Teduglutide - Indications, Side Effects, and Pharmacological Aspects

Overview

Teduglutide is a medication used to treat individuals with short bowel syndrome who require parenteral nutrition (nutrition administered through a vein). It imitates glucagon-like peptide-2 or GLP-2, a hormone that is naturally produced in the lower intestine. Teduglutide functions by stimulating certain gut receptors, which causes the production of chemicals that promote healthy intestinal growth and healing. This increases the depth and size of the intestinal lining, facilitating increased nutritional absorption. The United States Food and Drug Administration (USFDA) approved the Teduglutide on December 20, 2012.

Drug Group:

Teduglutide injection is a medication that belongs to a group of drugs known as glucagon-like peptide-2 or GLP-2 analogs. It improves the intestines' ability to absorb nutrients and liquids.

Indications:

Teduglutide is a medication used to treat adults and children aged one year and older who have short bowel syndrome (SBS) and need help getting nutrition through an IV (intravenous route or through the vein).

Contraindications:

None.

Dosage Forms and Available Strengths:

• Teduglutide is a white powder that has a dosage of five mg (milligrams) per single-dose vial.

• A prefilled syringe with 0.5 mL (milliliters) of sterile water for injection is included with it.

For Patients

What Is Short Bowel Syndrome?

Adults with short bowel syndrome (SBS) have less than 71 to 79 inches (180 to 200 centimeters) of small intestine remaining (normal length: 108 to 334 inches (275 to 850 centimeters). Due to this shortage, patients need more nutrition and water. Weight loss, diarrhea, greasy stools, malnourishment, and abnormalities in the body's salt balance are some of the symptoms. A colon transplant or long-term IV feeding are the two treatment options. A team approach is necessary for managing SBS to enhance patient outcomes.

What Are the Clinical Uses of Teduglutide?

Injectable Teduglutide is used to treat short bowel syndrome in patients requiring IV (intravenous) therapy for additional nutrition or fluids. It is a member of the class of drugs known as GLP-2 analogs. It facilitates improved nutrient and hydration absorption in the intestines.

How Should Teduglutide Be Used?

Teduglutide is a subcutaneous injection drug that is a powder that is combined with a liquid before being injected. The recommended dosage is one injection at the same time every day. Adhere to the doctor's directions and seek clarification if necessary. Never change the dosage or injection schedule without first talking to the doctor. In the event that an accidental overdose is administered, call the doctor right away.

Even if everything seems well, keep taking Teduglutide; do not discontinue it without consulting with a physician. The patient or someone helping them can give the shots. Make sure to follow the directions carefully when mixing and injecting the drug, and watch the doctor perform the initial demonstration.

Included in the Teduglutide package are:

• Powder vials.

• Syringes with liquid already filled.

• Alcohol swabs.

• Dosing syringes with needles.

• Needles for mixing.

Throw away all used syringes, vials, and needles in a container that can withstand punctures. Find out from the pharmacist or doctor how to properly dispose of this container. Make sure the solution is clear, colorless, or pale yellow, and particle-free before injecting. After mixing, use the solution within three hours.

Teduglutide should be injected into the stomach, thigh, or upper arm rather than a vein or muscle. Every day, switch up the injection site; stay away from painful, bruised, red, or hard spots. An information sheet about Teduglutide will be given by the doctor or pharmacist at the start of treatment and each time a refill is given. Consult it thoroughly and pose any queries. One can get more details on the FDA website.

What Are the Side Effects of Teduglutide?

Teduglutide injections may have adverse effects. If any of these symptoms are severe or persistent, let a doctor know:

• Skin issues around the injection site.

• Hives.

• Itching.

• Rash.

• Skin red patches.

• Headache.

• Gas.

• Changes in appetite.

• Trouble getting to sleep or remaining asleep.

• Runny nose.

• Cough.

• Sneezing.

• Symptoms are similar to the flu.

Certain adverse effects may be dangerous. If any of the following signs appear, get in touch with a physician right away:

• Abdominal pain, swelling, or soreness (stomach area).

• In the case of a stoma (a surgically created opening in the abdomen that permits the direct removal of bodily waste into a collection bag through the end of the colon) patients, swelling and obstruction at the stoma entrance.

• High temperature.

• Chills.

• Changes in the stool.

• Having trouble passing gas or having a bowel movement.

• Feeling nauseous.

• Throwing up.

• Dark urine.

• Skin or eye yellowing.

• Inflammation of the ankles or feet.

• Quick weight gain.

• Breathing difficulties.

An injection of Teduglutide may hasten the proliferation of aberrant cells, raising the risk of cancer. See a doctor about the dangers associated with using this drug. Additional negative effects from Teduglutide injections are possible. Inform a physician of any strange side effects one has while taking this drug.

What Are the Things to Inform the Doctor Before Taking Teduglutide?

Prior to administering Teduglutide:

• Report any allergies to Teduglutide, other drugs, or any of the substances in the Teduglutide injection to the physician and pharmacist. Consult the Medication Guide or request an ingredient list from the pharmacist.

• Tell the pharmacist and doctor about all other medications one consumes, including over-the-counter and prescription medications, vitamins, supplements, and herbal remedies. Mention using any antihistamines, sedatives, sleeping pills, tranquilizers, or drugs for mental illness, anxiety, or seizures (an uncontrollably high spike in electrical activity between brain cells). The doctor might have to monitor for adverse effects or change the dosage of medications.

• Let the doctor know if one has a history of cancer, polyps (abnormal tissue growth on a mucous membrane) in the intestines or rectum, high blood pressure, or illnesses affecting the gallbladder, heart, kidneys, or pancreas. Stomas are surgically formed openings from inside the body to the outside, commonly in the abdomen area.

• Be advised that Teduglutide may result in colon polyps or growths. Before beginning Teduglutide, the doctor will perform a colonoscopy (a process that allows the doctor to examine the entire colon or large intestine) six months later. After a year, the procedure will be repeated, and thereafter, at least every five years. If polyps are discovered, they must be extracted. If a polyp is found to have malignancy (cancer), the doctor might suggest quitting Teduglutide.

• Let the doctor know whether the patient is nursing a baby, intends to get pregnant, or is already pregnant. If the patient becomes pregnant while taking Teduglutide, let the doctor know right away.

Dietary Consideration: Maintain the same diet unless advised otherwise by the doctor.

Missed Dose: Inject the missed dose as soon as it is remembered that day. Inject the next dose the following day at the usual time. Do not inject two doses on the same day.

Storage: Store Teduglutide away from children's reach in its original container, kept tightly closed. Keep out of the bathroom and store at room temperature, away from sources of heat and moisture. Teduglutide should not be frozen. Utilize the Teduglutide injection powder prior to the expiration date indicated on the kit's "Use By" sticker.

Disposal: Get rid of unnecessary prescriptions the right way to keep kids, dogs, and other people from consuming them. Teduglutide should not be flushed down the toilet. A pharmaceutical take-back program is the most effective way to get rid of it. To find out more about take-back initiatives in the area, speak with the pharmacist or get in touch with the recycling and trash departments.

Safety Advice: Keep any medications out of children's reach and sight. Many items are easily accessed by young children and are not child-resistant, such as inhalers, eye drop vials, and weekly pill minders. After using the medication, always secure the safety cap and store it somewhere secure, out of children's reach and sight.

For Doctors

Mechanism of Action: Teduglutide is a synthetic variation of glucagon-like peptide-2 (GLP-2), a human peptide that is spontaneously produced by cells in the lower intestine. GLP-2 lessens the production of stomach acid and aids in boosting blood flow to the intestines and portal vein. Teduglutide functions by attaching itself to neurons in the gut wall, myofibroblasts under the intestinal lining, and GLP-2 receptors present in certain intestinal cells. Substances such as nitric oxide, keratinocyte growth factor (KGF), and insulin-like growth factor (IGF)-1 are released when these receptors are active.

Pharmacodynamics:

• Intestinal Fluid Absorption: Over the course of a 21-day research, 17 people with short bowel syndrome underwent Teduglutide testing. The daily doses given to the participants were 0.03, 0.1, and 0.15 mg/kg (milligrams per kilogram), which is equivalent to 0.6 to three times the therapeutic level. With the exception of the lowest dose (0.03 mg/kg), all doses markedly increased the amount of intestinal fluid absorbed by about 750 to 1000 mL (milliliters) daily. These dosages also caused an increase in the depth of the intestinal crypts and the height of the intestinal villi.

• Cardiac Electrophysiology: The QT interval was not considerably impacted by Teduglutide at five times the recommended dose, suggesting that there was no meaningful effect on heart rhythm.

Pharmacokinetics:

• Absorption: About 88 percent of Teduglutide that is injected subcutaneously into healthy individuals enters the bloodstream. After injection, Teduglutide takes three to five hours to reach its peak blood level. A typical dose in individuals with short bowel syndrome (SBS) results in a peak blood concentration of 36 ng/mL (nanograms per milliliter), with a continuous quantity of 0.15 µg•hr/mL (micrograms per hour per milliliter) over time. In the body, Teduglutide does not accumulate despite repeated dosages. The blood level of Teduglutide grows in tandem with the dose.

• Distribution: Teduglutide is distributed throughout the body in healthy individuals in a manner similar to blood volume.

• Elimination: Teduglutide is broken down by the body into smaller components like amino acids and peptides, which are many ways natural hormones are.

• Excretion: The kidneys eliminate Teduglutide mostly from the blood at a rate that is comparable to the kidneys' blood-filtering rate (GFR). Before it is eliminated, it remains in the body for roughly two hours in healthy individuals and 1.3 hours in those with SBS.

What Is the Prescribed Dosage and Method of Administration for Teduglutide?

• Administration:

  • Adults: Can administer themselves or receive administration from a caregiver.

  • Children: Cannot self-administer medicine. Children weighing less than ten kg (kilograms) should not use the five mg kit.

• Pre-treatment Tests (Within Six Months of Beginning Teduglutide):

  • Adults: Advised to have a complete colonoscopy with polyp removal.

  • Children: Check for blood clots in the stool. Get a sigmoidoscopy or colonoscopy if blood is discovered.

  • Every patient: Verify the initial levels of lipase, amylase, alkaline phosphatase, and bilirubin.

• Suggested Dosage and Method of Administration

  • Dosage: 0.05 mg/kg (milligrams per kilogram) subcutaneous injection per day.

  • Injection Sites: Switch between the quadrants of the abdomen, arms, and thighs.

  • Renal Impairment Adjustment: 0.025 mg/kg daily for end-stage renal disease or moderate-to-severe kidney problems.

• Colonoscopy Schedule:

  • Adults: If no polyps are discovered, a follow-up colonoscopy will be performed after a year, then every five years, more often in the presence of polyps.

  • Children: Stool testing every year. after a year of treatment, then every five years, or in the event of unexplained gastrointestinal bleeding, a colonoscopy or sigmoidoscopy.

• Testing in the Lab: Every six months, additional diagnostic procedures, such as imaging, are required if notable alterations are found.

• Discontinuation: After stopping Teduglutide, electrolyte and fluid imbalances may result. Watch for these problems in patients.

Guidelines for Preparation:

• Reconstitution:

  • Fill the Teduglutide vial with 0.5 mL of sterile water.

  • After letting it sit for thirty seconds, roll the vial gently for fifteen seconds.

  • After two minutes, check to see if any powder has remained undissolved. If it is, roll gently once more.

  • Particles should not be present in the clear solution. If it has particles or is discolored, throw it away.

• Using Reconstituted Solution:

  • Take out a maximum of 0.38 mL (3.8 mg) to be dosed from the vial.

  • Utilize three hours after preparing. Throw away any leftover solution.

  • Avoid shaking or freezing just for one use.

Drug Interactions: Teduglutide's mechanism of action may increase the body's absorption of other oral drugs. Certain adult participants in studies who were taking Teduglutide in addition to benzodiazepines reported mental health changes. A patient taking Teduglutide with other oral medications should be constantly monitored for any side effects from those treatments, and the dosage of those medications may need to be reduced. This is especially true for medications that have a narrow safety margin or require cautious dosing.

Overdose: During eight days, the maximum dosage of Teduglutide evaluated in clinical trials was 80 mg (milligrams) per day, and no unanticipated adverse effects were seen. When taking Teduglutide in excess, a patient should be regularly monitored by a physician.

Clinical Studies: Research on using Teduglutide to treat individuals with SBS has demonstrated promising outcomes for both adult and pediatric patients. In a trial with a placebo, adults receiving Teduglutide saw a minimum 20 percent decrease in their need for parenteral nutrition (PN) as opposed to 30 percent of those receiving a placebo. An extension study showed that the effects persisted for two years, with a mean reduction in PN volume of 66 percent and 93 percent of participants maintaining or enhancing their response. Significant PN volume reductions were confirmed by additional research, and some people were completely weaned off of PN. Promising results were also observed in pediatric trials: 38 percent of children aged one to 17 reduced PN infusion by at least one day per week, and 69 percent of them achieved a 20 percent reduction in PN volume. Children's follow-up studies upheld these gains, demonstrating the effectiveness of Teduglutide in lowering PN reliance and improving the quality of life for SBS patients.

Warnings and Precautions:

• Possibility of Cancer Growth: Teduglutide may raise the chance of cancer and other abnormal tissue growth. Use Teduglutide for people who have a high risk of cancer only if the advantages outweigh the dangers. Teduglutide should be stopped if gastrointestinal cancer develops. Continue Teduglutide for other cancers after carefully weighing the risks and benefits.

• Colorectal Polyps: If an adult has a colonoscopy, have any polyps removed within six months of beginning Teduglutide. After a year, have a follow-up every five years or more frequently if necessary. Teduglutide should be stopped if colorectal cancer is discovered. Before beginning Teduglutide in children, check their stools for hidden blood. If blood is found, do a colonoscopy or sigmoidoscopy. Maintain yearly stool tests throughout the course of treatment, and have a colonoscopy or sigmoidoscopy done after the first year of treatment and then every five years after that, or if there is any new or unexplained bleeding.

• Small Bowel Tumors: Keep an eye out for benign tumors in the small intestine and remove them if detected. If small bowel cancer is found, discontinue Teduglutide immediately.

• Intestinal Obstruction: In the event of an intestinal or stomal obstruction, stop Teduglutide for a short while and take care of the obstruction. When the obstruction clears, restart Teduglutide if clinically indicated.

• Biliary and Pancreatic Disease: Gallstones and inflammation have been described in cases of pancreatic and biliary disease. Check alkaline phosphatase and bilirubin levels six months before beginning Teduglutide treatment and every six months after that, or more frequently if problems develop. Since pancreatitis has also been documented, measure the levels of lipase and amylase six months before beginning medication and then every six months after that, if necessary.

• Fluid Imbalance and Overload: Reevaluate the usage of Teduglutide if cardiac problems develop, and modify fluid intake if fluid overload happens, particularly in patients with heart disease. After stopping Teduglutide, keep an eye on the hydration and electrolyte balance.

• Increased Absorption of Other Medications: Keep an eye on patients who are taking drugs with limited safety margins because Teduglutide can make it more likely that these drugs will need to be taken at different dosages.

Use in Specific Populations:

• Pregnancy: Based on case reports, there is no evidence of a higher risk of serious birth abnormalities, miscarriage, or adverse effects on the mother or child in pregnant women who use Teduglutide. On the other hand, malnutrition poses a concern to pregnant women with small bowel syndrome, which can have detrimental effects on both the mother and the unborn child. The active ingredient, Teduglutide, did not harm the fetus in animal experiments when administered at higher levels than in human doses. In the United States, the overall risk of miscarriage and birth abnormalities is estimated to be 15 to 20 percent and 2 to four percent, respectively. Severe malnutrition during pregnancy can result in premature birth, low birth weight, growth problems, birth deformities, and even neonatal death in women with small bowel syndrome.

• Lactation: No information is available on the presence of Teduglutide in human milk, its effects on breastfed infants, or how much milk is produced. Nonetheless, Teduglutide is present in nursing rats' milk, although exposure to breastfed babies is thought to be minimal. It is not advised to breastfeed a newborn while receiving Teduglutide medication due to the possible serious hazards it poses, including cancer.

• Use in Pediatrics: Teduglutide’s efficacy and safety in children younger than a year old have not been shown. However, for kids with short bowel syndrome who require parenteral care and are between the ages of one and 17, Teduglutide has been shown to be both safe and effective. This finding is supported by subsequent studies on youngsters as well as studies conducted on adults. In these investigations, Teduglutide was used to treat 41 pediatric patients, and 29 of them underwent up to 94 weeks of observation. The observed side effects resembled those reported by adults.

• Geriatric Use: In studies including 134 patients, 19 of them were 65 years of age or older, and five of them were 75 years of age or older. Younger and older patients did not significantly differ in safety or effectiveness; however, sensitivity levels may vary amongst elderly people.

• Renal Impairment: Teduglutide exposure rises with the degree of impairment in patients with mild to severe kidney issues. For both children and adults with substantial renal disease (eGFR less than 60 mL/min/1.73 m² or milliliters of cleansed blood per minute per body surface), the dosage should be cut in half.

• Hepatic Impairment: Patients with significant liver impairment have not been investigated with Teduglutide. On the other hand, people with mild to severe hepatic impairment do not require a dosage change.