doxycycline

dox-i-SYE-kleen

Therapeutic Classification: anti-infectives

Pharmacologic Classification: tetracyclines

REMS

Treatment of various infections caused by unusual organisms, including:
- Mycoplasma,
- Chlamydia,
- Rickettsia,
- Borellia burgdorferi.
Treatment of inhalational anthrax (postexposure) and cutaneous anthrax.
Treatment of gonorrhea and syphilis in penicillin-allergic patients.
Prevention of exacerbations of chronic bronchitis.
Treatment of acne.
Treatment of inflammatory lesions associated with rosacea (Oracea only).
Malaria prophylaxis.

Inhibits bacterial protein synthesis at the level of the 30S bacterial ribosome.
Low-dose products used in the management of periodontitis inhibit collagenase.

Therapeutic effects:

Bacteriostatic action against susceptible bacteria.

Spectrum:

Includes activity against some gram-positive pathogens:
- Bacillus anthracis (anthrax),
- Clostridium perfringens,
- Clostridium tetani,
- Listeria monocytogenes,
- Nocardia,
- Propionibacterium acnes,
- Actinomyces israelii.
Active against some gram-negative pathogens:
- Haemophilus influenzae,
- Legionella pneumophila,
- Yersinia enterocolitica,
- Yersinia pestis,
- Neisseria gonorrhoeae,
- Neisseria meningitidis.
Also active against several other pathogens, including:
- Mycoplasma,
- Treponema pallidum,
- Chlamydia,
- Rickettsia,
- Borrelia burgdorferi.

Absorption: Well absorbed from the GI tract.

Distribution: Widely distributed, some CSF and good bone penetration.

Metabolism/Excretion: 20–40% excreted unchanged in urine; some inactivation in intestine and some enterohepatic circulation with excretion in bile and feces.

Half-Life: 14–17 hr (↑ in severe renal impairment).

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	1–2 hr	1.5–4 hr	12 hr
IV	rapid	end of infusion	12 hr

Contraindicated in:

Hypersensitivity;
Some products contain alcohol or bisulfites and should be avoided in patients with known hypersensitivity or intolerance;
OB: ↑risk of bone growth inhibition and permanent staining of teeth in infant if used during 2nd or 3rd trimesters; may be used to treat anthrax in pregnant women due to the seriousness of the disease;
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential (↑ risk of intracranial hypertension if overweight or have a previous history of intracranial hypertension);
Pedi: Children <8 yr (may cause permanent staining of teeth) (may be used to treat anthrax or Rocky Mountain spotted fever in children <8 yr due to the seriousness of these diseases).

Derm: photosensitivity, DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, EXFOLIATIVE DERMATITIS, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

GI: diarrhea, nausea, vomiting, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), dysphagia, esophagitis, glossitis, HEPATOTOXICITY, PANCREATITIS

Hemat: blood dyscrasias

Local: phlebitis

Neuro: headache, intracranial hypertension

Misc: hypersensitivity reactions, superinfection

Drug-drug:

May ↑ effect of warfarin.
May ↓ effectiveness of estrogen-containing oral contraceptives.
Antacids, calcium, iron, and magnesium form insoluble compounds (chelates) and ↓ absorption and effectiveness of tetracyclines; this effect is minimal with doxycycline.
Cholestyramine, colestipol, and bismuth subsalicylate may ↓ absorption and effectiveness.
Barbiturates, carbamazepine, or phenytoin may ↓ effectiveness.
Isotretinoin may ↑ risk of intracranial hypertension; avoid concurrent use.

Drug-Food:

Calcium in foods or dairy products may ↓ absorption by forming insoluble compounds (chelates); this effect is minimal with doxycycline.

More Common Infections

PO (Adults and Children >8 yr and >45 kg): Most infections: 100 mg every 12 hr on the 1st day, then 100–200 mg once daily or 50–100 mg every 12 hr. Gonorrhea: 100 mg every 12 hr for 7 days or 200 mg once daily for 7 days (delayed-release tablets) or 300 mg followed 1 hr later by another 300-mg dose. Uncomplicated urethral, endocervical, or rectal infection caused by Chlamydia trachomatis: 100 mg every 12 hr for 7 days. Syphilis (early): 100 mg every 12 hr for 14 days. Syphilis (>1 yr duration): 100 mg every 12 hr for 4 wk. Malaria prophylaxis: 100 mg once daily (2 mg/kg once daily for children >8 yr). Lyme disease: 100 mg twice daily; Periodontitis: 20 mg twice daily; Rosacea: 40 mg once daily in morning.
PO (Children >8 yr and <45 kg): Less severe infections: 2.2 mg/kg every 12 hr on the 1st day, then 2.2–4.4 mg/kg once daily or 1.1–2.2 mg/kg every 12 hr.
PO (Children >45 kg): Severe or life-threatening infections (Rocky Mountain spotted fever): 100 mg every 12 hr.
PO (Children <45 kg): Severe or life-threatening infections (Rocky Mountain spotted fever): 2.2 mg/kg every 12 hr.

Inhalational Anthrax (Postexposure)

PO IV (Adults and Children >45 kg): 100 mg IV every 12 hr; change to 100 mg PO every 12 hr when clinically appropriate for a total of 60 days; one or two other anti-infectives may be added initially, depending on clinical situation.
PO IV (Children ≤45 kg): 2.2 mg/kg IV every 12 hr; change to 2.2 mg/kg PO every 12 hr when clinically appropriate for a total of 60 days; one or two other anti-infectives may be added initially, depending on clinical situation.

Cutaneous Anthrax

PO (Adults ): 100 mg every 12 hr for 60 days; some patients may require IV therapy initially depending on clinical situation.
PO (Children >8 yr and >45 kg): 100 mg every 12 hr; some patients may require IV therapy initially depending on clinical situation.
PO (Children >8 yr and ≤45 kg): 2.2 mg/kg every 12 hr; some patients may require IV therapy initially depending on clinical situation.
PO (Children ≤8 yr): 2.2 mg/kg every 12 hr; some patients may require IV therapy initially depending on clinical situation.

(Generic available)

Immediate-release tablets: 20 mg; 50 mg; 75 mg; 100 mg; 150 mg
Immediate-release capsules: 50 mg; 75 mg; 100 mg; 150 mg
Delayed-release tablets: 50 mg; 60 mg; 75 mg; 100 mg; 150 mg; 200 mg
Delayed-release capsules (Oracea): 40 mg
Oral suspension raspberry flavor: 25 mg/5 mL
Oral syrup raspberry-apple flavor: 50 mg/5 mL
Powder for injection: 100 mg/vial

Infection: Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
- Obtain specimens for culture and sensitivity before starting therapy. First dose may be given before receiving results.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care provider promptly as a sign of CDAD. May begin up to several weeks following cessation of therapy.
Assess for rash periodically during therapy. May cause SJS or TEN. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, or eosinophilia.
IV: Assess IV site frequently; may cause thrombophlebitis.

Lab Test Considerations:

Monitor renal and hepatic function and CBC periodically during long-term therapy.
- May ↑ AST, ALT, serum alkaline phosphatase, bilirubin, and amylase.
- May cause false ↑ in urinary catecholamine levels.

Do not confuse Oracea with Orencia.
- May cause yellow-brown discoloration and softening of teeth and bones if administered prenatally or during early childhood. Not recommended for children <8 yr of age or during pregnancy or lactation, unless used for the treatment of anthrax.
- Oracea is only indicated for rosacea, not for infections.
PO: Administer around the clock, ≥1 hr before or 2 hr after meals. May be taken with food or milk if GI irritation occurs. Administer with 8 ounces (240 mL) of liquid and ≥1 hr before going to bed to avoid esophageal ulceration. Use calibrated measuring device for liquid preparations. Shake liquid preparations well. Do not administer within 1–3 hr of other medications.
- Capsules may also be administered by carefully opening and sprinkling capsule contents on a spoonful of applesauce. The applesauce should be swallowed immediately without chewing and followed with an 8-ounce glass of cool water to ensure complete swallowing of the capsule contents. The applesauce should not be hot, and it should be soft enough to be swallowed without chewing. If mixture cannot be taken immediately, discard; do not store for later use.
- DNC: Do not open, break, crush, or chew extended-release capsules and tablets.
- To prepare doses for infants and children exposed to anthrax (used only in a Declared Public Health Emergency): Place one 100-mg tablet in a small bowl and crush to a fine powder with a metal spoon, leaving no large pieces. Add 4 level teaspoons of low-fat milk, low-fat chocolate milk, regular chocolate milk, chocolate pudding, or an apple juice and sugar mixture made by combining 4 teaspoons of sugar and 4 teaspoons of apple juice. Mix food or drink and doxycycline powder until powder dissolves. Mixture is stable in a covered container for 24 hr if refrigerated (if made with milk or pudding) or at room temperature (if made with juice). Number of teaspoons to administer/dose is based on child's weight (0–12.5 lbs: ½ teaspoon; 12.5–25 lbs: 1 teaspoon; 25–37.5 lbs: 1½ teaspoons; 37.5–50 lbs: 2 teaspoons; 50–62.5 lbs: 2½ teaspoons; 62.5–75 lbs: 3 teaspoons; 75–87.5 lbs: 3½ teaspoons; 87.5–100 lbs: 4 teaspoons).
- Avoid administration of calcium, antacids, magnesium-containing medications, sodium bicarbonate, or iron supplements within 1–3 hr of oral doxycycline.

IV Administration:

IV doxycycline is a vesicant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry warm compresses. Initiate hyaluronidase antidote for refractory cases in addition to supportive management. For hyaluronidase, inject a total of 1 mL (15 units/mL) intradermally or SUBQ as five separate 0.2-mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30–60 min if no resolution.
Intermittent Infusion: Reconstitution: Reconstitute each 100 mg with 10 mL of sterile water or 0.9% NaCl for injection. Diluent: Dilute reconstituted solution further in 100–1000 mL of 0.9% NaCl, D5W, D5/LR, Ringer’s, or lactated Ringer’s solution. Solution is stable for 12 hr at room temperature and 72 hr if refrigerated. If diluted with D5/LR or lactated Ringer’s solution, administer within 6 hr. Protect solution from direct sunlight.Concentration: Concentrations 1 mcg/mL or >1 mg/mL are not recommended.
Rate: Administer over a minimum of 1–4 hr. Avoid rapid administration. Avoid extravasation.
Y-Site Compatibility:
- acyclovir
- alemtuzumab
- amikacin
- aminophylline
- amiodarone
- anidulafungin
- argatroban
- arsenic trioxide
- ascorbic acid
- atracurium
- atropine
- azithromycin
- aztreonam
- benztropine
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium chloride
- calcium gluconate
- cangrelor
- carboplatin
- carmustine
- caspofungin
- cefotaxime
- ceftolozane/tazobactam
- ceftriaxone
- chlorpromazine
- cisatracurium
- cisplatin
- clindamycin
- cyanocobalamin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- edetate disodium
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- epoetin alfa
- eptifibatide
- ertapenem
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- filgrastim
- fluconazole
- fludarabine
- fosphenytoin
- gemcitabine
- gentamicin
- glycopyrrolate
- granisetron
- hydromorphone
- idarubicin
- ifosfamide
- imipenem/cilastatin
- imipenem/cilastatin/relebactam
- insulin, regular
- irinotecan
- isavuconazonium
- isoproterenol
- labetalol
- leucovorin
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- melphalan
- meperidine
- meropenem/vaborbactam
- mesna
- methadone
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- minocycline
- mitoxantrone
- morphine
- multivitamins
- mycophenolate
- nalbuphine
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- oxytocin
- paclitaxel
- pamidronate
- pantoprazole
- papaverine
- pentamidine
- phentolamine
- phenylephrine
- phytonadione
- plazomicin
- potassium chloride
- procainamide
- prochlorperazine
- promethazine
- propofol
- propranolol
- protamine
- pyridoxine
- remifentanil
- rituximab
- rocuronium
- sargramostim
- sodium acetate
- succinylcholine
- sufentanil
- sulbactam/durlobactam
- tacrolimus
- telavancin
- theophylline
- thiamine
- thiotepa
- tirofiban
- tobramycin
- topotecan
- trastuzumab
- vancomycin
- vasopressin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zoledronic acid
Y-Site Incompatibility:
- allopurinol
- aminocaproic acid
- amphotericin B deoxycholate
- amphotericin B liposomal
- ampicillin
- ampicillin/sulbactam
- azathioprine
- cefazolin
- cefiderocol
- cefotetan
- cefoxitin
- ceftazidime
- cefuroxime
- chloramphenicol
- dantrolene
- dexamethasone
- diazepam
- diazoxide
- erythromycin
- fluorouracil
- folic acid
- furosemide
- ganciclovir
- gemtuzumab ozogamicin
- heparin
- hydrocortisone
- indomethacin
- ketorolac
- methotrexate
- methylprednisolone
- mitomycin
- nafcillin
- oxacillin
- palonosetron
- pemetrexed
- penicillin G
- pentobarbital
- phenobarbital
- phenytoin
- piperacillin/tazobactam
- potassium acetate
- sodium bicarbonate
- trimethoprim/sulfamethoxazole
- tedizolid

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take medication around the clock and to finish the drug completely as directed, even if feeling better. Take missed doses as soon as possible unless it is almost time for next dose; do not double doses. Advise patient that sharing of this medication may be dangerous.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
- Advise patient to avoid taking antacids, calcium, magnesium-containing medications, sodium bicarbonate, and iron supplements within 1–3 hr of oral doxycycline.
- Instruct patient to notify health care provider immediately if rash, diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care providers.
- Advise patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
- Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) or intracranial hypertension (headache, blurred vision, diplopia, vision loss). Women who are overweight, are of childbearing age, or have a history of intracranial hypertension are at greater risk for developing doxycycline-associated intracranial hypertension. Skin rash, pruritus, and urticaria should also be reported.
- Instruct patient to notify health care provider of medication regimen before treatment or surgery.
- Caution patient to discard outdated or decomposed doxycycline; they may be toxic.
- Advise women of reproductive potential to use a nonhormonal method of contraception while taking doxycycline and until next menstrual period. Advise patient to notify health care provider promptly if pregnancy is planned or suspected or if breastfeeding. May be used for short term. Consider developmental and health benefits of breastfeeding with the mother’s clinical need for doxycycline and any potential adverse effects on the breastfed child from doxycyline or from the underlying maternal condition.
- Instruct patient to notify health care provider if symptoms do not improve within a few days for systemic preparations.
Malaria Prophylaxis: Advise patient to avoid being bitten by mosquitoes by using protective measures, especially from dusk to dawn (staying in well-screened areas, using mosquito nets, covering the body with clothing, using an effective insect repellent). Doxycycline prophylaxis should begin 1–2 days before travel to the malarious area and continued daily while in the malarious area; after leaving the malarious area, it should be continued for 4 more weeks to avoid development of malaria. Do not exceed 4 mo.

Bacteriostatic action against susceptible bacteria.

Acticlate, Doryx, Doryx MPC, Doxy, Oracea, Targadox, ~~Vibramycin~~

Apprilon, Doxycin, Doxytab, Periostat

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