Pharmaceutical care - drugs used in IBD Flashcards
Before drug modifications where the absorption of Mesalazine occur?
Primarily all within the small intestine, therefore would be inappropriate for the indication of UC which would require drug targeting of the large intestine.
Describe the modifications made to Mesalazine for colonic drug delivery?
In sulfasalazine, Mesalazine is bound to a sulfapyridine via an azo-bond.
The drug is delivered to the colon and the active drug Mesalazine is absorbed there as it is the colonic bacterium present within the colon that releases azo-reductase which cleaves the azo-bond releasing the active drug.
What is the outcome of Sulfapyridine when it is released from the drug molecule?
Absorbed by the colon
Metabolised in the liver
Excreted in the urine
What is the outcome of Mesalazine when it is released from the drug molecule?
Mesalazine exerts a topical effect on the mucosa.
30% of the free drug is absorbed
Metabolised locally and in the liver to an inactive form and free/conjugated drug is
excreted in the urine or faeces
What are the contra-indications of Sulfasalazines?
Hypersensitivity to sulfapyridine/sulfonamides or 5-
aminosalicylate/salicylates
What are the cautions of Sulfasalazine use?
History of asthma (due to causing dyspnoea and cough and therefore cautioned with those with a reduced pulmonary reserve)
Risk of haematological toxicity (ability to cause blood disorders)
Renal and hepatic impairment (metabolism and excretion routes are dependent)
Glucose-6-dehydrogenase (G6PD) deficiency
Slow acetylator status (sulfapyridine undergoes acetylation before excretion)
What are the common side effects of sulfasalazines?
Headaches
Nausea
Fever
Rash
Reversible infertility in men
Reduced white cell count
What are some of the common patient reported symptoms?
Loss of appetite
Nausea
Sensitivity to sunlight
Nervousness
How common are headaches with sulfasalazine use?
Occur in up to 1/3 of patients
But is more commonly associated with higher doses
Reduced rate when the dose is increased gradually
What are some of the uncommon and rare side effects associated with sulfasalazine use?
Uncommon:
Pancreatitis
Rare:
Hepatitis
Pneumonitis
Skin reactions
Kidney inflammation / renal impairment
Haemolysis
What are the monitoring parameters for sulfasalazine?
FBC and LFTs: Before initiation and every second week for first 3 months, then monthly for three months then every 3 months
Creatinine/eGFR – Monthly for 3 months then as indicated
All are as indicated, if there are deteriorations in results you would expect an increase in monitoring frequency
What symptoms would you advise patients to look out for whilst taking sulfasalazine?
Sore throat, fever, malaise, jaundice and unexpected non-specific illness - may indicate myelospuppression, haemolysis or hepatotoxicity
What can sulfasalazine stain?
Urine
Contact lenses
State the four delivery mechanisms for Mesalazine and give brand examples.
Attachment to other carrier molecules (olsalazine – mesalazine dimer, could either be drug-carrier or drug-drug)
* pH dependent formulations (Salafalk/granules)
* Time dependent formulations (Pentasa/granules)
* Multi-matrix system (Mezavant)
Are there specific patient groups that would benefit for one Mesalazine formulation over another?
No, there doesn’t appear to be any evidence to suggest that certain formulations of Mesalazine are more beneficial for certain patients.
Instead a formulation choice is made upon disease distribution, efficacy, side effects, release profile and patient preference
What is the purpose of using enteric coated Mesalazine?
Prevents early disintegration of the drug in the upper gastrointestinal system by binding the drug to a pH sensitive carrier molecule.
What is the difference between Eudragit S and Eudragit L- which would be more appropriate for UC?
Eudragit S is sensitive and will dissolve at a pH greater than or equal to 7.
Eudragit L is sensitive and will dissolve at a pH greater than or equal to 6.
As the duodenum has a pH of 6-7 and the ileum has a pH of above 7- choice is dependent of which part of the large bowel is affected by UC.
It is also important to consider that the pH of the large bowel is reduced by IBD
What is Eudragit S and L made from?
Methyl acrylate copolymer coating
How does time dependent drug delivery of Mesalazine work?
Consists of microspheres of mesalazine encapsulated in ethylcellulose semi-permeable membrane.
The release of the drug is dependent upon time and moisture and independent of the pH.
How does the multi-matrix system work?
Mesalazine incorporated into lipophilic matrix and enterically coated (so will dissolve at a pH greater than 7).
The matrix will swell up to form a gel allowing slow diffusion and enabling delivery of the drug to the terminal ileum and entire colon.
What is the formulation, optimal pH for drug release and site of release for Asacol MR / Mesren?
Formulation: enteric coat with Eudragit S
Optimal drug release pH: greater than seven
Site of release: Terminal ileum and large bowel
What is the formulation, optimal pH for drug release and site of release for Salofalk?
Formulation: enteric coat with Eudragit L
Optimal drug release pH: greater than six
Site of release: mid to terminal ileum and large bowel
What is the formulation, optimal pH for drug release and site of release for Salofalk granules?
Formulation: Matrix core with Eudragit L coating
Optimal drug release pH: greater than six
Site of release: mid to terminal ileum and large bowel
What is the formulation, optimal pH for drug release and site of release for Octasa?
Formulation: Enteric coat with Eudragit S
Optimal drug release pH: greater than seven
Site of release: Terminal ileum and large bowel
What is the formulation, optimal pH for drug release and site of release for Pentasa/granules?
Formulation: Ethylcellulose semi
permeable membrane
microspheres
Optimal drug release pH: time dependent
Site of release: Duodenum to rectum
What is the formulation, optimal pH for drug release and site of release for Mesavant XL?
Formulation: Film coated with Eudragit S
and L
Optimal drug release pH: greater than 6-7
Site of release: Terminal ileum and colon
What are some important considerations to make regarding the different formulations of Aminosalicylates?
Licensing is different for the different preparations (doses and administration different)
Difference in formulation should allow different release profile
For mild to moderate UC, there does not appear to be a disparity in the safety and efficacy of the different formulations
Different profiles- systemic exposure is comparable
What is the monitoring required for Mesalazine?
Renal function (creatinine/eGFR), urea, electrolytes, LFTs, FBC – prior to initiation
and periodically (until stabilised and routinely)
-Renal function – 6-monthly
-Urea, electrolytes, LFTs, FBC – 6-monthly to annually
What is the rate of adverse events of aminosalicylates?
20-30%
When are liquid enemas used and when are foam enemas used?
Liquid enemas are used to treat regions up to the splenic flexure whereas foam enemas can only go up to the proximal sigmoid colon.
What are the two available Mesalazine liquid enemas that are available?
Pentasa (1gram in 100mL)
Salofalk (2 grams in 59mL)
What is the foam Mesalazine enema that is available?
Salofalk 1gram per accuation
What is the licensing/indication for Pentasa liquid enema?
For the treatment of UC affecting the distal colon and rectum
What is the licensing/indication for Salofalk liquid enema?
Treatment and prophylaxis of acute
attacks of mild UC in the rectum, sigmoid colon & descending colon
What is the licensing/indication for Salofalk foam enema?
Active, mild UC of the sigmoid colon and rectum.
Do foam or liquid enemas tend to be preferred?
Foam as they are easier to retain and administer
What is the adult dosing for each of the enemas?
Pentasa: 1g (one enema) once
daily at bedtime.
Salofalk foam: Two metered applications (2g) once daily at bedtime for 4-6 weeks (can also divide doses)
Salofalk liquid: 2g (one enema) once
daily at bedtime.
Not licensed for children under 18
What are some of the adverse effects associated with Pentasa?
Pruritus, rectal discomfort and urge to
defecate.
What are some of the adverse effects associated with foam Salofalk?
Abdominal distension, anal discomfort,
application site irritation, painful rectal tenesmus.
What are some of the adverse effects associated with liquid Salofalk?
None listed in the summary of product characteristics
What area can suppositories be used to treat?
Indicated for use in disease up to the
rectosigmoid junction
Are suppositories or enemas better for rectal delivery?
Suppositories deliver the drug more effectively to the rectum
What are the three available suppositories of Mesalazine available?
Pentasa 1gram
Salofalk 1gram
Salofalk 50mmg
When is Pentasa suppository 1 gram indicated/licensed?
Treatment of ulcerative proctitis
When is the Salofalk suppository 1 gram indicated/licensed?
Treatment of acute mild to moderate UC of the rectum.
When is the Salofalk suppository 500mg indicated/licensed?
Management of mild and moderate episodes of UC of the rectum
What is the adult dosing frequency of the Pentasa 1 gram suppository?
Acute treatment: 1suppository daily for 2-4
weeks.
Maintenance treatment:1 suppository daily
What is the adult dosing frequency of the Salofalk 1 gram suppository?
1 suppository daily, preferably at bedtime.
Duration of use to be determined by the physician
What is the adult dosing frequency of the Salofalk 500mg suppository?
1-2 suppositories, 2-3 times daily.
Dosage should be adjusted to suit the
progress of the condition
Are any of the suppositories licensed in children?
No
What are the side effects of the Pentasa 1 gram suppository?
Pruritus, rectal discomfort and urge to
defecate.
What interventions should be made prior to the initiation of Azathioprine or Mercaptopurine?
FBC, U&E and LFT
Screen for HCV, HIV, HBV / VZV
Vaccinate – influenza and pneumococcal
Ensure cervical screening up to date
Check TPMT (ThioPurine MethylTransferase) – dose altered dependent
on result
* Avoid in patients with very low TPMT
Why is it required for females to undergo cervical screening before initiation of a thiopurine drug?
As there is an increased risk of cervical dysplasia among women with IBD on thiopurines, which is the precursor to cervical cancer.
What does the enzyme thiopurine methyl transferase do?
It is responsible for the methylation and inactivation of 6-Mercaptopurine. In patients with low levels of this enzyme it is recommended to reduce the dose or potentially avoid altogether as it can lead to toxic levels of the active drug increasing the risk of myelosuppression and other adverse side effects.
What is the ongoing monitoring required for Azathioprine or Mercaptopurine?
FBC, U&E and LFT – at least at 2, 4, 8 and 12 and then 3-monthly
What are the contra-indications of Azathioprine and Mercaptopurine?
Hypersensitivity
Serious infection
Pancreatitis
Impaired bone marrow
What are the cautions of Azathioprine and Mercaptopurine?
Reduced TPMT
Renal and hepatic impairment
What advice would you give to patients if they are taking Azathioprine or Mercaptopurine?
Reduce exposure to the sun, due to increased risk of skin cancers
Take with meals to reduce the risk of nausea (any nausea resolves within a few weeks) – Reduce dose and give with allopurinol/switch to mercaptopurine
What symptoms would you advise patients to look out for whilst on Azathioprine or Mercaptopurine?
Ulceration of the throat, fever, infections, bruising, bleeding (myelosuppression)
What should you do if the patient also takes Allopurinol?
Reduce Azathioprine dose to 1/4 of original dose
