Terbinafine and fungal nails

There are too many topical anti-fungal preparations currently on the market to list them all here. Their success also varies enormously and is covered in another blog. click here to read.

Having visited your Podiatrist or GP and had your nail infection confirmed as fungal, there are three main options.

• Do nothing
• Try an over-the-counter or prescription anti-fungal topical application
• GP prescribed oral medication

There are two mainly used oral anti-fungal medicines – itraconazole and terbinafine. This blog will look specifically at terbinafine (hydrocloride) because at Maidenhead Podiatry we are frequently asked about its potential side effects.

Liver problems were only reported in 0.1% of patients. 1 in 1000; but only 1 in 50,000 to 1 in 120,000 were serious

What is terbinafine (hydrochloride)?

Terbinafine is an allylamine drug, meaning it works by inhibiting squalene epoxidase, an enzyme involved in the synthesis of ergosterol, a component in fungal cell walls.

Terbinafine is available as cream, gel, spray and, of course, tablets for oral administration at the time of writing.

What is the history of terbinafine?

It is used in the treatment of onychomycosis or fungal nails (as well as a range of fungal skin infections). Terbinafine has been available since the early 1990s in the UK and the late 1990s in USA, but there has always been some reluctance regarding its potential side effects particularly those affecting the liver when taken orally.

When terbinafine was first deployed as a new antifungal, the choices for treatment of fungal nails were limited. Topical treatments were often, and remain, disappointing.

Until the 90s, oral griseofulvin and ketoconazole were the oral drugs of choice, indicated for dermatophyte or fungal nail infection, but they were far from effective. Generally, they required long courses with a narrow spectrum of activity leading to many patients giving up when they experienced unpleasant side effects.

The idea of a new, modern, antifungal drug was appealing with subsequent studies suggesting it had twice the success rate of griseofulvin and it became widely used in the treatment of dermatophyte nail infections.

How is terbinafine metabolised?

As with many drugs, terbinafine is metabolised by the liver and excreted by the kidneys, consequently a reduction in function of either of those two organ systems could result in serious problems and correct prescribing is crucial.

Terbinafine is highly lipophilic (combining with or dissolving lipids) and tends to accumulate in hair, skin, nails, and fatty tissue where it inhibits fungal growth..

What about terbinafine and liver damage?

The possibility of liver disease (hepatotoxicity) with terbinafine has long been known and drug manufacturers have highlighting that it should not be prescribed for patients with liver disease. Terbinafine, like nearly all classes of medications, has been shown to be able to induce idiosyncratic liver injury or drug induced liver injury (DILI), but that doesn’t mean it will.

The causes of DILI are many, although pre-existing liver disease may play a part. In otherwise healthy individuals it’s cause and reason for development is unclear, although genetic susceptibility may be responsible. As a consequence, The British National Formulary advises it should not be used in patients with known liver disorders. For those that are prescribed the drug, they should have liver function tests before starting and periodically after 4–6 weeks of treatment to assess liver function.

The test monitors the levels of liver enzymes present in the bloodstream. Elevation of these enzyme levels can signal early changes in liver function. Tablets are often prescribed a month at a time, the next month being prescribed only following a successful test.

Is terbinafine safe?

Hepatotoxicity or liver function problems are rare but the more common side effects in patients taking the drug include

• gastro-intestinal upset,
• taste disturbances,
• headache
• rashes

Further, liver problems may not be as common as is perceived. A 1996 British study reviewed 9879 patients who had taken the oral terbinafine. Half of these had other illnesses and conditions and were taking other medications at the same time. 14% reported various side effects but only half of these were thought to be related to the terbinafine as reported by their physicians.

Liver problems were only reported in 0.1% of patients. 1 in 1000

(14 cases) of which 10 cases were classified as minor and transient elevations in liver enzymes. In addition, some of these patients were found to have pre-existing history of liver disease (gall bladder disease, alcohol related changes, hepatitis and cirrhosis).

There were no terbinafine associated deaths.

The National Library of Medicine Liver Toxicity Database report on terbinafine shows less than one percent of patients see an increase in liver enzymes in the bloodstream and most resolve with stopping treatment. It estimates the probability of developing elevated liver enzymes levels requiring stopping treatment is about 0.31% for 2 to 6 weeks’ treatment and 0.44% for treatment lasting longer than 8 weeks.

It concludes that clinically apparent liver injury from terbinafine occurs rarely, in around 1 in 50,000 to 120,000 prescriptions.

How do I decide?

Remember,

• no drug can ever be 100% effective for everyone so success isn’t guaranteed
• successful resolution doesn’t mean you can’t get it again
• re-infection within 12 months is not only possible but likely
• successful resolution must be followed by an anti-fungal regime
• leaving a fungal nail untreated rarely causes problems

As with most classes of drugs, terbinafine can potentially lead to liver problems. However, the data from the above control suggests that oral terbinafine is safer than perhaps it is perceived, and minor side effects are far more likely for most patients than serious liver damage.

Data from studies suggest the risk of serious liver injury to be between 1 in 50 000 and 1 in 120 000

Despite its rarity, patients taking terbinafine who exhibit any of the symptoms of liver problems (nausea, vomiting, abdominal pain, fatigue, anorexia, general itching and dark urine) should urgently be referred for further assessment.

If you would like more information , or to make an appointment with one of our Podiatrists, call on 01628 773588 or email info@maidenheadpodiatry.co.uk.