RETROVIR 250 mg Capsules

Contents of the leaflet

1. Leaflet accompanying the packaging: patient information
2. Retrovir, 100 mg, hard capsules
3. Retrovir, 250 mg, hard capsules
   1. Read the leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
4. What is Retrovir and what is it used for
5. Important information before taking Retrovir
   1. When not to take Retrovir
   2. Warnings and precautions
   3. Retrovir and other medicines
   4. Pregnancy, breastfeeding, and fertility
   5. Driving and using machines
   6. Retrovir contains sodium
6. How to take Retrovir
   1. Adults and adolescents with a body weight of at least 30 kg
   2. Children with a body weight of at least 8 kg and less than 30 kg
   3. Children with a body weight of less than 4 kg
   4. Dosing for the prevention of mother-to-child transmission of HIV and for newborns
   5. Changes in dosage due to hematologic adverse reactions
   6. Dosing in elderly patients
   7. Dosing in patients with impaired renal function
   8. Dosing in patients with impaired hepatic function
   9. Overdose of Retrovir
   10. Missed dose of Retrovir
7. Possible side effects
   1. Reporting side effects
8. How to store Retrovir
9. Contents of the pack and other information
   1. What Retrovir contains
   2. What Retrovir looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder
   5. Manufacturer
   6. Date of last revision of the leaflet:

Leaflet accompanying the packaging: patient information

Retrovir, 100 mg, hard capsules

Retrovir, 250 mg, hard capsules

Zidovudine

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• The medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Retrovir and what is it used for

Retrovir contains zidovudine as the active substance. Zidovudine belongs to a group of antiviral medicines called nucleoside reverse transcriptase inhibitors (NRTIs). Retrovir capsules are used in adults and children in combination with other antiretroviral medicines to treat HIV infection. Retrovir is also used in pregnant women (after the 14th week of pregnancy) who have been diagnosed with HIV, and in newborns born to these women, to reduce the risk of transmission of HIV from mother to fetus.

2. Important information before taking Retrovir

When not to take Retrovir

• if you are allergic to zidovudine or any of the other ingredients of this medicine (listed in section 6);
• in patients who have a very low number of neutrophils (a type of white blood cell) or a very low hemoglobin level in the blood;
• in newborns with hyperbilirubinemia who require treatment other than phototherapy, or with increased transaminase activity exceeding 5 times the upper limit of normal.

If you have any doubts, consult your doctor.

Warnings and precautions

Before starting Retrovir, discuss it with your doctor, pharmacist, or nurse. The medicine does not cure HIV infection, it only slows down its progression and allows the disease to be kept under control. Due to HIV infection, other infections or diseases related to HIV may develop. Retrovir should be used under the supervision of a doctor experienced in the treatment of patients with HIV or AIDS. Retrovir should be taken every day. You should regularly consult your doctor. Do not stop taking the medicine without consulting your doctor first. Transmission of HIV from mother to child during pregnancy may occur despite the use of the medicine to prevent such transmission. Anemiaand neutropeniaZidovudine may affect the production of red blood cells, leading to anemia. The main symptoms of this condition are fatigue and shortness of breath. Less commonly, a decrease in the production of a certain type of white blood cell may occur, which can increase the susceptibility to infections. Your doctor may recommend periodic blood tests to monitor the number of certain blood cells. These changes are usually reversible. Taking Retrovir with ribavirin may cause or exacerbate existing anemia. If you experience symptoms of anemia (such as fatigue and shortness of breath), you should contact your doctor, who will decide whether to stop taking Retrovir. Lactic acidosisThe group of medicines to which Retrovir belongs (NRTIs) may cause a condition called lactic acidosis. Lactic acidosis, if it occurs, usually develops after several months of treatment. Deep, rapid breathing, drowsiness, and other non-specific symptoms, such as nausea, vomiting, abdominal pain, may indicate the development of lactic acidosis. This rare but serious side effect occurs more frequently in women, especially those who are overweight. Liver disease, particularly liver enlargement, hepatitis, and liver steatosis, may also increase the risk of this condition. During Retrovir treatment, your doctor will closely monitor your condition to detect any symptoms that may indicate the development of lactic acidosis. Fat redistributionTreatment with Retrovir or other zidovudine-containing medicines may cause loss of fat tissue in the legs, arms, and face ( lipoatrophy). Your doctor should monitor you for lipoatrophy. If you notice any loss of fat tissue in your legs, arms, or face, you should tell your doctor. If such symptoms occur, your doctor will assess whether to discontinue Retrovir and use alternative HIV treatment. After stopping Retrovir, reversal of fat loss may be observed after several months, and the lost fat tissue may not be fully regained. Lipid and glucose levels in the bloodDuring HIV treatment, lipid and glucose levels in the blood may increase. This is partly related to improved health and lifestyle, and sometimes, in the case of lipid levels in the blood, to the effect of anti-HIV medicines. Your doctor will recommend tests to detect these changes. Liver disease (hepatitis)If you have had liver disease in the past, you should discuss it with your doctor. In patients with chronic viral hepatitis B or C, treated with antiretroviral medicines, there may be an increased risk of severe and potentially life-threatening side effects from the liver, and blood tests may be necessary to monitor liver function. Immune reactivation syndromeIn some patients with advanced HIV infection (AIDS), who have had opportunistic infections in the past, symptoms of inflammation caused by the previous infection may appear soon after starting anti-HIV treatment. It is believed that these symptoms result from the improvement in the body's ability to respond to infections, allowing it to fight infections that may not have caused symptoms. If you notice any symptoms of inflammation, you should contact your doctor immediately. Autoimmune diseases (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported in the context of immune recovery (immune reactivation). However, the time to their onset is more variable, and these diseases, often with non-specific symptoms, may appear many months after starting treatment. Use in elderly patients and patients with impaired renal and hepatic functionYou should consult your doctor, who may decide to adjust the dose (see "How to take Retrovir"). Bone necrosisSome patients have reported a condition called bone necrosis, which may be caused by multiple factors (including corticosteroid use, alcohol consumption, severe immunosuppression, and increased body mass index). If you experience limb pain, stiffness, or difficulty moving, you should contact your doctor. Patients with co-existing hepatitis C virus infectionDuring zidovudine treatment as part of an HIV treatment regimen, cases of worsening anemia (associated with ribavirin administration) have been reported, although the exact mechanism of this phenomenon has not been fully explained. Due to the increased risk of anemia, concomitant administration of ribavirin and zidovudine is not recommended. Your doctor may consider replacing zidovudine with another medicine in the antiretroviral treatment regimen if it has been previously established. This is particularly important in patients who have had anemia associated with zidovudine treatment in the past.

Retrovir and other medicines

Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. This includes medicines available without a prescription, including herbal medicines. The following medicines should not be taken with Retrovir:

• rifampicin (an antibiotic),
• stavudine (used to treat HIV infections).

Retrovir may interact with some medicines, which may increase the risk of side effects. If you are taking any of the following medicines, you should inform your doctor (or consult your doctor if you are unsure):

• phenytoin, valproic acid (used to treat epilepsy),
• oxazepam, lorazepam (used to treat anxiety),
• acetylsalicylic acid (aspirin), ketoprofen, naproxen (used as anti-inflammatory, antipyretic, and analgesic medicines),
• codeine (a cough medicine),
• morphine (used to treat pain),
• methadone (used as a heroin substitute in addiction treatment),
• indomethacin (used to treat rheumatoid arthritis),
• cimetidine (used to treat gastric and duodenal ulcers),
• clofibrate (used to treat lipid disorders),
• isoniazid (an antiviral medicine that affects the immune system),
• probenecid (used to treat goutand similar diseases, and used in combination with certain antibiotics to increase their effectiveness),
• pentamidine, atovaquone (used to treat parasitic infections, such as pneumocystosis),
• amphotericin, co-trimoxazole (used to treat bacterial and fungal infections),
• pyrimethamine (used to treat malariaand other parasitic infections),
• dapsone (used to prevent pneumocystis pneumoniaand treat skin infections),
• fluconazole or flucytosine (used to treat fungal infections, such as thrush),
• ganciclovir, interferon (used to treat viral infections),
• clarithromycin (an antibiotic),
• lamivudine (used to treat HIV infections and hepatitis B virus),
• vincristine, vinblastine, or doxorubicin (used to treat cancer).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine. Retrovir should be used during pregnancy only if the benefits outweigh the risks to the fetus. The use of Retrovir in pregnant women (after the 14th week of pregnancy) with HIV infection and in newborns born to these women significantly reduces the risk of transmission of HIV from mother to child. If you are pregnant or plan to become pregnant, you should contact your doctor to discuss the possible risks and benefits of antiretroviral therapy for you and your child. If you have taken Retrovir during pregnancy, your doctor may recommend regular check-ups to monitor the development of your child. During these check-ups, blood tests and other diagnostic tests may be performed. Zidovudine, the active substance of Retrovir, passes into breast milk. If you are taking Retrovir, you should not breastfeed. It is not recommendedfor HIV-infected women to breastfeed, as HIV can be transmitted to the child through breast milk. If you are breastfeeding or considering breastfeeding, you should consult your doctor as soon as possible.

Driving and using machines

No studies have been conducted on the effects of Retrovir on the ability to drive and use machines. When deciding to drive or use machines, you should take into account your health and possible side effects of Retrovir.

Retrovir contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule, which means it is essentially "sodium-free".

3. How to take Retrovir

Retrovir should be taken as directed by your doctor. If you have any doubts about the dosage, consult your doctor or pharmacist. The prescribed doses may vary from patient to patient and depend on several factors, including the stage of the disease. To ensure that the entire dose is administered, the capsules should be swallowed whole, without opening them. However, if you are unable to swallow the capsules, they can be opened and the contents mixed with a small amount of semi-liquid food or liquid and given to the patient immediately after preparation.

Adults and adolescents with a body weight of at least 30 kg

The usual dose is 250 mg or 300 mg twice daily, in combination with other antiretroviral medicines.

Children with a body weight of at least 8 kg and less than 30 kg

Alternatively, for children with a body weight between 28 kg and 30 kg, the following dose can be used: For children with a body weight of at least 4 kg and less than 8 kgand for patients who have difficulty swallowing capsules, it is recommended to use zidovudine in the form of an oral solution in appropriate doses (see the patient information leaflet for Retrovir, 50 mg/5 ml, oral solution).

Children with a body weight of less than 4 kg

There are no sufficient data to recommend a specific dosage for children with a body weight of less than 4 kg.

Dosing for the prevention of mother-to-child transmission of HIV and for newborns

Pregnant women after the 14th week of pregnancy are given Retrovir orally at a dose of 500 mg per day (i.e., 100 mg five times a day) until the start of labor. During labor, Retrovir is administered as an intravenous infusion, initially at a dose of 2 mg/kg body weight over one hour, followed by a continuous intravenous infusion at a dose of 1 mg/kg body weight per hour until the umbilical cord is clamped. Newborns are given Retrovir orally at a dose of 0.2 ml/kg body weight (2 mg/kg body weight) every 6 hours, starting before 12 hours of age and continuing until 6 weeks of age. To ensure accurate dosing in newborns, syringes with a decimal scale (0.1 ml) should be used. For example, newborns weighing 2.0 kg and 5.0 kg should be given 0.4 ml (4 mg zidovudine) and 1.0 ml (10 mg zidovudine) of the oral solution, respectively, four times a day. If oral administration is not possible, Retrovir should be administered intravenously every 6 hours at a dose of 1.5 mg/kg body weight in a 30-minute intravenous infusion. If a cesarean section is planned, the intravenous infusion of Retrovir should be started 4 hours before the operation. If the operation is not performed, the infusion should be stopped and oral administration started.

Changes in dosage due to hematologic adverse reactions

If the hemoglobin level decreases to 7.5-9.0 g/100 ml (4.65-5.59 mmol/l) or the neutrophil count decreases to 0.75-1.0 × 10^9/l, your doctor may decide to reduce the dose or discontinue Retrovir (see "Important information before taking Retrovir").

Dosing in elderly patients

Your doctor may recommend regular monitoring tests before starting and during Retrovir treatment in this age group.

Dosing in patients with impaired renal function

In patients with severe renal impairment (creatinine clearance ≤ 10 ml/min) and in patients with end-stage renal disease undergoing hemodialysis or peritoneal dialysis, a dose of 100 mg every 6 to 8 hours (300 to 400 mg per day) is recommended.

Dosing in patients with impaired hepatic function

In patients with liver cirrhosis, accumulation of the medicine in the body may occur. Your doctor may decide to adjust the dose or extend the interval between doses, especially if symptoms of poor tolerance occur.

Overdose of Retrovir

If you have taken more than the recommended dose of Retrovir, you should inform your doctor or pharmacist or contact the nearest emergency department for advice.

Missed dose of Retrovir

It is very important to take the recommended dose of Retrovir every day, as this will ensure the greatest effectiveness of the treatment. If you miss a dose, you should take it as soon as possible. Then, continue treatment as directed. Do not take a double dose to make up for the missed dose.

4. Possible side effects

Like all medicines, Retrovir can cause side effects, although not everybody gets them. During HIV treatment, it is not always possible to determine whether a particular side effect is caused by Retrovir, other medicines taken at the same time, or the HIV infection itself. Therefore, it is very important to inform your doctor about any changes in your health. You should not be overly concerned after reading the following list of side effects, as you may not experience them. The profile of side effects in adults and children is similar. Very common side effects(occurring in more than 10 in 100 patients)

• headache, nausea.

Common side effects(occurring in 1 to 10 in 100 patients)

• anemia (low red blood cell count) and neutropenia or leukopenia (low white blood cell count). If the red blood cell count decreases, you may experience symptoms of fatigue and shortness of breath. A decrease in the white blood cell count may increase the susceptibility to infections,
• increased liver enzyme activity, bilirubin levels, and lactic acid levels,
• dizziness,
• muscle pain, malaise,
• vomiting, abdominal pain, diarrhea.

Uncommon side effects(occurring in 1 to 10 in 1,000 patients)

• decrease in platelet count (cells that play a crucial role in blood clotting). In people with a low platelet count, there may be an increased tendency to bleed and bruise,
• decrease in blood cell count (pancytopenia) with bone marrow hypoplasia (bone marrow with a reduced number of cells),
• weakness, fever, generalized pain,
• muscle disorders,
• shortness of breath,
• bloating,
• itching, rash.

Rare side effects(occurring in less than 1 in 1,000 patients)

• anxiety, depression, insomnia, drowsiness, seizures, confusion, sensory disturbances,
• taste disorders, loss of appetite, changes in the mouth with non-uniform discoloration, indigestion, pancreatitis, liver disorders, such as liver enlargement, hepatitis, and liver steatosis,
• changes in fat distribution or accumulation in the body,
• frequent urination, breast enlargement in men,
• a heart condition called cardiomyopathy,
• selective aplasia (a condition where the bone marrow fails to produce red blood cells),
• changes in nail and skin color, increased sweating, hives, flu-like symptoms, cough, chills, chest pain,
• lactic acidosis without decreased oxygen levels in the blood.

Very rare side effects(occurring in less than 1 in 10,000 patients)

• aplastic anemia (anemia caused by bone marrow failure).

Some patients taking NRTIs have reported a condition called lactic acidosis, which is caused by increased production of lactic acid in the body (see section 2 "Important information before taking Retrovir"). During HIV treatment, lipid and glucose levels in the blood may increase (see section 2 "Important information before taking Retrovir"). Retrovir may cause loss of fat tissue in the legs, arms, and face ( lipoatrophy, see section 2 "Important information before taking Retrovir").

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Retrovir

Keep the medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month stated. The batch number of the medicine is stated on the packaging after Lot. Do not store above 30°C. Store in a dry place. Protect from light. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Retrovir contains

Hard capsules 100 mg

• The active substance of the medicine is zidovudine. Each capsule contains 100 mg of zidovudine.
• The other ingredients of the medicine are: cornstarch, microcrystalline cellulose, sodium carboxymethylcellulose (type A), magnesium stearate.
• The hard gelatin capsule contains: gelatin, titanium dioxide (E 171), black ink opacode 10A1 with the composition: shellac, iron oxide black (E 172), propylene glycol, ammonium hydroxide, 28%.

Hard capsules 250 mg

• The active substance of the medicine is zidovudine. Each capsule contains 250 mg of zidovudine.
• The other ingredients of the medicine are: cornstarch, microcrystalline cellulose, sodium carboxymethylcellulose (type A), magnesium stearate.
• The hard gelatin capsule contains: gelatin, titanium dioxide (E 171), indigo carmine (E 132), black ink opacode 10A1 with the composition: shellac, iron oxide black (E 172), propylene glycol, ammonium hydroxide, 28%.

What Retrovir looks like and contents of the pack

Hard capsules 100 mg
The pack contains 100 capsules in 10 blisters of PVC/Aluminum, in a cardboard box.
The capsules are opaque, white, with black printing GSYJU on the capsule body.
Hard capsules 250 mg
The pack contains 40 capsules in 4 blisters of PVC/Aluminum, in a cardboard box.
The capsules are opaque, with a blue cap and a white body, with black printing GSJV2 on the capsule body.

Marketing authorization holder and manufacturer

Marketing authorization holder

ViiV Healthcare BV
Van Asch van Wijckstraat 55H
3811 LP Amersfoort
Netherlands

Manufacturer

Delpharm Poznań Spółka Akcyjna
Grunwaldzka 189
60-322 Poznań
Poland
To obtain more detailed information about this medicine, please contact the local representative of the marketing authorization holder:
GSK Services Sp. z o.o.
ul. Rzymowskiego 53
02-697 Warsaw
tel. 22-576-90-00

Date of last revision of the leaflet: