Package insert/product label
Generic name: pancrelipase
Pharmaceutical form:capsule, delayed release
Drug class: Digestive enzymes
1. Indications and use of Zenpep
ZENPEP®Used for Exocrine Pancreatic Insufficiency Due To Cystic Fibrosis Or Other Conditions.
2. Dosage and administration of Zenpep
2.1 Dosage
ZENPEP is not interchangeable with other pancrelipase products.
ZENPEP is administered orally. Treatment should be started at the lowest recommended dose and gradually increased. Dosing of ZENPEP should be individualized based on clinical symptoms, the degree of steatorrhea present, and dietary fat content (see dosage limitations below).
Dosing recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences.1, 2, 3ZENPEP shall be administered in a manner consistent with the Congressional recommendations in the following sections, with one exception. Congress recommends doses of 2000 to 4000 units of lipase for infants up to 12 months of age. ZENPEP comes in a capsule containing 3,000 lipase units. The recommended dose of ZENPEP for infants up to 12 months is 3000 lipase units. Patients can be dosed based on a dosing schedule based on fat intake or actual body weight.
Babies (up to 12 months)
Babies can receive 3000 units of lipase (one capsule) per 120 ml of formula or breastfeeding. Do not mix ZENPEP capsule contents directly into formula or breast milk prior to administration[see Dosage and Administration (2.2)].
Children over 12 months and under 4 years
Enzyme dosing should start with 1,000 units of lipase/kg of body weight per meal for children under 4 years of age up to a maximum of 2,500 units of lipase/kg of body weight per meal (or less than or equal to 10,000 units of lipase/ kg of body weight per day), or less than 4,000 lipase units/g of ingested fat per day.
Children from 4 years old and adults
Enzyme dosing should start with 500 lipase units/kg body weight per meal for persons over 4 years of age up to a maximum of 2,500 lipase units/kg body weight per meal (or less than or equal to 10,000 units of lipase/kg of body weight per day), or less than 4,000 units of lipase/g of fat ingested per day.
Typically, half the prescribed dose of ZENPEP for a complete individual meal should be administered with each snack. The total allowance should reflect approximately three meals plus two or three snacks per day.
Enzyme doses expressed in lipase units/kg body weight per meal should be reduced in elderly patients because they weigh more but tend to consume less fat per day. kg of body weight.
Dosage Limitations
Dosing should not exceed the maximum recommended dose established by the Cystic Fibrosis Foundation Consensus Conference guidelines.1, 2, 3
If symptoms and signs of steatorrhea persist, the dose may be increased by a healthcare professional. Patients should be instructed not to increase the dose alone. There is great variation between individuals in terms of enzymes. Therefore, a range of doses is recommended. Dosage changes may require a adjustment period of several days. If doses exceed 2500 lipase units/kg body weight per meal, further investigation is required.
Doses greater than 2,500 lipase units/kg body weight per meal (or more than 10,000 lipase units/kg body weight per day) should be used with caution and only if proven effective with 3-day fecal fat measurements , indicating a significantly improved fat absorption coefficient. Doses greater than 6,000 lipase units/kg body weight per meal have been associated with colonic strictures suggestive of fibrotic colon disease in children with cystic fibrosis younger than 12 years of age[see Warnings and Precautions (5.1)]. Patients currently receiving doses greater than 6000 lipase units/kg body weight per meal should be reviewed and the dose reduced immediately or titrated to a lower range.
2.2 Administration
ZENPEP should always be taken as prescribed by a healthcare professional.
Babies (up to 12 months)
ZENPEP should be administered to infants immediately before each feeding at a dose of 3000 lipase units (one capsule) per 120 ml of breastmilk replacer or per feeding. The contents of the capsule can be administered with a small amount of applesauce or other acidic food with a pH of 4.5 or less (eg commercially available banana or pear preparations). The contents of the capsule can also be administered directly into the mouth. Administration should be followed by breast milk or formula. Capsule contentshould notmixed directly into formula or breast milk as this may reduce effectiveness. Care must be taken not to crush, chew or hold ZENPEP in the mouth to avoid irritation of the oral mucosa.
Kids and adults
ZENPEP should be taken with or between meals, with plenty of fluids.ZENPEP capsules and capsule contents must not be crushed or chewed.Capsules must be swallowed whole.
For patients who are unable to swallow capsules intact, capsules can be gently opened and contents sprinkled with small amounts of soft acidic food with a pH of 4.5 or less (e.g.,
ZENPEP - soft food mixture should be swallowed immediately, without crushing or chewing, followed by water or juice to ensure complete swallowing. Care must be taken to ensure that no medication is trapped in the mouth.
3. Pharmaceutical forms and dosages
The active ingredient in ZENPEP evaluated in clinical trials is lipase. ZENPEP is administered with lipase units.
ZENPEP is available in 7 color-coded capsule strengths.
Other active ingredients include protease and amylase. Each ZENPEP capsule contains the specified amounts of lipase, protease and amylase.
Capsules of all strengths are colored as follows:
- •
- 3,000 USP units of lipase. 10,000 USP units of protease. 14,000 USP Amylase Capsules have white opaque cap and white opaque body, red imprint with "APTALIS 3"
- •
- 5,000 USP units of lipase. 17,000 USP units of protease. 24,000 USP Unit Amylase Capsules have white opaque cap and white opaque body, blue imprint with "APTALIS 5"
- •
- 10,000 lipase USP units. 32,000 USP units of protease. 42,000 USP Units of Amylase Capsules have yellow opaque cap and white opaque body, blue imprint with "APTALIS 10"
- •
- 15,000 USP units of lipase. 47,000 USP units of protease. 63,000 USP Units of Amylase Capsules have red opaque cap and white opaque body, blue imprint with "APTALIS 15"
- •
- 20,000 USP units of lipase. 63,000 USP units of protease. 84,000 USP Units of Amylase Capsules have opaque green cap and opaque white body, blue imprint with "APTALIS 20"
- •
- 25,000 USP units of lipase. 79,000 USP units of protease. 105,000 USP Units of Amylase Capsules have opaque blue cap and opaque white body, blue imprint with "APTALIS 25"
- •
- 40,000 lipase USP units. 126,000 USP units of protease. 168,000 USP Units of Amylase Capsules have orange opaque cap and white opaque body, blue imprint with "APTALIS 40"
4. Contraindications
No
5. Warnings and precautions
5.1 Fibrous colonopathy
Fibrotic colonopathy has been reported after treatment with various pancreatic enzyme products. Fibrotic colonopathy is a rare serious side effect that was first described in association with the use of high doses of pancreatic enzymes, usually with use over a long period of time, and is most often reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrotic colonic disease remains unknown.Dosesof pancreatic enzyme products greater than 6,000 lipase units/kg body weight per meal has been associated with colonic strictures in children younger than 12 years of age.1Patients with fibrotic disease of the colon should be closely monitored because some patients may be at risk of developing strictures. It is not certain whether fibrotic colon disease will go into remission. It is generally recommended, unless clinically indicated, that enzyme doses be less than 2500 lipase units/kg body weight per day. meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g of fat eaten per day[see Dosage and Administration (2.1)].
Doses greater than 2,500 lipase units/kg body weight per meal (or more than 10,000 lipase units/kg body weight per day) should be used with caution and only if proven effective with 3-day fecal fat measurements , indicating a significantly improved fat absorption coefficient. Patients receiving doses greater than 6000 lipase units/kg body weight per meal should be evaluated and the dose reduced immediately or titrated to a lower range.
5.2 Possibility of irritation of the oral mucosa
Care must be taken to ensure that no medication is trapped in the mouth. ZENPEP must not be crushed, chewed or mixed with food with a pH value greater than 4.5. These actions may disrupt the protective intestinal mucosa, resulting in premature enzyme release, oral mucosal irritation, and/or loss of enzyme activity.[see Dosage and Administration (2.2) and patient counseling information (17.1)]. For patients unable to swallow capsules intact, capsules can be gently opened and contents added to a small amount of soft acidic food with a pH of 4.5 or less, such as applesauce. ZENPEP Soft Food Mix should be swallowed immediately followed by water or juice to ensure complete swallowing.
5.3 Potential risk of hyperuricemia
Caution should be exercised when ZENPEP is prescribed to patients with gout, renal insufficiency or hyperukaemia. Pig-derived pancreatic enzyme products contain purines that can increase blood uric acid levels.
5.4 Potential exposure to viruses from the origin of the product
ZENPEP is derived from the pancreatic tissue of pigs used for food. Although the risk of transmission of an infectious agent to humans from ZENPEP has been reduced by screening for certain viruses during manufacture and inactivating certain viruses during manufacture, there is a theoretical risk of transmission of viral diseases, including diseases caused by new or unidentified viruses. . Thus, the presence of porcine viruses that can infect humans cannot be definitively ruled out. However, there have been no reported cases of infectious diseases associated with the use of porcine pancreas extracts.
5.5 Allergic reactions
Caution should be exercised when pancrelipase is administered to a patient with a known porcine protein allergy. Serious allergic reactions, including anaphylaxis, asthma, urticaria and pruritus, have been reported rarely with other pancreatic enzyme products with different formulations of the same active ingredient (pangrelipase). The risks and benefits of continuing ZENPEP therapy in patients with severe allergy should be weighed against the patient's overall clinical needs.
6. Adverse effects/side effects
More serious side effects reported with different pancreatic enzyme products of the same active ingredient (pangrelipase) include fibrotic colonopathy, hyperukaemia and allergic reactions.[see Warnings and Precautions (5)].
6.1 Experience with clinical trials
As clinical trials are conducted under widely varying conditions, rates of adverse reactions observed in clinical trials with one drug cannot be directly compared with frequencies in clinical trials with another drug and may not reflect frequencies seen in clinical practice.
The short-term safety of ZENPEP was evaluated in two clinical studies conducted in 53 patients aged 1 to 23 years with exocrine pancreatic insufficiency (EPI) due to CF. In both studies, ZENPEP was administered in doses of approx. 5,000 units of lipase per kg per day for treatment durations from 19 to 42 days. The population was almost evenly distributed by gender and approximately 96% of patients were Caucasian.
Study 1 was a randomized, double-blind, placebo-controlled, 2-treatment crossover study of 34 patients aged 7 to 23 years with EPI due to CF. In this study, patients were randomized to receive ZENPEP at individually titrated doses (not to exceed 2500 lipase units per kg per meal) or matching placebo for 6 to 7 days of treatment, followed by crossover to the alternative treatment for an additional 6 to 7 days. . days. days. The average exposure to ZENPEP during this study, including the titration and open-crossing period, was 30 days.
The incidence of adverse events (regardless of causality) was similar during double-blind treatment with ZENPEP (56%) and placebo (50%). The most common adverse events reported during the study were gastrointestinal disturbances, which were reported more frequently during placebo treatment (41%) than during ZENPEP treatment (32%), and headache, which was reported more frequently. frequency during treatment with ZENPEP (15%) than during treatment with placebo (0). The type and frequency of side effects were similar in children (7-11 years old), adolescents (12-16 years old) and adults (over 18 years old).
As clinical trials are conducted under controlled conditions, observed incidences of side effects may not reflect frequencies seen in clinical practice.
table 1lists treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 6%) treated with ZENPEP or placebo in study 1. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology.
| Preferred MedDRA system class primary organ term | ZENPEP | Placebo |
| gastrointestinal problems | ||
| Abdominal pain | 6 (18%) | 9 (28%) |
| Inflation | 2 (6%) | 3 (9%) |
| Nervous system disorders | ||
| Headache | 5 (15%) | |
| Injuries, poisoning and procedural complications | ||
| Hematoma | 2 (6%) | |
| researches | ||
| the weight dropped | 2 (6%) | 2 (6%) |
| Respiratory, thoracic and mediastinal diseases | ||
| Cough | 2 (6%) | |
| General disorders and conditions of administration | ||
| early saturation | 2 (6%) |
Study 2 was an open-label, uncontrolled study of 19 patients aged 1 to 6 years with EPI due to CF. After a 4- to 14-day screening period for current PEP, Study 2 patients received ZENPEP in individually titrated doses ranging from 2,300 to 10,000 lipase units per day. kg of body weight per day, with an average of approx. 5,000 units of lipase per kg of body weight. weight per day (not to exceed 2,500 lipase units per kg per meal) for 14 days. There was no comparator treatment and adverse events were collected from patient diary entries and at each study visit.
The most commonly reported adverse reactions were gastrointestinal, including abdominal pain and steatorrhea, and were similar in type and frequency to those reported in the double-blind, placebo-controlled trial (Study 1).
6.2 Post-Launch Experience
Post-marketing data for ZENPEP are available as of 2009. The following side effects have been identified following post-approval use of Zenpep. As these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or demonstrate a causal relationship to drug exposure.
The most commonly reported side effects are gastrointestinal disturbances (including bloating, abdominal pain, diarrhoea, flatulence, constipation and nausea) and skin disorders (including itching, hives and rash).
In patients at risk for abnormal blood glucose levels, glycemic control may be affected by the administration of pancreatic enzyme replacement therapy. Additional glucose monitoring should be considered in these patients.
Delayed and immediate release pancreatic enzyme products with different formulations of the same active ingredient (pangrelipase) have been used to treat patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions such as chronic pancreatitis. The long-term safety profile of these products is described in the medical literature. More serious side effects include fibrotic disease of the colon, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinomas, and severe allergic reactions such as anaphylaxis, asthma, urticaria, and itching.
In general, pancreatic enzyme products have a well-defined and favorable risk-benefit profile in exocrine pancreatic insufficiency.
7. Interactions with medications
No drug interactions were identified. No formal interaction studies have been performed.
8. Use in specific populations
8.1 Pregnancy
Risk overview
Published data from case reports on the use of pangrelipase in pregnant women have not identified a drug-related risk of serious birth defects, miscarriage, or other adverse maternal or fetal outcomes. Pancrelipase is poorly absorbed systemically. Therefore, maternal use is not expected to result in fetal drug exposure. Animal reproduction studies have not been performed with pancrelipase.
The estimated historical risk of serious birth defects and miscarriage for the indicated population is unknown. All pregnancies carry a historical risk of birth defects, loss, or other adverse outcomes. In the general US population, the estimated historical risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
8.2 Breastfeeding
Risk overview
There are no data on the presence of pancrelipase in human or animal milk, effects on the infant or effects on milk production. Pancrelipase is poorly absorbed systemically after oral administration, therefore maternal use is not expected to result in clinically relevant exposure of infants to the drug. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ZENPEP and any adverse effects of ZENPEP on the infant or underlying maternal conditions.
8.4 Pediatric use
The short-term safety and efficacy of ZENPEP were evaluated in 2 clinical studies in pediatric patients aged 1 to 17 years with EPI due to CF.
Study 1 was a randomized, double-blind, placebo-controlled crossover study of 34 patients, 26 of whom were children, including 8 children aged 7 to 11 years and 18 adolescents aged 12 to 17 years. Safety and efficacy in pediatric patients in this study were similar to those in adult patients.[see side effects (6.1) and clinical studies (14)].
Study 2 was a single open-label study in 19 patients aged 1 to 6 years with EPI due to CF. When patients' regimens were switched from their usual PEP regimen to ZENPEP at similar doses, patients experienced similar control of their clinical symptoms.
The safety and efficacy of pancreatic enzyme products with different pancrelipase formulations consisting of the same active ingredient (lipases, proteases and amylases) for the treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis have been described in the medical literature and through clinical experience.
Dosing for pediatric patients should be in accordance with guidelines recommended by the Cystic Fibrosis Foundation Consensus Conference[see Dosage and Administration (2.1)]. Doses of other pancreatic enzyme products greater than 6,000 lipase units/kg body weight per meal have been associated with fibrotic colonic disease and colonic stricture in children younger than 12 years of age.[see Warnings and Precautions (5.1)].
8.5 Geriatric Use
Clinical studies of ZENPEP did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in response between elderly and younger patients.
10. Overdose
In study 1, a 10-year-old patient received 10,856 units of lipase per kg of body weight from ZENPEP over a one-day period. The patient did not experience side effects as a result of the dose increase, nor did he experience side effects during a 44-day follow-up period. No abnormalities were observed in safety laboratory tests (chemistry, hematology, urinalysis or uric acid).
Chronic high doses of pancreatic enzyme products have been associated with fibrotic disease of the colon and colonic stricture.[see Dosage and Administration (2.1) and warnings and precautions (5.1)]. High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia and should be used with caution in patients with a history of hyperuricemia, gout, or renal failure.[see Warnings and Precautions (5.3)].
11. Description of Zenpep
ZENPEP is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains several classes of enzymes, including porcine lipases, proteases, and amylases.
Pancrelipase is a cream colored powder. It is miscible with water and practically insoluble or insoluble in alcohol and ether.
Each oral capsule contains enteric-coated pellets (1.8-1.9 mm for 3000 and 5000 Lipase Units USP, 2.2-2.5 mm for 10,000, 15,000, 20,000, 25,000, 25,000, 20,000 P USP Units) .
The active ingredient evaluated in clinical trials is lipase. ZENPEP is administered with lipase units.
Other active ingredients include protease and amylase.
The inactive ingredients in ZENPEP include colloidal silicon dioxide, croscarmellose sodium, hydrogenated castor oil, hypromellose phthalate, magnesium stearate, microcrystalline cellulose, talc and triethyl citrate and are contained in hypromellose capsules. Red ink printed on 3,000 capsules contains DC 1510 defoamer, industrial denatured alcohol, C.I. 77491-E172 red iron oxide, n-butyl alcohol, shellac and soy lecithin.
3,000 USP lipase units; 10,000 USP units of protease. 14,000 amylase USP units. The capsules have an opaque white cap and an opaque white body marked 'APTALIS 3'. The peels contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide and water.
Blue ink printed on 5,000, 10,000, 15,000, 20,000, 25,000, and 40,000 capsules contains dehydrated alcohol, FD&C Blue #2 C.I. 73015-E132 aluminum lake, isopropyl alcohol, n-butyl alcohol, propylene glycol, shellac, and strong solution of ammonia.
5,000 USP lipase units; 17,000 USP units of protease. 24,000 amylase USP units. The capsules have an opaque white cap and an opaque white body marked 'APTALIS 5'. The peels contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide and water.
10,000 Lipase USP Units; 32,000 USP units of protease. 42,000 amylase USP units. The capsules have an opaque yellow cap and an opaque white body marked 'APTALIS 10'. The peels contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide, water and yellow iron oxide.
15,000 USP lipase units; 47,000 USP units of protease. 63,000 amylase USP units. The capsules have an opaque red cap and an opaque white body marked 'APTALIS 15'. The peels contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, red iron oxide, titanium oxide and water.
20,000 USP lipase units; 63,000 USP units of protease. 84,000 amylase USP units. The capsules have an opaque green cap and an opaque white body marked 'APTALIS 20'. Peels contain carnauba wax or talc, carrageenan, FD&C Blue #2, hypromellose, potassium chloride, titanium oxide, water, and yellow iron oxide.
25,000 USP lipase units; 79,000 USP units of protease. 105,000 amylase USP units. The capsules have an opaque blue cap and an opaque white body marked 'APTALIS 25'. Peels contain carnauba wax or talc, carrageenan, FD&C Blue #2, hypromellose, potassium chloride, titanium oxide and water.
40,000 Lipase USP Units; 126,000 USP units of protease. 168,000 amylase USP units. The capsules have an opaque orange cap and an opaque white body, imprinted with “APTALIS 40”. Peels contain FD&C Yellow #6, hypromellose, titanium oxide and water.
12. Zenpep – Clinical Pharmacology
12.1 Mechanism of action
The pancreatic enzymes in ZENPEP catalyze the hydrolysis of fats into monoglycerides, glycerol and free fatty acids, proteins into peptides and amino acids, and starch into dextrins and short-chain sugars such as maltose and maltose in the duodenum and proximal small intestine, which serves as the digestive system. enzymes normally secreted by the pancreas.
12.3 Pharmacokinetics
The pancreatic enzymes in ZENPEP are enteric coated to minimize destruction or inactivation by stomach acid. ZENPEP is designed to release most enzymes in vivo at pH greater than 5.5. Pancreatic enzymes are not absorbed from the gastrointestinal tract in appreciable amounts.
13. Non-clinical toxicology
13.1 Carcinogenesis, mutagenesis, impaired fertility
Carcinogenicity, genetic toxicology and animal fertility studies have not been performed.
14. Clinical studies
The short-term safety and efficacy of ZENPEP were evaluated in 2 studies conducted in 53 patients aged 1 to 23 years with exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF).
Study 1 was a randomized, double-blind, placebo-controlled crossover study of 34 patients aged 7 to 23 years with EPI due to CF. The final analysis population was limited to 32 patients who completed both double-blind treatment periods and were included in the efficacy analysis population. Patients were randomized to receive ZENPEP or matching placebo for 6 to 7 days of treatment, followed by crossover to the alternative treatment for an additional 6 to 7 days. The mean dose during the controlled treatment periods ranged from a mean dose of 3900 lipase units per kg per day to 5700 lipase units per kg per day. All patients consumed a high-fat diet (greater than or equal to 100 grams of fat per day) during the treatment period.
The primary efficacy measure was the mean difference in coefficient of fat absorption (CFA) between ZENPEP treatment and placebo. AFC was determined by collecting 72-hour stools during both treatments, where both excretion and fat intake were measured. Each patient's CFA during placebo treatment was used as the untreated CFA value.
Mean CFA was 88% with ZENPEP treatment compared to 63% with placebo treatment. The mean difference in CFA was 26 percentage points in favor of ZENPEP treatment with a 95% confidence interval (19, 32) and p≤0.001.
Subgroup analyzes of CFA results showed that the mean change in CFA was greater in patients with lower CFA values without treatment (placebo) compared with patients with higher CFA values without treatment (placebo). There were similar responses to ZENPEP by age and sex.
Study 2 was an open-label, uncontrolled study of 19 patients aged 1 to 6 years (mean age 4 years) with EPI due to CF. About half of the patients were between 1 and 3 years old. Study 2 compared a measure of fat malabsorption, the fecal fat test, before (during treatment with another commercial PEP) and after oral administration of Zenpep capsules with each meal or snack.
All patients in Study 2 were converted to ZENPEP from their usual PEP regimen. After a 4- to 14-day screening period for current PEP, Study 2 patients received ZENPEP in individually titrated doses ranging from 2,300 to 10,000 lipase units per day. kg of body weight per day, with an average of approx. 5,000 units of lipase per kg of body weight. weight per day (not to exceed 2,500 lipase units per kg per meal) for 14 days. There was no washout period. In general, patients experienced similar control of fat malabsorption by the fecal fat test when switched to ZENPEP therapy at similar doses.
15. References
- 1.
- Borowitz DS, Grand RJ, Durie PR, et al. Use of pancreatic enzyme supplementation in patients with cystic fibrosis associated with fibrotic disease of the colon.Pediatric Magazine. 1995; 127: 681-684.
- 2.
- Borowitz DS, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis.Journal of Nutrition in Pediatric Gastroenterology. September 2002; 35: 246-259.
- 3.
- Stallings VA, Start LJ, Robinson KA, et al. Evidence-based practical recommendations for the nutritional management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review.Journal of the American Dietetic Association. 2008; 108: 832-839.
- 4.
- Smyth RL, Ashby D, O'Hea U, et al. Fibrous colonopathy in cystic fibrosis: results of a case-control study.9Lanceta. 1995; 346: 1247-1251.
- 5.
- FitzSimmons SC, Burkhart GA, Borowitz DS, et al. High-dose pancreatic enzyme supplementation and fibrotic colonic disease in children with cystic fibrosis.New England Journal of Medicine. 1997; 336: 1283-1289.
16. How Zenpep is provided
ZENPEP®(pangrelipase) Delayed-release capsules
3,000 USP units of lipase. 10,000 USP units of protease. 14,000 amylase USP units.
Each ZENPEP capsule is supplied as a two-piece hypromellose capsule with an opaque white cap and white body with a red radial imprint and printed with “APTALIS 3”.containing1.8-1.9 mm enteric coated spheres. Capsules are available in bottles with:
- O
- 100 capsules (NDC 73562-113-01)
ZENPEP®(pangrelipase) Delayed-release capsules
5,000 USP units of lipase. 17,000 USP units of protease. 24,000 amylase USP units.
Each ZENPEP capsule is supplied as a two-piece hypromellose capsule with white opaque cap and white body with blue radial imprint and printed with “APTALIS 5”.containing1.8-1.9 mm enteric coated spheres. Capsules are available in bottles with:
- O
- 100 capsules (NDC 73562-115-01)
ZENPEP®(pangrelipase) Delayed-release capsules
10,000 lipase USP units. 32,000 USP units of protease. 42,000 amylase USP units.
Each ZENPEP capsule is supplied as a two-piece hypromellose capsule with an opaque yellow cap and a white body with blue radial imprint and printed with "APTALIS 10", containing 2.2-2.5 mm enteric coated pellets. Capsules are available in bottles with:
- O
- 100 capsules (NDC 73562-110-01)
ZENPEP®(pangrelipase) Delayed-release capsules
15,000 USP units of lipase. 47,000 USP units of protease. 63,000 amylase USP units.
Each ZENPEP capsule is supplied as a two-piece hypromellose capsule with an opaque red cap and a white body with blue radial imprint and printed with "APTALIS 15", containing 2.2-2.5 mm enteric coated pellets. Capsules are available in bottles with:
- O
- 100 capsules (NDC 73562-111-01)
ZENPEP®(pangrelipase) Delayed-release capsules
20,000 USP units of lipase. 63,000 USP units of protease. 84,000 amylase USP units.
Each ZENPEP capsule is supplied as a two-piece hypromellose capsule with an opaque green cap and a white body with blue radial imprint and imprint "APTALIS 20" containing 2.2-2.5 mm enteric coated beads. Capsules are available in bottles with:
- O
- 100 capsules (NDC 73562-112-01)
ZENPEP®(pangrelipase) Delayed-release capsules
25,000 USP units of lipase. 79,000 USP units of protease. 105,000 amylase USP units.
Each ZENPEP capsule is supplied as a two-piece hypromellose capsule with an opaque blue cap and a white body imprinted with blue radial and imprinted “APTALIS 25”, containing 2.2-2.5 mm enteric coated beads. Capsules are available in bottles with:
- O
- 100 capsules (NDC 73562-116-01)
ZENPEP®(pangrelipase) Delayed-release capsules
40,000 lipase USP units. 126,000 USP units of protease. 168,000 amylase USP units.
Each ZENPEP capsule is supplied as a two-piece hypromellose capsule with an orange opaque cap and a white body with blue radial imprint and printed "APTALIS 40" containing 2.2-2.5 mm enteric coated beads. Capsules are available in bottles with:
- O
- 100 capsules (NDC 73562-114-01)
Storage and handling
original observer:
Avoid excessive heat. Store at room temperature (68-77°F, 20-25°C), short trips up to 15-40°C (59-104°F) are permissible. Protect from moisture. AFTER OPENING, BOTTLE MUST BE KEPT NEAR LEAKS between uses to PROTECT FROM MOISTURE.
Repackaged HDPE container:
Avoid excessive heat. Store at 30°C (86°F) for up to 6 months. Short excursions at 15-40°C (59-104°F) are permitted for up to 30 days. Protect from moisture. AFTER OPENING, BOTTLE MUST BE KEPT NEAR LEAKS between uses to PROTECT FROM MOISTURE.
Supplied in sealed packaging (USP).
Keep out of reach of children.
ZENPEP Delayed Release Capsules DO NOT CRUSH.
17. Patient counseling information
See FDA-approved patient labeling (Guidance on medication)
17.1 Dosage and administration
- •
- Advise patients and caregivers that ZENPEP should only be taken as directed by their healthcare professionals. Patients should be advised that the total daily dose should not exceed 10,000 lipase units/kg body weight per day. day unless clinically indicated. This should be especially emphasized for patients who eat a lot of snacks and meals a day. Patients should be advised that if a dose is missed, the next dose should be taken with their next meal or snack as indicated. Doses should not be doubled.[see Dosage and Administration (2)].
- •
- Advise patients and families that ZENPEP must always be taken with food. Patients should be advised that ZENPEP delayed-release capsules should not be crushed or chewed, as this may cause premature release of enzymes and/or loss of enzyme activity. Patients should swallow capsules intact with adequate amounts of liquid during meals. If necessary, the contents of the capsule can also be sprinkled on soft and acidic foods.[see Dosage and Administration (2)].
- •
- Instruct patients to inform their physician if they are pregnant or planning to become pregnant while taking ZENPEP[see Use in Specific Populations (8.1)].
- •
- Instruct patients and caregivers to inform the healthcare professional if the patient has a history of abnormal glucose levels prior to initiating ZENPEP therapy[see Post-Purchase Experience (6.2)].
17.2 Fibrous colonopathy
Advise patients and caregivers to follow dosing instructions carefully, as doses of pancreatic enzyme products greater than 6,000 lipase units/kg body weight per meal (10,000 lipase units/kg body weight/day) have been associated with Colon strictures in children under 12 years of age.[see Dosage and Administration (2)].
17.3 Allergic reactions
Advise patients and family members to contact their healthcare professional immediately if allergic reactions to ZENPEP occur[see Warnings and Precautions (5.5)].
Distributed by:
Nestlé HealthCare Nutrition, Inc.
Bridgewater, Nova Jersey 08807
For more information, call Nestlé HealthCare Nutrition at 1-833-920-2178.
©2020 Nestlé
All trademarks are owned by Société des Produits Nestlé S.A., Vevey, Switzerland or used under license.
Patented. See www.nestlehealthscience.us/patents.
v1.0USPI113
73499NT10
Guidance on medication
| Pharmacy GUIDE |
| Read this Medication Guide before you start taking ZENPEP and every time you get a refill. There may be new information. This information is not a substitute for talking with your doctor about your medical condition or treatment. |
| What is the most important information I should know about ZENPEP? ZENPEP may make you more likely to get a rare bowel disease called fibrotic colonopathy. This condition is serious and may require surgery. The risk of developing this condition can be reduced by following the dosage instructions provided by your doctor.Call your doctor right away if you haveunusual or serious:
Take ZENPEP exactly as prescribed.Chorustake more or less ZENPEP than your doctor tells you to. |
| What is ZENPEP?
|
| What should I tell my doctor before taking ZENPEP? Before taking ZENPEP, tell your doctor about all of your medical conditions, including if you:
Tell your doctor about all medications you take, including prescription and over-the-counter drugs, vitamins, and dietary or herbal supplements. Know the medication you are taking. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. |
| How should I take ZENPEP?
Administration of ZENPEP to children and adults
Administration of ZENPEP to Infants(children up to 12 months):
|
| What are the possible side effects of ZENPEP? ZENPEP can cause serious side effects, including:
Call your doctor right away if you have any of these symptoms. The most common ZENPEP side effects include;
Other possible side effects ZENPEP and other pancreatic enzyme products are made from the pancreas of pigs, the same pigs that humans eat pork. These pigs can transmit viruses. Although it has never been reported, it may be possible for a person to contract a viral infection from consuming porcine pancreatic enzyme products. Tell your doctor if you have any side effects that bother you or do not go away. These are not all possible side effects of ZENPEP. Ask your doctor or pharmacist for more information. Call your doctor for medical advice about side effects. You can report side effects to the FDA by calling 1-800-FDA-1088. You may also report side effects to Nestlé HealthCare Nutrition at 1-833-920-2178. |
| How should I store ZENPEP?
Keep ZENPEP and all medicines out of the reach of children. |
| General information about ZENPEP Medications are sometimes prescribed for purposes other than those listed in a medication guide. Do not use ZENPEP for a condition for which it was not prescribed. Do not give ZENPEP to other people, even if they have the same symptoms as you. It can hurt them. This medication guide summarizes the most important information about ZENPEP. If you want more information, talk to your doctor. You can ask your pharmacist or doctor for information about ZENPEP intended for healthcare professionals. For more information, visit www.ZENPEP.com or call 1-833-920-2178. |
| What are the ingredients in ZENPEP? Active ingredient:lipase, protease, amilase Inactive Ingredients:colloidal silicon dioxide, croscarmellose sodium, hydrogenated castor oil, hypromellose phthalate, magnesium stearate, microcrystalline cellulose, talc and triethyl citrate in hypromellose capsules. Red radial print on capsule with 3000 strength Contains, DC 1510 Antifoam, Industrial Methylated Alcohol, Iron Oxide Red C.I. 77491-E172, n-butyl alcohol, shellac and soy lecithin. Blue radial print on 5,000, 10,000, 15,000, 20,000, 25,000 and 40,000 capsule strengths contains dehydrated alcohol, FD&C Blue #2 C.I. 73015-E132 aluminum lake, isopropyl alcohol, n-butyl alcohol, propylene glycol, shellac and strong ammonia solution. Capsule Ingredients:
|
| Distributed by: For more information, call Nestlé HealthCare Nutrition at 1-833-920-2178. ©2020 Nestlé All trademarks are owned by Société des Produits Nestlé S.A., Vevey, Switzerland or used under license. |
This medication guide has been approved by the US Food and Drug Administration.
Revised on 03/2020
v1.0MG113
73499NT10
MAIN DISPLAY PANEL - Lipase 3000 Units USP
12480856 NDC73562-113-01
Zenpep®
(pangrelipase)
Delayed release capsules
Kun Rx
DOSAGE BY LIPASE UNITS:
Lipase 3,000 USP units
Protease 10,000 USP Units
Amylase 14,000 USP units
Distribute the medication guide to each patient
100 delayed-release capsules
MAIN DISPLAY PANEL - Lipase 5,000 Units USP
12480843 NDC73562-115-01
Zenpep®
(pangrelipase)
Delayed release capsules
Kun Rx
DOSAGE BY LIPASE UNITS:
Lipase 5,000 USP units
Protease 17,000 USP units
Amylase 24,000 USP units
Distribute the medication guide to each patient
100 delayed-release capsules
MAIN DISPLAY PANEL - Lipase 10,000 Units USP
Bottle label NDC 73562-110-01
12480847 NDC73562-110-01
Zenpep®
(pangrelipase)
Delayed release capsules
Kun Rx
DOSAGE BY LIPASE UNITS:
Lipase 10,000 USP units
Protease 32,000 USP units
Amylase 42,000 USP units
Distribute the medication guide to each patient
100 delayed-release capsules
MAIN DISPLAY PANEL - Lipase 15,000 Units USP
12408049 NDC73562-111-01
Zenpep®
(pangrelipase)
Delayed release capsules
Kun Rx
DOSAGE BY LIPASE UNITS:
Lipase 15,000 USP units
Protease 47,000 USP units
Amylase 63,000 USP units
Distribute the medication guide to each patient
100 delayed-release capsules
MAIN DISPLAY PANEL - Lipase 20,000 Units USP
12480857 NDC 73562-112-01
Zenpep®
(pangrelipase)
Delayed release capsules
Kun Rx
DOSAGE BY LIPASE UNITS:
Lipase 20,000 USP units
Protease 63,000 USP units
Amylase 84,000 USP units
Distribute the medication guide to each patient
100 delayed-release capsules
MAIN DISPLAY PANEL - Lipase 25,000 Units USP
12480860 NDC73562-116-01
Zenpep®
(pangrelipase)
Delayed release capsules
Kun Rx
DOSAGE BY LIPASE UNITS:
Lipase 25,000 USP units
Protease 79,000 USP Units
Amylase 105,000 USP units
Distribute the medication guide to each patient
100 delayed-release capsules
MAIN DISPLAY PANEL - Lipase 40,000 Units USP
12480870 NDC73562-114-01
Zenpep®
(pangrelipase)
Delayed release capsules
Kun Rx
DOSAGE BY LIPASE UNITS:
Lipase 40,000 USP units
Protease 126,000 USP units
Amylase 168,000 USP units
Distribute the medication guide to each patient
100 delayed-release capsules