AccessPak for HIV PEP Basic

Name: AccessPak for HIV PEP Basic

What is AccessPak for HIV PEP Basic (emtricitabine and tenofovir)?

Emtricitabine and tenofovir are antiviral medicines that prevent human immunodeficiency virus (HIV) from multiplying in your body.

Emtricitabine and tenofovir is a combination medicine used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). This medicine is not a cure for HIV or AIDS, but it can be used to treat HIV in adults and children who are at least 12 years old and weigh at least 17 kilograms (37 pounds).

The Truvada brand of this medicine may be used together with safer-sex practices to reduce the risk of becoming infected with HIV. You must be HIV-negative and an adult to use Truvada for this purpose. Truvada may not provide protection from disease in every person.

Emtricitabine and tenofovir may also be used for purposes not listed in this medication guide.

How should I take AccessPak for HIV PEP Basic (emtricitabine and tenofovir)?

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

You may take this medicine with or without food.

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

While using this medicine, you may need frequent blood tests. Your kidney and liver function, or bone mineral density may also need to be checked.

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 emtricitabine and tenofovir.

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

AccessPak for HIV PEP Basic (emtricitabine and tenofovir) side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Early symptoms of lactic acidosis may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Call your doctor at once if you have:

  • sudden or unusual bone pain;

  • kidney problems--little or no urination, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath; or

  • liver problems--nausea, swelling around your midsection, upper stomach pain, unusual tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Emtricitabine and tenofovir may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with emtricitabine and tenofovir. Tell your doctor if you have:

  • signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

  • chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

  • cold sores, sores on your genital or anal area;

  • rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

  • trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common side effects may include:

  • headache, dizziness, feeling depressed or tired;

  • sleep problems (insomnia), strange dreams;

  • stomach pain;

  • weight loss; or

  • rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For Healthcare Professionals

Applies to emtricitabine / tenofovir: oral kit, oral tablet

General

Side effects have been reported for emtricitabine and/or tenofovir disoproxil fumarate (DF) when taken in combination with other antiretroviral agents. The most common side effects reported in HIV-1-infected patients during a clinical study of efavirenz, emtricitabine, and tenofovir DF included diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. In this trial, emtricitabine-tenofovir DF (with efavirenz) was used from weeks 96 to 144, replacing emtricitabine plus tenofovir DF (with efavirenz).

In HIV-1-uninfected individuals in preexposure prophylaxis trials, the most common side effects reported with emtricitabine-tenofovir DF were headache, abdominal pain, and decreased weight.[Ref]

Metabolic

Emtricitabine-tenofovir DF:
-Very common (10% or more): Increased fasting cholesterol (up to 22%)
-Common (1% to 10%): Decreased phosphorus, increased fasting triglycerides, altered serum glucose, weight loss, hyperglycemia, increased alkaline phosphatase

Emtricitabine and tenofovir alafenamide:
-Frequency not reported: Increased total cholesterol, increased low-density lipoprotein (LDL) cholesterol, increased high-density lipoprotein (HDL) cholesterol, increased triglycerides

Emtricitabine:
-Common (1% to 10%): Hyperglycemia, hypertriglyceridemia, increased or decreased serum glucose
-Frequency not reported: Lactic acidosis

Tenofovir DF:
-Very common (10% or more): Hypophosphatemia, increased triglycerides
-Common (1% to 10%): Anorexia, weight loss, increased serum glucose
-Uncommon (0.1% to 1%): Hypokalemia
-Rare (less than 0.1%): Lactic acidosis

Antiretroviral therapy:
-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased blood lipid levels, increased glucose levels[Ref]

Increased fasting cholesterol (greater than 240 mg/dL: up to 22%), decreased phosphorus (2.5 to less than the lower limit of normal: up to 7%; less than 2 mg/dL: up to 10%), increased fasting triglycerides (greater than 750 mg/dL: up to 5%), altered serum glucose (less than 40 mg/dL or greater than 250 mg/dL: up to 3%), hyperglycemia (greater than 250 mg/dL: up to 2%), and increased alkaline phosphatase (greater than 550 units/L: 1%) have been reported with emtricitabine-tenofovir DF.

In clinical trials, the following mean increases were reported in antiretroviral therapy-naive patients after using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat for 48 weeks: total cholesterol increased by 30 mg/dL, LDL cholesterol by 15 mg/dL, HDL cholesterol by 7 mg/dL, and triglycerides by 29 mg/dL.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Hypokalemia and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Hypokalemia, lactic acidosis, and hypophosphatemia have also been reported during postmarketing experience with tenofovir DF.[Ref]

Hepatic

Increased AST (1.25 to less than 2.5 times the upper limit of normal [1.25 to less than 2.5 x ULN]: up to 14%; greater than 2.6 x ULN: up to 5%), ALT (1.25 to less than 2.5 x ULN: up to 14%; greater than 2.6 x ULN: up to 7%), and bilirubin (greater than 2.5 x ULN: up to 3%) have been reported with emtricitabine-tenofovir DF.

Increased AST (greater than 180 units/L) and ALT (greater than 215 units/L) have been reported in 3% and 2% of males using emtricitabine-tenofovir DF, respectively. Increased AST (greater than 170 units/L) and ALT (greater than 170 units/L) have been reported in 3% and 2% of females using emtricitabine-tenofovir DF, respectively.

Severe acute exacerbations of hepatitis have been reported in patients with hepatitis B after discontinuation of this drug and were associated with liver failure and liver decompensation in some emtricitabine-treated patients.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Hepatic steatosis and hepatitis have also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine-tenofovir DF:
-Very common (10% or more): Increased AST (up to 14%), increased ALT (up to 14%)
-Common (1% to 10%): Increased bilirubin
-Frequency not reported: Severe acute exacerbations of hepatitis B

Emtricitabine:
-Common (1% to 10%): Increased serum AST and/or increased serum ALT, hyperbilirubinemia
-Frequency not reported: Liver failure, liver decompensation

Tenofovir DF:
-Common (1% to 10%): Increased transaminases (AST and/or ALT)
-Rare (less than 0.1%): Hepatic steatosis, hepatitis
-Frequency not reported: Lactic acidosis/severe hepatomegaly with steatosis
-Postmarketing reports: Increased liver enzymes (primarily AST, ALT, GGT)[Ref]

Hematologic

Decreased neutrophils (1000 to 1300/mm3: up to 13%; less than 750/mm3: up to 5%) and hemoglobin (8.5 to 10 mg/dL: 4%; less than 9.4 mg/dL: up to 2%) have been reported with emtricitabine-tenofovir DF.[Ref]

Emtricitabine-tenofovir DF:
-Very common (10% or more): Decreased neutrophils (up to 13%)
-Common (1% to 10%): Decreased hemoglobin

Emtricitabine:
-Common (1% to 10%): Neutropenia
-Uncommon (0.1% to 1%): Anemia

Tenofovir DF:
-Common (1% to 10%): Decreased neutrophils[Ref]

Respiratory

Emtricitabine-tenofovir DF:
-Very common (10% or more): Pharyngitis (up to 13%)
-Common (1% to 10%): Sinusitis, upper respiratory tract infections, nasopharyngitis

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Increased cough, pneumonia, rhinitis

Emtricitabine:
-Very common (10% or more): Rhinitis, increased cough

Tenofovir DF:
-Common (1% to 10%): Pneumonia
-Postmarketing reports: Dyspnea[Ref]

Gastrointestinal

Increased serum amylase (greater than 175 units/L: up to 8%), pancreatic amylase (greater than 2 x ULN: up to 3%), and serum lipase (greater than 2 x ULN: up to 3%) have been reported with emtricitabine-tenofovir DF.

In clinical trials, nausea was the most common side effect reported in antiretroviral therapy-naive HIV-1-infected patients using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat.

Pancreatitis, abdominal pain, and increased amylase have also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Diarrhea, nausea, increased serum amylase, abdominal pain, increased pancreatic amylase, increased serum lipase, vomiting
-Frequency not reported: Flatulence

Emtricitabine and tenofovir alafenamide:
-Common (1% to 10%): Nausea

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Dyspepsia, abdominal pain

Emtricitabine:
-Very common (10% or more): Diarrhea, nausea, abdominal pain
-Common (1% to 10%): Increased amylase (including increased pancreatic amylase), increased serum lipase, vomiting, dyspepsia

Tenofovir DF:
-Very common (10% or more): Diarrhea, vomiting, nausea
-Common (1% to 10%): Abdominal pain, abdominal distension, flatulence, dyspepsia, increased serum amylase
-Uncommon (0.1% to 1%): Pancreatitis[Ref]

Psychiatric

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Depression, insomnia, abnormal dreams, anxiety

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Anxiety

Emtricitabine:
-Very common (10% or more): Insomnia, abnormal dreams
-Common (1% to 10%): Depressive disorders

Tenofovir DF:
-Very common (10% or more): Depression
-Common (1% to 10%): Insomnia, anxiety[Ref]

Nervous system

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Dizziness, headache
-Frequency not reported: Somnolence

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Peripheral neuropathy (including neuropathy, peripheral neuritis), paresthesia

Emtricitabine:
-Very common (10% or more): Dizziness, headache
-Common (1% to 10%): Neuropathy/peripheral neuritis, paresthesia

Tenofovir DF:
-Very common (10% or more): Dizziness, headache
-Common (1% to 10%): Peripheral neuropathy (including neuropathy, peripheral neuritis)[Ref]

Other

Asthenia has also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Fatigue, syphilis, secondary syphilis

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Pain, fever

Emtricitabine:
-Very common (10% or more): Asthenia
-Common (1% to 10%): Pain

Tenofovir DF:
-Very common (10% or more): Pain, asthenia
-Common (1% to 10%): Chest pain, fever
-Frequency not reported: Higher 1,25 vitamin D levels

Antiretroviral therapy:
-Frequency not reported: Increased weight[Ref]

Dermatologic

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Rash event (including rash, maculopapular rash, exfoliative rash, generalized rash, macular rash, pruritic rash, vesicular rash)

Emtricitabine:
-Very common (10% or more): Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, allergic reaction)
-Common (1% to 10%): Skin discoloration (palmar-plantar hyperpigmentation)
-Frequency not reported: Lipodystrophy
-Postmarketing reports: Angioedema

Tenofovir DF:
-Very common (10% or more): Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash)
-Common (1% to 10%): Sweating
-Uncommon (0.1% to 1%): Lipodystrophy
-Rare (less than 0.1%): Angioedema[Ref]

Rash has also been reported during postmarketing experience with tenofovir DF.[Ref]

Musculoskeletal

Increased creatine kinase (males: greater than 990 units/L; females: greater than 845 units/L) has been reported in up to 9% of patients using emtricitabine-tenofovir DF.

In clinical trials, a significant decline in BMD was seen in 15% of therapy-naive HIV-1-infected patients using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat. In virologically-suppressed tenofovir DF-treated patients who switched to emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean BMD increased between baseline and week 48; decreased BMD was also reported.

Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy may occur as a result of proximal renal tubulopathy.

Rhabdomyolysis, muscular weakness, and myopathy have also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Increased creatine kinase, bone fractures
-Frequency not reported: Decreased bone mineral density (BMD)

Emtricitabine and tenofovir alafenamide:
-Very common (10% or more): Decreased BMD
-Uncommon (0.1% to 1%): Fractures (excluding fingers and toes)
-Frequency not reported: Increased biochemical markers of bone metabolism, increased BMD

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Myalgia, arthralgia, back pain

Emtricitabine:
-Very common (10% or more): Increased creatine kinase
-Common (1% to 10%): Myalgia, arthralgia

Tenofovir DF:
-Very common (10% or more): Increased creatine kinase
-Common (1% to 10%): Myalgia, arthralgia, back pain
-Uncommon (0.1% to 1%): Rhabdomyolysis, muscular weakness
-Rare (less than 0.1%): Myopathy
-Frequency not reported: Decreased BMD, increased biochemical markers of bone metabolism
-Postmarketing reports: Osteomalacia (manifested as bone pain and which may contribute to fractures)

Combination antiretroviral therapy:
-Frequency not reported: Osteonecrosis[Ref]

Renal

Increased creatinine (1.1 to 1.3 x ULN: up to 2%; greater than 1.4 x ULN: less than 1%) has been reported with emtricitabine-tenofovir DF.

In 2 trials in antiretroviral therapy-naive HIV-1-infected patients (median estimated glomerular filtration rate [eGFR] 115 mL/min at baseline) using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine increased by 0.1 mg/dL from baseline to week 48; median UPCR was 44 mg/g at baseline and at week 48. In a trial in virologically-suppressed tenofovir DF-treated patients (mean eGFR 112 mL/min at baseline) who switched to emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine was similar to baseline; median UPCR was 61 mg/g at baseline and 46 mg/g at week 48. In a trial in renal dysfunction patients (baseline eGFR 30 to 69 mL/min) using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine was 1.5 mg/dL at baseline and week 24; median UPCR was 161 mg/g at baseline and 93 mg/g at week 24.

Proximal renal tubulopathy generally resolved or improved after tenofovir DF was stopped; however, decreased CrCl did not completely resolve in some patients after stopping the drug. Rhabdomyolysis, osteomalacia, bone abnormalities (infrequently contributing to fractures), hypokalemia, muscular weakness, myopathy, and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, nephrogenic diabetes insipidus, and acute tubular necrosis have also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Increased creatinine

Emtricitabine and tenofovir alafenamide:
-Frequency not reported: Increased serum creatinine, decreased urine protein-to-creatinine ratio (UPCR), worsening renal function

Tenofovir DF:
-Uncommon (0.1% to 1%): Increased creatinine
-Rare (less than 0.1%): Renal failure (acute and chronic), acute tubular necrosis, proximal renal tubulopathy (including Fanconi syndrome), nephrogenic diabetes insipidus
-Frequency not reported: New onset or worsening renal impairment
-Postmarketing reports: Renal insufficiency, interstitial nephritis (including acute cases)

Tenofovir prodrugs:
-Frequency not reported: Renal impairment (including renal failure, Fanconi syndrome)[Ref]

Genitourinary

Emtricitabine-tenofovir DF:
-Common (1% to 10%): Proteinuria, urethritis, urinary tract infection, hematuria, genital ulceration, anogenital warts
-Uncommon (0.1% to 1%): Proteinuria, glycosuria

Tenofovir DF:
-Common (1% to 10%): Glycosuria, hematuria
-Uncommon (0.1% to 1%): Proteinuria
-Postmarketing reports: Polyuria[Ref]

Increased glycosuria (3+ or greater: less than 1%) and hematuria (greater than 75 red blood cells/high power field: up to 3%) have been reported with emtricitabine-tenofovir DF.

Proteinuria has also been reported during postmarketing experience with tenofovir DF.[Ref]

Immunologic

Emtricitabine-tenofovir DF:
-Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Hypersensitivity

Emtricitabine:
-Common (1% to 10%): Allergic reaction

Tenofovir DF:
-Postmarketing reports: Allergic reaction (including angioedema)[Ref]

Endocrine

Tenofovir DF:
-Frequency not reported: Higher serum parathyroid hormone levels[Ref]

Some side effects of AccessPak for HIV PEP Basic may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Adult Dose for HIV Infection

Emtricitabine 200 mg-tenofovir alafenamide 25 mg (1 tablet) orally once a day
Emtricitabine 200 mg-tenofovir DF 300 mg (1 tablet) orally once a day

Comments:
-Patients should be tested for HBV infection before starting this drug.
-In all patients, estimated CrCl, urine glucose, and urine protein should be assessed before starting emtricitabine-tenofovir alafenamide and should be monitored during therapy.
-Emtricitabine-tenofovir alafenamide is recommended for patients at least 35 kg.
-Emtricitabine-tenofovir DF is not recommended as a component of a triple nucleoside regimen; it should not be used with other emtricitabine-containing, tenofovir-containing, or lamivudine-containing products.
-Use of emtricitabine-tenofovir DF in therapy-experienced patients should be guided by laboratory testing and treatment history.

Use: In combination with other antiretroviral agents, for treatment of HIV-1 infection

Usual Adult Dose for Pre-Exposure Prophylaxis

Emtricitabine 200 mg-tenofovir DF 300 mg (1 tablet) orally once a day

Comments:
-This drug should be used only as part of a comprehensive prevention plan that includes other prevention measures (e.g., safer sex practices); this drug is not always effective in preventing acquisition of HIV-1.
-Uninfected individuals should be advised to strictly adhere to the dosing regimen; efficacy of this drug in reducing risk of acquiring HIV-1 strongly correlated with adherence.
-The manufacturer product information (and current guidelines) should be consulted for further guidance.

Use: In combination with safer sex practices, for preexposure prophylaxis to reduce the risk of sexually acquired HIV-1 in uninfected individuals at high risk

Usual Adult Dose for Nonoccupational Exposure

US CDC recommendations: Emtricitabine 200 mg-tenofovir DF 300 mg (1 tablet) orally once a day
Duration of therapy: 28 days

Comments:
-This drug plus (raltegravir or dolutegravir) is recommended as the preferred regimen for nonoccupational postexposure prophylaxis of HIV infection in adults (including pregnant women) with CrCl at least 60 mL/min; this drug plus darunavir/ritonavir is recommended as an alternative regimen for such patients. If other alternatives are considered, this drug is recommended as a component in various regimens.
-Prophylaxis should be started as soon as possible, within 72 hours of exposure.
-Current guidelines should be consulted for additional information.

Other Comments

Administration advice:
-May take with or without food
-Ensure children are able to swallow the tablet whole.
-Do not use emtricitabine-tenofovir alafenamide as PrEP to reduce risk of sexually-acquired HIV-1 in high-risk adults.
-Consult the manufacturer product information regarding missed doses.

Storage requirements:
-Store in original bottle; keep bottle tightly closed.

General:
-As part of patient counseling, healthcare providers must review the emtricitabine-tenofovir DF Medication Guide with each uninfected individual using this drug for PrEP.

Monitoring:
-Hepatic: Hepatic function of HBV-infected patients with clinical and laboratory follow-up (for at least several months after stopping this drug)
-Infections/Infestations: For chronic HBV in all individuals (before therapy); for HIV-1 (before starting and at least every 3 months during PrEP)
-Metabolic: Serum phosphorus in all individuals at risk of renal dysfunction (before starting and periodically during therapy) or with mild renal dysfunction (routinely)
-Musculoskeletal: Bone mineral density in patients with history of pathologic bone fracture or other risk factors for osteoporosis or bone loss
-Renal: Estimated CrCl in all individuals using emtricitabine-tenofovir DF (before starting and as clinically appropriate during therapy); estimated CrCl, urine glucose, and urine protein in all patients using emtricitabine-tenofovir alafenamide or in all individuals using emtricitabine-tenofovir DF who are at risk of renal dysfunction (before starting and periodically during therapy) or who have mild renal dysfunction (routinely)

Patient advice:
-Read the US FDA-approved patient labeling (Patient Information [emtricitabine-tenofovir alafenamide] or Medication Guide [emtricitabine-tenofovir DF]).
-Stop this drug if symptoms suggesting lactic acidosis or pronounced hepatotoxicity develop.
-If you also have HBV, do not stop emtricitabine-tenofovir alafenamide without consulting healthcare provider.
-Do not stop emtricitabine-tenofovir DF without consulting healthcare provider.

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