Bio-Gest

A peptide that is a homopolymer of Glutamic Acid (Bio-Gest).

Each hard-gelatin capsule contains Pancreatin (Bio-Gest) (pancreas powder) 150 mg corresponding to amylase 8000 Ph Eur units, lipase 10,000 Ph Eur units and protease 600 Ph Eur units. It also contains the following excipients: Core Pellet: Macrogol 4000. Pellet Coating: Hypermellose phthalate, dimethicone 1000, triethyl citrate, cetyl alcohol. Capsule: Iron oxide (E172), titanium dioxide (E171), sodium lauryl sulphate, gelatin.

Diastase + Pepsin (Bio-Gest) is indicated as a digestive aid and for the treatment of acid indigestion, sour stomach, flatulence, epigastric distress, dyspepsia, eructation and to increase appetite.

Betaine (Bio-Gest)® (Betaine (Bio-Gest) anhydrous for oral solution) is indicated for the treatment of homocystinuria to decrease elevated homocysteine blood levels. Included within the category of homocystinuria are:

• Cystathionine beta-synthase (CBS) deficiency
• 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency
• Cobalamin cofactor metabolism (cbl) defect

Concentration and memory disturbances such as:

* forgetfulness

* mental exhaustion

* learning difficulties

* lack of motivation

liver, bile, and pancreas disorders

Pancreatic insufficiency

Pancreatic enzyme supplements commonly cause gastrointestinal adverse effects such as abdominal discomfort and nausea and vomiting. They may also cause buccal and perianal irritation, particularly in infants. Colonic strictures (fibrosing colonopathy) have occurred, mainly in children with cystic fibrosis receiving high doses of Pancreatin (Bio-Gest) preparations; the use of high doses in patients with cystic fibrosis should preferably be avoided. Adequate hydration should be maintained at all times in patients receiving higher strength preparations.

dyspepsia without hyperacidity, oral vehicle

Betaine (Bio-Gest) is a nutrient that is important for functioning of the heart and blood vessels. Betaine (Bio-Gest) works in the body by preventing the build-up of an amino acid called homocysteine. This amino acid can harm blood vessels and contribute to heart disease, stroke, or circulation problems.

Betaine (Bio-Gest) is a byproduct of sugar beet processing.

Betaine (Bio-Gest) is used to reduce homocysteine levels in people with a genetic condition called homocystinuria, in which the amino acid builds up in the body. Betaine (Bio-Gest) is not a cure for homocysteinuria.

Betaine (Bio-Gest) may also be used for purposes not listed in this medication guide.

Pancreatin (Bio-Gest) (pancrelipase) is a combination of three enzymes (proteins): lipase, protease, and amylase. These enzymes are normally produced by the pancreas and are important in the digestion of fats, proteins, and sugars.

Pancreatin (Bio-Gest) is used to replace these enzymes when the body does not have enough of its own. Certain medical conditions can cause this lack of enzymes, including cystic fibrosis, chronic inflammation of the pancreas, or blockage of the pancreatic ducts.

Pancreatin (Bio-Gest) may also be used following surgical removal of the pancreas.

Pancreatin (Bio-Gest) may also be used for purposes not listed in this medication guide.

Dosage

The usual dosage in adult and pediatric patients is 6 grams per day administered orally in divided doses of 3 grams twice daily. In pediatric patients less than 3 years of age, dosage may be started at 100 mg/kg/day divided in twice daily doses, and then increased weekly by 50 mg/kg increments.

Therapy with Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) should be directed by physicians knowledgeable in the management of patients with homocystinuria. Patient response to Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) can be monitored by homocysteine plasma levels. Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts. Response (by homocysteine plasma levels) usually occurs within several days and steady state within a month. Plasma methionine concentrations should be monitored in patients with CBS deficiency.

Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients. However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous).

Administration

The prescribed amount of Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) should be measured with the measuring scoop provided (one level 1.7 mL scoop is equal to 1 gram of Betaine (Bio-Gest) anhydrous powder) and then dissolved in 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula, or mixed with food for immediate ingestion.

How supplied

Dosage Forms And Strengths

Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) is a white, granular, hygroscopic powder for oral solution available in bottles containing 180 grams of Betaine (Bio-Gest) anhydrous.

Storage And Handling

Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) is available in plastic bottles containing 180 grams of Betaine (Bio-Gest) anhydrous. Each bottle is equipped with a plastic child-resistant cap and is supplied with a polystyrene measuring scoop. One level scoop (1.7 mL) is equal to 1 gram of Betaine (Bio-Gest) anhydrous powder.

NDC 66621-4000-1 180 g/bottle

Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) can be ordered by calling Accredo Health Group, Inc., Customer service at 1-888-454-8860

Storage

Store at room temperature, 15 – 30 °C (59 – 86 °F). Protect from moisture.

Distributed in the U.S. by: Rare Disease Therapeutics, Inc. 2550 Meridian Blvd., Suite 150 Franklin, TN 37067.

Pancreatin (Bio-Gest) is not interchangeable with other pancrelipase products.

Pancreatin (Bio-Gest) is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of Pancreatin (Bio-Gest) should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet as described in the Limitations on Dosing below.

Administration

Infants (up to 12 months)

Pancreatin (Bio-Gest) should be administered to infants immediately prior to each feeding, using a dosage of 3,000 lipase units per 120 mL of formula or prior to breast-feeding. Contents of the capsule may be administered directly to the mouth or with a small amount of applesauce. 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 Pancreatin (Bio-Gest) is not crushed or chewed or retained in the mouth, to avoid irritation of the oral mucosa.

Children and Adults

Pancreatin (Bio-Gest) should be taken during meals or snacks, with sufficient fluid. Pancreatin (Bio-Gest) 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 added to a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce, at room temperature. The Pancreatin (Bio-Gest)-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.

Dosage

Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences.1, 2, 3 Pancreatin (Bio-Gest) should be administered in a manner consistent with the recommendations of the Cystic Fibrosis Foundation Consensus Conferences (also known as Conferences) provided in the following paragraphs, except for infants. Although the Conferences recommend doses of 2,000 to 4,000 lipase units in infants up to 12 months, Pancreatin (Bio-Gest) is available in a 3,000 lipase unit capsule. Therefore, the recommended dose of Pancreatin (Bio-Gest) in infants up to 12 months is 3,000 lipase units per 120 mL of formula or per breast-feeding. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.

Additional recommendations for pancreatic enzyme therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy are based on a clinical trial conducted in these populations.

Infants (up to 12 months)

Pancreatin (Bio-Gest) is available in the strength of 3,000 USP units of lipase thus infants may be given 3,000 lipase units (one capsule) per 120 mL of formula or per breast-feeding. Do not mix Pancreatin (Bio-Gest) capsule contents directly into formula or breast milk prior to administration.

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 Pancreatin (Bio-Gest) 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.

Adults with Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis or Pancreatectomy

The initial starting dose and increases in the dose per meal should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet.

In one clinical trial, patients received Pancreatin (Bio-Gest) at a dose of 72,000 lipase units per meal while consuming at least 100 g of fat per day. Lower starting doses recommended in the literature are consistent with the 500 lipase units/kg of body weight per meal lowest starting dose recommended for adults in the Cystic Fibrosis Foundation Consensus Conferences Guidelines. If symptoms and signs of steatorrhea persist, the dosage may be increased by the 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 stricture, indicative of fibrosing colonopathy, in children less than 12 years of age. 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.

How supplied

Dosage Forms And Strengths

The active ingredient in Pancreatin (Bio-Gest) evaluated in clinical trials is lipase. Pancreatin (Bio-Gest) is dosed by lipase units.

Other active ingredients include protease and amylase. Each Pancreatin (Bio-Gest) delayed-release capsule strength contains the specified amounts of lipase, protease, and amylase as follows:

• 3,000 USP units of lipase; 9,500 USP units of protease; 15,000 USP units of amylase delayed-release capsules have a white opaque cap with imprint “Pancreatin (Bio-Gest) 1203” and a white opaque body.
• 6,000 USP units of lipase; 19,000 USP units of protease; 30,000 USP units of amylase delayed-release capsules have an orange opaque cap with imprint “Pancreatin (Bio-Gest) 1206” and a blue opaque body.
• 12,000 USP units of lipase; 38,000 USP units of protease; 60,000 USP units of amylase delayed-release capsules have a brown opaque cap with imprint “Pancreatin (Bio-Gest) 1212” and a colorless transparent body.
• 24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP units of amylase delayed-release capsules have an orange opaque cap with imprint “Pancreatin (Bio-Gest) 1224” and a colorless transparent body.
• 36,000 USP units of lipase; 114,000 USP units of protease; 180,000 USP units of amylase delayed-release capsules have a blue opaque cap with imprint “Pancreatin (Bio-Gest) 1236” and a colorless transparent body.

Pancreatin (Bio-Gest) (pancrelipase) Delayed-Release Capsules

3,000 USP units of lipase; 9,500 USP units of protease; 15,000 USP units of amylase

Each Pancreatin (Bio-Gest) capsule is available as a two piece hypromellose capsule with a white opaque cap with imprint “Pancreatin (Bio-Gest) 1203” and a white opaque body that contains tan colored, delayed-release pancrelipase supplied in bottles of:

70 capsules (NDC 0032-1203-70)

Pancreatin (Bio-Gest) (pancrelipase) Delayed-Release Capsules

6,000 USP units of lipase; 19,000 USP units of protease; 30,000 USP units of amylase

Each Pancreatin (Bio-Gest) capsule is available as a two-piece gelatin capsule with orange opaque cap with imprint “Pancreatin (Bio-Gest) 1206” and a blue opaque body that contains tan-colored, delayed-release pancrelipase supplied in bottles of:

100 capsules (NDC 0032-1206-01)

250 capsules (NDC 0032-1206-07)

Pancreatin (Bio-Gest) (pancrelipase) Delayed-Release Capsules

12,000 USP units of lipase; 38,000 USP units of protease; 60,000 USP units of amylase

Each Pancreatin (Bio-Gest) capsule is available as a two-piece gelatin capsule with a brown opaque cap with imprint “Pancreatin (Bio-Gest) 1212” and a colorless transparent body that contains tan-colored, delayed-release pancrelipase supplied in bottles of:

100 capsules (NDC 0032-1212-01)

250 capsules (NDC 0032-1212-07)

Pancreatin (Bio-Gest) (pancrelipase) Delayed-Release Capsules

24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP units of amylase

Each Pancreatin (Bio-Gest) capsule is available as a two-piece gelatin capsule with orange opaque cap with imprint “Pancreatin (Bio-Gest) 1224” and a colorless transparent body that contains tan-colored, delayed-release pancrelipase supplied in bottles of:

100 capsules (NDC 0032-1224-01)

250 capsules (NDC 0032-1224-07)

Pancreatin (Bio-Gest) (pancrelipase) Delayed-Release Capsules

36,000 USP units of lipase; 114,000 USP units of protease; 180,000 USP units of amylase

Each Pancreatin (Bio-Gest) capsule is available as a two-piece gelatin capsule with blue opaque cap with imprint “Pancreatin (Bio-Gest) 1236” and a colorless transparent body that contains tan-colored, delayed-release pancrelipase supplied in bottles of:

100 capsules (NDC 0032-3016-13)

250 capsules (NDC 0032-3016-28)

Storage and Handling

Pancreatin (Bio-Gest) must be stored at room temperature up to 25°C (77°F) and protected from moisture. Temperature excursions are permitted between 25°C to 40°C (77°F and 104°F) for up to 30 days. Product should be discarded if exposed to higher temperature and moisture conditions higher than 70%. After opening, keep bottle tightly closed between uses to protect from moisture.

Bottles of Pancreatin (Bio-Gest) 3,000 USP units of lipase must be stored and dispensed in the original container.

Do not crush Pancreatin (Bio-Gest) delayed-release capsules or the capsule contents.

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.

2 Borowitz DS, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. Journal of Pediatric Gastroenterology Nutrition. 2002 Sep; 35: 246-259.

3 Stallings VA, Stark LJ, Robinson KA, et al. Evidence-based practice recommendations for nutrition-related 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 Dominguez-Munoz JE. Pancreatic enzyme therapy for pancreatic exocrine insufficiency. Current Gastroenterology Reports. 2007; 9: 116-122.

Manufactured by: Abbott Laboratories GmbH, Hannover, Germany. Marketed by: AbbVie Inc., North Chicago, IL 60064, U.S.A. Revised: September, 2012

See also:
What is the most important information I should know about Betaine (Bio-Gest)?

You should not use Betaine (Bio-Gest) if you are allergic to it.

To make sure you can safely take Betaine (Bio-Gest), tell your doctor about all of your medical conditions.

Follow the directions on your prescription label. Do not use in larger or smaller amounts or for longer than recommended. Your doctor may occasionally change your dose to make sure you get the best results.

Betaine (Bio-Gest) must be mixed with water, juice, milk, food or infant formula just before taking it.

Stop using Betaine (Bio-Gest) and call your doctor at once if you have an unusual headache, dizziness, neck pain or stiffness, problems with memory or speech, changes in your mental state, vision changes, decreased consciousness, or seizure (black-out or convulsions).

Betaine (Bio-Gest) is only part of a complete program of treatment that may also include other vitamin and mineral supplements and a special diet. Follow your diet and medication routines very closely.

Glutamic Acid (Bio-Gest) is generally free of side effects for the vast majority of people who take it; however, people with kidney or liver disease should not consume high intakes of amino acids without consulting a healthcare professional, Because over stimulation of glutamate receptors is thought to be a possible cause of certain neurological diseases (e.g., amyotrophic lateral sclerosis [Lou Gehrigs disease] and epilepsy), people with a neurological disease should consult of physician before supplementing with glutamate.

none known

See also:
What is the most important information I should know about Pancreatin (Bio-Gest)?

Hypersensitivity to Pancreatin (Bio-Gest) or to any of the excipients of Pancreatin (Bio-Gest).

Use Betaine (Bio-Gest) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Betaine (Bio-Gest) by mouth with or without food.
• Shake the bottle gently before removing the cap.
• Use the scoop that comes with Betaine (Bio-Gest) to measure your dose. Ask your pharmacist for help if you are unsure of how to measure your dose.
• Mix the prescribed amount of medicine with 4 to 6 ounces of water, juice, milk, or formula until it is completely dissolved. You may also mix Betaine (Bio-Gest) with food. Swallow the mixture right away.
• Replace the cap tightly after each dose.
• If you miss a dose of Betaine (Bio-Gest), take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Betaine (Bio-Gest).

Use Pancreatin (Bio-Gest) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Pancreatin (Bio-Gest) comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Pancreatin (Bio-Gest) refilled.
• Take Pancreatin (Bio-Gest) by mouth with each meal or snack as directed by your doctor.
• Swallow Pancreatin (Bio-Gest) whole with enough liquid to swallow it completely. Do not break, crush, chew, or hold Pancreatin (Bio-Gest) in your mouth before swallowing. Doing so may increase the risk of mouth irritation from Pancreatin (Bio-Gest). Follow with a glass of water or juice. Contact your doctor if you experience mouth irritation while taking Pancreatin (Bio-Gest).
• If the patient is an infant (up to 12 months old), open the capsule and sprinkle the contents into the infant's mouth or over a small amount of applesauce at room temperature. Do NOT mix Pancreatin (Bio-Gest) directly in breast milk or formula. If sprinkled onto applesauce, give the mixture to the infant right away. After giving Pancreatin (Bio-Gest), follow it with breast milk or formula. Be sure that none of the medicine is crushed, chewed, or left in the mouth.
• If the patient is an adult or child older than 12 months old who cannot swallow the capsule whole, open it and sprinkle the contents over a small amount of acidic soft food (such as applesauce) at room temperature. Mix the medicine with the food and swallow the entire mixture right away, followed by a glass of water or juice. Be sure that none of the medicine is crushed, chewed, or left in the mouth. Check with your doctor if you are unsure which foods you may mix with Pancreatin (Bio-Gest).
• If you miss a dose of Pancreatin (Bio-Gest), skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once or take a dose without a snack or a meal.

Ask your health care provider any questions you may have about how to use Pancreatin (Bio-Gest).

This medication contains digestive enzymes, which are natural substances needed by the body to help break down and digest food. It is used when the pancreas cannot make or does not release enough digestive enzymes into the gut to digest the food. Depending on the amount of enzymes in your product, it may be used for indigestion, as a supplement, or as replacement therapy (e.g., in chronic pancreatitis, cystic fibrosis, cancer of the pancreas, after surgery on the pancreas or gut).

Some supplement products have been found to contain possibly harmful impurities/additives. Check with your pharmacist for more details about the brand you use.

The FDA has not reviewed this product for safety or effectiveness. Consult your doctor or pharmacist for more details.

How to use Pancreatin (Bio-Gest) 4X

Take this medication by mouth with meals and snacks as directed by your doctor.

The dosage is based on your medical condition, diet, and response to treatment.

If you are using the tablet form of the medication, make sure not to keep it in the mouth because doing so can cause irritation to the gums and cheeks. Swallow the medication with water. For the chewable tablets, chew thoroughly before swallowing.

If you are using the capsule form of the medication and swallowing is difficult, the capsule may be opened and the powder mixed with food or liquid.

Be careful not to inhale any of the powder because doing so can irritate the inside of the nose or cause an asthma attack.

Use this medication regularly to get the most benefit from it.

If your doctor has recommended that you follow a special diet, it is very important to follow the diet to get the most benefit from this medication.

Do not change brands or dosage forms of this product without consulting your doctor or pharmacist. Different products may contain different amounts of the digestive enzymes.

Tell your doctor if your condition persists or worsens.

See also:
What other drugs will affect Betaine (Bio-Gest)?

The sedative effect of this medicine will be increased if it is taken with any of the following, which can also cause drowsiness:

* alcohol

* antipsychotics, eg chlorpromazine, haloperidol

* baclofen

* barbiturates, eg phenobarbital, amobarbital

* benzodiazepines, eg diazepam, temazepam

* MAOI antidepressants, eg phenelzine

* other sleeping tablets, eg zopiclone

* sedating antihistamines, eg chlorphenamine, hydroxyzine, promethazine

* strong opioid painkillers, eg morphine, codeine

* tricyclic and related antidepressants eg amitriptyline, maprotiline.

This medicine may increase the anti-blood-clotting effects of oral anticoagulant medicines such as warfarin. If you are taking warfarin your doctor may want to check your blood-clotting time (INR) after you start and stop treatment with this medicine.

If a furosemide injection is administered to someone who has taken this medicine, it may cause sweating, hot flushes and changes in blood pressure due to a hypermetabolic state caused by an effect on thyroid hormone.

No well-known drug interactions with Glutamic Acid (Bio-Gest)

none known

See also:
What other drugs will affect Pancreatin (Bio-Gest)?

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: acarbose, miglitol.

See also:
What are the possible side effects of Betaine (Bio-Gest)?

Adverse Reactions in Clinical Studies

The most serious adverse reaction reported with Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) treatment is the development of hypermethioninemia and cerebral edema in patients with CBS Deficiency.

The assessment of clinical adverse reactions is based on a survey study of 41 physicians, who treated a total of 111 homocystinuria patients with Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous). Adverse reactions were retrospectively recalled and were not collected systematically in this open-label, uncontrolled, physician survey. Thus, this list may not encompass all types of potential adverse reactions, reliably estimate their frequency, or establish a causal relationship to drug exposure. The following adverse reactions were reported (Table 1):

Table 1: Number of Patients with Adverse Reactions to Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) by Physician Survey

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In postmarketing experience with Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous), severe cerebral edema and hypermethioninemia have been reported within 2 weeks to 6 months of starting Betaine (Bio-Gest) therapy, with complete recovery after discontinuation of Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous). All patients who developed cerebral edema had homocystinuria due to CBS deficiency and had severe elevation in plasma methionine levels (range 1,000 to 3,000 μM). As cerebral edema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to Betaine (Bio-Gest) therapy has been postulated as a possible mechanism of action.

The following adverse reactions have been reported in patients during postmarketing use of Betaine (Bio-Gest) (Betaine (Bio-Gest) anhydrous) : anorexia, agitation, depression, irritability, personality disorder, sleep disturbed, dental disorders, diarrhea, glossitis, nausea, stomach discomfort, vomiting, hair loss, hives, skin odor abnormalities, and urinary incontinence.

Not available

none known

See also:
What are the possible side effects of Pancreatin (Bio-Gest)?

The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) that are described elsewhere in the label include fibrosing colonopathy, hyperuricemia and allergic reactions.

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 practice.

The short-term safety of Pancreatin (Bio-Gest) was assessed in clinical trials conducted in 121 patients with exocrine pancreatic insufficiency (EPI): 67 patients with EPI due to cystic fibrosis (CF) and 25 patients with EPI due to chronic pancreatitis or pancreatectomy were treated with Pancreatin (Bio-Gest).

Cystic Fibrosis

Studies 1 and 2 were randomized, double-blind, placebo-controlled, crossover studies of 49 patients, ages 7 to 43 years, with EPI due to CF. Study 1 included 32 patients ages 12 to 43 years and Study 2 included 17 patients ages 7 to 11 years. In these studies, patients were randomized to receive Pancreatin (Bio-Gest) at a dose of 4,000 lipase units/g fat ingested per day or matching placebo for 5 to 6 days of treatment, followed by crossover to the alternate treatment for an additional 5 to 6 days. The mean exposure to Pancreatin (Bio-Gest) during these studies was 5 days.

In Study 1, one patient experienced duodenitis and gastritis of moderate severity 16 days after completing treatment with Pancreatin (Bio-Gest). Transient neutropenia without clinical sequelae was observed as an abnormal laboratory finding in one patient receiving Pancreatin (Bio-Gest) and a macrolide antibiotic.

In Study 2, adverse reactions that occurred in at least 2 patients (greater than or equal to 12%) treated with Pancreatin (Bio-Gest) were vomiting and headache. Vomiting occurred in 2 patients treated with Pancreatin (Bio-Gest) and did not occur in patients treated with placebo; headache occurred in 2 patients treated with Pancreatin (Bio-Gest) and did not occur in patients treated with placebo.

The most common adverse reactions (greater than or equal to 4%) in Studies 1 and 2 were vomiting, dizziness, and cough. Table 1 enumerates adverse reactions that occurred in at least 2 patients (greater than or equal to 4%) treated with Pancreatin (Bio-Gest) at a higher rate than with placebo in Studies 1 and 2.

Table 1: Adverse Reactions Occurring in at Least 2 Patients (greater than or equal to 4%) in Cystic Fibrosis (Studies 1 and 2)

An additional open-label, single-arm study assessed the short-term safety and tolerability of Pancreatin (Bio-Gest) in 18 infants and children, ages 4 months to 6 years, with EPI due to cystic fibrosis. Patients received their usual pancreatic enzyme replacement therapy (mean dose of 7,000 lipase units/kg/day for a mean duration of 18.2 days) followed by Pancreatin (Bio-Gest) (mean dose of 7,500 lipase units/kg/day for a mean duration of 12.6 days). There were no serious adverse reactions. Adverse reactions that occurred in patients during treatment with Pancreatin (Bio-Gest) were vomiting, irritability, and decreased appetite, each occurring in 6% of patients.

Chronic Pancreatitis or Pancreatectomy

A randomized, double-blind, placebo-controlled, parallel group study was conducted in 54 adult patients, ages 32 to 75 years, with EPI due to chronic pancreatitis or pancreatectomy. Patients received single-blind placebo treatment during a 5-day run-in period followed by an intervening period of up to 16 days of investigatordirected treatment with no restrictions on pancreatic enzyme replacement therapy. Patients were then randomized to receive Pancreatin (Bio-Gest) or matching placebo for 7 days. The Pancreatin (Bio-Gest) dose was 72,000 lipase units per main meal (3 main meals) and 36,000 lipase units per snack (2 snacks). The mean exposure to Pancreatin (Bio-Gest) during this study was 6.8 days in the 25 patients that received Pancreatin (Bio-Gest).

The most common adverse reactions reported during the study were related to glycemic control and were reported more commonly during Pancreatin (Bio-Gest) treatment than during placebo treatment.

Table 2 enumerates adverse reactions that occurred in at least 1 patient (greater than or equal to 4%) treated with Pancreatin (Bio-Gest) at a higher rate than with placebo.

Table 2: Adverse Reactions in at Least 1 Patient (greater than or equal to 4%) in the Chronic Pancreatitis or Pancreatectomy Trial

Postmarketing Experience

Postmarketing data from this formulation of Pancreatin (Bio-Gest) have been available since 2009. The following adverse reactions have been identified during post approval use of this formulation of Pancreatin (Bio-Gest). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal disorders (including abdominal pain, diarrhea, flatulence, constipation and nausea), skin disorders (including pruritus, urticaria and rash), blurred vision, myalgia, muscle spasm, and asymptomatic elevations of liver enzymes have been reported with this formulation of Pancreatin (Bio-Gest).

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 reactions included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus.