Drug Interactions between elagolix / estradiol / norethindrone and tizanidine

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with inhibitors of CYP450 1A2 may significantly increase the plasma concentrations and pharmacologic effects of tizanidine, which is a sensitive substrate of the isoenzyme. In 10 healthy volunteers, administration of a single 4 mg dose of tizanidine following pretreatment with the potent CYP450 1A2 inhibitor fluvoxamine (100 mg orally once daily for 4 days) increased tizanidine peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 12- and 33-fold, respectively, compared to placebo. The mean elimination half-life of tizanidine was prolonged from 1.5 to 4.3 hours. Similarly, pretreatment with the moderate CYP450 1A2 inhibitor ciprofloxacin (500 mg orally twice daily for 3 days) increased Cmax and AUC of a single 4 mg dose of tizanidine by an average of 7- and 10-fold, respectively, compared to placebo. Pharmacologic effects of tizanidine as measured by changes in blood pressure, heart rate, performance testing, subjective drug effect, and drowsiness were significantly greater with both fluvoxamine and ciprofloxacin compared to placebo. Vemurafenib, another moderate CYP450 1A2 inhibitor, increased tizanidine AUC by 4.7-fold. The interaction was also suspected in a 70-year-old patient treated with tizanidine who developed low heart rate, low body temperature, dry mouth, and anuresis two weeks after initiating fluvoxamine. A retrospective review of patient medical records at the hospital where the patient was admitted revealed a significantly higher incidence of tizanidine-related adverse effects in patients treated concomitantly with fluvoxamine than that reported for tizanidine alone in the product labeling (26.1% vs. 5.3%), and those who experienced adverse effects were older and received higher dosages of both drugs than those who did not have adverse effects with the combination. Another CYP450 1A2 inhibitor, rofecoxib, has also been reported to potentiate the adverse effects of tizanidine. There have been postmarketing reports of adverse events mostly involving the nervous system (e.g., hallucinations, psychosis, somnolence, hypotonia) and cardiovascular system (e.g., hypotension, tachycardia, bradycardia) during concomitant use of tizanidine and rofecoxib. In all cases, adverse events resolved following discontinuation of one or both drugs. Rechallenge's were not performed.

MANAGEMENT: Concomitant use of tizanidine with CYP450 1A2 inhibitors should generally be avoided. Otherwise, caution is advised if coadministration is required. Dosage adjustments may be necessary in patients who experience excessive adverse effects of tizanidine such as drowsiness, dizziness, lightheadedness, hypotension, and bradycardia.

Ask your doctor before using norethindrone together with tiZANidine. This can cause drowsiness, confusion, slow heart rate, shallow breathing, feeling light-headed, fainting, or coma. You may need a dose adjustment if you take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Estradiol and other estrogen-containing medications may reduce the effectiveness of elagolix in treating your condition. If you require contraception, it is recommended that you use a non-hormonal form of contraception during treatment with elagolix and for one week after its discontinuation. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Elagolix may reduce the blood levels and effects of norethindrone. If you are using low-dose oral contraceptives, you may have an increased risk of breakthrough bleeding and unintended pregnancy. You should discuss the use of alternative or additional methods of birth control with your healthcare provider. If you take hormone replacement for menopause, notify your doctor if your medication is no longer controlling your symptoms or you experience abnormal bleeding. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.