Retrovir

Package Leaflet: Information for the Patient

Retrovir, 50 mg/ 5 ml, Oral Solution

Zidovudine

Read All of This Leaflet Carefully Before Taking This Medicine.

• 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 Experience Any Side Effects, Tell 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 Retrovir Is and What It Is 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 Retrovir Is and What It Is Used For

Retrovir Contains Zidovudine as the Active Ingredient. Zidovudine Belongs to a Group of Antiviral Medicines Called Nucleoside Reverse Transcriptase Inhibitors (NRTI). Retrovir Oral Solution Is Used in Adults and Children in Combination with Other Antiretroviral Medicines to Treat HIV Infection. Retrovir Is Also Used in Pregnant Women (After 14 Weeks of Pregnancy) Who Have HIV Infection, and in Newborns Born to These Women, to Reduce the Risk of Passing 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 Transaminases Exceeding 5 Times the Upper Limit of Normal.

If You Are in Doubt, Consult Your Doctor.

Warnings and Precautions

Before Taking Retrovir, Discuss This with Your Doctor, Pharmacist, or Nurse. The Medicine Does Not Cure HIV Infection; It Only Slows Down Its Progression and Helps to 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 the Treatment of HIV-Infected Patients or Patients with AIDS. Retrovir Should Be Taken Every Day. You Should Regularly Consult Your Doctor. Do Not Stop Taking the Medicine Without Consulting Your Doctor First. The Transmission of HIV from Mother to Child Can Occur Despite the Use of Retrovir 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 May 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. The Use of Retrovir with Ribavirin May Cause or Exacerbate Existing Anemia. If You Experience Symptoms of Anemia (Such as Fatigue and Shortness of Breath), You Should Consult Your Doctor, Who Will Decide Whether to Discontinue Retrovir. Lactic AcidosisThe Group of Medicines to Which Retrovir Belongs (NRTI) 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 Diseases, Particularly Liver Enlargement, 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 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 Discontinuation of Retrovir, Reversal of Fat Loss May Be Observed After Several Months, and the Lost Fat May Not Be Fully Recovered. Lipid and Glucose Levels in the BloodDuring HIV Treatment, Lipid and Glucose Levels in the Blood May Increase. This Is Partly Related to the Improvement of the Patient's Condition and Lifestyle, and Sometimes, in the Case of Lipid Levels, to the Effect of Anti-HIV Medicines. Your Doctor Will Recommend Tests to Detect These Changes. Liver Diseases (Hepatitis)If You Have Had Liver Diseases 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 It May Be Necessary to Perform Blood Tests to Monitor Liver Function. Immune Reconstitution SyndromeIn Some Patients with Advanced HIV Infection (AIDS), Who Have Had Opportunistic Infections in the Past, Symptoms of Inflammation May Appear Soon After Starting Anti-HIV Treatment. It Is Believed That These Symptoms Are Due to the Improvement of the Body's Ability to Respond to Infections, Which May Have Been Present but Not Causing Symptoms. If You Notice Any Symptoms of Inflammation, You Should Immediately Consult Your Doctor. Autoimmune Diseases (Such as Graves' Disease, Polymyositis, and Guillain-Barré Syndrome) Have Also Been Reported in the Context of Immune Reconstitution. However, the Time to Onset Is More Variable, and These Diseases, Often with Non-Specific Symptoms, May Appear Several Months After Starting Treatment. Use in Elderly Patients and Patients with Renal or Hepatic ImpairmentYou Should Consult Your Doctor, Who May Decide to Adjust the Dose (See Section: "How to Take Retrovir"). Bone NecrosisIn Some Patients, a Condition Called Bone Necrosis Has Been Reported, Which May Be Caused by Several Factors (Including the Use of Corticosteroids, Alcohol Consumption, Severe Immunosuppression, and Elevated Body Mass Index). If You Experience Limb Pain, Stiffness, or Difficulty Moving, You Should Consult Your Doctor. Patients with Co-Infection with Hepatitis C VirusDuring the Use of Zidovudine as Part of the HIV Treatment Regimen, Cases of Worsening Anemia (Associated with Ribavirin Administration) Have Been Noted, Although the Exact Mechanism of This Phenomenon Has Not Been Fully Explained. Due to the Increased Risk of Anemia, the Concomitant Administration of Ribavirin and Zidovudine Is Not Recommended. Your Doctor Will Consider the Possibility of Replacing Zidovudine with Another Medicine in the Antiretroviral Treatment Regimen, If It Has Been Previously Established. This Is Especially Important in Patients Who Have Had Anemia Associated with Zidovudine Administration 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 Used with Retrovir:

• Rifampicin (an Antibiotic),
• Stavudine (Used to Treat HIV Infection).

Retrovir May Interact with Certain 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 Heroin Substitute in the Treatment of Addiction),
• Indomethacin (Used to Treat Rheumatoid Arthritis),
• Cimetidine (Used to Treat Peptic Ulcer Disease and Duodenal Ulcer),
• Clofibrate (Used to Treat Lipid Disorders),
• Isoprinosine (an Antiviral Medicine That Affects the Immune System),
• Probenecid (Used to Treat Goutand Other Similar Diseases, and Used in Combination with Certain Antibiotics to Increase Their Effectiveness),
• Pentamidine, Atovaquone (Used to Treat Parasitic Infections, Such as Pneumocystosis),
• Ampotericin, 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 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 Are Planning 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 14 Weeks of Gestation) with HIV Infection and in Newborns Born to These Women Significantly Reduces the Risk of Mother-to-Child Transmission of HIV. If You Are Pregnant or Plan to Become Pregnant, You Should Consult 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 Visits to Monitor the Development of Your Child. During These Visits, Blood Tests and Other Diagnostic Tests May Be Performed. Zidovudine, the Active Ingredient 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, as HIV Can Be Transmitted 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 Condition and Possible Side Effects of Retrovir.

Retrovir Contains Maltitol Liquid, Sorbitol (E 420), Propylene Glycol (E 1520), Sodium Benzoate (E 211) and

The Medicine Contains 640 Mg of Maltitol Liquid per 1 Ml. If You Have Been Diagnosed with Intolerance to Some Sugars, You Should Consult Your Doctor Before Taking the Medicine. The Medicine May Have a Mild Laxative Effect. The Energy Value Is 2.3 Kcal/G of Maltitol. The Medicine Contains 51.2 Mg of Sorbitol (E 420) per 1 Ml (a Component of Maltitol Liquid). Sorbitol Is a Source of Fructose. If You Have Been Diagnosed with Intolerance to Some Sugars or Have Been Diagnosed with Hereditary Fructose Intolerance, a Rare Genetic Disease in Which the Body Does Not Break Down Fructose, You Should Consult Your Doctor Before Taking the Medicine or Giving It to Your Child. The Medicine Contains 9.6 Mg of Propylene Glycol (E 1520) per 1 Ml (a Component of the Strawberry Flavor and "White Sugar" Flavor Composition). Before Administering the Medicine to a Child Under 4 Weeks of Age, You Should Consult Your Doctor or Pharmacist, Especially If the Child Is Taking Other Medicines Containing Propylene Glycol or Alcohol. The Medicine Contains 2 Mg of Sodium Benzoate (E 211) per 1 Ml. The Medicine Contains Sodium Benzoate, Which May Increase the Risk of Jaundice (Yellowing of the Skin and Eyes) in Newborns (Up to 4 Weeks of Age). This Medicine Contains Less Than 1 Mmol of Sodium (23 Mg) per Maximum Recommended Daily Dose of 600 Mg (60 Ml), Which Means That It Is Essentially "Sodium-Free".

3. How to Take Retrovir

Retrovir Should Be Taken as Directed by Your Doctor. If You Are in Doubt About the Dosage, Consult Your Doctor or Pharmacist. The Prescribed Dose May Vary from Patient to Patient and Depends on Several Factors, Including the Stage of the Disease.

Adults and Adolescents with a Body Weight of at Least 30 Kg

The Usual Dose Is 250 Mg (25 Ml) or 300 Mg (30 Ml) Twice a Day, in Combination with Other Antiretroviral Medicines.

Children with a Body Weight of at Least 9 Kg and Less Than 30 Kg

The Recommended Dose of Retrovir Is 0.9 Ml/Kg Body Weight (9 Mg/Kg Body Weight) Twice a Day, in Combination with Other Antiretroviral Medicines (e.g., a Dose of 13.5 Ml of Oral Solution Twice a Day for a Child Weighing 15 Kg), Up to a Maximum Dose of 300 Mg (30 Ml) Twice a Day.

Children with a Body Weight of at Least 4 Kg and Less Than 9 Kg

The Recommended Dose of Retrovir Is 1.2 Ml/Kg Body Weight (12 Mg/Kg Body Weight) Twice a Day, in Combination with Other Antiretroviral Medicines (e.g., a Dose of 6 Ml of Oral Solution Twice a Day for a Child Weighing 5 Kg).

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 14 Weeks of Gestation Should Receive Retrovir Orally at a Dose of 500 Mg per Day (i.e., 100 Mg Five Times a Day) Until the Onset of Labor. During Labor, Retrovir Should Be Administered Intravenously Initially at a Dose of 2 Mg/Kg Body Weight Over 1 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 Should Receive 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 Gradation of 0.1 Ml Should Be Used. For Example, Newborns Weighing 2.0 Kg and 5.0 Kg Should Receive 0.4 Ml (4 Mg of Zidovudine) and 1.0 Ml (10 Mg of Zidovudine) of Oral Solution, Respectively, Four Times a Day. If Oral Administration Is Not Possible in Newborns, Retrovir Should Be Administered Intravenously Every 6 Hours at a Dose of 1.5 Mg/Kg Body Weight Over 30 Minutes. If a Cesarean Section Is Planned, the Intravenous Infusion of Retrovir Should Be Started 4 Hours Before the Operation. If the Operation Is Cancelled, the Infusion Should Be Discontinued and Oral Administration Should Be Initiated.

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 Section: "Important Information Before Taking Retrovir").

Dosing in Elderly Patients

Your Doctor May Recommend Regular Monitoring 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 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 May Occur. Your Doctor May Decide to Adjust the Dose or Prolong the Interval Between Doses, Especially If Symptoms of Poor Tolerance Occur.

Overdose

If You Have Taken More Than the Prescribed Dose of Retrovir, You Should 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 Effect 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 Too 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 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 (Cells Involved in Blood Clotting). In Patients with Decreased Platelet Count, There May Be an Increased Risk of Bleeding and Bruising,
• Decreased Blood Cell Count (Pancytopenia) with Bone Marrow Hypoplasia (Hypocellular Bone Marrow),
• 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 Disorders,
• Taste Disorders, Loss of Appetite, Changes in the Mouth with Non-Uniform Color, Nausea, Pancreatitis, Liver Disorders, Such as Liver Enlargement, Fatty Liver,
• Changes in Fat Distribution or Accumulation in the Body,
• Frequent Urination, Breast Enlargement in Men,
• Cardiomyopathy (a Disease of the Heart Muscle),
• Selective Aplasia (Aplastic Anemia) of the Red Blood Cell System,
• 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 NRTI, 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"). The Use of Retrovir May Cause Loss of Fat from the Legs, Arms, and Face (Lipoatrophy, See Section 2 "Important Information Before Taking Retrovir").

Reporting of Side Effects

If You Experience Any Side Effects, Including Those Not Listed in This Leaflet, You Should 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 Expiration Date Stated on the Packaging. The Expiration Date Refers to the Last Day of the Month Indicated. The Batch Number of the Medicine Is Stated on the Packaging: Lot. Do Not Store Above 30°C. 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 Ingredient of Retrovir Is Zidovudine. 5 Ml of Oral Solution Contains 50 Mg of Zidovudine.
• The Other Ingredients Are: Maltitol Liquid, Glycerol (E 422), Citric Acid Anhydrous, Sodium Benzoate (E 211), Sodium Saccharin, Strawberry Flavor Composition, "White Sugar" Flavor Composition, Purified Water.

What Retrovir Looks Like and Contents of the Pack

The Pack Contains 200 Ml of Oral Solution in an Amber Glass Bottle with a Plastic Cap and a Polypropylene Oral Syringe with a Capacity of 1 Ml or 10 Ml, with a Polyethylene (HDPE) Plunger, Packaged in a Transparent Polypropylene Film, in a Cardboard Box. The Oral Solution Is a Yellowish Liquid with a Strawberry Flavor.

Marketing Authorization Holder and Importer

Marketing Authorization Holder

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

Importer

ViiV Healthcare Trading Services UK Limited 12 Riverwalk, Citywest Business Campus Dublin 24, Ireland For More Information, Contact the 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: June 2022