Doxycycline Hyclate, Doxycycline Monohydrate
Doxycycline Hyclate, Doxycycline Monohydrate
Vibramycin, Monodox, Doxy Caps, and generic brands
Фармакокинетика и механизм действия
Tetracycline antibiotic. Mechanism of action of tetracyclines is to bind to the 30S ribosomal subunit and inhibit protein synthesis. The action of tetracyclines is usually bacteriostatic. It has a broad spectrum of activity, including bacteria, some protozoa, Rickettsia, and Ehrlichia. In dogs, after oral administration the half-life is 12.6 hours, the volume of distribution is 1.7 L/kg and oral absorption is 66%, producing a peak concentration of 4.5 mcg/mL. In horses, 10 mg/kg intragastric had a half-life of 13.8 hours with oral absorption of 17%, and a peak concentration of 0.48 mcg/mL. Indications and Clinical Uses Doxycycline is usually the drug of choice for treating tickborne diseases in animals. Efficacy has been demonstrated in research studies and in some clinical studies. It is used for treating infections caused by bacteria, some protozoa, Rickettsia, and Ehrlichia. Doxycycline administered to cats with infections caused by Mycoplasma or Chlamydophilia felis (formerly Chlamydia psittaci) at 10-15 mg/kg once daily PO, or 5 mg/kg q12h PO, has been effective in eliminating the organism and improving clinical signs. In dogs, 5 mg/kg q12h PO for 3-4 weeks has cleared Ehrlichia canis from blood and tissues. Doxycycline is recommended by the American Heartworm So-ciety to be added to treatment of canine heartworm disease. It is used for heartworm disease because of the activity against the organism Wolbachia. This may improve mi-crofiliaricidal effect when combined with ivermectin, improve response to adulticidal treatment with melarsomine, and decrease injury to pulmonary vessels. In horses, it has been used to treat ehrlichiosis, but also has been used to treat other diseases (e.g., re-spiratory infections) when oral treatment is indicated. In recent years, doxycycline has become unavailable or more expensive. If other oral alternatives are needed, minocy-cline hydrochloride is an acceptable substitute (see minocycline section for more details).
Tetracyclines may cause renal tubular necrosis at high doses and can affect boneand teeth formation in young animals. However, doxycycline has not been re-ported to cause the problems with chelation to calcium and teeth discoloration in animals. Doxycycline administered orally to cats has caused esophageal irritation, tissue injury, and esophageal stricture. This may be caused by solid-dose formula-tions (primarily doxycycline hyclate rather than doxycycline monohydrate) becom-ing entrapped in the esophagus. Passage into the stomach by giving the cat water or food after administration is advised to prevent this effect. Doxycycline given IV to horses has been fatal; however, it has been administered safely to horses PO, al-though diarrhea is possible. In two equine studies there were no adverse effects reported from oral administration. In another study, one of the horses in a phar-macokinetic trial developed signs of enteritis and colic.
Противопоказания и применение с острожностью
Ordinarily tetracyclines should not be administered to young animals because it can
affect bone and teeth formation. However, it has been better tolerated in children
than other tetracyclines. If solid-dose forms are administered to cats, lubricate the
tablet/capsule, or follow with food or water to ensure passage into stomach. Do
not administer rapidly IV. Do not administer solution IM or SQ. Do not administer
IV to horses under any circumstances; acute death has been reported from this use.
Tetracyclines bind to compounds containing calcium, which decreases oral
absorption. However, this is less of a problem with doxycycline than with other
tetracyclines. Doxycycline has been mixed with milk prior to oral administration
to children without decreasing efficacy.
Many pharmacokinetic and experimental studies have been conducted in small
animals. Doxycycline is ordinarily considered the drug of choice for Rickettsia and
Ehrlichia infections in dogs. Doxycycline is more effective than enrofloxacin for
Ehrlichia. When used with ivermectin (6 mcg/kg weekly) for heartworm treatment,
doxycycline was administered at a dose of 10 mg/kg per day intermittently for sev-
eral months (e.g., 20 months out of 36 months). To prepare doxycycline IV infusion
solution, add 10 mL to a 100-mg vial or 20 mL to a 200-mg vial and then further
dilute for IV use in 100 to 1000 mL of lactated Ringer’s solution or 5% dextrose.
Infuse over 1 to 2 hours (see “Stability and Storage” section).
Мониторинг пациента и лабораторные исследования
Susceptibility testing: CLSI break points for sensitive organisms are #0.25 mcg/mL for testing isolates from dogs. Breakpoints for cats are not established, but similar values are recommended. Tetracycline can be used as the class representative for sus-ceptibility to doxycycline. Organisms that are susceptible to tetracycline are also con-sidered susceptible to doxycycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline or minocycline or both.
Стабильность и условия хранения
- Doxycycline is available in a 10-mg/mL oral suspension, 50-, 75-, 100-, and150-mg tablets, and 50- and 100-mg capsules (doxycycline hyclate).
- Doxycycline lease formulation (Oracea) contains 10-mg delayed release and 30-mg immediate
release in one capsule.
- Doxycycline hyclate injection is available in a 100- and
200-mg injection vial.
Дозы для животных
Store in a tightly sealed container, protected from light, and at room temperature.
Avoid mixing with cations such as iron, calcium, aluminum, and zinc. However,
doxycycline tablets have been mixed with milk and immediately administered to chil-
dren without loss of potency. Doxycycline hyclate for injection will retain potency for
12 hours at room temperature or 72 hours refrigerated after reconstitution at con-
centrations up to 1 mg/mL. IV solutions are stable in lactated Ringer’s solution or
5% dextrose for 6 hours at room temperature. Protect IV solutions from light. If
frozen after reconstitution with sterile water, solutions of 10 mg/mL are potent for
8 weeks. Doxycycline calcium or doxycycline monohydrate commercial suspension
for people is stable for two weeks at room temperature, if stored in light-resistant
container after reconstitution with water. Doxycycline tablets may be crushed and
mixed with food, drinks (milk or pudding), and are stable for 24 hours at room tem-
perature. If doxycycline is prepared in a compounded formulation, it may be unsta-
ble. Doxycycline hyclate formulated in Ora Plus and Ora Sweet as a suspension re-
tained potency for only 14 days. Other suspensions prepared for animals also may be
unstable. Observe for dark color change (dark brown) as evidence of loss of potency.
When doxycycline hyclate and doxycycline monohydrate was compounded in an oil-
based suspension, it was stable for 180 days. However the suspension precipitates in
the container and vigorous mixing is suggested prior to administration.
Dogs and Cats
• 5 mg/kg q12h PO or IV. 10 mg/kg q24h PO.
• Rickettsia (dogs): 5 mg/kg q12h.
• Ehrlichia (dogs): 5 mg/kg q12h for at least 14 days.
• Hemoplasmosis (cats): 10 mg/kg, PO, once daily for 7 days.
• Heartworm treatment (dogs): 10 mg/kg q12h, PO, administered for 28 days prior
to adulticide treatment. It may be administered in combination with ivermectin.
• Mix four 100-mg doxycycline hyclate capsules with 1 L water (400 mg/L). Shake
to make solution and offer as only source of water to birds to eliminate bacteria.
Alternatively, 25 mg/kg PO q12h for 3 weeks.
Large Animal Dosage
• Dose: 10-20 mg/kg q12h PO. For Lawsonia intracellularis: 20 mg/kg PO q24h
for 3 weeks.
Horses: 10-20 mg/kg q12h PO. The higher dose of 20 mg/kg is recommended
for most bacterial infections. For Lawsonia intracellularis: 20 mg/kg PO, q24h,
for 3 weeks.
• Horses: Do not administer IV.