CONTRAINDICATIONS
Acarbose is contraindicated in patients with known hypersensitivity to the drug and in patients with
diabetic ketoacidosis, or cirrhosis. Acarbose is also contraindicated in patients with inflammatory
bowel disease, colonic ulceration, partial intestinal obstruction, or in patients predisposed to intestinal
obstruction. In addition, acarbose is contraindicated in patients who have chronic intestinal diseases
associated with marked disorders of digestion or absorption and in patients who have conditions that
may deteriorate as a result of increased gas formation in the intestine.
PRECAUTIONS
General
Hypoglycemia: Because of its mechanism of action, acarbose when administered alone should not
cause hypoglycemia in the fasted or postprandial state. Sulfonylurea agents may cause
hypoglycemia. Because acarbose given in combination with a sulfonylurea will cause a further
lowering of blood glucose, it may increase the hypoglycemic potential of the sulfonylurea. Oral
glucose (dextrose), whose absorption is not inhibited by acarbose should be used instead of sucrose
(cane sugar) in the treatment of mild to moderate hypoglycemia. Sucrose, whose hydrolysis to
glucose and fructose is inhibited by acarbose, is unsuitable for the rapid correction of hypoglycemia.
Severe hypoglycemia may require the use of either intravenous glucose infusion or glucagon
injection.
Elevated Serum Transaminase Levels: In clinical trials, at doses of 50 mg t.i.d. and 100 mg t.i.d.,
the incidence of serum transaminase elevations with acarbose was the same with placebo. In
long-term studies (up to 12 months, and including acarbose doses up to 300 mg t.i.d.) conducted in
the United States, treatment-emergent elevations of serum transaminases (AST and/or ALT)
occurred in 15% of acarbose-treated patients as compared to 7% of placebo-treated patients.
These serum transaminase elevations appear to be dose related. At doses greater than 100 mg
t.i.d., the incidence of serum transaminase elevations greater than three times the upper limit of
normal was two to three times higher in the acarbose group than in the placebo group. These
elevations were asymptomatic, reversible, more common in females, and, in general, were not
associated with other evidence of liver dysfunction.
In international post-marketing experience with acarbose in over 500,000 patients, 19 cases of
serum transaminase elevations > 500 IU/L (12 of which were associated with jaundice) have been
reported. Fifteen of these 19 cases received treatment with 100 mg t.i.d or greater and 13 of 16
patients for whom weight was reported weighed < 60 kg. In the 18 cases where follow-up was
recorded, hepatic abnormalities improved or resolved upon discontinuation of acarbose.
Loss of Control of Blood Glucose: When diabetic patients are exposed to stress such as fever,
trauma, infection, or surgery, a temporary loss of control of blood glucose may occur. At such
times, temporary insulin therapy may be necessary.
Information for the Patient
Patients should be told to take acarbose orally three times a day at the start (with the first bite) of
each main meal. It is important that patients continue to adhere to dietary instructions, a regular
exercise program, and regular testing of urine and/or blood glucose.
Acarbose itself does not cause hypoglycemia even when administered to patients in the fasted
state. Sulfonylurea drugs and insulin, however, can lower blood sugar levels enough to cause
symptoms or sometimes life-threatening hypoglycemia. Because acarbose given in combination with
a sulfonylurea or insulin will cause a further lowering of blood sugar, it may increase the
hypoglycemic potential of these agents. The risk of hypoglycemia, its symptoms and treatment, and
conditions that predispose to its development should be well understood by patients and responsible
family members. Because acarbose prevents the breakdown of table sugar, patients should have a
readily available source of glucose (dextrose, D-glucose) to treat symptoms of low blood sugar
when taking acarbose in combination with a sulfonylurea or insulin.
If side effects occur with acarbose, they usually develop during the first few weeks of therapy.
They are most commonly mild-to-moderate gastroinstestinal effects, such as flatulence, diarrhea, or
abdominal discomfort and generally diminish in frequency and intensity with time.
Laboratory Tests
Therapeutic response to acarbose should be monitored by periodic blood glucose tests.
Measurement of glycosylated hemoglobin levels is recommended for the monitoring of long-term
glycemic control.
Acarbose, particularly at doses in excess of 50 mg t.i.d., may give rise to elevations of serum
transaminases and, in rare instances, hyperbilirubinemia. It is recommended that serum
transaminase levels be checked every three months during the first year of treatment with acarbose
and periodically thereafter. If elevated transaminases are observed, a reduction in dosage or
withdrawal of therapy may be indicated, particularly if the elevations persist.
Renal Impairment
Plasma concentrations of acarbose in renally impaired volunteers were proportionally increased
relative to the degree of renal dysfunction. Long-term clinical trials in diabetic patients with
significant renal dysfunction (serum creatinine > 2.0 mg/dL) have not been conducted. Therefore,
treatment of these patients with acarbose is not recommended.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Nine chronic toxicity/carcinogenicity studies were conducted in three animal species (rat, hamster,
dog) including two rat strains (Sprague-Dawley and Wistar)
In the first rat study, Sprague-Dawley rats received acarbose in feed at high doses (up to
approximately 500 mg/kg body weight) for 104 weeks. Acarbose treatment resulted in a significant
increase in the incidence of renal tumors (adenomas and adenocarcinomas) and benign Leydig cell
tumors. This study was repeated with a similar outcome. Further studies were performed to
separate direct carcinogenic effects of acarbose from indirect effects resulting from the
carbohydrate malnutrition induced by the large doses of acarbose employed in the studies. In one
study using Sprague-Dawley rats, acarbose was mixed with feed but carbohydrate deprivation was
prevented by the addition of glucose to the diet. In a 26-month study of Sprague-Dawley rats,
acarbose was administered by daily postprandial gavage so as to avoid the pharmacologic effects of
the drug. In both of these studies, the increase incidence of renal tumors found in the original studies
did not occur. Acarbose was also given in food and by postprandial gavage in two separate studies
in Wistar rats. No increased incidence of renal tumors was found in either of these Wistar rat
studies. In two feeding studies of hamsters, with and without glucose supplementation, there was no
evidence of carcinogenicity.
Acarbose showed no mutagenic activity when tested in six in vitro and three in vivo assays.
Fertility studies conducted in rats after oral administration produced no untoward effect on fertility
or on the overall capability to reproduce.
Pregnancy, Teratogenic Effects, Pregnancy Category B
The safety of acarbose in pregnant women has not been established. Reproduction studies have
been performed in rats at doses up to 480 mg/kg (corresponding to 9 times the exposure in humans,
based on drug blood levels) and have revealed no evidence of impaired fertility or harm to the fetus
due to acarbose. In rabbits, reduced maternal body weight gain, probably the result of
pharmacodynamic activity of high doses of acarbose in the intestines, may have been responsible
for a slight increase in the number of embryonic losses. However, rabbits given 160 mg/kg acarbose
(Corresponding to 10 times the dose in man, based on body surface area) showed no evidence of
embryotoxicity and there was no evidence of teratogenicity at a dose 32 times the dose in man
(based on body surface area). There are, however, no adequate and well-controlled studies of
acarbose in pregnant women. Because animal reproduction studies are not always predictive of the
human response, this drug should be used during pregnancy only if clearly needed. Because current
information strongly suggests that abnormal blood glucose levels during pregnancy are associated
with a higher incidence of congenital anomalies as well as increase neonatal morbidity and mortality,
most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as
close to normal as possible.
Nursing Mothers
A small amount of radioactivity has been found in the milk of lactating rats after administration of
radiolabled acarbose. It is not known whether this drug is excreted in human milk. Acarbose should
not be administered to a nursing woman.
Pediatric Use
Safety and effectiveness of acarbose in pediatric patients have not been established.