What are the potential side effects of terbinafine (antifungal medication) in a patient with a history of cutaneous sporotrichosis and tuberculosis?

Side Effects of Terbinafine

Terbinafine is generally well-tolerated with most adverse events being mild to moderate in severity, but serious hepatotoxicity, permanent taste/smell disturbances, and severe skin reactions require immediate discontinuation and warrant careful patient counseling before initiation. 1

Common Side Effects (Occur Frequently)

The most frequently reported adverse effects include 1:

• Headache
• Diarrhea
• Rash
• Dyspepsia (indigestion)
• Liver enzyme abnormalities
• Pruritus (itching)
• Taste disturbance
• Nausea
• Abdominal pain
• Flatulence

In clinical trials for sporotrichosis specifically, adverse events were frequent but predominantly mild to moderate, requiring drug discontinuation in only 2 of 35 patients (6%) receiving the higher 1000 mg daily dose 2. One patient discontinued terbinafine due to skin rash in a study of 50 patients 3.

Serious and Potentially Irreversible Side Effects

Hepatotoxicity (Liver Damage)

This is the most critical safety concern and can progress to liver failure requiring transplantation or resulting in death. 1

Patients must be monitored for these warning signs 1:

• Persistent nausea or anorexia
• Fatigue or vomiting
• Right upper abdominal pain
• Jaundice (yellowing of skin/eyes)
• Dark urine or pale stools

Baseline liver function tests (ALT and AST) are mandatory before starting terbinafine, and the drug should be discontinued immediately if hepatotoxicity symptoms develop. 1

Taste and Smell Disturbances

• Change in taste or complete loss of taste occurs commonly and typically improves within several weeks after stopping terbinafine, but may last for a long time or become permanent 1
• Change in smell or loss of smell may also occur and can be prolonged or permanent 1
• These sensory changes can lead to poor appetite, unwanted weight loss, and secondary mood disturbances 1

Severe Skin and Allergic Reactions

Patients must seek immediate medical attention if they develop 1:

• Skin rash, hives, or mouth sores
• Blistering and peeling of skin
• Swelling of face, eyes, lips, tongue, or throat
• Trouble swallowing or breathing
• Progressive skin rash that is scaly, red, shows scarring, or loss of pigment
• Unusual sensitivity to the sun leading to rash

Terbinafine should be permanently discontinued if a petechial rash or severe cutaneous reaction develops. 1

Depressive Symptoms

Patients should report any new or worsening 1:

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

Lupus Erythematosus (New Onset or Worsening)

Stop terbinafine if patients develop 1:

• Erythema and scaling
• Loss of pigment
• Unusual photosensitivity resulting in rash

Dose-Dependent Tolerability

In the definitive randomized trial for sporotrichosis, adverse events were slightly more frequent with 1000 mg/day compared to 500 mg/day, but the majority remained mild to moderate 2. The higher dose achieved an 87% cure rate versus 52% with the lower dose, with no relapses in the high-dose group versus 6 relapses in the low-dose group 2. This evidence supports using 500 mg twice daily (1000 mg/day total) despite the marginally higher adverse event frequency, given the substantially superior efficacy. 4

Special Population Considerations

Pregnancy and Breastfeeding

• Terbinafine is FDA pregnancy category B (not expected to harm unborn baby) 1
• However, pregnant women should discuss risks and benefits with their physician before starting terbinafine 4
• Terbinafine passes into breast milk and could affect a nursing baby 1
• For pregnant patients with sporotrichosis, local hyperthermia is an alternative for fixed cutaneous disease 4

Drug Interactions

Terbinafine may interact with 1:

• Antidepressants
• Antihypertensives and cardiac medications
• Desipramine
• Caffeine
• Cyclosporine
• Fluconazole
• Rifampin
• Cimetidine

Clinical Context for Sporotrichosis Treatment

While terbinafine shows efficacy for sporotrichosis, itraconazole remains the first-line agent with 90-100% success rates 4. Terbinafine is recommended as second-line therapy when patients fail initial itraconazole treatment or when drug interactions preclude itraconazole use 4. In one study of 50 patients where itraconazole was contraindicated due to drug interactions, 250 mg/day terbinafine achieved 96% cure rate with excellent tolerability 3.

Critical Monitoring Requirements

• Baseline liver function tests (ALT/AST) before initiating therapy 1
• Counsel patients to report hepatotoxicity symptoms immediately 1
• Warn about potential for permanent taste/smell loss 1
• Advise minimizing sun exposure due to photosensitivity risk 1
• Monitor for depressive symptoms and skin reactions 1