Vemlidy

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Vemlidy may affect the way other medicines work, and other medicines may affect how Vemlidy works. 

Especially tell your healthcare provider if you take: 

• Any of the following anticonvulsant medications
  • carbamazepine (Tegretol, Equetro, Carbatrol)
  • phenytoin (Dilantin, Phenytek)
  • phenobarbital
  • oxcarbazepine (Trileptal)
  • primidone (Mysoline)
• Medications used to treat tuburculosis like rifampin (Rifadin) and rifapentine (Priftin)
• Rifabutin (Mycobutin)
• Tipranavir (Aptivus)
• Adefovir (Hepsera)
• St. John's Wort

This is not a complete list of Vemlidy drug interactions. Ask your doctor or pharmacist for more information. 

Vemlidy can cause serious side effects, including:

• feeling very weak or tired
• have unusual (not normal) muscle pain
• have trouble breathing
• have stomach pain with
  • nausea (feel sick to your stomach)
  • vomiting
• feel cold, especially in your arms and legs
• feel dizzy or lightheaded
• have a fast or irregular heartbeat

• Your skin or the white part of your eyes turns yellow (jaundice).
• dark "tea-colored" urine
• light-colored bowel movements (stools)
• loss of appetite for several days or longer
• nausea
• stomach pain

You may be more likely to get lactic acidosis or severe liver problems if you are female, very overweight (obese), or have been taking Vemlidy for a long time.
 

• Do not let your Vemlidy run out. Refill your prescription or talk to your healthcare provider before your tenofovir is all gone.
• Do not stop taking Vemlidy without first talking to your healthcare provider.
• If you stop taking Vemlidy, your healthcare provider will need to check your health often and do blood tests regularly to check your HBV infection. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking Vemlidy. 
• Talk to your doctor about taking an HIV test before starting treatment with Vemlidy for chronic hepatitis B. You should also get a test for HBV if you are taking tenofovir for treatment of HIV.

Other serious side effects of Vemlidy that can occur include:

• New or worse kidney problems can happen in some people who take Vemlidy. If you have had kidney problems in the past or need to take another medicine that can cause kidney problems, your healthcare provider may need to do blood tests to check your kidneys during your treatment with Vemlidy.
• Bone problems can happen in some people who take Vemlidy. Bone problems include bone pain, softening or thinning (which may lead to fractures). Your healthcare provider may need to do additional tests to check your bones.
• Changes in body fat can happen in some people who take antiviral medicines. These changes may include increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the main part of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known.
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider if you start having new symptoms after starting your HIV medicine. 

Before you start treatment with tenofovir, your doctor may perform tests to make sure you do not have HIV (if you are being treated for hepatitis B) or hepatitis B (if you are being treated for HIV).

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Take this medicine at the same time each day.

Some forms of tenofovir should be taken with food. Carefully follow all instructions on your medicine label.

Tenofovir oral powder should be mixed with soft food such as applesauce, yogurt, or baby food. Do not mix the oral powder with liquid.

If a child is taking this medication, tell your doctor if the child has any changes in weight. Tenofovir doses are based on weight in children.

While using tenofovir, you may need frequent blood tests. Your liver and kidney function may also need to be checked.

Use tenofovir regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Do not stop using tenofovir without first talking to your doctor.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

If you have hepatitis B you may develop liver symptoms after you stop taking this medication, even months after stopping. Your doctor may want to check your liver function for several months after you stop using tenofovir. Visit your doctor regularly.

Avoid drinking alcohol. It may increase your risk of liver damage.

Taking this medicine will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Weak inhibitor of CYP3A in vitro;25 243 244 245 does not induce or inhibit other CYP isoenzymes, including CYP1A2, 2B6, 2C8, 2C9, 2C19, or 2D6.25 243 244 245

Substrate of P-glycoprotein (P-gp) transport system.1 3

Substrate of breast cancer resistance protein (BCRP).1 3

The following drug interactions are based on studies using tenofovir alafenamide fumarate or are predicted to occur.1

Drugs Affecting P-glycoprotein Transport System

P-gp inducers: Decreased absorption of tenofovir alafenamide expected;1 may result in decreased tenofovir alafenamide concentrations and loss of therapeutic effect.1

P-gp inhibitors: Possible increased absorption of tenofovir alafenamide resulting in increased plasma concentrations of the drug.1

Drugs Affecting Breast Cancer Resistance Protein

BCRP inhibitors: Possible increased absorption of tenofovir alafenamide resulting in increased plasma concentrations of the drug.1

Nephrotoxic Drugs or Drugs Eliminated by Renal Excretion

Drugs that reduce renal function or compete for active tubular secretion: Possible increased concentrations of tenofovir and/or concomitant drug;1 possible increased risk of adverse effects.1

Specific Drugs

• Importance of reading patient information provided by the manufacturer.1

• Importance of taking tenofovir alafenamide with food and on a regular dosing schedule and avoiding missed doses since this may result in development of resistance.1

• Importance of informing patients that severe acute exacerbations of HBV infection have been reported following discontinuance of HBV treatment, including tenofovir alafenamide.1 Advise patients not to discontinue tenofovir alafenamide without first informing a clinician.1

• Importance of informing patients that if they have or develop HIV infection and are not receiving effective HIV treatment, use of tenofovir alafenamide alone may increase the risk of development of resistance to HIV treatment.1

• Advise patients that renal impairment, including cases of acute renal failure or Fanconi syndrome, has been reported in patients receiving tenofovir prodrugs.1

• Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have occurred in patients receiving drugs similar to tenofovir alafenamide.1 Importance of immediately contacting a clinician and discontinuing tenofovir alafenamide if clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity occur.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, as well as any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Inform patients about the pregnancy registry to monitor fetal outcomes of pregnant women exposed to tenofovir alafenamide.1 (See Pregnancy under Cautions.)

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Take this medicine exactly as directed by your doctor. Do not take it more often, and do not take it for a longer time than your doctor ordered. Certain tests may be needed before you start this medicine. Talk to your doctor if you have questions.

This medicine comes with a patient information leaflet. Read and follow the information carefully. Read it again each time you refill your prescription in case there is new information. Ask your doctor if you have any questions.

Keep taking tenofovir for the full time of treatment, even if you begin to feel better. Do not stop taking it without checking first with your doctor. When your supply of the medicine is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of the medicine.

Swallow the tablet whole. Do not crush, break, or chew it. Take this medicine with food.

Do not change or stop using this medicine without checking first with your doctor.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For treatment of chronic hepatitis B infection:
    • Adults—25 milligrams (mg) once a day with food.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep the bottle tightly closed. Use the medicine dispensed only in its original container.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Vemlidy, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Vemlidy (tenofovir alafenamide). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Vemlidy.

Review Date: October 4, 2017

Tablets: 25 mg of tenofovir alafenamide (equivalent to 28 mg of tenofovir alafenamide fumarate) yellow, round, film-coated tablets, debossed with "GSI" on one side of the tablet and "25" on the other side.

Clinical Trials in Adults with Chronic Hepatitis B Virus Infection and Compensated Liver Disease

The efficacy and safety of Vemlidy in the treatment of adults with chronic hepatitis B virus infection with compensated liver disease are based on 48-week data from two randomized, double-blind, active-controlled studies, Study 108 (N=425) and Study 110 (N=873). In both studies, besides study treatment, patients were not allowed to receive other nucleosides, nucleotides, or interferon.

In Study 108, HBeAg-negative treatment-naïve and treatment-experienced subjects with compensated liver disease (no evidence of ascites, hepatic encephalopathy, variceal bleeding, INR <1.5× ULN, total bilirubin <2.5× ULN, and albumin >3.0 mg/dL) were randomized in a 2:1 ratio to receive Vemlidy 25 mg (N=285) once daily or tenofovir disoproxil fumarate 300 mg (N=140) once daily for 48 weeks. The mean age was 46 years, 61% were male, 72% were Asian, 25% were White, 2% were Black, and 1% were other races. 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 subjects had a history of cirrhosis.

In Study 110, HBeAg-positive treatment-naïve and treatment-experienced subjects with compensated liver disease were randomized in a 2:1 ratio to receive Vemlidy 25 mg (N=581) once daily or tenofovir disoproxil fumarate 300 mg (N=292) once daily for 48 weeks. The mean age was 38 years, 64% were male, 82% were Asian, 17% were White, and 1% were Black or other races. 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 subjects had a history of cirrhosis.

In both studies, randomization was stratified on prior treatment history (nucleoside naïve or experienced) and baseline HBV DNA (<7, ≥7 to <8, and ≥8 log10 IU/mL in Study 108; and <8 and ≥8 log10 IU/mL in Study 110). The efficacy endpoint in both trials was the proportion of subjects with plasma HBV DNA levels below 29 IU/mL at Week 48. Additional efficacy endpoints include the proportion of subjects with ALT normalization, HBsAg loss and seroconversion, and HBeAg loss and seroconversion in Study 110.

Treatment outcomes of Studies 108 and 110 at Week 48 are presented in Table 9 and Table 10.

In Study 108, the proportion of subjects with cirrhosis who achieved HBV DNA <29 IU/mL at Week 48 was 92% (22/24) in the Vemlidy group and 93% (13/14) in the TDF group. The corresponding proportions in Study 110 were 63% (26/41) and 67% (16/24) in the Vemlidy and TDF groups, respectively.

You should not take Vemlidy if you are allergic to tenofovir.

Do not take Vemlidy together with adefovir (Hepsera), or with combination medicines that contain tenofovir (Atripla, Complera, Genvoya, Odefsey, Stribild, or Truvada).

Vemlidy should not be used to treat patients with chronic hepatitis B in a child younger than 18 years old.

To make sure this medicine is safe for you, tell your doctor if you have:

• liver disease (especially if you also have HIV);

• kidney disease (renal impairment); or

• low bone mineral density.

Some people taking Vemlidy develop a serious condition called lactic acidosis. This may be more likely in women, in people who are overweight or have liver disease, and in people who have taken medication similar to tenofovir for a long time. Talk with your doctor about your risk.

This medication is not expected to be harmful to an unborn baby.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of tenofovir on the baby.

Tenofovir can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using Vemlidy to treat hepatitis B.

Vemlidy can harm your kidneys. This effect is increased when you also use certain other medicines, including: antivirals, chemotherapy, injected antibiotics, medicine for bowel disorders, medicine to prevent organ transplant rejection, and some pain or arthritis medicines (including aspirin, Tylenol, Advil, and Aleve). In clinical trials there have been no cases of Fanconi syndrome or Proximal Renal Tubulopathy.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• atazanavir (Reyataz);

• darunavir (Prezista);

• didanosine (Videx);

• ledipasvir and sofosbuvir (Harvoni); or

• lopinavir and ritonavir (Kaletra).

This list is not complete. Other drugs may interact with tenofovir, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed in this medication guide.