- ACRONYMS AND DEFINITIONS
- A1C - Hemoglobin A1C
- ADA - American Diabetes Association
- CrCl - Creatinine clearance
- DM - Diabetes mellitus
- GI - Gastrointestinal
- DRUGS IN CLASS
- Amylin analogs
- Pramlintide (Symlin®)
- MECHANISM OF ACTION
- Amylin
- Amylin is a hormone secreted by the pancreas
- Amylin is secreted with insulin in response to food consumption
- Pramlintide is a synthetic version of amylin
- Amylin has the following physiological effects
- Slows gastric emptying (the rate at which food is emptied from the stomach into the small intestine)
- Suppresses glucagon secretion (glucagon stimulates glucose release from the liver)
- Suppresses appetite
- FDA-APPROVED INDICATIONS
- Type one and type two diabetes
- Symlin is indicated as an adjunctive treatment in patients with type one or type two diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy
- TYPE ONE DIABETES
| Effects of Pramlintide on Type 1 DM when added to insulin for 6 months | ||
|---|---|---|
| Pramlintide 60 mcg three times a day (N=164) |
Placebo (N=154) |
|
| Change in HgA1C | -0.44% |
-0.19% |
- Body weight effects
- Pramlintide tends to cause a small amount of weight loss
- A review of pramlintide trials in the Annals of Family Medicine found that type 1 diabetics on pramlintide lost an average of 1 - 3 pounds [2]
- Cholesterol effects
- Pramlintide does not appear to have a significant Cholesterol effects [4]
- Clinical outcomes
- There have been no long-term studies evaluating the effects of pramlintide on clinical outcomes
- ADA recommendations
- StraightHealthcare analysis
- Pramlintide is not widely prescribed. It is expensive and has a modest effect on blood sugars.
- There are no long-term safety and clinical outcome data on pramlintide
- TYPE TWO DIABETES
| Effects of Pramlintide on Type 2 DM when added to insulin and oral meds for 6 months | ||
|---|---|---|
| Pramlintide 120 mcg before meals (N=166) |
Placebo (N=161) |
|
| Change in HgA1C | -0.66% | -0.32% |
- Body weight effects
- Pramlintide tends to cause a small amount of weight loss
- A review of pramlintide trials in the Annals of Family Medicine found that patients on pramlintide lost an average of 1 - 4 pounds [2]
- Cholesterol effects
- Pramlintide does not appear to have a significant Cholesterol effects [4]
- Clinical outcomes
- There have been no long-term studies evaluating the effects of pramlintide on clinical outcomes
- ADA recommendations
- StraightHealthcare analysis
- Pramlintide is not widely prescribed. It is expensive and has a modest effect on blood sugars.
- There are no long-term safety and clinical outcome data on pramlintide
- SIDE EFFECTS
- Gastrointestinal side effects
- Gastrointestinal side effects are the most common side effects of pramlintide
| Trials in type one diabetics | ||
|---|---|---|
| Side effect | Pramlintide 30 - 60 mcg 3 times a day | Placebo |
| Nausea | 48% | 17% |
| Decreased appetite | 17% | 2% |
| Vomiting | 11% | 7% |
| Trials in type two diabetics | ||
|---|---|---|
| Side effect | Pramlintide 120 mcg 2 times a day | Placebo |
| Nausea | 28% | 12% |
| Decreased appetite | 9% | 2% |
| Vomiting | 8% | 4% |
- Low blood sugar (hypoglycemia)
- When pramlintide is taken with premeal insulin, the risk for hypoglycemia is increased
- The risk is particularly high in Type 1 diabetics
- In trials, up to 17% of Type 1 diabetics experienced severe hypoglycemia when starting pramlintide
- The pramlintide manufacturer recommends that the dose of rapid- or short-acting premeal insulin be reduced by 50% when initiating pramlintide
- Blood sugars should also be checked frequently when initiating therapy
- Patients at high-risk for hypoglycemia should not use pramlintide [1]
- See hypoglycemia for a review of hypoglycemia and its treatment
- Patients at high-risk for hypoglycemia include the following:
- Patients with erratic or uncontrolled blood sugars
- Patients with frequent low blood sugars
- Patients with difficulty recognizing low blood sugar symptoms
- Patients with compliance issues [1]
- Injection site reactions
- Redness, swelling, and itching may occur at the site of injection
- These reactions usually clear within a few days to a few weeks [1]
- CONTRAINDICATIONS
- Contraindications
- Hypersensitivity reaction
- Hypoglycemia unawareness
- Confirmed gastroparesis
- Additional considerations
- The manufacturer states that the following patients should not be considered for pramlintide therapy:
- Poor compliance with current insulin regimen
- Poor compliance with prescribed self blood glucose monitoring
- HbA1C > 9%
- Recurrent severe hypoglycemia requiring assistance during the past 6 months
- Require the use of drugs that stimulate gastrointestinal motility
- Pediatric patients
- PRECAUTIONS
- KIdney Disease
- CrCl ≥ 15 ml/min: no dose adjustment necessary
- CrCl < 15 ml/min: has not been studied
- Liver disease
- Pramlintide has not been studied in patients with significant liver disease
- Manufacturer makes no specific dosage recommendation [1]
- Slow gastric emptying (gastroparesis)
- Stomach disorders that slow the emptying of the stomach (ex. diabetic gastroparesis) may be worsened by pramlintide
- Patients with gastroparesis should not take pramlintide
- Certain medications may not be absorbed properly when taken with pramlintide (see drug interactions below) [1]
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Pramlintide
- Alpha-glucosidase inhibitors (acarbose, miglitol) - Alpha-glucosidase inhibitors slow the absorption of carbohydrates and may increase the risk of hypoglycemia
- Drugs that slow gastrointestinal motility - pramlintide slows gastrointestinal motility. This effect may be potentiated when it is taken with other drugs that slow motility.
- Drugs that slow gastrointestinal motility include:
- Anticholinergic medications
- Antihistamines (Benadryl®, doxepin, etc.)
- Antipsychotics (Zyprexa®, etc)
- Bladder agents (Ditropan®, Detrol®, etc.)
- Opiate pain medications (hydrocodone, morphine, etc.)
- Tricyclic antidepressants (Elavil®, imipramine, etc.)
- Drugs affected by slowed gastrointestinal motility
- When a person consumes food or medications, they are partially digested in the stomach
- The stomach then "empties" food and medications into the small intestine
- Pramlintide slows the process of stomach emptying
- Since most medications are absorbed in the small intestine, slowing of stomach emptying by pramlintide can affect the absorption of medications
- In many cases, the overall effect on the drug's efficacy is not significant
- In order to avoid a possible interaction, drugs that may potentially be affected should be taken 1 hour prior or 2 hours after pramlintide
- Drugs that may be affected by slowed gastric emptying:
- Oral Contraceptives
- Antibiotics
- Pain medication (Tylenol®, opiates, etc.)
- Drugs with a narrow therapeutic index
- Carbamazepine (Tegretol®)
- Cyclosporine (Neoral®)
- Digoxin
- Levothyroxine (Synthroid®)
- Lithium
- Phenytoin (Dilantin®)
- Tacrolimus (Prograf®)
- Theophylline (Theo-24®)
- Warfarin (Coumadin®) [9]
- Metabolism and clearance
- Metabolism of pramlintide is not well-defined
- LONG-TERM SAFETY
- Pramlintide was FDA-approved in 2005
- The long-term effectiveness and safety of pramlintide has not been established
- DOSING
- Dosage forms
- Prefilled pen injector (SymlinPen®)
- SymlinPen® 60 - 1.5 ml per pen (1000 mcg/ml)
- SymlinPen® 120 - 2.7 ml per pen (1000 mcg/ml)
- Each carton comes with 2 pens
- Needles
- Uses BD Ultra-Fine™ pen needles
- Price
- No generic (> $150/month)
- Dosing
- Type 1 diabetes
- Starting: 15 mcg immediately prior to each major meal
- Maintenance: 60 mcg immediately prior to each major meal
- Max: 60 mcg three times a day
- Reduce premeal insulin dose by 50% when initiating to avoid severe hypoglycemia
- Major meal is defined as ≥ 250 calories or ≥ 30g of carbohydrates
- Increase dose by 15 mcg every 3 days if nausea is controlled
- If 30 mcg dose is not tolerated, discontinue pramlintide
- Inject subcutaneously into thigh or abdomen. Rotate injection site.
- Do not inject at same site as insulin
- Type 2 diabetes
- Starting: 60 mcg immediately prior to each major meal
- Maintenance: 120 mcg immediately prior to each major meal
- Max: 120 mcg three times a day
- Reduce premeal insulin dose by 50% when initiating to avoid severe hypoglycemia
- Major meal is defined as ≥ 250 calories or ≥ 30g of carbohydrates
- Increase dose after 3 days if nausea is controlled
- Inject subcutaneously into thigh or abdomen. Rotate injection site.
- Do not inject at same site as insulin
- Storage
- Unused pens, refrigerated
- Good until expiration date
- Used pens, refrigerated or room temp
- Good for 30 days
- BIBLIOGRAPHY
- 1 - Pramlintide PI
- 2 - PMID 21060125
- 3 - PMID 17698615
- 4 - PMID 18031595
- 5 - PMID 18945920
- 6 - PMID 17003291
- 7 - PMID 11919132
- 8 - PMID 21193625
- 9 - North Carolina Pharmacy Practice Act. Article 4A. 90-85.28(b1).
- 10 - PMID 12610038
- 11 - PMID 15498087