Case Presentation

1. PANCRELIPASE (CREON)
USE IN
PANCREATIC DISORDERS
Shiny Parsai
Froedtert General Medicine Rotation
University of Iowa PharmD Candidate 2016

2. OUTLINE
• Patient presentation
• Pancreatic disorders
• Pancrelipase (Creon)
• Questions

3. PATIENT BACKGROUND

4. PATIENT PRESENTATION
• PS, 66 year old, retired, white male
• Height: 6’0” Weight: 67.7kg(149.2lbs)
• BMI: 20kg/m2 (normal)
• CrCl 78.2ml/min (normal renal function)
• No known drug allergies
• Social History
• Married
• Current smoker with 75 year pack history
• Drank 8 to 10 beers a day until he stopped drinking 3 weeks ago
• Family history non-contributory
• Insured
• Admitted to Froedtert Wednesday 8/19/2015

5. PATIENT PRESENTATION
• Chief complaint
• Epigastric abdominal pain
• Nausea and vomiting
• History of illness
• Lost 26 pounds over the last month with decreased appetite
• Hospitalized recently 8/3 - 8/18 at another hospital
• Abdominal pain and dehydration
• MRI showed pancreatic cyst measuring 6 X 6 X 4 cm
• Physical Exam
• HEENT: + bilaterial horizontal nystagmus
• Diagnosis
• Alcoholic pancreatitis

6. PATIENT PRESENTATION
Past medical history
• Pancreatitis and pancreas mass requiring
Whipple procedure (2007)
• Barrett's esophagus
• Depression
• Diverticulosis
• Hypertension
• Hyperlipidemia
• Appendectomy (1965)
Immunization history – up to date
• Influenza (10/20/2014)
• Next immunization due Fall 2015
• Pneumococcal PPSV23 (12/19/2014)
• Next dose PCV13 due after 12/19/2015
• TetanusTd (11/23/2012)
• Next booster dose in 7 years

7. ABNORMAL LABS
• BP 86/48 (hypotensive)
• Glucose 205 (65 – 99 mg/dL)
• HgB 11 (13.7-17.5g/dL)
• Hct 33 (40-51%)
• RBC 3.5 (4.6-6.1 10e6uL)
• Lipase 9 (23-85 U/L)

8. PRIORTO ADMISSION MEDICATIONS
Drug Dose Indication
Aspirin 81 mg PO 1 tablet daily INDICATION: cardiovascular prevention
B complex vitamin Unknown PO 1 tablet daily INDICATION: supplementation
Citalopram 40 mg PO 1 tablet daily INDICATION: depression
Insulin glargine 10 units SQ Inject nightly INDICATION: diabetes type 2
Lansoprazole 30 mg PO 1 capsule daily INDICATION: barrett’s esophagus
Multivitamin Unknown PO 1 tablet daily INDICATION: supplementation
Omega3 fatty acids 1000 mg PO 2 capsule twice a day INDICATION: supplementation
Oxycodone IR 5 mg PO 1-2 tablets every 6 hours as needed INDICATION: pain
Pancrelipase (Creon DR) 24,000 units PO Take 2-3 capsules by mouth three times daily with meals/snacks
INDICATION: pancreatic disorder
Zaleplon 5 mg PO 1 capsule nightly as needed INDICATION: insomnia

9. DISEASE BACKGROUND

10. PANCREAS1,2,3
• Digestion and absorption of nutrients
• Key enzymes
• Amylase – hydrolyzes starch into sugars (ex: rice, potatoes)
• Lipase – hydrolyzes fats
• Fat soluble vitamins A, D, E, K
• PS taking multivitamin and omega 3 fatty acids
• Trypsin – hydrolyzes proteins
• Chymotrypsin – hydrolyzes proteins
• Cleavage of vitamin B12 from protein
• PS taking vitamin B supplementation
• Disorders associated with pancreatic insufficiency
• Cystic fibrosis
• Pancreatitis
• Effects
• Pancreatic insufficiency leads to malabsorption, weight loss, steatorrhea, gas, diarrhea

11. WHIPPLE PROCEDURE – pancreatic mass4
• Removes head of pancreas, portion
of common bile duct, gallbladder,
duodenum of small intestine,
pylorus of stomach, and surrounding
lymph nodes
• Reconnect the remaining pancreas
and digestive organs
• Surgery lasts between 5- 8 hours
• Pancreatic insufficiency and
maldigestion occurs in up to 80% of
patients following gastric, duodenal,
or pancreatic surgery

12. ALCOHOLIC PANCREATITIS – background5
• Epidemiology
• Between 4.8 and 24.2 cases per 100,000 in the U.S.
• One-third of acute pancreatitis cases in the U.S. are alcohol induced
• Risk increases with amount and duration of alcohol consumption
• Smoking may have an additive effect with alcohol in inducing pancreatitis
• 80% - 95% of people who abuse alcohol also smoke
• Incidence of alcoholism is 10x more likely in smokers than nonsmokers
• Potentiates pancreatic microcirculatory impairment by ethanol
• Induces leukocyte aggregation and adhesion

13. ALCOHOLIC PANCREATITIS – pathophysiology5
• Mechanism not entirely clear
• Alcohol metabolism
• Oxidative
• Non-oxidative
• Alcohol could impair blood flow to
pancreas causing hypoxia and build
up of free radicals

14. ALCOHOLIC PANCREATITIS – symptoms/diagnosis6
• Symptoms
• Epigastric or left upper quadrant pain
• Radiation to the back, chest, or flanks (nonspecific)
• Intensity of the pain severe (variable)
• Diagnosis
• Presence of 2 of the 3 following criteria
• Abdominal pain consistent with the disease
• Serum amylase and/or lipase greater than three times the upper limit of normal
• Characteristic findings from abdominal imaging
• Contrast-enhanced computed tomography (CECT) and / or MRI of pancreas
• Reserved for patients in whom the diagnosis is unclear or who fail to improve clinically within
the first 48 – 72 h after hospital admission or to evaluate complications

15. PSTREATMENT GOALS
• Treat acute alcoholic pancreatitis
• Alleviate pancreatic inflammation and pain
• Correct the underlying cause
• Resolve hypotension
• Prevent DVTs
• SCDs and starting enoxaparin after GI consult procedure
• Resolve hypergylycemia

16. ACG GUIDELINES – management of acute pancreatitis6
• Hydration
• 250 - 500 ml/hr isotonic crystalloid solution for all patients unless
cardiovascular, renal, or other related comorbidities
• Early aggressive intravenous hydration is most beneficial during the first 12 -
24 hr and may have little benefit beyond this (strong recommendation,
moderate evidence)
• PS - 0.9% NaCl infusion continuous 100ml/hr  BP normalized to 100/58 HR 76
• Antibiotics
• Treat extrapancreatic infection (ex: UTI, pneumonia)
• Prophylactic antibiotics in severe acute pancreatitis is not recommended
• PS – no antibiotics given

17. ADDITIONALTREATMENT – pharmacological
• Pancrelipase
• Not for acute pancreatitis management
• PS – appropriate based on chronic pancreatitis, prior Whipple procedure,
and pancreatic insufficiency
• Pain management
• Nonopioids (acetaminophen, ibuprofen)
• Opiods
• PS – taking oxycodone 5mg Q6hr PRN

18. ADDITIONALTREATMENT – nonpharmacological6
• NPO
• Allows pancreas to rest
• PS - Esophagogastroduodenoscopy scheduled forThursday 8/20
• Supplementation
• Patients with chronic pancreatitis are often malnourished
• Malnutrition may be due to inadequate pancrelipase enzyme treatment not alcoholism
• Dominguez-Munoz et al. (2007) showed that treatment with higher enzyme doses
resulted in normal nutrition measures regardless of alcohol use
• PS – taking B complex: B12>2000(211-946pg/ml), multivitamin, and omega 3 fatty acids
• Avoid alcohol – PS stopped drinking 3 weeks ago
• Smoking cessation – PS received NICODERM CQ 7mg/24 hour patch Q24 hrs
• Small, low fat meals, with plenty of fluids

19. DRUG BACKGROUND

20. PANCRELIPASE – indications/contraindications9
• FDA approved indications
• Conditions causing pancreatic insufficiency
• Cystic fibrosis
• Chronic Pancreatitis
• Pancreatectomy
• Contraindications
• None

21. PANCRELIPASE – ingredients9
• Natural product harvested from the porcine pancreatic glands
• Patients may be allergic to pork product (rare)
• Patient may refuse treatment due to religious reasons (muslims,
orthodox jews)
• Pigs used to produce pancrelipase because pigs are omnivores and
produce all the enzymes needed
• No other sources of pancrelipase available
• Contains amylase, lipase, and protease

22. PANCRELIPASE – formulation7,8,9
• Formulation
• Delayed-release capsules because replacement enzymes are
destroyed by stomach acid
• Designed to release enzymes at pH ≥ 5.5
• Microspheres allows enzymes to mix with food and empty from the
stomach into the duodenum at the same rate as the food

23. CREON WITH GASTRIC ACID SUPPRESSANTS10
• Retrospective Analysis to Investigate the Effect of Concomitant
Use of Gastric Acid Suppressing Drugs on the Efficacy and Safety
of Creon in Patients With Pancreatic Exocrine Insufficiency
• 34 trials, 1142 unique subjects
• Concomitant use of PPI/H2RAs
• Result
• Efficacy of Creon not affected by concomitant PPI/H2RA
• Acid suppression is not routinely required with pancreatic enzyme
replacement therapy
• PS – taking lansoprazole for Barrett’s esophagus

24. PANCRELIPASE – alternative treatment2
• Options
• Creon (Abbvie Pharmaceuticals)
• Pancrelipase (Generic)
• Pancreaze (Janssen Pharmaceuticals)
• Pertzye (Digestive Care)
• Ultresa (Aptalis)
• Viokace (Aptalis)
• Zenpep (Aptalis)
• No head-to-head tests comparing these products
• Not AB rated for bioequivalence

25. PANCRELIPASE – FDA8
• Pancreatic enzymes predate the 1938 of the FDA approval act
• FDA allowed these products to be grandfathered in
• 2004 review found inconsistencies in formulation, composition,
enzymatic activities, dosage, stability, bioavailability, and
manufacturing processes of enzymes that could significantly
compromise the safety and effectiveness
• Announced new drug application approval requirement by 2008
• Limited oversight and variability among the preparations

26. CREON – dosing8
• Not interchangeable with any other pancrelipase product
• Dosing based on age and available for infants and older
• Adults with exocrine pancreatic insufficiency due to chronic pancreatitis or
pancreatectomy
• Individualize based on symptoms, steatorrhea, and fat content of diet
• Dosed by lipase units
• Approx 1000-2000 units lipase/kg/meal or 2000-4,000 units lipase/gram dietary fat
• PS – taking 24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP
units of amylase 2-3 capsules by mouth three times daily with meals/snacks
• Dose should not exceed 2,500 units of lipase/kg/meal or 10,000 units lipase/kg/day
• Fibrosing colonopathy – abdominal pain, distension, vomiting, and constipation

27. CREON – administration8
• Do not split, chew, or crush capsules
• Swallow whole with plenty of water to avoid oral mucosa irritation
• If unable to swallow
• Open the capsules and mix with soft, acidic food such as applesauce
• Swallow the mixture right after mixing without chewing or crushing
• Drink a full glass of water or juice immediately
• Timing
• Dominguez-Mumoz et al. (2004) found that efficacy of pancreatic enzyme supplements for the
treatment of exocrine pancreatic insufficiency may be optimized by administration during or
after meals
• Missed dose
• Skip the missed dose and take your usual dose with your next meal or snack
• Do not take a double dose to make up for a missed one

28. CREON – adverse effects8
• Occurring in at least 1 chronic pancreatitis or pancreatectomy patient (greater
than or equal to 4%)
• Hyperglycemia/hypoglycemia
• Abdominal pain
• Abnormal feces, flatulence, frequent bowel movements
• Nasopharyngitis
• Occurring in at least 2 cystic fibrosis patients (greater than or equal to 4%)
• Vomiting
• Dizziness
• Cough

29. ADDITIONAL INFORMATION

30. PROGNOSIS11,12
• GI Consult
• Esophagogastroduodenoscopy performed
• Possible infected fluid
• Await final cytology results
• Avoid aspirin and NSAIDS
• Possible drugs associated with acute pancreatitis
• Probable mechanism of inhibition of prostaglandins that otherwise cause pancreatic duct constriction
• Start antibiotics for infected pseudocyst
• Patient mistakenly discharged onThursday 8/20
• Error realized on Friday 8/21 and patient called to discuss readmission
• Outpatient antibiotics prescribed
• Augmentin 875-125mg 1 tablet BID for 14 days
• Follow up with PCP for iron deficiency anemia

31. CREON – financial support13
• CREON Co-Pay Assistance Program
• Savings up to $50 per month on CREON prescriptions

32. REFERENCES
1. Damerla V et al. Pancreatic Enzyme Supplementation in Pancreatic Cancer. J Support Oncol 2008;6:393–396 Volume 6, Number 8.
2. MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2005 Aug 12]. Pancrealipase; [updated 2005 Jul 19;
reviewed 2005 May 4; cited 2005 Aug 12]; [about 2 p.]. Available from: https://www.nlm.nih.gov/medlineplus/druginfo/meds/a604035.html.
3. Image available from: http://www.livescience.com/34789-pancreatic-cancer-radiation-chemotherapy-treatment.html
4. Mayo clinic. Whipple procedure. Available from: http://www.mayoclinic.org/tests-procedures/whipple-procedure/basics/definition/prc-
20021393.
5. Chowdhury P et al. Pathophysiology of alcoholic pancreatitis: An overview. World J Gastroenterol 2006; 12(46): 7421-7427.
6. Tenner S et al. American College of Gastroenterology Guideline: Management of Acute Pancreatitis. Am J Gastroenterology. 2013
Sep;108(9):1400-15; 1416.
7. Dominguez-Munoz JE et al. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic
pancreatitis. Clin Gastroenterol Hepatol. 2007;5:484–488.
8. Ferrone M. Pancreatic Enzyme Pharmacotherapy. Pharmacotherapy. Volume 27, Number 6, 2007.
9. Creon [package insert]. North Chicago, IL. AbbVie Inc; 2015.
10. Whitcomb DC. Clinical update Advances in the treatment of pancreatic insufficiency. Gastroenterology & Hepatology Volume 7, Issue 4
April 2011.
11. Sander-Struckmeier S et al. Retrospective Analysis to Investigate the Effect of Concomitant Use of Gastric Acid Suppressing Drugs on the
Efficacy and Safety of Pancrelipase/Pancreatin (CREON) in Patients With Pancreatic Exocrine Insufficiency. Pancreas & Volume 42,
Number 6, August 2013.
12. Kaurich T. Drug-induced acute pancreatitis Tracie. Bayl Univ Med Cent. 2008;21(1):77–81.
13. Tisdale JE. Drug-Induced Diseases: Prevention, Detection, and Management. ASHP; Second Edition (February 11, 2010).
14. Image available from https://www.creon.com/CFPatients/ActivateCopayCard.

33. QUESTIONS?