A larger, lab-scale photocatalytic suspended-bed reactor using TiO sol-gel-coated expanded clay granules as a bed material was evaluated for oxidative removal of the persistent pharmaceuticals doxycycline, prednisolone, amoxicillin, and sulfamethizole, as well as their mixture, in ppm concentrations. The photocatalytic degradation potential of drug molecules increases as their adsorption affinity increases towards TiO-containing coatings. The performance of the photocatalytic reactor in the removal of drugs was improved by optimizing the fluidization process parameters. The reactor operation at high bed loadings is determined by the abrasion resistance of the catalyst coating. The long-term stability of the coated bed was enhanced by optimal loading, achieving a higher removal rate while placing moderate mechanical stress on the coated granules. The photocatalytic pretreatment decreased the toxicity of doxycycline solutions to several bacterial strains, including the environmental bacterium Pseudomonas putida and bacterial strains freshly isolated from the activated sludge. The treatment of doxycycline-containing water with a combination of photocatalytic treatment and bio-oxidation resulted in 98% removal of the target in the bioreactor outlet, with no deterioration in the operation of the biological process.