What are the potential side effects of terbinafine (antifungal medication) in patients, particularly those with pre-existing medical conditions or a history of liver disease or allergies?

Terbinafine Side Effects

Terbinafine is generally well tolerated with gastrointestinal and dermatological side effects being most common, but requires careful monitoring for rare but serious hepatotoxicity, particularly in patients with pre-existing liver disease, and carries risk of potentially permanent taste and smell disturbances. 1, 2

Common Side Effects

Gastrointestinal disturbances are the most frequently reported adverse effects, accounting for 49% of side effects in postmarketing surveillance: 1

• Nausea 1, 2
• Diarrhea 1, 2
• Abdominal pain 2
• Dyspepsia 2
• Flatulence 2

Dermatological reactions occur in 23% of reported side effects: 1

• Rash 1, 2
• Pruritus 1, 2
• Urticaria 1
• Eczema 1

Other common effects include headache and liver enzyme abnormalities. 2

Serious Adverse Effects Requiring Immediate Discontinuation

Hepatotoxicity (Most Critical)

Liver failure, including cases requiring transplantation or resulting in death, has occurred in patients with and without pre-existing liver disease. 2

Key hepatotoxicity considerations:

• The incidence of serious adverse events is 0.04%, but hepatotoxicity is the most concerning complication 1
• Severity is worse in patients with active or chronic liver disease 2
• Terbinafine is contraindicated in patients with active or chronic liver disease 1, 2
• Clearance is decreased in severe liver disease 1

Mandatory monitoring requirements: 2

• Baseline liver function tests (LFTs) must be obtained before prescribing 2
• Complete blood count should be obtained alongside baseline LFTs 1, 3
• Periodic monitoring of LFTs is recommended during treatment 2
• Additional baseline testing required for: patients with history of heavy alcohol consumption, hepatitis, or hematological abnormalities 1, 3

Warning signs requiring immediate discontinuation: 2

• Persistent nausea, anorexia, or fatigue
• Vomiting or right upper abdominal pain
• Jaundice, dark urine, or pale stools
• Elevation of liver function tests

Taste and Smell Disturbances (Potentially Permanent)

Taste disturbance, including complete loss of taste, can be severe enough to cause decreased food intake, weight loss, and depressive symptoms. 2

Critical characteristics: 1, 2

• Occurs in approximately 1 in 400 patients 1
• May resolve within several weeks after discontinuation
• Can be prolonged (>1 year) or permanent 2
• Patients must be warned of this risk before treatment 1

Smell disturbance, including loss of smell, follows similar patterns and may also be prolonged or permanent. 2

Discontinue terbinafine immediately if taste or smell disturbances occur. 2

Severe Skin Reactions

Rare but life-threatening cutaneous reactions include: 1, 2

• Stevens-Johnson syndrome 1, 2
• Toxic epidermal necrolysis 1, 2

Discontinue treatment immediately if progressive skin rash occurs. 2

Hematologic Effects

Transient decreases in absolute lymphocyte counts (ALC) occur, with 1.7% of patients experiencing ALC <1000/mm³ on multiple occasions. 2

Severe neutropenia has been reported but is reversible upon discontinuation: 2

• Monitor complete blood counts if treatment exceeds 6 weeks in immunodeficient patients 2
• If neutrophil count <1,000 cells/mm³, discontinue terbinafine immediately 2
• Obtain CBC if clinical signs of secondary infection occur 2

Depressive Symptoms

Depressive symptoms have been reported during postmarketing surveillance. 2

Monitor for: 2

• Feelings of sadness or worthlessness
• Changes in sleep pattern
• Loss of energy or interest in daily activities
• Mood changes or restlessness

Contraindications and Special Populations

Absolute Contraindications

• Active or chronic liver disease 1, 2
• History of allergic reaction to oral terbinafine (risk of anaphylaxis) 2
• Severe renal impairment (creatinine clearance ≤50 mL/min) 3

Renal Impairment

Terbinafine is contraindicated rather than dose-adjusted in renal impairment because it is primarily cleared by the kidneys. 3

For patients with CrCl ≤50 mL/min, alternative options include: 3

• First choice: Topical therapy (amorolfine 5% lacquer or ciclopirox 8% lacquer) 3
• Second choice: Itraconazole if hepatic function is normal and systemic therapy is essential 3

Pregnancy and Breastfeeding

Terbinafine should not be started during pregnancy without discussing with your physician. 2

Terbinafine passes into breast milk and may harm the baby. 2

Drug Interactions

Terbinafine has minimal drug-drug interactions compared to azole antifungals. 1

The only potentially significant interaction is with drugs metabolized by cytochrome P450 2D6 isoenzyme: 1, 2

• Desipramine 2
• Other antidepressants 2
• Beta-blockers for blood pressure or heart problems 2

Other notable interactions: 2

• Plasma concentrations reduced by rifampin 1, 2
• Plasma concentrations increased by cimetidine 1, 2
• May affect caffeine metabolism 2
• May interact with cyclosporine 2

Clinical Monitoring Algorithm

Before initiating treatment: 1, 3, 2

1. Obtain baseline liver function tests (ALT, AST) 1, 3, 2
2. Obtain complete blood count 1, 3
3. Screen for contraindications (active liver disease, severe renal impairment, allergy history) 1, 3, 2
4. Warn patients about potentially permanent taste/smell disturbances 1, 2
5. Educate patients on hepatotoxicity warning signs 2

During treatment: 1, 3, 2

• Monitor hepatic function tests, particularly if treatment extends beyond one month 1, 3
• Consider monitoring CBC if treatment continues beyond 6 weeks in immunodeficient patients 2
• Instruct patients to report immediately: taste/smell changes, depressive symptoms, skin reactions, or signs of liver injury 2

Common Pitfalls to Avoid

Do not prescribe terbinafine without baseline liver function testing, even in patients without known liver disease, as hepatotoxicity can occur in previously healthy individuals. 2

Do not minimize the risk of permanent taste disturbance - patients must understand this may be irreversible before consenting to treatment. 1, 2

Do not attempt dose adjustment in renal impairment - terbinafine is contraindicated, not dose-adjustable, in CrCl ≤50 mL/min; use alternative therapy instead. 3

Do not ignore elevated liver enzymes - discontinue immediately if biochemical or clinical evidence of liver injury develops. 2