Lixisenatide

Indications

Lixisenatide is used for: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with, type 2 diabetes mellitus

Adult Dose

Subcutaneous Adjunct to Type 2 diabetes mellitus Adult: Initially, 10 mcg once daily for 14 days, given within 1 hour before morning or evening meal. May increase dose to 20 mcg once daily starting on day 15. Missed dose should be given within 1 hour of the next meal.

Child Dose

Renal Dose

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

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

Contra Indications

Documented hypersensitivity; hypersensitivity reactions, including anaphylaxis, have occurred with lixisenatide

Precautions

Patient with history of hypersensitivity or pancreatitis, volume depletion, severe gastrointestinal disease (e.g. gastroparesis). Not intended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Renal impairment (including ESRD). Pregnancy and lactation.

Pregnancy-Lactation

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 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

Interactions

Increased risk of hypoglycaemia with sulfonylureas or basal insulin. May reduce the rate of absorption of oral medications (e.g. antibiotics, paracetamol, oral contraceptives).

Adverse Effects

Side effects of Lixisenatide : >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

Mechanism of Action

Lixisenatide binds to and activates glucagon-like peptide-1 (GLP-1) receptor to stimulate glucagon-dependent insulin secretion, suppress glucagon secretion and slow gastric emptying.