insulin glargine/lixisenatide

General

Pronunciation:
in-su-lin glar-jeen/lix-i-sen-a-tide

Trade Name(s)

• Soliqua 100/33

Ther. Class.
hormones
antidiabetics

Pharm. Class.
pancreatics
glucagon like peptide 1 glp 1 receptor agonists

Indications

Adjunct to diet and exercise in the treatment of type 2 diabetes mellitus.

Action

•  Insulin glargine– Lowers blood glucose by stimulating glucose update in skeletal muscle and fat and by inhibiting hepatic glucose production.
•  Lixisenatide– Acts as an agonist at the glucagon-like peptide-1 (GLP-1) receptor resulting in augmented glucose-dependent insulin secretion and slowing of gastric emptying.

Therapeutic Effect(s):

Improved glycemic control.

Pharmacokinetics

Insulin Glargine

Absorption: Provides slower prolonged absorption and a relatively constant concentrations over 24 hr.

Distribution: Identical to endogenous insulin.

Metabolism and Excretion: Partially metabolized at the site of injection to active insulin metabolites. Metabolized by liver, spleen, kidney, muscle.

Half-life: 5–6 min (prolonged in diabetic patients; biological half-life is longer).

Lixisenatide

Absorption: Bioavailability following subcut injection unknown.

Distribution: Extensively distributed to tissues.

Metabolism and Excretion: Degraded by proteolytic enzymes and excreted primarily through urine.

Half-life: 3 hr

TIME/ACTION PROFILE (blood levels)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to either component;
• Hypoglycemia;
• History of pancreatitis;
• End-stage renal disease;
• Severe gastroparesis.

Use Cautiously in:

• Renal/hepatic impairment (↑ risk of hypoglycemia);
• Concomitant use with pioglitazone or rosiglitazone (↑ risk of fluid retention and worsening HF);
• Patients with visual impairment who may rely on audible clicks to dial their dose;
• OB:  Use only if potential benefit to mother exceeds risk to fetus;
• Lactation: Consider breast feeding only if potential benefit outweighs risks to infant;
• Pedi:  Safety and effectiveness not established;
• Geri:  May be more sensitive to hypoglycemia effects.

Adverse Reactions/Side Effects

CNS: headache

CV: peripheral edema

Endo: HYPOGLYCEMIA

F and E: hypokalemia

GI: PANCREATITIS, nausea, vomiting, abdominal distention, abdominal pain, constipation, ↓ appetite, diarrhea, dyspepsia, flatulence

GU: renal impairment (in association with nausea, vomiting, diarrhea, or dehydration)

Local: erythema, injection site reactions, lipodystrophy, pruritus

Metabolic: weight gain

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Beta blockers  and  clonidine  may mask some of the signs and symptoms of hypoglycemia.
• Albuterol, atypical antipsychotics, corticosteroids, danazol, diuretics, epinephrine, estrogens, isoniazid, niacin, oral contraceptives, phenothiazines, protease inhibitors, and  thyroid supplements  may require ↑ dose of insulin glargine/lixisenatide.
• ACE inhibitors, angiotensin II receptor blockers, antidiabetic agents, disopyramide, fibrates, fluoxetine, MAO inhibitors, octreotide, pentoxifylline, salicylates, and  trimethoprim/sulfamethoxazole  may require ↓ dose of insulin glargine/lixisenatide.
• Alcohol, beta-blockers, clonidine, lithium, and  pentamidine  may require ↑ or ↓ dose of insulin glargine/lixisenatide.
• Concurrent use with  pioglitazone  or  rosiglitazone  may ↑ risk of fluid retention and worsening HF.
• May alter the absorption of concurrently administered  oral medications  (take  antibiotics  and acetaminophen  ≥1 hr before insulin glargine/lixisenatide; take  oral contraceptives  ≥1 hr before or ≥11 hr after insulin glargine/lixisenatide).

Route/Dosage

SC (Adults):  Naïve to basal insulin or to a GLP-1 receptor agonist, currently on GLP-1 receptor agonist, or currently receiving <30 units/day of basal insulin– 15 units (15 units insulin glargine/5 mcg lixisenatide) once daily (discontinue basal insulin or GLP-1 receptor agonist); may ↑ dose by 2–4 units every week until achieve adequate glycemic control (max dose = 60 units/day [60 units insulin glargine/20 mcg lixisenatide);  Currently receiving 30–60 units/day of basal insulin (with or without a GLP–1 receptor agonist)– 30 units (30 units insulin glargine/10 mcg lixisenatide) once daily (discontinue basal insulin or GLP-1 receptor agonist); may ↑ dose by 2–4 units every week until achieve adequate glycemic control (max dose = 60 units/day [60 units insulin glargine/20 mcg lixisenatide).

Availability

Solution for subcut injection: insulin glargine 100 units/lixisenatide 33 mcg/mL in 3–mL prefilled pens

Assessment

• Assess for symptoms of hypoglycemia (anxiety; restlessness; tingling in hands, feet, lips, or tongue; chills; cold sweats; confusion; cool, pale skin; difficulty in concentration; drowsiness; nightmares or trouble sleeping; excessive hunger; headache; irritability; nausea; nervousness; tachycardia; tremor; weakness)and hyperglycemia (confusion, drowsiness; flushed, dry skin; fruit-like breath odor; rapid, deep breathing, polyuria; loss of appetite; unusual thirst) periodically during therapy.
• Monitor for signs and symptoms of hypersensitivity reactions (rash, swelling of face, lips, tongue or throat, difficulty breathing or swallowing, feeling faint or dizzy, tachycardia, hypotension, laryngeal edema, bronchospasm), especially in patient with history of anaphylaxis or angioedema with another GLP-1 receptor agonist.
• Monitor for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to back and may or may not be accompanied by vomiting). Promptly discontinue insulin glargine/lixisenatide and initiate treatment if pancreatitis is suspected. Do not restart insulin glargine/lixisenatide if pancreatitis is confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis.
• Monitor body weight periodically. Changes in weight may necessitate changes in insulin dose.

Lab Test Considerations: Monitor blood glucose every 6 hr during therapy, more frequently in ketoacidosis and times of stress. Hemoglobin A1C may be monitored every 3–6 mo to determine effectiveness.

• Monitor serum potassium in patients at risk for hypokalemia (those using potassium-lowering agents, those receiving IV insulin) periodically during therapy.
• Monitor renal function when starting or ↑ insulin glargine/lixisenatide dose in patients with renal impairment and in patients with severe GI reactions.

Toxicity Overdose:

Overdose is manifested by symptoms of hypoglycemia. Mild hypoglycemia may be treated by ingestion of oral glucose. Severe hypoglycemia is a life-threatening emergency; treatment consists of IV glucose, glucagon, or epinephrine. Recovery from hypoglycemia may be delayed due to the prolonged effect of subcut insulin glargine.

Potential Diagnoses

• Imbalanced nutrition: more than body requirements (Indications) 
• Noncompliance (Patient/Family/Teaching) 

Implementation

• Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
• SC Administer  Soliqua 100/33  once daily within the hour prior to first meal of day. Inject into abdomen, thigh, or upper arm. Rotate sites with each dose. Do not split dose or dilute or mix with other insulins. Solution is clear and colorless to almost colorless; do not inject solutions that are cloudy, discolored, or contain particulate matter. Solution is stable for 28 days at room temperature; discard pen after 28 days, even if medication remains in pen.

Patient/Family Teaching

• Instruct patient on correct technique for administration, timing of dose and concurrent oral medications, storage of medication, and disposal of used needles. Training should include a practice injection. If a dose is missed, omit and take next day dose at scheduled time; do not double doses in same day. Advise patient to read  Medication Guide and Instructions for Use before starting therapy and with each Rx refill in case of changes.
• Inform patient that pen needles are not included with pen and must be purchased separately. Use new pen with each dose. Advise patient which needle length and gauge should be used.
• Caution patient not to share pen and needles, even if needle is changed. May cause transmission of blood-borne pathogens.
• Advise patient to stop taking lixisenatide and notify health care professional immediately if signs and symptoms of hypersensitivity or pancreatitis occur.
• Explain to patient that insulin glargine/lixisenatide helps control hyperglycemia but does not cure diabetes. Therapy is usually long term.
• Inform patient that insulin glargine/lixisenatide may cause lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in injected areas.
• Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hyperglycemic or hypoglycemic episodes.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications or alcohol.
• Advise patient to notify health care professional if nausea, vomiting, or fever develops, if unable to eat regular diet, or if blood sugar levels are not controlled.
• Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water, and notify health care professional. Risk of hypoglycemia is ↑ if sulfonylureas or basal infusion are taken concurrently with insulin glargine/lixisenatide.
• Caution patient to maintain adequate hydration (2 L liquid/day) to minimize risk or renal failure.
• Patients with diabetes mellitus should carry a source of sugar (candy, glucose gel) and identification describing their disease and treatment regimen at all times.
• Emphasize the importance of regular follow-up, especially during first few wk of therapy.
• Rep:  Advise female patient taking oral contraceptives to take them at ≥1 hr before or 11 hr after insulin glargine/lixisenatide dose. Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Improved glycemic control in patients with type 2 diabetes.