Tizanidine and clinically relevant interactions

Tizanidine and clinically relevant interactions

Tizanidine is an active substance in the group of centrally acting muscle relaxants for the treatment of muscle spasms and spasticity. Due to pharmacokinetic interactions, it cannot be administered together with strong CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin.

Key words: Tizanidine, Sirdalud, pharmacokinetic interactions, drug interactions, muscle relaxant, antispasmodic agent, CYP1A2 inhibitors, fluvoxamine, ciprofloxacin

Incident data


Case: 2019

Age group: 52

Sex: female

Medicinal products: Sirdalud®, Floxyfral®

Active substances: tizanidine, fluvoxamine

Indication: tizanidine: fibromyalgia
                fluvoxamine: schizoaffective disorder

ADR: bradycardia, pharmacokinetic interaction

Outcome: recovered

A few days after starting to take tizanidine, the patient was admitted to hospital as an emergency with bradycardia (heart rate 40/min). Tizanidine was stopped immediately. The patient has been taking fluvoxamine to treat a schizoaffective disorder for some considerable time. Her heart rate normalised after ceasing to take tizanidine. The treating physicians concluded that the bradycardia was caused by the known pharmacokinetic interaction between tizanidine and fluvoxamine.


Case: 2019

Age group: 70

Sex: male

Medicinal products: Sirdalud®, ciprofloxacin

Active substances: tizanidine, ciprofloxacin

Indication: Sirdalud: spasticity in multiple sclerosis
                Ciprofloxacin: urinary tract infection

ADR: bradycardia, syncope, pharmacokinetic interaction

Outcome: recovered

Ten days after starting to take ciprofloxacin, the patient experienced multiple syncopal episodes. On admission to hospital, a new occurrence of bradycardia (heart rate 50/min) was identified. The patient has multiple sclerosis and has been taking tizanidine regularly for some years.

Tizanidine and ciprofloxacin were stopped when the patient was admitted to hospital, and he did not experience any further syncopes. His heart rate had normalised by the time he was discharged.

Summary and recommendation

The muscle relaxant/antispasmodic agent tizanidine cannot be used concurrently with a strong CYP1A2 inhibitor such as fluvoxamine or ciprofloxacin, and administration concurrently with moderate CYP1A2 inhibitors is not recommended. The latter include some antiarrhythmic agents (amiodarone, propafenone), fluoroquinolones such as norfloxacin, and oral contraceptives.

Concurrent administration of CYP1A2 inhibitors can increase tizanidine plasma levels. This may lead to a persistent, clinically significant fall in blood pressure and to other known adverse drug reactions of tizanidine such as bradycardia or syncope.