TIZANIDINE HYDROCHLORIDE capsule, gelatin coated

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

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

Tilgjengelig fra:

Apotex Corp.

INN (International Name):

TIZANIDINE HYDROCHLORIDE

Sammensetning:

TIZANIDINE 2 mg

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

Tizanidine is indicated for the management of spasticity. Because of the short duration of therapeutic effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important [see Dosage and Administration (2.1)] . Tizanidine is contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions (7.1, 7.2)] . Risk Summary There are no adequate data on the developmental risk associated with use of tizanidine in pregnant women. In animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see Animal Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of tizanidine (0.3 to 100 mg/kg/day) to pregnant rats during the period of organogenesis resulted in embryofetal and postnatal offspring mortality and reductions in body weight at doses of 30 mg/kg/day and above. Maternal toxicity was observed at the highest dose tested. The no-effect dose for embryofetal developmental toxicity in rats (3 mg/kg/day) is similar to the maximum recommended human dose (MRHD) of 36 mg/day on a body surface area (mg/m2 ) basis. Oral administration of tizanidine (1 to 100 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal and postnatal offspring mortality at all doses. Maternal toxicity was observed at the highest dose tested. Oral administration of tizanidine (10 and 30 mg/kg/day) during the perinatal period of pregnancy (2 to 6 days prior to delivery) resulted in increased postnatal offspring mortality at both doses. A no-effect dose for embryofetal developmental toxicity in rabbit was not identified. The lowest dose tested (1 mg/kg/day) is less than the MRHD on a mg/m2 basis. In a pre- and postnatal development study in rats, oral administration of tizanidine (3 to 30 mg/kg/day) resulted in increased postnatal offspring mortality. A no-effect dose for pre- and postnatal developmental toxicity was not identified. The lowest dose tested (3 mg/kg/day) is similar to the MRHD on a mg/m2 basis, respectively. Risk Summary There are no data on the presence of tizanidine in human milk, the effects on the breastfed infant, or the effects on human milk production. Animal studies have reported the presence of tizanidine in the milk of lactating animals. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tizanidine and any potential adverse effects on the breastfed infant from tizanidine or from the underlying maternal condition. There are no adequate and well-controlled studies in humans on the effect of tizanidine on female or male reproductive potential. Oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see Nonclinical Toxicology (13.1)] . Safety and effectiveness in pediatric patients have not been established. Tizanidine 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 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 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. Tizanidine 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, individual doses should be reduced during titration. 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 tizanidine common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdosage [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 minimize the 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/m2 basis. These transient withdrawal signs (increased locomotion, body twitching, and aversive behavior toward the observer) were not reversed by naloxone administration.

Produkt oppsummering:

Tizanidine Hydrochloride Capsules 2 mg are available as hard gelatin capsules with blue opaque body and blue opaque cap imprinted “APO T2” in black ink. They are supplied as follows:   Bottles of 30 (NDC 60505-2648-3) Bottles of 150 (NDC 60505-2648-7) Bottles of 1000 (NDC 60505-2648-8) Tizanidine Hydrochloride Capsules 4 mg are available as hard gelatin capsules with white opaque body and blue green opaque cap imprinted “APO T4” in black ink. They are supplied as follows:   Bottles of 30 (NDC 60505-2649-3) Bottles of 150 (NDC 60505-2649-7) Bottles of 1000 (NDC 60505-2649-8) Tizanidine Hydrochloride Capsules 6 mg are available as hard gelatin capsules with blue opaque body and blue opaque cap imprinted “APO T6” in black ink. They are supplied as follows:   Bottles of 30 (NDC 60505-2650-3) Bottles of 150 (NDC 60505-2650-7) Bottles of 1000 (NDC 60505-2650-8) Store at 20º C to 25º C (68º F to 77º F); excursions permitted from 15º C to 30º C (59º F to 86º F) [see USP Controlled Room Temperature].   Dispense in a tight, light-resistant container [see USP]. Dispense in containers with child resistant closure.

Autorisasjon status:

Abbreviated New Drug Application

Preparatomtale

TIZANIDINE HYDROCHLORIDE- TIZANIDINE HYDROCHLORIDE CAPSULE, GELATIN
COATED
APOTEX CORP.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TIZANIDINE
HYDROCHLORIDE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
TIZANIDINE HYDROCHLORIDE CAPSULES.
TIZANIDINE HYDROCHLORIDE CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 1996
INDICATIONS AND USAGE
Tizanidine is a central alpha-2-adrenergic agonist indicated for the
management of spasticity. Because of
the short duration of therapeutic effect, treatment with tizanidine
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-hour
intervals, 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 days
between increases; total daily
dose should not exceed 36 mg (2.1)
Tizanidine pharmacokinetics differs between tablets and capsules, and
when taken with or without food.
These differences could result in a change in tolerability and control
of symptoms (2.1, 12.3)
To discontinue tizanidine, decrease dose slowly to minimize the risk
of withdrawal and rebound
hypertension, tachycardia, and hypertonia (2.2)
DOSAGE FORMS AND STRENGTHS
Capsules 2 mg, 4 mg and 6 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 should not be used with other
α -adrenergic agonists (5.1, 7.7)
Risk of liver injury: monitor ALTs; discontinue tizanidine if liver
injury occurs (5.2)
Sedation: Tizanidine may interfere with everyday activities; sedative
effects of tizanidine, alcohol, and
other CNS depressants are additive (5.3, 7.5, 7.6)
Hallucinations: consider discontinuation of tizanidine (