Tenofovir Side Effects

It is possible that some side effects of tenofovir may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to tenofovir: oral powder, oral tablet

As well as its needed effects, tenofovir may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking tenofovir, check with your doctor immediately:

Less common
  • Chest pain
  • cough
  • fever or chills
  • tightness in the chest
  • troubled breathing
Rare
  • Abdominal or stomach discomfort
  • decreased appetite
  • diarrhea
  • fast, shallow breathing
  • general feeling of discomfort
  • muscle pain or cramping
  • unusual tiredness or weakness
Incidence not known
  • Agitation
  • bone pain
  • changes in urination
  • confusion
  • convulsions or seizures
  • depression
  • fast heartbeat
  • increased blood pressure
  • increased thirst
  • muscle twitching
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • stupor
  • swelling of the face, fingers, or lower legs
  • vomiting
  • weight gain
  • yellow eyes or skin

Some tenofovir side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Back pain
  • lack or loss of strength
  • pain
  • redness of the skin
  • skin rash, itching skin, hives or welts
Less common
  • Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • heartburn or indigestion
  • joint pain or swelling
  • muscle pains or stiffness
  • passing of gas
  • redistribution or accumulation of body fat
  • weight loss

For Healthcare Professionals

Applies to tenofovir: oral powder, oral tablet

General

The most common side effects (10% or more; Grades 2 to 4) reported during controlled clinical trials in patients with HIV-1 infection included rash, diarrhea, headache, pain, depression, asthenia, and nausea. The most common side effects associated with tenofovir in combination with other antiretrovirals have included mild to moderate gastrointestinal events (such as nausea, diarrhea, vomiting, and flatulence) in therapy-experienced patients and mild to moderate gastrointestinal events and dizziness in therapy-naive patients. Less than 1% of patients in clinical trials discontinued therapy due to gastrointestinal side effects.

The most common side effects (greater than 5%) reported during controlled clinical trials in patients with chronic hepatitis B and compensated liver disease included nausea, abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain, and skin rash. In patients with chronic hepatitis B and decompensated liver disease, the most common side effects reported during a controlled trial included abdominal pain, nausea, insomnia, pruritus, vomiting, dizziness, and pyrexia.[Ref]

Gastrointestinal

Abdominal pain (any severity: 22%), nausea (any severity: 20%), and vomiting (any severity: 13%) have been in patients with chronic hepatitis B and decompensated liver disease (n=45).[Ref]

Very common (10% or more): Abdominal pain (any severity: 22%), nausea (any severity: 20%), diarrhea (Grades 2 to 4: up to 16%), vomiting (any severity: 13%), nausea (Grades 2 to 4: up to 11%)
Common (1% to 10%): Vomiting (Grades 2 to 4: up to 7%), flatulence (Grades 2 to 4: up to 4%), dyspepsia (Grades 2 to 4: up to 4%), anorexia (Grades 2 to 4: up to 4%)
Postmarketing reports: Pancreatitis, abdominal pain, elevated amylase[Ref]

Metabolic

Very common (10% or more): Elevated fasting cholesterol (Grade 3/4: up to 22%), elevated creatine kinase (Grade 3/4: up to 12%), elevated triglycerides (Grade 3/4: up to 11%)
Common (1% to 10%): Elevated serum amylase (Grade 3/4: up to 9%), elevated fasting triglycerides (Grade 3/4: up to 4%), weight loss (Grades 2 to 4: up to 4%), elevated serum glucose (Grade 3/4: up to 3%), elevated alkaline phosphatase (Grade 3/4: 1%), elevated serum lipase (Grade 3/4: 1%), lipodystrophy (Grades 2 to 4: 1%)
Frequency not reported: Significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C telopeptide, urinary N telopeptide), serum phosphorus less than 2 mg/dL, redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")
Postmarketing reports: Lactic acidosis, hypokalemia, hypophosphatemia[Ref]

Serum phosphorus less than 2 mg/dL was reported in a patient with chronic hepatitis B and decompensated liver disease.

Hypokalemia and hypophosphatemia may occur due to proximal renal tubulopathy.[Ref]

Dermatologic

Very common (10% or more): Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, exfoliative rash, generalized rash, macular rash, pruritic rash, vesicular rash; Grades 2 to 4: up to 18%), pruritus (any severity: 16%)
Common (1% to 10%): Sweating (Grades 2 to 4: up to 3%)
Rare (less than 0.1%): Lichenoid drug eruption with eosinophilia (at least 1 case)
Postmarketing reports: Rash[Ref]

Pruritus (any severity: 16%) has been reported in patients with chronic hepatitis B and decompensated liver disease (n=45).[Ref]

Nervous system

Insomnia (any severity: 18%) and dizziness (any severity: 13%) were reported in patients with chronic hepatitis B and decompensated liver disease (n=45).[Ref]

Very common (10% or more): Insomnia (any severity: 18%), headache (Grades 2 to 4: up to 14%), dizziness (any severity: 13%)
Common (1% to 10%): Dizziness (Grades 2 to 4: up to 8%), insomnia (Grades 2 to 4: up to 5%), peripheral neuropathy (including peripheral neuritis and neuropathy; Grades 2 to 4: up to 5%)
Frequency not reported: Somnolence, paresthesia[Ref]

Other

Pyrexia (any severity: 11%) was reported in patients with chronic hepatitis B and decompensated liver disease (n=45).[Ref]

Very common (10% or more): Pain (Grades 2 to 4: up to 13%), pyrexia (any severity: 11%), asthenia (Grades 2 to 4: up to 11%)
Common (1% to 10%): Fatigue (Grades 2 to 4: 9%), back pain (Grades 2 to 4: up to 9%), fever (Grades 2 to 4: up to 8%), abdominal pain (Grades 2 to 4: up to 7%), chest pain (Grades 2 to 4: up to 3%)
Frequency not reported: Higher 1,25 vitamin D levels
Postmarketing reports: Asthenia[Ref]

Psychiatric

Very common (10% or more): Depression (Grades 2 to 4: up to 11%)
Common (1% to 10%): Anxiety (Grades 2 to 4: 6%)
Frequency not reported: Abnormal dreams

Hepatic

Death due to progression of liver disease has been reported in 4% of patients with chronic hepatitis B and decompensated liver disease (n=45).

On-treatment ALT or hepatic flares have been reported in patients with chronic hepatitis B.

Severe acute exacerbations of hepatitis have been reported in patients with hepatitis B after discontinuation of tenofovir.[Ref]

Common (1% to 10%): Elevated alanine transaminase (ALT; Grade 3/4: up to 10%), elevated aspartate transaminase (AST; Grade 3/4: up to 5%), death due to progression of liver disease (4%)
Frequency not reported: On-treatment ALT or hepatic flares, lactic acidosis/severe hepatomegaly with steatosis (including fatal cases), severe acute exacerbations of hepatitis
Postmarketing reports: Hepatic steatosis, hepatitis, elevated liver enzymes (primarily AST, ALT, gamma glutamyltransferase)[Ref]

Renal

Common (1% to 10%): Confirmed increase in serum creatinine of 0.5 mg/dL (9%)
Frequency not reported: New onset or worsening renal impairment, nephritis, decreased urine volume
Postmarketing reports: Renal insufficiency, renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, acute tubular necrosis, nephrogenic diabetes insipidus, interstitial nephritis (including acute cases)[Ref]

A confirmed increase in serum creatinine of 0.5 mg/dL was reported in 9% of patients with chronic hepatitis B and decompensated liver disease (n=45); however, since tenofovir and decompensated liver disease may have an impact on renal function, the contribution of tenofovir to renal impairment in these patients is difficult to ascertain.

Rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, and hypophosphatemia may occur as a result of proximal renal tubulopathy.[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia (Grades 2 to 4: 5%), myalgia (Grades 2 to 4: up to 4%)
Rare (less than 0.1%): Clinically relevant fractures (excluding fingers and toes; at least 4 cases)
Frequency not reported: Decreased bone mineral density, increased biochemical markers of bone metabolism
Postmarketing reports: Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy[Ref]

Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy may occur due to proximal renal tubulopathy.[Ref]

Respiratory

Common (1% to 10%): Sinusitis (Grades 2 to 4: 8%), upper respiratory tract infections (Grades 2 to 4: 8%), nasopharyngitis (Grades 2 to 4: 5%), pneumonia (Grades 2 to 4: up to 5%)
Frequency not reported: Nasal congestion
Postmarketing reports: Dyspnea[Ref]

Hematologic

Common (1% to 10%): Decreased neutrophils (Grade 3/4: up to 3%)[Ref]

Genitourinary

Common (1% to 10%): Hematuria (Grade 3/4: up to 7%), glycosuria (Grade 3/4: up to 3%)
Postmarketing reports: Proteinuria, polyuria[Ref]

Endocrine

Frequency not reported: Higher serum parathyroid hormone levels

Immunologic

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

Hypersensitivity

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

References

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2. Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. NIH. National Institutes of Health "Guidelines for the use of antiretroviral agents in pediatric HIV infection. Available from: URL: http://aidsinfo.nih.gov/guidelines/html/2/pediatric-treatment-guidelines/0" ([2012 Nov 5]):

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4. HHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC). NIH. National Institutes of Health "Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available from: URL: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf." ([2011 Oct 14]):

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6. Blum MR, Chittick GE, Begley JA, Zong J "Steady-state pharmacokinetics of emtricitabine and tenofovir disoproxil fumarate administered alone and in combination in healthy volunteers." J Clin Pharmacol 47 (2007): 751-9

7. Munoz de Benito RM, Arribas Lopez JR "Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone." Expert Rev Anti Infect Ther 4 (2006): 523-535

8. Piacenti FJ "An update and review of antiretroviral therapy." Pharmacotherapy 26 (2006): 1111-33

9. Warnke D, Barreto J, Temesgen Z "Antiretroviral drugs." J Clin Pharmacol 47 (2007): 1570-9

10. Baeten JM, Donnell D, Ndase P, et al. "Antiretroviral prophylaxis for HIV prevention in heterosexual men and women." N Engl J Med 367 (2012): 399-410

11. "Drugs for HIV infection." Med Lett Drugs Ther 43 (2001): 103-8

12. Blaas S, Schneidewind A, Gluck T, Salzberger B "Acute renal failure in HIV patients with liver cirrhosis receiving tenofovir: a report of two cases." AIDS 20 (2006): 1786-7

13. Fux CA, Christen A, Zgraggen S, Mohaupt MG, Furrer H "Effect of tenofovir on renal glomerular and tubular function." AIDS 21 (2007): 1483-5

14. Shepp DH, Curtis S, Rooney JF "Causes and consequences of hypokalemia in patients on tenofovir disoproxil fumarate." AIDS 21 (2007): 1479-81

15. Cirino CM, Kan VL "Hypokalemia in HIV patients on tenofovir." AIDS 20 (2006): 1671-3

16. Izzedine H, Launay-Vacher V, Deray G "Antiviral drug-induced nephrotoxicity." Am J Kidney Dis 45 (2005): 804-17

17. Woolley IJ, Veitch AJ, Harangozo CS, Moyle M, Korman TM "Lichenoid drug eruption to tenofovir in an HIV/hepatitis B virus co-infected patient." AIDS 18 (2004): 1857-8

18. Borras-Blasco J, Navarro-Ruiz A, Borras C, Castera E "Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection." J Antimicrob Chemother 62 (2008): 879-88

19. "A once-daily combination tablet (Atripla) for HIV." Med Lett Drugs Ther 48 (2006): 78-9

20. Frampton JE, Croom KF "Efavirenz/Emtricitabine/Tenofovir disoproxil fumarate: triple combination tablet." Drugs 66 (2006): 1501-12

21. "Drugs for HIV infection." Treat Guidel Med Lett 7 (2009): 11-22

22. Callens S, De Schacht C, Huyst V, Colebunders R "Pancreatitis in an HIV-infected person on a tenofovir, didanosine and stavudine containing highly active antiretroviral treatment." J Infect 47 (2003): 188-9

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25. Roling J, Schmid H, Fischereder M, Draenert R, Goebel FD "HIV-Associated Renal Diseases and Highly Active Antiretroviral Therapy-Induced Nephropathy." Clin Infect Dis 42 (2006): 1488-95

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