“Is Valtrex Bad for my Liver?”

Let’s face it.  Technical stuff can be a bit confusing.  Medical technical stuff can be even worse.  Many people have a hard time deciphering their medicine labels and much misinformation and is spread as a result.  We’ve dissected the entire US Valtrex manual, including the patient label, so that you can better understand it.

We often hear claims on the Internet that Valtrex can cause “severe liver damage”.  This is untrue.  That isn’t an opinion; it’s a proven fact.  Not only has it not been shown to cause “severe liver damage”, but with dozens of millions patients worldwide, it hasn’t shown to be the cause severe liver damage or liver failure in anyone.  The only thing it has been shown to do is:

A: raise ALT levels temporarily in certain populations (the elderly, small children and HIV+ patients)
B: alter the readings of liver and kidney tests, as Valtrex does have a numerical impact on the very same markers which liver and kidney tests use to determine function.

That said, people who have existing kidney disease, or are in high-risk groups for kidney disease, should speak with their doctor about whether or not Valtrex is right for them.   There is no such recommendation for those with liver issues.  In fact, no adjustment in dosage is recommend for anyone , even those with existing liver disease.  (Please read the full article to see detailed reasons and precautions regarding Valtrex)

Introduction

Valacyclovir is a nucleoside analogue antiviral agent and prodrug of acyclovir which is used in therapy of herpes and varicella-zoster virus infections. Valacyclovir has been associated with rare instances mild, clinically apparent liver injury.

[“liver injury” is not to be confused with liver failure;  liver injury is raised ALT levels, which return to normal shortly after cessation of the medication.  Many medications have this same effect.  The liver simply works a bit harder while taking medications.]

Background

Valacyclovir (sometimes spelled valaciclovir) is an acyclic purine nucleoside analogue that is rapidly converted to acyclovir once absorbed. Valacyclovir has greater oral bioavailability than acyclovir and has similar activity against herpes viruses, including herpes simplex 1 and 2, cytomegalovirus, Ebstein-Barr virus and varicella-zoster. Once converted to acyclovir, the drug is phosphorylated intracellularly by viral kinases. The resultant triphosphate competes with guanosine for incorporation into viral DNA, blocking viral DNA polymerase activity. Because its activation requires the presence of viral kinases, valacyclovir is only activated in virally infected cells.  Valacyclovir is indicated for therapy of mucocutaneous and genital herpes simplex infections, both type 1 and 2 and for herpes zoster. Valacyclovir was approved for use in the United States in 1995 and is widely used in the treatment and prophylaxis of genital and mucocutaneous herpes simplex infection. Valacyclovir is available as capsules of 500 mg and 1000 mg generically and under the brand name of Valtrex. The usually recommended dose in adults is 500 to 1000 mg once or twice daily. Side effects are uncommon but include headache, dizziness and gastrointestinal upset.

Hepatotoxicity

Oral therapy with valacyclovir is associated with a low rate of mild-to-moderate serum aminotransferase elevations, but these are usually asymptomatic and self-limited, even with continuation of therapy. Complicating the attribution of liver test abnormalities to valacyclovir therapy is the fact that enzyme elevations are not uncommon during the course of varicella-zoster infection (shingles) and and can progress to clinically apparent hepatitis and even acute liver failure (the infection causes the issue, not the medicine).  Clinically apparent liver disease* (temporarily-reduced liver function) due to valacyclovir itself is rare, but isolated reports have been published.  The time to onset of the effect was short (1-2 weeks) and the course mild with few symptoms and rapid resolution (Case 1).   The pattern of non-permanent liver injury described was mixed hepatocellular-cholestatic.  Immunoallergic features and autoantibodies were absent.  (Translation: in rare instances, it has shown to have a temporary, mild effect on liver function, but they were quickly resolved.  No permanent damage was done.)

Mechanism of Injury

After absorption, valacyclovir is converted to acyclovir by the liver which is metabolized intracellularly in viral infected cells and is excreted largely unchanged by the kidneys.  Valacyclovir is not activated in cells without viral kinases, perhaps accounting for the absence or rarity of hepatic injury. (basically, it does nothing to uninfected cells).

Valtrex Manual & Patient Label:

We’ve attached the full United States Valtrex Manual & Patient Label.  Go ahead and read through the .pdf yourself.  We’ve marked it up for you. [note: you may have to download the file to read the comments.  Otherwise, we’ve posted a comments summary below.

click here to view full size

[gview file=”http://projectaccept.org/wp-content/uploads/2013/07/Valtrex_US_Patient_Label.pdf”]

You should be able to read the comments if you download the .pdf

Comment Summary:

Adverse Reactions:

No adverse liver reactions reported.

Dosage Instructions:

Who should not be taking Valtrex:

Those with a clinically significant hypersensitivity (allergy) to valacyclovir or acyclovir.

Acute (temporary) Renal Issues have been reported in:

• Elderly patients with or without reduced renal function (recommended adjusted dosages are provided for the elderly)
• Patients with underlying/existing kidney disease who took larger than recommended doses for their level of renal function (recommended adjusted dosages are provided)
• Patients who receive other nephrotoxic drugs (caution is recommended when mixing Rx drugs)
• Patients without adequate hydration (drink more water)
• People with existing nervous system disorders (discontinue treatment is a problem arises)

All Known Adverse Reactions:

• Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome  (TTP/HUS)
• Acute renal failure (temporary reduction in kidney function
• Central Nervous System Effects
• Headache
• Nausea
• Abdominal Pain

Various other self-reported effects exist.  However, those are not proven to be caused by the drug or shown in research to be caused by the drug.  (No more so that reporting that getting in a car accident in the afternoon was caused by the breakfast you ate that morning actually makes it true.)  They are merely patient-side assumptions that the drug may have caused the effect.  Those reports are compiled and the volume of reports are monitored to see if any true trends actually develop, in which case more research may be performed in order to determine whether or not a cause-effect relationship may actually exist and to determine how to remedy the situation.

Hepatic  (Liver) Impairment:

The only mention of liver impairment is as follows:

Administration of Valtrex to patients with moderate (clinically-proven cirrhosis) or severe (with and without ascites and biopsy-proven cirrhosis) liver disease indicated that the rate, but not the extent of conversion of valacyclovir to acyclovir is reduced, and the acyclovir half-life is not affected.  Dosage modification is not recommended for patients with cirrhosis.

That’s it. the only mention of “Liver Damage” says that even those who have existing liver damage don’t won’t require a modified dosage.

Liver Testing:

Valtrex may or may not impact the accuracy of the testing on how well the liver and kidneys function.

Drug Resistance:

HIV/AIDS patients are the only ones in whom HSV has shown to develop some resistance to Valtrex.

Talk to your doctor about precautions regarding Valtrex:

• If you had a bone marrow transplant or kidney transplant
• If you are have HIV or AIDS
• If you have kidney problems
• If you are age 65 or older
• If you are pregnant or planning to become pregnant
• If you are breastfeeding
• about all the other drugs and herbal supplements you are taking (Valtrex may affect other medicines and other medicines may affect Valtrex)

Valtrex, taken as directed, has been proven quite safe and effective.   Now, for something really scary, go look at What Supplements Would Say if They Required Warning Labels

Sources:

1. LiverTox – National Institutes of Health – National Library of Medicine