RUKOBIA

1 Dosing Considerations As with all antiretroviral drugs, therapy should be initiated by a healthcare professional experienced in the management of HIV infection. 2 Recommended Dose and Dosage Adjustment Adults The recommended dose of RUKOBIA in adults is one 600 mg tablet taken orally twice daily with or without food.

Tablets should be swallowed whole, and not be split, crushed or chewed.

Pediatrics (< 18 years of age):

Safety and efficacy of RUKOBIA have not been established in pediatric patients less than 18 years of age.

RUKOBIA, fostemsavir Page 5 of 39 Geriatrics (≥ 65 years of age):

Clinical studies of RUKOBIA did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from adult patients < 65 years of age. 3 Pharmacokinetics). 3 Pharmacokinetics). 5 Missed Dose If the patient misses a dose of RUKOBIA, the patient should take RUKOBIA as soon as possible.

The patient should not take a double dose to make up for the missing dose.

). Particular diligence should be applied in initiating or maintaining effective hepatitis B therapy (referring to treatment guidelines) when starting RUKOBIA in patients co-infected with hepatitis B. Immune Immune Reconstitution Inflammatory Syndrome During the initial phase of treatment, patients responding to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as MAC, CMV, PCP and TB), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have also been reported to occur in the setting of immune reconstitution, however the time to onset is more variable, and can occur many months after initiation of treatment and sometimes can be an atypical presentation.

Sexual Health • Fertility There are no data on the effects of fostemsavir on human male or female fertility. Animal studies indicate no effects of fostemsavir on male or female fertility at clinically relevant doses (see 16 NON-CLINICAL TOXICOLOGY).

RUKOBIA, fostemsavir Page 7 of 39 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions The concomitant use of RUKOBIA and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of RUKOBIA and possible development of resistance due to reduced exposure of temsavir or possible prolongation of QTc interval from increased exposure to temsavir.

Consider the potential for drug interactions prior to and during therapy with RUKOBIA, review concomitant medications during therapy with RUKOBIA, and monitor for the adverse reactions associated with the concomitant drugs (see

, General [Removed] 05/2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................

4 1 INDICATIONS .............................................................................................................. 1 Pediatrics ...............................................................................................................

2 Geriatrics................................................................................................................ 4 2 CONTRAINDICATIONS .................................................................................................

4 4 DOSAGE AND ADMINISTRATION................................................................................. 1 Dosing Considerations ........................................................................................... 2 Recommended Dose and Dosage Adjustment .......................................................

5 Missed Dose ........................................................................................................... 5 5 OVERDOSAGE .............................................................................................................

5 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................ 5 7 WARNINGS AND PRECAUTIONS .................................................................................. 1 Special Populations ................................................................................................

• RUKOBIA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

• RUKOBIA is contraindicated in combination with strong cytochrome P450 (CYP3A) inducers as significant decreases in temsavir (the active moiety of fostemsavir) plasma concentrations may occur which may result in loss of virologic response.

These drugs include, but are not limited to (see 9 DRUG INTERACTIONS): o Anticonvulsants: carbamazepine, phenytoin o Antineoplastic: mitotane o Androgen receptor inhibitor: enzalutamide o Antimycobacterial: rifampin o St John’s wort (Hypericum perforatum) (see 9 DRUG INTERACTIONS, Drug-herb Interactions)