From the Guidelines
Low or borderline alkaline phosphatase levels generally do not require modification of long-term terbinafine treatment. Terbinafine, typically prescribed at 250 mg daily for 6-12 weeks for fingernail infections or 12-16 weeks for toenail infections, is primarily metabolized by the liver and can occasionally cause hepatotoxicity 1. However, monitoring should focus on liver transaminases (ALT, AST) rather than alkaline phosphatase. Before starting terbinafine, baseline liver function tests should be obtained, with follow-up testing recommended after 4-6 weeks of therapy 1. If a patient has pre-existing liver disease or develops symptoms of liver dysfunction (jaundice, dark urine, fatigue, abdominal pain), more frequent monitoring or dose adjustment may be necessary. Low alkaline phosphatase itself is not typically associated with terbinafine toxicity and is more commonly related to conditions like malnutrition, zinc deficiency, or certain genetic disorders. The decision to modify treatment should be based on a comprehensive assessment of liver function, not solely on alkaline phosphatase levels.
Some key points to consider when prescribing terbinafine include:
- Terbinafine is licensed at a dose of 250 mg per day for 6 weeks in fingernail and 12–16 weeks in toenail infection 1
- Patients should be re-evaluated 3–6 months after treatment initiation and further treatment should be given if the disease persists 1
- Terbinafine has been shown to be more effective than itraconazole in dermatophyte onychomycosis, with higher efficacy rates and lower relapse rates 1
- Monitoring for terbinafine toxicity should focus on liver transaminases (ALT, AST) rather than alkaline phosphatase, with baseline liver function tests and follow-up testing recommended after 4-6 weeks of therapy 1
Overall, the current evidence suggests that low or borderline alkaline phosphatase levels do not require modification of long-term terbinafine treatment, and that monitoring should focus on liver transaminases (ALT, AST) rather than alkaline phosphatase.
From the Research
Alkaline Phosphatase Levels and Terbinafine Treatment
- There is no direct evidence to suggest that low or borderline alkaline phosphatase levels require modification of treatment with long-term Terbinafine 2, 3, 4, 5, 6.
- Terbinafine is commonly prescribed for onychomycosis and has been associated with rare cases of severe cholestatic drug-induced liver injury, which may be idiosyncratic 2, 5.
- The pharmacokinetics and pharmacology of terbinafine suggest that it is effective in treating dermatophyte infections, with minimal potential for drug-drug interactions 3.
- Studies have compared the efficacy and safety of different terbinafine treatment regimens, including intermittent and continuous dosing, but have not specifically addressed the issue of alkaline phosphatase levels 3, 4.
- Low serum alkaline phosphatase levels have been observed in patients with chronic liver diseases, and may be associated with less biochemical evidence of active disease 6.
Terbinafine-Associated Hepatic Injury
- Terbinafine has been associated with hepatic injury, including mixed cholestatic-hepatocellular type of hepatitis, which may be idiosyncratic rather than a direct hepatotoxic reaction 5.
- In some cases, terbinafine-associated hepatic injury has been characterized by elevated alkaline phosphatase, aminotransferase, and gamma-glutamyl transferase levels, which may persist even after cessation of treatment 5.
Monitoring and Treatment
- Clinicians should remain vigilant for complications associated with terbinafine treatment, including hepatic injury, and monitor patients regularly for signs of adverse effects 2, 5.
- The optimal treatment regimen for onychomycosis with terbinafine remains continuous treatment, rather than intermittent or pulsed dosing 4.