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Issues for surgery

Loss of control of spasticity if omitted.

Risk of potentially fatal withdrawal symptoms if omitted (see Further information).

Risk of CNS depression if continued (see Interactions with common anaesthetic agents and Interactions with other common medicines used in the perioperative period).

Risk of QT-interval prolongation if continued (see Interactions with common anaesthetic agents and Interactions with other common medicines used in the perioperative period).

Advice in the perioperative period

Elective and emergency surgery 

Continue.

Consider checking liver function tests (LFTs) pre-operatively (see Further information).

For patients who may decide to quit smoking during the perioperative period see Further information.

Post-operative advice

Restart post-operatively as soon as next dose is due.

Interactions with common anaesthetic agents

Hypotension

Tizanidine can increase the risk of hypotension when used concomitantly with inhalational or intravenous anaesthetics.

Bradycardia

Tizanidine can increase the risk of bradycardia when used concomitantly with the following:

• alfentanil, fentanyl or remifentanil
• neostigmine
• propofol
• suxamethonium

CNS Depression

See also Interactions with other common medicines used in the perioperative period.

Tizanidine has CNS depressant effects which may be additive with other medicines that also have CNS depressant effects such as:

• benzodiazepines
• inhalational anaesthetics and intravenous anaesthetics
• local anaesthetics
• opioids

(Consult British National Formulary for available drugs in each class.)

QT-interval prolongation

Tizanidine prolongs the QT-interval. Co-administration with other medicines known to prolong the QT-interval must be based on careful assessment of the potential risks and benefits for each patient.

Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include:

• desflurane, isoflurane, sevoflurane*
• thiopental (theoretical)**

*monitor ECG if concurrent use unavoidable; if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances, e.g. hypokalaemia) use greater caution.

**monitor ECG with concurrent use if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances, e.g. hypokalaemia).

Sevoflurane

Also see QT-interval prolongation above.

Premedication with oral tizanidine appears to reduce the MAC of sevoflurane by 18%; the relevance of this has not yet been established but is not expected to be clinically significant. 

Interactions with other common medicines used in the perioperative period

Hypotension

Tizanidine can increase the risk of hypotension when used concomitantly with the antiemetics droperidol and prochlorperazine. 

CNS depression

See also Interactions with common anaesthetic agents.

Tizanidine has CNS depressant effects which may be additive with other medicines that also have CNS depressant effects such as:

• antiemetics (e.g. cyclizine, prochlorperazine)
• opioids

(Consult British National Formulary for available drugs in each class.)

Hypokalaemia

Dexamethasone and hydrocortisone may cause hypokalaemia, increasing the risk of torsades de pointes, which might be additive with the effects of tizanidine. This is unlikely to be an issue where corticosteroids are used as single doses to reduce post-operative nausea and vomiting or as cover for patients at risk of adrenal insufficiency. However, bear in mind should continued corticosteroid treatment be necessary post-operatively.

QT-interval prolongation

Tizanidine prolongs the QT-interval. Concurrent use with other drugs that can prolong the QT-interval might increase the risk.

Medicines that may be used in the perioperative period that are known to prolong the QT-interval include:

• ciprofloxacin – AVOID (see also ciprofloxacin below)
• clarithromycin*
• domperidone – AVOID
• droperidol*
• erythromycin (particularly intravenous)*
• granisetron*
• haloperidol – if concurrent use unavoidable monitor ECG for all patients (risk further increased if risk factors present)
• loperamide*
• ondansetron*
• prochlorperazine (theoretical risk)*

*monitor ECG with concurrent use if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances, e.g. hypokalaemia)

Ciprofloxacin

In addition to the increased risk of QT-interval prolongation ciprofloxacin markedly increases both exposure to tizanidine and adverse effects. Concomitant use of tizanidine and ciprofloxacin is contraindicated, however if concomitant use is unavoidable consider tizanidine dose reduction prior to starting ciprofloxacin and monitor closely for bradycardia, marked hypotension, sedation, and QT interval prolongation.

Further information

Withdrawal

Rebound hypertension and tachycardia have occurred after abrupt withdrawal of tizanidine, especially when it has been taken long term or in high doses or with antihypertensive medications. In extreme cases this rebound hypertension may lead to cerebrovascular accident therefore gradual dose reduction with blood pressure monitoring is advised.

LFTs

Tizanidine has been associated with hepatic dysfunction. LFTs should be monitored monthly for the first four months if daily dose exceeds 12mg or if patient reports unexplained nausea, anorexia or fatigue. If recent LFTs are not available and symptoms present, consider checking pre-operatively.

Manufacturer advises treatment should be discontinued if liver enzymes are persistently raised, patient develops jaundice or reports symptoms suggestive of hepatitis.

Smoking cessation

Tobacco is known to induce CYP1A2 which the main route of metabolism for tizanidine. Quitting smoking pre-operatively improves surgical outcomes through reducing risk of post-operative complications. If a patient decides to quit smoking during the perioperative period it must be remembered that smoking cessation can reduce tizanidine clearance. Patients should be advised to discuss smoking cessation with their prescriber as dosage adjustments may be necessary.

References

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press.[Accessed 27^th May 2024]

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. [Accessed on 27^thMay 2024]

Summary of Product Characteristics – Tizagelan (tizanidine) 2mg tablets. G.L Pharma UK Limited. Accessed via www.medicines.org.uk 27/05/2024 [date of revision of the text October 2021]

Faculty of Public Health, The Royal College of Surgeons of Edinburgh, The Royal College of Anaesthetists, ash (action on smoking and health). Joint Briefing: Smoking and surgery. April 2016. Available at www.rcoa.ac.uk[Accessed on 27^th May 2024].