Tizanidine: Watch Out for Drugs Interacting With This Muscle Relaxant

Tizanidine (ZANAFLEX) is a muscle relaxant that has been around since 1996. Last year, more than 3.8 million prescriptions were filled for the drug in the U.S. It does not affect the muscles directly, but rather directs the central nervous system to relax the muscles.  

Drugs that reduce the elimination of tizanidine, increase blood levels

Probably the most dangerous drug interactions with tizanidine occur when it is taken with drugs that inhibit its elimination from the body. The resultant buildup of tizanidine in the blood can cause toxicity, overwhelming the organs and leading to side effects such as difficulty breathing or dangerously low blood pressure that can result in falling.  

The drugs in this category are those that inhibit the liver enzyme CYP1A2, since tizanidine is metabolized mainly by that enzyme. Several drugs inhibit this enzyme, and should not be taken with tizanidine.

Fluvoxamine (LUVOX). This combination should absolutely be avoided. Fluvoxamine, one of the anti-depressant selective serotonin reuptake inhibitors (SSRIs), is a potent inhibitor of CYP1A2. In one study, when tizanidine was taken with fluvoxamine, tizanidine blood levels were 33 times higher than when tizanidine was taken alone. Other SSRIs are less likely to interact with tizanidine and are preferable to fluvoxamine in this situation.

Ciprofloxacin (CIPRO). The combination of tizanidine and ciprofloxacin also should be avoided. The antibiotic ciprofloxacin also inhibits CYP1A2 and has been shown to substantially increase tizanidine blood levels in healthy subjects, producing decreased blood pressure, drowsiness and decreased motor skills. Another antibiotic in the ciprofloxacin family (enoxacin, brand name PENETREX) also is a potent inhibitor of CYP1A2 and can be expected to interact with tizanidine similarly to ciprofloxacin.

Other members of the ciprofloxacin family such as gemifloxacin (FAC- TIVE), levofloxacin (LEVAQUIN), lomefloxacin (MAXAQUIN), moxifloxacin (AVELOX) and ofloxacin (FLOXIN) probably do not have much effect on tizanidine levels.

Oral Contraceptives. Women taking oral contraceptives have been shown to develop increases in tizanidine blood levels. The magnitude of this increase is not as large as with fluvoxamine or ciprofloxacin, but it still may be enough to increase the side effects of tizanidine. Women who take oral contraceptives should use doses of tizanidine that are as low as possible and watch for side effects.

Other CYP1A2 Inhibitors. Other drugs that can inhibit CYP1A2 (and may thus increase tizanidine blood levels) include atazanavir (REYATAZ), cimetidine (TAG- AMET), mexiletine (MEXITIL), tacrine (COGNEX), zafirlukast (AC- COLATE) and zileuton (ZYFLO).

Combining tizanidine with other sedatives

One of the most common side effects of tizanidine is sedation. Because of this, it is important to be careful in taking the medication with other drugs that also have sedative effects because the combination can cause further increases in sedation. These include anti-anxiety agents; sleeping pills; antidepressants such as amitriptyline (ELAVIL), amoxapine (ASCENDIN), clomipramine (ANAFRANIL), doxepin (SINEQUAN) and nortriptyline (AVENTYL); certain antihistamines such as diphenhydramine (BENADRYL); and some anti-seizure medications such as phenytoin (DILANTIN).

Alcohol can create a double whammy effect when taken with tizanidine because the combination can result in both heightened sedative effects and increased tizanidine blood levels. You should not drink alcohol frequently or in large amounts if you are taking tizanidine.

Tizanidine also has a tendency to lower blood pressure somewhat. If you are already taking blood pressure-lowering medications, the combination occasionally results in an excessive and possibly dangerous decrease in blood pressure. Your blood pressure needs to be monitored when tizanidine is started, stopped or if the dosage is changed.

What You Can Do

Certain medications should not be taken with tizanidine, such as the CYP1A2 inhibitors fluvoxamine, ciprofloxacin and enoxacin; avoid these combinations completely as there are satisfactory alternatives for each. Other CYP1A2 inhibitors, as listed above, should be used only if necessary, and then with careful attention to tizanidine toxicity.

If tizanidine is used with other sedatives, be careful that the combination does not result in excessive sedation.

If you use tizanidine with blood pressure-lowering medications, watch for excessive decreases in blood pressure and pause, briefly, if going from lying to sitting or sitting to standing positions to decrease your chances of falling because of sudden lowering of your blood pressure.

Food increases the amount of tizanidine absorbed, so it is a good idea to take tizanidine consistently with regard to meals.

Table. Drugs that Interact with Tizanidine