Topical enemas and suppositories

Glucocorticosteroids

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

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

Aminosalicylate (5ASA, mesalazine)

Oral: 5ASA (Pentasa, Salofalk 1g 120+5), (Mezavant 1.2g 120+5), (Asacol 1.6g +4)

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 enema 4 gUndefined

SALOFALK suppository: 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: (30+1)

Image result for pentasa suppositories

Biologicals

anti-TNF therapies

Infliximab (® Remicade, ®Inflectra, ®Renflexis) 100 mg for IV infusion is supplied as a lyophilised powder in individually-boxed single-use glass vials with rubber stoppers and aluminium crimps protected by plastic caps biosimilars (ITEM CODE: PEN 12353E/2D/34E//13225C, SYRINGE #12367X/437N/25Q ) -The evidence supports higher anti-TNF drug levels correlate with higher efficacy; however, no high quality, interventional data are available. Current PFCD target healing (drainage +-MRI)/closure rare TDM >9 50%,>12 90%, >18 95%. - Caveat: RCTs needed to prove this hypothesis and surgery (abscess drainage, seton placement, fistulectomy, fistulotomy, ligation, and advancement flaps) considered. lower IFX/ADA levels in failures may = higher inflammatory burden/drug clearance. cohort studies =low sample sizes, patient selection variability, failure to stratify fistulas different types, noobjective endpoints. PROACTIVE protocol: ≥25 µg/mL at week 2, ≥20 µg/mL at week 6 and ≥10 µg/mL during maintenance therapy.

optimal, individualized dosing strategy for PFCD need to factor in higher dosing sub-groups do not always have better outcomes with variability dependent on high body weight, low albumin, and presence of ATI, shortening interval more effective than increasing dose: ATLAS =  "mismatch in
serum and tissue drug levels in high inflammatory burden patients" - areas of severe luminal inflammation act as a ‘sink’ for  drug = diminished localised tissue drug levels = reduced concentration and, therefore, efficacy in another area of inflammation

Subcutaneous  infliximab (®Remsima) 120mg/mL PEN

  • luminal Crohn's not fistulising medicare program
  • must have 2 doses IV infliximab before balance (2 +2) or continuing (2 + 5) to 24 weeks

 

Adalimumab (®Humira)  induction 80mg (3 +0) or 40mg (6 +0) then balance to week 14 40mg (2+2) then continuing to last dose week 22 (2+5)

Adalimumab Biosimilars (40mg/0.8ml:®Amgevita, ®Hadlima, ®Hyrimoz, ®Idacio; 40mg/0.4ml Yuflyma) -Streamline only available ( FCD 11524/LCD 11631/UC 11579),   for these biosimilars (ITEM CODE: PEN 12353E/2D/34E//13225C, SYRINGE #12367X/437N/25Q ) - TDM 4.9=8ugmL LCD (+/->10 FCD)
Subtherapeutic < 4.9 ug/mL
Therapeutic 4.9 to 8.0 ug/mL
Supratherapeutic > 8.0 ug/mL

Phone: 1800 700 270 option 6

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

SIMPONI® Dosing: 4-week dosing after 3 starter injections

Starting SIMPONI®

SIMPONI® (golimumab) Dosing

2 injections on first day,
followed by 1 injection 2 weeks later

.Image result for golimumab australia syringe pen

Induction: 100mg  3+0 and 1+1,  with 12 week review. continuing 1+5anti-adhesion therapies

Vedolizumab (Entyvio):

Iintravenous: Powder for Injection is supplied as a sterile, white to off-white lyophilized cake or powder in a single-use vial. Each single-use vial contains 300 mg of vedolizumab. Each pack of ENTYVIO contains 1 glass vial

Subcutaneous: after minimum 2 IV doses - get the balance or switch at any time.  108mg/0.68mL PEN every 2 weekse

Initial: IV 2 doses wk 0, 2 then week -16 (6 pens) review 12 weeks = script IV 1+1 plus Pen 2+2 OR  if IV 3 dose (wk 0,2,6)  then  wk 14-16 PEN = script IV 1+2 then PEN 2+0

Switching IV to SCI during continuing - submit new CDAI/Mayo and get script 2+5 ie. 12 PENS for 26 weeks OR if not submitting new CDAI/MAYO you only get balance eg. after two IVI (week 0 and 8)  you switch, you get balance from week 16 -26 for 8 weeks only ie. PEN 2+2

Grandfathering - need initial form with past data proving eligibility PLUS continuing form showing remission PLUS cover letter.

anti IL12/23 therapy

Ustekinumab (Stelara):  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. 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
  • >55 kg to 85 kg: 390 mg IV
  • >85 kg: 520 mg IV

It takes at least 1 hour to receive the full dose of medicine. After the one-time IV infusion,  STELARA® is given as an 90mg injection under the skin (as two subcutaneous 45mg injections  in 0.5 mL vials) every 8 weeks. There are 6 injections during the first year of treatment. The doctor can administer at his or her office, or  decide if the patient or a caregiver may give injections at home.

Related imageImage result for stelara 90

induction  wk0 IV 2-4 +0 then wk 8 SCI 2 +0 - review at 12 weeks, then continuation 2+2

PBS forms:

Ulcerative colitis

Crohn's

Pharma Access Programs:

Abbvie Portal (Humira)

Celltrion Care (Remsima/Yuflyma)

Pharmacist and Customer Support: 07 2000 4124
JustMeds Pty Ltd: PO BOX 1070 Burleigh 4220

E: pharmacist@justmeds.com.au
www.Justmeds.com.au

Janssen Pro (Remicade/Stelara)

Pfizer access program - Inflectra

Organon -

EntyvioAccess (Vedolizumab)

patient support:

Takeda Pathway

 

 

Small molecules

Thiopurines: mercaptopurine, azathioprine, tioguanine

 

SIP inhibitors: ozanimod (ZEPOSIA)

Zeposia UC HCP Checklist

Zeposia PBS Codes

Zeposia UC Patient Booklet

Clinician's Guide to Ozanimod

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JAK inhibitors

 

 

5ASA Tablets

SASP/Mesalazine

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

 

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

 

Gastro-oesophageal

PPI, H2A

LES relaxants: nitrates, calcium antagonists (nifedipine, amlodipine)

GORD: LES incompetence, impaired oesophageal mucosa resistance, decreased esophageal clearance

GABAB agonist baclofen (short term trials: reduce TLESRs, increases LOS pressure, reflux episodes, and reflux-related symptoms, increase gsatric emptying). Side effects such as drowsiness and dizziness should be monitored while on baclofen therapy. (TLESR  on manometry: swallow LES pressure declines >3mmHg to <2 mmHg above intragastric pressure for >5s post  OR LES relaxations>10s)

neuromodulation: tricyclics (amitriptyline or nortriptyline if drowsiness)

Prokinetics

challenges:  a) little correlation found between the gastric emptying accelerating effects of various agents and symptom responses. b) factors other than measurable gastric emptying are involved in symptoms in affected individual, c) effective but non-selective agents have been abandoned eg. cholinergics caused intolerable bladder spasms, cisapride lead to hERG channel-mediated cardiac arrhythmias, such as Torsades de Pointes and ventricular tachycardia even without risk factors or tegasarod and cardiac effects d) "safety first” policy for non-life threatening conditions stifles drug development for severely disabling disorders, such as gastroparesis, pseudo-obstruction and severe IBS. e) In the management of the more complex and multifactorial disorders, while the search for highly specific agent is logical given the problems that have arisen as a consequence of unexpected adverse events, there may be some advantages to a “dirty” drug. For example, a drug with 5-HT4 agonist (promotility) and 5-HT3 antagonist (visceral analgesic) would seem attractive in IBS. In another arena, the unexpected but apparent anti-nociceptive effects of the pro-secretory agent, linaclotide, may contribute to its benefits on pain in constipation-predominant IBS and the neuroprotective effects of prucalopride may have significant implications for the long-term outlook of enteric neuropathic disorders. Antihistamines (Bendadryl diphenhydramine), antidepressants (amitriptyline, citalopram, mirtazapine, doxepin), antipsychotics (haloperidol, quetiapine), antibiotics/antifungals (macrolides, metronidazole with alcohol, azoles) all can prolong QTc f) Combination therapy addressing symptoms (i.e. nausea), pain, abnormal gastric function, and psychological therapy for more refractory patients; g) differential diagnoses might show a similar presentation eg. peptic ulcer disease, gastric cancer, coeliac disease, abdominal angina for gastroparesis, anastomotic ulcers, internal herniation and gallbladder disease for early dumping syndrome and insulinoma, surreptitious use of glucose-lowering medication for late dumping

 

cholinergics- muscarinic M2-type receptor agonist: Neostigmine for Ogilvie’s syndrome and pyridostigmine for pseudo-obstruction;

dopamine agonists  metoclopramide (DA, 5HT3/4 antagonist, modest anticholinesterase activity; SE fatigue, sleepiness, depression, akathisia, anxiety, hyperactivity, dyskinesia), domperidone 10-20mg qid (DA2 - breast tenderness and galactorrhea, cardiac - needs close monitoring)

serotonin agonists:  mosapride (selective 5HT4/3: minimal affinity for 5-HT1/2, dopamine D2, or adrenergic receptors) 5 mg tds 8 weeks or i CR (loose stools, dry mouth, malaise and headache <5% of patients, does not cause QT prolongation); Prucalopride (highly selective 5-HT4 agonist, very low affinity for other 5-HT receptors and for the hERG-K+ cardiac channels . Its high affinity for the 5-HT4 receptor confers greater efficacy for prucalopride while low affinity for the hERG-K+ channel explains why it has not been shown to be arrhythmogenic; together they confer a major therapeutic advantage for prucalopride over cisapride); Mirtazapine 15mg 6pm (tetracyclic antidepressant -5-HT 1a/2a+c/3 -functional dyspepsia -central and peripheral 5-HT1A receptors - theoretically leads to gastric fundus relaxation, 5-HT3 receptors  antiemetic effect, 5HT2 anti-anxiety)

Macrolide: motilin receptor agonist intravenous erythromycin  (3 mg/kg every 8 hours) and continues with oral administration (250 mg three times a day) for 5 to 7 day, Azithromycin similar; tachyphylaxis within 4 weeks, slowed with lower dosages; P-450 3A inhibitors, Less QTc prolongation and drug interactions with azithromycin

Botulinum toxin (Botox®)

Others for nausea and vomiting:

complementaries: ginger, peppermint drops, and some homeopathic remedies;  melatonin, and herbal medications such as iberogast (STW5, derived from Iberis amara) and capsaicin (component of red pepper)  some benefit in adults with FD
Selective serotonin 5HT3 antagonists: ondansetron ( 4-8 mg tds po, IV, PR) and granisetron
Phenothiazines: most commonly prochlorperazine (Stemetil®)
Antihistamines: cyclizine, diphenhydramine (H1A),  Cyproheptadine (Periactin™ - H1A/muscarinic, HT antagonist, CBB)

neurokinin-1 receptor NK1 RA: aprepitant  125mg daily

anticholingeric - antimuscarinic agent - Scopolamine patch

benzodiazepine - lorazepam (anecdotal chemotherapy studies- anticipatory nausea)

Others for abdominal/chest pain modulation:

Psychosocial therapies (particularly for severe pain, impaired QOL, mood/anxiety disorders): stress management, cognitive behavioral therapy, relaxation therapy, gut directed hypnotherapy, biofeedback, social worker to assist with home/work/education/financial modifications/support
Neuromodulators reduce visceral hypersensitivity (normal motility/FD/EPS subtype) Tricyclics (amitriptyline, nortriptyline), mirtazapine (nausea/weight loss) or Gabapentinoids
Cyproheptadine (younger PDS subtype with early satiety)
Proton pump inhibitors (pantoprazole, omeprazole, lansoprazole, rabeprazole, esomeprazole);  particularly helpful in patients with overlapping symptoms of dyspepsia and gastro-oesophageal reflux disease

Others for abdominal bloating:
Antifoaming/surfactants (alter elasticity of gas bubbles,  ease gastric gas passage): simethicone and activated charcoal
Erythromycin
Metoclopramide
Antibiotics: Metronidazole (Flagyl ®) or Trimethoprim/sulfamethoxazole (TMP/SMX Bactrim®) or  Rifaximin (antibiotic that lacks intestinal absorption and is highly active against aerobic and anaerobic bacteria which may overpopulate digestive tract)

Probiotics:  Bifidobacterium infantis has demonstrated positive effects in RCTs.16 RCTs, B. infantis 35624 reduce intestinal inflammation and showed significant improvement in the composite score for abdominal pain/discomfort, bloating/distention and/or bowel movement difficulty compared with placebo

 

 

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 QTc 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 QTc 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 QTc syndrome should be confirmed with a 12 lead ECG. If the ECG shows prolongation of the QTc 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 QTc interval. An association with a medication that prolongs the QTc 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 QTc prolongation beyond normal limits. If QTc prolongation is observed, it is advisable to stop the offending drug or switch to an alternative drug that has no such effect.