Quintasa (5-Aminosalicylic Acid)

QUINTASA®

Ferring

5-Aminosalicylic Acid

Lower Gastrointestinal Anti-inflammatory

Action And Clinical Pharmacology: 5-aminosalicylic acid (5-ASA) has been recognized as the therapeutically active moiety of sulfasalazine, a drug used to treat inflammatory bowel disease. 5-ASA has in vitro and in vivo pharmacologic effects that decrease leukotriene production, scavenge for free radicals and inhibit leukocyte chemotaxis. While its exact mode of action is currently unknown, any of these biochemical mechanisms may play a role in the clinical effectiveness of 5-ASA.

Regardless of its mode of action, 5-ASA appears to exert its therapeutic effect by topical action on the affected areas of inflammation. Dosage forms designed for rectal administration, such as enemas and suppositories are, therefore, especially suited to deliver the active ingredient, 5-ASA, directly to the affected areas along the mucosal lumen of the rectum, sigmoid and distal large bowel.

The local and systemic bioavailability of 5-ASA enema and suppositories were assessed in 12 healthy volunteers during steady-state conditions. Systemic absorption of 5-ASA was low; 15% of the 2 g daily dose was recovered in the urine (mostly as the acetylated metabolite) after administration of the enema, with 10% urinary recovery observed after administration of the suppositories. This compares to 20 to 30% of the 5-ASA dose being absorbed systemically following oral administration.

Maximum plasma concentrations of 5-ASA and of N-acetyl-5-ASA (approximately) 0.7 µg/mL and 1.2 µg/mL respectively for the enema; 0.3 µg/mL and 0.8 µg/mL respectively for the suppositories) were reached 2 hours following administration of the enema and 5 to 6 hours following administration of the suppositories.

More importantly, local availability, as shown by recovery of free 5-ASA in the feces, is higher for both the enema (mean 30%) and the suppositories (mean 45%) than for the oral dosage forms of 5-ASA.

Indications And Clinical Uses: Rectal Suspension: For the treatment of acute distal ulcerative colitis extending to the splenic flexure and for long-term maintenance therapy in order to maintain remission and prevent relapse of active disease.

Suppositories: For the treatment of acute ulcerative proctitis and for long-term maintenance therapy in order to maintain remission and prevent relapse of active disease.

Contra-Indications: Hypersensitivity to salicylic acid derivatives. Severely impaired hepatic and/or renal function. Contraindicated in patients with peptic ulcer.

Manufacturers’ Warnings In Clinical States: Impaired Renal or Hepatic Function: Caution should be exercised if 5-ASA is administered to patients with impaired renal or hepatic function.

Single reports of nephrotic syndrome and interstitial nephritis associated with 5-ASA therapy have been described in the literature. Animal studies have demonstrated a dose-dependent nephrotoxicity. Patients with pre-existing renal disease, increased BUN or serum creatinine, or proteinuria should be carefully monitored.

Pregnancy: 5-ASA should be used during pregnancy only if clearly needed. 5-ASA is known to cross the placental barrier.

Lactation: Caution should be exercised when 5-ASA is administered to a nursing woman.

Children: The safety and efficacy of 5-ASA have not been established in children. The potential benefits of its use should be weighed against the possible risks.

Precautions: General: 5-ASA has been associated with the production of an acute intolerance syndrome which may be difficult to distinguish from flare of inflammatory bowel disease. Symptoms include cramping, acute abdominal pain and bloody diarrhea, sometimes fever, headache and rash. If acute intolerance syndrome is suspected, prompt withdrawal is required. If a rechallenge is performed later in order to validate the hypersensitivity, it should be carried out under close medical supervision at reduced dose and only if clearly needed.

In ulcerative colitis studies, most patients who were intolerant or hypersensitive to sulfasalazine were able to take 5-ASA without evidence of allergic reaction (e.g., rash, fever, pruritus) or intolerance. Nevertheless, caution should be exercised when 5-ASA is used in patients known to be allergic to sulfasalazine. These patients should be instructed to discontinue therapy if signs of rash or fever become apparent.

Semen abnormalities and infertility in men, which are associated with sulfasalazine, have not been reported with 5-ASA during controlled clinical trials. Semen quality significantly improved when patients were transferred from sulfasalazine to 5-ASA.

Drug Interactions: There are no known interactions between 5-ASA and other drugs.

Adverse Reactions: The nature and frequency of adverse events reported during clinical trials involving over 200 patients treated with 5-ASA were similar to those observed with the oral dosage forms, were not dose-related and were not significantly different from those seen with placebo.

When considering all clinical trials together, more than 1 750 patients have received Quintasa therapy, with either oral or rectal dosage forms. Generally, 5-ASA was well tolerated. The following events were reported infrequently (i.e., less than 1%) during trials. In many cases the relationship to 5-ASA has not been established.

Gastrointestinal: abdominal distention, anorexia, duodenal ulcer, eructation, esophageal ulcer, fecal incontinence, gastrointestinal bleeding, increased alkaline phosphatase, melena, dysphagia, mouth ulcer, oral moniliasis, rectal bleeding, rectal urgency, AST increase, stool abnormalities (color or texture change), thirst.

Dermatological: acne, alopecia, dry skin, eczema, erythema nodosum, nail disorder, photosensitivity, pruritus, sweating.

CNS: dizziness, insomnia, somnolence, paresthesia.

Cardiovascular: vasodilation.

Other: albuminuria, asthenia, breast pain, ecchymosis, edema, fever, leg cramps, malaise, menorrhagia, myalgia, urinary frequency.

Isolated case reports have described pericarditis, pancreatitis, nephrotic syndrome and interstitial nephritis associated with 5-ASA.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: There is no clinical experience with 5-ASA overdosage. 5-ASA is an aminosalicylate and symptoms of salicylate toxicity may be possible, such as: tinnitus, vertigo, headache, confusion, drowsiness, sweating, hyperventilation, vomiting and diarrhea. Severe intoxication with salicylates can lead to disruption of electrolyte balance and blood pH, hyperthermia, and dehydration. Since 5-ASA is an aminosalicylate, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage. This includes prevention of further gastrointestinal tract absorption by emesis and, if necessary by gastric lavage. Fluid and electrolyte imbalance should be corrected by the administration of appropriate i.v. therapy. Adequate renal function should be maintained.

Dosage And Administration: Rectal Suspension: The recommended dose ranges from 1 to 4 g of 5-ASA, depending on disease activity, self-administered once daily at bedtime, in unit dose packages containing 1 g, 2 g or 4 g of 5-ASA. Dosage may be adjusted according to the individual patient’s needs consistent with therapeutic goals. Prolonged retention is expected to achieve the best therapeutic response.

Suppositories: The usual dose is 1 suppository containing 1 g of 5-ASA, self-administered once daily at bedtime. Prolonged retention is expected to achieve the best therapeutic response. The frequency of dosage may be adjusted according to the individual patient’s needs consistent with therapeutic goals.

Availability And Storage: Enema: Each unit dose (100 mL) of rectal suspension enema contains: 5-ASA 1 g, 2 g or 4 g. Nonmedicinal ingredients: hydrochloric acid, purified water, sodium acetate, sodium edetate, sodium metabisulfite. Cartons of 7 enemas. Plastic bags are included in the carton to aid in hygenic disposal of enema bottles.

Suppositories: Each suppository contains: 5-ASA 1 g. Nonmedicinal ingredients: magnesium stearate, polyethyleneglycol, povidone, talc. Cartons of 30 suppositories in individual foil pouches with finger protectors. Store at controlled room temperature below 25°C. Dispense in the respective unit-dose containers.

QUINTASA® Ferring 5-Aminosalicylic Acid Lower Gastrointestinal Anti-inflammatory

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