Core IBD therapies

Core foundational therapies like 5-ASA, prednisone, thiopurines, and methotrexate remain highly effective and are often the best choice depending on the individual case. While newer complex therapies for IBD, represent exciting advancements, these time-tested therapies have been rigorously studied and are supported by decades of robust evidence for their safety and efficacy.

Glucocorticosteroids

Glucocorticoids (GCs) are powerful anti-inflammatory and immunomodulatory agents used to treat many acute and chronic inflammatory diseases. GCs remain basic treatment for moderate-to-severe IBD, autoimmune liver disease, in addition to other digestive autoimmune conditions, but their use is limited by several important adverse drug effects. Topical administration of a second-generation of GCs, such as budesonide, represents a valid alternative to use of older, systemic GCs. Administration of second-generation GCs shows promisingly high topical activity and less systemic toxicity, but maintenance therapy with these new GCs is still associated with multiple adverse effects.

Prednisone/Prednisolone tablets: 1mg (100 +1), 5mg (60+4), 25mg (30+4)

Budesonide

3 commercial available formulations:

Entocort 3mg MR capsule 90+2 streamline 12607

Budenofalk 3mg enteric capsule 50x2+1 streamline 12607 or foam

Cortiment 9mg (MMX) prolonged release (NOT ON PBS) 30+1

Pharmacologic Profile & Formulations

Budesonide is a potent, locally acting glucocorticoid with high topical anti-inflammatory activity and extensive first-pass hepatic metabolism. This profile allows targeted mucosal therapy with lower systemic side effect burden compared to conventional corticosteroids like prednisone.

Bioavailability: ~10–15% (9-21% due to high hepatic extraction via CYP3A4)
Plasma half-life: ~3–5 hours
Metabolism: Hepatic CYP3A to inactive metabolites
Systemic exposure increases in patients with hepatic impairment or with CYP3A4 inhibitors (e.g. ketoconazole, grapefruit juice)

Enteric coated Formulations for ileocolonic delivery:

Formulation	Release pH	Anatomical Release	PK Profile
Entocort™ EC	~5.5	Proximal small intestine	Early release → fast peak (C<sub>max</sub>)
Budenofalk™	~6.4	Distal ileum → proximal colon	Delayed release → smoothed PK profile
Cortiment™ MMX	~7.0	Entire colon	pH-triggered release → delayed peak & sustained exposure

Compounded suspensions or opened capsules: allow proximal gut or oral mucosa contact
AUC values were comparable across formulations, confirming equivalent systemic exposure despite differing release patterns

Dose Equivalence and Side Effect Profile

A "dual equivalence" model is useful for therapeutic decision-making, and explaining why budesonide can be effective without the full burden of steroid toxicity:

budesonide 3mg ≈ prednisone 5mg of SE ≈ pred 40mg for topical effect

Based on pharmacodynamic comparisons:

0.375 mg/3mg budesonide ≈ 5 mg/40mg prednisone in terms of topical anti-inflammatory effect but with much lower systemic impact.

For systemic safety/side effects comparisons:

think of 3 mg budesonide ≈ 5 mg prednisone — a useful rule of thumb when planning long-term maintenance therapy
Inhaled budesonide ≠ oral budesonide in terms of systemic exposure. Inhaled: 30–40% systemic VS Oral (e.g. Entocort™): ~10–15% systemic: 3 mg inhaled budesonide can approximate 15–20 mg oral prednisone in systemic effect and side effects

Caveats: Budesonide is safer than prednisone, but not risk-free. In long-term use—particularly beyond 3 to 6 months—it is important to monitor for subtle adrenal suppression, mild Cushingoid features, and silent bone loss, especially in postmenopausal patients or those with prior corticosteroid exposure.

At doses ≤3 mg/day, systemic effects are rare and bone mineral density is typically preserved, though at-risk populations still warrant monitoring.
At 6–9 mg/day for more than 6–12 months, there is a low but real risk of biochemical adrenal suppression (reported in up to 25–30% of patients, usually subclinical), mild Cushingoid changes, weight gain, mood changes, acne and potential bone loss, though fracture risk remains low and not consistently demonstrated.
Individual sensitivity varies; patients with liver disease or those on CYP3A4 inhibitors may have increased systemic absorption and thus higher risk. While its low systemic bioavailability gives budesonide a favourable safety profile, clinical vigilance remains essential during prolonged therapy > 6 months.

Clinical Role Across GI and Hepatic Disorders

Condition	Formulation / Delivery Strategy
Oral cavity / Oesophagus (e.g. lichen planus, eosinophilic oesophagitis)	Compounded budesonide slurry (e.g. sucralose or Mylanta suspension)
Stomach / Duodenum (e.g. lymphocytic or collagenous gastritis, eosinophilic gastritis)	Opened capsule or compounded solution (liquid or paste) to ensure foregut contact
Jejunum / Ileum / Right colon (e.g. Crohn’s disease)	Entocort™ EC: Delayed-release capsules target terminal ileum and right colon
Entire colon (e.g. UC, microscopic colitis)	Budenofalk™ MMX or similar colonic-release budesonide
Liver (Autoimmune Hepatitis)	Entocort™ EC offers targeted portal delivery, used in non-cirrhotic AIH or when prednisone-sparing is needed
Mouth ulcers (off-label, contact slurry)	Compounded budesonide paste/swish-and-spit formulations

Evidence and Limitations

Crohn’s disease:
- 9 mg/day budesonide was as effective as 40–30 mg/day prednisone over 2–3 months in mild-to-moderate ileal CD
- Lower systemic AE rates (33% vs 55%)
Autoimmune Hepatitis:
- Budesonide induced complete biochemical remission more effectively than prednisone in non-cirrhotic AIH (Manns et al., Gastroenterology 2010) namely ALT/AST normal + IgG <ULN within 6 months. Remission = HAI of 0-3/18 on biopsy at 12 months treatment. Intolerance = any adverse event possibly related to potential discontinuation of the drug including hypertension, diabetes, osteoporotic fractures, psychosis, acne. Although in a Spanish 2023 cohort chosen for cases with less disease activity, budesonide achieved significantly lower complete biochemical response rates (49%, n=105) compared with prednisolone (87%, n=276). However, it can be considered as a first-line treatment option for AIH in patients with mild flare-ups (ALT/AST <2xULN) with biochemical response similar in both treatment groups. Also, prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%). Muratori et al. in Bologna found that 36 (54.5%) of 66 partial or non-responders experienced progression of liver disease despite GCS/AZAT/MP. Second-line therapies include MMF, tacrolimus, purine synthesis inhibitors (allopurinol/MP, 6-thioguanine), MTX.
Microscopic colitis:
- Multiple trials show 9 mg/day induces remission, and 3 mg/day may maintain it
Limitations:
- Not effective in more severe or fulminant disease
- Caution in cirrhosis due to increased systemic drug levels
- Compounding for foregut use is off-label and unregulated

Conclusion

Budesonide is a versatile corticosteroid with segment-specific application across the entire digestive tract and liver. Its favourable side effect profile, when used appropriately, offers a steroid-sparing option in selected patients. However, clinical judgment is essential, especially in longer courses >6 months, off-label gastric or oral use, and in patients with hepatic dysfunction or prior corticosteroid intolerance.

Topical enemas and suppositories

Colifoam: a foam enema supplied in an aerosol can filled with white, odourless, muco-adherent, expanding foam and fitted with gold ferrule and white nozzle. Plastic applicator with plunger included in the carton is used to administer COLIFOAM into the rectum. One aerosol can contains 21.1 g foam, equivalent to approximately 14 applications. Each applicator full of COLIFOAM contains approximately 90-100mg hydrocortisone

Predsol Enema: prednisolone (as sodium phosphate) 20 mg/100 mL enema, 7 x 100 mL - 28 (4x7) +3

Predsol suppository prednisolone 5mg PR 10x3+3

Aminosalicylate (5ASA, mesalazine)

Oral: 5ASA (Pentasa, Salofalk 1g 60*2 =120+5), (Mezavant 1.2g 60*4 ie. 240+5), (Asacol 1.6g 60*=120+4)

Sulfasalazine (SALAZOPYRIN): Standard tablets 500 mg Yellow-orange, round, scored tablets; marked with `KPh' on the one side and `101' on the other side. These tablets are supplied in bottles of 100 tablets. SALAZOPYRIN EN-TABS 500 mg Yellow-orange, elliptical convex, enteric coated tablets; marked with `KPh' on the one side and `102' on the other side. Both are supplied in bottles of 100 tablets. When starting sulfasalazine, start by taking 1 tablet once a day for 3 days, then 1 tablet twice a day for 3 days, then increase to 2 tablets twice a day thereafter up to 4-8 twice a day

Mezavant tablets: are packed in polyamide/aluminium/PVC foil blister packs with aluminium pushthrough foil. Pack size 60 or 120 tablets. Not all sizes may be marketed. The tablets are presented as red-brown, ellipsoidal, film-coated tablets, debossed on one side with S476

Pentasa:

Salofalk foam enema: available in an aluminium pressurised container with a metering valve containing 80 g of foam and 14 disposable applicators for the administration of the foam. The disposable unit consists of an applicator tip protected by a polyethylene cover and lubricated with white petrolatum. The unit has a one-way valve to prevent back flow of the dispensed product. Each can contains sufficient foam for 14 applications (equivalent to 7 doses of 2 g mesalazine). SALOFALK foam is presented as a white greyish to slightly reddish violet, creamy firm foam

Salofalk enema: one enema bottle contains either 2 g/60 mL or 4 g/60 mL.

SALOFALK suppository (30+1): light beige coloured, torpedo-shaped suppositories in white plastic strip packs, contains 1 g mesalazine

Pentasa Enema: supplied in packs of 7 plastic bottles. Each bottle is protected by an aluminium foil bag

Pentasa suppository: (28+1)

Thiopurines

Methotrexate (Crohn's)

Methotrexate

Methotrexate is an immune-modifying medicine used to treat Crohn’s disease. It can reduce inflammation, help maintain remission and reduce the need for corticosteroids such as prednisolone.

Most people tolerate low-dose methotrexate well, and regular blood tests help us make sure treatment remains safe.

The main thing to remember: methotrexate is taken ONCE A WEEK — never every day.

Why use methotrexate?

Methotrexate helps settle the inappropriate immune activity that causes inflammation in Crohn’s disease.

It may:

reduce diarrhoea, bleeding and abdominal pain
help control inflammation and allow the bowel to heal
maintain remission
reduce the need for corticosteroids
help some inflammatory joint symptoms associated with Crohn’s disease.

Methotrexate may also sometimes be used together with a biologic, particularly an anti-TNF medicine, where it can reduce the formation of antibodies against the biologic.

The doses used for Crohn’s disease are much lower than the high doses of methotrexate sometimes used to treat cancer.

How long until I feel better?

Methotrexate works gradually.

Some people notice improvement within 4–8 weeks, although it commonly takes around 6–12 weeks to judge its effect properly.

We will follow how you are feeling and, where appropriate, blood tests, stool tests or other measures of bowel inflammation to make sure it is working.

What dose will I take?

Methotrexate is taken once a week, either:

as an injection under the skin (subcutaneous methotrexate), or
as tablets.

For active Crohn’s disease, we commonly start with an injection because absorption is more reliable. A frequently used starting dose is 25 mg once weekly, although your individual dose may differ.

Once Crohn’s disease is well controlled, some patients use a lower maintenance dose, commonly around 15 mg once weekly.

Your prescription will tell you exactly how much to take.

The important safety rule

Methotrexate is taken once a week, not once a day.

Choose one regular day of the week and make this your methotrexate day.

If you are ever unsure when or how much to take, check with your pharmacist, GP or gastroenterology team before taking another dose.

Injection or tablets?

For Crohn’s disease we often begin with subcutaneous methotrexate because absorption is more predictable, particularly at higher doses.

The injection goes into the fatty layer under the skin of the abdomen or thigh. Most people find this straightforward once shown how to do it, and either you or a family member can usually give it at home.

How to self-inject methotrexate – Arthritis Australia

Can I change from injections to tablets?

Yes. Once Crohn’s disease is well controlled, some people prefer tablets for convenience.

At higher oral doses, above 15mg tablets, methotrexate may not be absorbed quite as reliably when the whole dose is taken as tablets at once. In selected patients who have already responded well to injections, we may therefore prescribe the weekly tablet dose in two portions 8-12 hours apart on the same day.

For example, part may be taken in the morning and the remainder later that day.

This is still one weekly treatment.

Only split your tablets if your doctor has specifically asked you to do so. If Crohn’s disease becomes less well controlled after changing to tablets, we can simply reconsider the dose or return to injections.

Why do I take folic acid?

Folic acid (vitamin B9) helps reduce some of the side effects of methotrexate, particularly nausea, mouth ulcers and tiredness.

Your prescription will tell you how much folic acid to take and on which days.

A common regimen in our practice is two folic acid 5 mg "sandwiched" on the day before and the day after the methotrexate, but your individual instructions may differ.

eg. Friday: Folate 5mg x 2

Saturday: Methotrexate

Sundday: Folate 5mg x 2

What if I forget my methotrexate?

If you remember within a day or two of your usual day, it can generally be taken then.

If you are several days late:

do not double your dose
do not take two doses close together to catch up
check with your pharmacist, GP or gastroenterology team if you are unsure.

Missing an occasional dose is unlikely to cause harm, but taking too much methotrexate can be dangerous.

What side effects can occur?

Most people taking low-dose methotrexate do not develop serious problems.

The more common side effects are usually mild and often improve with time.

These can include:

nausea or reduced appetite
feeling tired, heavy or a little “foggy”, particularly the following day
mild stomach upset or diarrhoea
mouth ulcers
headache
mild hair thinning
increased sensitivity to sunlight
mild changes in liver blood tests.

Taking methotrexate in the evening or with food can sometimes reduce nausea. Folic acid also helps.

If side effects are troublesome, please let us know. Often we can improve them by adjusting the dose, timing or way the methotrexate is given rather than having to stop treatment.

Blood-test monitoring

Regular blood tests are an important part of using methotrexate safely.

They usually include:

full blood count
liver function
kidney function.

Tests are more frequent when treatment is first started or the dose changes. Once everything is stable, they are usually needed much less often.

The purpose of these tests is to pick up changes early, before they cause problems.

What if I get sick?

Methotrexate slightly reduces some immune-system activity, but most people continue their usual work, school, travel and social activities normally.

If you develop a significant infection or fever and are unwell enough that you would normally change your plans for the day, it is reasonable to miss that week’s methotrexate until you have recovered.

If you are unsure, contact your GP or gastroenterology team.

A few uncommon problems to know about

Serious side effects are uncommon, but it is useful to know what to look out for.

Please seek medical advice if you develop:

a persistent high fever or significant infection
severe or persistent mouth ulcers
unexplained bruising or bleeding
yellowing of the skin or eyes
a widespread or severe rash.

New cough or breathlessness

Methotrexate can rarely cause inflammation in the lungs.

If you develop a new unexplained dry cough or shortness of breath, do not take another dose until you have sought medical advice.

This complication is unusual, but we mention it because it is important to recognise if it occurs.

Other medicines

Tell doctors, dentists and pharmacists that you take methotrexate.

Most commonly used medicines can still be taken, but there are a few important interactions.

Trimethoprim

Trimethoprim and trimethoprim/sulfamethoxazole can interact seriously with methotrexate.

Australian brands include:

Alprim
Bactrim
Resprim
Resprim Forte.

If another doctor is considering one of these antibiotics, make sure they know you take methotrexate so they can choose an appropriate alternative or advise you safely.

It is also sensible to check before starting new over-the-counter, herbal or naturopathic medicines.

Alcohol

Both alcohol and methotrexate can affect the liver.

You do not necessarily need to avoid alcohol completely, but it is sensible to keep alcohol intake low and avoid binge drinking.

If you have fatty liver, abnormal liver tests or other liver disease, discuss this with your doctor.

Vaccinations

Vaccination is encouraged while taking methotrexate.

In particular, keep routine vaccinations up to date, including:

influenza
COVID-19
pneumococcal vaccination
shingles vaccination where appropriate
HPV vaccination where appropriate.

Some live vaccines need individual consideration, particularly if you take other immune-modifying medicines as well. Check with your doctor before receiving a live vaccine.

Where possible, we review vaccination needs before starting treatment.

Chickenpox and shingles

If you have significant contact with someone with chickenpox or shingles and you have never had chickenpox or been vaccinated against it, contact your doctor for advice.

For most people who are already immune, ordinary contact does not require any special action.

Pregnancy

Methotrexate must not be taken during pregnancy because it can harm a developing baby.

If you could become pregnant, reliable contraception is needed while taking methotrexate.

If you would like to become pregnant, please talk with us first. We can plan when to stop methotrexate and make sure your Crohn’s disease remains well controlled on an appropriate alternative treatment.

If you unexpectedly become pregnant while taking methotrexate, stop methotrexate and contact your doctor promptly for specialist advice.

Planning to father a pregnancy

The evidence for men taking low-dose methotrexate around conception is much more reassuring than older advice suggested.

If you are planning to father a pregnancy, mention this to your gastroenterologist so we can discuss your individual situation.

Do not stop effective Crohn’s treatment without discussing it first.

Breastfeeding

Methotrexate is generally not recommended while breastfeeding.

If you are planning a pregnancy or breastfeeding, let us know early so treatment can be planned around you.

Looking after yourself

There are only a few things you really need to remember:

take methotrexate once weekly
take your folic acid as prescribed usually as a sandwich on day before and after
have your blood tests when requested
keep vaccinations up to date
keep alcohol intake modest
tell all healthcare professionals you take methotrexate
check before starting new medicines if you are unsure
let us know if side effects are troublesome.

Continue your usual Crohn’s disease monitoring even when you are feeling completely well.

When should I contact my doctor?

Please contact your gastroenterology team or GP if you:

develop a significant or persistent infection or fever
develop a new unexplained dry cough or shortness of breath
have severe or persistent mouth ulcers
notice unusual bruising or bleeding
develop jaundice
have side effects that are making treatment difficult
become pregnant or are planning pregnancy
are prescribed trimethoprim, Bactrim, Resprim or Alprim
would like to change from injections to tablets
are unsure how much methotrexate to take.

The bottom line

Methotrexate is a well-established treatment for Crohn’s disease. Most people tolerate low-dose treatment well, and regular blood tests allow us to identify problems early.

The main safety rule is simple:

Take methotrexate once a week — never every day.

If something does not feel right or you are unsure about your dose, contact your pharmacist, GP or gastroenterology team rather than trying to work it out yourself.

Further information

Reliable Australian information is available from:

Crohn’s & Colitis Australia
Gastroenterological Society of Australia (GESA)
Australian Rheumatology Association
Arthritis Australia

This information is general and does not replace individual medical advice. Your dose, route of administration, folic acid regimen and blood-test schedule may differ according to your individual circumstances.

PBS Complex Drugs Program for IBD

Inflammatory Bowel Disease (IBD) treatment has evolved to include a growing class of complex drugs, many of which target one of five key inflammatory pathways: anti-TNF agents, anti-integrins, IL-12/23 inhibitors, JAK inhibitors, and S1P receptor modulators. These therapies differ from traditional small molecules in their structure, mechanism, and site of action—often requiring advanced delivery systems or biologic manufacturing processes. While these drugs offer the promise of greater precision and efficacy, they also introduce new challenges in monitoring, sequencing, and managing long-term safety. This section explores each mechanism in practical terms, helping patients and clinicians navigate the expanding landscape of IBD therapeutics.

5 distinct mechanisms:

anti-TNF
- infliximab (IV:®Remicade, ®Inflectra, ®Renflexis; SC:®Remsima)
- adalimumab (®Humira, ®Abrilada, ®Amgevita, ®Hadlima,®Hyrimoz; ® Adaclip, ®Hadlima, ®Yuflyma)
- golimumab (®Simponi)
anti-adhesion: vedolizumab (®Entyvio)
anti-IL12/23: ustekinumab (®Stelara)
JAK inhibitors: upaticitinib (®Rinvoq), tofacitinib (®Xeljanz)
SIP inhibitors: etrasimod (®Velsipity), ozanimod (®Zeposia)

Biologics

anti-TNF: infliximab (IV®Remicade, ®Ixifi, ®Renflexis; SC ®Remsima)

Infliximab

Clinician prescribing reference. PBS restrictions and authority codes change — confirm the linked PBS item before prescribing.

Patients: this page is written for clinicians. Do not start, stop or change infliximab without discussing it with your treating team. Patient information ↓

Before starting infliximab

Check before the first dose:

No active serious infection or undrained abscess

TB: risk assessment + IGRA (± chest X-ray according to risk/local protocol)

Hepatitis B: HBsAg, anti-HBc and anti-HBs; consider HCV/HIV as appropriate

Baseline: FBC, UEC, LFT, CRP

Vaccinations: review immunisation and VZV status; give required live vaccines before immunosuppression where possible

Ask about heart failure, demyelinating disease, previous malignancy and recurrent/serious infection

Pregnancy/preconception: do not stop effective infliximab solely because of pregnancy; coordinate IBD and obstetric care. Infliximab crosses the placenta, so flag in-utero exposure to the infant’s treating team. In Australia, rotavirus vaccine is given on the routine schedule after in-utero infliximab exposure; BCG and other live vaccines are deferred until at least 6 months.

Do not commence infliximab during a serious active infection. Seek specialist advice with significant demyelinating disease or heart failure. Doses >5 mg/kg are contraindicated in moderate–severe (NYHA III–IV) heart failure.

Australian Immunisation Handbook — biologic exposure in utero

IV infliximab

Current Australian IV brands: Remicade®, Remsima®, Inflectra®, Renflexis® and Ixifi®. Brand availability varies between PBS items and indications.

TGA infliximab Product Information

Standard dosing

5 mg/kg IV at weeks 0, 2 and 6, then every 8 weeks.

Calculate the dose by weight and prescribe sufficient 100 mg vials to provide the calculated dose.

Round the number of vials required up — do not round the administered dose up to the next 100 mg.

Initial PBS treatment

Initial treatment for Crohn’s disease and moderate–severe UC is Authority Required. Use the current PBS restriction/application for the indication and request the quantity required for the patient’s weight and approved treatment course.

Do not rely on a memorised “5 vials + 2 repeats” rule in heavier patients — request the required quantity through the authority process.

PBS quick links — IV infliximab

Always click the item before prescribing. The number beside it is only a quick reference to the streamlined code currently displayed on that PBS page.

Indication Public hospital Private hospital

Acute severe UC (ASUC) 10067W · 4524 10057H · 9632

Complex refractory fistulising Crohn’s (FCD) 11423F · 19207 11432Q · 19150

Severe luminal Crohn’s (LCD) 11400B · 18819 11396T · 18868

Moderate–severe UC 11461F · 12042 11796W · 12074

For FCD, LCD and UC these are continuing-treatment items. ASUC has its own acute-severe restriction.

Brand availability differs by PBS item. Check the brands shown on the linked item rather than assuming the same authority code applies to every infliximab brand.

Acute severe ulcerative colitis

Infliximab is an established rescue treatment for appropriately selected IV steroid-refractory ASUC.

5 mg/kg remains the usual first dose.

PREDICT-UC found that an initial 10 mg/kg dose was not superior to 5 mg/kg, and standard, accelerated and intensified induction strategies did not significantly differ in clinical response, three-month remission or colectomy.

Routine accelerated/high-dose induction is therefore not required. Individualised intensification may still be considered in selected patients with severe inflammatory burden or rapid drug clearance.

PREDICT-UC trial

Remsima® SC

Infliximab 120 mg/mL pen

Dose: 120 mg SC every 2 weeks.

Starting infliximab with Remsima SC

Week 0: infliximab 5 mg/kg IV
Week 2: infliximab 5 mg/kg IV
Week 6: Remsima SC 120 mg
Then: 120 mg SC every 2 weeks

This is two IV loading doses followed by SC treatment, rather than completing the usual three-dose IV induction.

Switching from maintenance IV infliximab

Give the first Remsima SC dose 8 weeks after the last IV infusion, then 120 mg every 2 weeks.

PBS quick links — Remsima SC

Severe luminal Crohn’s disease

Initial SC supply:
12551N — Authority Required · 2 pens + 2 repeats

Continuing:
12560C — Streamlined 18869 · 2 pens + 5 repeats

Complex refractory fistulising Crohn’s disease

Initial SC supply:
13055D — Authority Required · 2 pens + 2 repeats

Continuing:
13060J — Streamlined 19110 · 2 pens + 5 repeats

Ulcerative colitis

Initial SC supply:
12575W — Authority Required · 2 pens + 2 repeats

Continuing / switching from IV:
12587L — Streamlined 17434 · 2 pens + 5 repeats

Dose optimisation and TDM

IV infliximab

Higher infliximab exposure is generally associated with better outcomes, but the concentration required depends on the disease phenotype, inflammatory burden and treatment target.

Reactive TDM

Check infliximab concentration ± anti-drug antibodies with:

primary non-response

secondary loss of response

recurrent inflammatory activity

unexpectedly high inflammatory burden or suspected rapid clearance.

Interpret the result with objective disease activity — CRP, faecal calprotectin, endoscopy and/or imaging as appropriate.

Low drug + active inflammation: usually optimise exposure by shortening the interval and/or increasing dose.

Adequate drug + active inflammation: consider mechanistic failure and changing treatment class.

Proactive TDM

Proactive TDM during IV infliximab maintenance is reasonable, particularly in patients at higher risk of rapid clearance or immunogenicity, although the evidence is not definitive.

Current evidence supports only a weak recommendation for proactive IV infliximab TDM during maintenance and does not support routine proactive TDM during induction.

Avoid treating a single numerical trough target as universal.

Clinical practice guideline on proactive biologic TDM

Perianal fistulising Crohn’s disease

Higher infliximab exposure is associated with a greater likelihood of fistula healing.

However, there is no universally validated infliximab concentration that guarantees fistula healing or closure.

Do not use cohort-derived thresholds such as 9, 12 or 18 µg/mL as absolute targets.

Management should integrate:

adequate infliximab exposure

control of luminal inflammation

drainage of abscesses

seton/surgical management where required

clinical examination and appropriate pelvic imaging.

High inflammatory burden may increase infliximab clearance and act as a pharmacological “sink”; interval shortening and/or dose escalation may therefore be required in selected patients.

Infliximab levels and perianal fistula healing

Remsima SC TDM

Do not apply IV infliximab trough targets directly to SC infliximab.

SC infliximab produces higher and much flatter serum concentrations across the two-week dosing interval.

Observational data suggest concentrations around 12–14 µg/mL are associated with clinical/biochemical remission, but this is not a validated universal therapeutic target, and higher exposure may be required for more stringent outcomes.

Because concentrations are relatively stable throughout the two-week dosing cycle, SC levels are less dependent on obtaining a true pre-dose “trough” than IV infliximab.

Use SC TDM particularly when there is:

loss of response

unexpectedly active disease

concern about adherence

suspected unusual pharmacokinetics.

Interpret the concentration in clinical context rather than escalating solely to reach a number.

SC infliximab concentration data — ENEIDA

Reducing anti-drug antibodies

Anti-drug antibodies can increase infliximab clearance, lower drug exposure, increase infusion-reaction risk and contribute to loss of response.

Combination therapy

For Crohn’s disease, ECCO 2024 recommends starting infliximab with a thiopurine and continuing infliximab + thiopurine combination therapy for a minimum of 6–12 months.

Once durable remission is established, withdrawal of the thiopurine can be considered individually, taking into account disease phenotype, previous immunogenicity, treatment targets and thiopurine risk.

Methotrexate can also reduce immunogenicity and may be considered when a thiopurine is unsuitable, although the evidence for combination efficacy is strongest for thiopurines.

ECCO 2024 Crohn’s medical treatment guideline

Maintain adequate exposure

Give induction and maintenance treatment on time

Avoid unnecessary treatment interruptions

Investigate objective inflammatory activity rather than repeatedly escalating treatment on symptoms alone

Use TDM when pharmacokinetic failure or immunogenicity is suspected.

If anti-drug antibodies develop

Interpret drug concentration + ADA + objective disease activity together.

Low drug + no/low ADA
→ optimise dose and/or shorten interval.

Low drug + detectable ADA
→ low-level antibodies may sometimes be overcome by improving exposure ± adding an immunomodulator; persistent high-level antibodies usually favour changing therapy.

Adequate drug + active inflammation
→ consider mechanistic failure and switch class.

ADA reported despite adequate circulating drug
→ interpret cautiously and consider repeating the assay if the result does not fit the clinical picture.

ADA titres are assay-specific. Do not use universal numerical definitions of “low” and “high” antibody titres.

Restarting infliximab after an interruption

A prolonged treatment interruption increases the risk of immunogenicity and infusion reactions.

Before restarting:

establish why treatment was stopped

confirm that infliximab remains the appropriate treatment

consider concomitant immunomodulation where appropriate

consider early infliximab/ADA testing after re-exposure, particularly if there has been a substantial drug holiday or previous immunogenicity.

Do not use a single fixed “restart recipe” for every patient.

Premedication may reduce some infusion symptoms but should not be relied upon to prevent anti-drug antibody formation.

Patient information and support

Patients should receive clear instruction on:

why infliximab is being used

IV versus SC administration

infection precautions

vaccination

what to do if unwell before an infusion/injection

pregnancy and infant vaccination where relevant

how and when treatment response will be assessed.

Remsima patient support

Local prescribing / compassionate-access logistics

Keep manufacturer and pharmacy logistics separate from the clinical prescribing guide because these arrangements may change independently of PBS prescribing rules.

Remsima / Celltrion

Celltrion professional portal

Local practice arrangement: route compassionate-access scripts and dispensing requirements through the relevant pharmacist/program.

Hard-copy PBS and compassionate-access scripts currently sent to:

Inservio HomeReply
Paid 91672
Frenchs Forest NSW 1640

Celltrion@inserviohome.com.au
1300 803 901

Confirm these program details before use if there has been any change in manufacturer or pharmacy arrangements.

Indication	Public hospital	Private hospital
Acute severe UC (ASUC)	10067W · 4524	10057H · 9632
Complex refractory fistulising Crohn’s (FCD)	11423F · 19207	11432Q · 19150
Severe luminal Crohn’s (LCD)	11400B · 18819	11396T · 18868
Moderate–severe UC	11461F · 12042	11796W · 12074

anti-TNF: adalimumab (®Humira, ®Abrilada, ®Amgevita, ®Hadlima,®Hyrimoz; ® Adaclip, ®Hadlima, ®Yuflyma)

Adalimumab (Pen vs Syringe, Citrate vs no-citrate)

Which to Choose?

Syringes: experienced users, less plastic waste, control of injection speed can reduce discomfort.
Pens: ease of use, consistency, or individuals new to self-injections with simple, one-button operation, concealing needle helpful if needle phobia
Citrate: prioritise stability or longer shelf life during extended travel, when refrigeration unreliable - 40mg/0.8ml ®Abrilada, ®Amgevita, ®Hadlima,®Hyrimoz)
Citrate-free: if experience significant pain or irritation with citrate-based options, need proper storage and handling particularly during travel - 80mg/0.8ml ®Humira, ®Yuflyma (induction only); 40mg/0.4ml ® Adaclip, ®Hadlima, ®Humira, ®Yuflyma

Induction: week 0 (160mg) week 2 (80mg); week 4, 6, 8, 10, 12, 14 (40mg)

PBS scripts x 2: ADA 80mg (3 +0) or 40mg (6 +0) then balance 40mg (2+2)

First continuing (40mg) week 0, 2; 4, 6; 8, 10; 12, 14; 16, 18; 20, 22

PBS script: ADA 40mg quantity 2+ repeats 5 (2+5)

Subsequent continuing

Biosimilar Streamline codes

citrate (40mg/0.8ml) FCD 11524 (2+5)/LCD 11631 (2+5)/UC (4+5), for these biosimilars (ITEM CODE: PEN 12353E/2D/34E, SYRINGE #12367X/437N/25Q ) - TDM 4.9=8ugmL LCD (+/->10 FCD)

citrate-free (40mg/0.4mL) FCD11524+13230H/LCD 11631+13225C/UC 16991+13211H (4+5)

Dose optimisation:

PBS: weekly ADA - UC (streamlined 4+5), CD (written 4+5); FCD PBS NOT AVAILABLE - need compassionate application

Celltrion (Yuflyma)

please post all hard copy Celltrion scripts (compassionate +/- pbs) to their Mandatory Pharmacist:

A: Inservio Home
Reply Paid 91672
Frenchs Forest NSW 1640
E: Celltrion@inserviohome.com.au
T: 1300 803 901

Abbvie (Humira)

Patient support programs:

Yuflyma

Potential targets (luminal Crohn's and UC):

Subtherapeutic < 4.9 ug/mL
Therapeutic 4.9 to 8.0 ug/mL
Supratherapeutic > 8.0 ug/mL

Notes

No “toxic” level is defined — “supratherapeutic” means above the range usually required.

Always interpret levels with antibody results and clinical context.

For fistulising disease, consistently higher drug exposure is needed compared to luminal disease:

Subtherapeutic: < 7–8 µg/mL (very unlikely to be effective for fistula healing).
Target/therapeutic: 10–15 µg/mL (associated with optimal fistula outcomes).
Above target: > 15 µg/mL — not clearly toxic, but if disease is controlled you might consider de-escalation, particularly if cost or safety is an issue.

If patient is well at a lower level (e.g. 3–4 μg/mL), escalation is not always required.

anti-TNF: golimumab (®Simponi)

Golimumab (Simponi): an anti-tumour necrosis factor (TNF) alpha treatment delivered through an under-the-skin injection monthly. The therapy is especially helpful for those who have to travel a long distance to receive infusions. It is pbs listed for ulcerative colitis not Crohn's.

Induction: 3 starter injections then every 4-week dosing

week 0 (2*100mg injections) then week 2 (1*100mg injection) then week 6, 10 (PBS: 100mg 3+0 and 1+1, with 12 week review)

Continuing 1+5 for week 0, 4, 8, 12, 16, 20

Anti-adhesion therapy: Vedolizumab (Entyvio)

Vedolizumab (Entyvio) – PBS Prescribing Guide

Updated August 2026 — incorporates Crohn’s PBS changes from 1 July 2026

Ulcerative Colitis (UC)

IV vedolizumab 300 mg

Public: 10384M
Private: 10398G
Initial 1: new patient
Initial 2: change/recommencement after biological medicine break <5 years
Initial 3: recommencement after biological medicine break ≥5 years
Continuing and balance of supply available

SC vedolizumab 108 mg/0.68 mL every 2 weeks

Initial: 12644L
Balance of supply: 12647P
Continuing / switch from IV to SC: 12639F

Crohn’s Disease (CD)

IV vedolizumab 300 mg

Public: 10390W
Private: 10415E

From 1 July 2026 Crohn’s uses the targeted-therapy treatment-cycle rules:

Initial 1: new patient
Initial 2: change/recommencement after targeted-therapy break <12 months
Initial 3: recommencement after targeted-therapy break ≥12 months
Continuing and balance of supply available
Eligible transition from non-PBS therapy commenced as a paediatric patient where applicable

Additional week-10 IV dose — Crohn’s only

If inadequate response after IV doses at weeks 0, 2 and 6:

Public: 14630B
Private: 14614E
Initial 4: additional vedolizumab 300 mg IV at week 10

SC vedolizumab 108 mg/0.68 mL every 2 weeks

Initial: 12638E
Balance of supply: 12620F
Continuing: 12654B

Chronic Pouchitis

IV vedolizumab 300 mg only

Public: 14670D
Private: 14679N
Initial 1: new patient
Initial 2: recommencement after a break in biological medicine
Balance of supply
Continuing

PBS SC vedolizumab is not listed for pouchitis.

Dosing and Switching

Standard IV induction — UC and Crohn’s

300 mg IV at weeks 0, 2 and 6
Standard IV maintenance: 300 mg every 8 weeks
Crohn’s: if inadequate early response, an additional PBS-funded 300 mg IV dose at week 10 may be given under Initial 4

SC maintenance

108 mg SC every 2 weeks
Requires at least 2 IV vedolizumab doses
First SC dose replaces the next scheduled IV dose

Practical initial SC scripts

After 2 IV doses at weeks 0 and 2

Start SC at week 6
SC weeks 6, 8, 10, 12, 14 and 16
Request 2 pens + 2 repeats

After 3 IV doses at weeks 0, 2 and 6

Start SC at week 14
SC weeks 14 and 16
Request 2 pens + 0 repeats

Crohn’s after 4 IV doses at weeks 0, 2, 6 and 10

Start SC at week 14
SC weeks 14 and 16
Request 2 pens + 0 repeats

Patients already established on IV maintenance may switch to SC by giving the first SC dose in place of the next scheduled IV infusion.

Continuing SC Script

2 pens + 5 repeats
Total 12 pens
Provides 24 weeks treatment

If fewer doses are supplied than required to complete the approved initial or continuing treatment period, use the appropriate balance-of-supply item.

Important PBS Change from 1 July 2026

Crohn’s:

Old 5-year biological-medicine treatment-cycle framework replaced by the targeted-therapy / 12-month framework:

break <12 months → Initial 2
break ≥12 months → Initial 3 / new treatment-cycle criteria

Ulcerative colitis:

Remains under the biological-medicine / 5-year treatment-cycle framework.

Quick Code Check

	UC	Crohn’s
IV public	10384M	10390W
IV private	10398G	10415E
SC initial	12644L	12638E
SC balance	12647P	12620F
SC continuing	12639F	12654B
Week-10 IV	—	14630B / 14614E
Pouchitis IV	14670D / 14679N	—

Always confirm the live PBS restriction when prescribing, particularly treatment-cycle eligibility, response-assessment and authority requirements.

Dose optimisation:

Entyvio (Vedolizumab)

Patient support programs:

Entyvio

anti-IL12/23: ustekinumab (®Stelara, ®Steqeyma)

Ustekinumab (®Stelara, ®Steqeyma) PBS Prescribing Guide

Mechanism:
Monoclonal antibody targeting the p40 subunit shared by interleukin-12 and interleukin-23, modulating immune responses involved in IBD.

PBS Notes:
- Authority required for both initial and continuing use
- Balance of supply (BOS) available when transitioning phases
- Dose based on clinical response, tolerability, and safety profile
Ustekinumab (®Stelara or ®Steqeyma) is a human IgG1κ monoclonal antibody that binds to a subunit and inhibits the biological activity of the proinflammatory cytokines interleukin IL-12 and IL-23, which are involved in the pathophysiology of Crohn’s disease and ulcerative colitis. It is administered as a one time intravenous, induction tiered dose (260–520 mg) based on body weight (ustekinumab 130 mg/26 mL injection, 26 mL vial)

≤55 kg: 260 mg IV (2 vials)
>55 kg to 85 kg: 390 mg IV (3 vials)
>85 kg: 520 mg IV (4 vials)

It takes at least 1 hour to receive the full dose of medicine. After the one-time IV infusion, ustekinumab (brands: ®Stelara or ®Steqeyma) is given as an 90mg injection under the skin (as one 90mg in 1mL syringe OR two 45mg in 0.5 mL vials or syringe) every 8 (4-12) weeks. The doctor may give in rooms, or if the patient or a caregiver is trained, they may give injections at home. Patients are typically review at week 12 of the first infusion when it is decided whether to continue the every 8-12 week program. There are 3 injection days during the first subsequent treatment cycle over 6 months of treatment. Each 6 month treatment cycle requires a formal assessment. For example if ustekinumab works successfully you can expect

Induction: week 0 infusion via IV cannula (2-3+0) THEN week 8 subcut injection (2+0 OR 1+0) THEN review at 12 weeks THEN

first continuation subcut injection (2+2 OR 1+2) and subsequent continuing every 6 months

Dosing Summary:

Induction: Single weight based IV 5mg/mL infusion (260-520mg)

®Stelara/®Steqeyma 130 mg/26 mL (®Stl130v/®Stq130v)

≤55 kg: 260 mg (2 vials)
>55 kg to 85 kg: 390 mg (3 vials)
>85 kg: 520 mg (4 vials)

PLUS

8 week subcutaneous injection (90mg)

Maintenance: subcutaneous injection (90 mg) every 8 (4-12) weeks

®Steqeyma/®Stelara 90mg/1 mL syringes (®Stq90s/®Stl90s),
®Steqeyma 45 mg/0.5mL syringe (®Stq45s)
®Stelara 45 mg/0.mL vial (®Stl45v)

initial
- ®Stq130v/®Stl130v private 13255P, public 13272M
- ®Stq90s/®Stl90s: 1+0 13273N
continuing/BOS/telephone first continuing
- ®Stq90s/®Stl90s: 1+1 13261Y
- ®Stq90s/®Stl90s: 1+2 13261Y
Streamline subsequent continuing (q12wk only)
- ®Stq90s: 16945 1+2 14918E

initial infusion
- ®Stq130v/®Stl130v private 11164N , public 11182M
initial/first continuing/BOS:
- ®Stq90s 1+0 14934B
- ®Stq45s 2+0 14898D
- ®Stl45v 2+0 11178H
Streamline subsequent continuing 16913:
- ®Stq45s 2+2 14909Q
- ®Stq90s 1+2 14926N

FCD

initial
- ®Stq130v/®Stl130v private 13804M public 13781H
- ®Stq90s/®Stl90s 1+0 13805N
continuing/BOS/telephone subsequent continuing
- ®Stq90s/®Stl90s 1+1 13789R
- ®Stq90s/®Stl90s 1+2 13789R
Streamline subsequent continuing 16909
- ®Stq90s 1+1 14907N

------------------------------------------------------------------

Dose optimisation

Stelara® (ustekinumab) — Janssen

Janssen Pro – Stelara

Mandatory dispensing pharmacy: JustMeds

Contact

Phone: 02 5850 0794
Phone: 07 2000 4124
After hours: 0488 032 247
SMS: +61 485 866 011
Email: rx@justmeds.com.au

Email a copy of the prescription to:
rx@justmeds.com.au

Post the original prescription to:

JustMeds
PO Box 598
Mosman NSW 2088

SteQeyma® (ustekinumab) — Celltrion

SteQeyma – Celltrion

Mandatory dispensing pharmacy: Inservio Home

Contact

Phone: 1300 803 901
Email: Celltrion@inserviohome.com.au

Post all original prescriptions (PBS and compassionate supply) to:

Inservio Home
Reply Paid 91672
Frenchs Forest NSW 1640

Patient support programs:

This program gives patients the ability to have their medicine delivered to their home, and the option of receiving their IV infusion of STELARA at home (as well as in-home training for subsequent self-injection). They also provide education, starter kit, medical supplies, reminder service.

Stelara (password: StelaraIBD)

Small molecules

JAK inhibitors: upaticitinib (®Rinvoq), tofacitinib (®Xeljanz)

JAK inhibitors: Upadacitinib (Rinvoq) modified release tablets

Upadacitinib (Rinvoq) – PBS Prescribing Guide

Updated August 2026 — incorporates Crohn’s PBS changes from 1 July 2026

Mechanism

Selective, reversible JAK1 inhibitor. Upadacitinib inhibits signalling by multiple JAK-dependent inflammatory cytokines and is taken orally once daily.

Ulcerative Colitis (UC)

Induction — 45 mg once daily

13262B — 45 mg tablet, 28 + 3 repeats

45 mg once daily for 8 weeks
If inadequate therapeutic benefit at week 8, continue 45 mg daily for a further 8 weeks
Maximum induction period: 16 weeks
Cease if satisfactory clinical response has not been achieved by week 16

PBS initial treatment

Initial 1: new patient — untreated with biological medicine
Initial 2: change/recommencement after biological medicine break <5 years
Initial 3: recommencement after biological medicine break >5 years
Balance of supply available

Practical pearl: direct change from vedolizumab or another PBS biological therapy to Rinvoq is Initial 2 — a treatment break is not required.

Maintenance

15 mg once daily

13250J — 28 + 5 repeats

30 mg once daily

13249H — 28 + 5 repeats

Use the lowest effective maintenance dose.

30 mg may be considered for refractory, severe or extensive disease, or where 15 mg does not provide satisfactory control.

For patients ≥65 years, the recommended maintenance dose is 15 mg daily.

UC dose modification

For changing dose during established PBS-subsidised treatment:

13256Q — 15 mg, 28 + 1 repeat
13265E — 30 mg, 28 + 1 repeat

Crohn’s Disease (CD)

Initial induction — 45 mg once daily

13771T — 45 mg tablet, 28 + 2 repeats

45 mg once daily for 12 weeks

Extended induction — if inadequate benefit at week 12

13762H — 30 mg tablet, 28 + 2 repeats

30 mg once daily for a further 12 weeks
Covers weeks 12–24
Cease if there is no evidence of therapeutic benefit after 24 weeks total treatment

Do not continue 45 mg for the second 12 weeks — the extended-induction dose is 30 mg daily.

PBS treatment cycle — from 1 July 2026

Crohn’s now uses the targeted-therapy / 12-month treatment-cycle framework:

Initial 1: untreated with targeted therapy
Initial 2: change/recommencement after targeted-therapy break <12 months
Initial 3: recommencement after targeted-therapy break >12 months
Balance of supply available

A direct change from vedolizumab or another targeted therapy to Rinvoq is therefore Initial 2.

Maintenance

15 mg once daily

13768P — 28 + 5 repeats

30 mg once daily

13746L — 28 + 5 repeats

Use the lowest effective maintenance dose.

30 mg may be considered for refractory, severe or extensive disease, or inadequate response to 15 mg, provided the patient is not at increased VTE, cardiovascular or malignancy risk.

For patients ≥65 years, use 15 mg once daily for maintenance.

Review ongoing treatment every 3–6 months.

Quick Pre-Start Check

1. Confirm active IBD and exclude infection

Before attributing symptoms to active UC/CD:

CRP
Faecal calprotectin
If active diarrhoea/flare: C. difficile testing
Consider enteric stool PCR/culture depending on presentation, travel and exposures
Consider parasites where epidemiologically appropriate
CMV testing is not routine — consider endoscopy/biopsy in severe, steroid-refractory or otherwise suspicious colitis

Establishing CRP/FCP before treatment also gives a useful objective baseline for response.

2. Baseline blood tests

FBC + differential
EUC / creatinine / eGFR
LFT
Lipids
CRP
Consider HbA1c/glucose as part of cardiovascular-risk assessment

Do not start Rinvoq if:

ANC <1.0 × 10⁹/L
ALC <0.5 × 10⁹/L
Hb <80 g/L

3. Infection screen

IGRA / TB screen
HBsAg, anti-HBc, anti-HBs
HCV antibody ± HCV RNA if positive
HIV as part of usual pre-immunosuppression screening

Do not start with active TB or another active serious infection.

Positive/previous HBV is not automatically an exclusion, but requires assessment of reactivation risk and appropriate monitoring/prophylaxis.

4. Vaccinations

Ideally bring vaccinations up to date before starting, particularly:

Shingrix — 2 doses
Influenza
COVID-19
Pneumococcal vaccination according to immunocompromised schedule
Hepatitis B if non-immune and indicated
Other age/risk-appropriate vaccination

Shingrix

Adults becoming immunocompromised through JAK-inhibitor therapy should receive 2 doses of Shingrix, generally 1–2 months apart.

Ideally vaccinate before Rinvoq where disease activity allows, but Shingrix is non-live and treatment does not necessarily need to be delayed until both doses are completed.

VZV-IgG positivity or prior shingles is not a substitute for Shingrix.

Avoid live attenuated vaccines during or immediately before Rinvoq. If live vaccination such as varicella/MMR is genuinely required, arrange it before immunosuppression according to vaccination guidelines.

JAK Safety Check Before Prescribing

Specifically ask/document:

Age ≥65
Current or previous long-term smoking
Previous MI, stroke, peripheral arterial disease or other ASCVD
Other significant cardiovascular risk factors
Previous DVT/PE or arterial thrombosis
Major surgery or prolonged immobilisation
Combined hormonal contraception/HRT
Known thrombophilia
Current or previous malignancy
Significant skin-cancer risk/history
Recurrent or serious infections
Pregnancy/breastfeeding

For patients ≥65, long-term current/past smokers, patients with cardiovascular risk or malignancy risk, Rinvoq should generally be used only where there is no suitable treatment alternative.

Avoid Rinvoq where there is an increased thrombosis risk or significant VTE risk factors.

Periodic skin examination is sensible in patients at increased skin-cancer risk.

ECG?

Routine ECG is not required before Rinvoq.

Upadacitinib does not prolong QTc at therapeutic or supratherapeutic concentrations.

Do an ECG for the usual clinical reasons rather than because the patient is starting Rinvoq, for example:

palpitations or abnormal pulse
syncope/presyncope
suspected arrhythmia
cardiac/ischaemic symptoms
known significant cardiac disease where an ECG is otherwise clinically indicated
major electrolyte disturbance or another drug/condition independently requiring QT assessment

An ECG does not substitute for cardiovascular-risk assessment. Check BP, smoking, lipids, diabetes and established vascular disease.

VTE / DVT Prophylaxis

Do not routinely anticoagulate an outpatient simply because Rinvoq induction is 45 mg.

Hospitalised active IBD: pharmacological VTE prophylaxis should generally be given unless contraindicated
Severe ambulatory flare with additional VTE risk factors: individual thromboprophylaxis can be considered
Assess the patient's VTE risk carefully before choosing a JAK inhibitor

Pregnancy / Breastfeeding

Do not use during pregnancy
Pregnancy test before treatment where relevant
Effective contraception during treatment and for 4 weeks after the final dose
Do not use while breastfeeding

Renal / Hepatic Function and Drug Interactions

Renal impairment

eGFR ≥30 mL/min/1.73 m²

Standard UC/CD dosing may be used

eGFR <30 mL/min/1.73 m²

Induction: 30 mg once daily
Maintenance: 15 mg once daily

Rinvoq has not been adequately studied in end-stage renal disease / dialysis.

Hepatic impairment

Mild–moderate hepatic impairment: no dose adjustment required
Severe hepatic impairment (Child-Pugh C): Rinvoq is not recommended

Important interactions

Check for strong CYP3A4 inhibitors/inducers.

With a strong CYP3A4 inhibitor, the PI recommends for UC/CD:

Induction 30 mg daily
Maintenance 15 mg daily

Examples worth checking include potent azole antifungals and clarithromycin.

Strong CYP3A4 inducers such as rifampicin or phenytoin may reduce Rinvoq exposure and efficacy.

Avoid grapefruit/grapefruit juice.

Do not combine Rinvoq with another JAK inhibitor or intentionally use it concurrently with potent immunosuppressive/biological therapy.

Monitoring After Starting

Clinical response + CRP/FCP
FBC/differential and LFT periodically
Renal function as clinically appropriate
Lipids at 12 weeks, then according to lipid-management guidelines
Monitor for infection
Reassess cardiovascular, malignancy and VTE risk over time

Advise patients to seek urgent review for:

symptoms suggesting DVT/PE
serious infection
herpes zoster
sudden new visual disturbance — retinal vein occlusion has been reported with JAK inhibitors including upadacitinib

Choosing Rinvoq

Rinvoq can be particularly attractive where:

rapid oral therapy is preferred
there has been inadequate response to a previous advanced therapy such as vedolizumab
the patient prefers a once-daily tablet over injections/infusions
there is coexisting inflammatory disease that may also respond to upadacitinib, such as rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis or atopic dermatitis

Coexisting inflammatory disease may favour Rinvoq, but it should not automatically be described as “first-line rescue” — assess the individual benefit/risk profile and use indication-appropriate dosing.

Quick PBS Code Check

	UC	Crohn’s
45 mg initial	13262B — +3	13771T — +2
Extended induction	same 45 mg item to week 16	13762H — 30 mg +2
15 mg maintenance	13250J — +5	13768P — +5
30 mg maintenance	13249H — +5	13746L — +5
15 mg dose modification	13256Q — +1	—
30 mg dose modification	13265E — +1	—

Always confirm the live PBS restriction when prescribing, particularly treatment-cycle eligibility, authority and response-assessment requirements.

More information on upaticinib

and more here

SIP inhibitors: etrasimod (®Velsipity), ozanimod (®Zeposia)

S1P receptor modulators

etrasimod and ozanimod
work by reducing the movement of certain immune cells that contribute to inflammation in your gut (bind to S1P receptor on lymphocytes, the cel then internalises them, interfering with lymphocyte mobilisation and exit from draining lymph nodes in the tissue)
aiming to control symptoms and improve your quality of life
They are effective and well-studied, and your healthcare team will monitor your progress closely.
If you have any questions, feel free to ask.

etrasimod (Velsipidy®)

Velsipidy Checklist

ozanimod (Zeposia®)

Zeposia UC HCP Checklist

Zeposia PBS Codes

Zeposia UC Patient Booklet

Clinician's Guide to Ozanimod

Authority applications

Services Australia's PBS Complex Drugs Programs Inquiry Line: 1800 700 270 option 6 Monday to Friday, 8 am to 5 pm:

Indications:

Ulcerative colitis ( IFX-iv, GOL, OZAN, ETRA, TOFA, UPA, USTE, VEDO-iv/sc)

MAYO 6(or pM 6 RB2/SF2) on 3/12 5ASA+AZAT/6MP

Crohn's (ADA, IFX, UPA, USTE, VEDO)

CDAI 300 (or 220+>50cm SI) on 6/52+AZAT/6MP/MTX 3/12

Fisulising Crohn's disease (ADA, IFX-iv/sc, UST)

Chronic pouchitis (VEDO)

>1yr IPAA, mPDAI 5+endo 2

HPOS forms upload only needed for:

initial treatment (UC, CD, FCD, CP)
- CDAI must be with 1/12 of stopping system therapy (steroid or thiopurine or MTX)
- unless all 4 systemic therapies contraindicated
change or recommence (after <5 yr break) or stop (UC, CD, FCD)
first Crohn's (CD, FCD) continuing (all)
subsequent Crohn's (CD, FCD) continuing for non-biosimilar agents (eg. ®Remsima, UPA, ®Stelara, VEDO) OR weekly CD biosimilar 4+5

Streamlined approval available for:

subsequent continuing treatments with PBS-subsidised biosimilar brands after first continuing application approval (ie. infliximab, adalimumab, ustekinumab q12wk only)

Crohn's (6 months)
Fistulising Crohn's (6 months)
Ulcerative colitis - ASUC (wk 2, 6) + UC (6 months)+UC (6 months weekly ADA 4+5)

Phone/HPOS approval for:

UC - continuing treatment (non-biosimilars eg. ®Remicade, ®Humira, USTE, VEDO-IV/SC, ETRA, OZAN, GOL, TOFA, UPA)
CD - unlisted quantity and repeats (eg. weekly adalimumab or q8wk ®Steqyema) or ®Remicade
extended induction period - upadacitinib (8-16wks) or IV vedolizumab (14-24 wk) for Crohn's
balance of supply applications

Toxicity severity descriptors for prednisone, thiopurines, methotrexate need to be included on forms

Dose optimisation/compassionate access programs:

PBS: q8wk ustekinumab 1+2 phone (1+1 q12wk ®Steqyema streamlined); weekly ADA - UC (streamlined 4+5), CD (written 4+5), FCD (PBS NOT AVAILABLE, need compassionate)

Abbvie (Humira)

Celltrion [Yuflyma (adalimumab), Remsima SC (infliximab) and SteQeyma (ustekinumab)]

please post all hard copy Celltrion scripts (compassionate +/- pbs) to their Mandatory Pharmacist:

A: Inservio Home
Reply Paid 91672
Frenchs Forest NSW 1640
E: Celltrion@inserviohome.com.au
T: 1300 803 901

Janssen Pro (Remicade infliximab/Stelara ustekinumab)

Pfizer - Inflectra (infliximab)

Entyvio (Vedolizumab)

Patient support programs:

Remsima

Stelara (password: StelaraIBD)

Entyvio

Yuflyma

Viral hepatitis

Chronic hepatitis B infection

Entecavir 500mcg 60+5 authority code:

4993 (non-cirrhotic + HBVDNA > 2,000 IU/mL or 20,000/eAg + chronic liver injury on bx/LFT);

5036 (cirrhosis CTP A+ DNA detectable + if CTP B/C -ascites, variceal bleeding, encephalopathy, alb<30, Bil>30 discuss transplant unit

NSW Health 3 year consent form 100 co-payments

CLINICIAN / REGISTRAR REFERENCE — Drugs affecting DGBI symptoms. NOT for the public patient page. Doses omitted by design — use eTG / product information / local formulary. Availability reflects a Jan 2026 knowledge cutoff — confirm current TGA registration / PBS status. Self-contained: open in a browser, or drop into a login-restricted page. Prints cleanly (landscape). -->

Drugs affecting DGBI symptoms — clinician reference

Registrar / VMO reference. Not for the public patient page. Starting doses are titration guides only — confirm against eTG / product information / local formulary.

Corrections applied to the source table: “physostigmine” → pyridostigmine (oral, off-label slow-transit constipation / CIPO; also dysautonomia — see row); physostigmine is a CNS-penetrant agent for anticholinergic toxicity, not a gut prokinetic. Opioid entry expanded to include narcotic bowel syndrome / opioid-induced hyperalgesia, not just OIC. Agents not marketed in Australia removed (cisapride, tegaserod, mosapride, eluxadoline, lubiprostone, plecanatide, tenapanor, alosetron). IBS-specific therapeutics separated from general drug GI effects.

Start low, go slow — dosing principles

Neuromodulators: begin at the lowest dose, titrate every 1–2 weeks to the lowest effective dose. Warn that early effects (sedation, dry mouth, nausea) usually settle within 1–2 weeks; allow an adequate trial (~6–8 weeks at target dose) before judging response; frame explicitly as gut–brain dosing, not psychiatric dosing.
Fibre: introduce one fibre at a time, start low and increase gradually over weeks with adequate fluid. Too-rapid escalation causes bloating, gas and pain and is the main driver of early discontinuation.
Reassess tolerability and response before each escalation; stop if no benefit after an adequate trial.

Helps / therapeutic Worsens Bidirectional / dose-dependent

Gut–brain neuromodulators (central + peripheral)

Agent / class	Effect	Mechanism	Notes
Tricyclics — amitriptyline, nortriptyline, imipramine	Bidirectional	Central noradrenaline/5-HT reuptake inhibition dampens visceral afferent signalling and pain; peripheral antimuscarinic action slows transit.	First-line neuromodulator for DGBI pain, esp. IBS-D (constipating effect useful). Low gut–brain doses. Nortriptyline better tolerated (less anticholinergic/sedation).Dose: start 10 mg nocte; ↑ by 10 mg every 1–2 wk; usual 10–30 mg (max ~50–75 mg if tolerated/needed).
Duloxetine (SNRI)	Helps	NA/5-HT reuptake inhibition; descending inhibitory modulation of visceral pain.	Useful where pain + comorbid anxiety/depression; weight-neutral. Can worsen nausea early. Not constipating (option if TCA transit effect unwanted).Dose: start 30 mg mane; ↑ to 60 mg after 1–2 wk if needed.
Mirtazapine	Helps	5-HT3 and H1 antagonism; central appetite stimulation; antiemetic.	Targets nausea, early satiety, poor appetite/weight loss — functional dyspepsia (PDS), CNVS, rumination-adjacent presentations. Sedating (nocte).Dose: start 15 mg nocte; usual 15–30 mg (lower dose often more sedating).
Gabapentinoids — pregabalin, gabapentin	May help	α2δ voltage-gated Ca²⁺ channel binding on DRG neurons → reduced neurotransmitter release; lowers central/peripheral visceral hypersensitivity.	Adjunct for hypersensitivity/pain; some evidence in functional dyspepsia and rectal hypersensitivity. Sedation, misuse potential — note current prescribing scrutiny.Dose: pregabalin start 25–75 mg nocte, ↑ slowly to 150–300 mg/day divided; gabapentin start 100 mg nocte/TDS, ↑ to 300 mg TDS+.
SSRIs	Bidirectional	↑ synaptic 5-HT; 5-HT4-driven prokinesis can accelerate transit.	Less useful for pain than TCA/SNRI; may help constipation-predominant pictures or comorbid anxiety; can precipitate diarrhoea.Dose: standard antidepressant dosing (not sub-therapeutic) — e.g. sertraline 50 mg, citalopram 20 mg; titrate as usual.

Prokinetics / motility agents

Agent	Effect	Mechanism	Notes
Domperidone	Helps	Peripheral D2 antagonist; enhances antroduodenal motility and gastric emptying; antiemetic.	Gastroparesis / PDS. QT prolongation — dose/duration limits, caution with other QT drugs.
Metoclopramide	Helps	D2 antagonist + 5-HT4 agonist; central and peripheral; antiemetic.	Short-term only — extrapyramidal / tardive dyskinesia risk (max ~5 days per current advice).
Erythromycin (low-dose)	Helps	Motilin receptor agonist → strong gastric prokinesis.	Gastroparesis; tachyphylaxis with continued use. QT / interactions.
Prucalopride	Helps motility	Selective 5-HT4 agonist → cholinergic enteric stimulation; prokinetic throughout the gut (gastric, small-bowel and colonic transit), not colon-only.	Registered AU (Resotran) for chronic constipation / STC. Off-label for gastroparesis / upper-GI dysmotility — evidence for accelerated gastric emptying. Cardiac-safe vs older 5-HT4 agents.Dose: 2 mg once daily (1 mg if >65 yr or renal impairment).
Pyridostigmine	May help	Oral cholinesterase inhibitor → ↑ ACh at enteric and autonomic ganglionic synapses; promotes colonic transit and enhances autonomic (ganglionic) transmission.	Off-label for slow-transit constipation / CIPO. Also used in dysautonomia — neurogenic orthostatic hypotension and POTS. Consider where gastroparesis coexists with a POTS-like autonomic syndrome (dual gut + autonomic benefit). (Correct agent — not physostigmine.)Dose: 30–60 mg BD–TDS.

Bowel- and lumen-directed agents

Agent / class	Effect	Mechanism	Notes
Loperamide	Helps IBS-D	Peripherally restricted μ-opioid agonist; slows transit, ↑ sphincter tone; does not cross BBB.	Symptomatic IBS-D / urgency. No central analgesia, no dependence at usual doses.
Secretagogue — linaclotide	Helps IBS-C	Guanylate cyclase-C agonist → ↑ luminal fluid + accelerated transit; also ↓ visceral afferent firing (analgesic).	Available AU (Constella). Diarrhoea is main dose-limiter.
Ondansetron (5-HT3 antagonist)	Helps IBS-D	Blocks 5-HT3 on vagal/spinal afferents → slow colonic transit, ↓ visceral hypersensitivity.	Off-label for IBS-D; available AU.
Hyoscine butylbromide	Helps pain/spasm	Antimuscarinic — blocks peripheral M-receptors, ↓ cholinergic smooth-muscle stimulation.	Poorly absorbed orally; useful PRN for cramping. Anticholinergic cautions (glaucoma, obstructive uropathy, tachyarrhythmia).Dose: 10–20 mg up to TDS–QID PRN.
Mebeverine	Helps pain/spasm	Direct smooth-muscle antispasmodic; ion-channel effects on excitability rather than anticholinergic blockade. Exact mechanism not fully settled.	No anticholinergic burden — option where antimuscarinic effects unwanted.Dose: 135 mg TDS before meals (or 200 mg MR BD).
Peppermint oil (enteric-coated)	Helps pain/spasm	Direct smooth-muscle relaxation, predominantly ↓ Ca²⁺ influx; menthol TRP-channel effects may contribute.	Best RCT evidence of the antispasmodics for IBS pain. Enteric-coat to limit LOS relaxation / heartburn.Dose: 1 enteric-coated capsule (~0.2 mL / 187 mg) TDS before meals.
Iberogast (STW-5)	Modulatory	Multi-herb, multi-target. Bidirectional motility modulation (fundic relaxation + ↑ antral contractility), Ca²⁺-dependent antispasmodic action, and reduced visceral afferent sensitivity (TRPA1/TRPV1); experimental interactions at 5-HT3, 5-HT4, M3 and opioid receptors — not a specific agonist/antagonist at any one.	Used in FD and IBS. Rare idiosyncratic hepatotoxicity (DILI) — TGA/EMA safety actions; counsel re: hepatic warning signs, review if relevant symptoms. Current AU product is the 6-herb reformulation (greater celandine removed), but DILI reports persisted post-reformulation — don't present it as fully resolved. Most mechanistic data are from the older 9-herb STW-5.Dose: 20 drops TDS with meals.
Bile acid sequestrants — cholestyramine, colesevelam	Bidirectional	Bind excess colonic bile acids → ↓ secretory diarrhoea (BAD); overcorrection → constipation/bloating.	Consider BAD in IBS-D / post-cholecystectomy / terminal ileal disease. Colesevelam better tolerated.
Rifaximin	May help	Gut-restricted antibiotic; modulates luminal bacterial density/composition without systemic dysbiosis.	Off-label for IBS-D/bloating (AU registration is HE / travellers' diarrhoea). Cost/access relevant.
Broad-spectrum antibiotics	Worsens	Disrupt commensal diversity → pathobiont overgrowth, osmotic/secretory diarrhoea; post-infective DGBI risk.	Relevant history in new-onset IBS.

Fibre supplements

Soluble fibre is preferred in IBS; introduce one at a time, start low and titrate over weeks (see dosing principles above). Adequate fluid throughout.

Fibre	Effect	Type / mechanism	Notes & dosing
Psyllium (ispaghula)	Helps (regulator)	Soluble, highly viscous, poorly fermented — a stool regulator, not a one-way laxative. Gel-forming: softens/adds water to hard slow-transit stool and binds excess luminal water to thicken loose stool. Low gas (resists fermentation, unlike bran). Not a stimulant (cf. senna) or motility-slower (cf. loperamide).	Works in IBS-C and IBS-D, but strongest/most consistent trial evidence is in constipation. ACG IBS guideline: strong recommendation for psyllium, explicitly not wheat bran (ispaghula NNT ~6–7; a 2026 meta-analysis reported RR ~1.53 for response). Direct IBS-D data sparser — used on mechanistic (water-binding) rationale. Same titration regardless of subtype.Dose: start ~5 g OD–BD with fluid; titrate every 5–7 days; practical target ~10 g BD (20 g/day). Full titration & formulation note below.
Partially hydrolysed guar gum (PHGG)	Helps	Soluble, fermentable but low gas-forming; prebiotic; regulates transit bidirectionally.	Well tolerated; useful where psyllium bloats. Tasteless/dissolves — good adherence.Dose: start ~3–5 g/day; usual 5–10 g/day. Evidence-based: pelvic-radiation diarrhoea RCT used 10 g BD.
Carob powder (carob pod flour)	Helps diarrhoea	Soluble fibre + polyphenolic tannins; bulking/antidiarrhoeal; bile-acid/water binding proposed.	Evidence mainly infective and drug-induced (e.g. nintedanib) diarrhoea — low quality, uncontrolled. Use carob pod flour, not locust bean gum.Dose: 7 g mane; if still loose after ~3 days, 7 g BD (14 g/day).
Green banana flour (resistant starch)	Helps diarrhoea	Resistant starch; colonic fermentation → SCFAs (butyrate, propionate, acetate) → ↑ Na⁺/water absorption and improved mucosal barrier.	RCT / meta-analysis evidence in paediatric acute & persistent infectious diarrhoea (faster resolution). No adult or drug-induced-diarrhoea trials — adult dose extrapolated, not validated.Dose: 5–7 g/day (extrapolated).
Wheat bran (insoluble)	Often worsens IBS	Insoluble, poorly water-holding; accelerates transit but mechanically irritant.	Not recommended in IBS — frequently worsens bloating, distension and pain. Favour soluble fibre instead. Included for completeness/contrast.If used: start low; discontinue if symptoms worsen.

Psyllium — practical dosing, titration & formulation

Start: ~5 g (a level teaspoon of husk) once–twice daily in water, with meals and adequate fluid.
Titrate: increase every 5–7 days by effect and gas/bloating. AGA technical review — begin with two daily doses with fluid/meals, reassess after 7–10 days; counsel that there is no immediate laxative-like response and that gassiness usually settles after several days.
Target / ceiling: ~10 g BD (20 g/day). Dose-ranging in IBS found 20 g/day optimal — superior to 10 g/day, no added benefit at 30 g/day; the pivotal RCT used ispaghula 10 g BD. Trial range 6–30 g/day.
Subtype: no separate IBS-C vs IBS-D regimen — same soluble gel-former, titrated the same way; mechanism is bulking/water-binding, not laxative stimulation.
Tolerability: bloating and flatulence are dose-related and the main limiters; slow titration + consistent fluid reduce dropout. (Primary-care RCT: AEs ~74% psyllium vs ~66% placebo; ~1 in 5 discontinued bran — reinforcing psyllium, not bran.)
Formulation: essentially all pivotal efficacy data used husk powder mixed in water (basis of the ACG strong rec, NNT ~6–7); powder allows flexible titration but must be mixed fresh (gels on standing), texture the main downside. Capsules/wafers are not separately validated in IBS — better for the texture-averse, but many capsules are needed to reach target dose, limiting adherence. Choose by tolerability/adherence, not comparative efficacy.

FORMULATION HYPOTHESIS — NOT EVIDENCE-BASED

Combination fibre for chronic diarrhoea (untested as a formulation)

Green banana or carob flour 5–7 g + PHGG 3–5 g + psyllium 3–4 g once daily; titrate to BD by tolerance and response — do not start at BD.

Mechanistically complementary — a bulking/absorptive base (green banana resistant starch → SCFA-driven Na⁺/water absorption, or carob → soluble fibre + tannins, water/bile-acid binding), PHGG (viscosity + prebiotic, low gas), psyllium (water-holding/viscosity, stool-firming). The individual component doses sit at the cautious end of their studied ranges (see table); the combination has not been tested as a formulation and is not an established regimen. A titration hypothesis for consideration, not a recommendation.

Drugs that commonly worsen or modify DGBI symptoms

Agent / class	Effect	Mechanism	Notes
Opioids (systemic)	Worsens	Enteric μ-agonism suppresses peristalsis/secretion (OIC); chronic use → central sensitisation and opioid-induced hyperalgesia / narcotic bowel syndrome — paradoxically escalating abdominal pain.	Key DGBI teaching point: escalating opioids for functional pain is counterproductive. PAMORAs for OIC; structured withdrawal for narcotic bowel.
GLP-1 receptor agonists	Worsens	Vagally-mediated delay of gastric emptying → nausea, bloating, early satiety; can mimic/unmask gastroparesis.	Increasingly common. Ask specifically — dose-titration, hold peri-procedure (aspiration risk), symptom overlap with FD.
NSAIDs	Worsens	COX inhibition → ↓ mucosal prostaglandins; erosions, ulceration, strictures; small-bowel enteropathy.	Reconsider as symptom driver; also confounds “normal endoscopy” narratives.
Proton pump inhibitors	Worsens	Hypochlorhydria shifts small-bowel/colonic microbiota → SIBO/dysbiosis-driven bloating.	Deprescribe where indication weak; consider in bloating-predominant pictures.
Metformin	Worsens	↑ enterochromaffin 5-HT release, bile acid pool expansion, microbiota shift → diarrhoea.	XR formulation / titration mitigates. Common IBS-D confounder in T2DM.
Calcium channel blockers	Bidirectional	Systemic CCBs slow colonic smooth muscle (constipation); gut-selective antispasmodic agents ↓ spasm/pain.	Verapamil notably constipating.
Antihistamines / anticholinergics	Bidirectional	Anticholinergic burden slows transit (constipation); gut H1/mast-cell blockade (e.g. ebastine) may ↓ visceral hypersensitivity.	Mast-cell/H1 angle is an active research area in IBS.
Antacids & iron salts	Bidirectional	Mg²⁺ and iron poorly absorbed → osmotic diarrhoea; Al³⁺/Ca²⁺ salts slow motility → constipation.	Simple, reversible symptom drivers — review the OTC/supplement list.

Effect labels describe typical direction on DGBI symptoms, not licensed indications. Mechanism/effect columns reflect established pharmacology; availability and PBS status reflect a Jan 2026 cutoff and must be confirmed against current TGA/PBS. Doses omitted intentionally — see eTG / product information. Clinician reference only; not medical advice for patients.

Clinician-only resource. Keep this page behind genuine server-side/WordPress authentication. It is not patient information and should not be indexed publicly.

Gut-directed hypnotherapy for DGBI — clinician guide

Evidence, patient selection, mechanism, delivery and review. Evidence is strongest for IBS. Use alongside formal training, current guidelines and local referral pathways.

Clinical framing: GDH is a brain–gut behavioural therapy, not a test of whether symptoms are psychological. It should be offered as one mechanism-based option within appropriate medical assessment. A response does not prove a psychological cause, and non-response does not invalidate a DGBI diagnosis.

1. Where the evidence is strongest

IBS

Strongest evidence base. The supplied 2025 meta-analysis included 12 studies (1,158 participants). High-volume delivery (≥7 sessions and ≥5 hours contact) and group delivery showed significant improvement in global IBS symptoms; pain improvement was significant across five studies with low heterogeneity.

Other DGBI

Randomised evidence also exists for functional dyspepsia, with smaller studies in non-cardiac chest pain, functional abdominal pain and related disorders. Evidence for reflux/globus is substantially weaker and largely case-series level in the supplied summary.

Recent trials also support digital delivery, but the supplied 2026 three-arm trial found therapist-delivered GDH more effective than psychoeducation and did not establish non-inferiority of smartphone self-guided treatment versus in-person therapy.

2. What symptoms may change?

Do not frame GDH as an analgesic-only intervention. Published IBS data show improvement across symptom domains, including abdominal pain, bloating, bowel-habit dissatisfaction and quality-of-life interference. Effects are not clearly restricted by IBS subtype in the supplied predictor data.

3. Mechanistic model — useful, but avoid overclaiming

Peripheral / gut

Reported effects include changes in rectal sensory thresholds and colonic motility. These findings suggest that treatment effects are not confined to conscious pain appraisal.

Afferent / central

Functional imaging studies show changes in brain responses to rectal distension and in functional connectivity, consistent with altered processing of visceral afferent input.

Autonomic / efferent

Heart and respiratory-rate changes and motility effects are consistent with altered autonomic balance. The literature does not directly separate vagal from spinal contributions to treatment response.

Do not claim that GDH “activates the vagus nerve” or the cholinergic anti-inflammatory pathway as an established human mechanism. In the supplied evidence, vagal/CAP involvement remains biologically plausible but indirect. No human IBD trial directly demonstrated vagal efferent firing, α7 nicotinic receptor engagement or macrophage cytokine suppression as the causal chain.

4. Who might be considered?

IBS with persistent or burdensome symptoms despite reasonable first-line management.
Patients who prefer a non-pharmacological brain–gut treatment or want to reduce reliance on medication.
Patients with prominent visceral hypersensitivity, symptom-related fear/hypervigilance or fluctuating multi-domain symptoms where a brain–gut approach fits the clinical formulation.
Selected patients with functional dyspepsia or other DGBI where the evidence and local expertise justify a trial.

Hypnotisability should not be used as a screening requirement; the supplied predictor literature reports that it does not reliably predict outcome.

5. When broader psychological or psychiatric care may need priority

The supplied Rome/predictor summaries suggest that significant untreated depression, severe anxiety, active trauma-related instability or dissociative pathology may reduce engagement, increase dropout or make a broader psychological treatment more appropriate before gut-specific GDH. Prediction is imperfect and inconsistent across studies, so these factors should inform rather than automatically exclude.

Escalate for specialist mental-health assessment where there is active suicidality, psychosis, severe dissociation, unstable trauma symptoms or another condition that makes focused hypnotic work clinically inappropriate.

6. Delivery

Element	Practical clinician guidance
Format	Therapist-delivered individual or group GDH has the strongest established evidence. Digital/self-guided options can be useful but should not be assumed equivalent to therapist delivery.
Dose / course	Published protocols vary. The supplied evidence suggests more consistent effects with higher-volume courses (≥7 sessions and ≥5 hours contact); 6- versus 12-session courses may be individualised according to severity, comorbidity and response.
Content	Focused attention/relaxation plus gut-directed imagery and suggestions aimed at normalising sensation, motility and gut–brain signalling. Home practice is commonly used.
Framing	Explain the biological model first. Avoid “it is stress” language. Preserve diagnostic safety and patient autonomy.
Outcome review	Agree in advance which symptoms/functions matter, when to review, what would count as worthwhile benefit and when to stop.

7. What to measure

Primary symptom burden (e.g. IBS-SSS where appropriate).
Pain frequency/intensity if pain is a key target.
Bloating/distension, stool pattern/urgency or upper-GI symptoms according to phenotype.
Quality of life and functional interference.
Treatment burden, adherence/home practice and whether the patient considers the change worthwhile.

Use a pre-agreed review point rather than continuing indefinitely without evidence of benefit.

8. Durability

Long-term data are a strength of GDH. In the supplied Manchester follow-up, 81% of initial responders maintained improvement for up to six years. A 2025 nurse-administered follow-up reported broadly stable response rates through two years. These figures apply to responders/cohorts studied and should not be presented as a guaranteed individual outcome.

9. IBD: separate symptom treatment from disease control

GDH has been studied in ulcerative colitis, including a remission-maintenance RCT and small mechanistic studies showing changes in inflammatory mediators. However, the supplied evidence does not establish a direct vagal/CAP mechanism and is not sufficient to position GDH as a replacement for evidence-based anti-inflammatory therapy.

In IBD, use GDH—if used at all—as an adjunct for symptom burden, coping or selected remission-maintenance contexts, while objectively monitoring inflammatory disease according to standard care.

10. Common questions for clinicians

Does a response mean the symptoms were psychological?

No. Improvement after a brain–gut behavioural therapy is compatible with modulation of physiological signalling at multiple levels. Treatment response does not determine aetiology.

Does the patient need to believe in hypnosis?

No. Engagement and willingness to practise matter, but the supplied evidence does not support using hypnotisability as a requirement for treatment.

Is GDH mainly a vagal therapy?

No. The supplied literature supports effects across peripheral, afferent, central and autonomic levels. Direct vagal-versus-spinal pathway attribution has not been demonstrated.

Can an app replace a trained therapist?

Not automatically. Digital GDH can be effective, but the supplied 2026 comparison did not establish non-inferiority to therapist-delivered GDH.

Selected references from the supplied evidence set

Adler EC, Levine EH, Ibarra AN, et al. Gut-Directed Hypnotherapy for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. Neurogastroenterology & Motility. 2025.
Miller V, Carruthers HR, Morris J, et al. Hypnotherapy for irritable bowel syndrome: an audit of one thousand adult patients. Aliment Pharmacol Ther. 2015.
Anderson EJ, Peters SL, Gibson PR, Halmos EP. Comparison of Digitally Delivered Gut-Directed Hypnotherapy Program With an Active Control for Irritable Bowel Syndrome. Am J Gastroenterol. 2025.
Snijkers JTW, Bosman MHMA, Winkens B, et al. In-Person Therapist-Delivered Hypnotherapy Versus Smartphone-Based Self-Guided Hypnotherapy in IBS: A Multicentre Three-Armed Randomised Controlled Trial. Gut. 2026.
Gonsalkorale WM, Miller V, Afzal A, Whorwell PJ. Long Term Benefits of Hypnotherapy for Irritable Bowel Syndrome. Gut. 2003.
Lövdahl J, Blomqvist-Storm M, Palsson OS, et al. Nurse-Administered Gut-Directed Hypnotherapy for Irritable Bowel Syndrome: A Two-Year Follow-Up Study. UEG Journal. 2025.
Keefer L, Ballou SK, Drossman DA, et al. A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology. 2022.
Vasant DH, Whorwell PJ. Gut-focused hypnotherapy for Functional Gastrointestinal Disorders: Evidence-base, practical aspects, and the Manchester Protocol. Neurogastroenterology & Motility. 2019.
Peters SL, Muir JG, Gibson PR. Review article: gut-directed hypnotherapy in the management of irritable bowel syndrome and inflammatory bowel disease. Aliment Pharmacol Ther. 2015.

Clinician reference only. The supplied evidence set contains heterogeneous trials, audits and reviews; treatment protocols and patient-selection rules are not fully standardised. Confirm current evidence, contraindications and local professional requirements before implementing GDH clinically.

Gastro-oesophageal Reflux Disease (GORD)

Pathophysiology of GORD

LES Incompetence
Impaired Oesophageal Mucosal Resistance
Decreased Oesophageal Clearance

TLESR Criteria (on Manometry)

Swallow-induced LES pressure declines >3mmHg to <2mmHg above intragastric pressure for >5s post-swallow
OR
LES relaxations >10s

1. Proton Pump Inhibitors (PPIs)

Pantoprazole, Omeprazole, Lansoprazole, Rabeprazole, Esomeprazole
Best for patients with overlapping dyspepsia and gastro-oesophageal reflux disease (GORD).
Long-term use should be monitored due to potential side effects (e.g., osteoporosis, microbiome changes).

2. H2 Receptor Antagonists (H2As)

Famotidine, Cimetidine, Ranitidine (withdrawn in some markets due to safety concerns), Nizatidine

3. Lower Oesophageal Sphincter (LES) Relaxants

Nitrates
Calcium Channel Blockers (Nifedipine, Amlodipine)

4. GABA(B) Agonist: Baclofen

Short-term trials suggest reduces transient LES relaxations (TLESRs), increases LOS pressure, reduces reflux episodes, and improves reflux-related symptoms.
Also increases gastric emptying.
Side effects: Drowsiness, dizziness—monitor while on therapy.

5. Neuromodulation

Tricyclic Antidepressants (TCAs): Amitriptyline, Nortriptyline (Nortriptyline preferred if drowsiness is a concern).

Prokinetics: An Overview

Prokinetic agents are medications designed to enhance gastrointestinal motility by accelerating gastric emptying. However, the relationship between their physiological effects and symptom relief remains complex. This document explores the challenges and considerations in prokinetic therapy, available treatment options, and the evolving approach to managing motility disorders.

Challenges in Prokinetic Therapy

Symptom Response vs. Gastric Emptying

There is limited correlation between the acceleration of gastric emptying and symptom relief, suggesting that factors beyond measurable gastric motility play a role in patient outcomes.

Multiple Contributing Factors

Symptoms in conditions like gastroparesis, functional dyspepsia, and irritable bowel syndrome (IBS) are influenced by complex mechanisms beyond gastric emptying alone.

Safety Concerns with Prokinetics

Effective but non-selective agents have been abandoned due to intolerable side effects:

Cholinergics: Caused significant bladder spasms.
Cisapride: Linked to cardiac arrhythmias (Torsades de Pointes, ventricular tachycardia), leading to its withdrawal.
Tegaserod: Raised concerns regarding cardiac safety.

Drug Development Constraints

A strict "safety-first" policy for non-life-threatening conditions limits the development of new drugs for debilitating motility disorders such as gastroparesis and intestinal pseudo-obstruction.

Potential Benefits of Multi-Targeted ("Dirty") Drugs

While highly selective agents are preferred to minimize adverse effects, some multi-target drugs may provide enhanced symptom relief:

5-HT4 agonist & 5-HT3 antagonist combinations: May be beneficial in IBS.
Linaclotide: Primarily a pro-secretory agent, but also has unexpected pain-relieving effects in constipation-predominant IBS.
Prucalopride: A highly selective 5-HT4 agonist with potential neuroprotective effects relevant to enteric neuropathic disorders.

QT Prolongation Risk Across Drug Classes

Many commonly used medications can prolong the QT interval, necessitating careful patient monitoring. These include:

Antihistamines: Diphenhydramine
Antidepressants: Amitriptyline, citalopram, mirtazapine
Antipsychotics: Haloperidol, quetiapine
Macrolide antibiotics: Erythromycin, azithromycin

Comprehensive Management Approach

Given the multifactorial nature of motility disorders, an integrative approach addressing nausea, pain, gastric function, and psychological health may improve outcomes.

Differential Diagnoses

Conditions that may mimic gastroparesis or other motility disorders include:

Peptic ulcer disease, gastric cancer, coeliac disease, abdominal angina.
Anastomotic ulcers, internal herniation, gallbladder disease (for early dumping syndrome).
Insulinoma or surreptitious use of glucose-lowering medications (for late dumping syndrome).

Prokinetic Agents and Related Therapies

Cholinergic Agents

Neostigmine (muscarinic M2 agonist) – Used in Ogilvie’s syndrome.
Pyridostigmine (Reversible acetylcholinesterase (AChE) inhibitor) – Used for pseudo-obstruction.

Dopamine Antagonists

Metoclopramide (DA, 5-HT3/4 antagonist, mild anticholinesterase activity) – Side effects: fatigue, sleepiness, depression, akathisia, anxiety, dyskinesia.
Domperidone (DA2 antagonist) – 10–20 mg QID; requires cardiac monitoring due to potential QT prolongation.

Serotonin Agonists

Mosapride (selective 5-HT4/3) – Minimal QT prolongation risk, common side effects include mild GI disturbances.
Prucalopride (highly selective 5-HT4 agonist) – Greater efficacy with minimal cardiac risks.
Mirtazapine (tetracyclic antidepressant, 5-HT1A/2A/3 antagonist) – May contribute to fundus relaxation, antiemetic, and anxiolytic effects.

Macrolide Antibiotics (Motilin Receptor Agonists)

Erythromycin (IV: 3 mg/kg every 8 hours; Oral: 250 mg TID) – Risk of tachyphylaxis; use at lower doses may prolong efficacy.
Azithromycin – Similar efficacy with less QT prolongation.

Other Treatments

Botulinum Toxin (Botox®) – Occasionally used for pyloric dysfunction.
Complementary Therapies – Ginger, peppermint, Iberogast, melatonin, and capsaicin may offer symptomatic relief in functional dyspepsia.
5-HT3 Antagonists – Ondansetron (4–8 mg TID PO, IV, PR), granisetron.
Phenothiazines – Prochlorperazine (Stemetil®) for nausea.
Antihistamines – Cyclizine, diphenhydramine, and cyproheptadine (Periactin™).
Neurokinin-1 Receptor Antagonists – Aprepitant (125 mg daily).
Anticholinergics – Scopolamine patch.
Benzodiazepines – Lorazepam (used in chemotherapy-related anticipatory nausea).
Itopride - D2 antagonist + acetylcholinesterase inhibitor (Used in Japan/Asia for PDS-type dyspepsia)
Cinitapride- 5-HT4 agonist + D2 antagonist - Used in Spain/India for functional dyspepsia & gastroparesis
Acotiamide- Acetylcholinesterase inhibition in the enteric nervous system → increases acetylcholine availability locally in the gastric wall - functional dyspepsia (PDS-subtype) - fullness, early satiety, meal-related discomfort, not so much epigastric burning (EPS subtype) -approved only in Japan and India for PDS-type functional dyspepsia

Conclusion

While prokinetic therapy plays a key role in managing gastrointestinal motility disorders, challenges remain due to limited symptom correlation, safety concerns, and regulatory constraints. A balanced approach, integrating pharmacologic and non-pharmacologic strategies, is essential for optimizing patient outcomes. Future research may identify novel agents that offer enhanced efficacy with improved safety profiles.

Abdominal/Chest Pain Modulation

Psychosocial Therapies
- Strongly indicated for severe pain, impaired quality of life (QOL), and mood/anxiety disorders.
- Options include:
  - Cognitive Behavioral Therapy (CBT): Proven to help in functional gastrointestinal disorders (FGIDs).
  - Gut-Directed Hypnotherapy: Effective for visceral hypersensitivity and functional dyspepsia (FD).
  - Biofeedback: Useful for stress-related GI symptoms.
  - Social Support: Social workers may assist in workplace/home/school adjustments.
Neuromodulators (for Visceral Hypersensitivity & Functional Dyspepsia)
- Tricyclic Antidepressants (TCAs): Amitriptyline, nortriptyline (helpful even at low doses).
- Mirtazapine: Particularly useful for nausea and weight loss.
- Gabapentinoids (Gabapentin, Pregabalin): Reduce visceral pain sensitivity, may be beneficial in patients with FD and early satiety.
Serotonin Antagonist
- Cyproheptadine: Particularly beneficial for postprandial distress syndrome (PDS) subtype, especially in younger patients with early satiety.
Proton Pump Inhibitors (PPIs)
- Pantoprazole, Omeprazole, Lansoprazole, Rabeprazole, Esomeprazole
- Best for patients with overlapping dyspepsia and gastro-oesophageal reflux disease (GERD).
- Long-term use should be monitored due to potential side effects (e.g., osteoporosis, microbiome changes)

Management of Abdominal Bloating

1. Antifoaming Agents & Surfactants

Simethicone: Alters gas bubble elasticity, facilitating gas passage.
Activated Charcoal: May help reduce gas formation and odour.

2. Prokinetics

Erythromycin (low-dose): Motilin agonist, accelerates gastric emptying.
Metoclopramide: Dopamine antagonist, enhances gastric motility (long-term use may cause tardive dyskinesia).

3. Antibiotics for Suspected Bacterial Overgrowth

Rifaximin: Poorly absorbed, highly effective against both aerobic and anaerobic bacteria in small intestinal bacterial overgrowth (SIBO).
Metronidazole (Flagyl®) and Trimethoprim/Sulfamethoxazole (Bactrim®): Alternative options if Rifaximin is unavailable or ineffective.

4. Probiotics

Bifidobacterium infantis (35624 strain):
- Demonstrated positive effects in randomized controlled trials (RCTs).
- Reduces intestinal inflammation and improves symptoms of pain, bloating, and bowel movement difficulties compared to placebo.
Other probiotic strains:
- Lactobacillus GG and Saccharomyces boulardii may also be beneficial in select cases.

5. Digestive Enzymes

Lactase: Useful for lactose intolerance.
Alpha-galactosidase (Beano): Helps break down fermentable carbohydrates to reduce bloating.
Pancreatic enzyme supplements: Beneficial in pancreatic insufficiency to aid digestion.

6. Aperients (Laxatives) for Constipation-Related Bloating

A. Laxatives Less Likely to Cause Bloating

Osmotic Laxative: Polyethylene Glycol (PEG/Miralax) → Softens stools with minimal bloating.
Bulk-Forming Laxative: Methylcellulose (Citrucel) → Non-fermentable, less likely to cause gas.
Stimulant Laxative: Senna (low dose) → Effective for short-term relief of constipation-related bloating.
Natural Option: Kiwi Fruit → Increases bowel movement frequency with low bloating risk.

B. Laxatives That May Worsen Bloating

Lactulose & Magnesium Hydroxide: Can cause gas and bloating due to fermentation.
Psyllium (Metamucil): Fermentable fiber, can increase bloating if not taken with sufficient water.
Prunes (Dried Plums): Contain sorbitol and fructans, which may cause bloating in some individuals.

7. Dietary Approaches

Low FODMAP Diet:
- Well-established for reducing bloating and IBS symptoms.
Elemental Diet (for severe SIBO cases):
- Reduces fermentation and supports gut healing.

8. Herbal & Alternative Therapies

Peppermint Oil (Enteric-Coated):
- Works as an antispasmodic, reduces bloating.
- Clinical trials show benefits in IBS and functional dyspepsia.
Iberogast (Combination of Herbal Extracts):
- Includes chamomile, peppermint, licorice root.
- Helps functional dyspepsia, bloating, and motility disorders.
Ginger Extract:
- Stimulates gastric emptying, reduces nausea and bloating.

Diet:

gastroparesis (Postprandial fullness, early satiety, bloating, abdominal distension, nausea, and vomiting, abdominal pain, and dysphagia): "fork mashable"foods (low particle size diet), Low fat, low fiber foods small frequent meals

anti-dumping diet if rapid GE (

Early dumping syndrome (within 1 h after meal ingestion
Gastrointestinal symptoms: Abdominal pain, epigastric fullness, diarrhea, nausea, vomiting, borborygmi, and bloating
Vasomotor symptoms: desire to lie down, palpitations and tachycardia, fatigue, faintness, syncope, perspiration, headache, light-headedness, hypotension, flushing, and pallor

Late dumping syndrome (1–3 h after meal ingestion)
Neuroglycopenia: fatigue, weakness, confusion, hunger and syncope
Autonomic reactivity: perspiration, palpitations, tremor and irritability

(20% of patients suffer from symptoms of dumping syndrome after vagotomy and pyloroplasty, 40% after Roux-en-Y bypass and sleeve gastrectomy, and peak at 50% after esophagectomy): Eat small, frequent meals at least 6 times a day; Lie down as soon as you finish eating. Avoid: simple sugars such as sweets,high sugar soft drinks, cakes, and cookies. Avoid foods that are very hot or very cold. . These can trigger dumping syndrome symptoms. Do not drink liquids with your meal. Instead, drink liquids at least a 30 minutes to an hour after eating solid food. Encourage high-fibre, high-protein food

Prunes. Dried plums (prunes) not only contain fiber but also sorbitol and fructans, non-absorbable carbohydrates that, when fermented by colonic bacteria, create an osmotic load that can dramatically alter stool frequency and consistency. In an 8-week single-blind, randomized study with 40 constipated subjects, the number of CSBMs per week and stool consistency scores improved significantly (P < 0.05) with prunes when compared to psyllium. Straining and global constipation symptoms did not differ significantly between treatments.⁸⁷

Kiwi. In a recent study from Asia, 41 IBS-C patients and 16 healthy adults consumed 2 Hayward green kiwifruits per day for 4 weeks. Another 13 IBS-C patients served as controls. IBS-C patients that consumed kiwi fruit had a significantly faster colonic transit time than controls (P = 0.026). The IBS-C kiwifruit group also reported increases in defecation frequency and improvements in bowel function

Safe prescription of drugs which prolong the QTc interval

Drug-induced QT_c prolongation is not a universal phenomenon. Why some individuals are susceptible to this condition and others are not, is still unclear. They may possibly have a subclinical genetic mutation that is only revealed when they are exposed to certain drugs. Before prescribing a drug that is known to cause QT_c prolongation, it is important to enquire about any past history of syncope or cardiac arrest. Also obtain a detailed family history of syncope, sudden death at a younger age or congenital deafness⁵ (a feature of Jervell and Lange-Nielsen syndrome). Any suspicion of a congenital long QT_c syndrome should be confirmed with a 12 lead ECG. If the ECG shows prolongation of the QT_c interval, drugs which could make it worse should be avoided.

Co-administration of two or more implicated drugs or an offending drug with a substance capable of inhibiting its hepatic metabolism should be avoided. It is important to question the patient about the consumption of non-prescription medications (such as terfenadine and astemizole) before prescribing a drug which can prolong the QT_c interval. An association with a medication that prolongs the QT_c interval should be sought in patients who present with syncope or cardiac arrest. Such a relationship should particularly be looked for in patients with no cardiac history or relevant family history.

When an implicated drug is prescribed to a high-risk patient (Table 1), it is advisable to perform a 12 lead ECG within the first few days of treatment to look for QT_c prolongation beyond normal limits. If QT_c prolongation is observed, it is advisable to stop the offending drug or switch to an alternative drug that has no such effect.