Package Insert: Information for the User

Retrovir 250 mg Hard Capsules

zidovudine

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

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

Retrovir is used to treat HIV (Human Immunodeficiency Virus) infection.

The active ingredient of Retrovir is zidovudina. Retrovir belongs to a group of medications known as antiretrovirals. It belongs to a group of medications known as Inhibitors of the reverse transcriptase (RTIs).

Retrovir does not eliminate the HIV infection. It reduces the amount of virus in your body and keeps it at a low level. Retrovir also increases the count of CD4 cells in the blood. CD4 cells are a type of white blood cells important for fighting infections.

Retrovir is used in combination with other medications (combined treatment) to treat HIV in adults and children. To control the HIV infection and prevent the disease from worsening, you must take all your medications.

If you are pregnant, your doctor may prescribe Retrovir to help prevent the HIV from passing to the fetus. After birth, it is possible that the baby may also have to take Retrovir to prevent infection with HIV.

HIV infection is transmitted through sexual contact with an infected person or through contact with infected blood (for example, sharing injection needles).

Do not take Retrovir

• if you are allergic(hypersensitive) to zidovudine or any of the other components of Retrovir (listed in section 6)
• if you have very few white blood cells(neutropenia)or very few red blood cells(anemia).

Retrovir for newborns

Retrovir should not be administered to newborns with liver problems, including:

• some cases ofhyperbilirubinemia(high levels of a substance calledbilirubinin the blood that can cause yellow discoloration of the skin)
• other problems that cause high levels of liver enzymes in the blood.

Be especially careful with Retrovir

Some patients treated with Retrovir or combination HIV treatments have a higher risk of severe adverse reactions. Be aware of these possible risks if:

• you have ever had liver disease(including hepatitis B or C)
• you have significant obesity(especially if you are a woman).

• Speak with your doctor if you are affected by any of the above circumstances. You may need more doctor visits, even blood tests while taking the medication.See section 4 for more information.

Important symptoms to be aware of

In some patients with HIV infection, signs and symptoms, sometimes severe, may appear during treatment with Retrovir.

Read section 4 of this prospectus carefully, if you have any questions about this information:

• Consult with your doctor.

Other medications and Retrovir

Inform your doctor or pharmacist if you are using or have recently used other medications, including medications based on herbal remedies or those obtained without a prescription. Remember to inform your doctor or pharmacist if you start taking a new medication during treatment with Retrovir.

Do not take these medications with Retrovir:

• stavudine, to treat HIV infection
• ribavirinor injections ofganciclovir, to treat viral infections
• rifampicin, anantibiotic.

Some medications may increase your risk of adverse effects or make them worse, for example:,

• valproate sodium, used to treatepilepsy
• aciclovir,ganciclovirorinterferon, used to treatviral infections
• pyrimethamine, used to treatmalariaand other parasitic infections
• dapsone, used to preventpneumoniaand treatskin infections
• fluconazoleorflucitosine, used to treatinfections caused by fungisuch asCandida
• pentamidineoratovaquone, to treat parasitic infections such asPCP(Pneumocystis pneumonia)
• amphotericinorco-trimoxazole, used to treatinfections caused by fungi or bacteria
• probenecid, used to treatgoutand similar conditions, and administered with some antibiotics to make them more effective
• methadone, used as a substitute for heroin
• vincristine,vinblastineordoxorubicin, used to treatcancer.

• Inform your doctorif you are taking any of these medications.

Some of the medications that interact with Retrovir are:

• clarithromycin, anantibiotic
• phenytoin, used to treatepilepsy.

• Inform your doctorif you are taking clarithromycin or phenytoin. Your doctor may need to monitor you while taking Retrovir.

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant:

• Consult with your doctorabout the benefits and risks of taking Retrovir.

Women with HIV who take Retrovir have a lower risk of transmitting the infection to their baby.

Retrovir and similar medications may cause adverse effects in the fetus. If you have been taking Retrovir during your pregnancy, your doctor may request periodic blood tests and other diagnostic tests to monitor your child's development. In children whose mothers took INTIs during pregnancy, the benefit of HIV protection was greater than the risk of adverse effects.

Lactation

Do not recommendthat women with HIV breastfeed because the HIV infection can be transmitted to the baby through breast milk.

A small amount of the components of Retrovir may also pass into breast milk.

If you are breastfeeding or plan to breastfeed,you should consult with your doctor as soon as possible.

Driving and operating machines

Retrovir may affect your ability to drive and operate machines, as it may cause dizziness and other adverse effects that may make you less alert.

• Do not drive or operate toolsormachinesunless you feel well.

Retrovir contains sodium

This medication contains less than 23 mg ofsodium(1 mmol) per dose; this is, essentially “sodium-free”.

You will need periodic blood tests

During treatment with Retrovir, your doctor will ask you to have regular blood tests to check for adverse effects. For more information on adverse effects, see section 4 of this prospectus.

Maintain regular contact with your doctor

Retrovir helps you control your disease, but it does not cure HIV infection. You will need to take it every day to prevent your disease from getting worse. You may develop other infections associated with HIV infection.

• Maintain contact with your doctor and do not stop taking Retrovirwithout their advice.

Follow exactly the administration instructions for this medication as indicated by your doctor.If in doubt, consult your doctor or pharmacist again.

Swallow the hard capsules whole with a little water.

How much Retrovir will you need to take?

Adults and adolescents weighing at least30 kg:

The usual dose of Retrovir is 250 mg twice a day. Take the doses with 12 hours apart.

Children:

Children can take zidovudinein oral solutionor in 100 mg capsules.

Dosage during pregnancy and childbirth:

Retrovir is not recommended for pregnant women with less than 14 weeks of pregnancy. After the 14th week, your doctor may prescribe 500 mg, administered as 100 mg five times a day, until the onset of labor. During labor, your doctor may decide to use zidovudineinjectable until the umbilical cord is cut. It is possible that you will also be administered Retrovir to the newborn to prevent HIV infection.

Dosage in patients with renal or hepatic problems:

If you have severe kidney or liver problems, your doctor may decide to use a lower dose, depending on their function. Follow your doctor's advice.

If you take more Retrovir than you should

If you take more Retrovirthan you should,consult your doctor or pharmacist. If possible, show them the Retrovir packaging.

If you forget to take Retrovir

If you forget to take a dose, do not worry. You can take the next dose as soon as you remember, but not within two hours of the next dose. If you remember when there are less than two hours left until the next dose, simply skip the missed dose and take the next one at the usual time. Then continue your treatment as before.

Do not take a double dose to compensate for missed doses.

If you interrupt treatment with Retrovir

Do not stop taking Retrovir without medical advice

Take Retrovir for the time your doctor has indicated.Do not stop taking it unless your doctor tells you to.

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

Treatment with zidovudine (Retrovir) often causes a loss of fat from the legs, arms, and face (lipoatrophy). This loss of body fat has been shown not to be completely reversible after stopping zidovudine. Your doctor should watch for signs of lipoatrophy. If you notice any loss of fat in your legs, arms, and face, report it to your doctor. When these symptoms occur, Retrovir should be stopped and the HIV treatment changed.

Like all medications, this medication can cause side effects, although not everyone will experience them. Some side effects may be reflected in your blood tests, and may not appear until 4-6 weeks after starting Retrovir. If you experience any of these side effects, and if they are severe, your doctor may advise you to stop taking Retrovir.

Aside from the side effects described below, others may occur during HIV combination treatment.

• It is important to read the information on “Other possible side effects of HIV combination treatment.”

Very common side effects

May affect more than 1 in 10 people treated with Retrovir:

• headache
• nausea.

Common side effects

May affect up to 1 in 10 people treated with Retrovir:

• vomiting
• diarrhea
• stomach pain
• dizziness
• muscle pain
• general feeling of illness.

Common side effects that may show up in blood tests are:

• decrease in the number of red blood cells (anemia) and white blood cells (leucopeniaorneutropenia)
• increase in blood of liver enzymes
• increase ofbilirubin(a substance produced in the liver) in blood that may give a yellowish color to the skin.

Uncommon side effects

May affect up to 1 in 100 people treated with Retrovir:

• skin rash (redness, swelling, or itching of the skin)
• difficulty breathing
• fever (elevated temperature)
• generalized pain and fatigue
• flatulence
• weakness.

Uncommon side effects that may show up in blood tests are:

• reduction in the number of blood cells involved in blood clotting (trombocytopenia) or of all types of blood cells (pancytopenia).

Rare side effects

May affect up to 1 in 1,000 people treated with Retrovir:

• lactic acidosis (excess of lactic acid in the blood; see the section below, “Other possible side effects of HIV combination treatment”)
• liver changes, for example jaundice, liver enlargement, and fatty liver
• pancreatitis
• chest pain, cardiac changes
• seizures
• anxiety and depression, insomnia, lack of concentration, drowsiness
• indigestion, loss of appetite, alteration of taste
• changes in the color of nails, skin, or mucous membranes of the mouth
• influenza-like syndrome: chills, sweating, and cough
• tingling sensation in the skin (like having pins and needles)
• frequency of urination
• increase in the size of the breasts in men.

A rare side effect that may show up in blood tests is:

• decrease in the number of a type of red blood cells (aplastic anemia).

Very rare side effects

May affect up to 1 in 10,000 people treated with Retrovir:

A rare side effect that may show up in blood tests is:

• failure of the bone marrow in the production of new blood cells (aplastic anemia).

If you experience any type ofside effect

• Consult your doctor or pharmacist. This includes any possible side effects not mentioned in this leaflet.

Other possible side effects of HIV combination treatment

Other processes may develop during HIV treatment.

Infections may recur

People with advanced HIV infection (AIDS) have a weakened immune system and are more likely to develop serious infections (opportunistic infections). When these people start treatment, they may find that old infections, which were hidden, flare up, causing signs and symptoms of inflammation. These symptoms are probably caused because the immune system reacts to these infections.

Aside from opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also appear after you have started taking medications for your HIV infection. Autoimmune disorders may appear many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and rising to the trunk of the body, palpitations, tremors, or hyperactivity, report it to your doctor immediately to receive the necessary treatment.

If you have any symptoms of infection during treatment with Retrovir:

• Inform your doctor immediately. Do not take other medications without consulting your doctor.

Lactic acidosis is a rare but serious side effect

Some people who take Retrovir develop a condition called lactic acidosis, along with an enlarged liver. Lactic acidosis is due to an increase in lactic acid levels in the body. It is rare and usually develops after a few months of treatment. It can be potentially fatal, causing failure of internal organs.

Lactic acidosis is more likely to develop in patients with liver disease, or in obese people (with significant overweight), especially women.

The signs of lactic acidosis include:

• difficult breathing, rapid, and deep

• drowsiness

• numbnessorweaknessin the limbs
• loss of appetite,weight loss

• uncomfortable(nausea)andvomiting

• stomach pain.

During treatment, your doctor will monitor any sign that may indicate you are developing lactic acidosis. If you have any of the symptoms mentioned above, or if you are concerned about any other symptom:

• Visit your doctor as soon as possible.

You may have bone problems

Some patients who receive HIV combination treatment develop a bone disease calledosteonecrosis. With this disease, part of the bone tissue dies due to a reduction in blood supply to the bone.

People are more likely to develop this disease:

• if they have been taking combination treatment for a long time

• if they also take anti-inflammatory medications called corticosteroids
• if they drink alcohol
• if their immune system is severely weakened
• if they are overweight.

The signs of osteonecrosis include:

• stiffness in the joints

• pain(especially in the hip, knee, or shoulder)

• difficulty moving.

If you notice any of these symptoms:

• Inform your doctor.

Other effects that may appear in tests:

HIV combination treatment may also cause:

• increase of lactic acid in blood, which in rare cases may lead to lactic acidosis.

This effect may be shown in blood tests during treatment with Retrovir.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not mentioned in this leaflet. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after CAD.The expiration date is the last day of the month indicated.

Do not store at a temperature above30°C. Store in the original packaging.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Retrovir

The active ingredient is zidovudine. Each capsule contains 250 mg of zidovudine.

The other components are: cornstarch, microcrystalline cellulose, sodium carboxymethylcellulose, magnesium stearate, titanium dioxide (E171), gelatin, indigo carmine (E132), and opaque black printing ink 10A1 or 10A2 (lacquer, black iron oxide (E172), propylene glycol, ammonium hydroxide, 28% (only in opaque black ink 10A1), concentrated ammonia solution (only in opaque black ink 10A2), potassium hydroxide (only in opaque black ink 10A2)).

Appearance of the product and content of the container

Retrovir 250 mg are hard gelatin capsules, opaque, white body and blue cap, marked with the code “GSJV2” printed in black ink. They are packaged in blisters and supplied in containers of 40 capsules.

Holder of the marketing authorization

ViiV Healthcare, S.L.

P.T.M. C/ Severo Ochoa, 2

28760 Tres Cantos (Madrid)

Tel: + 34 900 923 501

es-ci@viivhealthcare.com

Responsible for manufacturing

Delpharm Poznan Spólka Akcyjna - ul. Grunwaldzka 189 – (60-322 Poznan) – Poland

Last review date of this leaflet:April 2021.

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/