Interactions between jolivette(norethindrone) and Zanaflex (tizanidine)
norethindrone and tizanidine (Major Drug-Drug)
GENERALLY AVOID: Coadministration with oral contraceptives may significantly increase the plasma concentrations and pharmacologic effects of tizanidine. The proposed mechanism is inhibition of tizanidine metabolism via CYP450 1A2. Retrospective evaluation of population pharmacokinetic data following single- and multiple-dose administration of tizanidine revealed an approximately 50% decrease in the clearance of tizanidine in women receiving oral contraceptives compared to women not receiving oral contraceptives. In a study of 30 healthy volunteers administered a single 4 mg dose of tizanidine, mean peak plasma concentration (Cmax) of tizanidine was 3.0 times higher and mean area under the plasma concentration-time curve (AUC) was 3.9 times greater in women using an oral contraceptive containing ethinyl estradiol and gestodene than in women not on the contraceptive. In one contraceptive user, the tizanidine AUC exceeded the mean AUC of the control subjects by nearly 20 times. There were no significant differences in the elimination half-life or time to peak concentration in plasma (Tmax) of tizanidine between the groups. Tizanidine to metabolite ratios in plasma and urine were 2 to 10 times higher in the contraceptive users than in control subjects, and the excretion of unchanged tizanidine into urine was on average 3.8 times greater in the contraceptive group. In addition, both the systolic and diastolic blood pressures were lowered by tizanidine more in the contraceptive users (29 mmHg and 21 mm Hg, respectively) than in the control subjects (17 mmHg and 13 mmHg, respectively). The interaction has also been reported with other CYP450 1A2 inhibitors such as fluvoxamine, ciprofloxacin, and rofecoxib.
MANAGEMENT: The use of tizanidine in combination with oral contraceptives or other CYP450 1A2 inhibitors should generally be avoided. Caution is advised if concurrent use is clinically necessary. Dosage adjustments may be required in patients who experience excessive adverse effects of tizanidine such as drowsiness, dizziness, lightheadedness, hypotension, bradycardia, or syncope.
