Retrovir

Package Leaflet: Information for the Patient

Retrovir, 10 mg/ml, Concentrate for Solution for Infusion

Zidovudine

Read All of This Leaflet Carefully Before You Start Taking This Medicine Because It Contains Important Information for You.

• You should 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. Do not pass it on to others. It may harm them, even if their symptoms 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 and Other Information

• 1. What is Retrovir and What is it Used For
• 2. Before You Take 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 antiretroviral medicines called nucleoside reverse transcriptase inhibitors (NRTIs).
Retrovir, concentrate for solution for infusion, is used for the short-term treatment of patients with severe symptoms of human immunodeficiency virus (HIV) infection, also known as acquired immune deficiency syndrome (AIDS), who are unable to take oral forms of the medicine.
Retrovir is also used in pregnant women (after 14 weeks of pregnancy) who have been diagnosed with HIV, as well as in newborns born to these women, to reduce the risk of transmission of HIV from mother to child.

2. Before You Take 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 with very low neutrophil counts (a type of white blood cell) or very low hemoglobin levels;
• in newborns with hyperbilirubinemia who require treatment other than phototherapy, or with elevated liver enzymes exceeding 5 times the upper limit of normal.

If you are unsure, consult your doctor.

Warnings and Precautions

Before taking Retrovir, discuss this with your doctor, pharmacist, or nurse.
This medicine does not cure HIV infection, it only slows down the progression of the disease and allows the condition 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. During proper treatment, access to adequate medical care is necessary, ensuring, for example, the possibility of monitoring hematological parameters, including viral load, CD4 cell count, and blood transfusions if necessary.
Transmission of HIV from mother to child during pregnancy may occur despite the use of this medicine to prevent such transmission.
Anemia and Neutropenia
Zidovudine 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 risk of 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 worsen 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 Acidosis
The 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. During treatment with Retrovir, your doctor will closely monitor your condition to detect any symptoms that may indicate the development of lactic acidosis.
Fat Redistribution
Treatment 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, you should tell your doctor. If such symptoms occur, your doctor will assess whether to stop Retrovir and use alternative HIV treatment. After stopping Retrovir, reversal of fat loss may be observed after several months, and lost fat may not be fully regained.
Lipid and Glucose Levels in the Blood
During 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 this 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 Reconstitution Syndrome
In some patients with advanced HIV infection (AIDS), who have previously had opportunistic infections, 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 disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported in the context of immune reconstitution, when the immune system starts to recover. However, the time to onset is more variable, and these diseases, often with non-specific symptoms, may occur several months after starting treatment.
Use in Elderly Patients and Patients with Renal or Hepatic Impairment
You should consult your doctor, who may decide to adjust the dose (see section "How to Take Retrovir").
Bone Necrosis
In some patients, a condition called bone necrosis has been reported, which may be caused by various factors (including the use of corticosteroids, 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 Infection
During treatment with zidovudine 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, concurrent administration of ribavirin and zidovudine is not recommended. Your doctor may consider replacing zidovudine with an alternative medicine in the antiretroviral regimen, especially if you have previously experienced anemia associated with zidovudine.

Retrovir and Other Medicines

Tell your doctor about all medicines you are taking or have recently taken, including those obtained 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 (in case of doubt, consult your doctor):

• 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),
• isoprinosine (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 to treat skin infections),
• fluconazole or flucytosine (used to treat fungal infections, such as thrush),
• ganciclovir, interferon (used to treat viral infections),
• lamivudine (used to treat HIV infections 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 are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Retrovir should only be used during pregnancy if the benefits outweigh the risks to the baby.
Treatment with Retrovir in pregnant women (after 14 weeks of pregnancy) with HIV infection, as well as in newborns born to these women, significantly reduces the risk of transmission of HIV from mother to child. If you are pregnant or planning to become pregnant, you should consult your doctor to discuss the potential 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 the development of your baby. 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 of the risk of transmitting HIV 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 potential side effects of Retrovir.

Retrovir Contains Sodium

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

3. How to Take Retrovir

The recommended dose of Retrovir, concentrate for solution for infusion, is administered by slow intravenous infusion over a period of more than one hour.
Retrovir solution for infusion should not be administered intramuscularly.

Dilution

Retrovir, concentrate for solution for infusion, should be diluted before administration (see Instructions for Useat the end of the leaflet).

Dosage

Retrovir, concentrate for solution for infusion, should only be administered to patients for as long as they are unable to take oral therapy.
Adult Dosage
Retrovir is usually administered at a dose of 1 mg/kg body weight or 2 mg/kg body weight every 4 hours.
The currently recommended dose of Retrovir in oral form, as part of a combination antiretroviral regimen, is 500-600 mg per day in two or three divided doses.
Pediatric Dosage
Data on the use of Retrovir, concentrate for solution for infusion, in children are limited. Doses of 80-160 mg/m²every 6 hours (320-640 mg/m²per day) have been used.
The currently recommended dose of Retrovir in oral form, as part of a combination antiretroviral regimen, is 360-480 mg/m²per day in 3-4 divided doses, which corresponds to an intravenous dose of 240-320 mg/m²per day in 3-4 divided doses.
Dosage for Prevention of Mother-to-Child Transmission of HIV and for Newborns
Pregnant women after 14 weeks 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 over one hour at a dose of 2 mg/kg body weight, 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 oral solution, respectively, four times a day.
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 stopped and oral administration should be started.
Dose Adjustments for 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 × 10⁹/l, your doctor may decide to reduce the dose or stop Retrovir (see section "Before You Take Retrovir").
Dose Adjustments for Elderly Patients
Your doctor may recommend regular monitoring tests before and during treatment with Retrovir.
Dose Adjustments for Patients with Renal Impairment
In patients with severe renal impairment (creatinine clearance ≤ 10 ml/min), your doctor may decide to reduce the dose to 1 mg/kg body weight, administered 3-4 times a day.
In patients with end-stage renal disease undergoing hemodialysis or peritoneal dialysis, a dose of 100 mg is recommended every 6-8 hours.
Dose Adjustments for 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 extend the interval between doses, especially if signs of poor tolerance appear.

Overdose of Retrovir

If you have accidentally taken more than the prescribed dose of Retrovir, you should contact your doctor or the nearest hospital emergency department immediately.

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 too concerned about 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 risk of 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, drowsiness, seizures, dementia, sensory disturbances,
• taste disorders, loss of appetite, changes in the mouth with non-uniform discoloration, indigestion, pancreatitis, liver disorders, such as liver enlargement, 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 (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 due to bone marrow failure).

In some patients taking NRTIs, a condition called lactic acidosis has been reported, which occurs due to increased production of lactic acid in the body (see section 2 "Before You Take Retrovir").
During HIV treatment, lipid and glucose levels in the blood may increase (see section 2 "Before You Take Retrovir").
Treatment with Retrovir may cause loss of fat from the legs, arms, and face (lipoatrophy, see section 2 "Before You Take Retrovir").

Reporting Side Effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist.
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 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. 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

• The active substance is zidovudine. Each vial contains 200 mg of zidovudine.
• The other ingredients are: hydrochloric acid, sodium hydroxide, water for injections.

What Retrovir Looks Like and Contents of the Pack

Retrovir, concentrate for solution for infusion, is a clear, colorless to slightly yellowish, sterile aqueous solution with a pH of approximately 5.5. It is packaged in orange glass vials with bromobutyl rubber stoppers and aluminum caps, in a cardboard box.
The pack contains 5 vials of 20 ml each.

Marketing Authorization Holder and Manufacturer

Manufacturer

GlaxoSmithKline Manufacturing S.P.A.
Strada Provinciale Asolana No. 90
San Polo di Torrile 43056
Parma
ItalyGSK Services Sp. z o.o.
ul. Rzymowskiego 53
02-697 Warsaw
tel. 22-576-90-00

Date of Last Revision of the Leaflet:

Marketing Authorization Holder

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

Information for Healthcare Professionals

INSTRUCTIONS FOR USE

Retrovir, concentrate for solution for infusion, should be administered, after dilution, by slow intravenous infusion over 60 minutes.
Retrovir, concentrate for solution for infusion, should not be administered intramuscularly.
Dilution
Retrovir, concentrate for solution for infusion, should be diluted before administration.
The appropriate volume of concentrate (see section 3 "How to Take Retrovir") should be added to 5% glucose solution for infusion and mixed to achieve a zidovudine concentration of 2 mg/ml or 4 mg/ml.
Such dilutions retain their physicochemical properties for up to 48 hours at both 5°C and 25°C.
The product does not contain preservatives, so dilution should be performed under aseptic conditions, preferably immediately before administration, and any unused portion of the product should be discarded.
Do not use the product if, before or after dilution, or during administration, visible turbidity appears.