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| ［Description ］SHENITING Tablets contain
tolterodine tartrate. The active moiety, tolterodine, is a |
| muscarinic receptor antagonist. The chemical name
of tolterodine tartrate is (R)-N, N-diisopropyl-3-(2- |
| hydroxy-5-methylphenyl)-3-phenylpropanamine L-hydrogen
tartrate. The empirical formula of |
| tolterodine tartrate is C26H37NO7,
and itsmolecular weight is 475.6. SHENITING Tablets is a film- |
| coated tablet. White inside after ripping off
its coating. |
| |
［Pharmacological Action］SHENITING Tablets
are indicated for the treatment of patients with an overactive
bladder with symptoms of urinary frequency, urgency, or urge
incontinence. Tolterodine is a competitive muscarinic receptor
antagonist. In the anesthetized cat, tolterodine shows a selectivity
for the urinary bladder over salivary glands; however, the clinical
relevance of this finding has not been established.
After oral administration, tolterodine is metabolized in the
liver, resulting in the formation of the 5-hydroxymethyl derivative,
a major pharmacologically active metabolite. The 5-hydroxymethyl
metabolite(DD01), which exhibits an antimuscarinic activity
similar to that of tolterodine, contributes significantly to
the therapeutic effect. Both tolterodine and the 5-hydroxymethyl
metabolite exhibit a high specificity for muscarinic receptors,
since both show negligible activity or affinity for other neurotransmitter
receptors and other potential cellular targets, such as calcium
channels. |
| |
 ［Absorption
Distribution Excretion］After oral administration, tolterodine
is rapidly absorbed, at least 77% of the radiolabeled dose was
absorbed. The pharmacokinetics profile of tolterodine is linear
over the dose range 1 to 4mg. And does not appear to be affected
by age or gender. Peak serum tolterodine concentrations (Cmax)
of 2.5ug/L were achieved 2.5 hours after oral administration
of a 2mg dose. The area under the serum concentration-time curve
was 11.8ug/L·h. Corresponding values for DD01 were quite similar
(2.2ug/L and 12.1ug/L·h).
Tolterodine is highly bound to plasma proteins, Unbound concentrations
of tolterodine average 3.7% ±0 .13% over the concentration range
achieved in clinical studies. The 5-hydroxymethyl metabolite
is not extensively protein bound, with unbound fraction concentrations
averaging 36% ± 4.0%. The blood to serum ratio of tolterodine
and the 5-hydroxymethyl metabolite averages 0.6 and 0.8, respectively,
indicating that these compounds do not distribute extensively
into erythrocytes. The volume of distribution of tolterodine
following administration of a 1.28-mg intravenous dose is 113
± 26.7 L.
Tolterodine is extensively metabolized by the liver following
oral dosing. The primary metabolic route involves the oxidation
of the 5-methyl group and is mediated by the cytochrome P450
2D6 and leads to the formation of a pharmacologically active
5-hydroxy-methyl metabolite. Further metabolism leads to formation
of the 5-carboxylic acid and N-dealkylated 5-carboxylic acid
metabolites, which account for 51% ± 14% and 29% ± 6.3% of the
metabolites recovered in the urine, respectively.
Elimination half-life of tolterodine is 2～3 hours, DD01 is 3～4
hours.
Following administration of a 5-mg oral dose of 14C-tolterodine
to healthy volunteers, 77% of radioactivity was recovered in
urine and 17% was recovered in feces. Less than 1% (<2.5%
in poor metabolizers) of the dose was recovered as intact tolterodine,
and 5% to 14% (<1% in poor metabolizers) was recovered as
the active 5-hydroxymethyl metabolite. Most of the radioactivity
was recovered within the first 24 hours.
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［Indications and Usage］SHENITING Tablets
are indicated for the treatment of patients with an overactive
bladder with symptoms of urinary frequency, urgency, or urge
incontinence.
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| ［Dosage and Administration］The initial
recommended dose is 2 mg twice daily. The dose may be lowered
to 1 mg twice daily based on individual response and tolerability.
For patients with significantly reduced hepatic function or
who are currently taking drugs that are inhibitors of cytochrome
P450 3A4, the recommended dose is 1 mg twice daily. |
| |
| ［Contraindications］SHENITING Tablets are
contraindicated in patients with urinary retention, gastric
retention, or uncontrolled narrow-angle glaucoma, serious myasthenia
gravis, serious ulcerative colitis, or toxic megacolon. SHENITING
is also contraindicated in patients who have demonstrated hypersensitivity
to the drug or its ingredients. |
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| ［Adverse Reactions］Adverse events considered
to be treatment-related were dry mouth, dyspepsia, headache,
constipation, and dry eyes. Dry mouth, constipation, abnormal
vision (accommodation abnormalities), dry eyes, and urinary
retention are expected side effects of anti-muscarinic agents.
Tolterodine is well tolerated. |
| |
［Precautions］ Risk of Urinary Retention
and Decreased Gastrointestinal Motility: SHENITING Tablets should
be administered with caution to patients with clinically significant
bladder outflow obstruction because of the risk of urinary retention
and to patients with gastrointestinal obstructive disorders,
such as pyloric stenosis, because of the risk of gastric retention.
Controlled Narrow-Angle Glaucoma: SHENITING should be used with
caution in patients being treated for narrow-angle glaucoma.
Reduced Hepatic and Renal Function: Patients with significantly
reduced hepatic function should not receive doses of SHENITING
greater than 1 mg twice daily. Patients with renal impairment,
autonomic nervous or hiatal hernia should be treated with caution.
SHENITING should be used during pregnancy only if the potential
benefit for the mother justifies the potential risk for the
fetus.
It is not known whether tolterodine is excreted in human milk;
therefore, administration of SHENITING should be discontinued
during nursing.
The safety and effectiveness of SHENITING in pediatric patients
have not been established.
Patients driving, operation machinery or working in danger should
informed that tolterodine my produce blurred vision. |
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| ［Specification］ 2 mg。 |
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| ［Packaging］plastic aluminum package. |
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| ［Storage］ put in a cool place, and away
from light. |
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| ［Expiry Date］ one year from the date of
manufacturing. |
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