Pramlintide Acetate - A New Frontier in Diabetes Treatment

Overview:

Pramlintide acetate is a drug used to treat type 1 and type 2 diabetes. It is an amylinomimetic (mimics the action of amylin in the body to reduce blood sugar levels) and acts by bringing down elevated blood sugar levels. The United States Food and Drug Administration approved Pramlintide for its use to control diabetes mellitus in 2005. It is used as an adjunct drug in patients receiving preprandial insulin therapy who do not have adequate glycemic control from their insulin therapy. It is available as a subcutaneous (under the skin) solution for injection. If the patient experiences symptoms of sudden lowering of blood pressure (sweating, fast heartbeat, dizziness, or blackout), report to a healthcare professional for the necessary medical intervention.

How Does Pramlintide Acetate Work?

Pramlintide acetate is a synthetic analog of the hormone amylin, which is normally produced by the pancreas in response to meals. It works by slowing stomach emptying, reducing appetite, and increasing feelings of fullness, and it also helps to lower the amount of glucose that is produced by the liver. The injection should be taken before meals for adequate control of blood glucose levels.

Available Doses and Dosage Forms:

Pramlintide acetate is available in two different dosage forms:

• Injectable Solution: This is the most common form of Pramlintide and is available in two different strengths: 60 mcg/mL and 90 mcg/mL. The injectable solution is usually administered subcutaneously (under the skin) before meals.

• Pen-Injector: Pramlintide acetate is also available as a pen-injector, which is pre-filled with the medication and is used to deliver the medication subcutaneously. The Pen-injector is available in 60 mcg and 90 mcg doses.

The usual starting dose of Pramlintide acetate is 60 mcg before the first and second meals of the day. The dosage is adjusted based on the individual's blood sugar levels and under the guidance of a physician.

Warnings:

The warnings and precautions of Pramlintide include

• Hypoglycemia (Low Blood Sugar): Pramlintide may cause low blood sugar (hypoglycemia) when used in combination with other diabetes medications, such as insulin, especially in patients with Type 1 diabetes.

• Mixing: Never mix Pramlintide acetate with Insulin due to the increased drug interaction and severe drop in blood sugar levels.

• Drugs: Talk with the healthcare provider regarding the medications that the patient is taking before starting therapy with Pramlintide.

For Patients:

What Is Diabetes Mellitus?

Diabetes mellitus is a long-term medical disorder where the body struggles to control blood sugar (glucose) levels. This occurs because the pancreas is not producing sufficient insulin, a hormone that controls blood sugar, or because the body's cells are not responding properly to insulin. There are two main types of diabetes: type 1 and type 2.

• Type 1 Diabetes: Also known as insulin-dependent diabetes, which is when the immune system of the body attacks and destroys insulin-producing cells in the pancreas. This results in the person having to take insulin injections for the rest of their life.

• Type 2 Diabetes: It is also known as non-insulin dependent diabetes, is much more common, and is brought on by a confluence of environmental and genetic factors. It often develops in adulthood and is associated with obesity, poor diet, and lack of exercise.

If not treated properly, both types of diabetes can cause major health issues. This includes heart disease, stroke, kidney failure, blindness, nerve damage, and others.

When and Why to Take Pramlintide Acetate?

Pramlintide is typically taken just before meals, and its main function is to slow stomach emptying and reduce the amount of glucose released into the bloodstream after eating. This helps to prevent post-meal blood sugar spikes and improve overall glucose control.

Pramlintide is also known to increase feelings of fullness and suppress hunger, which can aid in weight loss management in people with diabetes.

It is important to note that Pramlintide is only available by prescription and should be used under the guidance of a healthcare professional. It should not be used in people who are allergic to amylin or Pramlintide or in people with severe problems with digestion or stomach emptying.

How Effective Is Pramlintide Acetate?

Pramlintide acetate is an injectable medication that is used as an adjunct to insulin therapy in people with type 1 and types 2 diabetes to improve glucose control. It works by slowing down the rate at which food empties from the stomach, which can help reduce post-meal blood sugar spikes.

Clinical studies have shown that Pramlintide acetate can be effective in improving glucose control in people with diabetes. It has been found to lower hemoglobin A1c (HbA1c) levels, which is a measure of long-term blood sugar control, and to reduce the frequency of hypoglycemia (low blood sugar) episodes.

However, it is important to note that Pramlintide acetate may not be suitable for everyone and that it should be used in combination with insulin therapy under the supervision of a healthcare professional. Additionally, it can cause side effects such as nausea, vomiting, and stomach discomfort.

Overall, Pramlintide acetate has been found to be an effective adjunct to insulin therapy in people with type 1 and type 2 diabetes and has been demonstrated to improve glucose control and reduce the frequency of hypoglycemia. However, it should be used under the supervision of a healthcare professional and may not be suitable for everyone.

Things to Inform the Doctor Before Taking Pramlintide Acetate:

Before starting treatment with Pramlintide acetate it is important to inform the healthcare provider of certain information to ensure that the medication is safe and effective for use.

The Patient Should Inform the Healthcare Provider if the Patient Has:

• Any medical conditions, particularly those related to the pancreas, liver, or kidney.

• A history of pancreatitis or other risk factors for pancreatitis.

• A history of allergies, particularly to insulin or other medications.

• A history of low blood sugar (hypoglycemia) or other complications related to diabetes.

• Any other medications, vitamins, or supplements that the patient is currently taking. Some medications may interact with Pramlintide acetate and affect its effectiveness or safety.

• If pregnant, planning to become pregnant, or breastfeeding.

It is important to inform the healthcare provider if the patient has any other conditions that may affect the ability to use Pramlintide acetate safely, such as if the patient has difficulty swallowing or has a history of depression or other mental health conditions.

Follow the instructions of the healthcare provider regarding the use of Pramlintide acetate, and inform them of any new symptoms or side effects that the patient experiences while taking the medication.

What Are the Side Effects of Pramlintide Acetate?

Report to the doctor for necessary medical intervention if any symptoms of drug allergy are experienced while taking the drug. The symptoms include breathlessness, swelling of the face and lips, etc.

The other common side effects of Pramlintide acetate include

• Hypoglycemia (Low Blood Sugar): Pramlintide acetate when used with insulin, can raise the risk of hypoglycemia.

• Dizziness: It can happen when blood sugar levels drop too low.

• Injection Site Reactions: This can include redness, swelling, and pain at the site of the injection.

• Fatigue: Some people may feel tired when they first start taking Pramlintide acetate.

• Nausea: The most frequent side effect is nausea, usually occurring when treatment is first started. It usually decreases over time.

• Vomiting: Vomiting may occur along with nausea.

• Diarrhea.

• Headache.

Note that not everyone will experience these side effects, and they may vary in intensity. If the patient experiences any severe side effects, contact the healthcare provider immediately.

Also, notify the healthcare provider of any side effects the patient experiences while taking Pramlintide acetate. They can take the necessary measures to manage or reduce side effects and ensure that the treatment is as safe and effective as possible.

How to Use Pramlintide Acetate?

• Administer less insulin at lunchtime when starting Pramlintide acetate.

• The patient must check the blood sugar as directed by the doctor, which may include before and after each meal and before going to bed.

• The initial injection of the drug for those with type 1 diabetes is typically 15 micrograms (mcg).

• Just before a substantial meal, subcutaneously inject the drug under the skin. At least 250 calories or 30 grams of carbohydrates must be included in a large meal.

• The healthcare practitioner will advise the patient to gradually raise the drug dosage if the patient has not had any nausea for three days or more after changing the dose. If the doctor does not instruct the patient to increase the drug dosage, do not do so.

• As soon as the drug dose has been altered, report any nausea or low blood sugar to the healthcare professional immediately away.

• To better control the blood sugar, the healthcare professional might adjust the insulin dose the patient is taking. The ideal insulin dosage for the patient should be disclosed by the doctor.

Administration:

• To minimize the danger of injection site responses, it should be at room temperature before injection.

• Do not administer in combination with Insulin. Administer just before each large meal (containing greater than or equal to 250 kilocalories or greater than or equal to 30 g of carbohydrates).

• Administer to the thigh or abdomen and changes the sites with each administration.

• The injection may be carried out using four, five, or six-millimeter needles regardless of age or body mass index. The drug should be injected at a 90-degree angle (except while injecting in a slim abdomen in which a 45-degree angle is advised).

What Should Be Done if a Dose Is Missed?

Additional injections should not be given if a dose is missed. Wait until the next meal and administer the usual dose with that meal. Do not inject double doses to make up for a missed dose.

What Should Be Done to Treat Pramlintide Acetate Overdose?

If the patient suspects an overdose or experiences severe side effects, contact the healthcare provider or seek immediate medical attention. Treatment for an overdose of Pramlintide acetate will vary depending on the symptoms and severity of the overdose.

Storage of Pramlintide Acetate

• Pramlintide acetate vials should be kept chilled until they are opened.

• Vials that have been opened can be stored in the refrigerator or at room temperature for up to 28 days. After 28 days, any unsealed vial- regardless of whether the medication is still inside- should be discarded.

• Any vial that is over its expiration date, has been frozen, heated above room temperature (77°F/25°C), or has been kept at room temperature for longer than 28 days should be thrown away.

• Keep all medications away from children.

Avoid Self-Medication:

Avoid taking this drug without the proper directions from a pharmacist or doctor. Avoid recommending the medication to others, and do not take it on someone else's advice. Different people react to medications differently, and some may even react worse. Hence, follow the directions provided by the healthcare professional for drug use.

For Doctors:

Indication

Pramlintide acetate is indicated for the treatment of type 1 and type 2 diabetes mellitus.

Dosing:

Type 1 Diabetes Mellitus:

Adult Dosing (18 to 64 Years):

Initiation of Therapy: Reduce mealtime insulin by 50 percent and then start at 15 mcg subcutaneously immediately before major meals; titration, 15 mcg increments (to 30 mcg, 45 mcg, or 60 mcg) when no clinically significant nausea has occurred for at least three days.

Type 2 Diabetes Mellitus:

Initiation of Therapy: Reduce mealtime insulin by 50 percent and then initiate at 60 mcg subcutaneously immediately prior to major meals; maintenance, increase to 120 mcg subcutaneously prior to major meals when no clinically significant nausea has occurred for at least three days.

Dosing Considerations:

• Mild to Severe Renal Impairment: No adjustment necessary.
• Dialysis: Avoid use in patients undergoing dialysis.
• Significant Nausea Persisting at the 45 or 60 Mcg Dose in Type 1 Diabetes: Decrease dose to 30 mcg; if 30 mcg is not tolerated, consider discontinuation of Pramlintide acetate
• Significant Nausea Persisting at the 120 Mcg Dose in Type 2 Diabetes: Decrease dose to 60 mcg.

Pharmacology:

Mechanism of Action:

Pramlintide acts to improve glycemic control by modulating the rate of gastric emptying, preventing the rise in glucagon levels after meals, and by increasing feelings of satiety, which leads to lower calorie intake and accelerates weight loss. Amylin has activity in a number of digestive and gluco-dynamic processes, and by mimicking its activity, Pramlintide works to improve glycemic control. There seem to be at least three different receptor complexes that bind to amylin very specifically.

Pharmacodynamics:

Amylin is a glucoregulatory hormone produced by pancreatic beta cells and released into the bloodstream is produced by pancreatic beta cells and released into the bloodstream in a manner akin to insulin after a meal. Pramlintide is a synthetic analog of amylin. Diabetes patients are lacking in amylin, just like insulin. It is offered as a salt of acetate. A 37-amino acid polypeptide, Pramlintide differs structurally from human amylin by substituting proline for the amino acids alanine, serine, and serine at positions 25, 28, and 29, respectively.

Pharmacokinetics:

Absorption:

Pramlintide acetate is administered subcutaneously and is rapidly absorbed into the bloodstream with a bioavailability of 30 to 40 percent.

Distribution:

Pramlintide acetate does not exhibit extensive protein binding. Around 40 percent of the drug remains unbound in the plasma.

Metabolism:

Pramlintide acetate is metabolized primarily through the renal route, with little to no metabolism by other organs.

Excretion:

Pramlintide acetate is primarily excreted through the kidneys, with less than one percent excreted in the feces. The half-life of Pramlintide acetate is approximately 50 minutes.

Toxicity:

Non-Clinical Toxicity:

Pramlintide was not associated with carcinogenicity, mutagenicity, or impairment in fertility as per animal studies.

Clinical Toxicity:

Toxicity from Pramlintide acetate may be manifested as hypoglycemia. To manage this effect, it is important to monitor blood glucose levels closely and adjust the dosage of insulin and other diabetes medications as needed. Patients should also be instructed to eat a consistent diet and maintain regular mealtimes to minimize the risk of hypoglycemia.

Warnings and Precautions:

Immunologic: The patients may experience hypersensitivity reactions such as erythema, edema, or pruritus at the site of injection.

Concurrent Use:

Avoid the use of drugs that stimulate gastrointestinal motility. Oral medications in which rapid onset or threshold concentration is critical for effects such as analgesics, antibiotics, and oral contraceptives; administered at least one hour before or two hours after injection.

Endocrine and Metabolic:

Avoid administering to patients with low adherence to their insulin regimens or self-monitoring of blood sugar, repeated bouts of severe hypoglycemia needing help during the previous six months, or HbA1c values of more than nine percent.

Mixing Products: Never mix Insulin and Pramlintide acetate. Both these medications have to be administered separately. Due to the increased potential of spreading bloodborne diseases, pens are only to be used by one patient at a time and should never be shared, even if the needle is changed.

Contraindications:

Pramlintide acetate is contraindicated in the following cases

• In patients with confirmed gastroparesis.

• In patients with a known history of hypersensitivity to the drug or any product components.

Drug Interactions:

The drug-drug interactions of Pramlintide are as listed:

• Chloroquine.

• Ciprofloxacin.

• Delafloxacin.

• Enoxacin.

• Gatifloxacin.

• Gemifloxacin.

• Grepafloxacin.

• Hydroxychloroquine.

• Insulin.

• Insulin Aspart, Recombinant.

• Insulin Bovine.

• Insulin Degludec.

• Insulin Detemir.

• Insulin Glargine, Recombinant.

• Insulin Glulisine.

• Insulin Lispro, Recombinant.

• Lanreotide.

• Levofloxacin.

• Lomefloxacin.

• Moxifloxacin.

• Norfloxacin.

• Octreotide.

• Ofloxacin.

• Pasireotide.

• Sparfloxacin.

• Thioctic Acid.

• Trovafloxacin.

• Acebutolol.

• Atenolol.

• Betaxolol.

• Bisoprolol.

• Carteolol.

• Carvedilol.

• Celiprolol.

• Esmolol.

• Labetalol.

• Levobunolol.

• Metipranolol.

• Metoprolol.

• Nadolol.

• Nebivolol.

• Oxprenolol.

• Penbutolol.

• Pindolol.

• Practolol.

• Propranolol.

• Sotalol.

• Timolol.

Other Specifications:

Pramlintide Acetate in Pregnant Women:

Pramlintide is a pregnancy category C drug. It is not currently recommended for use in pregnant women as safety and efficacy have not been established in this population. Consult with a healthcare provider to determine the best treatment plan during pregnancy.

Pramlintide Acetate in Lactating Women:

There is limited information available on the use of Pramlintide acetate in lactating women. It is not known if the drug is excreted in human milk or if it could cause harm to a breastfeeding infant. As such, consult with a healthcare provider to determine the best treatment plan while breastfeeding.

Pramlintide Acetate in Geriatrics:

There is limited information on the use of Pramlintide acetate in geriatric populations. Therefore, it is important for healthcare providers to closely monitor elderly patients for any adverse effects and adjust the dosage accordingly.

Pramlintide Acetate in Patients With Renal Impairment:

Pramlintide acetate is metabolized and excreted by the kidneys, so patients with renal impairment may be at an increased risk of adverse effects from the drug. If a patient with renal impairment is being considered for treatment with Pramlintide acetate, it is important to monitor them closely for adverse effects and adjust the dosage as necessary.

Pramlintide Acetate in Patients With Hepatic Impairment:

If a patient with hepatic impairment is being considered for treatment with Pramlintide acetate, it is important to monitor them closely for adverse effects and adjust the dosage as necessary.