Revised: November 2013 N

Please download to get full document.

View again

of 6
All materials on our website are shared by users. If you have any questions about copyright issues, please report us to resolve them. We are always happy to assist you.
Information Report
Category:

Medicine, Science & Technology

Published:

Views: 0 | Pages: 6

Extension: PDF | Download: 0

Share
Related documents
Description
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PANCREAZE safely and effectively. See full prescribing information for PANCREAZE. PANCREAZE (pancrelipase)
Transcript
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PANCREAZE safely and effectively. See full prescribing information for PANCREAZE. PANCREAZE (pancrelipase) delayed-release capsules Initial U.S. Approval 2010 Revised: November 2013 N Capsules: 16,800 USP units of lipase; 40,000 USP units of protease; 70,000 USP units of amylase. Capsules have a salmon opaque body and clear cap, printed with McNEIL and MT 16 (3) Capsules: 21,000 USP units of lipase; 37,000 USP units of protease; 61,000 USP units of amylase. Capsules have a white opaque body and cap, printed with McNEIL and MT 20 (3) INDICATIONS AND USAGE PANCREAZE is a combination of porcine-derived lipases, proteases, and amylases indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions (1) DOSAGE AND ADMINISTRATION Dosage PANCREAZE is not interchangeable with any other pancrelipase product. Infants (up to 12 months) Infants may be given 2,000 to 4,000 lipase units per 120 ml of formula or per breastfeeding. (2.1) Do not mix PANCREAZE capsule contents directly into formula or breast milk prior to administration. (2.2) Children Older than 12 Months and Younger than 4 Years Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day. (2.1) Children 4 Years and Older and Adults Enzyme dosing should begin with 500 lipase units/kg of body weight per meal to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day. (2.1) Limitations on Dosing Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines. (2.1) Administration PANCREAZE should be swallowed whole. For infants or patients unable to swallow intact capsules, the contents may be sprinkled on soft acidic food with a ph of 4.5 or less, e.g., applesauce. (2.2) DOSAGE FORMS AND STRENGTHS Capsules: 4,200 USP units of lipase; 10,000 USP units of protease; 17,500 USP units of amylase. Capsules have a yellow opaque body and clear cap, printed with McNEIL and MT 4 (3) Capsules: 10,500 USP units of lipase; 25,000 USP units of protease; 43,750 USP units of amylase. Capsules have a pink opaque body and clear cap, printed with McNEIL and MT 10 (3) CONTRAINDICATIONS None. (4) WARNINGS AND PRECAUTIONS Fibrosing colonopathy is associated with high-dose use of pancreatic enzyme replacement. Exercise caution when doses of PANCREAZE exceed 2,500 lipase units/ kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day). (5.1) To avoid irritation of oral mucosa, do not chew PANCREAZE or retain in the mouth. (5.2) Exercise caution when prescribing PANCREAZE to patients with gout, renal impairment, or hyperuricemia. (5.3) There is theoretical risk of viral transmission with all pancreatic enzyme products including PANCREAZE. (5.4) Exercise caution when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. (5.5) ADVERSE REACTIONS Treatment-emergent adverse events occurring in at least 2 patients (greater than or equal to 10%) receiving PANCREAZE or placebo are abdominal pain, abdominal pain upper, flatulence, diarrhea, abnormal feces, and fatigue. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals Inc., at or FDA at FDA-1088 or USE IN SPECIFIC POPULATIONS Pediatric Patients The safety and effectiveness of PANCREAZE were assessed in pediatric patients, aged 6 to 30 months old and aged 8 to 17 years old. (8.4) The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase in pediatric patients have been described in the medical literature and through clinical experience. (8.4) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: November 2013 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Dosage 2.2 Administration 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Fibrosing Colonopathy 5.2 Potential for Irritation to Oral Mucosa 5.3 Potential for Risk of Hyperuricemia 5.4 Potential Viral Exposure from the Product Source 5.5 Allergic Reactions 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Postmarketing Experience 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION 17.1 Dosing and Administration 17.2 Fibrosing Colonopathy 17.3 Allergic Reactions [* Sections or subsections omitted from the full prescribing information are not listed] 1 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE PANCREAZE (pancrelipase) is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions. 2 DOSAGE AND ADMINISTRATION 2.1 Dosage PANCREAZE is not interchangeable with other pancrelipase products. PANCREAZE is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of PANCREAZE should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet (see Limitations on Dosing below). Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences. 1,2,3 PANCREAZE should be administered in a manner consistent with the recommendations of the Conferences provided in the following paragraphs. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme. Infants (up to 12 months) Infants may be given 2,000 to 4,000 lipase units per 120 ml of formula or per breastfeeding. Do not mix PANCREAZE capsule contents directly into formula or breast milk prior to administration [see Dosage and Administration (2.2)]. Children Older than 12 Months and Younger than 4 Years Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal for children less than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day. Children 4 Years and Older and Adults Enzyme dosing should begin with 500 lipase units/kg of body weight per meal for those older than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day. Usually, half of the prescribed PANCREAZE dose for an individualized full meal should be given with each snack. The total daily dose should reflect approximately three meals plus two or three snacks per day. Enzyme doses expressed as lipase units/kg of body weight per meal should be decreased in older patients because they weigh more but tend to ingest less fat per kilogram of body weight. Limitations on Dosing Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines. 1,2,3 If symptoms and signs of steatorrhea persist, the dosage may be increased by a healthcare professional. Patients should be instructed not to increase the dosage on their own. There is great inter-individual variation in response to enzymes; thus, a range of doses is recommended. Changes in dosage may require an adjustment period of several days. If doses are to exceed 2,500 lipase units/kg of body weight per meal, further investigation is warranted. 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. Doses greater than 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures, indicative of fibrosing colonopathy, in children with cystic fibrosis less than 12 years of age [see Warnings and Precautions (5.1)]. Patients currently 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. 2.2 Administration PANCREAZE should always be taken as prescribed by a healthcare professional. Infants (up to 12 months) PANCREAZE should be administered to infants immediately prior to each feeding, using a dosage of 2,000 to 4,000 lipase units per 120 ml of formula or per breast-feeding. Contents of the capsule may be sprinkled on small amounts of acidic soft food with a ph of 4.5 or less (e.g., applesauce) and given to the infant within 15 minutes. Contents of the capsule may also be administered directly to the mouth. Administration should be followed by breast milk or formula. Contents of the capsule should not be mixed directly into formula or breast milk as this may diminish efficacy. Care should be taken to ensure that PANCREAZE is not crushed or chewed or retained in the mouth, to avoid irritation of the oral mucosa. Children and Adults PANCREAZE should be taken during meals or snacks, with sufficient fluid. PANCREAZE capsules and capsule contents should not be crushed or chewed. Capsules should be swallowed whole. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled on small amounts of acidic soft food with a ph of 4.5 or less (e.g., applesauce). The PANCREAZE-soft food mixture should be swallowed immediately without crushing or chewing, and followed with water or juice to ensure complete ingestion. Care should be taken to ensure that no drug is retained in the mouth. 3 DOSAGE FORMS AND STRENGTHS The active ingredient in PANCREAZE evaluated in clinical trials is lipase. PANCREAZE is dosed by lipase units. PANCREAZE is available in 4 color coded capsule strengths. Other active ingredients include protease and amylase. Each PANCREAZE capsule strength contains the specified amounts of lipase, protease, and amylase as follows: 4,200 USP units of lipase; 10,000 USP units of protease; 17,500 USP units of amylase capsules have a yellow opaque body and clear cap, printed with McNEIL and MT 4 10,500 USP units of lipase; 25,000 USP units of protease; 43,750 USP units of amylase capsules have a pink opaque body and clear cap, printed with McNEIL and MT 10 16,800 USP units of lipase; 40,000 USP units of protease; 70,000 USP units of amylase capsules have a salmon opaque body and clear cap, printed with McNEIL and MT 16 21,000 USP units of lipase; 37,000 USP units of protease; 61,000 USP units of amylase capsules have a white opaque body and cap, printed with McNEIL and MT 20 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 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 strictures 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. 1 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 (2.1)]. 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. 5.2 Potential for Irritation to Oral Mucosa Care should be taken to ensure that no drug is retained in the mouth. PANCREAZE 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 (2.2) and Patient Counseling Information (17)]. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled to a small amount of acidic soft food with a ph of 4.5 or less, such as applesauce. The PANCREAZEsoft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion. 5.3 Potential for Risk of Hyperuricemia Caution should be exercised when prescribing PANCREAZE to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels. 5.4 Potential Viral Exposure from the Product Source PANCREAZE is sourced from pancreatic tissue from swine used for food consumption. Although the risk that PANCREAZE 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. 2 5.5 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 PANCREAZE treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient. 6 ADVERSE REACTIONS The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions [see Warnings and Precautions (5)]. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The short-term safety of PANCREAZE was assessed in two clinical trials conducted in 57 patients with exocrine pancreatic insufficiency (EPI) due to CF. Study 1 was conducted in 40 patients, ages 8 years to 57 years; Study 2 was conducted in 17 patients, ages 6 months to 30 months. In Study 1, PANCREAZE was administered in a dose of approximately 6,300 lipase units per kilogram per day for lengths of treatment ranging from 8 to 26 days; in Study 2, PANCREAZE was administered in four treatment arms (doses of 1,375, 2,875, 4,735, and 5,938 lipase units per kilogram per day) for lengths of treatment ranging from 6 to 11 days. The population was nearly evenly distributed in gender, and approximately 96% of patients were Caucasian. Study 1 was a randomized, double-blind, placebo-controlled study of 40 patients, ages 8 to 57 years, with EPI due to CF. In this study, patients received PANCREAZE at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) for 14 days, followed by randomization to PANCREAZE or matching placebo for 7 days of treatment. The mean exposure to PANCREAZE during this study, including titration period and randomized withdrawal period, was 18 days. The incidence of adverse events (regardless of causality) was higher during placebo treatment (60%) than during PANCREAZE treatment (40%). The most common adverse events reported during the study were gastrointestinal complaints, which were reported more commonly during placebo treatment (55%) than during PANCREAZE treatment (30%). The type and incidence of adverse events were similar in children (8 to 11 years), adolescents (12 to 17 years), and adults (greater than 18 years). Table 1 enumerates treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 10%) treated with either PANCREAZE or placebo in Study 1. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology. Table 1: Treatment-Emergent Adverse Events Occurring in at Least 2 Patients (Greater Than or Equal to 10%) in Either Treatment Group of the Placebo-Controlled, Clinical Study of PANCREAZE PANCREAZE (N=20) n (%) Placebo (N=20) n (%) MedDRA Primary System Organ Class Preferred Term Gastrointestinal Disorders Abdominal pain 2 (10%) 3 (15%) Abdominal pain upper 1 (5%) 3 (15%) Flatulence 1 (5%) 3 (15%) Diarrhea 0 (0%) 4 (20%) Abnormal feces 0 (0%) 3 (15%) General Disorders and Administration Site Conditions Fatigue 0 (0%) 2 (10%) Study 2 was a randomized, investigator-blinded, dose-ranging study of 17 patients, ages 6 months to 30 months, with EPI due to CF. All patients were transitioned from their usual PEP treatment to PANCREAZE at 375 lipase units per kilogram body weight per meal for a 6 day run-in period. Patients were then randomized to receive PANCREAZE at one of four doses (375, 750, 1,125, and 1,500 lipase units per kilogram body weight per meal) for 5 days. Adverse events were collected on patient diary entries and at each study visit. The most commonly reported adverse events were gastrointestinal, including diarrhea and vomiting, and were similar in type and frequency across treatment arms and to those reported in the double-blind, placebo-controlled trial (Study 1). 6.2 Postmarketing Experience Postmarketing data for PANCREAZE have been available since The safety data are similar to those described below. Delayed- and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, a
Recommended
View more...
We Need Your Support
Thank you for visiting our website and your interest in our free products and services. We are nonprofit website to share and download documents. To the running of this website, we need your help to support us.

Thanks to everyone for your continued support.

No, Thanks
SAVE OUR EARTH

We need your sign to support Project to invent "SMART AND CONTROLLABLE REFLECTIVE BALLOONS" to cover the Sun and Save Our Earth.

More details...

Sign Now!

We are very appreciated for your Prompt Action!

x