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Repan and Tizanidine Hydrochloride

Determining the interaction of Repan and Tizanidine Hydrochloride and the possibility of their joint administration.

Check result:
Repan <> Tizanidine Hydrochloride
Relevance: 09.10.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Caffeine may significantly increase the blood levels and effects of tiZANidine in some patients. This may cause blood pressure to fall excessively, especially when you rise from a sitting or lying position. The risk of other side effects such as drowsiness, dizziness, lightheadedness, fainting, and irregular heart rhythm may also increase. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring 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.

Professional:

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.

References
  • Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ "Fluvoxamine drastically increases concentrations and effects of tizanidine: A potentially hazardous interaction." Clin Pharmacol Ther 75 (2004): 331-41
  • "Product Information. Vioxx (rofecoxib)." Merck & Co, Inc, West Point, PA.
  • "Product Information. Zelboraf (vemurafenib)." Genentech, South San Francisco, CA.
  • Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ "Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism." Clin Pharmacol Ther 76 (2004): 598-606
  • Momo K, Doki K, Hosono H, Homma M, Kohda Y "Drug interaction of tizanidine and fluvoxamine." Clin Pharmacol Ther 76 (2004): 509-10
  • Granfors MT, Backman JT, Laitila J, Neuvonen PJ "Tizanidine is mainly metabolized by cytochrome P450 1A2 in vitro." Br J Clin Pharmacol 57 (2004): 349-53
  • "Product Information. Zanaflex (tizanidine)." Acorda Therapeutics, Hawthorne, NY.
  • Momo K, Homma M, Kohda Y, Ohkoshi N, Yoshizawa T, Tamaoka A "Drug interaction of tizanidine and ciprofloxacin: Case report." Clin Pharmacol Ther 80 (2006): 717-9
Repan

Generic Name: acetaminophen / butalbital / caffeine

Brand name: Capacet, Esgic, Fioricet, Margesic, Medigesic, Orbivan, Repan, Vanatol LQ, Zebutal, Esgic-Plus, Arcet, Isocet, Pharmagesic, Anoquan, Two-Dyne, Tenake, Anolor 300, Femcet, Geone, Tencet, Triad, Fiorpap, Dolmar, Endolor, Ezol, Ide-cet, G-1, Minotal, Mygracet, Pacaps, Alagesic, Americet, Nonbac, Dolgic LQ, Dolgic Plus, Vanatol S, Alagesic LQ

Synonyms: n.a.

Tizanidine Hydrochloride

Generic Name: tizanidine

Brand name: Zanaflex

Synonyms: Tizanidine, TiZANidine

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

Interaction with food and lifestyle
Disease interaction