CREON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CREON (CREON).
Pancreatic enzyme replacement therapy; lipase, amylase, and protease hydrolyze fats, proteins, and starches respectively, compensating for exocrine pancreatic insufficiency.
| Metabolism | Not metabolized; enzymes are biologically degraded in the gastrointestinal tract. |
| Excretion | Pancrelipase undergoes proteolytic digestion in the gastrointestinal tract; the enzymes are not absorbed systemically. Any residual activity is eliminated in feces. Renal excretion is negligible. |
| Half-life | Not applicable, as pancreatic enzymes act locally in the GI tract and are not systemically absorbed. The enzymes are inactivated by gastric acid and pepsin, resulting in an effective half-life of 30–45 minutes in the duodenum. |
| Protein binding | Negligible; pancreatic enzymes are not systemically absorbed and do not bind to plasma proteins. |
| Volume of Distribution | Not applicable; the enzymes remain in the gastrointestinal lumen and are not distributed to tissues. |
| Bioavailability | Oral: Not systemically bioavailable. The enzymes act locally in the gut lumen. Bioavailability is defined by the amount of active enzyme reaching the duodenum, which is highly variable and depends on formulation, dose, and patient factors (e.g., gastric pH, meal composition). |
| Onset of Action | Oral administration: Onset of lipolytic and proteolytic activity occurs within 15–30 minutes after ingestion, corresponding to gastric emptying and duodenal delivery. |
| Duration of Action | Oral administration: The duration of enzyme activity in the small intestine is approximately 1–2 hours, depending on transit time and pH. Multiple capsules may be needed for prolonged meals. |
500 to 4,000 lipase units per gram of fat intake per meal, orally, with meals; typical adult dose: 25,000 to 75,000 lipase units per meal, up to 150,000 units/day. Capsules should be swallowed whole with water or juice; do not crush or chew.
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | No dose adjustment required for renal impairment; however, caution in severe impairment due to potential electrolyte disturbances. |
| Liver impairment | No specific recommendations; use with caution in severe hepatic impairment due to altered protein binding and metabolism. |
| Pediatric use | 1,000 to 2,500 lipase units/kg per meal for infants up to 12 months; 500 to 4,000 lipase units/kg per meal for children older than 12 months. Maximum dose: 10,000 lipase units/kg/day or 4,000 lipase units per gram of fat intake. |
| Geriatric use | Dosing same as adults; monitor for gastrointestinal adverse effects and drug interactions. Consider lower initial doses due to potential reduced fat tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CREON (CREON).
| Breastfeeding | Excretion into breast milk is unlikely due to minimal systemic absorption. M/P ratio not applicable. Considered compatible with breastfeeding. |
| Teratogenic Risk | CREON (pancrelipase) is not absorbed systemically; fetal exposure is negligible. No teratogenicity reported in animal studies or human data. No known risk in any trimester. |
| Fetal Monitoring | Monitor maternal nutritional status and pancreatic insufficiency symptoms. No specific fetal monitoring required. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to pork proteins or any component of the formulation.","Acute pancreatitis or acute flare of chronic pancreatitis (relative; use with caution)."]
| Precautions | ["Fibrosing colonopathy reported with high doses (>10,000 lipase units/kg/day), especially in cystic fibrosis patients.","Allergic reactions possible (e.g., urticaria, anaphylaxis).","Avoid crushing or chewing capsules to prevent oral mucosal irritation.","Monitor for hyperuricosuria and hyperuricemia due to high purine content.","May interfere with iron absorption; monitor iron status in long-term use."] |
| Food/Dietary | Avoid mixing capsule contents with alkaline foods or liquids (e.g., milk, ice cream, pudding, custard, tea). Acidic foods (applesauce, fruit juices, gelatin) are acceptable. Do not chew capsules or mix contents with hot foods. Maintain adequate hydration during treatment. No specific food restrictions. Fat content of meals determines dose; advise consistent dietary fat intake. |
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| Fertility Effects | No known effects on fertility. Pancrelipase does not alter reproductive function. |
| Clinical Pearls | Do not crush or chew capsules; administer with meals or snacks. For patients with difficulty swallowing, capsules may be opened and contents mixed with acidic soft food (e.g., applesauce, pears). Do not mix with alkaline foods (e.g., milk, ice cream, pudding). Ensure adequate hydration during therapy. Monitor for symptoms of fibrosing colonopathy with high doses (>10,000 lipase units/kg/day). Adjust dose based on fat content of meals rather than body weight alone. Concomitant use of proton pump inhibitors may enhance efficacy in patients with suboptimal response. |
| Patient Advice | Take this medication exactly as prescribed with every meal or snack. · Do not crush or chew the capsules; swallow whole or open and sprinkle on soft acidic food. · Do not hold the capsule contents in your mouth or mix with alkaline foods. · Drink plenty of fluids while taking this medication. · If you miss a dose, skip it and take the next dose at the usual time with your next meal; do not double dose. · Contact your doctor if you experience unusual abdominal pain, bloating, or changes in bowel movements. · Report any new or worsening symptoms, as you may need dose adjustment. |