TIZANIDINE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TIZANIDINE HYDROCHLORIDE (UNII: B53E3NMY5C) (TIZANIDINE - UNII:6AI06C00GW)

Available from:

REMEDYREPACK INC.

INN (International Name):

TIZANIDINE HYDROCHLORIDE

Composition:

TIZANIDINE 4 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Tizanidine tablet is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine tablets should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration ( 2.1) ]. Tizanidine hydrochloride is contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions ( 7.1, 7.2 ) ]. Pregnancy Category C Tizanidine hydrochloride has not been studied in pregnant women. Tizanidine hydrochloride should be given to pregnant women only if the benefit outweighs the risk to the unborn fetus. Reproduction studies performed in rats at a dose of 3 mg/kg, equal to the maximum recommended human dose on a mg/m 2 basis, and in rabbits at 30 mg/kg, 16 times the maximum recommended human dose on a mg/m 2 basis, did not show evidence of teratogenicity. Tizanidine at doses that are equal to and up to 8 times the maximum recommended human dose on a mg/m 2 basis increased gestation duration in rats. Prenatal and postnatal pup loss was increased and developmental retardation occurred. Post-implantation loss was increased in rabbits at doses of 1 mg/kg or greater, equal to or greater than 0.5 times the maximum recommended human dose on a mg/m 2 basis. 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 tizanidine hydrochloride is administered to a nursing woman. Safety and effectiveness in pediatric patients have not been established. Tizanidine hydrochloride is known to be substantially excreted by the kidney, and the risk of adverse 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 in dose selection, and it may be useful to monitor renal function. Clinical studies of tizanidine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Cross-study comparison of pharmacokinetic data following single dose administration of 6 mg tizanidine hydrochloride showed that younger subjects cleared the drug four times faster than the elderly subjects. In elderly patients with renal insufficiency (creatinine clearance <25 mL/min), tizanidine clearance is reduced by more than 50% compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. During titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. Monitor elderly patients because they may have an increased risk for adverse reactions associated with tizanidine hydrochloride. Tizanidine hydrochloride is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. In patients with renal insufficiency (creatinine clearance < 25 mL/min) clearance was reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. These patients should be monitored closely for the onset or increase in severity of the common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdose. [see Dosage and Administration ( 2.2), Warnings and Precautions (5.7) and Clinical Pharmacology ( 12.3 )] The influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. Because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine. [see Dosing and Administration (2.3), Warnings and Precautions ( 5.2), and Clinical Pharmacology ( 12.3) ]. Abuse potential was not evaluated in human studies. Rats were able to distinguish tizanidine from saline in a standard discrimination paradigm, after training, but failed to generalize the effects of morphine, cocaine, diazepam, or phenobarbital to tizanidine. Tizanidine is closely related to clonidine, which is often abused in combination with narcotics and is known to cause symptoms of rebound upon abrupt withdrawal. Three cases of rebound symptoms on sudden withdrawal of tizanidine have been reported. The case reports suggest that these patients were also misusing narcotics. Withdrawal symptoms included hypertension, tachycardia, hypertonia, tremor, and anxiety. Withdrawal symptoms are more likely to occur in cases where high doses are used, especially for prolonged periods, or with concomitant use of narcotics. If therapy needs to be discontinued, the dose should be decreased slowly to minimizethe risk of withdrawal symptoms [see Dosage and Administration ( 2.2) ]. Monkeys were shown to self-administer tizanidine in a dose-dependent manner, and abrupt cessation of tizanidine produced transient signs of withdrawal at doses > 35 times the maximum recommended human dose on a mg/m 2 basis. These transient withdrawal signs (increased locomotion, body twitching, and aversive behavior toward the observer) were not reversed by naloxone administration.

Product summary:

Tizanidine Tablets USP, 4 mg are white to off white, oval, flat, beveled edged tablets debossed with “R180” on one side and “quadrisecting score” on other side. The tablets are available in NDC: 70518-0133-00 NDC: 70518-0133-01 NDC: 70518-0133-02 NDC: 70518-0133-03 PACKAGING: 60 in 1 BOTTLE PLASTIC PACKAGING: 90 in 1 BOTTLE PLASTIC PACKAGING: 15 in 1 BOTTLE PLASTIC PACKAGING: 30 in 1 BOTTLE PLASTIC Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Dispense in containers with child resistant closure. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

TIZANIDINE- TIZANIDINE TABLET
REMEDYREPACK INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TIZANIDINE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
TIZANIDINE TABLETS.
TIZANIDINE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1996
INDICATIONS AND USAGE
Tizanidine tablet is a central alpha-2-adrenergic agonist indicated
for the management of spasticity.
Because of the short duration of therapeutic effect, treatment with
tizanidine tablet should be reserved for
those daily activities and times when relief of spasticity is most
important. (1)
DOSAGE AND ADMINISTRATION
Recommended starting dose: 2 mg; dose can be repeated at 6 to 8
hourintervals, up to a maximum of
3 doses in 24 hours (2.1)
Dosage can be increased by 2 mg to 4 mg per dose, with 1 to 4
daysbetween increases; total daily
dose should not exceed 36 mg (2.1)
Tizanidine pharmacokinetics differs between tablets and capsules,
andwhen taken with or without food.
These differences could result in achange in tolerability and control
of symptoms ( 2.1, 12.3)
To discontinue tizanidine tablet, decrease dose slowly to minimize the
risk of withdrawal and rebound
hypertension, tachycardia, and hypertonia ( 2.2)
DOSAGE FORMS AND STRENGTHS
Tablets 4 mg (3)
CONTRAINDICATIONS
Concomitant use with potent inhibitors of CYP1A2, such as fluvoxamine
or ciprofloxacin ( 4, 5.5, 7.1,
7.2)
WARNINGS AND PRECAUTIONS
Hypotension: monitor for signs and symptoms of hypotension, in
particular in patients receiving
concurrent antihypertensives; tizanidine hydrochloride should not be
used with other α
-adrenergic
agonists ( 5.1, 7.7)
Risk of liver injury: monitor ALTs; discontinue tizanidine
hydrochloride if liver injury occurs ( 5.2)
Sedation: tizanidine hydrochloride may interfere with everyday
activities; sedative effects of tizanidine
hydrochloride, alcohol, and other CNS depressants are additive ( 5.3,
7.5, 7.6)
Hallucinations: consider discontinuation of tizanidine hydrochloride (
5.4)
Les