Retrovir

Package leaflet: Information for the patient

Retrovir, 100 mg, hard capsules
Retrovir, 250 mg, hard capsules
Zidovudinum
Please read the entire leaflet carefully before taking this medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Retrovir is and what it is 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 Retrovir is and what it is used for

Retrovir contains zidovudine as the active substance. Zidovudine belongs to a group of antiviral medicines known as nucleoside reverse transcriptase inhibitors (NRTIs).
Retrovir capsules are used in adults and children in combination with other antiretroviral medicines for the treatment of human immunodeficiency virus (HIV) infection.
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 levels of neutrophils (a type of white blood cells) in the blood, or very low haemoglobin concentration;
• 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 any doubt, consult a doctor.
Warnings and precautions
Before starting Retrovir, discuss this with your doctor, pharmacist, or nurse.
Retrovir does not cure HIV infection; it only suppresses its progression and helps keep the disease under control. Due to HIV infection, other infections or HIV-related illnesses may still develop.
Retrovir should be used under the supervision of a physician experienced in managing HIV-infected or AIDS patients.
Retrovir must be taken daily.
Regular contact with the treating physician is essential. Do not discontinue Retrovir without first consulting your doctor.
Transmission of HIV from mother to child during pregnancy may still occur despite treatment intended to prevent such transmission.
Anaemia and neutropenia
Zidovudine may affect the production of red blood cells, leading to anaemia. The main symptoms of this condition are fatigue and shortness of breath. Less frequently, patients may experience reduced production of certain white blood cells, increasing susceptibility to infections. The treating physician may recommend periodic blood tests to monitor levels of certain blood cells. These changes are usually reversible.
Concurrent use of Retrovir and ribavirin may cause or worsen existing anaemia.
If symptoms of anaemia occur (such as fatigue and shortness of breath), contact your doctor, who will decide whether Retrovir should be discontinued.
Lactic acidosis
Retrovir belongs to a group of drugs (NRTIs) that 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 nonspecific symptoms such as nausea, vomiting, and abdominal pain may indicate the development of lactic acidosis. This rare but serious adverse effect occurs more frequently in women, especially those who are overweight. Liver diseases, particularly hepatomegaly, hepatitis, and fatty liver, may also increase the risk of this condition. During Retrovir treatment, your doctor will closely monitor your condition to detect any symptoms suggesting lactic acidosis.
Fat redistribution
Treatment with Retrovir or other zidovudine-containing medicines may cause loss of fat tissue in the legs, arms, and face (lipoatrophy). The physician should monitor the patient for signs of lipoatrophy. If any loss of fat tissue in the legs, arms, or face is observed, inform your doctor. If such symptoms occur, your doctor will assess whether Retrovir should be discontinued and alternative HIV treatment initiated. After stopping Retrovir, reversal of fat loss may be noticeable after several months, but the lost fat tissue may not be fully regained.
Blood lipid and glucose levels
During HIV treatment, blood lipid and glucose levels may increase. This is partly related to improved health status and lifestyle, and sometimes, in the case of blood lipids, to the effects of anti-HIV drugs. 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 drugs may have an increased risk of severe, potentially life-threatening liver-related adverse effects, and blood tests to monitor liver function may be necessary.
Immune reconstitution syndrome
In some patients with advanced HIV infection (AIDS), objective and subjective inflammatory symptoms caused by prior opportunistic 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 previously remained asymptomatic. If any inflammatory symptoms are noticed, contact your doctor immediately.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported following immune status improvement (immune reconstitution). However, the onset of these conditions is more variable, and they often present with nonspecific 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
Osteonecrosis has been reported in some patients, which may be associated with multiple 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 with concomitant hepatitis C virus infection
Exacerbation of anaemia associated with ribavirin administration has been reported during zidovudine use as part of HIV treatment regimens, although the exact mechanism is not fully understood. Due to increased risk of anaemia, concomitant use of ribavirin and zidovudine is not recommended. The doctor may consider replacing zidovudine with another antiretroviral agent if previously included in the treatment regimen. This is particularly important in patients with a history of zidovudine-associated 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 infections).

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 your doctor):

• phenytoin, valproic acid (used in the treatment of epilepsy),
• oxazepam, lorazepam (used for anxiety states),
• acetylsalicylic acid (aspirin), ketoprofen, naproxen (used as anti-inflammatory, antipyretic, and analgesic agents),
• codeine (a cough suppressant),
• morphine (used in pain treatment),
• 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 agent affecting the immune system),
• probenecid (used in the treatment of gout and similar conditions, and used concomitantly with certain antibiotics to enhance their effectiveness),
• pentamidine, atovaquone (used in the treatment of parasitic infections such as pneumocystosis),
• amphotericin, 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),
• clarithromycin (an antibiotic),
• lamivudine (used in the treatment of HIV infections and hepatitis B virus infection),
• 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 is planning to have a child, 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 (after week 14 of gestation) 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 treating physician to discuss potential adverse effects and the benefits and risks of antiretroviral therapy for both herself and the child.
If Retrovir was taken during pregnancy, the doctor may recommend regular visits to monitor the child's development. During these visits, blood tests and other diagnostic tests 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
Studies on the effect of Retrovir on the ability to drive vehicles and operate machinery have not been conducted. 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 capsule, i.e., the medicine is considered "sodium-free".

3. How to take Retrovir

Retrovir should be taken exactly as prescribed by the doctor. If in doubt about dosage, consult a doctor or pharmacist.
Dosages prescribed for individual patients may vary and depend on several factors, including the stage of the disease.
To ensure the full dose is administered, capsules should be swallowed whole without opening them. However, if a patient is unable to swallow the capsule, it may be opened and the powder inside mixed with a small amount of semisolid food or liquid, then administered immediately after preparation.
Adults and adolescents weighing at least 30 kg
The usual dose is 250 mg or 300 mg twice daily, in combination with other antiretroviral medicines.
Children weighing at least 8 kg but less than 30 kg

Alternatively, in children with a body weight from 28 kg to 30 kg, the following may be used:

In children with body weight of at least 4 kg but less than 8 kg and in patients who have
difficulty swallowing capsules, zidovudine is recommended in the form of an oral solution at
appropriate doses (please refer to the patient leaflet for Retrovir 50 mg/5 ml, oral solution).
Children with body weight less than 4 kg
There are insufficient data to recommend a specific dosage regimen in children with body weight
less than 4 kg.
Dosing for prevention of HIV transmission from mother to fetus
and newborn
Pregnant women should receive Retrovir orally starting from the 14th week of pregnancy at a dose of 500 mg per day (i.e. 100 mg five times daily) until the onset of labour. During labour, Retrovir should be administered initially 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. The newborn should receive Retrovir orally at a dose of 0.2 ml/kg body weight (2 mg/kg body weight) every 6 hours, starting within 12 hours after birth and continuing until the newborn reaches 6 weeks of age. To ensure accurate dosing in newborns, syringes with appropriate capacity and decimal scale markings (0.1 ml) should be used. For example, newborns weighing 2.0 kg and 5.0 kg should receive 0.4 ml (4 mg zidovudine) and 1.0 ml (10 mg zidovudine) of the oral solution, respectively, four times daily.
If oral administration of the drug to the newborn is not possible, Retrovir should be administered intravenously every 6 hours at a dose of 1.5 mg/kg body weight as a 30-minute intravenous infusion.
If a caesarean section is planned, intravenous infusion of Retrovir should be started 4 hours before surgery. If the procedure is cancelled, the infusion should be discontinued and oral administration initiated.
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 count decreases to 0.75–1.0 × 10^9/l, the physician may decide to reduce the dose or discontinue Retrovir (see section: "Important information before using Retrovir").
Dosing in elderly patients
The physician may recommend appropriate monitoring tests before and during Retrovir treatment in this age group.
Dosing in patients with renal impairment
In patients with severe renal impairment (creatinine clearance ≤ 10 ml/min) and in patients with end-stage renal failure undergoing haemodialysis or peritoneal dialysis, a dose of 100 mg every 6 to 8 hours (300 to 400 mg daily) is recommended.
Dosing 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, especially if signs of poor drug tolerance occur.
Administration of a higher than recommended dose of Retrovir
If a patient has taken more than the recommended dose, contact a doctor or pharmacist immediately, or go to the nearest emergency department for advice.
Missed dose of Retrovir
It is very important to take the recommended dose of Retrovir every day to ensure maximum treatment effectiveness. If a dose is missed, it should be taken as soon as possible. Then continue treatment as prescribed. Do not take a double dose to make up for a missed dose.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
During HIV treatment, it is not always possible to determine whether an adverse symptom is caused by Retrovir, 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 concerned after reading the list of adverse reactions below, as they may not occur. 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 red blood cell count) and neutropenia or leukopenia (low white blood cell count). If the number of red blood cells decreases, patients may experience symptoms of 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 bleeding and bruising,
• Decreased blood cell counts (pancytopenia) with bone marrow hypoplasia (hypocellular bone marrow),
• Weakness, fever, generalised pain,
• Muscle function disorders,
• Breathlessness,
• 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 mucosal changes with uneven pigmentation, dyspepsia, pancreatitis, liver disorders such as liver enlargement and hepatic steatosis,
• Changes in distribution or accumulation of body fat,
• Frequent urination, gynaecomastia (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 observed, 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 Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 4921301, Fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl .
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Retrovir

Keep this medicine out of 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 medicine's batch number is indicated on the packaging after: Lot.
Do not store above 30 °C. Store in a dry place. 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. These measures will help protect the environment.

6. Contents of the pack and other information

What Retrovir contains
Hard capsules 100 mg

• The active substance is zidovudine. Each capsule contains 100 mg of zidovudine.
• The other ingredients are: maize starch, microcrystalline cellulose, sodium carboxymethylstarch (type A), magnesium stearate.
• The components of the hard gelatin capsule shell are: 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 is zidovudine. Each capsule contains 250 mg of zidovudine.
• The other ingredients are: maize starch, microcrystalline cellulose, sodium carboxymethylstarch (type A), magnesium stearate.
• The components of the hard gelatin capsule shell are: 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 PVC/Aluminium blisters, in a cardboard carton.
The capsules are opaque, white in colour, with a black imprint "GSYJU" on the body of the capsule.

Hard capsules 250 mg
The pack contains 40 capsules in 4 PVC/Aluminium blisters, in a cardboard carton.
The capsules are opaque, with a blue cap and a white body, with a black imprint "GSJV2" on the body of the capsule.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
ViiV Healthcare BV
Van Asch van Wijckstraat 55H
3811 LP Amersfoort
The Netherlands

Manufacturer
Delpharm Poznań Spółka Akcyjna
Grunwaldzka 189
60-322 Poznań
Poland

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
GSK Services Sp. z o.o.
ul. Rzymowskiego 53
02-697 Warszawa
Poland
Tel: 22-576-90-00