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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(PRAM lin tide)
Generic Available (U.S.)
No
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089141.pdf, must be dispensed with this medication.
Brand Names: U.S.
Pharmacologic Category
Use: Labeled Indications
Adjunctive treatment with mealtime insulin in type 1 diabetes mellitus (insulin dependent, IDDM) patients who have failed to achieve desired glucose control despite optimal insulin therapy
Adjunctive treatment with mealtime insulin in type 2 diabetes mellitus (noninsulin dependent, NIDDM) patients who have failed to achieve desired glucose control despite optimal insulin therapy, with or without concurrent sulfonylurea and/or metformin
Pregnancy Risk Factor
C
Pregnancy Considerations
Due to adverse events observed in some animal studies, pramlintide is classified as pregnancy category C. Based on in vitro data, pramlintide has a low potential to cross the placenta. Maternal hyperglycemia can be associated with adverse effects in the fetus, including macrosomia, neonatal hyperglycemia, and hyperbilirubinemia; the risk of congenital malformations is increased when the Hb A1c is above the normal range. Diabetes can also be associated with adverse effects in the mother. Poorly-treated diabetes may cause end-organ damage that may in turn negatively affect obstetric outcomes. Physiologic glucose levels should be maintained prior to and during pregnancy to decrease the risk of adverse events in the mother and the fetus. Until additional safety and efficacy data are obtained, the use of pramlintide is generally not recommended in the routine management of diabetes mellitus during pregnancy. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
It is not known if pramlintide is present in breast milk. The manufacturer recommends that pramlintide be used in nursing women only when the potential benefit to the mother outweighs the possible risk to the infant.
Contraindications
Hypersensitivity to pramlintide or any component of the formulation; confirmed diagnosis of gastroparesis; hypoglycemia unawareness
Warnings/Precautions
Boxed warnings:
• Insulin/glucose-lowering agents: See “Concurrent drug therapy issues” below.
Disease-related concerns:
• Gastroparesis: Avoid use in patients with conditions or concurrent medications likely to impair gastric motility (eg, anticholinergics); do not use in patients requiring medication(s) to stimulate gastric emptying.
• Nausea: Use with caution in patients with a history of nausea.
• Neuropathic conditions: Use with caution in patients with neuropathic conditions which may mask signs/symptoms of hypoglycemia.
Concurrent drug therapy issues:
• Antihypertensives: Use caution with certain antihypertensive agents (eg, beta-adrenergic blockers) which may mask signs/symptoms of hypoglycemia.
• Insulin/glucose-lowering agents: [U.S. Boxed Warning]: Coadministration with insulin may induce severe hypoglycemia (usually within 3 hours following administration); coadministration with insulin therapy is an approved indication, but does require an initial dosage reduction of insulin and frequent pre- and post-blood glucose monitoring to reduce risk of severe hypoglycemia. Concurrent use of other glucose-lowering agents may increase risk of hypoglycemia.
Other warnings/precautions:
• Appropriate use: Avoid use in patients with poor compliance with their insulin regimen and/or blood glucose monitoring. Do not use in patients with Hb A1c levels >9% or recent, recurrent episodes of hypoglycemia; obtain detailed history of glucose control (eg, Hb A1c, incidence of hypoglycemia, glucose monitoring, and medication compliance) and body weight before initiating therapy. Use caution in patients with visual or dexterity impairment. Patients should use caution when driving or operating heavy machinery until effects on blood sugar are known.
Adverse Reactions
>10%:
Central nervous system: Headache (5% to 13%)
Gastrointestinal: Nausea (28% to 48%), anorexia (≤17%), vomiting (7% to 11%)
Endocrine & metabolic: Severe hypoglycemia (type 1 diabetes ≤17%)
Miscellaneous: Inflicted injury (8% to 14%)
1% to 10%:
Central nervous system: Fatigue (3% to 7%), dizziness (2% to 6%)
Endocrine & metabolic: Severe hypoglycemia (type 2 diabetes ≤8%)
Gastrointestinal: Abdominal pain (2% to 8%)
Respiratory: Cough (2% to 6%), pharyngitis (3% to 5%)
Neuromuscular & skeletal: Arthralgia (2% to 7%)
Miscellaneous: Allergic reaction (≤6%)
Postmarketing and/or case reports: Injection site reactions
Metabolism/Transport Effects
None known.
Drug Interactions
Anticholinergics: Pramlintide may enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Exceptions: Levocabastine (Nasal); Paliperidone. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Use caution with ethanol (may increase hypoglycemia).
Herb/Nutraceutical: Use caution with garlic, chromium, gymnema (may increase hypoglycemia).
Storage
Store unopened vials at 2°C to 8°C (36°F to 46°F); do not freeze. Opened vials may be kept refrigerated or at room temperature ≤30°C (≤86°F). Discard opened vial after 30 days. Protect from light.
Mechanism of Action
Synthetic analog of human amylin cosecreted with insulin by pancreatic beta cells; reduces postprandial glucose increases via the following mechanisms: 1) prolongation of gastric emptying time, 2) reduction of postprandial glucagon secretion, and 3) reduction of caloric intake through centrally-mediated appetite suppression
Pharmacodynamics/Kinetics
Duration: 3 hours
Protein binding: ~60%
Metabolism: Primarily renal to des-lys1 pramlintide (active metabolite)
Bioavailability: ~30% to 40%
Half-life elimination: ~48 minutes
Time to peak, plasma: 20 minutes
Excretion: Primarily urine
Dosage
SubQ: Adults: Note: When initiating pramlintide, reduce current insulin dose (including rapidly- and mixed-acting preparations) by 50% to avoid hypoglycemia.
Type 1 diabetes mellitus (insulin dependent, IDDM): Initial: 15 mcg immediately prior to meals; titrate in 15 mcg increments every 3 days (if no significant nausea occurs) to target dose of 30-60 mcg (consider discontinuation if intolerant of 30 mcg dose)
Type 2 diabetes mellitus (noninsulin dependent, NIDDM): Initial: 60 mcg immediately prior to meals; after 3-7 days, increase to 120 mcg prior to meals if no significant nausea occurs (if nausea occurs at 120 mcg dose, reduce to 60 mcg)
If pramlintide is discontinued for any reason, restart therapy with same initial titration protocol.
Dosage adjustment in renal impairment: No dosage adjustment required; not evaluated in dialysis patients
Administration: Other
Do not mix with other insulins; administer subcutaneously into abdominal or thigh areas at sites distinct from concomitant insulin injections (do not administer into arm due to variable absorption); rotate injection sites frequently. Allow solution to reach room temperature before administering; may reduce injection site reactions. For oral medications in which a rapid onset of action is desired, administer 1 hour before, or 2 hours after pramlintide, if possible. When using the pen-injector, do not transfer drug to a syringe; dosing errors could occur.
Monitoring Parameters
Prior to initiating therapy: Hb A1c, hypoglycemic history, body weight. During therapy: urine sugar and acetone, pre- and postprandial and bedtime serum glucose, electrolytes, Hb A1c, lipid profile
Dietary Considerations
Dietary modification based on ADA recommendations is a part of therapy; pramlintide to be administered prior to major meals consisting of ≥250 Kcal or ≥30 g carbohydrates
Patient Education
This medication is used to control diabetes; it is not a cure. It is imperative to follow other components of prescribed treatment (eg, diet and exercise regimen). This medication cannot be mixed with insulin. Use a different syringe for each medication. If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Monitor glucose levels as directed by prescriber. You may experience nausea, headache, fatigue, or dizziness. Report unresolved nausea or vomiting and hypoglycemic reactions.
Geriatric Considerations
Patients must be able to adhere to their insulin regimen and self-monitor their blood glucose. In premarketing studies, the change in the Hb A1c values and hypoglycemia frequencies did not differ by age. Monitor regimen closely. Intensive glucose control (HbA1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly" to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient's functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other disease states. An HbA1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% is acceptable for frail elderly patients, those with a duration of illness >10 years, or those with comorbid conditions and requiring combination diabetes medications. Patients who are unable to accurately draw up their dose will need assistance, such as prefilled syringes. Initial doses may require considerations for renal function in the elderly with dosing adjusted subsequently based on blood glucose monitoring. For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness or fatigue
Mental Health: Effects on Psychiatric Treatment
GI side effects are common; concomitant use with SSRIs, lithium, and valproic acid may produce additive effects. Psychotropics with anticholinergic properties may produce synergistic impairment of gastric motility if used with pramlintide.
Nursing: Physical Assessment/Monitoring
Monitor for hypoglycemia. Teach patient appropriate injection techniques and syringe/needle disposal.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution, as acetate:
SymlinPen®: 1000 mcg/mL (2.7 mL) [120 pen-injector]
SymlinPen®: 1000 mcg/mL (1.5 mL) [60 pen-injector]
Symlin®: 600 mcg/mL (5 mL [DSC])
Pricing: U.S. (www.drugstore.com)
Solution (SymlinPen 120)
1000 mcg/mL (5.4): $461.64
References
American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus -- 2012,” Diabetes Care, 2012, 35(Suppl ):11-63.
Handelsman Y, Mechanick JI, Blonde L, et al, “American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan,” Endocr Pract, 2011, 17(Suppl 2):1-53.
Rodbard HW, Jellinger PS, Davidson JA, et al, “Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control,” Endocr Pract, 2009, 15(6):540-59.
Lexi-Comp.com
Last full review/revision February 2012
Content last modified February 2012
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