Asacol Hd Information
Asacol hd (Mesalamine) Indications And Usage
Asacol hd (Mesalamine) is indicated for the treatment of moderately active ulcerative colitis. Safety and effectiveness of Asacol hd (Mesalamine) beyond 6 weeks has not been established.
Asacol hd (Mesalamine) Dosage And Administration
For the treatment of moderately active ulcerative colitis, the recommended dose of Asacol hd (Mesalamine) in adults is two 800 mg tablets to be taken three times daily with or without food, for a total daily dose of 4.8 g, for a duration of 6 weeks. Asacol hd (Mesalamine) use beyond 6 weeks has not been evaluated. Asacol hd (Mesalamine) should be swallowed whole without cutting, breaking, or chewing. One Asacol hd (Mesalamine) 800 mg tablet has not been shown to be bioequivalent to two Asacol 400 mg tablets
Asacol hd (Mesalamine) Dosage Forms And Strengths
Asacol hd (Mesalamine) delayed-release tablets are available as red-brown, capsule-shaped tablets containing 800 mg mesalamine and imprinted with “PG 800” in black.
Asacol hd (Mesalamine) Contraindications
Asacol hd (Mesalamine) is contraindicated in patients with hypersensitivity to salicylates or aminosalicylates or to any of the components of Asacol hd (Mesalamine) tablets.
Asacol hd (Mesalamine) Warnings And Precautions
Renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis, and, rarely, renal failure, has been reported in patients taking products such as Asacol hd (Mesalamine) that contain or are converted to mesalamine.
It is recommended that all patients have an evaluation of renal function prior to initiation of Asacol hd (Mesalamine) and periodically while on therapy. Exercise caution when using Asacol hd (Mesalamine) in patients with known renal dysfunction or history of renal disease.
In animal studies (rats, mice, dogs), the kidney was the principal organ for toxicity .
Asacol hd (Mesalamine) Adverse Reactions
The most serious adverse reactions seen in Asacol hd (Mesalamine) clinical trials or with other products that contain or are metabolized to mesalamine were:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Asacol hd (Mesalamine) has been evaluated in 896 patients with ulcerative colitis in controlled studies. Three six-week, active-controlled studies were conducted comparing Asacol hd (Mesalamine) 4.8 g/day with Asacol (mesalamine) 2.4 g/day as control in patients with mildly to moderately active ulcerative colitis. In these studies, 727 patients were dosed with the Asacol hd (Mesalamine) tablet and 732 patients were dosed with the Asacol 400 mg tablet. (One Asacol hd (Mesalamine) 800 mg tablet has not been shown to be bioequivalent to two Asacol 400 mg tablets .)
The most common reactions reported in the Asacol hd (Mesalamine) group were headache (4.7%), nausea (2.8%), nasopharyngitis (2.5%), abdominal pain (2.3%), exacerbation of ulcerative colitis (2.3%), diarrhea (1.7%), and dyspepsia (1.7%); Table 1 enumerates adverse drug reactions that occurred in the three studies. The most common reactions in the primary efficacy population of patients with moderately active ulcerative colitis (602 patients dosed with Asacol hd (Mesalamine) and 618 patients dosed with the Asacol 400 mg tablet) were the same as all treated patients. The majority of adverse reactions with Asacol hd (Mesalamine) in the double-blind, active-controlled trials were mild or moderate in severity and were reversible.
Discontinuations due to adverse reactions occurred in 3.9% of patients in the Asacol hd (Mesalamine) group and in 4.2% of patients in the Asacol 400 mg tablet comparator group. The most common cause for discontinuation was gastrointestinal symptoms associated with ulcerative colitis.
Severe adverse reactions occurred in 7.6% of patients in the Asacol hd (Mesalamine) group and in 7.6% of patients in the Asacol 400 mg tablet comparator group. Most of these reactions were gastrointestinal symptoms related to ulcerative colitis. Serious adverse reactions occurred in 0.8% of patients in the Asacol hd (Mesalamine) group and in 1.8% of patients in the Asacol 400 mg tablet comparator group. The majority involved the gastrointestinal system.
In addition to the adverse reactions reported above in clinical trials involving the Asacol hd (Mesalamine) tablet, the adverse events listed below have been reported in controlled clinical trials, open label studies, literature reports, or foreign and domestic marketing experience with Asacol 400 mg tablets or other products that contain or are metabolized to mesalamine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole
Cardiovascular
Gastrointestinal
Hepatic
Hematologic
Musculoskeletal
Neurological/Psychiatric
Respiratory/Pulmonary
Skin
Special Senses
Laboratory Abnormalities
Asacol hd (Mesalamine) Drug Interactions
No formal drug interaction studies have been performed using Asacol hd (Mesalamine) with other drugs.
Asacol hd (Mesalamine) Use In Specific Populations
Pregnancy Category B: Reproduction studies have been performed in rats at oral doses up to 480 mg/kg/day (about 0.8 times the recommended human treatment dose of 4.8 g/day based on body surface area) and rabbits at oral doses up to 480 mg/kg/day (about 1.6 times the recommended human treatment dose of 4.8 g/day based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to mesalamine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Mesalamine is known to cross the placental barrier.
Clinical studies of Asacol hd (Mesalamine) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger patients. In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing Asacol hd (Mesalamine) . Reports from uncontrolled clinical studies and postmarketing reporting systems for Asacol (mesalamine) suggested a higher incidence of blood dyscrasias, i.e., agranulocytosis, neutropenia, pancytopenia, in patients who were 65 years or older. Caution should be taken to closely monitor blood cell counts during mesalamine therapy.
Mesalamine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when prescribing this drug therapy. It is recommended that all patients have an evaluation of renal function prior to initiation of Asacol hd (Mesalamine) therapy and periodically while on Asacol hd (Mesalamine) therapy .
Asacol hd (Mesalamine) Overdosage
There is no specific antidote for mesalamine overdose and treatment for suspected acute severe toxicity with Asacol hd (Mesalamine) should be symptomatic and supportive. This may include prevention of further gastrointestinal tract absorption, correction of fluid electrolyte imbalance, and maintaining adequate renal function. Asacol hd (Mesalamine) is a pH dependent delayed release product and this factor should be considered when treating a suspected overdose.
Single oral doses of 5000 mg/kg mesalamine suspension in mice (approximately 4.2 times the recommended human dose of Asacol hd (Mesalamine) based on body surface area), 4595 mg/kg in rats (approximately 7.8 times the recommended human dose of Asacol hd (Mesalamine) based on body surface area) and 3000 mg/kg in cynomolgus monkeys (approximately 10 times the recommended human dose of Asacol hd (Mesalamine) based on body surface area) were lethal.
Asacol hd (Mesalamine) Description
Each Asacol hd (Mesalamine) delayed-release tablet for oral administration contains 800 mg of mesalamine, an anti-inflammatory drug. Asacol hd (Mesalamine) delayed-release tablets have an outer protective coat consisting of a combination of acrylic based resins, Eudragit S (methacrylic acid copolymer B, NF) and Eudragit L (methacrylic acid copolymer A, NF). The inner coat consists of an acrylic based resin, Eudragit S, which dissolves at pH 7 or greater, releasing mesalamine in the terminal ileum and beyond for topical anti-inflammatory action in the colon. Mesalamine (also referred to as 5-aminosalicylic acid or 5-ASA) has the chemical name 5-amino-2-hydroxybenzoic acid; its structural formula is:
Inactive Ingredients
Asacol hd (Mesalamine) Clinical Pharmacology
Plasma concentrations of mesalamine (5-aminosalicylic acid; 5-ASA) and its metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) are highly variable following administration of Asacol hd (Mesalamine) tablets. The time to peak plasma concentration (t) is prolonged for mesalamine and N-Ac-5-ASA with the median values from various studies ranging from 10 to 16 hours, reflecting the delayed-release characteristics. Based on cumulative urinary recovery of mesalamine and N-Ac-5-ASA from single dose studies in healthy volunteers, approximately 20% of the orally administered mesalamine in Asacol hd (Mesalamine) tablets is systemically absorbed. The absorbed mesalamine is rapidly acetylated in the gut mucosal wall and by the liver to N-Ac-5-ASA which is excreted mainly by the kidney. The PK parameters following administration of 1600 mg three times daily in healthy subjects are shown in Table 2.
A high fat meal does not affect the extent of systemic exposure to mesalamine after single-dose administration of Asacol hd (Mesalamine) , but mesalamine C decreases by 47% and t is delayed by 14 hours under fed conditions.
One Asacol hd (Mesalamine) 800 mg tablet has not been shown to be bioequivalent to two Asacol 400 mg tablets. In a single dose, cross-over pharmacokinetic study in 20 healthy volunteers, the mean mesalamine C was 36% lower and the mean mesalamine AUC was 25% lower with administration of one Asacol hd (Mesalamine) 800 mg tablet relative to two Asacol 400 mg tablets. Because the mechanism of action of mesalamine appears to be topical, the impact of these differences in measures of systemic exposure on clinical efficacy is not known.
Asacol hd (Mesalamine) Nonclinical Toxicology
In animal studies (rats, mice, dogs), the kidney was the principal organ for toxicity. (In the following, comparisons of animal dosing to recommended human dosing are based on body surface area and a 4.8 g/day dose for a 50 kg person.)
Mesalamine causes renal papillary necrosis in rats at single doses of approximately 750 mg/kg to 1000 mg/kg (1.3 to 1.7 times the recommended human dose). Doses of 170 and 360 mg/kg/day (about 0.3 and 0.6 times the recommended human dose) given to rats for six months produced papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia.
In mice, oral doses of 4000 mg/kg/day (approximately 3.4 times the recommended human dose) for three months produced tubular nephrosis, multifocal/diffuse tubulo-interstitial inflammation, and multifocal/diffuse papillary necrosis.
In dogs, single doses of 6000 mg (approximately 6.25 times the recommended human dose) of delayed-release mesalamine tablets resulted in renal papillary necrosis but were not fatal. Renal changes have occurred in dogs given chronic administration of mesalamine at doses of 80 mg/kg/day (0.5 times the recommended human dose).
Asacol hd (Mesalamine) How Supplied/storage And Handling
Asacol hd (Mesalamine) tablets are available as red-brown, capsule-shaped tablets containing 800 mg mesalamine and imprinted with “PG 800” in black.
NDC 0149-0783-01 Bottle of 180
Store at controlled room temperature 20° to 25°C (68° to 77°F) [See USP].
Asacol hd (Mesalamine) Patient Counseling Information
Procter & Gamble Pharmaceuticals, Inc., Cincinnati, OH 45202,under license from Medeva Pharma Suisse AG (registered trademark owner).
Made in Germany, D-64331 Weiterstadt
U.S. Patent Nos. 5,541,170; 5,541,171; and 6,893,662 and other patents pending.
Asacol hd (Mesalamine)
