Gattex One-Vial

Gattex One-Vial® (Gattex One-Vial [rDNA origin]) for injection is indicated for the treatment of adult patients with Short Bowel Syndrome (SBS) who are dependent on parenteral support.

Gattex One-Vial (Gattex One-Vial) is a man-made form of an amino acid that affects the processes of growth and function of cells in the stomach and intestines.

Gattex One-Vial is used to treat short bowel syndrome in adults.

Gattex One-Vial may also be used for purposes not listed in this medication guide.

Dosing Information

The recommended daily dose of Gattex One-Vial is 0.05 mg/kg body weight administered by subcutaneous injection once daily. Alternation of sites for subcutaneous injection is recommended, and can include the thighs, arms, and the quadrants of the abdomen. Gattex One-Vial should not be administered intravenously or intramuscularly. If a dose is missed, that dose should be taken as soon as possible on that day. Do not take 2 doses on the same day.

Monitoring to Assess Safety

A colonoscopy (or alternate imaging) of the entire colon with removal of polyps should be done within 6 months prior to starting treatment with Gattex One-Vial. A follow-up colonoscopy (or alternate imaging) is recommended at the end of 1 year of Gattex One-Vial. If no polyp is found, subsequent colonoscopies should be done no less frequently than every 5 years. If a polyp is found, adherence to current polyp follow-up guidelines is recommended.

Patients should undergo initial laboratory assessments (bilirubin, alkaline phosphatase, lipase and amylase) within 6 months prior to starting treatment with Gattex One-Vial. Subsequent laboratory assessments are recommended every 6 months. If clinically meaningful elevation is seen, further diagnostic workup is recommended as clinically indicated (ie, imaging of the biliary tract, liver, or pancreas).

Dosage Modifications in Renal Impairment

Reduce the dose by 50% in patients with moderate and severe renal impairment (creatinine clearance less than 50 mL/min), and end-stage renal disease.

Discontinuation of Treatment

Discontinuation of treatment with Gattex One-Vial may result in fluid and electrolyte imbalance. Therefore, patients' fluid and electrolyte status should be carefully monitored.

Preparation for Administration

Reconstitute each vial of Gattex One-Vial by slowly injecting the 0.5 mL of preservative-free Sterile Water for Injection provided in the prefilled syringe. Allow the vial containing Gattex One-Vial and water to stand for approximately 30 seconds and then gently roll the vial between your palms for about 15 seconds. Do not shake the vial. Allow the mixed contents to stand for about 2 minutes. Inspect the vial for any undissolved powder. If undissolved powder is observed, gently roll the vial again until all material is dissolved. Do not shake the vial. If the product remains undissolved after the second attempt, do not use. Gattex One-Vial does not contain any preservatives and is for single-use only. Discard any unused portion. The product should be used within 3 hours after reconstitution.

See also:
What is the most important information I should know about Gattex One-Vial?

You should not use Gattex One-Vial if you are allergic to it, or if you have cancer of the stomach, intestines, liver, gallbladder, or pancreas.

Before using Gattex One-Vial, tell your doctor if you have heart disease, kidney disease, intestinal polyps, a blockage in your stomach or intestines, a colostomy or ileostomy, or a history of gallbladder or pancrease problems.

Gattex One-Vial can make it easier for your body to absorb any medicines you take by mouth. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

While using Gattex One-Vial, you may need frequent blood tests (every 6 months), and then a colonoscopy after 1 year of treatment. If you use this medication long-term, you may need a colonoscopy every 5 years.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Stop using Gattex One-Vial and call your doctor at once if you have severe constipation or stomach cramps.

Use Gattex One-Vial as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Gattex One-Vial comes with an extra patient information sheet called a Medication Guide. It also comes with an additional patient leaflet with detailed instructions for use. Read them carefully. Read them again each time you get Gattex One-Vial refilled.
• Gattex One-Vial must be mixed before you inject it. It should be used within 3 hours of mixing. Contact your health care provider if you have any questions about how to mix Gattex One-Vial.
• If there is any powder in the vial that did not dissolve after mixing, gently roll the vial between your hands for 15 seconds. Do not shake Gattex One-Vial.
• Do not use Gattex One-Vial if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Use the proper technique taught to you by your doctor. Inject deep under the skin, NOT into muscle or a vein.
• Be sure to rotate injection sites (eg, thigh, upper arm, stomach) from one injection to the next. Do not inject medicine into skin that is tender, bruised, red, or hard.
• Gattex One-Vial may affect medicines taken by mouth, which may increase the risk of their side effects. Be sure to tell your doctor about all of the other medicines that you are taking. Contact your doctor with any concerns you might have about taking your other medicines.
• Throw away any unused medicine that has been mixed, even if the vial is not empty. Do not store for future use.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Gattex One-Vial, use it as soon as possible that day. If you do not remember until the next day, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses on the same day.

Ask your health care provider any questions you may have about how to use Gattex One-Vial.

Use: Labeled Indications

Short bowel syndrome: Treatment of short bowel syndrome in adults and pediatric patients ≥1 year of age who are dependent on parenteral support.

See also:
What other drugs will affect Gattex One-Vial?

Potential For Increased Absorption Of

Oral Medications

Based upon the pharmacodynamic effect of Gattex One-Vial, there is a potential for increased absorption of concomitant oral medications, which should be considered if these drugs require titration or have a narrow therapeutic index.

Concomitant Drug Therapy

Clinical interaction studies were not performed. No inhibition or induction of the cytochrome P450 enzyme system has been observed based on in vitro studies although the relevance of in vitro studies to an in vivo setting is unknown.

See also:
What are the possible side effects of Gattex One-Vial?

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.

Across all clinical studies, 595 subjects were exposed to at least one dose of Gattex One-Vial (249 patient-years of exposure; mean duration of exposure was 22 weeks). Of the 595 subjects, 173 subjects were treated in Phase 3 SBS studies (134/173 [77%] at the dose of 0.05 mg/kg/day and 39/173 [23%] at the dose of 0.10 mg/kg/day).

The most commonly reported ( ≥ 10%) adverse reactions in subjects treated with Gattex One-Vial across all clinical studies (N = 595) were: abdominal pain (31.3%); injection site reactions (21.8%); nausea (18.8%); headaches (16.3%); abdominal distension (14.8%); upper respiratory tract infection (11.9%).

The rates of adverse reactions in subjects with SBS participating in 2 randomized, placebo-controlled, 24-week, double-blind clinical studies (Study 1 and Study 3) are summarized in Table 1. Only those reactions with a rate of at least 5% in the Gattex One-Vial group, and greater than placebo group, are summarized in Table 1. The majority of these reactions were mild or moderate. Of subjects receiving Gattex One-Vial at the recommended dose of 0.05 mg/kg/day, 88.3% (n=68/77) experienced an adverse reaction, as compared to 83.1% (n=49/59) for placebo. Many of these adverse reactions have been reported in association with the underlying disease and/or parenteral nutrition.

Table 1: Adverse reactions in ≥ 5% of Gattex One-Vial-treated SBS subjects and more frequent than placebo: Studies 1 and 3

In placebo-controlled Studies 1 and 3, 12% of patients in each of the placebo and Gattex One-Vial study groups experienced an injection site reaction.

Adverse Reactions of Special Interest

Malignancy. Three subjects were diagnosed with malignancy in the clinical studies, all of whom were male and had received Gattex One-Vial 0.05 mg/kg/day in Study 2. One subject had a history of abdominal radiation for Hodgkin's disease two decades prior to receiving Gattex One-Vial and prior liver lesion on CT scan, and was diagnosed with metastatic adenocarcinoma of unconfirmed origin after 11 months of exposure to Gattex One-Vial. Two subjects had extensive smoking histories, and were diagnosed with lung cancers (squamous and non-small cell) after 12 months and 3 months of Gattex One-Vial exposure, respectively.

Colorectal Polyps. In the clinical studies, 13 subjects were diagnosed with polyps of the G.I. tract after initiation of study treatment. In the SBS placebo-controlled studies, 1/59 (1.7%) of subjects on placebo and 1/109 (0.9%) of subjects on Gattex One-Vial 0.05 mg/kg/day were diagnosed with intestinal polyps (inflammatory stomal and hyperplastic sigmoidal after 3 and 5 months, respectively). The remaining 11 polyp cases occurred in the extension studies - 2 colorectal villous adenomas (onset at 6 and 7 months in Gattex One-Vial 0.10 and 0.05 mg/kg/day dose groups, respectively), 2 hyperplastic polyp (onset 6 months in Gattex One-Vial 0.10 mg/kg/day dose group and 24 months in Gattex One-Vial 0.05 mg/kg/day dose group), 3 colorectal tubular adenomas (onset between 24 and 29 months in Gattex One-Vial 0.05 mg/kg/day dose group), 1 serrated adenoma (onset at 24 months in Gattex One-Vial 0.05 mg/kg/day dose group), 1 colorectal polyp biopsy not done (onset at 24 months in Gattex One-Vial 0.05 mg/kg/day dose group), 1 rectal inflammatory polyp (onset at 10 months in the Gattex One-Vial 0.05 mg/kg/day dose group, and 1 small duodenal polyp (onset at 3 months in Gattex One-Vial 0.05 mg/kg/day dose group).

Gastrointestinal Obstruction. Overall, 12 subjects experienced one or more episodes of intestinal obstruction/stenosis: 6 in SBS placebo-controlled studies and 6 in the extension studies. The 6 subjects in the placebo-controlled trials were all on Gattex One-Vial: 3/77 (3.9%) on Gattex One-Vial 0.05 mg/kg/day and 3/32 (9.4%) on Gattex One-Vial 0.10 mg/kg/day. No cases of intestinal obstruction occurred in the placebo group. Onsets ranged from 1 day to 6 months. In the extension studies, 6 additional subjects (all on Gattex One-Vial 0.05 mg/kg/day) were diagnosed with intestinal obstruction/stenosis with onsets ranging from 6 days to 19 months. Two of the 6 subjects from the placebo-controlled trials experienced recurrence of obstruction in the extension studies. Of all 8 subjects with an episode of intestinal obstruction/stenosis in these extension studies, 2 subjects required endoscopic dilation and 1 required surgical intervention.

Gallbladder, Biliary and Pancreatic Disease. For gallbladder and biliary disease in the placebo-controlled studies, 3 subjects were diagnosed with cholecystitis, all of whom had a prior history of gallbladder disease and were in the Gattex One-Vial 0.05 mg/kg/day dose group. No cases were reported in the placebo group. One of these 3 cases had gallbladder perforation and underwent cholecystectomy the next day. The remaining 2 cases underwent elective cholecystectomy at a later date. In the extension studies, 4 subjects had an episode of acute cholecystitis; 3 subjects had new-onset cholelithiasis; and 1 subject experienced cholestasis secondary to an obstructed biliary stent. For pancreatic disease in the placebo-controlled studies, 1 subject (Gattex One-Vial 0.05 mg/kg/day dose group) had a pancreatic pseudocyst diagnosed after 4 months of Gattex One-Vial. In the extension studies, 1 subject was diagnosed with chronic pancreatitis; and 1 subject was diagnosed with acute pancreatitis.

Fluid Overload. In the placebo-controlled trials, fluid overload was reported in 4/59 (6.8%) of subjects on placebo and 9/77 (11.7%) subjects on Gattex One-Vial 0.05 mg/kg/day. Of the 9 cases in the Gattex One-Vial group, there were 2 cases of congestive heart failure (CHF), 1 of whom was reported as a serious adverse event and the other as non-serious. The serious case had onset at 6 months, and was possibly associated with previously undiagnosed hypothyroidism and/or cardiac dysfunction.

Concomitant

Oral Medication

Immunogenicity

Consistent with the potentially immunogenic properties of medicinal products containing peptides, administration of Gattex One-Vial may trigger the development of antibodies. Based on data from two trials in adults with SBS (a 6-month randomized placebo-controlled trial, followed by a 24-month open-label trial), the incidence of anti-Gattex One-Vial antibody was 3% (2/60) at Month 3, 18% (13/74) at Month 6, 25% (18/71) at Month 12, 31% (10/32) at Month 24 and 48% (14/29) at Month 30 in subjects who received subcutaneous administration of 0.05 mg/kg Gattex One-Vial once daily. The anti-Gattex One-Vial antibodies were cross-reactive to native glucagon-like peptide (GLP-2) in 5 of the 6 subjects (83%) who had anti-Gattex One-Vial antibodies. Anti-Gattex One-Vial antibodies appear to have no impact on short term (up to 2.5 years) efficacy and safety although the long-term impact is unknown.

In the same two trials, a total of 36 subjects were tested for neutralizing antibodies: 9 of these subjects had no neutralizing antibodies, and the remaining 27 subjects had no detectable neutralizing antibodies although, the presence of Gattex One-Vial at low levels in these study samples could have resulted in false negatives (no neutralizing antibody detected although present).

Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying diseases. For these reasons, comparison of the incidence of antibodies to Gattex One-Vial with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Gattex One-Vial. 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 Gattex One-Vial exposure.

Cardiac disorders: Cardiac Arrest, Cardiac

Failure Nervous system disorders: Cerebral Hemorrhage