SymlinPen pramlintide acetate 1000 ug/mL Injection, 2 cartridges
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Amylin Analog class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Pramlintide is used with mealtime insulin to control blood sugar levels in people who have diabetes. Pramlintide is only used to treat patients whose blood sugar could not be controlled by insulin or insulin and an oral medication for diabetes. Pramlintide is in a class of medications called antihyperglycemics. It works by slowing the movement of food through the stomach. This prevents blood sugar from rising too high after a meal, and may decrease appetite and cause weight loss. Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, inc...
Read the full MedlinePlus article ↗- When you add pramlintide to your routine, both it and your insulin lower blood sugar at the same time — and together they can push your blood sugar dangerously low. Cutting your me...
- Why do I have to cut my insulin dose when I start SymlinPen?
- Yes, nausea is the most common side effect, especially in the first few weeks. The good news is that it tends to get better on its own as your body adjusts, particularly when the d...
- I feel really nauseated after my injection — is that normal, and will it go away?
Patient education
Supplement & herbal interactions
Pramlintide may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII Q40Q9N063P
Acetic acid is a weak organic acid commonly used in medicines as a buffer and pH adjuster. It helps maintain the proper acidity level to ensure the drug remains stable and effective in its formulation.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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2.25 mg / 1 mL
UNII GGO4Y809LO
Metacresol is a preservative derived from coal tar or petroleum. It prevents bacterial and fungal growth in liquid medicines, helping keep the product safe and stable during storage.
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UNII 4550K0SC9B
Sodium acetate is a salt derived from acetic acid. It acts as a buffer to help maintain the medicine's pH stability and may serve as a preservative or solubilizer in liquid formulations.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $217.521 | $1,174.61 / 5.4 ml |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| SymlinPen 1000 ug/mLthis 00310-6627-02 | AstraZeneca | 2 cartridges | $217.521 | — | Availability likely | — |
| SymlinPen 1000 ug/mL 00310-6615-02 | AstraZeneca | 2 cartridges | $330.952 | — | Availability likely | +52% |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00310-6627-02 You're viewing this | 2 CARTRIDGE in 1 CARTON (0310-6627-02) / 2.7 mL in 1 CARTRIDGE | 2015-01-08 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SEVERE HYPOGLYCEMIA SYMLIN use with insulin increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia occurs, it is seen within 3 hours following a SYMLIN injection. Serious injuries may occur if severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities.
Appropriate patient selection, careful patient instruction, and insulin dose reduction are critical elements for reducing this risk. WARNING: SEVERE HYPOGLYCEMIA See full prescribing information for complete boxed warning. • SYMLIN use with insulin has been associated with an increased risk of severe hypoglycemia, particularly in patients with type 1 diabetes. • Hypoglycemia risk may be reduced by appropriate patient selection, careful patient instruction, and insulin dose reduction (5.1 , 5.2) .
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE SYMLIN is indicated as an adjunctive treatment in patients with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. SYMLIN is an amylin analog indicated for patients with type 1 or type 2 diabetes who use mealtime insulin and have failed to achieve desired glycemic control despite optimal insulin therapy (1) .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Upon initiation of SYMLIN, reduce mealtime insulin dose by 50%. Monitor glucoses frequently and individualize subsequent insulin dose adjustments (2.1) . • Type 1 Diabetes: Start at 15 mcg subcutaneously before major meals. Increase in 15 mcg increments to a maximum premeal dose of 30 or 60 mcg; if not tolerated, reduce to 30 mcg, as tolerated (2.2) . • Type 2 Diabetes: Start at 60 mcg subcutaneously before major meals then increase to 120 mcg before meals, as tolerated (2.2) . • Wait at least 3 days between dose titrations to minimize nausea (2.1) .
2.1Important Considerations Pertaining to SYMLIN and Insulin Dose Adjustments SYMLIN dosage differs depending on whether the patient has type 1 or type 2 diabetes [see Dosage and Administration (2.2 , 2.3) ]. SYMLIN should be used only in patients who can fully understand and adhere to proper insulin adjustments and glucose monitoring. Insulin and SYMLIN dose adjustments should be made only as directed by a healthcare professional skilled in the use of insulin.
When initiating SYMLIN, reduce mealtime insulin doses, including premixed insulins, by 50% to reduce the risk of hypoglycemia. To reduce the risk of nausea, wait at least 3 days before titrating SYMLIN to the next dose increment. Monitor blood glucoses frequently, including pre- and post-meals and at bedtime, particularly when initiating SYMLIN or increasing the SYMLIN dose.
After the initial 50% reduction in mealtime insulin dose, individualize insulin dose adjustments based on glycemic control and tolerability (e.g., if nausea occurs it may affect the dose of insulin required). An increased frequency of mild-to-moderate hypoglycemia should be viewed as a warning sign of increased risk for severe hypoglycemia. If SYMLIN therapy is discontinued for any reason (e.g., surgery or illnesses), the same initiation protocol should be followed when SYMLIN therapy is reinstituted [see Dosage and Administration (2.2) ].
2.2Patients with Type 2 Diabetes Using Mealtime Insulin Reduce mealtime insulin doses (including premixed insulins) by 50%, then initiate SYMLIN at 60 mcg subcutaneously, injecting immediately prior to each major meal. Increase the SYMLIN dose from 60 to 120 mcg prior to each major meal when no clinically significant nausea has occurred for at least 3 days. If significant nausea persists at the 120 mcg dose, the SYMLIN dose should be decreased to 60 mcg.
2.3Patients with Type 1 Diabetes Reduce mealtime insulin doses by 50%, then initiate SYMLIN at 15 mcg subcutaneously, injecting immediately prior to each major meal. Increase the SYMLIN dose to the next increment (30, 45, or 60 mcg) when no clinically significant nausea has occurred for at least 3 days. If significant nausea persists at the 45 or 60 mcg dose level, the SYMLIN dose should be decreased to 30 mcg.
If the 30 mcg dose is not tolerated, discontinuation of SYMLIN therapy should be considered.
2.4Administration SYMLIN should be administered subcutaneously immediately prior to each major meal (≥250 kcal or containing ≥30 grams of carbohydrate). SYMLIN should be at room temperature before injecting to reduce potential injection site reactions. Each SYMLIN dose should be administered subcutaneously into the abdomen or thigh.
Administration into the arm is not recommended because of variable absorption. Injection sites should be rotated so that the same site is not used repeatedly. The injection site selected should also be distinct from the site chosen for any concomitant insulin injection.
SYMLIN and insulin should always be administered as separate injections. SYMLIN should not be mixed with any type of insulin. If a SYMLIN dose is missed, wait until the next scheduled dose and administer the usual amount.
2.5Discontinuation of Therapy SYMLIN therapy should be discontinued if there is: • recurrent unexplained hypoglycemia that requires medical assistance. • persistent clinically significant nausea. • noncompliance with self-m…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS SYMLIN is supplied as a sterile injection in the following dosage forms: • 1.5 mL disposable multidose SymlinPen ® 60 pen-injector containing 1000 mcg/mL pramlintide (as acetate). • 2.7 mL disposable multidose SymlinPen ® 120 pen-injector containing 1000 mcg/mL pramlintide (as acetate). • 1.5 mL SymlinPen ® 60 disposable multidose pen-injector, (1000 mcg/mL) for 15, 30, 45, and 60 mcg doses (3) . • 2.7 mL SymlinPen ® 120 disposable multidose pen-injector, (1000 mcg/mL) for 60 and 120 mcg doses (3) .
⛔ Contraindications ▾
4 CONTRAINDICATIONS SYMLIN is contraindicated in patients with any of the following: • serious hypersensitivity reaction to SYMLIN or to any of its product components. • hypoglycemia unawareness. • confirmed gastroparesis. • Prior serious hypersensitivity reaction to SYMLIN or its ingredients (4) • Hypoglycemia unawareness (4) • Confirmed gastroparesis (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Severe hypoglycemia: Increased risk particularly for type 1 diabetes. Upon initiation of SYMLIN, reduce mealtime insulin dose by 50% and frequently monitor blood glucoses (5.2) . • Never share a SymlinPen between patients, even if the needle is changed (5.3) . • Do not mix SYMLIN and insulin: Mixing can alter the pharmacokinetics of both products. Administer as separate injections (5.4 , 7.1) . • Slows gastric emptying: Administer concomitant oral medications at least 1 hour before or 2 hours after SYMLIN if rapid onset or threshold concentration is critical (5.6 , 7.2) .
5.1Patient Selection Proper patient selection is critical to the safe and effective use of SYMLIN. Before initiating SYMLIN, the patient's HbA1c, recent blood glucose monitoring data, history of insulin-induced hypoglycemia, current insulin regimen, and body weight should be reviewed. SYMLIN therapy should only be considered in patients with type 1 diabetes or patients with type 2 diabetes using mealtime insulin who fulfill the following criteria: • have failed to achieve adequate glycemic control despite individualized insulin management. • are receiving ongoing care under the guidance of a healthcare professional skilled in the use of insulin and supported by the services of diabetes educator(s).
Patients meeting any of the following criteria should NOT be considered for SYMLIN therapy: • poor compliance with current insulin regimen. • poor compliance with prescribed self blood glucose monitoring. • have a HbA1c >9%. • recurrent severe hypoglycemia requiring assistance during the past 6 months. • presence of hypoglycemia unawareness. • confirmed diagnosis of gastroparesis. • require the use of drugs that stimulate gastrointestinal motility. • pediatric patients. SYMLIN should be prescribed with caution to persons with visual or dexterity impairment.
5.2Hypoglycemia SYMLIN alone does not cause hypoglycemia. However, SYMLIN is indicated to be coadministered with mealtime insulin therapy, and in this setting there is an increased risk of severe hypoglycemia, particularly in patients with type 1 diabetes. If severe hypoglycemia associated with SYMLIN occurs, it is usually seen within the first 2 to 3 hours following a SYMLIN injection.
If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries or death may occur. Therefore, when introducing SYMLIN therapy, appropriate precautions need to be taken to avoid increasing the risk for severe hypoglycemia. These precautions include frequent monitoring of pre- and post-meal glucose combined with an initial 50% reduction in doses of mealtime insulin [see Dosage and Administration (2.1 , 2.2 ) ].
Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes; diabetic neuropathy; use of medications such as beta-blockers, clonidine, guanethidine, or reserpine; or intensified glycemic control. The addition of any anti-diabetic medication, such as SYMLIN, to an existing regimen of one or more anti-diabetic medications (e.g., sulfonylurea), or other medications that can increase the risk of hypoglycemia may necessitate further insulin dose adjustments and particularly close monitoring of blood glucose.
5.3Never Share a SymlinPen Between Patients SymlinPen must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
5.4Never Mix SYMLIN and Insulin Mixing SYMLIN and insulin can alter the pharmacokinetics of both products which may result in inadequate glucose control or hypoglycemia. Therefore, SYMLIN and insulin must always be administered as separate injections and should never be mixed [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ].
5.5Concomitantly Administered Oral Medications SYMLIN slows gastric emptying, which may delay the absorption of con…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. • Most common adverse reactions (incidence ≥5% and higher incidence than placebo): nausea, vomiting, anorexia, headache (6.1) . To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trial Experience Adverse Reactions (Excluding Hypoglycemia) Adverse reactions (excluding hypoglycemia, which is discussed separately below) commonly associated with SYMLIN when coadministered with a fixed dose of insulin in the 26- to 52-week, placebo-controlled trials in patients with type 1 diabetes and patients with type 2 diabetes on mealtime insulin are presented in Table 1 and Table 2, respectively. Table 1: Patients with Type 1 Diabetes: Common Adverse Reactions (Incidence ≥5% and Greater Incidence with SYMLIN Compared to Placebo) in 3 Pooled Placebo-Controlled Trials Long-Term, Placebo-Controlled Studies SYMLIN 30 or 60 mcg 3 Times Daily + Insulin Placebo + Insulin (N=716) % (N=538) % Nausea 48 17 Anorexia 17 2 Inflicted Injury Examples of inflicted injury included among others, abrasions, bruises, burns, fractures, lacerations, and muscle strains.
14 10 Vomiting 11 7 Arthralgia 7 5 Fatigue 7 4 Allergic Reaction 6 5 Dizziness 5 4 Table 2: Patients with Type 2 Diabetes on Insulin: Common Adverse Reactions (Incidence ≥5% and Greater Incidence with SYMLIN Compared to Placebo) in 2 Pooled Placebo-Controlled Trials Long-Term, Placebo-Controlled Studies SYMLIN 120 mcg 2 Times Daily + Insulin Placebo + Insulin (N=292) % (N=284) % Nausea 28 12 Headache 13 7 Anorexia 9 2 Vomiting 8 4 Abdominal pain 8 7 Fatigue 7 4 Dizziness 6 4 Cough 6 4 Pharyngitis 5 2 Most adverse reactions were gastrointestinal in nature.
The incidence of nausea is higher at the beginning of SYMLIN treatment and decreases with time in most patients. Gradual titration of the SYMLIN dose minimizes the incidence and severity of nausea [see Dosage and Administration (2) ]. Severe Hypoglycemia Coadministration of SYMLIN with mealtime insulin increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes [see Boxed Warning and Warnings and Precautions (5.1) ].
Two definitions of severe hypoglycemia were used in the SYMLIN clinical trials. Patient-ascertained severe hypoglycemia was defined as an episode of hypoglycemia requiring the assistance of another individual (including help administering oral carbohydrate) or requiring the administration of glucagon, intravenous glucose, or other medical intervention. Medically-assisted severe hypoglycemia was defined as an episode of hypoglycemia that was classified as a serious event by the investigator or that required glucagon, intravenous glucose, hospitalization, paramedic assistance or an emergency room visit.
The incidence of severe hypoglycemia during the SYMLIN clinical development program is summarized in Table 3 and Table 4. Table 3: Incidence and Event Rate of Severe Hypoglycemia in Six-Month, Placebo-Controlled Trials and Dose Titration Trial in Patients with Type 1 Diabetes Long-Term, Placebo-Controlled Studies (No Insulin Dose-Reduction During Initiation) Placebo-Controlled Dose Titration Study SYMLIN + Insulin Placebo + Insulin SYMLIN + Insulin Placebo + Insulin Severe Hypoglycemia 0 to 3 Months (n=716) >3 to 6 Months (n=576) 0 to 3 Months (n=538) >3 to 6 Months (n=470) 0 to 3 Months (n=148) >3 to 6 Months (n=133) 0 to 3 Months (n=147) >3 to 6 Months (n=138) Patient-Ascertained Patient-ascertained severe hypoglycemia: Requiring the assistance of another individual (including help ingesting oral carbohydrate) and/or requiring the administration of glucagon injection, intravenous glucose, or other medical intervention.
Event Rate (events/pat…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Insulin The pharmacokinetic parameters of pramlintide are altered when SYMLIN is mixed in the same syringe with regular, NPH, and 70/30 premixed formulations of recombinant human insulin. SYMLIN and insulin must not be mixed and must be administered as separate injections [see Dosage and Administration (2.4) , Warnings and Precautions (5.4) , and Clinical Pharmacology (12.3) ].
7.2Oral Medications SYMLIN has the potential to delay the absorption of concomitantly administered oral medications. When the rapid onset or threshold concentration of a concomitant orally administered medication is a critical determinant of effectiveness (such as with analgesics, antibiotics, and oral contraceptives), the medication should be administered at least 1 hour prior to SYMLIN injection or 2 hours after SYMLIN injection [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3) ].
7.3Drugs Affecting Gastrointestinal Motility Due to its effects on gastric emptying, SYMLIN should not be considered for patients taking medications that alter gastrointestinal motility (e.g., anticholinergic agents such as atropine) or medications that slow the intestinal absorption of nutrients (e.g., alpha-glucosidase inhibitors). Patients using these medications have not been studied in SYMLIN clinical trials [see Warnings and Precautions (5.6) ].
7.4Drugs Affecting Glucose Metabolism The following are examples of medications that may increase the susceptibility to hypoglycemia when administered with SYMLIN: anti-diabetic products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics. SYMLIN and these drugs should be coadministered with caution.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Available data from a small number of reports in the manufacturer’s safety database on SYMLIN use in pregnant women are not sufficient to determine a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations ). Ex-vivo studies using term perfused human, rabbit, and rat placentas indicate that SYMLIN has low potential to cross the maternal/fetal placental barrier.
In animal reproduction studies, congenital abnormalities were observed in fetuses of pregnant rats but not in fetuses of pregnant rabbits exposed during organogenesis to pramlintide at 10 times the clinical dose of 360 mcg/day, based on exposure (see Data ). The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
Data Animal Data Developmental and reproductive toxicity studies with SYMLIN were performed in pregnant rats and rabbits. Increases in congenital abnormalities (neural tube defect, cleft palate, exencephaly) were observed in fetuses of pregnant rats administered pramlintide subcutaneously during organogenesis at 0.3 and 1 mg/kg/day (10 and 47 times the human dose of 360 mcg/day based on AUC, respectively), but not at 3mg/kg/day. Administration of pramlintide to pregnant rabbits during organogenesis resulted in maternal toxicity but did not increase fetal malformations at doses up to 0.3 mg/kg/day (9 times the human dose of 360 mcg/day based on AUC).
8.2Lactation Risk Summary There is no data on the presence of pramlintide in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SYMLIN and any potential adverse effects on the breastfed child from SYMLIN or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness of SYMLIN in pediatric patients have not been established.
8.5Geriatric Use SYMLIN has been studied in patients ranging in age from 15 to 84 years of age, including 769 patients ≥65 to 75 years of age and 87 patients ≥75 years of age. No consistent differences in the efficacy and safety of SYMLIN have been observed in older patients, but greater sensitivity in some older individuals cannot be ruled out. As is recommended for all patients, SYMLIN and insulin regimens should be carefully managed to minimize the risk of severe hypoglycemia.
8.6Renal Impairment The dosing requirements for SYMLIN are not altered in patients with mild (creatinine clearance [Cl Cr ] 60-89 mL/min), moderate (Cl Cr 30-59 mL/min) or severe renal impairment (Cl Cr 15-29 mL/min). SYMLIN has not been studied in patients with end-stage renal disease [see Clinical Pharmacology (12.3) ] .
8.7Hepatic Impairment SYMLIN use has not been studied in patients with hepatic impairment [see Clinical Pharmacology (12.3) ] .
8.8Gender No consistent differences in the efficacy and safety of SYMLIN have been observed between men and women in SYMLIN clinical trials (n=2799 for male and n=2085 for female).
8.9 Race/Ethnicity No consistent differ…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available data from a small number of reports in the manufacturer’s safety database on SYMLIN use in pregnant women are not sufficient to determine a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations ). Ex-vivo studies using term perfused human, rabbit, and rat placentas indicate that SYMLIN has low potential to cross the maternal/fetal placental barrier.
In animal reproduction studies, congenital abnormalities were observed in fetuses of pregnant rats but not in fetuses of pregnant rabbits exposed during organogenesis to pramlintide at 10 times the clinical dose of 360 mcg/day, based on exposure (see Data ). The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
Data Animal Data Developmental and reproductive toxicity studies with SYMLIN were performed in pregnant rats and rabbits. Increases in congenital abnormalities (neural tube defect, cleft palate, exencephaly) were observed in fetuses of pregnant rats administered pramlintide subcutaneously during organogenesis at 0.3 and 1 mg/kg/day (10 and 47 times the human dose of 360 mcg/day based on AUC, respectively), but not at 3mg/kg/day. Administration of pramlintide to pregnant rabbits during organogenesis resulted in maternal toxicity but did not increase fetal malformations at doses up to 0.3 mg/kg/day (9 times the human dose of 360 mcg/day based on AUC).
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of SYMLIN in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use SYMLIN has been studied in patients ranging in age from 15 to 84 years of age, including 769 patients ≥65 to 75 years of age and 87 patients ≥75 years of age. No consistent differences in the efficacy and safety of SYMLIN have been observed in older patients, but greater sensitivity in some older individuals cannot be ruled out. As is recommended for all patients, SYMLIN and insulin regimens should be carefully managed to minimize the risk of severe hypoglycemia.
🆘 Overdosage ▾
10 OVERDOSAGE Single 10 mg doses of SYMLIN (83 times the maximum recommended dose of 120 mcg for patients with type 2 diabetes) were administered to 3 healthy volunteers. All 3 individuals reported severe nausea associated with vomiting, diarrhea, vasodilatation, and dizziness. No hypoglycemia was reported. Pramlintide has a short half-life (approximately 48 minutes in healthy individuals). Initiate supportive measures in the case of overdose.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Pramlintide is an analog of human amylin. Amylin is colocated with insulin in secretory granules and cosecreted with insulin by pancreatic beta cells in response to food intake. Amylin and insulin show similar fasting and postprandial patterns in healthy individuals (Figure 1).
Figure 1: Secretion Profile of Amylin and Insulin in Healthy Adults In patients with type 1 and type 2 diabetes, there is reduced secretion from pancreatic beta cells of both insulin and amylin in response to food. Amylin affects the rate of postprandial glucose appearance through a variety of mechanisms, as determined by nonclinical studies. Amylin slows gastric emptying (i.e., the rate at which food is released from the stomach to the small intestine) without altering the overall absorption of nutrients.
In addition, amylin suppresses glucagon secretion (not normalized by insulin alone), which leads to suppression of endogenous glucose output from the liver. Amylin also regulates food intake due to centrally-mediated modulation of appetite. In human studies, pramlintide, acting as an amylin analog, slows gastric emptying, reduces the postprandial rise in plasma glucagon, and modulates satiety leading to decreased caloric intake.
Figure 1
12.2Pharmacodynamics In clinical studies in patients with type 1 diabetes and patients with type 2 diabetes using mealtime insulin, SYMLIN reduced mean postprandial glucose concentrations, reduced glucose fluctuations, and reduced food intake. Reduction in Postprandial Glucose Concentrations In a randomized, single-blind, placebo-controlled, crossover study, 19 subjects with type 2 diabetes using insulin lispro, 19 subjects with type 1 diabetes using regular human insulin, and 21 subjects with type 1 diabetes using insulin lispro underwent mixed-meal tests.
SYMLIN administered subcutaneously immediately prior to a meal reduced plasma glucose concentrations following the meal when used with mealtime insulin (rapid-acting insulin analogs or regular human insulin) (Figure 2). When rapid-acting insulin analogs were used, plasma glucose concentrations tended to rise during the interval between 150 minutes following SYMLIN injection and the next meal [see Dosage and Administration (2) ]. Figure 2: Postprandial Plasma Glucose Profiles in Patients with Type 1 Diabetes or Type 2 Diabetes Receiving SYMLIN and Insulin Compared to Those Receiving Insulin Alone While SYMLIN reduces postprandial glucose, clinical studies employing a controlled hypoglycemic challenge have demonstrated that SYMLIN does not alter the counter-regulatory hormonal response to insulin-induced hypoglycemia.
Likewise, in SYMLIN-treated patients, the perception of hypoglycemic symptoms was not altered with plasma glucose concentrations as low as 45 mg/dL. In a separate clinical trial pramlintide also reduced the 24-hour glucose fluctuations based upon 24-hour glucose monitoring. Figure 2 Reduced Food Intake A single, subcutaneous dose of 30 mcg of SYMLIN to patients with type 1 diabetes and 120 mcg of SYMLIN to patients with type 2 diabetes administered 1 hour prior to an unlimited buffet meal was associated with reductions in total caloric intake (placebo-subtracted mean changes of ~21% and 23%, respectively), which occurred without decreases in meal duration.
12.3Pharmacokinetics Absorption The absolute bioavailability of pramlintide following a single subcutaneous dose of SYMLIN is approximately 30% to 40%. Subcutaneous administration of different doses of SYMLIN into the abdominal area or thigh of healthy individuals showed a linear, dose-dependent increase in maximum plasma concentrations (C max ) and overall exposure (AUC) (Table 5). Table 5: Mean Pharmacokinetic Parameters Following Administration of Single Subcutaneous Doses of SYMLIN Subcutaneous Dose (mcg) AUC (0-∞) (pmol*min/L) C max (pmol/L) T max (min) Elimination t ½ (min) 30 3750 39 21 55 60 6778 79 20 49 90 8507 102 19 51 120 11970 147 21 48…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Pramlintide is an analog of human amylin. Amylin is colocated with insulin in secretory granules and cosecreted with insulin by pancreatic beta cells in response to food intake. Amylin and insulin show similar fasting and postprandial patterns in healthy individuals (Figure 1).
Figure 1: Secretion Profile of Amylin and Insulin in Healthy Adults In patients with type 1 and type 2 diabetes, there is reduced secretion from pancreatic beta cells of both insulin and amylin in response to food. Amylin affects the rate of postprandial glucose appearance through a variety of mechanisms, as determined by nonclinical studies. Amylin slows gastric emptying (i.e., the rate at which food is released from the stomach to the small intestine) without altering the overall absorption of nutrients.
In addition, amylin suppresses glucagon secretion (not normalized by insulin alone), which leads to suppression of endogenous glucose output from the liver. Amylin also regulates food intake due to centrally-mediated modulation of appetite. In human studies, pramlintide, acting as an amylin analog, slows gastric emptying, reduces the postprandial rise in plasma glucagon, and modulates satiety leading to decreased caloric intake.
Figure 1
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING SYMLIN Injection is available in the following package sizes: • SymlinPen ® 60 pen-injector, containing 1000 mcg/mL pramlintide (as acetate) Two 1.5 mL disposable multidose pen-injectors (NDC 0310-6615-02) • SymlinPen ® 120 pen-injector, containing 1000 mcg/mL pramlintide (as acetate) Two 2.7 mL disposable multidose pen-injectors (NDC 0310-6627-02) Storage and Handling SYMLIN pen-injectors not in use: Refrigerate (2°C to 8°C; 36°F to 46°F), and protect from light. Do not freeze. Do not use if product has been frozen.
Unused SYMLIN (opened or unopened) should not be used after the expiration (EXP) date printed on the carton and the label. SYMLIN pen-injectors in use: After first use, refrigerate or keep at a temperature not greater than 86°F (30°C) for 30 days. Use within 30 days, whether or not refrigerated.
Storage conditions are summarized in Table 9. Table 9: Storage Conditions Dosage Form Unopened (not in use) Refrigerated Open (in use) Refrigerated or Temperature up to 86°F (30°C) 1.5 mL pen-injector Until Expiration Date Use Within 30 Days 2.7 mL pen-injector
📦 Storage and Handling ▾
Storage and Handling SYMLIN pen-injectors not in use: Refrigerate (2°C to 8°C; 36°F to 46°F), and protect from light. Do not freeze. Do not use if product has been frozen.
Unused SYMLIN (opened or unopened) should not be used after the expiration (EXP) date printed on the carton and the label. SYMLIN pen-injectors in use: After first use, refrigerate or keep at a temperature not greater than 86°F (30°C) for 30 days. Use within 30 days, whether or not refrigerated.
Storage conditions are summarized in Table 9. Table 9: Storage Conditions Dosage Form Unopened (not in use) Refrigerated Open (in use) Refrigerated or Temperature up to 86°F (30°C) 1.5 mL pen-injector Until Expiration Date Use Within 30 Days 2.7 mL pen-injector
📋 Description ▾
11 DESCRIPTION SYMLIN ® (pramlintide acetate) injection is an anti-diabetic medication for use in patients with diabetes treated with insulin. Pramlintide is a synthetic analog of human amylin, a naturally occurring neuroendocrine hormone synthesized by pancreatic beta cells that contributes to glucose control during the postprandial period. Pramlintide is provided as an acetate salt of the synthetic 37-amino acid polypeptide, which differs in amino acid sequence from human amylin by replacement with proline at positions 25 (alanine), 28 (serine), and 29 (serine).
The structural formula of pramlintide acetate is shown below: Pramlintide acetate is a white powder that has a molecular formula of C 171 H 267 N 51 O 53 S 2 • × C 2 H 4 O 2 (3≤ × ≤8); the molecular weight is 3949.4. Pramlintide acetate is soluble in water. SYMLIN is formulated as a clear, isotonic, sterile solution for subcutaneous administration.
The disposable multidose SymlinPen ® pen-injector contains 1000 mcg/mL of pramlintide (as acetate). The formulation contains 2.25 mg/mL of metacresol as a preservative, D-mannitol as a tonicity modifier, acetic acid, sodium acetate as pH modifiers, and water for injection. SYMLIN has a pH of approximately 4.0.
Pramlintide Acetate Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Risk of Hypoglycemia Discuss the risk and consequences of hypoglycemia and approaches to minimize its occurrence. Inform patients about the importance of self-management practices including glucose monitoring and timing of dosing.
In addition, reinforce the importance of adherence to meal planning, physical activity, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications. Never Share a SymlinPen Between Patients Advise patients that they must never share a SymlinPen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens. Never Mix SYMLIN and Insulin Inform patients that SYMLIN and insulin should always be administered as separate injections and never be mixed.
Show patients how to administer SYMLIN using the pen-injector. Advise patients to use a new needle for each injection. Instructions Instruct patients on the proper injection technique and proper storage of SYMLIN.
Refer patients to the SYMLIN Medication Guide and Patient Instructions for Use for additional information. Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 SYMLIN and SymlinPen are registered trademarks of the AstraZeneca group of companies.
💬 Medication Guide ▾
MEDICATION GUIDE SYMLIN ® (SĬM-lĭn) (pramlintide acetate) injection for subcutaneous use Read this Medication Guide and Instructions for Use that come with your SYMLIN before you start using it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment.
What is the most important information I should know about SYMLIN? SYMLIN can cause serious side effects, including : • severe low blood sugar (hypoglycemia) . Even when SYMLIN is carefully added to your mealtime insulin therapy, your blood sugar may drop too low, especially if you have type 1 diabetes.
If this severe low blood sugar (hypoglycemia) happens, it is seen within 3 hours after a SYMLIN injection. Symptoms of severe low blood sugar and low blood sugar include: o lightheadedness o dizziness o shakiness o sweating o hunger o fast heartbeat o trouble concentrating or confusion o change in vision o headache o irritability o drowsiness People who have severely low blood sugar have had injuries while driving their car, operating heavy machinery or doing other dangerous activities. You and your healthcare provider should talk about a plan to treat low blood sugar.
You should have fast-acting sugar (such as hard candy, glucose tablets, juice) or glucagon for injection with you at all times. Call your healthcare provider if you have severe low blood sugar or if you have low blood sugar more often than normal. You have a higher chance of getting severe low blood sugar if you: o do not follow your healthcare provider’s instructions to reduce your insulin use before meals o use more SYMLIN or insulin than prescribed by your healthcare provider o change your insulin dose without checking your blood sugar o eat less food than your usual meal o are sick and cannot eat o are more active than usual o have a low blood sugar level before eating o drink alcohol SYMLIN is used with insulin to lower blood sugar, especially high blood sugar that happens after meals.
SYMLIN is taken at mealtimes. The use of SYMLIN does not replace your daily insulin but may lower the amount of insulin you need, especially before meals. Do not share your SymlinPen with other people, even if the needle has been changed.
You may give other people a serious infection, or get a serious infection from them. What is SYMLIN? SYMLIN is an injectable prescription medicine used to treat adults with type 1 and type 2 diabetes to control blood sugar.
SYMLIN is used when your mealtime insulin dose has not controlled your blood sugar well enough. It is not known if SYMLIN is safe and effective in children. Who should not use SYMLIN?
Do not use SYMLIN if you: • are allergic to SYMLIN or any ingredients in SYMLIN. See the end of this Medication Guide for a complete list of ingredients in SYMLIN. • cannot tell when your blood sugar is low (hypoglycemia unawareness) • have a stomach problem called gastroparesis. This is when your stomach does not empty as fast as it should.
What should I tell my healthcare provider before using SYMLIN? Before you use SYMLIN, tell your healthcare provider about all of your medical conditions, including if you: • are pregnant or plan to become pregnant. It is not known if SYMLIN will harm your unborn baby.
You and your healthcare provider should decide how to best control your blood sugar levels during pregnancy. • are breastfeeding or plan to breastfeed. It is not known if SYMLIN passes into your breast milk. You and your healthcare provider should decide about the best way to feed your baby if you are using SYMLIN.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SYMLIN slows stomach emptying and can affect medicines that need to pass through the stomach quickly. How should I use SYMLIN? • Read the “Instructions for Use” and the Medication Guide and that come wit…