URETRON D/S

Uretron ™ D/S tablets for oral administration Each tablet contains: Methenamine 81.6 mg Sodium Phosphate Monobasic 40.8 mg Phenyl Salicylate 36.2 mg Methylene Blue 10.8 mg Hyoscyamine Sulfate 0.12 mg HYOSCYAMINE SULFATE. [620-61-1][3(S)-endo]-α-(Hydroxymethyl)-benzeneacetic acid 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester sulfate(2:1)(salt); 1αH,5αH-tropan-3α-ol(-)-tropate(ester) sulfate(2:1)(salt);3α-tropanyl S-(-)-tropate; l-tropic acid ester with tropine; l-tropine tropate. C 34 H 48 N 2 O 10 S. Hyoscyamine Sulfate is an alkaloid of belladonna. Exists as a white crystalline powder. Its solutions are alkaline to litmus. Affected by light, it is slightly soluble in water; freely soluble in alcohol; sparingly soluble in ether. METHENAMINE. [100-97-0] 1,3,5,7-Tetraazatricyclo [3.3.1.-1 3,7 ] decane; hexamethylenetetramine; HMT; HMTA; hexamine; 1,3,5,7-tetraazaadamantane hexamethylenemine; Uritone; Urotropin. C 6 H 12 N 4 ; mol wt 140.19; C 51.40%, H 8.63%, N 39.96%. Methenamine (hexamethylenetetramine) exists as colorless, lustrous crystals or white crystalline powder. Its solutions are alkaline to litmus. Freely soluble in water, soluble in alcohol and in chloroform. METHYLENE BLUE. [61-73-4] 3,7-Bis(dimethylamino) phenothiazin-5-ium chloride; C.I. Basic Blue 9; methylthioninium chloride; tetramethylthionine chloride; 3,7-bis(dimethylamino) phenazathionium chloride. C 16 H 18 ClN 3 S; mol wt 319.85, C 60.08%, H 5.67%, Cl 11.08%, N 13.14%, S 10.03%. Methylene Blue (Methylthionine chloride) exists as dark green crystals. It is soluble in water and in chloroform; sparingly soluble in alcohol. PHENYL SALICYLATE. [118-55-8] 2-Hydroxybenzoic acid phenyl ester; Salol. C 13 H 10 O 3 ; mol wt 214.22, C 72.89%, H 4.71%, O 22.41%. Made by the action of phosphorus oxy-chloride on a mixture of phenol and salicylic acid. Phenyl Salicylate exists as white crystals with a melting point of 41°-43° C. It is very slightly soluble in water and freely soluble in alcohol. SODIUM PHOSPHATE MONOBASIC. [7558-80-7] Phosphoric acid sodium salt (1:1); Sodium biphosphate; sodium dihydrogen phosphate; acid sodium phosphate; monosodium orthophosphate; primary sodium phosphate; H 2 NaO 4 P; mol wt 119.98, H 1.68%, Na 19.16%, O 53.34%, P 25.82%. Monohydrate, white, odorless slightly deliquesce crystals or granules. At 100° C loses all its water; when ignited it converts to metaphosphate. It is freely soluble in water and practically insoluble in alcohol. The aqueous solution is acid. pH of 0.1 molar aqueous solution at 25° C: 4.5. Uretron D/S tablets contain inactive ingredients: Crospovidone, Dicalcium Phosphate, FD&C Blue #1 Aluminum Lake, Magnesium Stearate, Microcrystalline Cellulose, Polyethylene Glycol, Polyvinyl Alcohol, Stearic Acid, Talc, and Titanium Dioxide.

Uretron D/S tablets are indicated for the treatment of symptoms of irritative voiding. Indicated for the relief of local symptoms, such as inflammation, hypermotility, and pain, which accompany lower urinary tract infections. Indicated for the relief of urinary tract symptoms caused by diagnostic procedures.

Adults - O ne tablet orally 4 times per day followed by liberal fluid intake. Older Children - Dosage must be individualized by physician. Not recommended for use in children six years of age or younger.

Hypersensitivity to any of the ingredients is possible. Risk benefits should be carefully considered when the following medical problems exist: cardiac disease (especially cardiac arrhythmias, congestive heart failure, coronary heart disease, and mitral stenosis); gastrointestinal tract obstructive disease; glaucoma; myasthenia gravis, acute urinary retention may be precipitated in obstructive uropathy (such as bladder neck obstruction due to prostatic hypertrophy).

Cardiovascular: rapid heartbeat, flushing Central Nervous System: blurred vision, dizziness, drowsiness Genitourinary: difficult micturition, acute urinary retention Gastrointestinal: dry mouth, nausea and vomiting Respiratory: shortness of breath or trouble breathing Serious allergic reactions to this drug are rare. Seek immediate medical attention if you notice symptoms of a serious allergic reaction, including itching, rash, severe dizziness, swelling or trouble breathing. This medication can cause urine and sometimes stools to turn blue to blue-green. This effect is harmless and will subside after medication is stopped. Call your doctor or physician for medical advice about side effects. To report SUSPECTED ADVERSE REACTIONS, contact A.G. Marin Pharmaceuticals at 305-593-5333 or FDA at 1-800-FDA-1088, www.fda.gov/medwatch. Drug interactions As a result of hyoscyamine's effects on gastrointestinal motility and gastric emptying, absorption of other oral medications may be decreased during concurrent use with this combination medication. Methylene blue inhibits a range of CYP isozymes in vitro, including 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5. This interaction could be more pronounced with narrow therapeutic index drugs that are metabolized by one of these enzymes (e.g., digoxin, warfarin, phenytoin, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus). However, the clinical relevance of these in vitro interactions is unknown. Urinary alkalizers and thiazide diuretics: May cause the urine to become alkaline reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde. Antimuscarinics : Concurrent use may intensify antimuscarinic effects of hyoscyamine because of secondary antimuscarinic activities of these medications. Antacids/antidiarrheals: Concurrent use may reduce absorption of hyoscyamine resulting in decreased therapeutic effectiveness. Concurrent use with antacids may cause urine to become alkaline reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde. Doses of these medications should be spaced 1 hour apart from doses of hyoscyamine. Antimyasthenics: Concurrent use with hyoscyamine may further reduce intestinal motility, therefore, caution is recommended. Ketoconazole and hyoscyamine may cause increased gastrointestinal pH. Concurrent administration with hyoscyamine may result in marked reduction in the absorption of ketoconazole. Patients should be advised to take this combination at least 2 hours after ketoconazole. Monoamine oxidase (MAO) inhibitors: Concurrent use with hyoscyamine may intensify antimuscarinic side effects. Opioid (narcotic) analgesics may result in increased risk of severe constipation. Sulfonamides: These drugs may precipitate with formaldehyde in the urine increasing the danger of crystalluria. Patients should be advised that the urine and/or stools may become blue to blue-green as a result of the excretion of methylene blue.

As a result of hyoscyamine's effects on gastrointestinal motility and gastric emptying, absorption of other oral medications may be decreased during concurrent use with this combination medication. Methylene blue inhibits a range of CYP isozymes in vitro, including 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5. This interaction could be more pronounced with narrow therapeutic index drugs that are metabolized by one of these enzymes (e.g., digoxin, warfarin, phenytoin, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus). However, the clinical relevance of these in vitro interactions is unknown. Urinary alkalizers and thiazide diuretics: May cause the urine to become alkaline reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde. Antimuscarinics : Concurrent use may intensify antimuscarinic effects of hyoscyamine because of secondary antimuscarinic activities of these medications. Antacids/antidiarrheals: Concurrent use may reduce absorption of hyoscyamine resulting in decreased therapeutic effectiveness. Concurrent use with antacids may cause urine to become alkaline reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde. Doses of these medications should be spaced 1 hour apart from doses of hyoscyamine. Antimyasthenics: Concurrent use with hyoscyamine may further reduce intestinal motility, therefore, caution is recommended. Ketoconazole and hyoscyamine may cause increased gastrointestinal pH. Concurrent administration with hyoscyamine may result in marked reduction in the absorption of ketoconazole. Patients should be advised to take this combination at least 2 hours after ketoconazole. Monoamine oxidase (MAO) inhibitors: Concurrent use with hyoscyamine may intensify antimuscarinic side effects. Opioid (narcotic) analgesics may result in increased risk of severe constipation. Sulfonamides: These drugs may precipitate with formaldehyde in the urine increasing the danger of crystalluria. Patients should be advised that the urine and/or stools may become blue to blue-green as a result of the excretion of methylene blue.

STORAGE Dispense in a tight, light-resistant container as defined in the USP/NF with a child resistant closure. Store at controlled room temperature 20°-25°C (68°-77°F). Keep in a cool, dry place. Keep container tightly closed.