Pramlintide

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Contents 1 Description 2 Mechanism of Action 3 Time Required for Therapeutic Response 4 Pharmacokinetics 5 Special Population Pharmacokinetics 6 Indications and Dosage 6.1 FDA Approved Indications 6.2 Dosage Adjustment 6.3 Dosage Limits 7 Administration 8 Monitoring Parameters 9 Contraindications/Precautions 9.1 Contraindications 9.2 Precautions 9.3 Pregnancy indications 9.4 Breast-feeding indications[1] 10 Drug-Drug, -Food, -Herb Interactions 11 Adverse Reactions/Side Effects [1] [12] 12 Overdosage Measures 13 Product Information and Distribution 14 Patient Information 15 References 16 PUBMED References 16.1 Efficacy Trial Articles 16.2 Therapeutic Class Comparison Articles 16.3 Pharmacokinetics Articles 16.4 Drug Interaction Articles 16.5 Adverse Effects Articles 16.6 Pharmacoeconomic Articles 17 External Links	This page is not completed and has not been reviewed for accuracy. You are reading a non-certified PubDrug document. This document is incomplete and not ready for final editing, review, and certification. Until this document is certified, any registered PubDrug user may edit its content. Authored by: jrs38 Certified by: certifier signature (type four tildes) Pramlintide quick reference Image:Type image name here (.png file extension already included).png
	Pramlintide general drug information
	Pronunciation	PRAM-lin-tide (.wav file)
	Trade Name(s)	Symlin
	How Supplied	Subcutaneous injection
	Generic Availability	No
	Patent Expiry Date	December 29 2009; March 8 2011; September 7 2013; January 9 2018
	Classification	Antihyperglycemics
	Schedule	Rx
	Pregnancy Category	C
	Breast-feeding	There are no adequate studies of pramlintide in nursing mothers, and it is not known if pramlintide is excreted in human breast milk.
	Pramlintide chemical information
	IUPAC Name	not available
	Empirical Formula	not available
	Molecular Weight	4186.6 Daltons g/mol
	pharmacokinetic information  |  [ pharmacogenomic information]

Description

Amylin is a naturally occuring neuroendocrine hormone present in humans that is constructed in the pancreas and contributes to glucose control after meals. Pramlintide is a synthetic analog of human amylin.Pramlintide is not present, or non-functioning in patients with diabetes, much like insulin. When used in conjunction with insulin, pramlintide can help patients achieve improved glucose control with additional benefits that cannot be obtained by insulin alone. ^[1] Pramlintide has also been shown to help control high glucose levels without inducing hypoglycemia, with limited side effects. ^[2]

Mechanism of Action

Pramlintide slows gastric emptying thereby aiding in the absorption of glucose and increasing satiety. This also decreases the secretion of glucagon which counteracts the role of insulin and amylin with the body.^{[1] [3]}

Time Required for Therapeutic Response

• Initial: exact time is unspecified, however hypoglycemic events will be experienced within 3 hours of excessive injection ^[1]

Pharmacokinetics

Absorption
Pramlintide is almost completely absorbed upon injection. The body mass index or amount of adipose tissue in the patient does not appear to affect absorption or bioavailability. Pramlintide may also affect the absorption of other medications by decreasing the transit time a medication is within the intestine.^[4]

Distribution
Pramlintide is not extensively bound to blood cells or albumin, and the drug’s distribution is minimally affected by the availability of binding sites.

Metabolism
The drug is metabolized predominantly in the kidneys with a half-life of approximately 48 minutes. ^[5]

Excretion
Although metabolized in the kidney, renal function does not appear to have a significant affect on drug clearance. In clinical trials, patients with moderate or severe impairment of renal function did not appear to have reduced drug clearance or increased effects of pramlintide.

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Special Population Pharmacokinetics

• Renal insufficiency: Patients with compromised renal function as defined as having a ClCr greater than 20ml/min but less than 50ml/min, did not have increased serum levels of pramlintide, with respect to patients with normal renal funciton, however some deposition may occur. ^[6]
• Hepatic insufficiency: Studies are yet to be conducted on the effect of pramlintide on patients with compromised hepatic function, although the drug is primarily eliminated through the kidneys, therefore hepatic dysfunction is not expected to affect blood concentrations of pramlintide.
• Hemodialysis: No studies have been conducted on patients on dialysis.
• Geriatric: No age-related variance in the activity of pramlintide have been seen in the geriatric population.
• Pediatric: Not yet evaluated
• Gender: No study has been conducted to evaluate gender effects on pramlintide pharmacokinetics.

Indications and Dosage

FDA Approved Indications

Diabetes Mellitus Type I ^[7]

• Starting dose:
  • subcutaneously inject 15mcg immediatenly prior to meals. Reduce preprandial insulin dose by 50% when initiating.
• Maintenance dose:
  • 60mcg is highest possible dose, once achieved adjust preprandial insulin to obtain proper glucose control.
• Titration schedule: Increase the dose by 15mcg increments when there is no nausea for greater than three days.

Diabetes Mellitus Type II ^[8]

• Starting dose:
  • 60mcg immediatlely prior to meals; increase the dosage to 120 mcg once there is no nausea for 3-7 days.
• Maintenance dose:
  • 120mcg is highest possible dose, once achieved adjust preprandial insulin to obtain proper glucose control.

Dosage Adjustment

Renal insufficiency: No current suggestions.
Hepatic insufficiency: No current suggestions.
Hemodialysis: No studies have been done on dialysis patients.
Geriatric: No studies have been conducted in the elderly population.
Pediatric: Currently not reccommended, however evidence does suggest safety for type I diabetics. ^[9]
Gender: No gender difference evaluations have been conducted.

Dosage Limits

• Adults: 120mcg/dose SC
• Elderly: 120mcg/dose SC
• Adolescents and children: Not reccommended

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Administration

• Route: Subcutaneous
• Method:
  • Pramlintide should be given immediately prior to each major meal, with a 50% reduction in the dose of the preprandial insulin.
  • Visually inspect the drug for particles and discoloration, do not use if cloudy or discolored.
  • Do not mix pramlintide with insulin
  • Always use a new syringe and needle for each dose administered.

Monitoring Parameters

• Monitor metabolic parameters such as glucose and hemoglobin A1C.

Contraindications/Precautions

Contraindications

• Patients with a known hypersensitivity to pramlintide
• Patients with a confirmed diagnosis of gastroparesis, due to decrease in gastric emptying ^[10]
• Hypoglycemia unawareness

Precautions

• Hypoglycemia
• Renal Impairment ^[6]

• Hepatic Impairment
• Allergy/Injection site Reaction

Pregnancy indications

Category C

• No adequate and well-controlled studies have been conducted in pregnant women. Studies in perfused human placenta indicate that pramlintide has low potential to cross the maternal/fetal placental barrier. ^[11]

Breast-feeding indications^[1]

• Pramlintide should be administered to nursing women only if it is determined by the health care professional that the potential benefit outweighs the potential risk to the infant.

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Drug-Drug, -Food, -Herb Interactions

Click the link above to go to the drug interactions page.

Adverse Reactions/Side Effects ^{[1] [12]}

Pramlintide Adverse Reactions Chart

Incidence	Body System	Adverse Reactions
>10%	All	Nausea 28%; Headache 13%; Hypoglycemia 11.1%
1-10%	CNS	Dizziness 6%; Fatigue 7%
	GI	Anorexia 9%; Vomitting 8%, Abdominal Pain 8%; Pharyngitis 5%
	Respiratory	Coughing 6%
<1%	All	-

Overdosage Measures

• Overdose can manifest as severe nausea, associated with vomitting, diarrhea, vasodilatation, and dizziness. In a controlled study 10mg doses were administered to three healthly volunteers, no hypoglycemia was reported.

Treatment:

• Pramlintide has a short half life and in the case of an overdose supportive measures should be carried out.

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Product Information and Distribution

Note: appearance only available for brand-name product

Dose/form	Drug color(s)	Drug shape	Markings or odor/flavor
Solution 0.6mg/mL	clear	-	Vial marked with concentration

• Inactive ingredients for solution: metacresol, D-mannitol, acetic acid, sodium acetate

Patient Information

• Pramlintide is given at mealtimes, and does not replace daily insulin.
• Reduce the amount of insulin being adminstered before meals by 50% once therapy with pramlintide has begun.
• Patients may experience low blood sugar, should this occur it will happen within 3 hours of administration. This will manifest as inability to think clearly or operate machinery.
• This should only be used in patient who cannot obtain glucose control on their current medications, and is an adjunt therapy.
• Never directly mix pramlintide with insulin. ^[13]
• Store pramlintide vials in the refrigerator until opened, once opened they may be stored at room temperature or in the refrigerator for 28 days. discard any opened medication after 28 days.
• If a dose is missed, do not take it. Skip that dose and resume treatment at the next interval.

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References

1. ↑ ^{1.0 1.1 1.2 1.3 1.4} Symlin® [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc., Mar. 2005.
2. ↑ Whitehouse F, Kruger DF, Fineman M, Shen L, Ruggles JA, Maggs DG, Weyer C, Kolterman OG.A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care. 2002 Apr;25(4):724-30.
3. ↑ Young A.Inhibition of gastric emptying. Adv Pharmacol. 2005;52:99-121.
4. ↑ Kellmeyer TA, Kesty NC, Wang Y, Frias JP, Fineman MS.Pharmacokinetics of an oral drug (acetaminophen) administered at various times relative to subcutaneous injection of pramlintide in subjects with type 2 diabetes. J Clin Pharmacol. 2007 Jul;47(7):798-805.
5. ↑ Vine W, Smith P, LaChappell R, Blase E, Lumpkin R, Young A.Nephrectomy decreases amylin and pramlintide clearance in rats.Horm Metab Res. 1998 Aug;30(8):514-7.
6. ↑ ^6.0 6.1 Gong W, Liu ZH, Zeng CH, Peng A, Chen HP, Zhou H, Li LS.Amylin deposition in the kidney of patients with diabetic nephropathy. Kidney Int. 2007 Jul;72(2):213-8.
7. ↑ Edelman S, Garg S, Frias J, Maggs D, Wang Y, Zhang B, Strobel S, Lutz K, Kolterman O. A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes. Diabetes Care. 2006 Oct;29(10):2189-95.
8. ↑ Karl D, Philis-Tsimikas A, Darsow T, Lorenzi G, Kellmeyer T, Lutz K, Wang Y, Frias JP. Pramlintide as an adjunct to insulin in patients with type 2 diabetes in a clinical practice setting reduced A1C, postprandial glucose excursions, and weight.Diabetes Technol Ther.2007;9(2):191-9.
9. ↑ Heptulla RA, Rodriguez LM, Bomgaars L, Haymond MW.The role of amylin and glucagon in the dampening of glycemic excursions in children with type 1 diabetes. Diabetes. 2005 Apr;54(4):1100-7.
10. ↑ Kong MF, King P, Macdonald IA, Stubbs TA, Perkins AC, Blackshaw PE, Moyses C, Tattersall RB.Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM.Diabetologia. 1997 Jan;40(1):82-8.
11. ↑ Hiles RA, Bawdon RE, Petrella EM. Ex vivo human placental transfer of the peptides pramlintide and exenatide (synthetic exendin-4). Hum Exp Toxicol. 2003 Dec;22(12):623-8.
12. ↑ Thompson RG, Peterson J, Gottlieb A, Mullane J. Effects of pramlintide, an analog of human amylin, on plasma glucose profiles in patients with IDDM: results of a multicenter trial. Diabetes. 1997 Apr;46(4):632-6.
13. ↑ Weyer C, Fineman MS, Strobel S, Shen L, Data J, Kolterman OG, Sylvestri MF. Properties of pramlintide and insulin upon mixing. Am J Health Syst Pharm. 2005 Apr 15;62(8):816-22.

PUBMED References

Efficacy Trial Articles

1. Smith SR, Blundell JE, Burns C, Ellero C, Schroeder BE, Kesty NC, Chen KS, Halseth AE, Lush CW, Weyer C. Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E620-7.
2. Chapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Lush CW, Chen K, Lacerte C, Burns C, McKay R, Weyer C, Horowitz M. Low-dose pramlintide reduced food intake and meal duration in healthy, normal-weight subjects. Obesity (Silver Spring). 2007 May;15(5):1179-86.
3. Chapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Strobel S, Wang Y, Burns C, Lush C, Weyer C, Horowitz M. Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes. Diabetologia. 2005 May;48(5):838-48.
4. Maggs DG, Fineman M, Kornstein J, Burrell T, Schwartz S, Wang Y, Ruggles JA, Kolterman OG, Weyer C. Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes: a dose-timing study. Diabetes Metab Res Rev.2004 Jan-Feb;20(1):55-60.
5. Fineman MS, Koda JE, Shen LZ, Strobel SA, Maggs DG, Weyer C, Kolterman OG. The human amylin analog, pramlintide, corrects postprandial hyperglucagonemia in patients with type 1 diabetes. Metabolism. 2002 May;51(5):636-41.
6. Levetan C, Want LL, Weyer C, Strobel SA, Crean J, Wang Y, Maggs DG, Kolterman OG, Chandran M, Mudaliar SR, Henry RR. Impact of pramlintide on glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions among patients with type 1 diabetes intensively treated with insulin pumps.Diabetes Care. 2003 Jan;26(1):1-8.
7. Hollander PA, Levy P, Fineman MS, Maggs DG, Shen LZ, Strobel SA, Weyer C, Kolterman OG. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care.2003;26(3):784-90.
8. Hollander P, Ratner R, Fineman M, Strobel S, Shen L, Maggs D, Kolterman O, Weyer C.Addition of pramlintide to insulin therapy lowers HbA1c in conjunction with weight loss in patients with type 2 diabetes approaching glycaemic targets. Diabetes Obes Metab. 2003 Nov;5(6):408-14.
9. Maggs D, Shen L, Strobel S, Brown D, Kolterman O, Weyer C. Effect of pramlintide on A1C and body weight in insulin-treated African Americans and Hispanics with type 2 diabetes: a pooled post hoc analysis.Metabolism.2003;52(12):1638-42.

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Therapeutic Class Comparison Articles

Not available

Pharmacokinetics Articles

1. Kellmeyer TA, Kesty NC, Wang Y, Frias JP, Fineman MS. Pharmacokinetics of an oral drug (acetaminophen) administered at various times relative to subcutaneous injection of pramlintide in subjects with type 2 diabetes.J Clin Pharmacol.2007 Jul;47(7):798-805.
2. Kenley RA, Tracht S, Stepanenko A, Townsend M, L'Italien J.Kinetics of pramlintide degradation in aqueous solution as a function of temperature and pH. AAPS PharmSciTech. 2000 Mar 18;1(2):E7.
3. Kenley RA, Tracht S, Stepanenko A, Townsend M, L'Italien J.Kinetics of pramlintide degradation in aqueous solution as a function of temperature and pH. AAPS PharmSciTech. 2000 Mar 18;1(2):E7.

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Drug Interaction Articles

1. Kapoor D, Goodwin E, Channer KS, Jones TH.Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006 Jun;154(6):899-906.
2. de Araújo PS, de Alencar Ximenes RA, Lopes CF, Duarte JY, da Silva MM, Carneiro EM.Antiretroviral treatment for HIV infection/AIDS and the risk of developing hyperglycemia and hyperlipidemia.Rev Inst Med Trop Sao Paulo. 2007 Mar-Apr;49(2):73-8.

Adverse Effects Articles

1. Singh-Franco D, Robles G, Gazze D. Pramlintide acetate injection for the treatment of type 1 and type 2 diabetes mellitus. Clin Ther. 2007 Apr;29(4):535-62.

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Pharmacoeconomic Articles

None yet available

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External Links

Patient information pages

• [American Diabetes Association]

Other resources

• [FDA website on Pramlintide]
• [MedlinePlus Page for Pramlintide]

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