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Ultresa

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Ultresa

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Fibrosing Colonopathy

Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.4,5 Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic stricture in children less than 12 years of age.1 Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day [see DOSAGE AND ADMINISTRATION].

Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.

Potential for Irritation to Oral Mucosa

Care should be taken to ensure that no drug is retained in the mouth. ULTRESA should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity [see DOSAGE AND ADMINISTRATION and PATIENT INFORMATION] For patients who are unable to swallow intact capsules, the contents may be sprinkled on applesauce, yogurt and other acidic soft food with pH 4.5 or less. The ULTRESA-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.

Potential for Risk of Hyperuricemia

Caution should be exercised when prescribing ULTRESA to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.

Potential for Viral Exposure from the Product Source

ULTRESA is sourced from pancreatic tissue from pigs used for food consumption. Although the risk that ULTRESA will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.

Allergic Reactions

Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase). The risks and benefits of continued ULTRESA treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.

Patient Counseling Information

“See FDA-approved patient labeling (Medication Guide)

Dosing and Administration

  • Instruct patients and caregivers that ULTRESA should only be taken as directed by their doctor. Patients should be advised that the total daily dose should not exceed 10,000 lipase units/kg body weight/day unless clinically indicated. This needs to be especially emphasized for patients eating multiple snacks and meals per day. Patients should be informed that if a dose is missed, the next dose should be taken with the next meal or snack as directed. Doses should not be doubled. [see DOSAGE AND ADMINISTRATION].
  • Instruct patients and caregivers that ULTRESA should always be taken with food. Patients should be advised that ULTRESA delayed-release capsules must not be crushed or chewed as doing so could cause early release of enzymes and/or loss of enzymatic activity and irritation of the oral mucosa. Patients should swallow the intact capsules with adequate amounts of liquid at mealtimes. If necessary, the capsules contents can also be sprinkled on soft acidic foods. [see DOSAGE AND ADMINISTRATION].
  • Any unused portion of capsule contents should be discarded, and not used for subsequent dosing. The remaining exposed contents may lose potency and become less effective. [see DOSAGE AND ADMINISTRATION]
  • Instruct patients that use of ULTRESA in children is limited by the available capsule dosage strengths and their ability to provide the recommended dose based on age and weight. Instruct patients that attempting to divide the capsule contents in small fractions to deliver small doses of lipase is not recommended. [see DOSAGE AND ADMINISTRATION]

Fibrosing Colonopathy

Advise patients and caregivers to follow dosing instructions carefully, as doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures (a rare bowel disorder) in children below the age of 12 years. [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Allergic Reactions

Advise patients and caregivers to contact their doctor immediately if allergic reactions to ULTRESA develop.

Pregnancy and Breast Feeding

  • Instruct patients to notify their physician if they are pregnant or are thinking of becoming pregnant during treatment with ULTRESA. [see Use In Specific Populations]
  • Instruct patients to notify their physician if they are breast feeding or are thinking of breast feeding during treatment with ULTRESA [see Use In Specific Populations]

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed with pancrelipase.

Use In Specific Populations

Pregnancy

Teratogenic effects - Pregnancy Category C

Animal reproduction studies have not been conducted with pancrelipase. It is also not known whether pancrelipase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ULTRESA should be given to a pregnant woman only if clearly needed. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a pregnant woman with exocrine pancreatic insufficiency. Adequate caloric intake during pregnancy is important for normal maternal weight gain and fetal growth. Reduced maternal weight gain and malnutrition can be associated with adverse pregnancy outcomes.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ULTRESA is administered to a nursing woman. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a nursing mother with exocrine pancreatic insufficiency.

Pediatric Use

The short-term safety and efficacy of ULTRESA were assessed in two clinical studies in pediatric patients with exocrine pancreatic insufficiency due to cystic fibrosis; one study included patients aged 8 years to 17 years, and the other included patients aged 7 years to 11 years.

Study 1 was a randomized, double-blind, placebo-controlled crossover study of 31 patients with exocrine pancreatic insufficiency due to cystic fibrosis including 2 children aged 8 to 11 years, and 12 adolescents aged 12 to 17 years. The safety and efficacy in pediatric patients in this study were similar to that in adult patients [see ADVERSE REACTIONS and Clinical Studies].

Study 2 was an open-label study of 9 pediatric patients, ages 7 years to 11 years, with exocrine pancreatic insufficiency due to cystic fibrosis. Patients showed similar control of fat malabsorption as in the treatment arm of Study 1 [see ADVERSE REACTIONS and Clinical Studies].

The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase consisting of the same active ingredient (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis have been described in the medical literature and through clinical experience.

Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences. However, use of ULTRESA in children is limited by the available capsule dosage strengths and their ability to provide the recommended dose based on age and weight. Attempting to divide the capsule contents in small fractions to deliver small doses of lipase is not recommended [see DOSAGE AND ADMINISTRATION]. Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age [see WARNINGS AND PRECAUTIONS].

Geriatric Use

Clinical studies of ULTRESA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

REFERENCES

1. Borowitz DS, Grand RJ, Durie PR, et al. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Journal of Pediatrics. 1995; 127: 681-684.

4. Smyth RL, Ashby D, O'Hea U, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-control study. Lancet. 1995; 346: 1247-1251.

5. FitzSimmons SC, Burkhart GA, Borowitz DS, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. New England Journal of Medicine. 1997; 336: 1283-1289.

Last reviewed on RxList: 3/12/2012
This monograph has been modified to include the generic and brand name in many instances.

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