Consumer medicine information

Vemlidy

Tenofovir alafenamide

BRAND INFORMATION

Brand name

Vemlidy

Active ingredient

Tenofovir alafenamide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Vemlidy.

SUMMARY CMI

VEMLIDY®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using VEMLIDY?

VEMLIDY contains the active ingredient tenofovir alafenamide. VEMLIDY is used for the treatment of chronic (long-lasting) hepatitis B virus (HBV) in adults.

For more information, see Section 1. Why am I using VEMLIDY? in the full CMI.

2. What should I know before I use VEMLIDY?

Do not use if you have ever had an allergic reaction to VEMLIDY or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use VEMLIDY? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with VEMLIDY and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use VEMLIDY?

  • The usual dose is one VEMLIDY tablet orally, once daily.

More instructions can be found in Section 4. How do I use VEMLIDY? in the full CMI.

5. What should I know while using VEMLIDY?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using VEMLIDY.
Things you should not do
  • Do not stop using this medicine suddenly.
Driving or using machines
  • Be careful driving or operating machinery until you know how VEMLIDY affects you.
Looking after your medicine
  • Keep your VEMLIDY tablets in the bottle with the cap tightly closed until you take them.
  • Keep VEMLIDY tablets in a cool, dry place where it stays below 30°C.

For more information, see Section 5. What should I know while using VEMLIDY? in the full CMI.

6. Are there any side effects?

The most common side effect of VEMLIDY is nausea.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

VEMLIDY®

Active ingredient: tenofovir alafenamide

Consumer Medicine Information (CMI)

This leaflet provides important information about using VEMLIDY. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using VEMLIDY.

Where to find information in this leaflet:

1. Why am I using VEMLIDY?
2. What should I know before I use VEMLIDY?
3. What if I am taking other medicines?
4. How do I use VEMLIDY?
5. What should I know while using VEMLIDY?
6. Are there any side effects?
7. Product details

1. Why am I using VEMLIDY?

VEMLIDY contains the active ingredient tenofovir alafenamide. This active ingredient is an antiviral medicine, known as a nucleotide reverse transcriptase inhibitor (NtRTI).

VEMLIDY is used for the treatment of chronic (long-lasting) hepatitis B virus (HBV) in adults.

VEMLIDY works by interfering with the normal working of an enzyme (DNA polymerase) that is essential for the HBV to reproduce itself. VEMLIDY may help lower the amount of hepatitis B virus in your body by lowering the ability of the virus to multiply and infect new liver cells and can improve the inflammation and scar tissue caused by the hepatitis B virus in your liver. Lowering the amount of virus in your body may reduce the chance of developing cirrhosis, liver failure and liver cancer.

We do not know how long VEMLIDY may help treat your hepatitis. Sometimes viruses change in your body and medicines no longer work. This is called drug resistance.

It is not known if VEMLIDY is safe and effective for treatment of HBV in children or adolescents under 18 years of age.

2. What should I know before I use VEMLIDY?

Warnings

Do not use VEMLIDY if:

  • you are allergic to tenofovir alafenamide, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • you are taking any medicine that contains:
    - tenofovir disoproxil fumarate
    - adefovir dipivoxil

Check with your doctor if you:

  • have Human Immunodeficiency Virus (HIV) infection.
    - Your doctor may test you for HIV infection before starting VEMLIDY. If you have HIV and take VEMLIDY, the HIV virus may develop resistance and become harder to treat.
  • have any other medical conditions
    - Your doctor should do blood and urine tests to check your kidneys when starting and during treatment with VEMLIDY. Your doctor may tell you to stop taking VEMLIDY if you develop new or worse kidney problems.
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor can discuss with you the risks and benefits involved.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and VEMLIDY may interfere with each other. These include:

  • rifampicin, rifapentine, rifabutin (antibiotics used to treat infections, including tuberculosis);
  • St. John's Wort (Hypericum perforatum – herbal medicine used to treat depression);
  • carbamazepine, phenytoin, phenobarbital, oxcarbazepine (medicines used to treat epilepsy and prevent seizures).
  • itraconazole, ketoconazole (antifungals used to treat infections)

These medicines may be affected by VEMLIDY or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

Know the medicines you take. Keep a list of medicines and show it to your doctor and pharmacist when you get a new medicine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect VEMLIDY.

4. How do I use VEMLIDY?

How much to take / use

  • Take VEMLIDY exactly as your doctor tells you to take it.
  • The usual dose is one VEMLIDY tablet orally, once daily.

When to take / use VEMLIDY

  • VEMLIDY should be used at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.
  • It does not matter if you take this medicine before or after food.

If you forget to use VEMLIDY

VEMLIDY should be used regularly at the same time each day. It is important not to miss a dose of VEMLIDY. If you miss your dose at the usual time, take your missed dose right away unless it is almost time for your next dose.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

Continue with your regular dosing schedule.

If you are not sure what to do, ask your doctor or pharmacist.

If you use too much VEMLIDY

If you think that you have used too much VEMLIDY, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre by calling 13 11 26 (Australia) and 0800 764 766 (New Zealand), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using VEMLIDY?

Things you should do

  • Remind any doctor, dentist or pharmacist you visit that you are using VEMLIDY.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.
  • If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Things you should not do

  • Do not take VEMLIDY to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
  • Do not stop taking your medicine or lower the dosage without checking with your doctor. If you stop taking it suddenly, your condition may worsen or you may have unwanted side effects.
  • Do not take VEMLIDY if the packaging is torn or shows signs of tampering.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how VEMLIDY affects you.

Looking after your medicine

  • Keep your VEMLIDY tablets in the bottle with the cap tightly closed until you take them. If you take the tablets out of the bottle they may not keep well.
  • Keep VEMLIDY tablets in a cool, dry place where it stays below 30°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

This medicine helps most people with chronic HBV infection, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • nausea
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Allergy

Some of the following symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • chest pain or tightness
  • fainting
  • rash, itching or hives on the skin

These are very serious effects. If you have them, you may have a serious allergic reaction. You may need urgent medical attention or hospitalisation.

Do not take any more VEMLIDY and tell your doctor straight away, or go straight to the Emergency Department at your nearest hospital.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What VEMLIDY contains

Active ingredient
(main ingredient)		tenofovir alafenamide
Other ingredients
(inactive ingredients)
  • magnesium stearate
  • croscarmellose sodium
  • lactose monohydrate
  • microcrystalline cellulose
  • iron oxide yellow
  • polyethylene glycol
  • polyvinyl alcohol
  • purified talc
  • titanium dioxide
Potential allergensN/A

Do not take this medicine if you are allergic to any of these ingredients.

What VEMLIDY looks like

VEMLIDY tablets are round and yellow in colour. Each tablet has “GSI” on one side and “25” on the other side of the tablet.

VEMLIDY tablets are supplied in bottles containing 30 tablets.

AUST R 274395

Who distributes VEMLIDY

Australia

Gilead Sciences Pty Ltd
Level 28, 385 Bourke Street Melbourne, Victoria, 3000

This leaflet was prepared in January 2024.

VEMLIDY and GSI are trademarks of Gilead Sciences, Inc. or one of its related companies. Other brands listed are trademarks of their respective owners and are not trademarks of Gilead Sciences, Inc.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Vemlidy

Active ingredient

Tenofovir alafenamide

Schedule

S4

 

1 Name of Medicine

Vemlidy (tenofovir alafenamide 25 mg).
The active substance in Vemlidy tablets is tenofovir alafenamide.

2 Qualitative and Quantitative Composition

Vemlidy is available as tablets. Each Vemlidy tablet contains 25 mg of tenofovir alafenamide (equivalent to 28 mg of tenofovir alafenamide fumarate). Vemlidy tablets are yellow, round, film-coated, debossed with "GSI" on one side and "25" on the other side of the tablet. Contains lactose. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Vemlidy tablets are yellow, round, film-coated, debossed with "GSI" on one side and "25" on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Vemlidy is indicated for the treatment of chronic hepatitis B in adults.

4.2 Dose and Method of Administration

The recommended dose of Vemlidy is one tablet once daily, with or without food.

Children and adolescents up to 18 years of age.

No data are available on which to make a dose recommendation for patients younger than 18 years (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

Elderly.

No dose adjustment is required in patients aged 65 years and above (see Section 5.2 Pharmacokinetic Properties, Special populations).

Renal impairment.

No dose adjustment of Vemlidy is required in patients with renal impairment.

Hepatic impairment.

No dose adjustment of Vemlidy is required in patients with hepatic impairment (see Section 5.2 Pharmacokinetic Properties, Special populations).

4.3 Contraindications

Vemlidy tablets are contraindicated in patients with known hypersensitivity to the active substance or to any other component of the tablets.

4.4 Special Warnings and Precautions for Use

Exacerbation of hepatitis after discontinuation of treatment.

Discontinuation of anti-hepatitis B therapy, including Vemlidy, may be associated with severe acute exacerbations of hepatitis. Patients who discontinue Vemlidy should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted. In patients with advanced liver disease or cirrhosis, discontinuation of anti-hepatitis B therapy is not recommended since post-treatment exacerbation of hepatitis may lead to hepatic decompensation.

Hepatitis B and HIV coinfection.

Due to the risk of development of HIV-1 resistance, Vemlidy is not recommended for the treatment of HIV-1 infection. The safety and efficacy of Vemlidy have not been established in patients co-infected with HBV and HIV-1. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Vemlidy, and, if positive, an appropriate antiretroviral combination regimen that is recommended for patients co-infected with HIV-1 should be used.

Use with related products.

Vemlidy should not be coadministered with products containing tenofovir alafenamide, tenofovir disoproxil fumarate, or adefovir dipivoxil.

Paediatric use.

Safety and effectiveness of Vemlidy in children less than 18 years of age have not been established.

Use in renal impairment.

Post marketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide containing products; while most of these cases were characterised by potential confounders that may have contributed to the reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse events.
Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents, including non-steroidal anti-inflammatory drugs, are at increased risk of developing renal-related adverse reactions.
Prior to or when initiating Vemlidy, and during treatment with Vemlidy on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue Vemlidy in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
No dose adjustment of Vemlidy is required in patients with renal impairment. Vemlidy is not recommended in patients with end stage renal disease (estimated creatinine clearance below 15 mL per minute).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interaction studies have only been performed in adults.
Vemlidy should not be co-administered with medicinal products containing tenofovir disoproxil fumarate, tenofovir alafenamide or adefovir dipivoxil.

Medicinal products that may affect tenofovir alafenamide.

Tenofovir alafenamide is transported by P-gp and breast cancer resistance protein (BCRP). Medicinal products that are P-gp inducers (e.g. rifampicin, rifabutin, phenobarbital or St. John's wort) are expected to decrease plasma concentrations of tenofovir alafenamide, which may lead to loss of therapeutic effect of Vemlidy. Co-administration of such medicinal products with Vemlidy is not recommended.
Co-administration of Vemlidy with medicinal products that inhibit P-gp and BCRP may increase plasma concentration of tenofovir alafenamide. Vemlidy may be coadministered with P-gp or BCRP inhibitors.
Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro. The distribution of tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and/or OATP1B3.

Effect of tenofovir alafenamide on other medicinal products.

Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 in vitro. It is not an inhibitor or inducer of CYP3A in vivo.
Tenofovir alafenamide is not an inhibitor of human uridine diphosphate glucuronosyltransferase (UGT) 1A1 in vitro. It is not known whether tenofovir alafenamide is an inhibitor of other UGT enzymes.
Drug interaction information for Vemlidy with potential concomitant medicinal products is summarised in Table 1. The drug interactions described are based on studies conducted with tenofovir alafenamide, or are potential drug interactions that may occur with Vemlidy.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No human data on the effect of Vemlidy on fertility are available. There were no effects on fertility, mating performance or early embryonic development when tenofovir alafenamide was administered to male rats at a dose equivalent to 155 times the human dose based on body surface area comparisons for 28 days prior to mating and to female rats for 14 days prior to mating to Day 7 of gestation.
(Category B3)
Vemlidy (Pregnancy Category B3). There are no adequate and well-controlled studies with Vemlidy in pregnant women. Vemlidy should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Studies in animals have shown no evidence of teratogenicity (rats and rabbits) or an effect on reproductive function (rats) due to tenofovir alafenamide.
Embryonic fetal development studies performed in rats and rabbits revealed no evidence of impaired fertility or harm to the fetus. The embryo-fetal NOAELs in rats and rabbits occurred at tenofovir alafenamide exposures similar to and 51 times higher than, respectively, the exposure in humans at the recommended daily dose. Tenofovir alafenamide is rapidly converted to tenofovir, the observed tenofovir exposure in rats and rabbits were 54 and 85 times higher than human tenofovir exposures at the recommended daily doses, respectively.
 In animal studies it has been shown that tenofovir is secreted into milk. It is not known whether tenofovir alafenamide is secreted in human milk.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects of Vemlidy on the ability to drive and use machines have been performed.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

Adverse effects.

Clinical trials in adult patients with chronic hepatitis B.

The safety assessment of Vemlidy was based on pooled data to Week 96 data analysis from 1298 patients in two randomised, double-blind, active-controlled trials, Study 108 and Study 110, in adult patients with chronic hepatitis B. A total of 866 patients received one tablet of Vemlidy once daily (see Section 5.1 Pharmacodynamic Properties, Clinical trials). Further safety assessment was based on pooled data from Studies 108 and 110 from patients who continued to receive their original blinded treatment to Week 120 and additionally from patients who received open-label Vemlidy from Week 96 to Week 120.
Based on the Week 96 analysis, the most common adverse reactions (all Grades) reported in at least 10% of patients in the Vemlidy group was headache. The proportion of patients who discontinued treatment with Vemlidy or Viread due to adverse reactions, regardless of severity, was 1.5% and 0.9%, respectively. Table 2 displays the frequency of the adverse reactions (all Grades) greater than or equal to 5% in the Vemlidy group.
Additional adverse reactions occurring in greater than 1% to less than 5% of patients in Studies 108 and 110 included vomiting, rash, and flatulence.
The safety profile of Vemlidy in patients who continued to receive blinded treatment to Week 120 was similar to that at Week 96. The safety profile of Vemlidy in patients who remained on Vemlidy in the open-label phase to Week 120 was similar to that in patients who switched from Viread to Vemlidy at Week 96.

Virologically suppressed patients.

No additional adverse reactions to Vemlidy were identified through Week 48 in a double blind, randomized, active-controlled Study (GS-US-320-4018) in virologically suppressed subjects who switched from Viread to Vemlidy (N=243).

Patients with renal and/or hepatic impairment.

No additional adverse reactions to Vemlidy were identified through Week 24 in an open label clinical study (GS-US-320-4035) of virologically suppressed patients with moderate to severe renal impairment (eGFR by Cockcroft-Gault method 15 to 59 mL/min; N=78), end stage renal disease (ESRD) (eGFR < 15 mL/min) on hemodialysis (N=15), or moderate to severe hepatic impairment (N=31) who switched from another antiviral regimen to Vemlidy. Table 3 displays the summary of subjects meeting on-treatment liver-induced toxicity criteria (safety analysis set, Week 24).

Tabulated summary of adverse reactions.

The following adverse drug reactions have been identified with tenofovir alafenamide in patients with chronic hepatitis B (Table 4). The adverse reactions are listed by body system organ class and frequency based on the Week 96 analysis. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) or very rare (< 1/10,000).

Post marketing experience.

In addition to adverse reactions from clinical studies, the following adverse reactions were identified during postapproval use of products containing tenofovir alafenamide (TAF). Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made.

Renal and urinary disorders.

Acute renal failure, proximal renal tubulopathy, Fanconi syndrome.

Skin and subcutaneous tissue disorders.

Angioedema, urticaria.

4.9 Overdose

If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with Vemlidy consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.
Limited clinical experience is available at doses higher than the therapeutic dose of tenofovir alafenamide. A dose of 120 mg tenofovir alafenamide (4.8 times the dose in Vemlidy) was administered once daily for 28 days to 10 patients with chronic hepatitis B; no serious adverse reactions were reported. The effects of higher doses are unknown. Tenofovir is efficiently removed by haemodialysis with an extraction coefficient of approximately 54%.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia) and 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antiviral for systemic use, nucleoside and nucleotide reverse transcriptase inhibitors; ATC code: J05AF13.

Mechanism of action.

Tenofovir alafenamide is a phosphonamidate prodrug of tenofovir (2'-deoxyadenosine monophosphate analogue). Tenofovir alafenamide enters primary hepatocytes by passive diffusion with some contribution by hepatic uptake transporters, OATP1B1 and OATP1B3. Tenofovir alafenamide is primarily hydrolysed by carboxylesterase 1 in primary hepatocytes, and by cathepsin A in peripheral blood mononuclear cells (PBMCs) and other HIV target cells. Intracellular tenofovir is subsequently phosphorylated to the pharmacologically active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination.
Tenofovir has activity that is specific to hepatitis B virus and human immunodeficiency virus (HIV-1 and HIV-2). Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases that include mitochondrial DNA polymerase γ and there is no evidence of mitochondrial toxicity in vitro based on several assays including mitochondrial DNA analyses.

Antiviral activity.

The antiviral activity of tenofovir alafenamide was assessed in HepG2 cells against a panel of HBV clinical isolates representing genotypes A-H. The EC50 (50% effective concentration) values for tenofovir alafenamide ranged from 34.7 to 134.4 nanoM, with an overall mean EC50 of 86.6 nanoM. The CC50 (50% cytotoxicity concentration) in HepG2 cells was > 44,400 nanoM. In cell culture combination antiviral activity studies of tenofovir with the nucleoside reverse transcriptase inhibitors emtricitabine, entecavir, lamivudine, and telbivudine, no antagonistic activity was observed.

Resistance.

Sequence analysis was performed on paired baseline and on-treatment HBV isolates for patients who experienced virologic breakthrough (2 consecutive visits with HBV DNA ≥ 69 IU/mL after having been < 69 IU/mL, or 1.0-log10 or greater increase in HBV DNA from nadir) or patients with HBV DNA ≥ 69 IU/mL at Week 48 or Week 96 or at early discontinuation at or after Week 24.
In a pooled analysis of treatment-naïve and treatment-experienced patients receiving.
Vemlidy in Study 108 and Study 110, 27 and 87 patients qualified for resistance analyse at Week 48 and Week 96, respectively. No amino acid substitutions associated with resistance to Vemlidy were identified in these isolates (genotypic and phenotypic analyses).
In virologically suppressed patients receiving Vemlidy in Study 4018, no patient experienced a virologic blip (one visit with HBV DNA ≥ 69 IU/mL), virologic breakthrough or persistent viremia during treatment, and 0 of 243 (0.0%) patients qualified for resistance analysis through 48 weeks of Vemlidy treatment.

Cross-resistance.

The antiviral activity of tenofovir alafenamide was evaluated against a panel of isolates containing nucleos(t)ide reverse transcriptase inhibitor mutations in HepG2 cells. HBV isolates expressing the rtV173L, rtL180M, and rtM204V/I substitutions associated with resistance to lamivudine remained susceptible to tenofovir alafenamide (< 2-fold change in EC50). HBV isolates expressing the rtL180M, rtM204V plus rtT184G, rtS202G, or rtM250V substitutions associated with resistance to entecavir remained susceptible to tenofovir alafenamide. HBV isolates expressing the rtA181T, rtA181V, or rtN236T single substitutions associated with resistance to adefovir remained susceptible to tenofovir alafenamide; however, the HBV isolate expressing rtA181V plus rtN236T exhibited reduced susceptibility to tenofovir alafenamide (3.7-fold change in EC50). The clinical relevance of these substitutions is not known.

Effects on the electrocardiogram.

In a thorough QT/QTc study in 48 healthy patients, tenofovir alafenamide at the therapeutic dose or at a supratherapeutic dose 5 times the recommended therapeutic dose, did not affect the QT/QTc interval and did not prolong the PR interval.

Clinical trials.

Description of clinical studies. The efficacy and safety of Vemlidy in patients with chronic hepatitis B are based on 48 and 96-week data from two randomised, double-blind, active-controlled studies, GS-US-320-0108 ("Study 108") and GS-US-320-0110 ("Study 110"). The safety of Vemlidy is also supported by pooled data from patients in Studies 108 and 110 who remained on blinded treatment from Week 96 to Week 120 and additionally from patients in the open-label phase of Studies 108 and 110 from Week 96 to Week 120 (n = 361 remained on Vemlidy; n = 180 switched from Viread to Vemlidy at Week 96).
The efficacy and safety of Vemlidy in virologically suppressed adults with chronic hepatitis B are based on 48-week data from a randomized, double-blind, active controlled study, GS-US-320-4018 ("Study 4018"). The efficacy and safety of Vemlidy in virologically suppressed patients with chronic hepatitis B and moderate to severe renal impairment or ESRD on hemodialysis is based on 24-week data from an open-label study, GS-US-320-4035 ("Study 4035"), Part A. The efficacy and safety of Vemlidy in virologically suppressed patients with chronic hepatitis B and moderate to severe hepatic impairment is based on 24-week data from an open-label study, Study 4035, Part B. Table 5 presents a summary of the baseline disease characteristics by study part, cohort, and overall.
Adult patients with compensated liver disease. In Study 108, HBeAg-negative treatment-naïve and treatment-experienced patients with compensated liver function were randomised in a 2:1 ratio to receive Vemlidy (N=285) once daily or Viread (tenofovir disoproxil fumarate 300 mg; N=140) once daily. The mean age was 46 years, 61% were male, 72% were Asian, and 25% were White. 24%, 38%, and 31% had HBV genotype B, C, and D, respectively. 21% were treatment experienced (previous treatment with oral antivirals, including entecavir (N=41), lamivudine (N=42), tenofovir disoproxil fumarate (N=21), or other (N=18)). At baseline, mean plasma HBV DNA was 5.8 log10 IU/mL, mean serum ALT was 94 U/L, and 9% of patients had a history of cirrhosis.
In Study 110, HBeAg-positive treatment-naïve and treatment-experienced patients with compensated liver function were randomised in a 2:1 ratio to receive Vemlidy (N=581) once daily or Viread (300 mg; N=292) once daily. The mean age was 38 years, 64% were male, 82% were Asian, and 17% were White. 17%, 52%, and 23% had HBV genotype B, C, and D, respectively. 26% were treatment experienced (previous treatment with oral antivirals, including adefovir (N=42), entecavir (N=117), lamivudine (N=84), telbivudine (N=25), tenofovir disoproxil fumarate (N=70), or other (N=17)). At baseline, mean plasma HBV DNA was 7.6 log10 IU/mL, mean serum ALT was 120 U/L, and 7% of patients had a history of cirrhosis.
The primary efficacy endpoint in both trials was the proportion of patients with plasma HBV DNA levels below 29 IU/mL at Week 48.
Treatment outcomes of Studies 108 and 110 at Weeks 48 and 96 are presented in Table 6 and Table 7.
Vemlidy met the non-inferiority criteria in achieving HBV DNA less than 29 IU/mL when compared to Viread at Week 48. At Week 96, similar efficacy was demonstrated with Vemlidy compared to Viread.

Bone mineral density.

In a pooled analysis of Studies 108 and 110, the effects of Vemlidy compared to that of Viread on bone mineral density (BMD) change from baseline to Weeks 48 and 96 was assessed by dual-energy X-ray absorptiometry (DXA). As shown in Table 8, in patients with both baseline and Week 48, and with both baseline and Week 96, measurements in the Vemlidy group and in the Viread group for hip; and in the Vemlidy group and in the Viread group for spine; at Weeks 48 and 96, respectively, there were smaller decreases in BMD in the Vemlidy group as compared to Viread.
In patients who remained on blinded treatment beyond Week 96 in Studies 108 and 110, mean percentage change in BMD as assessed by DXA in each group at Week 120 was similar to that at Week 96. In the open-phase of Studies 108 and 110, mean percentage change in BMD from Week 96 to Week 120 in patients who remained on Vemlidy was +0.6% at the lumbar spine and 0% at the total hip, compared to +1.7% at the lumbar spine and +0.6% at the total hip in those who switched from Viread to Vemlidy at Week 96.

Changes in renal laboratory tests.

In a pooled analysis of Studies 108 and 110, laboratory tests were performed to compare the effect of Vemlidy to that of Viread on renal laboratory parameters. As shown in Table 9, statistically significant differences were observed between treatment groups for decreases in creatinine clearance, and changes in urine protein to creatinine ratio (UPCR), urine retinol binding protein (RBP) to creatinine ratio, and urine beta-2-microglobulin to creatinine ratio that favored Vemlidy at Weeks 48 and 96. There were no cases of Fanconi Syndrome or proximal renal tubulopathy (PRT) in either treatment group up to Week 96.
In patients who remained on blinded treatment beyond Week 96 in Studies 108 and 110, change from baseline in renal laboratory parameter values in each group at Week 120 were similar to those at Week 96. In the open-label phase of Studies 108 and 110, the mean change (±SD) in serum creatinine from Week 96 to Week 120 was -0.002 (0.10) mg/dL in those who remained on Vemlidy, compared to -0.008 (0.09) mg/dL in those who switched from Viread to Vemlidy at Week 96. In the open-label phase, the median change in eGFR from Week 96 to Week 120 was -0.6 mL/min in patients who remained on Vemlidy, compared to +1.8 mL/min patients who switched from Viread to Vemlidy at Week 96.

Changes in lipid laboratory tests.

In a pooled analysis of Studies 108 and 110, median changes in fasting lipid parameters from baseline to Week 96 were observed in both treatment groups. In the Vemlidy group, decreases in median fasting total cholesterol and HDL, and increases in median fasting direct LDL and triglycerides were observed, while the Viread group demonstrated reductions in all parameters (p < 0.001 for the difference between treatment groups for fasting total cholesterol, direct LDL, HDL, and triglycerides). Median (Q1, Q3) change from baseline at Week 96 in total cholesterol to HDL ratio was 0.3 (-0.1, 0.6) in the Vemlidy group and 0.2 (-0.1, 0.6) in the Viread group (p = 0.14 for the difference between treatment groups).

Virologically suppressed adult patients.

The efficacy and safety of switching from Viread to Vemlidy were evaluated in a randomized, double-blind, active-controlled study (Study 4018) of virologically suppressed chronic hepatitis B-infected adults (N=488). Patients must have been taking TDF 300 mg once daily for at least 12 months, with HBV DNA < LLOQ by local laboratory assessment for at least 12 weeks prior to screening and HBV DNA < 20 IU/mL at screening. Patients were stratified by HBeAg status (HBeAg-positive or HBeAg-negative) and age (≥ 50 or < 50 years) and randomized in a 1:1 ratio to either switch to Vemlidy (N=243) or stay on TDF 300 mg once daily (N=245). Mean age was 51 years (22% were ≥ 60 years), 71% were male, 82% were Asian, 14% were White, and 68% were HBeAg-negative. At baseline, mean serum ALT was 27 U/L, median eGFR by Cockcroft-Gault was 90.5 mL/min; 16% of patients had a history of cirrhosis.
The primary efficacy endpoint was the proportion of patients with plasma HBV DNA levels ≥ 20 IU/mL at Week 48 (as determined by the modified US FDA Snapshot algorithm).
Additional efficacy endpoints included the proportion of subjects with HBV DNA levels < 20 IU/mL, ALT normal and ALT normalization, HBsAg loss and seroconversion, and HBeAg loss and seroconversion.
Treatment outcomes of Study 4018 at Week 48 are presented in Table 10 and Table 11.
Vemlidy was noninferior in the proportion of subjects with HBV DNA ≥ 20 IU/mL at Week 48 when compared to Viread as assessed by the modified FDA Snapshot algorithm. Treatment outcomes (HBV DNA < 20 IU/mL by missing=failure) at Week 48 between treatment groups were similar across subgroups by age, sex, race, baseline HBeAg status, and ALT. See Table 11.

Bone mineral density.

In Study 4018, the mean percentage change in BMD from baseline to Week 48 as assessed by DXA was +1.7% with Vemlidy compared to -0.1% with Viread at the lumbar spine and +0.7% compared to -0.5% at the total hip. BMD declines of greater than 3% at the lumbar spine were experienced by 4% of Vemlidy patients and 17% of Viread patients at Week 48. BMD declines of greater than 3% at the total hip were experienced by 2% of Vemlidy patients and 12% of Viread patients at Week 48.

Changes in renal laboratory tests.

In Study 4018, median change from baseline to Week 48 in eGFR by Cockcroft-Gault method was +0.9 mL per minute in the Vemlidy group and -2.7 mL per minute in those receiving Viread.

Changes in lipid laboratory tests.

In Study 4018, median changes in fasting lipid parameters from baseline to Week 48 were observed in both treatment groups. In the Vemlidy group, increases in median fasting total cholesterol, LDL, HDL, and triglycerides were observed, while the Viread group demonstrated reductions in median fasting total cholesterol, HDL, and triglycerides, and a minimal median increase in LDL (p < 0.001 for the difference between treatment groups in all parameters). Median (Q1, Q3) change from baseline at Week 48 in total cholesterol to HDL ratio was 0.2 (-0.1, 0.5) in the Vemlidy group and 0.0 (-0.3, 0.3) in the Viread group (p < 0.001 for the difference between treatment groups).
Adult patients with renal and/or hepatic impairment.

Patients with renal impairment (study 4035, part A).

In Study 4035, Part A, the efficacy and safety of switching from another antiviral regimen to Vemlidy were evaluated in an open-label clinical study of virologically suppressed chronic hepatitis B-infected adults with moderate to severe renal impairment (eGFR by Cockcroft Gault method between 15 and 59 mL/min) (Cohort 1, N=78) or ESRD (eGFR by Cockcroft Gault method < 15 mL/min) on hemodialysis (Cohort 2, N=15). At baseline, 98% (91/93) of patients in Part A had baseline HBV DNA < 20 IU/mL and 66% (61/93) had an undetectable HBV DNA level. Median age was 65 years, 74% were male, 77% were Asian, 16% were White, and 83% were HBeAg-negative. Previous treatment with oral antivirals included TDF (Cohort 1, N=57; Cohort 2, N=1), lamivudine (N=46), adefovir dipivoxil (N=46), and entecavir (N=43). At baseline, 97% and 95% of patients had ALT ≤ ULN based on central laboratory criteria and 2018 AASLD criteria, respectively; median eGFR by Cockcroft-Gault was 43.2 mL/min (45.1 mL/min in Cohort 1 and 7.2 mL/min in Cohort 2); and 34% of patients had a history of cirrhosis.
Overall, 98% (91/93) of patients achieved HBV DNA < 20 IU/mL at Week 24 (Cohort 1, 97% [76/78]; Cohort 2, 100% [15/15]), and 73% (68/93) of patients had undetectable HBV DNA at Week 24 (Cohort 1, 76% [59/78]; Cohort 2, 60% [9/15]). Two patients in Cohort 1 discontinued treatment early (due to patient decision); last available HBV DNA for both of these patients was < 20 IU/mL. The overall mean (SD) change from baseline in ALT values was + 1 (11.3) U/L (Cohort 1, + 1 [11.9] U/L; Cohort 2, + 3 [7.9] U/L) at Week 24. For patients with ALT > ULN at baseline (all Cohort 1), ALT normalization was achieved for 67% (2/3) (central laboratory criteria) and 40% (2/5) (2018 AASLD criteria) at Week 24.
No patient had HBeAg or HBsAg loss or seroconversion at Week 24. The mean (SD) changes in HBsAg level from baseline were -0.05 (0.122) log10 IU/mL (-0.05 [0.124] log10 IU/mL for Cohort 1 and -0.07 [0.115] log10 IU/mL for Cohort 2) at Week 24.

Patients with hepatic impairment (study 4035, part B).

In Study 4035, Part B, the efficacy and safety of switching from another antiviral regimen to Vemlidy were evaluated in an open-label clinical study of 31 virologically suppressed chronic hepatitis B-infected adults with moderate to severe hepatic impairment (Child-Pugh Turcotte [CPT] B or C at screening or a history of CPT ≥ 7 with any CPT score ≤ 12 at screening). At baseline, 100% (31/31) of patients in Part B had baseline HBV DNA < 20 IU/mL and 65% (20/31) had an undetectable HBV DNA level. Median age was 57 years (19% ≥ 65 years), 68% were male, 81% were Asian, 13% were White, and 90% were HBeAg-negative. Previous treatment with oral antivirals included TDF (N=21), lamivudine (N=14), entecavir (N=14), and adefovir dipivoxil (N=10). At baseline, 87% and 68% of patients had ALT ≤ ULN based on central laboratory criteria and 2018 AASLD criteria, respectively; median eGFR by Cockcroft-Gault was 98.4 mL/min; 97% of patients had a history of cirrhosis, median (range) CPT score was 6 (5-10), and median (range) Model for End Stage Renal Disease (MELD) score was 10 (6-17).
All 31 patients achieved HBV DNA < 20 IU/mL at Week 24, and 77% (24/31) of patients had undetectable HBV DNA at Week 24. The overall mean (SD) change from baseline in ALT values was -1 (15.9) U/L at Week 24. For patients with ALT > ULN at baseline, ALT normalization was achieved for 50% (2/4) (central laboratory criteria) and 60% (6/10) (2018 AASLD criteria) at Week 24. Median change from baseline in CPT score and MELD score was 0 and -0.7, respectively, at Week 24.
No patients had HBeAg or HBsAg loss or seroconversion at Week 24. The mean (SD) change in HBsAg level from baseline was -0.05 (0.134) log10 IU/mL at Week 24. Table 12 summarises shifts from baseline in CPT score class at Week 24.
Patients with renal impairment (study 4035, part A and part B).

Bone mineral density.

In Study 4035, mean percentage change in BMD at the total hip and lumbar spine from baseline to Week 24 as assessed by DXA was +0.14% and +1.27% in patients with moderate to severe renal impairment (Part A, Cohort 1); +0.33% and +0.69% in patients with ESRD on hemodialysis (Part A, Cohort 2); and +0.32% and +1.26% in patients with moderate to severe hepatic impairment (Part B), respectively.

Changes in renal laboratory tests.

In study 4035, median change from baseline to week 24 in eGFR by Cockcroft-Gault method was +0.6 mL per minute in Part A, Cohort 1, and +3.0 mL per minute in Part B. In both treatment groups there were decreases from baseline in proteinuria (UPCR), albuminuria (UACR), tubular proteinuria (urine RBP to creatinine ratio and urine beta-2-microglobulin to creatinine ratio), and other measures of proximal renal tubular dysfunction in patients switching to Vemlidy, collectively indicating the reduced impact of tenofovir alafenamide on proximal renal tubular function. Changes from baseline in renal laboratory tests in Study 4035 are summarized in Table 13.

Changes in lipid laboratory tests.

In Study 4035, median changes in fasting lipid parameters from baseline to Week 24 were observed in both Part A, Cohorts 1 and 2, as well as Part B. Small increases in median fasting total cholesterol, LDL, HDL, and triglycerides were observed in patients with moderate to severe renal impairment (Part A, Cohort 1) and in patients with moderate to severe hepatic impairment (Part B) while small decreases in median fasting total cholesterol, LDL, HDL, and triglycerides were observed in patients with ESRD on hemodialysis (Part A, Cohort 2). Median (Q1, Q3) change from baseline at Week 24 in total cholesterol to HDL ratio was 0.0 (-0.3, 0.3) and 0.0 (-0.6, 0.2) in patients in Part A, Cohorts 1 and 2, respectively, and 0.1 (-0.1, 0.4) in patients in Part B.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration of Vemlidy under fasted conditions in adult patients with chronic hepatitis B, peak plasma concentrations were observed approximately 0.48 hours post-dose. The steady-state mean Cmax and AUClast for tenofovir alafenamide were 0.25 ± 0.11 microgram/mL and 0.15 ± 0.06 microgram.hr/mL, respectively.
Relative to fasting conditions, the administration of a single dose of Vemlidy with a high fat meal resulted in a 65% increase in tenofovir alafenamide exposure. This difference in exposure is not considered clinically relevant and Vemlidy may be administered without regard to food.

Distribution.

The binding of tenofovir to human plasma proteins is less than 0.7% and is independent of concentration over the range of 0.01-25 microgram/mL. The binding of tenofovir alafenamide to human plasma proteins in samples collected during clinical trials was approximately 80%.

Metabolism.

Metabolism is a major elimination pathway for tenofovir alafenamide in humans, accounting for > 80% of an oral dose. In vitro studies have shown that tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase 1 in hepatocytes; and by cathepsin A in PBMCs and macrophages. In vivo, tenofovir alafenamide is hydrolysed within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate. In clinical studies in patients with chronic hepatitis B, a 25 mg oral dose of tenofovir alafenamide in Vemlidy resulted in tenofovir diphosphate concentrations 7.6 fold higher in PBMCs and 89% lower concentrations of tenofovir in plasma as compared to a 300 mg oral dose of tenofovir disoproxil fumarate in Viread.
In vitro, tenofovir alafenamide is not metabolised by CYP1A2, CYP2C8, CYP2C9, CYP2C19, or CYP2D6. Tenofovir alafenamide is minimally metabolised by CYP3A4. Upon coadministration with the strong CYP3A inducer probe carbamazepine, tenofovir alafenamide exposure was not affected to a clinically significant extent. Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or UGT1A1. Tenofovir alafenamide is not an inhibitor or inducer of CYP3A in vivo.

Excretion.

Tenofovir alafenamide is eliminated following metabolism to tenofovir. Tenofovir alafenamide and tenofovir have a median plasma half-life of 0.51 and 32.37 hours, respectively. Tenofovir is renally eliminated by both glomerular filtration and active tubular secretion. Unlike tenofovir, tenofovir alafenamide is not a substrate for the renal transporters OAT1 and OAT3. Renal excretion of intact tenofovir alafenamide is a minor pathway with less than 1% of the dose eliminated in urine. The pharmacologically active metabolite, tenofovir diphosphate, has a half-life of 150-180 hours within PBMCs.

Linearity/non-linearity.

Tenofovir alafenamide exposures are dose proportional over the dose range of 8 to 125 mg.

Special populations.

Age, gender, and ethnicity.

No clinically relevant pharmacokinetic differences due to gender or ethnicity have been identified.
Population pharmacokinetics analysis of patients with chronic hepatitis B in Phase 1 and Phase 3 trials of Vemlidy showed that, within the age range studied (18 to 80 years), age did not have a clinically relevant effect on exposures of tenofovir alafenamide.

Geriatric use.

In clinical trials, Vemlidy has been administered to 89 patients aged 65 and over. No clinically significant differences in safety or efficacy have been observed between elderly patients and patients less than 65 years of age.

Patients with impaired renal function.

No clinically relevant differences in tenofovir alafenamide or tenofovir pharmacokinetics were observed between healthy patients and patients with severe renal impairment (estimated creatinine clearance from 15 to less than 30 mL per minute). Relative to patients with normal renal function (estimated creatinine clearance ≥ 90 mL/min), the tenofovir alafenamide and tenofovir systemic exposures in patients with severe renal impairment were 1.9-fold and 5.7-fold higher, respectively; the tenofovir exposure observed was in or below the range of that following administration of tenofovir disoproxil fumarate in patients with normal renal function. No dose adjustment is required in patients with renal impairment.
The pharmacokinetics of tenofovir alafenamide have not been evaluated in patients with creatinine clearance less than 15 mL per minute not on haemodialysis. Limited data are available in CHB patients with ESRD who are on chronic haemodialysis. Among CHB patients with ESRD on chronic haemodialysis (Study 4035 Part A Cohort 2, N=5) who received tenofovir alafenamide, higher exposures of the active moiety tenofovir were observed compared to another study in HIV patients with ESRD who were on chronic haemodialysis. The clinical significance of these higher exposures is not known.

Patients with hepatic impairment.

Clinically relevant changes in the pharmacokinetics of tenofovir alafenamide or its metabolite tenofovir were not observed in patients with mild, moderate, or severe hepatic impairment; no dosage adjustment is required in patients with hepatic impairment.

HIV and/or hepatitis C virus co-infection.

The pharmacokinetics of tenofovir alafenamide have not been fully evaluated in patients coinfected with HIV and/or hepatitis C virus.

5.3 Preclinical Safety Data

Genotoxicity.

Tenofovir alafenamide was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or rat micronucleus assays.

Carcinogenicity.

Because there is a lower tenofovir exposure in rats and mice after tenofovir alafenamide administration compared to tenofovir disoproxil fumarate, carcinogenicity studies were conducted only with tenofovir disoproxil fumarate. Long-term oral carcinogenicity studies of tenofovir disoproxil fumarate in mice and rats were carried out at exposures up to approximately 10 times (mice) and 4 times (rats) those observed in humans at the 300 mg therapeutic dose of tenofovir disoproxil fumarate for chronic hepatitis B. The tenofovir exposure in these studies was approximately 167 times (mice) and 5 times (rat) those observed in humans after administration of Vemlidy treatment. At the high dose in female mice, liver adenomas were increased at tenofovir exposures of 10 times (300 mg tenofovir disoproxil fumarate) and 167 times (for Vemlidy) greater than the tenofovir exposures in humans. In rats, the study was negative for carcinogenic findings.

6 Pharmaceutical Particulars

6.1 List of Excipients

Vemlidy tablets contain the following ingredients as excipients:

Tablet core.

Croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose.

Film-coating.

Iron oxide yellow, polyethylene glycol, polyvinyl alcohol, purified talc, titanium dioxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Vemlidy should be stored below 30°C.

6.5 Nature and Contents of Container

Vemlidy is supplied in high density polyethylene (HDPE) bottles containing 30 tablets and is closed with a child resistant closure.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Tenofovir alafenamide fumarate is the drug substance. The chemical name of tenofovir alafenamide fumarate is L-alanine, N-[(S)- [[(1R)-2-(6-amino-9H-purin-9-yl)-1- methylethoxy]methyl] phenoxyphosphinyl]-, 1-methylethyl ester, (2E)-2-butenedioate (2:1).
It has a empirical formula of C21H29O5N6P.½(C4H4O4) and a formula weight of 534.50. It has the following structural formula:
Tenofovir alafenamide fumarate is a white to off-white or tan powder with a solubility of 4.7 mg per mL in water at 20°C.

CAS number.

CAS registry number for tenofovir alafenamide: 379270-37-8.
CAS registry number for tenofovir alafenamide fumarate: 1392275-56-7.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes