Truvada

Package leaflet: Information for the user

Truvada 200 mg/245 mg film-coated tablets

emtricitabine/tenofovir disoproxil
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Truvada is and what it is used for

Truvada contains two active substances, emtricitabine and tenofovir disoproxil. Both active substances
are antiretroviral medicines used to treat HIV infection.
Emtricitabine is a nucleoside reverse transcriptase inhibitor and tenofovir is a nucleotide reverse transcriptase inhibitor. However, they are generally known as NRTIs and
work by interfering with the normal activity of an enzyme (reverse transcriptase) that is essential
for the virus to replicate.

• Truvada is used to treat human immunodeficiency virus type 1 (HIV-1) infection in adults.
• It is also used to treat HIV in adolescents aged 12 to less than 18 years weighing at least 35 kg who have previously been treated with other HIV medicines that are no longer effective or have caused undesirable effects.
  • Truvada must always be used in combination with other medicines for the treatment of HIV infection.
  • Truvada may be administered as a substitute for separate emtricitabine and tenofovir disoproxil given at the same doses.

This medicine is not a cure for HIV infection. While you are taking Truvada, you may
still develop infections or other diseases associated with HIV infection.

• Truvada is also used to reduce the risk of acquiring HIV-1 infection in adults and adolescents aged 12 to less than 18 years weighing at least 35 kg, when taken daily in combination with safe sex practices: See section 2 for a list of precautions to prevent HIV infection.

2. What you should know before taking Truvada

Do not take Truvada to treat HIV or to reduce the risk of getting HIV
if you are allergic to emtricitabine, tenofovir, tenofovir disoproxil, or any of the other components
of this medicine (listed in section 6).
If any of these conditions apply to you, inform your doctor immediately.
Before taking Truvada to reduce the risk of getting HIV:
Truvada can only help reduce the risk of getting HIV before you are infected.

• To start taking Truvada to reduce the risk of getting HIV, you must be HIV-negative. You must undergo an HIV test to ensure you do not already have an HIV infection. Do not take Truvada for risk reduction unless it has been confirmed that you are HIV-negative. People who have HIV must take Truvada in combination with other medicines.
• Many HIV tests may not detect a recent infection. If you develop flu-like illness, it could mean you have recently been infected with HIV. Possible signs of HIV infection include:
  • fatigue
  • fever
  • joint or muscle pain
  • headache
  • vomiting or diarrhoea
  • rash
  • night sweats
  • swollen lymph nodes in the neck or groin
    Tell your doctor if you experience flu-like symptoms within the month before starting Truvada or at any time while taking Truvada.

Warnings and precautions
While taking Truvada to reduce the risk of getting HIV:

• Take Truvada every day to reduce risk—not only when you think you may have been exposed to HIV. Do not skip any doses of Truvada and do not stop taking it. Skipping doses may increase your risk of acquiring HIV infection.
• Get tested for HIV regularly.
• If you think you may have been infected with HIV, inform your doctor immediately. Your doctor may perform additional tests to confirm you are still HIV-negative.
• Simply taking Truvada may not prevent you from getting HIV.
  • Always practice safe sex. Use condoms to reduce contact with semen, vaginal fluid, or blood.
  • Do not share personal items that may have blood or body fluids on them, such as toothbrushes or razor blades.
  • Do not share or reuse needles or other injection or medication delivery equipment.
  • Get tested for other sexually transmitted infections such as syphilis and gonorrhoea. These infections can make it easier to acquire HIV.

Talk to your doctor if you have further questions about how to avoid getting or transmitting HIV to
other people.
While taking Truvada to treat HIV or to reduce the risk of getting HIV:

• Truvada may affect your kidneys. Before and during treatment, your doctor may order blood tests to monitor proper kidney function. Inform your doctor if you have had kidney disease or if blood tests have shown kidney problems. Truvada should not be given to adolescents with kidney problems. If you have kidney problems, your doctor may advise you to stop taking Truvada or, if you already have HIV, to take Truvada less frequently. Truvada is not recommended if you have severe kidney disease or are on dialysis.
• Inform your doctor if you have osteoporosis, have had bone fractures in the past, or have bone problems.

Bone problems (manifesting as persistent or worsening bone pain, and sometimes resulting in fractures) may occur due to damage to the renal tubular cells (see section 4, Possible side effects). Inform your doctor if you experience bone pain or fractures.
Tenofovir disoproxil may also cause loss of bone mineral density. The greatest loss of bone mineral density has been observed in clinical studies where patients were treated for HIV with tenofovir disoproxil in combination with a boosted protease inhibitor.
In general, the long-term effects of tenofovir disoproxil on bone health and the future risk of fractures in adult and paediatric patients are uncertain.

• Inform your doctor if you have previously had liver problems, including hepatitis. HIV-infected patients who also have liver problems (including chronic hepatitis B or C), when treated with antiretrovirals, have a higher risk of severe and potentially fatal liver complications. If you have hepatitis B or C, your doctor will carefully evaluate the best treatment regimen for you.
• Find out your hepatitis B virus (HBV) status before starting Truvada. If you have HBV infection, there is a serious risk of liver problems if you stop taking Truvada, whether or not you have HIV. It is important that you do not stop taking Truvada without speaking to your doctor: see section 3, Do not stop treatment with Truvada.
• Inform your doctor if you are over 65 years old. Truvada has not been studied in patients over 65 years of age.
• Inform your doctor if you are lactose intolerant (see Truvada contains lactose below in this section).

Children and adolescents
Truvada is not indicated in children under 12 years of age.
Other medicines and Truvada
Do not take Truvada if you are already taking other medicines containing the components of Truvada
(emtricitabine and tenofovir disoproxil) or any other antiviral medicine containing tenofovir alafenamide, lamivudine, or adefovir dipivoxil.
Taking Truvada with other medicines that may harm the kidneys: it is particularly important to inform your doctor if you are taking any of the following medicines, including:

• aminoglycosides (for bacterial infection)
• amphotericin B (for fungal infection)
• foscarnet (for viral infection)
• ganciclovir (for viral infection)
• pentamidine (for infections)
• vancomycin (for bacterial infection)
• interleukin-2 (for cancer treatment)
• cidofovir (for viral infection)
• non-steroidal anti-inflammatory drugs (NSAIDs, used to relieve bone or muscle pain)

If you are taking another antiviral medicine called a protease inhibitor to treat HIV, your doctor may prescribe blood tests to monitor your kidney function more closely.
It is also important to inform your doctor if you are taking ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevir to treat hepatitis C infection.
Taking Truvada with other medicines containing didanosine (for the treatment of HIV infection): Taking Truvada with other antiviral medicines containing didanosine may increase the level of didanosine in the blood and may reduce CD4 cell count. When medicines containing tenofovir disoproxil and didanosine have been taken together, cases of pancreatitis and lactic acidosis (excess lactic acid in the blood) have rarely been reported, sometimes leading to death. Your doctor must carefully consider whether to treat you with tenofovir and didanosine in combination.
Inform your doctor if you are taking any of these medicines. Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Truvada with food and drink

• Truvada should be taken with food whenever possible.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
If you have taken Truvada during pregnancy, your doctor may request regular blood tests and other diagnostic examinations to monitor the child's development. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV has outweighed the risk of side effects.

• Do not breastfeed while being treated with Truvada. This is because the active substances of this medicine are excreted in breast milk.
• Breastfeeding is not recommended for HIV-positive women because HIV infection can be transmitted to the infant through breast milk.
• If you are breastfeeding or considering breastfeeding, you must discuss this with your doctor as soon as possible.

Driving and using machines
Truvada may cause dizziness. If dizziness occurs while taking Truvada, do not drive and do not use tools or machines.
Truvada contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Truvada contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., it is essentially “sodium-free”.

3. How to take Truvada

• Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

The recommended dose of Truvada for treating HIV is:

• Adults: one tablet daily, preferably taken with food.
• Adolescents aged 12 to less than 18 years weighing at least 35 kg: one tablet daily, preferably taken with food.

The recommended dose of Truvada to reduce the risk of acquiring HIV is:

• Adults: one tablet daily, preferably taken with food.
• Adolescents aged 12 to less than 18 years weighing at least 35 kg: one tablet daily, preferably taken with food.

If you have difficulty swallowing, you may use the back of a spoon to crush the tablet.
Then mix the powder in about 100 mL (half a glass) of water, orange juice, or grape juice
and drink immediately.

• Always take the dose prescribed by your doctor. This is important to ensure that your medicine remains fully effective and to reduce the risk of developing resistance to treatment. Do not change your dose unless your doctor tells you to.
• If you are being treated for HIV infection, your doctor will prescribe Truvada together with other antiretroviral medicines. Please refer to the package leaflet of the other antiretrovirals for instructions on how to take them.
• If you are taking Truvada to reduce the risk of acquiring HIV, take Truvada every day, not only when you think you may have been exposed to HIV.

Talk to your doctor if you have questions about how to avoid acquiring HIV or preventing transmission
of HIV to others.
If you take more Truvada than you should
If you accidentally take more Truvada than recommended, contact your doctor or
the nearest emergency department. Take the bottle of tablets with you so that you can easily describe
what you have taken.
If you miss a dose
It is important not to miss doses of Truvada.

• If you remember within 12 hours of your usual time of taking Truvada, take the tablet as soon as possible, preferably with food. Then take your next dose at the usual time.
• If you remember 12 hours or more after your usual time of taking Truvada, do not take the missed dose. Wait and take the next dose, preferably with food, at the usual time.

If you vomit within 1 hour of taking Truvada, take another tablet.
You should not take another tablet if you vomit more than 1 hour after taking Truvada.
Do not stop taking Truvada

• If you are taking Truvada for treatment of HIV infection, stopping the tablets may reduce the effectiveness of your anti-HIV therapy as prescribed by your doctor.
• If you are taking Truvada to reduce the risk of acquiring HIV, do not stop taking Truvada or miss doses. If you stop taking Truvada or miss doses, your risk of acquiring HIV infection may increase.

Do not stop taking Truvada without first talking to your doctor.

• If you have hepatitis B, it is especially important not to stop taking Truvada without first consulting your doctor. Blood tests may need to be repeated for several months after stopping treatment. In some patients with advanced liver disease or cirrhosis, stopping treatment is not recommended, as it may lead to worsening of hepatitis, which could be potentially fatal.

Contact your doctor immediately if you experience any new or unusual symptoms
after stopping treatment, particularly symptoms normally associated
with hepatitis B infection.
If you have any doubts about how to use this medicine, talk to your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Possible serious side effects:

• Lactic acidosis (excess lactic acid in the blood) is a rare but potentially fatal side effect. Lactic acidosis occurs more frequently in women, especially if overweight, and in people with liver disease. The following may be signs of lactic acidosis:
  • shortness of breath
  • drowsiness
  • feeling sick, vomiting
  • stomach pain

If you think you have lactic acidosis, seek medical advice 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 due to previous infections may occur shortly after starting anti-HIV treatment.

It is believed that these symptoms are due to an improved immune response, which enables the body to fight infections that may have been present without obvious symptoms.

• Autoimmune disorders, in which the immune system attacks healthy body tissue, may also occur after starting medicines to treat HIV infection. Autoimmune disorders may occur many months after starting treatment. Watch for the appearance of any symptoms of infection or other symptoms such as:
  • muscle weakness
  • weakness starting in the hands and feet and moving up towards the trunk
  • palpitations, tremor, or hyperactivity

If you notice these or other symptoms of inflammation or infection, seek medical advice immediately.
Possible side effects:
Very common side effects
(may affect more than 1 in 10 people)

• diarrhoea, vomiting, nausea
• dizziness, headache
• rash
• feeling weak

Blood tests may also show:

• reduced phosphate levels in the blood
• elevated creatine kinase

Common side effects
(may affect up to 1 in 10 people)

• pain, stomach ache
• difficulty sleeping, abnormal dreams
• digestive problems resulting from discomfort after meals, bloating, excess intestinal gas
• skin rashes (including red spots or pustules, sometimes with blisters and skin swelling), which may be an allergic reaction, itching, skin colour changes with appearance of dark patches
• other allergic reactions, such as wheezing, swelling, or feeling confused
• loss of bone mass

Blood tests may also show:

• decreased white blood cell count (this may make you more prone to infections)
• increased triglycerides (fatty acids), bile, or glucose in the blood
• problems with liver and pancreas

Uncommon side effects
(may affect up to 1 in 100 people)

• abdominal pain caused by inflammation of the pancreas
• swelling of the face, lips, tongue, or throat
• anaemia (low red blood cell count)
• muscle breakdown, muscle pain, or muscle weakness, which may occur due to damage to renal tubular cells

Blood tests may also show:

• reduced potassium in the blood
• increased creatinine in the blood
• changes in urine

Rare side effects
(may affect up to 1 in 1,000 people)

• lactic acidosis (see Possible serious side effects)
• fatty liver
• yellowing of the skin or eyes, itching, or abdominal pain caused by liver inflammation
• kidney inflammation, excessive urination and thirst, kidney failure, damage to renal tubular cells
• softening of the bones (with bone pain and sometimes fractures)
• back pain caused by kidney problems

Damage to renal tubular cells may be associated with muscle breakdown, softening of the bones (with bone pain and sometimes fractures), muscle pain, muscle weakness, and decreased potassium or phosphate levels in the blood.
If you notice any of the side effects listed above, or if any of them become severe, contact your doctor or pharmacist.
The frequency of the following side effects is not known.

• Bone problems. Some patients taking combination antiretroviral medicines such as Truvada may develop a bone disease called osteonecrosis (death of bone tissue caused by reduced blood supply to the bone). Long-term use of this type of medicine, use of corticosteroids, alcohol consumption, a severely weakened immune system, and being overweight may be among the many risk factors for developing this condition. Signs of osteonecrosis include:
  • joint stiffness
  • joint pain (especially in the hip, knee, and shoulder)
  • difficulty moving

If you notice any of these symptoms, contact your doctor.

During HIV treatment, an increase in weight and in blood lipid and glucose levels may occur. This is partly related to improved health status and lifestyle, and in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will monitor these changes.
Other effects in children

• Children who have been given emtricitabine have very commonly developed changes in skin pigmentation, including:
  • development of dark patches on the skin
• Children have commonly developed a low red blood cell count (anaemia)
  • this may cause tiredness or shortness of breath in the child

If you notice any of these symptoms, contact your doctor.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Truvada

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and carton after {Exp.}. The expiry date refers to the last day of that month.
Store in the original packaging to protect the medicine from moisture. Keep the bottle tightly closed.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Truvada contains

• The active substances are emtricitabine and tenofovir disoproxil. Each film-coated tablet of Truvada contains 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 excipients are sodium croscarmellose (E468), glycerol triacetate (E1518), hypromellose (E464), indigo carmine aluminium lake (E132), lactose monohydrate, magnesium stearate (E572), microcrystalline cellulose (E460), pregelatinized starch (gluten-free) and titanium dioxide (E171).

Description of the appearance of Truvada and contents of the pack
Truvada film-coated tablets are blue, capsule-shaped, marked on one side with the word “GILEAD” and on the other side with the number “701”. Truvada is supplied in bottles containing 30 tablets.
Each bottle contains a silica gel desiccant, which should be kept in the bottle to protect the tablets. The silica gel is contained in a separate sachet or small container and must not be swallowed.
The following pack sizes are available: outer packs containing 1 bottle of 30 film-coated tablets, 60 (2 bottles of 30) and 90 (3 bottles of 30) film-coated tablets. Not all 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 about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Gilead Sciences Belgium SRL-BV Gilead Sciences Ireland UC
Tél/Tel: + 32 (0) 24 01 35 50 Tel: + 353 (0) 1 686 1888

България Luxembourg/Luxemburg
Gilead Sciences Ireland UC Gilead Sciences Belgium SRL-BV
Тел.: + 353 (0) 1 686 1888 Tél/Tel: + 32 (0) 24 01 35 50

Česká republika Magyarország
Gilead Sciences s.r.o. Gilead Sciences Ireland UC
Tel: + 420 910 871 986 Tel.: + 353 (0) 1 686 1888

Danmark Malta
Gilead Sciences Sweden AB Gilead Sciences Ireland UC
Tlf: + 46 (0) 8 5057 1849 Tel: + 353 (0) 1 686 1888

Deutschland Nederland
Gilead Sciences GmbH Gilead Sciences Netherlands B.V.
Tel: + 49 (0) 89 899890-0 Tel: + 31 (0) 20 718 36 98

Eesti Norge
Gilead Sciences Ireland UC Gilead Sciences Sweden AB
Tel: + 353 (0) 1 686 1888 Tlf: + 46 (0) 8 5057 1849

Ελλάδα Österreich
Gilead Sciences Ελλάς Μ.ΕΠΕ. Gilead Sciences GesmbH
Τηλ: + 30 210 8930 100 Tel: + 43 1 260 830

España Polska
Gilead Sciences, S.L. Gilead Sciences Poland Sp. z o.o.
Tel: + 34 91 378 98 30 Tel.: + 48 22 262 8702

France Portugal
Gilead Sciences Gilead Sciences, Lda.
Tél: + 33 (0) 1 46 09 41 00 Tel: + 351 21 7928790

Hrvatska România
Gilead Sciences Ireland UC Gilead Sciences (GSR) S.R.L
Tel: + 353 (0) 1 686 1888 Tel: + 40 31 631 18 00

Ireland Slovenija
Gilead Sciences Ireland UC Gilead Sciences Ireland UC
Tel: + 353 (0) 214 825 999 Tel: + 353 (0) 1 686 1888

Ísland Slovenská republika
Gilead Sciences Sweden AB Gilead Sciences Slovakia s.r.o.
Sími: + 46 (0) 8 5057 1849 Tel: + 421 232 121 210

Italia Suomi/Finland
Gilead Sciences S.r.l. Gilead Sciences Sweden AB
Tel: + 39 02 439201 Puh/Tel: + 46 (0) 8 5057 1849

Κύπρος Sverige
Gilead Sciences Ελλάς Μ.ΕΠΕ. Gilead Sciences Sweden AB
Τηλ: + 30 210 8930 100 Tel: + 46 (0) 8 5057 1849

Latvija United Kingdom (Northern Ireland)
Gilead Sciences Ireland UC Gilead Sciences Ireland UC
Tel: + 353 (0) 1 686 1888 Tel: + 44 (0) 8000 113 700

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION OF THE TERMS OF THE MARKETING AUTHORISATION(S)

Scientific conclusions
Taking into account the assessment by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for emtricitabine/tenofovir disoproxil, the PRAC's scientific conclusions are as follows:
In light of the available data on decreased bone mineral density from clinical studies, literature and spontaneous reports, the PRAC considers that a causal relationship between emtricitabine/tenofovir disoproxil and decreased bone mineral density is at least a reasonable possibility. The PRAC also considers that the current warning/precaution regarding bone effects should be further strengthened. The PRAC has concluded that the product information for medicinal products containing emtricitabine/tenofovir disoproxil should be modified accordingly.

Following review of the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and rationale of the PRAC recommendation.

Grounds for the variation of the terms of the marketing authorisation(s)
Based on the scientific conclusions for emtricitabine/tenofovir disoproxil, the CHMP considers that the benefit-risk balance of the medicinal product(s) containing emtricitabine/tenofovir disoproxil remains favourable, subject to the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation(s).