indication

For the treatment of type 1 and type 2 diabetes mellitus as an adjunct to preprandial insulin therapy in patients without adequate glycemic control of insulin therapy.

pharmacology

Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline.

mechanism of action

Pramlintide is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, pramlintide acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss. There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3.

biotransformation

Metabolized primarily by the kidneys.

absorption

The absolute bioavailability of a single subcutaneous dose of pramlintide is approximately 30 to 40%.

half life

Approximately 48 minutes

route of elimination

Pramlintide is metabolized primarily by the kidneys.

drug interactions

Carbinoxamine: Pramlintide may enhance the anticholinergic effect of Anticholinergics such as carbinoxamine. These effects are specific to the gastrointestinal tract. Use caution during concomitant therapy with pramlintide and anticholinergics. Additive effects on reduced gastrointestinal motility may occur.

Clidinium: Pramlintide may enhance the anticholinergic effect of anticholinergics such as clidinium. These effects are specific to the GI tract. Use caution during concomitant therapy with pramlintide and anticholinergics. Additive effects on reduced GI motility may occur.

Doxylamine: May cause additive slowing of GI motility.

Thiothixene: The anticholinergic effects of Tranylcypromine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Tiotropium: The anticholinergic effects of Tiotropium may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Tolterodine: Additive reduction in gut motility may occur. Consider alternate therapy or use caution during concomitant therapy.

Tranylcypromine: The anticholinergic effects of Tranylcypromine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Trihexyphenidyl: The anticholinergic effects of Trihexyphenidyl may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Trimeprazine: The anticholinergic effects of Trimeprazine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Trimethobenzamide: The anticholinergic effects of Trimethobenzamide may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Trimipramine: The anticholinergic effects of Trimipramine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Triprolidine: The anticholinergic effects of Triprolidine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Trospium: The anticholinergic effects of Trospium may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Zuclopenthixol: May cause additive reduction in GI motility. Use caution or consider alternate therapy.