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Drug Details

ZANAFLEX

• Drug Class Description
  Central a2 -agonists (alpha- agonists).
• Generic Name
  Tizanidine
• Presentation
  Tablet White to off-white, circular flat bevelled edge tablet. Scored on one side, 'A' and 592 on the other side. White to off-white, circular flat bevelled edge tablet. Cross scored on one side, 'A' and 594 on the other side.
• Description
  Zanaflex tablets containing 2 mg of tizanidine as the hydrochloride. Zanaflex tablets containing 4 mg of tizanidine as the hydrochloride.
• Indications
  Treatment of spasticity associated with multiple sclerosis or with spinal cord injury or disease.
• Adult Dosage
  

  For oral administration

  The effect of Zanaflex on spasticity is maximal within 2-3 hours of dosing and it has a relatively short duration of action. The timing and frequency of dosing should therefore be tailored to the individual, and Zanaflex should be given in divided doses, up to 3-4 times daily, depending on the patient's needs. There is considerable variation in response between patients so careful titration is necessary. Care should be taken not to exceed the dose producing the desired therapeutic effect. It is usual to start with a single dose of 2 mg increasing by 2 mg increments at no less than half-weekly intervals.

  The total daily dose should not exceed 36 mg, although it is usually not necessary to exceed 24 mg daily. Secondary pharmacological effects may occur at therapeutic doses but these can be minimised by slow titration so that in the large majority of patients they are not a limiting factor.

   Patients with Renal impairment

  In patients with renal insufficiency (creatinine clearance < 25mL/min) treatment should be started with 2 mg once daily with slow titration to achieve the effective dose. Dosage increases should be in increments of no more than 2 mg according to tolerability and effectiveness. It is advisable to slowly increase the once-daily dose before increasing the frequency of administration. Renal function should be monitored as appropriate in these patients.

  Patients with Hepatic Impairment

  Zanaflex is contraindicated in patients with significantly impaired hepatic function

• Child Dosage
  

  Experience with Zanaflex in patients under the age of 18 years is limited. Zanaflex is not recommended for use in children.

• Elderly Dosage
  

  Experience in the elderly is limited and use of Zanaflex is not recommended unless the benefit of treatment clearly outweighs the risk. Pharmacokinetic data suggest that renal clearance in the elderly may be decreased by up to three fold.

• Contra Indications
  

  Hypersensitivity to tizanidine or any other component of the product.

  The use of Zanaflex in patients with significantly impaired hepatic function is contraindicated, because tizanidine is extensively metabolised by the liver.

  Concomitant use of tizanidine with fluvoxamine or ciprofloxacin is contra-indicated.

• Special Precautions
  

  Concomitant use of tizanidine with CYP1A2 inhibitors is not recommended.

  Use in Renal Impairment

  Patients with renal impairment may require lower doses and therefore caution should be exercised when using Zanaflex in these patients.

  Liver Function

  Hepatic dysfunction has been reported in association with Zanaflex. It is recommended that liver function tests should be monitored monthly for the first four months in all patients and in those who develop symptoms suggestive of liver dysfunction such as unexplained nausea, anorexia or tiredness. Treatment with Zanaflex should be discontinued if serum levels of SGPT and/or SGOT are persistently above three times the upper limit of normal range.

  Zanaflex tablets contain lactose. This medicine is not recommended in patients with the rare hereditary problem of galactose intolerance, of severe lactase deficiency or of glucose-galactose malabsorption.

  Zanaflex should be kept out of the reach and sight of children.

• Interactions
  

  As Zanaflex may induce hypotension it may potentiate the effect of antihypertensive drugs, including diuretics, and caution should therefore be exercised in patients receiving blood pressure lowering drugs. Caution should also be exercised when Zanaflex is used concurrently with βadrenoceptor blocking drugs or digoxin as the combination may potentiate hypotension or bradycardia.

  Caution should be exercised when Zanaflex is prescribed with drugs known to increase the QT interval.

  Concomitant use of tizanidine with fluvoxamine or ciprofloxacin, both CYP450 1A2 inhibitors in man, is contraindicated. Concomitant use of tizanidine with fluvoxamine or ciprofloxacin resulted in a 33-fold and 10-fold increase in tizanidine AUC, respectively. Clinically significant and prolonged hypotension may result along with somnolence, dizziness and decreased psychomotor performance. Co-administration of tizanidine with other inhibitors of CYP1A2 such as some antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, some fluoroquinolones (enoxacin, norfloxacin) and ticlopidine is not recommended.

  Pharmacokinetic data following single and multiple doses of Zanaflex suggested that clearance of Zanaflex was reduced by approximately 50% in women who were concurrently taking oral contraceptives. Although no specific pharmacokinetic study has been conducted to investigate a potential interaction between oral contraceptives and Zanaflex, the possibility of a clinical response and/or adverse effects occurring at lower doses of Zanaflex should be borne in mind when prescribing Zanaflex to a patient taking the contraceptive pill. Clinically significant drug-drug interactions have not been reported in clinical trials.

  Alcohol or sedatives may enhance the sedative action of Zanaflex.

• Adverse Drug Reactions
  

  The most frequently reported adverse events occurring in association with Zanaflex include drowsiness, fatigue, dizziness, dry mouth, nausea, gastrointestinal disturbances, and a reduction in blood pressure. With slow upward titration of the dose of Zanaflex these effects are usually not severe enough to require discontinuation of treatment. Insomnia, bradycardia and hallucinations have also been reported.

  The hallucinations are self-limiting, without evidence of psychosis, and have invariably occurred in patients concurrently taking potentially hallucinogenic drugs, e.g. anti-depressants. Increases in hepatic serum transaminases, which are reversible on stopping treatment, have occurred.

  Infrequent cases of acute hepatitis have been reported. Muscle weakness has been reported infrequently, although in controlled clinical trials it was clearly demonstrated that Zanaflex does not adversely affect muscle strength. Allergic reactions (e.g. pruritus and rash) have rarely been reported.