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 levels of glucose and lipids in the blood. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

Like all medications, this medication may produce adverse effects, although not all people will experience them. When treating HIV infection, it is not always possible to distinguish whether some unwanted effects are due to Stribild or other medications being taken at the same time or the disease caused by HIV itself.

Possible Serious Adverse Effects: Inform a Doctor Immediately

• Lactic acidosis (excess lactic acid in the blood) is a rare but potentially fatal side effect of some HIV medications. Lactic acidosis occurs more frequently in women, especially if they are overweight, and in people with liver disease. The following may be signs of lactic acidosis:
  • rapid and deep breathing
  • fatigue 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 weak immune system), signs and symptoms of inflammation from previous infections may occur shortly after starting HIV treatment. It is believed that these symptoms are due to an improvement in the body's immune response, which allows it to fight infections that may have been present without obvious symptoms. In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks the body's healthy tissues) may also occur after starting HIV treatment. Autoimmune disorders can occur many months after treatment begins. If you notice any symptoms of infection or other symptoms, such as muscle weakness, weakness that starts in the hands and feet and moves towards the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive necessary treatment.

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

Very Common Adverse Effects

(may affect more than 1 in 10 patients treated)

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

Lab tests may also show:

• decreased phosphate levels in the blood
• increased creatine kinase levels in the blood, which can cause muscle pain and weakness

Common Adverse Effects

(may affect up to 1 in 10 patients treated)

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

Lab tests may also show:

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

Uncommon Adverse Effects

(may affect up to 1 in 100 patients treated)

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

Lab tests may also show:

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

Rare Adverse Effects

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

• lactic acidosis (see Possible Serious Adverse Effects: Inform a Doctor Immediately)
• yellowing of the skin or eyes, itching, or abdominal pain (stomach) caused by hepatitis (inflammation of the liver)
• fatty liver
• kidney inflammation (nephritis)
• increased urine volume and feeling of thirst (nephrogenic diabetes insipidus)
• weakening of the bones (with bone pain and which can sometimes lead to fractures)

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

If you consider that any of the adverse effects you are experiencing is serious, inform your doctor.

Other Effects that May be Observed During HIV Treatment

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

• Bone problems. Some patients treated with combination antiretroviral medications like 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 medication for a long 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. The signs of osteonecrosis are:
  • joint stiffness
  • joint pain and discomfort (especially in the hip, knee, and shoulder)
  • difficulty moving

Other Effects in Children

• Children who were given emtricitabine very frequently experienced changes in skin color, including
  • dark spots on the skin
• Children frequently experienced low red blood cell count (anemia)
  • 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 adverse effects, consult your doctor or pharmacist, even if they are not listed in this leaflet.

Reporting Adverse Effects

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

5. Storage of Stribild

Keep this medication out of sight and reach of children.

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

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

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Stribild Composition

The active ingredients 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 ingredients are

Tablet core:

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

Film coating:

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

Appearance and Package Contents

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

This medication is available in packages of 1 bottle of 30 film-coated tablets and 90 (3 bottles of 30) film-coated tablets. Not all pack sizes may be marketed.

Marketing Authorization Holder

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Manufacturer

Gilead Sciences Ireland UC

IDA Business & Technology Park

Carrigtohill

County Cork

Ireland

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

Date of Last Revision of this Leaflet:<{MM/AAAA}> <{month AAAA}>.

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