Acarbose (Page 3 of 4)
Teratogenic Effects: Pregnancy Category B.
The safety of acarbose tablets 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 the 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 tablets 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 increased neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.
A small amount of radioactivity has been found in the milk of lactating rats after administration of radiolabeled acarbose. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, acarbose tablets should not be administered to a nursing woman.
Safety and effectiveness of acarbose tablets in pediatric patients have not been established.
Of the total number of subjects in clinical studies of acarbose tablets in the United States, 27 % were 65 and over, while 4 % were 75 and over. No overall differences in safety and effectiveness were observed between these subjects and younger subjects.
The mean steady-state area under the curve (AUC) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however, these differences were not statistically significant.
Gastrointestinal symptoms are the most common reactions to acarbose tablets. In U.S. placebo-controlled trials, the incidences of abdominal pain, diarrhea, and flatulence were 19%, 31%, and 74% respectively in 1255 patients treated with acarbose tablets 50-300 mg t.i.d., whereas the corresponding incidences were 9%, 12%, and 29% in 999 placebo-treated patients. In a one-year safety study, during which patients kept diaries of gastrointestinal symptoms, abdominal pain and diarrhea tended to return to pretreatment levels over time, and the frequency and intensity of flatulence tended to abate with time. The increased gastrointestinal tract symptoms in patients treated with acarbose tablets are a manifestation of the mechanism of action of acarbose and are related to the presence of undigested carbohydrate in the lower GI tract.
If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced.
Elevated Serum Transaminase Levels
Other Abnormal Laboratory Findings
Small reductions in hematocrit occurred more often in acarbose-treated patients than in placebo-treated patients but were not associated with reductions in hemoglobin. Low serum calcium and low plasma vitamin B6 levels were associated with acarbose tablets therapy but are thought to be either spurious or of no clinical significance.
Postmarketing Adverse Event Reports
Additional adverse events reported from worldwide postmarketing experience include fulminant hepatitis with fatal outcome, hypersensitive skin reactions (for example rash, erythema, exanthema and uticaria), edema, ileus/subileus, jaundice and/or hepatitis and associated liver damage, thrombocytopenia, and pneumatosis cystoides intestinalis (see PRECAUTIONS).
Pneumatosis Cystoides Intestinalis
There have been rare postmarketing reports of pneumatosis cystoides intestinalis associated with the use of alpha-glucosidase inhibitors, including acarbose tablets.Pneumatosis cystoides intestinalis may present with symptoms of diarrhea, mucus discharge, rectal bleeding, and constipation.Complications may include pneumoperitoneum, volvulus, intestinal obstruction, intussusception, intestinal hemorrhage, and intestinal perforation. If pneumatosis cystoides intestinalis is suspected, discontinue acarbose tablets and perform the appropriate diagnostic imaging.
To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Unlike sulfonylureas or insulin, an overdose of acarbose tablets will not result in hypoglycemia. An overdose may result in transient increases in flatulence, diarrhea, and abdominal discomfort which shortly subside. In cases of overdosage the patient should not be given drinks or meals containing carbohydrates (polysaccharides, oligosaccharides and disaccharides) for the next 4-6 hours.
DOSAGE AND ADMINISTRATION
There is no fixed dosage regimen for the management of diabetes mellitus with acarbose tablets or any other pharmacologic agent. Dosage of acarbose tablets must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dose of 100 mg t.i.d. Acarbose tablets should be taken three times daily at the start (with the first bite) of each main meal. Acarbose tablets should be started at a low dose, with gradual dose escalation as described below, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced.
During treatment initiation and dose titration (see below), one-hour postprandial plasma glucose may be used to determine the therapeutic response to acarbose tablets and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of acarbose tablets, either as monotherapy or in combination with sulfonylureas, insulin or metformin.
The recommended starting dosage of acarbose tablets is 25 mg given orally three times daily at the start (with the first bite) of each main meal. However, some patients may benefit from more gradual dose titration to minimize gastrointestinal side effects. This may be achieved by initiating treatment at 25 mg once per day and subsequently increasing the frequency of administration to achieve 25 mg t.i.d.
Once a 25 mg t.i.d. dosage regimen is reached, dosage of acarbose tablets should be adjusted at 4-8 week intervals based on one-hour postprandial glucose or glycosylated hemoglobin levels, and on tolerance. The dosage can be increased from 25 mg t.i.d. to 50 mg t.i.d. Some patients may benefit from further increasing the dosage to 100 mg t.i.d. The maintenance dose ranges from 50 mg t.i.d. to 100 mg t.i.d. However, since patients with low body weight may be at increased risk for elevated serum transaminases, only patients with body weight > 60 kg should be considered for dose titration above 50 mg t.i.d. (see PRECAUTIONS). If no further reduction in postprandial glucose or glycosylated hemoglobin levels is observed with titration to 100 mg t.i.d., consideration should be given to lowering the dose. Once an effective and tolerated dosage is established, it should be maintained.
The maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d. The maximum recommended dose for patients > 60 kg is 100 mg t.i.d.
Patients Receiving Sulfonylureas or Insulin
Sulfonylurea agents or insulin may cause hypoglycemia. Acarbose tablets given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the potential for hypoglycemia. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made.
Acarbose Tablets, USP are supplied as follows:
For 25 mg: White to off white, round, biconvex tablets, debossed with “HP” on one side and “147” on other side.
For 50 mg: White to off white, round, biconvex tablets, debossed with “HP” and “148” on one side and plain on other side.
For 100 mg: White to off white, round, biconvex tablets, debossed with “HP” and “149” on one side and plain on other side.
Acarbose Tablets, USP 25 mg/50 mg/100 mg are available in Bottles of 100, 500 & 1,000.
|Strength||NDC||Table t Identificatio n|
|Bottles of 100 with child-resistance closure Bottles of 500 with child-resistance closure Bottles of 1,000 with child-resistance closure||25 mg 25 mg 25 mg||23155-147-01 23155-147-05 23155-147-10||“HP” on one side and “147” on other side.|
|Bottles of 100 with child-resistance closure Bottles of 500 with child-resistance closure Bottles of 1,000 with child-resistance closure||50 mg 50 mg 50 mg||23155-148-01 23155-148-05 23155-148-10||“HP” and “148” on one side and plain on other side.|
|Bottles of 100 with child-resistance closure Bottles of 500 with child-resistance closure Bottles of 1,000 with child-resistance closure||100 mg 100 mg 100 mg||23155-149-01 23155-149-05 23155-149-10||“HP” and “149” on one side and plain on other side.|
Store at 20o to 25o C (68o to 77o F) [see USP Controlled Room Temperature]. Protect from moisture. For bottles, keep container tightly closed.
RA CHEM PHARMA LIMITED
Hyderabad – 500 076, INDIA
Avet Pharmaceuticals Inc.
East Brunswick, NJ 08816
Avet Pharmaceuticals Inc.
East Brunswick, NJ 088161.866.901.DRUG(3784)
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