Doxycycline hyclate is available as a lyophilized powder in vials containing the equivalent of 100 mg of doxycycline with ascorbic acid 480 mg and mannitol 300 mg or the equivalent of 200 mg of doxycycline with ascorbic acid 960 mg and mannitol 600 mg.3071
The 100- or 200-mg vials should be reconstituted with 10 mL or 20 mL, respectively, of sterile water for injection; sodium chloride; dextrose 5%; Ringer’s injection; Ringer’s injection, lactated; dextrose 5% in Ringer’s injection, lactated; Normosol M or R in dextrose 5%; or Plasma-Lyte 56 or 148 in dextrose 5%.3071 The resultant solution contains the equivalent of 10 mg/mL of doxycycline.3071 This reconstituted solution must be further diluted to a concentration of 0.1 to 1 mg/mL with a compatible infusion solution prior to use.3071
pH
Reconstituted solution: 1.8 to 3.3.3071
Osmolality
The osmolality of doxycycline (Elkins-Sinn) 1 mg/mL was determined to be 292 mOsm/kg in dextrose 5% and 310 mOsm/kg in sodium chloride 0.9%.1375
Doxycycline hyclate is administered by intravenous infusion, usually over 1 to 4 hours.3071 Rapid administration should be avoided.3071 The reconstituted solution should be diluted further with a compatible infusion solution to a concentration of 0.1 to 1 mg/mL.3071 Other parenteral routes (e.g., intramuscular, subcutaneous) are not recommended, and extravasation should be avoided.3071
Intact vials should be stored at controlled room temperature and should remain in the carton until time of use to protect from light.3071
Product labeling states diluted solutions in sodium chloride or dextrose 5% at concentrations between 0.1 to 1 mg/mL are stable for 48 hours when stored at 25°C under fluorescent light, but must be protected from direct sunlight during storage and infusion.3071 If refrigerated and protected from light, these solutions may be stored up to 72 hours prior to start of infusion and infusion must be completed within 12 hours.3071
Diluted solutions in Ringer's injection, Normosol M or R in dextrose 5%, or Plasma-Lyte 56 or 148 in dextrose 5% at concentrations between 0.1 to 1 mg/mL must be completely infused within 12 hours of reconstitution and must be protected from direct sunlight during infusion.3071 If refrigerated and protected from light, these solutions may be stored up to 72 hours prior to start of infusion and infusion must be completed within 12 hours.3071
Diluted solutions in Ringer's injection, lactated or dextrose 5% in Ringer's injection, lactated at approximately 1 mg/mL or lower but not less than 0.1 mg/mL, must be completely infused within 6 hours of reconstitution and must be protected from direct sunlight during infusion.3071
Because of the acidity of the solution, doxycycline hyclate may precipitate the free acids of barbiturate salts and sulfonamide derivatives. It may also adversely affect the stability of acid-labile drugs.6; 20; 22; 27
Freezing Solutions
Doxycycline hyclate reconstituted with sterile water for injection to 10 mg/mL is stated to be stable for 8 weeks when frozen at -20°C immediately following reconstitution.3071 Frozen solutions that have been completely thawed should not be heated.3071 Thawed solutions should not be refrozen.3071
Doxycycline (Pfizer) 10 mg/mL in sterile water for injection was stable for 8 weeks when frozen at -20°C. At a concentration of 1 mg/mL in dextrose 5%, doxycycline also showed no significant decomposition over 8 weeks at -20°C.310
Sorption
Doxycycline was shown not to exhibit sorption to PVC bags and tubing, polyethylene tubing, Silastic tubing, and polypropylene syringes.536; 606
Central Venous Catheter
Doxycycline (Fujisawa) 0.5 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
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