AURO-LAMIVUDINE/ZIDOVUDINE

2 Recommended Dose and Dosage Adjustment 01/2023 7 WARNINGS AND PRECAUTIONS, General 10/2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. 2 TABLE OF CONTENTS..............................................................................................................

2 PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................... 4 1 INDICATIONS ........................................................................................................................

1 Pediatrics ............................................................................................................................. 2 Geriatrics .............................................................................................................................

4 2 CONTRAINDICATIONS ........................................................................................................... 4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ......................................................................

4 4 DOSAGE AND ADMINISTRATION........................................................................................... 1 Dosing Considerations .........................................................................................................

2 Recommended Dose and Dosage Adjustment..................................................................... 5 Missed Dose ........................................................................................................................

6 5 OVERDOSAGE ....................................................................................................................... 6

section). 1 Dosing Considerations Auro-Lamivudine/Zidovudine may be administered with or without food. Because Auro-Lamivudine/Zidovudine is a fixed dose tablet, it should not be prescribed for patients requiring dosage adjustments, such as pediatric patients who weigh less than 40 kg with renal impairment (creatinine clearance <50 mL/min).

2 Recommended Dose and Dosage Adjustment Adults and Adolescents (> 12 years of age) weighing at least 30 kg The recommended oral dose of Auro-Lamivudine/Zidovudine for adults and adolescents weighing at least 30 kg is one tablet (containing 150 mg of lamivudine and 300 mg zidovudine) twice daily.

Dose Adjustment It is recommended that separate doses of lamivudine and zidovudine be administered to: pediatric patients weighing less than 30 kg or patients requiring dosing adjustments due to adverse events. See complete prescribing information for lamivudine and zidovudine for dosage Auro-Lamivudine/Zidovudine Product Monograph Page 6 of 53 adjustments.

Geriatrics No specific data are available, however special care is advised in this age group due to age associated changes such as the decrease in renal function and alteration of hematological parameters. Hepatic Insufficiency It is recommended that Auro-Lamivudine/Zidovudine not be used in patients with hepatic impairment.

For these patients, it is recommended that lamivudine and zidovudine be administered as separate tablets. Renal Insufficiency It is recommended that Auro-Lamivudine/Zidovudine not be used in patients with reduced renal function (creatinine clearance less than 30 mL/min).

For these patients, it is recommended that lamivudine and zidovudine be administered as separate tablets. The individual Product Monographs for lamivudine and zidovudine should be consulted for appropriate dosage adjustments. 3-fold higher lamivudine exposure (AUC) than patients with a creatinine clearance ≥50 mL per min.

In the original lamivudine registrational trials in combination with zidovudine, higher lamivudine exposures were associated with higher rates of hematologic toxicities (neutropenia and anemia), although discontinuations due to neutropenia or anemia each occurred in <1% of subjects.

Patients with a sustained creatinine clearance between 30 and 49 mL per min who receive Auro-Lamivudine/Zidovudine should be monitored for hematologic toxicities. If new or worsening neutropenia or anemia develop, dose adjustment of lamivudine, per lamivudine prescribing information, is recommended.

If lamivudine dose adjustment is indicated, Auro-Lamivudine/Zidovudine should be discontinued and the individual components should be used to construct the treatment regimen. 5 Missed Dose If you forget to take your medicine, take it as soon as you remember.

Then continue as before. 5 OVERDOSAGE There is no known antidote for Auro-Lamivudine/Zidovudine. Auro-Lamivudine/Zidovudine Product Monograph Page 7 of 53 If overdosage occurs the patient should be monitored, and standard supportive treatment applied as required.

Although no data is available, administration of activated charcoal may be used to aid in removal of unabsorbed drug. Because a negligible amount of lamivudine was removed via (4-hour) hemodialysis, continuous ambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous hemodialysis would provide clinical benefit in a lamivudine overdose event.

Hemodialysis and peritoneal dialysis appear to have a negligible effect on the removal of zidovudine while elimination of its primary metabolite, GZDV is enhanced. No specific signs or symptoms have been identified following acute overdose with lamivudine or zidovudine apart from those listed as adverse reactions.

For management of a suspected drug overdose, contact your regional poison control centre. 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 Dosage Form, Strength, Composition and Packaging Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Tablets/ 150 mg lamivudine and 300 mg zidovudine Cellulose Microcrystalline (Avicel PH 101), Cellulose Microcrystalline (Avicel PH 102), Hypromellose (6cP), Magnesium stearate (Ligarned MF-2-V), Macrogol 400, Polysorbate 80, Sodium Starch Glycolate (Promojel Type A), Silica colloidal anhydrous (Aerosil 200 pharma), Titanium Dioxide.

Auro-Lamivudine/Zidovudine tablets White to off-white, modified capsule shaped, biconvex, film-coated tablets with deep breakline in between ‘J’ and ‘59’ on one side and deep breakline on the other side. Available in blister Pack: 10 x 10’s and HDPE container 60’s, 100’s & 500’s counts.

7 WARNINGS AND PRECAUTIONS Please see the Serious Warnings and Precautions Box at the beginning of Part I: Health Professional Information. General Patients should be cautioned about the concomitant use of self-administered medications.

Auro-Lamivudine/Zidovudine is a fixed-dose combination of lamivudine and zidovudine. Auro- Lamivudine/Zidovudine should not be administered concomitantly with other products containing either lamivudine or zidovudine including 3TC Tablets and oral solution; RETROVIR Auro-Lamivudine/Zidovudine Product Monograph Page 8 of 53 Syrup and Solution for infusion, KIVEXA Tablets, DELSTRIGO Tablets, DOVATO Tablets, or TRIUMEQ Tablets.

Auro-Lamivudine/Zidovudine should also not be administered concomitantly with emtricitabine containing products, including ATRIPLA Tablets, EMTRIVA Capsules, TRUVADA Tablets, COMPLERA Tablets, STRIBILD Tablets, BIKTARVY Tablets, DESCOVY Tablets, GENVOYA Tablets, ODEFSEY Tablets, or SYMTUZA Tablets.

Patients receiving Auro-Lamivudine/Zidovudineor any other antiretroviral therapy may continue to develop opportunistic infections and other […]

, General 10/2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. 2 TABLE OF CONTENTS..............................................................................................................

2 PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................... 4 1 INDICATIONS ........................................................................................................................

1 Pediatrics ............................................................................................................................. 2 Geriatrics .............................................................................................................................

4 2 CONTRAINDICATIONS ........................................................................................................... 4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ......................................................................

4 4 DOSAGE AND ADMINISTRATION........................................................................................... 1 Dosing Considerations .........................................................................................................

2 Recommended Dose and Dosage Adjustment..................................................................... 5 Missed Dose ........................................................................................................................

6 5 OVERDOSAGE ....................................................................................................................... 6 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ..........................................

7 7 WARNINGS AND PRECAUTIONS ............................................................................................ 1 Special Populations............................................................................................................

1 Pregnant Women ........................................................................................................ 2 Breast-feeding.............................................................................................................

3 Pediatrics .................................................................................................................... 4 Geriatrics.....................................................................................................................

14 8 ADVERSE REACTIONS .......................................................................................................... 2 Clinical Trial Adverse Reactions .........................................................................................

4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data ......................................................................................................................................... 5 Post-Market Adverse Reactions.........................................................................................

16 9 DRUG INTERACTIONS.......................................................................................................... 2 Drug Interactions Overview ...............................................................................................

4 Drug-Drug Interactions ...................................................................................................... 19 10 CLINICAL PHARMACOLOGY ...............................................................................................

1 Mechanism of Action ....................................................................................................... 3 Pharmacokinetics ............................................................................................................

25 11 STORAGE, STABILITY AND DISPOSAL ................................................................................. 31 12 SPECIAL HANDLING INSTRUCTIONS...................................................................................

32 PART II: SCIENTIFIC INFORMATION ........................................................................................ 33 13 PHARMACEUTICAL INFORMATION....................................................................................

33 14 CLINICAL TRIALS ................................................................................................................ 3 Comparative Bioavailability Study ...................................................................................

35 15 MICROBIOLOGY ................................................................................................................ 36 16 NON-CLINICAL TOXICOLOGY .............................................................................................

39 17 SUPPORTING PRODUCT MONOGRAPHS............................................................................ 46 PATIENT MEDICATION INFORMATION ................................................................................... 47 Auro-Lamivudine/Zidovudine Product Monograph Page 4 of 53 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS Auro-Lamivudine/Zidovudine (lamivudine and zidovudine), in combination with other antiretrovirals, is indicated for the treatment of HIV infection.

1 Pediatrics Pediatrics (< 12 years of age): The safety and efficacy of lamivudine and zidovudine in pediatric patients less than 12 years of age have not been established. Auro-Lamivudine/Zidovudine is not recommended in children less than 12 years of age, as appropriate dose reduction for the weight of the child cannot be made.

(see 4 DOSAGE AND […]

• Auro-Lamivudine/Zidovudine is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of the product. For a complete listing see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section.

65 mmol/L)