What is the best oral medication for itching?

Best Oral Medicine for Itching

For general pruritus, second-generation non-sedating antihistamines such as loratadine 10 mg daily or cetirizine 10 mg daily are recommended as first-line oral therapy, with sedating first-generation antihistamines like diphenhydramine 25-50 mg reserved only for nighttime use when sleep is disrupted by itching. 1, 2

First-Line Oral Antihistamines

Daytime Treatment

• Non-sedating second-generation antihistamines are the preferred first choice for daytime pruritus management 1, 2
• Loratadine 10 mg daily is recommended as first-line systemic therapy with minimal central nervous system effects 1, 2
• Cetirizine 10 mg daily offers rapid onset of action and is available in generic formulations, though it may cause mild sedation 1, 2, 3
• Fexofenadine 180 mg daily provides relief with negligible sedation 1, 2

The evidence supporting second-generation antihistamines is strongest in histamine-mediated conditions like urticaria 1. However, for atopic dermatitis, the evidence is mixed—antihistamines show insufficient benefit for controlling eczema symptoms themselves, though they may help with comorbid allergic conditions 1, 4.

Nighttime Treatment (When Sleep is Disrupted)

• First-generation sedating antihistamines should only be used for nighttime pruritus when sleep loss is the primary concern 1
• Diphenhydramine 25-50 mg at bedtime may be considered based on sedative properties 1
• Hydroxyzine 25-50 mg at bedtime is an alternative sedating option 1, 5

Critical caveat: Sedating antihistamines should be strictly avoided in elderly patients due to fall risk, cognitive impairment, and anticholinergic burden 1, 6, 2. They may also negatively affect school performance in children 1.

Second-Line Oral Agents

When antihistamines fail or for specific types of pruritus:

Antiepileptic Agents

• Gabapentin 900-3600 mg daily is effective for neuropathic and refractory pruritus 1, 2
• Pregabalin 25-150 mg daily works through similar mechanisms, reducing peripheral and central itch mediators 1, 2
• These agents are recommended only as second-line treatment after antihistamine failure 1

Other Systemic Options

• Antidepressants: Doxepin (potent histamine antagonist), paroxetine, fluvoxamine, or mirtazapine may be considered 1, 2
• Opioid antagonists: Naltrexone or butorphanol for specific pruritus types 1
• NK-1 receptor antagonists: Aprepitant has shown benefit in drug-induced and refractory pruritus 1

Context-Specific Recommendations

Opioid-Induced Pruritus

• Naltrexone is the first-choice recommendation if opioid cessation is impossible 1
• Mirtazapine 30 mg daily or gabapentin 1200 mg daily can prevent morphine-induced pruritus in surgical settings 1, 6
• Ondansetron is not recommended as it does not reduce incidence or onset of opioid-induced pruritus 1, 6

Atopic Dermatitis

• Oral antihistamines are recommended only as adjuvant therapy, not primary treatment 1
• Evidence shows insufficient benefit for controlling AD symptoms except possibly for sleep improvement with sedating agents 1, 4, 7
• Short-term sedating antihistamines may help break the itch-scratch cycle but should not substitute for topical therapies 1

Elderly Patients

• Gabapentin is preferred over antihistamines for pruritus in elderly skin 1, 6
• Sedating antihistamines are contraindicated due to fall risk and cognitive effects 1, 6
• Second-generation antihistamines (cetirizine, loratadine, fexofenadine) are safer alternatives if antihistamines are needed 6, 2

Common Pitfalls to Avoid

• Do not use topical antihistamines due to insufficient evidence and increased risk of contact dermatitis 1
• Avoid long-term sedating antihistamines in elderly patients—may increase dementia risk 2
• Do not rely on antihistamines alone for non-histamine-mediated pruritus (e.g., atopic dermatitis, neuropathic itch) 1, 8, 4
• Crotamiton cream should not be used for generalized pruritus of unknown origin 1
• Dose adjustments are necessary in renal or hepatic impairment 2

Treatment Algorithm

1. Start with non-sedating second-generation antihistamine (loratadine 10 mg, cetirizine 10 mg, or fexofenadine 180 mg) for daytime relief 1, 2

2. If nighttime itching disrupts sleep, add low-dose first-generation antihistamine (diphenhydramine 25-50 mg) at bedtime only—except in elderly patients 1, 6

3. For inadequate response, consider:

   • Increasing antihistamine dose 1
   • Adding H2 antihistamines in combination (e.g., fexofenadine + cimetidine) 1
   • Switching to gabapentin 900-3600 mg daily or pregabalin 25-150 mg daily 1, 2

4. For specific etiologies, use targeted therapy:

   • Opioid-induced: naltrexone, mirtazapine, or gabapentin 1, 6
   • Cholestatic: ursodeoxycholic acid 2
   • Hepatic: rifampicin 2

5. If all oral therapies fail, consider systemic corticosteroids (0.5-2 mg/kg daily) for temporary relief of severe pruritus, or refer to specialist for phototherapy or immunosuppressive therapy 1