Is it safe to take 100mg doxycycline hyclate with 300 mg clindamycin?

Yes, it's safe.: There is no specific interaction. However, with all antibiotics, you should be aware that prolonged use of multiple antibiotics does tend to destroy the normal gut flora (normal bacteria in your intestinal tract) and allows for overgrowth of one particularly BAD type of bacteria called clostridium difficile (C. Diff). This can lead to prolonged bouts of diarrhea. So, be careful in the long term.