Theophylline (major): CYP1A2 inhibition. Loi 1997 (PMID:9023273): ciprofloxacin 500 mg q12h × 5d reduced theophylline CL by 23-33% (AUC ~1.39× increase). Theophylline narrow therapeutic index → monitor levels + reduce theophylline dose 30-50% on co-administration.
Tizanidine (contraindicated): CYP1A2 inhibition. Granfors 2004 (PMID:15592331): ciprofloxacin raised tizanidine AUC 10× (range 6-24×). Hypotension + sedation risk severe enough that the combination is contraindicated; fluvoxamine-tizanidine carries the same warning.
Caffeine (caution): CYP1A2 inhibition. Healy 1989 (PMID:2729942) verbatim: AUC "from 16.3 ± 6.6 to 25.9 ± 7.8 micrograms.h/ml" and CL "from 106 ± 41.6 to 58.2 ± 28.8 ml/min per 1.73 m2". 10 fasting xanthine-free males, 100 mg PO caffeine ± ciprofloxacin 750 mg q12h × 3 doses. AUC ratio 1.59×; Ki ≈ 7.5/0.59 = 12.73 µM. Clinically: jitter / insomnia magnified by chronic cipro at typical caffeine intakes.
Ropivacaine (caution): CYP1A2 inhibition (3-OH-ropivacaine formation). Jokinen 2003 (PMID:12610740) verbatim: "Ciprofloxacin decreased the mean clearance (CL) of ropivacaine by 31%". 9 healthy volunteers, double-blind crossover, cipro 500 mg PO bid × 2.5d → 0.6 mg/kg IV ropivacaine. Inter-individual range -52% to +39% CL change. AUC ratio 1/(1-0.31) = 1.45×; Ki ≈ 16.71 µM. Long-block regional anesthesia + cipro risks toxicity for high-end responders.
Clozapine (caution): CYP1A2 + minor CYP3A4 inhibition. Brouwers 2009 (PMID:19067475) — TWO CASE REPORTS, not a controlled crossover. Verbatim: "clozapine concentrations doubled over that time period". 58 y/o male on 300 mg/d clozapine, plasma doubled within 3 days of cipro initiation. Concentration ratio ~2×; Ki ≈ 7.5 µM (case-report provenance, less precise than controlled). Narrow TI: dose reduction or alternate antibiotic when combined.