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Sinusitis: Evidence-Based Prescribing

Note: Most acute sinusitis is viral. The 2025 AAO-HNS updated guideline (Payne et al., Otolaryngol Head Neck Surg, 2025) now recommends watchful waiting as an initial strategy for all patients with uncomplicated acute bacterial rhinosinusitis (ABRS), regardless of severity - not just mild cases. Antibiotics should be reserved for those who truly meet prescribing criteria.

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1. Determine If Antibiotics Are Indicated

Only ~20-50% of adults with sinusitis actually meet antibiotic prescribing criteria.

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2. Symptomatic Treatment (All Patients)

• Intranasal decongestant: Oxymetazoline 2 sprays each nostril twice daily - do NOT use >5 days
• Oral decongestant: Pseudoephedrine 120 mg (12-hour release) during the day
• Analgesic/antipyretic: Paracetamol (acetaminophen) or ibuprofen
• Saline nasal spray or wash: Higher-volume nasal saline washes are more effective than sprays
• Intranasal glucocorticoid: Particularly helpful if allergic component is suspected

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3. Antibiotic Selection (Acute Bacterial Sinusitis)

First-Line

The 2025 AAO-HNS guideline updated first-line therapy to amoxicillin with or without clavulanate (previously amoxicillin alone).

Penicillin Allergy

Reassess at 3-5 Days

• Amoxicillin-clavulanate (high-dose): 2000 mg/125 mg PO twice daily x 7 days
• Levofloxacin (use cautiously - risk of dysglycemia, peripheral neuropathy, tendinopathy, aortic rupture)

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4. Special Scenarios

Pediatric (3-36 months)

• High-dose amoxicillin: 30 mg/kg/dose three times daily (max adult dose)
• Alternative: Amoxicillin-clavulanate

Chronic Sinusitis (>12 weeks)

• Mainstay: Intranasal glucocorticoids - mometasone, fluticasone sprays, or budesonide rinses (especially with polyps)
• Oral glucocorticoids: 2-3 week course for refractory cases; reduces polyp size
• Macrolides: 3-month course has modest evidence in chronic sinusitis without polyps (e.g., azithromycin or clarithromycin - low-dose, anti-inflammatory use)
• Antibiotics (2-4 weeks): Commonly prescribed but evidence is poor for chronic sinusitis
• Antifungal agents: No benefit in any subtype of chronic sinusitis
• Saline washes: High-volume nasal irrigation is a key adjunct
• Surgery (FESS): Consider after failure of adequate medical therapy; particularly effective for chronic sinusitis with polyps

Allergic Fungal Sinusitis

• Medical therapy is classically ineffective
• Surgery is first-line, with perioperative glucocorticoids

Nosocomial Sinusitis

• Suspect in ICU patients with fever of unknown origin, especially those with nasotracheal intubation
• Requires culture-directed therapy; cover gram-negative organisms and S. aureus

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5. When to Refer or Image

• Lack of improvement after second-line antibiotic (3-5 days)
• Concern for complication (orbital, intracranial extension)
• Recurrent acute sinusitis (consider allergic/immunologic workup and anatomic imaging)
• Imaging modality of choice: Non-contrast CT of paranasal sinuses

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Sinusitis Medicines

• Amoxicillin-clavulanate
• Amoxicillin
• Cefuroxime
• Doxycycline
• Levofloxacin

• Oxymetazoline (nasal spray)
• Pseudoephedrine (oral)

• Paracetamol (Acetaminophen)
• Ibuprofen

• Mometasone
• Fluticasone
• Budesonide

• Prednisolone

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UTI Medicines

Uncomplicated Cystitis (Lower UTI) - First Line

• Nitrofurantoin
• Trimethoprim-Sulfamethoxazole (TMP-SMX / Co-trimoxazole)
• Fosfomycin
• Pivmecillinam

Uncomplicated Cystitis - Second Line

• Cefpodoxime
• Cefdinir
• Cefaclor
• Amoxicillin-clavulanate

Pyelonephritis (Upper UTI)

• Ciprofloxacin
• Levofloxacin
• Ceftriaxone (IV)
• Gentamicin (IV, initial empiric)
• TMP-SMX (oral step-down)
• Cefixime (oral step-down)

Complicated UTI / Urosepsis

• Piperacillin-tazobactam (IV)
• Meropenem (IV)
• Ertapenem (IV)
• Amikacin (IV)

Symptom Relief (Urinary Analgesic)

• Phenazopyridine (pain/burning relief only - NOT an antibiotic)

Pregnant Women (Safe Options)

• Nitrofurantoin
• Cephalosporins (oral)

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Note: Fluoroquinolones (ciprofloxacin, levofloxacin) are not recommended for uncomplicated cystitis - reserve for pyelonephritis or complicated UTI only.

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Causes of Night-Only Cough

Most Common

1. Asthma

2. GERD (Acid Reflux)

3. Postnasal Drip (Upper Airway Cough Syndrome)

4. Heart Failure

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Other Causes to Consider

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Key Questions to Help Find the Cause

• Do you have heartburn or a sour taste? → Think GERD
• Do you wheeze or feel chest tightness? → Think Asthma
• Do you take a blood pressure pill? → Check for ACE inhibitor
• Do your ankles swell and you feel breathless? → Think Heart Failure
• Do you have allergies or sinus problems? → Think Postnasal Drip
• Are you a smoker? → Think Chronic Bronchitis or COPD

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The three most common causes of chronic nocturnal cough are asthma, GERD, and postnasal drip - together accounting for the majority of cases. A doctor's evaluation is recommended to identify the exact cause.

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Rheumatoid Arthritis Medicines

Symptom Relief (Short-term)

• Ibuprofen
• Naproxen
• Diclofenac
• Celecoxib

• Prednisolone
• Methylprednisolone

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Conventional DMARDs (Disease-Modifying - First Line)

• Methotrexate (most common first-line)
• Hydroxychloroquine
• Sulfasalazine
• Leflunomide
• Azathioprine

Often combined: Methotrexate + Hydroxychloroquine + Sulfasalazine (triple therapy)

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Biologic DMARDs (if conventional DMARDs fail)

• Etanercept
• Adalimumab
• Infliximab
• Golimumab
• Certolizumab pegol

• Tocilizumab
• Sarilumab

• Rituximab

• Abatacept

• Anakinra

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JAK Inhibitors (targeted synthetic DMARDs)

• Tofacitinib
• Baricitinib
• Upadacitinib

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Supplement (given with Methotrexate)

• Folic acid (reduces methotrexate side effects)

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Rheumatoid Arthritis - Detailed Prescription Guide

Key principle: Start DMARDs early - as soon as diagnosis is confirmed. NSAIDs and steroids only provide symptom relief; only DMARDs slow/stop joint destruction.

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STEP 1 - Symptom Relief (While DMARDs take effect)

NSAIDs

• Ibuprofen 400-800 mg three times daily with food
• Naproxen 500 mg twice daily
• Diclofenac 50 mg twice or three times daily
• Celecoxib 100-200 mg twice daily (safer for stomach, used in patients with GI risk)

Corticosteroids (Steroids)

• Prednisolone 5-10 mg/day orally (low dose, long-term)
• Methylprednisolone IM or IV injection for acute severe flares

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STEP 2 - Conventional DMARDs (First Line - Disease Modifying)

1. Methotrexate (MTX) - THE cornerstone of RA treatment

• Dose: Start 7.5-10 mg once weekly, increase up to 20-25 mg/week
• Route: Oral or subcutaneous (SC route has better absorption and fewer GI side effects)
• Onset: 6-12 weeks
• Always give with: Folic acid 1 mg/day (reduces mouth sores and liver toxicity without reducing efficacy)
• Side effects: Liver toxicity, bone marrow suppression, mouth sores (stomatitis), nausea, fatigue, rare lung inflammation, risk of lymphoma
• Monitoring: LFTs + CBC monthly for 3 months, then every 3-4 months. Renal function also
• Contraindicated in: Pregnancy (teratogenic), liver disease, alcohol use, severe renal failure

2. Hydroxychloroquine (Plaquenil)

• Dose: 400-600 mg/day initially, then 200 mg/day maintenance
• Use: Mild RA, or combined with MTX and sulfasalazine (triple therapy)
• Onset: 3-6 months
• Key side effect: Retinopathy (eye damage) - rare but important
• Monitoring: Eye exam (ophthalmology) every 3 months - visual acuity, slit-lamp exam
• Safest DMARD - least toxic of the conventional DMARDs

3. Sulfasalazine (Azulfidine)

• Dose: Start low, increase to 2-3 g/day in 2 divided doses
• Use: Mild-moderate RA; good if MTX is contraindicated
• Side effects: GI upset (nausea, diarrhea), rash, low WBC. Check for sulfa allergy first.
• Monitoring: CBC + LFTs weekly for 1 month, then every 4-6 weeks

4. Leflunomide (Arava)

• Dose: Loading dose 100 mg/day x 3 days, then 20 mg/day maintenance
• Use: Alternative to MTX or combined with MTX
• Half-life: Very long (~2 weeks) due to liver recycling - stays in body up to 2 years
• Side effects: Liver injury, diarrhea, alopecia (hair loss), bone marrow suppression, lung disease
• Monitoring: LFTs + CBC monthly for 3-6 months, then every 2-3 months
• Contraindicated in: Pregnancy (teratogenic) - requires cholestyramine washout before conception

5. Azathioprine (Imuran)

• Dose: 50-100 mg/day, can increase to 2.5 mg/kg/day over 4-week intervals
• Use: Second or third-line; often used in combination
• Side effects: Bone marrow suppression, infection risk, GI distress, rare leukaemia
• Monitoring: LFTs weekly x 6 weeks, then monthly; also CBC

Triple Therapy Combination

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STEP 3 - Biologic DMARDs (If conventional DMARDs fail after 3-6 months)

TNF Inhibitors (Most commonly used biologics)

IL-6 Inhibitors

• Tocilizumab - 4-8 mg/kg IV every 4 weeks OR 162 mg SC every 1-2 weeks. Can be used as monotherapy (unlike most TNF inhibitors). Side effects: Upper respiratory infections, elevated liver enzymes, high BP, rarely GI perforation.
• Sarilumab - 200 mg SC every 2 weeks

B-cell Depleter

• Rituximab - 1000 mg IV x 2 doses given 2 weeks apart; repeated every 6 months. Used in patients who fail TNF inhibitors. Side effects: Infusion reactions, serious infections, progressive multifocal leukoencephalopathy (rare).

T-cell Co-stimulation Blocker

• Abatacept - 500-1000 mg IV monthly OR 125 mg SC weekly. Well tolerated; good option for patients with interstitial lung disease.

IL-1 Blocker

• Anakinra - 100 mg SC daily. Less commonly used now due to daily injection burden.

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STEP 4 - JAK Inhibitors (Targeted Synthetic DMARDs - Oral Biologics)

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Supplement Always Given Alongside DMARDs

• Folic acid 1 mg/day - given with methotrexate to reduce side effects
• Calcium + Vitamin D - for all patients on long-term corticosteroids (bone protection)
• Bisphosphonate (e.g., Alendronate) - if on steroids >3 months (prevent osteoporosis)

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Summary: Treatment Ladder

1. Diagnosis confirmed → Start DMARD immediately
2. First: Methotrexate (± Hydroxychloroquine ± Sulfasalazine)
3. Add low-dose steroids or NSAIDs for short-term symptom control
4. If no response in 3-6 months → Add/switch to Biologic DMARD (TNF inhibitor first)
5. If biologic fails → Switch to another biologic class OR JAK inhibitor
6. Severe refractory → Rituximab, Abatacept

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Monitoring Tests During RA Treatment

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BEFORE Starting Any Treatment (Baseline Tests)

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Drug-by-Drug Ongoing Monitoring Schedule

Methotrexate (MTX)

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Hydroxychloroquine (Plaquenil)

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Sulfasalazine

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Leflunomide

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Azathioprine

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Biologic DMARDs (All TNF inhibitors, IL-6 inhibitors, Rituximab, Abatacept)

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JAK Inhibitors (Tofacitinib, Baricitinib, Upadacitinib)

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Corticosteroids (Long-term use monitoring)

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Disease Activity Monitoring (At Every Clinic Visit)

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Quick Summary Table

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Kidney Stone (Nephrolithiasis) - Detailed Prescription Guide

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Types of Kidney Stones (Know the type to treat correctly)

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STEP 1 - Acute Attack: Pain Relief (Renal Colic)

NSAIDs - First Choice for Pain

• Ketorolac 15-30 mg IM or IV - preferred when patient has nausea/vomiting and cannot take oral medication
• Ibuprofen 200-400 mg orally every 4-6 hours (max 1.2 g/day) - for patients who can swallow
• Diclofenac 75 mg IM - another good option

Caution: NSAIDs can worsen kidney function. Always give adequate IV hydration (Normal Saline 75-150 mL/hour) alongside NSAIDs. Do NOT use in patients with dehydration or pre-existing kidney injury without fluids.

Opioids - Second Choice (if NSAIDs fail or are contraindicated)

• Morphine 2-4 mg IV every 4-6 hours
• Tramadol 50-100 mg orally
• Pethidine (Meperidine) - historically used but now less favored

Anti-nausea / Anti-vomiting (often needed alongside pain relief)

• Metoclopramide 10 mg IV or oral
• Ondansetron 4-8 mg IV or oral

IV Fluids

• Normal Saline (0.9% NaCl) at 75-150 mL/hour to maintain hydration
• High-volume fluids alone do NOT speed stone passage but protect kidneys from NSAID injury

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STEP 2 - Help the Stone Pass (Medical Expulsive Therapy)

Alpha-1 Blockers (Most effective for stone passage)

• Tamsulosin 0.4 mg orally once daily - drug of choice. Relaxes ureteral smooth muscle, increases stone passage rate by ~50%, reduces time to pass, and reduces need for pain medication
• Alfuzosin 10 mg once daily - alternative

Calcium Channel Blockers (Alternative)

• Nifedipine 30 mg once daily - used if alpha blocker not tolerated; best combined with a steroid

Continue medical expulsive therapy for 4-6 weeks while waiting for stone to pass. If stone does not pass, refer for surgery (ESWL, ureteroscopy, or PCNL).

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STEP 3 - Preventing Recurrence (By Stone Type)

A. Calcium Stones (Calcium Oxalate / Calcium Phosphate) - 70-80% of cases

• Increase fluid intake to produce >2 liters of urine per day (most important single step - reduces recurrence by 50%)
• Reduce sodium intake to <2 g/day (sodium causes calcium leakage into urine)
• Reduce animal protein intake
• Maintain normal dietary calcium (1000 mg/day from food, NOT supplements) - restricting calcium actually increases stone risk
• Avoid high-oxalate foods (spinach, nuts, cocoa, tea)

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B. Uric Acid Stones - 10-15% of cases

• Increase fluid intake (>2 L urine/day)
• Low purine diet (reduce red meat, organ meats, shellfish, beer)
• Reduce animal protein

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C. Struvite Stones (Infection Stones) - 10-15%

1. Complete surgical removal of the stone is required first (stones harbor bacteria - antibiotics alone cannot cure)
2. Long-term antibiotics based on culture sensitivity from stone fragments:
   • Common organisms: Proteus, Klebsiella, Staphylococcus, Pseudomonas
   • Continue at full dose until urine is sterile, then reduce to prophylactic dose
3. Monthly urine cultures until 3 consecutive sterile cultures, then monthly for 1 more year

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D. Cystine Stones (Rare - <1%)

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STEP 4 - When Surgery is Needed

• Stone causes complete obstruction
• Stone + infection (urological emergency)
• Stone causing acute kidney injury
• Pain that cannot be controlled with medication
• Stone >10 mm (unlikely to pass spontaneously)
• No passage after 4-6 weeks of medical expulsive therapy

• ESWL (Extracorporeal Shock Wave Lithotripsy) - sound waves break stone from outside; best for kidney stones <15 mm
• Ureteroscopy + Laser - scope passed up ureter; laser fragments the stone; best for ureteral stones
• PCNL (Percutaneous Nephrolithotomy) - scope through skin into kidney; best for large stones ≥15 mm

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Summary by Stone Type

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Most important single intervention for ALL stone types: Drink enough fluid to produce >2 litres of urine per day. This alone reduces recurrence by 50%.

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Allergic Bronchitis - Detailed Prescription Guide

Important note: "Allergic bronchitis" is not a distinct formal diagnosis. It describes bronchial inflammation triggered by allergens, and clinically overlaps with allergic asthma (most common) and acute bronchitis with bronchospasm. The treatment follows the same pathway as allergic/asthmatic bronchitis.

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Understanding the Condition

• Bronchial inflammation and swelling
• Increased mucus production
• Bronchospasm (airway narrowing) causing wheeze and cough
• Eosinophilic infiltration of the airway

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STEP 1 - Immediate Symptom Relief (Rescue Treatment)

Short-Acting Beta-2 Agonists (SABAs) - First and most important

• Salbutamol (Albuterol) - the gold standard rescue inhaler
  • MDI (metered dose inhaler): 2 puffs (200 mcg) every 4-6 hours as needed
  • Nebulization: 2.5 mg in 2.5 mL normal saline via nebulizer for severe attacks
  • Oral tablet: 2-4 mg three times daily (less effective than inhaled; used when inhaler not available)
• Levosalbutamol (Levalbuterol) - purified form, fewer side effects like palpitations
  • MDI: 1-2 puffs every 4-6 hours

Important: SABAs should ONLY be used as needed (rescue), not regularly scheduled. If you need them more than twice a week, you need a controller medicine (Step 2).

Short-Acting Anticholinergic (Add-on for severe attacks)

• Ipratropium bromide (Atrovent)
  • MDI: 2-4 puffs (40-80 mcg) every 6 hours
  • Often combined with salbutamol in a nebulizer for acute severe attacks (Combivent: salbutamol + ipratropium)
  • Works differently from beta-agonists - reduces mucus and further opens airways

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STEP 2 - Controller Medicines (Prevent inflammation - taken daily)

Inhaled Corticosteroids (ICS) - CORNERSTONE of allergic bronchitis/asthma control

• Always rinse mouth with water and gargle after using ICS inhaler (prevents oral thrush and hoarseness)
• Use a spacer device with MDI inhalers for better delivery
• Side effects of ICS: oral thrush (candidiasis), hoarseness, mild growth suppression in children (at high doses)

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STEP 3 - Combination Inhalers (ICS + Long-Acting Beta-Agonist)

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STEP 4 - Add-On Medications

Leukotriene Receptor Antagonists (Anti-inflammatory, oral)

• Montelukast (Singulair)
  • Adults: 10 mg orally once daily at night
  • Children 6-14 years: 5 mg chewable tablet once daily
  • Children 2-5 years: 4 mg granules/chewable once daily
  • Especially useful when allergic rhinitis coexists with bronchitis (treats both)
  • FDA warning: May cause mood changes, depression, suicidal thoughts in some patients (rare)
• Zafirlukast - 20 mg twice daily (less commonly used)

Antihistamines (For the allergic component)

• Cetirizine 10 mg once daily
• Loratadine 10 mg once daily
• Fexofenadine 120-180 mg once daily
• Desloratadine 5 mg once daily
• Levocetirizine 5 mg once daily

• Chlorpheniramine 4 mg every 6-8 hours
• Diphenhydramine 25-50 mg at bedtime

Long-Acting Anticholinergic (Add-on for persistent symptoms)

• Tiotropium (Spiriva) - 18 mcg once daily via DPI
  • Used as add-on in Step 4-5 when ICS + LABA is insufficient
  • Reduces exacerbations and improves lung function

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STEP 5 - Severe/Refractory Allergic Bronchitis - Oral Steroids & Biologics

Oral Corticosteroids (Short courses for acute flares)

• Prednisolone 30-40 mg/day for 5-7 days (short burst)
• Taper gradually if used >1 week
• Long-term oral steroids avoided due to serious side effects

Biologic (Monoclonal Antibody) Therapies - For severe allergic asthma/bronchitis

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Supportive / Symptom Relief Medicines

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Treatment Ladder (GINA Step Approach)

STEP 1 (Mild, occasional):
→ SABA (Salbutamol) as needed ONLY

STEP 2 (Symptoms >2x/week):
→ Low-dose ICS daily + SABA as needed
→ OR: Montelukast (alternative)

STEP 3 (Not controlled on Step 2):
→ Low-dose ICS + LABA (combination inhaler)
→ OR: Medium-dose ICS alone

STEP 4 (Still not controlled):
→ Medium-to-High dose ICS + LABA
→ Add Montelukast or Tiotropium

STEP 5 (Severe, refractory):
→ High-dose ICS + LABA + specialist referral
→ Biologic therapy (Omalizumab, Dupilumab, etc.)
→ Oral prednisolone at lowest effective dose

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Key Points to Remember

• Never use LABA without ICS - increases risk of asthma death
• Rinse mouth after every ICS inhaler use (prevents thrush)
• Salbutamol used >2x/week = needs a controller (daily ICS)
• Montelukast is particularly useful when patient has both allergic bronchitis AND allergic rhinitis
• Allergen avoidance is as important as medicines - identify and reduce exposure to triggers

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Breathlessness (Dyspnea) - What Could It Be?

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Organised by Onset

Acute Breathlessness (Sudden onset - hours to days)

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Chronic / Progressive Breathlessness (Weeks to months)

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Recurrent / Episodic Breathlessness

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By Body System

Lung Causes

• Asthma
• COPD
• Pneumonia
• Pulmonary embolism
• Interstitial lung disease / Pulmonary fibrosis
• Pleural effusion
• Pneumothorax
• Pulmonary hypertension
• Lung cancer
• Bronchiectasis
• Hypersensitivity pneumonitis

Heart Causes

• Heart failure (left or right sided)
• Coronary artery disease / Angina
• Cardiomyopathy
• Arrhythmias (fast AF, SVT)
• Pericardial effusion / Cardiac tamponade
• Constrictive pericarditis
• Valvular heart disease (aortic stenosis, mitral regurgitation)

Blood Causes

• Anaemia (iron deficiency, B12/folate deficiency, haemolytic)
• Carbon monoxide poisoning
• Methaemoglobinaemia

Chest Wall / Neuromuscular Causes

• Kyphoscoliosis (curved spine compressing lung)
• Motor neurone disease (ALS)
• Myasthenia gravis
• Guillain-Barré syndrome
• Diaphragm paralysis

Other Causes

• Severe obesity (reduced lung expansion)
• Pregnancy (raised diaphragm + increased oxygen demand)
• Deconditioning / Low fitness
• Anxiety / Panic disorder / Hyperventilation syndrome
• Thyrotoxicosis (overactive thyroid - increased metabolic demand)
• Metabolic acidosis (e.g., diabetic ketoacidosis - Kussmaul breathing)
• Post-COVID breathlessness syndrome

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Key Questions That Help Identify the Cause

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Red Flag Signs (Seek Emergency Care Immediately)

• Breathlessness at rest
• Blue lips or fingertips (cyanosis)
• Chest pain alongside breathlessness
• Coughing up blood
• Breathlessness + swollen painful leg (possible clot/PE)
• Breathlessness + swollen face/tongue (anaphylaxis)
• Confusion or drowsiness with breathlessness
• Very rapid breathing rate (>25 breaths/minute)

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Breathlessness always warrants proper evaluation. Key investigations include: chest X-ray, ECG, blood tests (full blood count, D-dimer, BNP), spirometry, oxygen saturation (pulse oximetry), and sometimes echocardiogram or CT chest depending on suspected cause.

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Ulcerative Colitis (UC) - Detailed Prescription Guide

Two goals in UC treatment: (1) Induce remission - stop the active flare, and (2) Maintain remission - keep the disease quiet long-term.

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Classify First: Disease Severity & Location

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STEP 1 - First-Line: 5-Aminosalicylates (5-ASA / Mesalamine)

Oral Preparations

Always give Folic acid 5 mg/week with sulfasalazine as it interferes with folate absorption.

Topical Preparations (Rectal - Superior to oral for distal disease)

Topical mesalamine is superior to topical hydrocortisone for distal UC with response rates of 75-90%.

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STEP 2 - Corticosteroids (Moderate-to-Severe UC or 5-ASA failure)

Oral Steroids

• Prednisolone 40-60 mg/day orally - most common
  • Most patients respond within 10-14 days
  • Taper: reduce by 5 mg/week once responding
  • Do NOT use long-term for maintenance
• Budesonide MMX (Cortiment) 9 mg/day orally x 8 weeks
  • Targeted-release formulation; acts in colon, minimal systemic absorption (only 9-21% bioavailability)
  • Fewer steroid side effects than prednisolone
  • Taper: reduce to 6 mg for 2 weeks, then 3 mg for 2 weeks

IV Steroids (Severe/Hospitalised Patients)

• IV Hydrocortisone 100 mg every 6-8 hours OR
• IV Methylprednisolone 40-60 mg/day
  • Use for acute severe colitis requiring hospitalisation
  • If no response after 3-5 days → escalate to IV ciclosporin or infliximab (rescue therapy)

• Steroid-responsive: Improve and stay in remission as steroids taper ✓
• Steroid-dependent: Improve but relapse when dose tapered → needs immunomodulator
• Steroid-resistant: Do not improve despite high-dose steroids → needs biologic

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STEP 3 - Immunomodulators (For steroid-dependent or steroid-resistant UC)

Thiopurines (Most commonly used)

• Azathioprine 1.5-2.5 mg/kg/day orally - most used
• 6-Mercaptopurine (6-MP) 1.5-2.0 mg/kg/day orally
  • Both are essentially interchangeable (azathioprine is converted to 6-MP in the body)
  • Onset: 3-6 months (slow - combine with steroids short-term while waiting)
  • Check TPMT enzyme level before starting (genetic test) - patients with low/absent TPMT get severe bone marrow suppression at normal doses

Ciclosporin (Emergency use only)

• IV Ciclosporin (Cyclosporine) 2-4 mg/kg/day IV
  • Used as rescue therapy in acute severe UC not responding to IV steroids after 3-5 days
  • Prevents urgent colectomy in ~70-80% of patients short-term
  • Bridge to longer-term therapy with azathioprine

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STEP 4 - Biologic Therapies (Moderate-to-Severe UC failing immunomodulators)

TNF-Alpha Inhibitors (Most used biologics in UC)

Infliximab is preferred over adalimumab or golimumab for UC - better efficacy especially in severe disease. Infliximab often combined with azathioprine to prevent antibody formation.

Gut-Selective Biologic (Preferred in patients at higher infection risk)

• Vedolizumab (Entyvio) - anti-integrin (α4β7), gut-selective mechanism
  • Induction: 300 mg IV at weeks 0, 2, 6
  • Maintenance: 300 mg IV every 8 weeks OR 108 mg SC every 2 weeks
  • Preferred in: elderly, prior infections, prior malignancy, multiple comorbidities
  • Slower onset than infliximab but excellent safety profile (gut-selective = lower systemic infection risk)

IL-12/23 Inhibitor

• Ustekinumab (Stelara) - now approved for UC
  • Induction: single IV dose (weight-based: ~260-520 mg)
  • Maintenance: 90 mg SC every 8-12 weeks
  • Good safety profile; used as second-line biologic after anti-TNF failure

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STEP 5 - JAK Inhibitors (Oral targeted therapies for moderate-to-severe UC)

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STEP 6 - Acute Severe UC (In-Hospital Emergency Protocol)

1. IV Hydrocortisone 100 mg every 6 hours OR IV Methylprednisolone 60 mg/day
2. IV fluids + correct electrolytes
3. Thromboprophylaxis (UC patients have high clot risk) - Low-molecular-weight heparin (e.g., Enoxaparin)
4. VTE prophylaxis with compression stockings
5. Nutritional support
6. Daily abdominal X-ray to monitor for toxic megacolon
7. Surgical team involved early

• IV Ciclosporin 2 mg/kg/day, OR
• IV Infliximab 5 mg/kg (rescue therapy)

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Summary Treatment Ladder

Mild UC (Proctitis):
→ Mesalamine suppository/enema (topical)

Mild-Moderate UC (Extensive):
→ Oral Mesalamine (2.4-4.8 g/day)
→ Add topical mesalamine if not responding

Moderate UC (5-ASA failure):
→ Oral Prednisolone 40 mg/day (taper over weeks)
→ Add Azathioprine (steroid-sparing, long-term)
→ Or Budesonide MMX if tolerability concern

Moderate-Severe UC (Steroid-dependent/resistant):
→ Biologic: Infliximab or Vedolizumab
→ ± Azathioprine combined with infliximab

Severe UC (Hospital):
→ IV Steroids → if no response → IV Ciclosporin or Infliximab
→ Failure → Colectomy

Maintenance of Remission:
→ Continue 5-ASA (mesalamine) long-term
→ Continue biologic or immunomodulator as needed

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Key Points

• 5-ASA is the first-line for mild-to-moderate UC and also for long-term maintenance
• Steroids only for induction - never for long-term maintenance
• Topical > oral for distal/rectal disease
• Screen for TB + Hepatitis B before all biologics
• Check TPMT before azathioprine/6-MP
• Anti-TNF drugs (infliximab) + azathioprine together = more effective but higher lymphoma risk
• Vedolizumab = safer option for high-risk patients (gut-selective)
• Persistent severe UC not responding = surgical colectomy is curative

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