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Miglitol


General


Pronunciation

(MIG li tol)


Brand Names: U.S.

  • Glyset

Indications


Use: Labeled Indications

Type 2 diabetes mellitus (noninsulin-dependent, NIDDM):

Monotherapy as an adjunct to diet to improve glycemic control in patients with type 2 diabetes mellitus (noninsulin-dependent, NIDDM) whose hyperglycemia cannot be managed with diet alone

Combination therapy with a sulfonylurea when diet plus either miglitol or a sulfonylurea alone do not result in adequate glycemic control. The effect of miglitol to enhance glycemic control is additive to that of sulfonylureas when used in combination.


Contraindications


Hypersensitivity to miglitol or any of component of the formulation; diabetic ketoacidosis; inflammatory bowel disease; colonic ulceration; partial intestinal obstruction or predisposition to intestinal obstruction; chronic intestinal diseases associated with marked disorders of digestion or absorption or with conditions that may deteriorate as a result of increased gas formation in the intestine


Dosing and Administration


Dosing: Adult

Type 2 diabetes (noninsulin dependent, NIDDM): Oral: Initial: 25 mg 3 times daily at the start of each meal; the dose may be increased to 50 mg 3 times daily after 4-8 weeks and continued for ~3 months; if glycosylated hemoglobin is not satisfactory, may further increase to maximum recommended dose: 100 mg 3 times daily


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

CrCl ≥25 mL/minute: No dosage adjustment necessary. Although miglitol is primarily excreted unchanged, the increased plasma levels in renal impairment are not expected to affect efficacy (clinical response is localized to the GI tract); however, the effects on adverse effects are unknown.

CrCl <25 mL/minute or SCr >2 mg/dL: Use not recommended (not adequately studied).


Dosing: Hepatic Impairment

No dosage adjustment necessary.


Administration

Administer orally at the start of each main meal.


Storage

Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Glyset: 25 mg, 50 mg, 100 mg

Generic: 25 mg, 50 mg, 100 mg


Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy


Monitoring Parameters

Monitor therapeutic response by periodic blood glucose tests; hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2016a]).


Adverse Reactions


>10%: Gastrointestinal: Flatulence (42%), diarrhea (29%), abdominal pain (12%)

1% to 10%: Dermatologic: Rash (4%)

<1% (Limited to important or life-threatening): Abdominal distention, gastrointestinal pain, ileus, nausea, paralytic ileus, pneumatosis cystoides intestinalis, subileus


Warnings/Precautions


Special Populations: Renal Function Impairment

Because miglitol is excreted primarily by the kidneys, accumulation is expected. However, dosage adjustment to correct the increased plasma concentrations is not feasible because miglitol acts locally.


Warnings/Precautions

Concerns related to adverse effects:

- GI symptoms: Most common reactions are gastrointestinal related; incidence of abdominal pain and diarrhea tend to diminish considerably with continued treatment.

- Hypoglycemia: Hypoglycemia is unlikely to occur with miglitol monotherapy but may occur with combination therapy (eg, sulfonylurea, insulin). In patients taking miglitol, oral glucose (dextrose) should be used instead of sucrose (cane sugar) in the treatment of mild-to-moderate hypoglycemia since the hydrolysis of sucrose to glucose and fructose is inhibited by miglitol. Correction of severe hypoglycemia may require the use of either glucagon or IV glucose.

Disease-related concerns:

- Renal impairment: Not recommended in severe impairment (serum creatinine >2 mg/dL or CrCl <25 mL/minute); has not been adequately studied.

- Stress-related states: It may be necessary to discontinue miglitol and administer insulin if the patient is exposed to stress (ie, fever, trauma, infection, surgery).

Concurrent drug therapy issues:

- Sulfonylureas and insulin: In combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea or insulin; dosage reduction of the sulfonylurea or insulin may be required.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been reported in animal reproduction studies.

In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2015; Kitzmiller 2008; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ACOG 2013; ADA 2015; Blumer 2013; Kitzmiller 2008). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (Kitzmiller 2008).

Miglitol is not currently recommended for use in pregnant women for the management of gestational diabetes mellitus (GDM) or type 2 diabetes mellitus (ACOG 2013; Blumer 2013).


Actions


Pharmacology

In contrast to sulfonylureas, miglitol does not enhance insulin secretion; the antihyperglycemic action of miglitol results from a reversible inhibition of membrane-bound intestinal alpha-glucosidases which hydrolyze oligosaccharides and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In patients with diabetes, this enzyme inhibition results in delayed glucose absorption and lowering of postprandial hyperglycemia.


Absorption

Saturable at high doses: 25 mg dose: Completely absorbed; 100 mg dose: 50% to 70% absorbed


Distribution

Vd: 0.18 L/kg


Metabolism

None


Excretion

Urine (as unchanged drug)


Time to Peak

2-3 hours


Half-Life Elimination

~2 hours


Protein Binding

<4%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience abdominal pain, flatulence, or diarrhea. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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