Retrovir

Patient Information Leaflet: Important Information

Retrovir, 100 mg, Hard Capsules

Retrovir, 250 mg, Hard Capsules

Zidovudine

Read the Leaflet Carefully Before Taking the Medication

• Keep this leaflet as 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. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform 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 HIV, and in newborns born to these women, to reduce the risk of passing HIV from mother to child.

2. Important information before taking Retrovir

When Not to Take Retrovir

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 helps keep the disease 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 treating patients with HIV or AIDS. Take Retrovir every day. Regularly consult your doctor. Do not stop taking the medicine without consulting your doctor first. Transmission of HIV from mother to child during pregnancy can occur despite the use of medicine to prevent it. 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 regular blood tests to monitor the number of certain blood cells. These changes are usually reversible. Taking Retrovir with ribavirin may cause or worsen existing anemia. If you experience symptoms of anemia (such as fatigue and shortness of breath), 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 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. While taking Retrovir, 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 from the legs, arms, and face (lipoatrophy). Your doctor should monitor you for signs of lipoatrophy. If you notice any loss of fat from your legs, arms, or face, 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 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, talk to 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 previously had an opportunistic infection, 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, 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 (reactivation). However, the time to onset is more variable, and these diseases, often with non-specific symptoms, may appear months after starting treatment. Use in elderly patients and patients with renal and hepatic impairmentConsult your doctor, who may decide to adjust the dose (see "How to take Retrovir"). Bone necrosisIn some patients, a condition called bone necrosis has been reported, which can be caused by many factors (including corticosteroids, alcohol consumption, severe immunosuppression, and increased body mass index). If you experience limb pain, stiffness, or difficulty moving, contact your doctor. Patients with co-existing hepatitis C virus infectionDuring the use of zidovudine as part of the 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 previously experienced anemia associated with zidovudine use.

Retrovir and Other Medicines

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

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

Retrovir may interact with some medicines, which can increase the risk of side effects. If you are taking any of the following medicines, 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 substitute for heroin in the treatment of addiction),
• indomethacin (used to treat rheumatoid arthritis),
• cimetidine (used to treat stomach ulcers and duodenal ulcers),
• clofibrate (used to treat lipid disorders),
• isoniazid (an antiviral medicine that affects the immune system),
• probenecid (used to treat gout and 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 malaria and other parasitic infections),
• dapsone (used to prevent pneumocystis pneumonia and 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 infection and hepatitis B virus infection),
• 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 baby, consult your doctor or pharmacist before taking this medicine. Retrovir should only be used during pregnancy if the benefits outweigh the risks to the baby. Taking Retrovir in pregnant women (after the 14th week of pregnancy) with HIV and in newborns born to these women significantly reduces the risk of passing HIV from mother to child. If you are pregnant or plan to become pregnant, you must consult your doctor to discuss the possible risks and benefits of antiretroviral therapy for you and your baby. If you have taken Retrovir during pregnancy, your doctor may recommend regular check-ups to monitor your baby's development. 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 their babies because HIV can be passed on to the baby through breast milk. If you are breastfeeding or thinking of 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

Take Retrovir exactly as your doctor has told you. If you are unsure about your dose, consult your doctor or pharmacist. The prescribed dose may vary from person to person and depends on several factors, including the stage of the disease. To ensure that the full dose is taken, swallow the capsules whole without opening them. However, if you are unable to swallow the capsules, you can open them and mix the contents with a small amount of semi-solid food or liquid and give the entire mixture to the patient immediately after preparation.

Adults and Adolescents Weighing at Least 30 kg

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

Children Weighing at Least 8 kg but Less Than 30 kg

Alternatively, for children weighing between 28 kg and 30 kg, the following doses can be used: For children weighing at least 4 kg but less than 8 kgand for patients who have difficulty swallowing capsules, zidovudine oral solution is recommended in appropriate doses (see the patient information leaflet for Retrovir, 50 mg/5 ml, oral solution).

Children Weighing Less Than 4 kg

There are insufficient data to recommend a specific dose for children weighing less than 4 kg.

Dosing for 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. For newborns, Retrovir is administered 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, for newborns weighing 2.0 kg and 5.0 kg, 0.4 ml (4 mg zidovudine) and 1.0 ml (10 mg zidovudine) of oral solution should be administered four times a day, respectively. If oral administration to the newborn 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 discontinued and oral administration should be started.

Dose Adjustment in Patients with 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 treatment with Retrovir.

Dosing in Patients with Renal Impairment

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 Hepatic Impairment

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

Overdose

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

Missed Dose

It is very important to take the prescribed dose of Retrovir every day to ensure the best effectiveness of the treatment. If you miss a dose, take it as soon as possible. Then continue with the treatment as recommended. 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)

• decreased platelet count (thrombocytopenia). In people with a low platelet count, there may be an increased tendency to bleed and bruise,
• decreased blood cell count (pancytopenia) with bone marrow hypoplasia,
• 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, somnolence, seizures, dementia, sensory disturbances,
• taste disorders, loss of appetite, changes in the mouth with non-uniform coloration, 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,
• cardiomyopathy (a disease of the heart muscle),
• selective aplasia (decrease) of the red blood cell-producing system,
• changes in nail and skin color, increased sweating, urticaria, 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 due to bone marrow failure).

In some patients taking NRTIs, a condition called lactic acidosis has been reported, 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"). Taking Retrovir may cause loss of fat from the legs, arms, and face (lipoatrophy, see section 2 "Important information before taking Retrovir").

Reporting Side Effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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 this 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 that are no longer needed. 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 Retrovir is zidovudine. Each capsule contains 100 mg of zidovudine.
• The other ingredients are: maize starch, microcrystalline cellulose, sodium carboxymethylcellulose (type A), magnesium stearate.
• The hard gelatin capsule contains: gelatin, titanium dioxide (E 171), black ink (Opacode 10A1) containing: shellac, iron oxide black (E 172), propylene glycol, ammonium hydroxide, 28%.

Hard capsules 250 mg

• The active substance of Retrovir is zidovudine. Each capsule contains 250 mg of zidovudine.
• The other ingredients are: maize starch, 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) containing: 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 white, opaque, with a black inscription GSYJU on the body of the capsule. Hard capsules 250 mg The pack contains 40 capsules in 4 blisters of PVC/Aluminum, in a cardboard box. The capsules are blue (cap) and white (body), opaque, with a black inscription GSJV2 on the body of the capsule.

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 For more detailed information on 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: