PRECAUTIONS
GENERAL
Risk of Urinary Retention: Sanctura should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.
Decreased Gastrointestinal Motility: Sanctura should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention (See CONTRAINDICATIONS). Sanctura, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis, intestinal atony and myasthenia gravis. Controlled Narrow-angle Glaucoma: In patients being treated for narrow-angle glaucoma, Sanctura should only be used if the potential benefits outweigh the risks and in that circumstance only with careful monitoring.
Patients with Renal Insufficiency: Dose modification is recommended in patients with severe renal insufficiency (CLcr < 30mL/min). In such patients, Sanctura should be administered as 20 mg once a day at bedtime (See DOSAGE AND ADMINISTRATION).
Patients with Hepatic Impairment: Caution should be used when administering Sanctura in patients with moderate or severe hepatic dysfunction (See CLINICAL PHARMACOLOGY: Pharmacokinetics in Special Populations).
INFORMATION FOR PATIENTS
Patients should be informed that anticholinergic agents, such as Sanctura, may produce clinically significant adverse effects related to anticholinergic pharmacological activity. For example, heat prostration (fever and heat stroke due to decreased sweating) can occur when anticholinergics such as Sanctura are used in a hot environment. Because anticholinergics such as Sanctura may also produce dizziness or blurred vision, patients should be advised to exercise caution. Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents.
Sanctura should be taken 1 hour prior to meals or on an empty stomach. If a dose is skipped, patients are advised to take their next dose 1 hour prior to their next meal.
DRUG INTERACTIONS
The concomitant use of Sanctura with other anticholinergic agents that produce dry mouth, constipation, and other anticholinergic pharmacological effects may increase the frequency and/or severity of such effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility.
Drugs Eliminated by Active Tubular Secretion: Although studies to assess drug-drug interactions with Sanctura have not been conducted, Sanctura has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion (e.g. digoxin, procainamide, pancuronium, morphine, vancomycin, metformin and tenofovir). Coadministration of Sanctura with drugs that are eliminated by active renal tubular secretion may increase the serum concentration of Sanctura and/or the coadministered drug due to competition for this elimination pathway. Careful patient monitoring is recommended in patients receiving such drugs (See CLINICAL PHARMACOLOGY: Excretion, and CLINICAL PHARMACOLOGY: Drug-Drug Interactions).
DRUG-LABORATORY-TEST INTERACTIONS
Interactions between Sanctura and laboratory tests have not been studied.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Carcinogenicity studies with trospium chloride were conducted in mice and rats. A 78-week carcinogenicity study in mice and a 104-week carcinogenicity study in rats were conducted at doses of 2, 20, and 200 mg/kg/day. No evidence of a carcinogenic effect was found in either mice or rats. The 200 mg/kg/day dose in the mouse and rat represents approximately 25 and 60 times, respectively, the human dose based on body surface area. At 200 mg/kg/day in the mouse and rat after 4 weeks the AUC was 34 and 753 ng·h/mL, respectively. The exposure in the rat is 8.6-fold higher than the AUC following 40 mg daily exposure in healthy young or elderly subjects (88 ng·h/mL).
Trospium chloride was not mutagenic in tests for detection of gene mutations in bacteria (Ames test) and mammalian cells (L5178Y mouse lymphoma and CHO cells) or in vivo in the rat micronucleus test.
No evidence of impaired fertility was observed in rats administered doses up to 200 mg/kg/day (about 10 multiples of the expected clinical exposure via AUC).
PREGNANCY: TERATOGENIC EFFECTS
Pregnancy Category C: Trospium chloride has been shown to cause maternal toxicity in rats and a decrease in fetal survival in rats administered approximately 10 times the expected clinical exposure (AUC). The no effect levels for maternal and fetal toxicity were approximately equivalent to the expected clinical exposure in rats, and about 5-6 times the expected clinical exposure in rabbits. No malformations or developmental delays were observed. There are no adequate and well controlled studies in pregnant women. Sanctura should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
NURSING MOTHERS
Trospium chloride (2 mg/kg PO and 50 µg/kg IV) was excreted, to a limited extent (<1%), into the milk of lactating rats. The activity observed in the milk was primarily from the parent compound. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Sanctura is administered to a nursing woman. Sanctura should be used during lactation only if the potential benefit justifies the potential risk to the newborn.
PEDIATRIC USE
The safety and effectiveness of Sanctura in pediatric patients have not been established.
GERIATRIC USE
Of the 591 patients with overactive bladder who received treatment with Sanctura in the two U.S., placebo-controlled, efficacy and safety studies, 249 patients (42%) were 65 years of age and older. Eighty-eight Sanctura-treated patients (15%) were >/= 75 years of age.
In these 2 studies, the incidence of commonly reported anticholinergic adverse events in patients treated with Sanctura (including dry mouth, constipation, dyspepsia, UTI, and urinary retention) was higher in patients 75 years of age and older as compared to younger patients. This effect may be related to an enhanced sensitivity to anticholinergic agents in this patient population (See CLINICAL PHARMACOLOGY: Pharmacokinetics in Special Populations and DOSAGE AND ADMINISTRATION). Therefore, based upon tolerability, the dose frequency of Sanctura may be reduced to 20 mg once daily in patients 75 years of age and older.
|
