Dosing and uses of Adlyxin (lixisenatide)
Adult dosage forms and strengths
SC solution in prefilled pen
- Starter dose (green pen)
- 50mcg/mL in 3mL prefilled pen (provides 14 doses of 10mcg/dose)
- Maintenance dose (burgundy pen)
- 100mcg/mL in 3 mL prefilled pen (provides 14 doses of 20mcg/dose)
Type 2 Diabetes Mellitus
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Starting dose: 10 mcg SC qDay for 14 days
Maintenance: Increase dose to 20 mcg SC qDay starting on Day 15
Dosage modifications
Renal impairment
- Mild (CrCl 60-89 mL/min): No dosage adjustment required; monitoring for changes in renal function recommended because of a higher incidence of hypoglycemia, nausea, and vomiting observed in these patients during clinical trials
- Moderate (CrCl 30 to <60 mL/min): No dosage adjustment required; closely monitoring for adverse GI adverse effects and for changes in renal function is recommended because these symptoms may lead to dehydration and acute renal failure and worsening of chronic failure in these patients
- Severe (CrCl 15 to <30 mL/min): Data are limited; there were only 5 patients with severe renal impairment in all controlled studies; lixisenatide exposure was higher in these patients; closely monitor for GI adverse effects and for changes in renal function
- End-stage renal disease (CrCl <15 mL/min): Not recommended; no therapeutic experience
Dosing Considerations
Limitations of use
- Has not been studied in patients with chronic pancreatitis or a history of unexplained pancreatitis; consider other antidiabetic treatment options
- Not a substitute for insulin
- Not indicated for patients with type 1 DM
- Not indicated for treatment of ketoacidosis
- Concurrent use with short-acting insulin has not been studied and is not recommended
- Has not been studied with gastroparesis and is not recommended in patients with gastroparesis
Pediatric dosage forms and strengths
Safety and efficacy not established
Adlyxin (lixisenatide) adverse (side) effects
>10%
Nausea (25%)
Hypoglycemia
- Coadministered with basal insulin +/- sulfonylurea (47.2%)
- Coadministered with basal insulin +/- metformin (28.3%)
- Coadministered with insulin glargine and metformin +/- thiazolidinedione (22%)
- Coadministered with sulfonylurea +/- metformin (14.5%)
1-10%
Vomiting (10%)
Headache (9%)
Diarrhea (8%)
Dizziness (7%)
Injection site reactions (4%)
Dyspepsia (3.2%)
Constipation (2.8%)
Attenuated glycemic response with high antibodies (ie, >100 nmol/L) (2.4%)
Abdominal distension (2.2%)
Upper abdominal pain (2.2%)
Abdominal pain (2%)
<1%
Anaphylaxis (0.1%)
Acute pancreatitis
Warnings
Contraindications
Documented hypersensitivity; hypersensitivity reactions, including anaphylaxis, have occurred with lixisenatide
Cautions
Anaphylaxis (0.1%) and other hypersensitivity reactions, including angioedema, have been reported; if hypersensitivity occurs, discontinue drug and promptly seek medical attention (see Contraindications)
Acute pancreatitis, including fatal, and nonfatal hemorrhagic or necrotizing pancreatitis reported postmarketing in patients treated with GLP-1 receptor agonists; observe for signs and symptoms (eg, persistent severe abdominal pain that sometimes radiates to the back which may or may not be accompanied by vomiting); promptly discontinue if suspected; if pancreatitis confirmed, do not restart drug
Do not share pen between patients, even if the needle is changed; pen-sharing poses risk for transmission of blood-borne pathogens
Risk for hypoglycemia increased if coadministered with a sulfonylurea or basal insulin
Acute kidney injury and worsening of chronic renal failure (sometimes requiring hemodialysis); some reports were in patients without known underlying renal disease; most of the reports described patients who had experienced nausea, vomiting, diarrhea, or dehydration
Antibody development to lixisenatide occurred in 70% of patients by week 24; a subset of patients (2.4%) with the highest antibody concentrations (ie, >100 nmol/L) showed an attenuated glycemic response; a higher incidence of allergic reactions and injection site reactions occurred in antibody-positive patients
Clinical studies have NOT shown macrovascular risk reduction with lixisenatide or any other antidiabetic drug
Drug interaction overview
- Lixisenatide delays gastric emptying, which may affect absorption of concomitantly administered oral medications
- Caution if coadministered with drugs that have a narrow therapeutic index or drugs that require careful clinical monitoring; if these medications are to be administered with food, patients should take them with a meal or snack when lixisenatide is not being administered
- Oral medications that are particularly dependent on minimum serum concentrations (eg, antibiotics) or medications in which a delayed effect may be undesirable (pain medications) should be administered 1 hr before lixisenatide
- Oral contraceptives should be taken at least 1 hr before lixisenatide administration or 11 hr after lixisenatide
- Risk of hypoglycemia when coadministered with sulfonylurea or basal insulin; dose reduction of sulfonylurea or basal insulin may be required
Pregnancy
Pregnancy
Limited data available are not sufficient to inform a drug-associated risk of major birth defects and miscarriage
Use during pregnancy only if the benefit justifies the potential risk to the fetus
Clinical considerations
- Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications
- Poorly control diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity
Animal data
- Lixisenatide administered to pregnant rats and rabbits during organogenesis was associated with visceral closure and skeletal defects at systemic exposures that decreased maternal food intake and weight gain during gestation, and that are 1x and 6x higher than the 20-mcg/day clinical dose, respectively, based on plasma AUC
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Animal data
- A study in lactating rats showed low (9.4%) transfer of lixisenatide and its metabolites into milk and negligible (0.01%) levels of unchanged lixisenatide peptide in the gastric contents of weaning offspring
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Adlyxin (lixisenatide)
Mechanism of action
Incretin mimetic; glucagonlike peptide-1 (GLP-1) receptor agonist; increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying
Absorption
Peak plasma concentration time: 1-3.5 hr
Peak plasma concentration increased with renal impairment
- Mild (CrCl 60-89 mL/min): Increased by 60%
- Moderate (CrCl 30-59 mL/min): Increased by 42%
- Severe (CrCl 15-29 mL/min): Increased by 83%
AUC increased with renal impairment
- Mild (CrCl 60-89 mL/min): Increased by 34%
- Moderate (CrCl 30-59 mL/min): Increased by 69%
- Severe (CrCl 15-29 mL/min): Increased by 124%
Distribution
Vd: 100 L
Metabolism
Not metabolized by the liver
Elimination
Half-life: 3 hr
Clearance: 25 L/hr
Presumed to be eliminated through glomerular filtration and proteolytic degradation
Administration
SC Preparation
The pen must be activated before the first use
Instruct patients and caregivers on preparation and use of the pen prior to first use
Training should include a practice injection
Visually inspect solution, it should appear clear and colorless; do not use if particulate matter or coloration is observed
SC Administration
Administer by SC injection in abdomen, thigh, or upper arm once daily
Rotate injection sites with each dose; do not use the same site for each injection
Administer an injection within 1 hr before the first meal of the day, preferable the same meal each day
Missed dose: If a dose is missed, administer within 1 hr prior to the next meaL
Storage
Before first use
- Keep refrigerated at 36-46°F (2-8°C)
- Do not freeze
- Protect the pen from light by keeping it in its original packaging
After first use
- Store at <86°F (30°C)
- Replace the pen cap after each use to protect from light
- Discard the pen 14 days after its first use
