Patient Information Leaflet

Retrovir, 10 mg/ml, concentrate for solution for infusion
Zidovudinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

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

Leaflet Contents

What Retrovir is and what it is used for
Important information before using Retrovir
How to use Retrovir
Possible side effects
How to store Retrovir
Contents of the pack and other information

1. What Retrovir is and what it is 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, i.e. acquired immunodeficiency syndrome (AIDS), who are unable to take oral forms of the medicine.
Retrovir is also used in pregnant women (after week 14 of pregnancy) who have been diagnosed with HIV, and in newborns born to these women, to reduce the risk of transmission of HIV infection from mother to child.

2. Important information before using Retrovir

When not to use Retrovir

if the patient is allergic to zidovudine or any of the other ingredients of this medicine (listed in section 6);
in patients who have very low blood levels of neutrophils (a type of white blood cells) or very low haemoglobin levels;
in newborns with hyperbilirubinaemia who require treatment other than phototherapy, or with increased aminotransferase activity exceeding 5 times the upper limit of normal.

If in doubt, consult a doctor.
Warnings and precautions
Before starting Retrovir, discuss this with your doctor, pharmacist, or nurse.
Retrovir does not cure HIV infection but only suppresses its progression and helps control the disease. Other infections or HIV-related conditions may still develop due to HIV infection.
Retrovir should be used under the supervision of a physician experienced in managing HIV-infected or AIDS patients. Appropriate medical support must be available during treatment, including monitoring of haematological parameters, viral load, CD4 cell counts, and blood transfusions if necessary.
Transmission of HIV from mother to child may still occur despite treatment with Retrovir intended to prevent such transmission.
Anaemia and neutropenia
Zidovudine may affect the production of red blood cells, leading to anaemia. The main symptoms include fatigue and shortness of breath. Less commonly, reduced production of certain white blood cells may occur, increasing susceptibility to infections. Your doctor may recommend periodic blood tests to monitor blood cell counts. These changes are usually reversible.
Concurrent use of Retrovir and ribavirin may cause or worsen existing anaemia. If symptoms of anaemia (such as fatigue and shortness of breath) occur, contact your doctor, who will decide whether Retrovir should be discontinued.
Lactic acidosis
Retrovir belongs to a group of medicines called NRTIs (nucleoside reverse transcriptase inhibitors), which may cause a condition known as 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, and abdominal pain may indicate lactic acidosis. This is a rare but serious adverse effect, occurring more frequently in women, especially those with significant overweight. Liver disorders, particularly hepatomegaly, hepatitis, and hepatic steatosis, may also increase the risk of this condition. During Retrovir treatment, your doctor will closely monitor your condition for any signs suggesting lactic acidosis.
Fat redistribution
Treatment with Retrovir or other zidovudine-containing medicines may cause loss of subcutaneous fat in the legs, arms, and face (lipodystrophy). Your doctor should monitor you for signs of lipodystrophy. If you notice any loss of fat in the legs, arms, or face, inform your doctor. If such symptoms occur, your doctor will assess whether Retrovir should be discontinued and alternative HIV treatment initiated. After stopping Retrovir, partial recovery of lost fat may occur over several months, but complete restoration may not be achieved.
Blood lipid and glucose levels
During HIV treatment, blood lipid and glucose levels may increase. This is partly due to improved health status and lifestyle factors, and sometimes due to anti-HIV drugs, particularly regarding blood lipid levels. Your doctor may recommend tests to detect these changes.
Liver disease (hepatitis)
If the patient has a history of liver disease, discuss this with your doctor.
Patients with chronic hepatitis B or C virus infection treated with antiretroviral medicines may have an increased risk of severe, potentially life-threatening liver-related adverse effects. Blood tests to monitor liver function may be necessary.
Immune Reconstitution Syndrome
In some patients with advanced HIV infection (AIDS), who have previously had opportunistic infections, signs and symptoms of inflammation caused by prior infections may appear shortly after starting antiretroviral therapy. These symptoms are believed to result from improved immune response, enabling the body to fight infections that were previously asymptomatic. If any inflammatory symptoms occur, contact your doctor immediately.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported following immune recovery (immune reconstitution). However, the onset time for these conditions is more variable, and they often present with non-specific symptoms appearing many months after starting treatment.
Use in elderly patients and patients with kidney or liver impairment
Consult your doctor, who may decide to adjust the dose (see section: "How to use Retrovir").
Osteonecrosis
Some patients have reported a condition called osteonecrosis, which may be associated with several factors (e.g. corticosteroid use, alcohol consumption, severe immunosuppression, high body mass index). If the patient experiences bone or joint pain, stiffness, or difficulty moving, they should contact their doctor.
Patients co-infected with hepatitis C virus
During treatment with zidovudine as part of an HIV regimen, cases of worsening anaemia associated with ribavirin administration have been reported, although the exact mechanism remains unclear. Due to increased risk of anaemia, concomitant use of ribavirin and zidovudine is not recommended. Your doctor may consider replacing zidovudine with another antiretroviral agent if previously included in the treatment regimen. This is particularly important in patients who previously experienced zidovudine-related anaemia.
Retrovir and other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines planned for future use. This includes over-the-counter medicines, including herbal remedies.
The following medicines should not be used together with Retrovir:

rifampicin (an antibiotic),
stavudine (used in the treatment of HIV infection).

Retrovir may interact with certain medicines, potentially increasing adverse effects. If the patient is taking any of the following medicines, inform the treating doctor (in case of doubt, consult a doctor):

phenytoin, valproic acid (used in the treatment of epilepsy),
oxazepam, lorazepam (used for anxiety),
acetylsalicylic acid (aspirin), ketoprofen, naproxen (used as anti-inflammatory, antipyretic, and analgesic agents),
codeine (cough suppressant),
morphine (used for pain relief),
methadone (used as a heroin substitute in addiction treatment (narcotics)),
indomethacin (used in the treatment of rheumatoid arthritis),
cimetidine (used in the treatment of peptic ulcer disease),
clofibrate (used in the treatment of lipid disorders),
isoprinosine (an antiviral immunomodulatory agent),
probenecid (used in the treatment of gout and similar conditions, and also used concomitantly with certain antibiotics to enhance their efficacy),
pentamidine, atovaquone (used in the treatment of parasitic infections such as pneumocystis pneumonia),
amphotericin B, co-trimoxazole (used in the treatment of bacterial and fungal infections),
pyrimethamine (used in the treatment of malaria and other parasitic infections),
dapsone (used to prevent pneumocystis pneumonia and in the treatment of skin infections),
fluconazole or flucytosine (used in the treatment of fungal infections, such as candidiasis),
ganciclovir, interferon (used in the treatment of viral infections),
lamivudine (used in the treatment of HIV and hepatitis B virus infections),
vincristine, vinblastine, or doxorubicin (used in the treatment of cancer).

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Retrovir should be used during pregnancy only if the benefits outweigh the potential risks to the child.
Use of Retrovir in HIV-infected pregnant women (beyond the 14th week of pregnancy) and in newborns born to these women significantly reduces the risk of mother-to-child transmission of HIV. If the patient is pregnant or planning pregnancy, she should consult her doctor to discuss potential adverse effects and the benefits and risks of antiretroviral therapy for both herself and her child.
If the patient took Retrovir during pregnancy, the doctor may recommend regular follow-up visits to monitor the child's development. During these visits, blood tests and other diagnostic procedures may be performed.
Zidovudine, the active substance in Retrovir, passes into breast milk. If the patient is taking Retrovir, she should not breastfeed.
Breastfeeding is not recommended for women infected with HIV, as HIV can be transmitted to the child through breast milk.
If the patient is breastfeeding or considering breastfeeding, she should consult her doctor as soon as possible.
Driving and operating machinery
No studies have been conducted on the effects of Retrovir on the ability to drive or operate machinery. When deciding to drive or operate machinery, the patient should consider their health status and possible adverse effects of Retrovir.
Retrovir contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, meaning it is considered "sodium-free".

3. How to use Retrovir

The recommended dose of Retrovir, concentrate for solution for infusion, should be administered as a slow intravenous infusion of the diluted solution lasting over one hour.
Retrovir, solution for infusion, must not be administered intramuscularly.
Dilution
Retrovir, concentrate for solution for infusion, must be diluted before administration (see Instructions for use at the end of this leaflet).
Dosage
Retrovir, concentrate for solution for infusion, should be administered to the patient only as long as oral treatment cannot be initiated.
Dosage in adults
Retrovir is usually administered at a dose of 1 mg/kg or 2 mg/kg body weight every 4 hours.
The currently recommended dose of oral Retrovir as part of a combination antiretroviral regimen is 500 to 600 mg daily, given in two or three divided doses.
Dosage in children and adolescents
Data on the use of Retrovir, concentrate for solution for infusion, in children are limited. Intravenous doses ranging from 80 to 160 mg/m² body surface area every 6 hours (320 to 640 mg/m²/day) have been used.
The currently recommended dose of oral Retrovir as part of a combination antiretroviral regimen is 360 to 480 mg/m²/day given in 3–4 divided doses, approximately equivalent to an intravenous dose of 240 to 320 mg/m²/day in 3–4 divided doses.
Dosage for prevention of maternal-fetal and perinatal HIV transmission
Pregnant women from the 14th week of gestation should receive oral Retrovir at a dose of 500 mg daily (i.e. 100 mg five times daily) until the onset of labour. During labour, Retrovir should be initially administered as a one-hour intravenous infusion at a dose of 2 mg/kg body weight, followed by continuous intravenous infusion at 1 mg/kg body weight per hour until clamping of the umbilical cord.
Newborn infants should receive oral Retrovir at a dose of 0.2 ml/kg body weight (2 mg/kg body weight) every 6 hours, starting within 12 hours of birth and continuing until the infant reaches 6 weeks of age. To ensure accurate dosing in newborns, syringes with decimal graduations (0.1 ml) should be used. For example, infants weighing 2.0 kg and 5.0 kg should receive 0.4 ml (4 mg zidovudine) and 1.0 ml (10 mg zidovudine) of oral solution, respectively, four times daily.
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 via a 30-minute intravenous infusion.
If a caesarean section is planned, intravenous infusion of Retrovir should be initiated 4 hours before surgery. If the procedure is cancelled, the infusion should be stopped and oral administration started.
Dosage adjustments in patients with haematological adverse effects
If haemoglobin concentration decreases to 7.5–9.0 g/100 ml (4.65–5.59 mmol/l) or neutrophil granulocyte count decreases to 0.75–1.0 × 10⁹/l, the physician may decide to reduce the dose or discontinue Retrovir (see section: "Important information before using Retrovir").
Dosage in elderly patients
The physician may recommend appropriate monitoring tests before and during Retrovir treatment in elderly patients.
Dosage in patients with renal impairment
In patients with severe renal impairment (creatinine clearance ≤ 10 ml/min), the physician may decide to reduce the dose to 1 mg/kg body weight administered 3 to 4 times daily.
In patients with end-stage renal failure undergoing haemodialysis or peritoneal dialysis, a dose of 100 mg every 6 to 8 hours is recommended.
Dosage in patients with hepatic impairment
In patients with hepatic cirrhosis, accumulation of the drug may occur. The physician may decide to adjust the dosage or prolong the interval between doses, particularly if signs of poor drug tolerance occur.
Administration of a higher than recommended dose of Retrovir
If a higher than recommended dose of Retrovir is accidentally administered, contact the treating physician or the nearest hospital emergency department immediately.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
During treatment for HIV infection, it is not always possible to determine whether an adverse symptom
is caused by Retrovir, by other medicines taken at the same time, or by the HIV infection itself.
For this reason, it is very important to inform your doctor about any changes in your health.
Patients should not become unduly alarmed after reading the list of adverse reactions below,
as these may not occur in their case. The adverse reaction profile in adults and children is similar.

Very common adverse reactions (occurring in more than 1 in 100 patients)

Headache, nausea.

Common adverse reactions (occurring in 1 to 10 in 100 patients)

Anaemia (low number of red blood cells) and neutropenia or leukopenia (low number of white blood cells). If the number of red blood cells decreases, patients may experience symptoms such as fatigue and breathlessness. A reduced number of white blood cells may increase susceptibility to infections,
Increased liver enzyme activity, bilirubin concentration, and lactic acid levels,
Dizziness,
Muscle pain, malaise,
Vomiting, abdominal pain, diarrhoea.

Uncommon adverse reactions (occurring in 1 to 10 in 1,000 patients)

Decreased platelet count (cells playing an important role in blood clotting). Patients with reduced platelet counts may experience increased tendency to bleeding and bruising,
Decreased blood cell counts (pancytopenia) with bone marrow hypoplasia (hypocellular bone marrow),
Weakness, fever, generalised pain,
Muscle function disorders,
Shortness of breath,
Flatulence,
Itching, rash.

Rare adverse reactions (occurring in less than 1 in 1,000 patients)

Anxiety, depression, insomnia, somnolence, seizures, mental dullness, sensory disturbances,
Taste disturbances, loss of appetite, oral cavity changes with uneven pigmentation, dyspepsia, pancreatitis, liver disorders such as liver enlargement, hepatic steatosis,
Changes in distribution or accumulation of body fat,
Frequent urination, breast enlargement in men,
Heart muscle disease known as cardiomyopathy,
Selective red blood cell aplasia,
Changes in nail and skin pigmentation, increased sweating, urticaria, influenza-like symptoms, cough, chills, chest pain,
Lactic acidosis without decreased blood oxygen levels.

Very rare adverse reactions (occurring in less than 1 in 10,000 patients)

Aplastic anaemia (anaemia due to bone marrow failure).

In some patients receiving NRTIs, a condition called lactic acidosis has been reported, which
results from increased production of lactic acid in the body (see section 2 "Important information before taking Retrovir").
During HIV treatment, blood levels of lipids and glucose may increase (see section 2 "Important information before taking Retrovir").
Treatment with Retrovir may cause loss of fat tissue in the legs, arms, and face (lipoatrophy, see section 2 "Important information before taking Retrovir").

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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.
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the 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 stated month.
The batch number is indicated on the packaging after: Lot.
Do not store above 30 °C. Protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the package and other information

What Retrovir contains

The active substance is zidovudine. Each vial contains 200 mg of zidovudine.
Other components 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, colourless to slightly yellowish, sterile aqueous solution with a pH of approximately 5.5. It is packed in amber glass vials closed with bromobutyl rubber stoppers and aluminium overseals, and placed in a cardboard carton.
The pack contains 5 vials of 20 ml each.

Marketing Authorisation Holder and Importer
Marketing Authorisation Holder Importer
ViiV Healthcare BV GlaxoSmithKline Manufacturing S.P.A.
Van Asch van Wijckstraat 55H Strada Provinciale Asolana No. 90
3811 LP Amersfoort San Polo di Torrile 43056
The Netherlands Parma
Italy

For further information, please contact the representative of the Marketing Authorisation Holder:
GSK Services Sp. z o.o.
ul. Rzymowskiego 53
02-697 Warszawa
tel. 22-576-90-00

Information for medical professionals
DIRECTIONS FOR USE
Retrovir, concentrate for solution for infusion, must be administered after dilution as a slow intravenous infusion lasting 60 minutes.
Retrovir, concentrate for solution for infusion, must not be administered intramuscularly.

Dilution
Retrovir, concentrate for solution for infusion, must be diluted before administration.
The appropriate volume of concentrate (see section 3. "How to use Retrovir") should be added to 5% glucose solution for infusion and mixed to achieve a final zidovudine concentration of 2 mg/ml or 4 mg/ml.

Such dilutions remain physicochemically stable for up to 48 hours at either 5 °C or 25 °C.
The product contains no preservatives; therefore, dilution should be carried out under sterile conditions, preferably immediately before administration, and any unused portion should be discarded.

Do not use the product if visible cloudiness or precipitation occurs before dilution, after dilution, or during administration.