doxycycline (Vibramycin, Monodox, Acticlate, Atridox, Avidoxy, Doxy, Doxycin, Doryx, Oracea, Periostat, Adoxa, Ocudox, Doryx MPC)

Dosing and uses of Vibramycin, Monodox (doxycycline)

• Adult
• Pediatric

 

Adult dosage forms and strengths

capsule

• 50mg (Monodox, generic)
• 75mg (Monodox)
• 100mg (Monodox, Vibramycin, generic)
• 150mg (Adoxa)

solution, reconstituted powder for IV

• 100mg (Doxy, generic)

syrup

• 50mg/5mL (Vibramycin)

oral suspension

• 25mg/5mL (Vibramycin, generic)

tablet

• 20mg (generic)
• 50mg (Adoxa, generic)
• 75mg (Acticlate, Adoxa, generic)
• 100mg (Adoxa, generic)
• 150mg (Acticlate, generic)

tablet, delayed-release

• 50mg (Doryx)
• 60mg (Doryx MPC)
• 75mg (generic)
• 100mg (generic)
• 120mg (Doryx MPC)
• 150mg (Doryx, generic)
• 200mg (Doryx)

capsule, delayed-release

• 40mg (Oracea, generic)

periodontal extended-release liquid

• 10%

 

General Dosage

Initial: 200 mg/day divided twice daily PO/IV on first day (IV may be given qDay), THEn

Maintenance: 100-200 mg/day qDay or divided q12hr PO/IV (IV may be given qDay)

Doryx MPC

• Mild to moderate infections: 240 mg PO divided q12hr on first day of treatment
• Maintenance: 120 mg PO qDay; in the management of more severe infections (particularly chronic infections of the urinary tract), 120 mg q12hr recommended

 

Specific Bacterial Infections

Typical dosage and frequency: 100 PO q12hr on day 1, then 100 mg PO qDay

Severe infections (particularly chronic infections of the urinary tract): 100 mg q12hr is recommended

Doryx MPC

• 240 mg/day divided twice daily PO on first day; THEN
• Maintenance: 120 mg PO qDay; for more severe infections administer BID (particularly chronic UTI)

Bartonella bacilliformis

• Bacillary angiomatosis, peliosis hepatitis, bacteremia, or osteomyelitis: 100 mg PO q12hr
• CNS infections: 100 mg q12 hr PO/IV with or without rifampin 300 mg PO/IV q12hr
• Equivalent dose of Doryx MPC: 120 mg PO BID

Brucellosis

• Brucellosis due to Brucella species
• 100 mg PO twice daily for 6 weeks with rifampin or streptomycin
• Equivalent dose of Doryx MPC: 120 mg PO BID

Cholera

• Indicated for cholera caused by Vibrio cholerae
• 300 mg PO once; adjunct to fluid and electrolyte replacement
• Equivalent dose of Doryx MPC is 360 mg PO

Other infections include

• Relapsing fever due to Borrelia recurrentis
• Plague due to Yersinia pestis
• Tularemia due to Francisella tularensis
• Campylobacter fetus infections caused by Campylobacter fetus

Gram-negative bacteria

• Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended
• Escherichia coli
• Enterobacter aerogenes
• Shigella species
• Acinetobacter species
• Urinary tract infections caused by Klebsiella species

 

Infections when Penicillin is Contraindicated

When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections:

-Syphilis caused by Treponema pallidum

-Yaws caused by Treponema pallidum subspecies pertenue

-Listeriosis due to Listeria monocytogenes

-Vincent’s infection caused by Fusobacterium fusiforme

-Actinomycosis caused by Actinomyces israelii

-Infections caused by Clostridium species

 

Acute Bacteria Rhinosinusitis

200 mg/day PO qDay or divided BID for 5-7 days

 

Respiratory Tract Infections

100 PO q12hr on day 1, then 100 mg PO qDay

Doryx MPC: 120 mg PO q12hr on day 1, then 120 mg PO qDay

Respiratory infections

• Respiratory tract infections caused by Mycoplasma pneumoniae
• Psittacosis (ornithosis) caused by Chlamydophila psittaci
• Indicated for the following microorganisms, when bacteriological testing indicates appropriate susceptibility to doxycycline:
• -RTIs caused by Haemophilus influenzae
• -RTIs caused by Klebsiella species
• -Upper RTIs caused by Streptococcus pneumoniae

 

Sexually Transmitted Diseases

CDC STD guidelines: MMWR Recomm Rep. June 5, 2015:64(RR3);1-137

Uncomplicated gonococcal infection of the cervix, urethra, and rectum: Ceftriaxone 250 mg IM once plus azithromycin 1 g PO once (preferred) or alternatively doxycycline 100 mg PO q12hr for 7 days

Uncomplicated urethral, endocervical, or rectal infection caused by Chlamydia trachomatis: 100 mg PO BID x 7 days

Nongonococcal urethritis caused by C. trachomatis and U. urealyticum: 100 mg PO BID x 7 days

Syphilis (early): Patients who are allergic to penicillin should be treated with doxycycline 100 mg PO BID x 2 weeks

Syphilis >1 year duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg PO BID x 4 weeks

Acute epididymo-orchitis caused by N. gonorrhoeae or C trachomatis: 100 mg PO BID x least 10 days

Equivalent dose of Doryx MPC is 120 mg PO BId

 

Periodontal Disease

100-200 mg PO qDay

Atridox: Apply subgingivally; dose depends on size, shape, and number of pockets treated

 

Rosacea

Oracea: 40 mg PO qAM; on an empty stomach

 

Chlamydia trachomatis

Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated as judged by immunofluorescence; also approved for inclusion conjunctivitis caused by chlamydia trachomatis

100 PO q12hr on day 1, then 100 mg PO qDay

Equivalent dose of Doryx MPC is 120 mg PO q12h on day 1, then 120 mg PO qDay

 

Anthrax

Postexposure prophylaxis: 100 mg PO BID for 60 days

Equivalent dose of Doryx MPC is 120 mg PO BID for 60 days

 

Malaria

Indicated for prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (ie, <4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strain

Prophylaxis: 100 mg PO qDay; begin taking 1-2 days before travel and continue daily during travel and for 4 weeks after traveler leaves malaria infested area

Severe infection (off-label): 100 mg PO/IV q12hr x 7 days with 3-7 days quinidine gluconate

Uncomplicated infection (off-label): 100 mg PO q12hr x 7 days with 3-7 days quinine sulfate depending on region

Equivalent dose of Doryx MPC is 120 mg

 

Intestinal Amebiasis

Indicated for adjunctive therapy to amebicides for acute intestinal amebiasis

100 PO q12hr on day 1, then 100 mg PO qDay

Equivalent dose of Doryx MPC is 120 mg PO q12h on day 1, then 120 mg PO qDay

 

Rickettsial Infections

Indicated for Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, and tick fevers caused by Rickettsiae

100 PO q12hr on day 1, then 100 mg PO qDay

Equivalent dose of Doryx MPC is 120 mg PO q12h on day 1, then 120 mg PO qDay

 

Infective Endocarditis

Suspected Bartonella infection with a negative culture: 100 mg PO BID x 6 weeks in combination with gentamicin and ceftriaxone

Positive culture Bartonella infection: 100 mg PO BID x 6 weeks in combination with gentamicin or rifampin

Equivalent dose of Doryx MPC is 120 mg PO BId

 

Purulent Cellulitis from Community Acquired MRSA (Off-label)

100 mg PO q12hr for 5-10 days

 

Dosing Considerations

Susceptible organisms

• Propionibacterium acnes, Actinomyces israelii, Acinetobacter spp, Bacillus anthracis, Bacteroides spp., Bartonella bacilliformis, Bartonella henselae, Bartonella quintana, Borrelia recurrentis, Brucella spp, Campylobacter jejuni, Chlamydia psittaci, Chlamydia trachomatis, Capnocytophaga canimorsus, Citrobacter diversus, Citrobacter freundii, Escherichia coli, Eikenella corrodens, Francisella tularensis, Haemophilus ducreyi, Helicobacter pylori, Klebsiella granulomatis, Klebsiella pneumoniae, Listeria monocytogenes, Mycoplasma hominis, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Propionibacterium acnes, Rickettsiae, Shigella spp., MRSA, Staphylococcus saprophyticus, Streptococcus spp, Treponema pallidum, Ureaplasma urealyticum, Vibrio cholerae, Yersinia enterocolitica, Yersinia pestis, VRE, mycobacteria other than tuberculosis

 

Pediatric dosage forms and strengths

capsule

• 50mg (Monodox, generic)
• 75mg (Monodox)
• 100mg (Monodox, Vibramycin, generic)
• 150mg (Adoxa)

solution, reconstituted powder for IV

• 100mg (Doxy, generic)

syrup

• 50mg/5mL (Vibramycin)

oral suspension

• 25mg/5mL (Vibramycin, generic)

tablet

• 20mg (generic)
• 50mg (Adoxa, generic)
• 75mg (Acticlate, Adoxa, generic)
• 100mg (Adoxa, generic)
• 150mg (Acticlate, generic)

tablet, delayed-release

• 50mg (Doryx)
• 60mg (Doryx MPC)
• 75mg (generic)
• 100mg (generic)
• 120mg (Doryx MPC)
• 150mg (Doryx, generic)
• 200mg (Doryx)

capsule, delayed-release

• 40mg (Oracea, generic)

 

General Dosing Guidelines

≤8 years: Not recommended for midle-to-moderate infections; may cause tooth discoloration and enamel hypoplasia during tooth development

>8 years, <45 Kg

• Load: 4.4 mg/kg/day PO/IV divided q12hr day 1
• Maintenance: 2.2-4.4 mg/kg/day IV/PO qDay (may divide BID for higher doses)
• Doryx MPC
  • Severe or life-threatening infections (eg, anthrax, Rocky Mountain spotted fever): 2.6 mg/kg PO BID
  • Less severe infections: 5.3 mg/kg PO divided into 2 doses on day 1, then a maintenance dose of 2.6 mg/kg PO qDay

>8 years, ≤45 kg

• 100 mg PO q12hr or 50 mg PO q6hr on day 1, followed by maintenance dose of 100 mg/day as single dose or as 50 mg q12hr
• Doryx MPC: Doryx MPC: 120 mg PO q12h on day 1, followed by maintenance dose of 120 mg/day; may increase frequency to q12hr for more severe infections, particularly chronic UTI

 

Anthrax

Postexposure prophylaxis

≤8 years: 2.2 mg/kg PO/IV q12hr for 60 days (change to amoxicillin as soon as penicillin susceptibility confirmed)

>8 years (≤45kg): 2.2 mg/kg PO/IV q12hr for 60 days (Doryx MPC: 2.6 mg/kg PO q12hr for 60 days)

>8 years (>45kg): 100 mg PO/IV q12hr for 60 days (Doryx MPC: 120 mg PO q12hr for 60 days)

 

Malaria

>8 years

Prophylaxis

• 2 mg/kg PO qDay; not to exceed 100 mg /day
• Doryx MPC: 2.4 mg/kg PO qDay
• Initiate treatment 1-2 days prior to travel to endemic area and continue for 4 weeks after leaving the area

Severe infection

• <45 kg: 2.2 mg/kg q12hr for 7 days with quinidine gluconate
• ≥45 kg (Off label): 100 mg PO/IV q12hr for 7 days with quinidine gluconate

Uncomplicated

• >8 years: 2.2 mg/kg; not to exceed 100 mg dose PO q12hr for 7 days with quinine sulfate

 

Tularemia

<45 kg: 2.2 mg/kg PO twice daily for 14-21 days

≥45 kg: 100 mg PO twice daily for 14-21 days

 

Cholera

Single dose: 7 mg/kg PO/IV; not to exceed 300 mg/dose; adjunct to fluid and electrolyte replacement

Multiple dose: 2 mg/kg PO/IV twice daily on day 1; THEN, 2 mg/kg qDay on days 2 and 3; not to exceed 100 mg/dose; adjunct to fluid and electrolyte replacement

 

Vibramycin, Monodox (doxycycline) adverse (side) effects

Frequency not defined

Anorexia

Dental discoloration

Diarrhea

Dysphagia

Enterocolitis

Erythema multiform

Esophageal ulcer

Esophagitis

Exacerbation of systemic lupus erythematosus

Exfoliative dermatitis

Glossitis

Headache

Hemolytic anemia

Hepatotoxicity

Hypoglycemia

Inflammatory anogenital lesion

Intracranial hypertension

Neutropenia

Pericarditis

Serum sickness

Skin hyperpigmentation

Toxic epidermal necrolysis

Thrombocytopenia

Upper abdominal pain

Urticaria

Drug rash with eosinophilia and systemic symptoms

 

Warnings

Contraindications

Documented hypersensitivity

 

Cautions

Not drug of choice for any staphylococcal infection

Risk of thrombophlebitis when given IV

History of candidiasis overgrowth

Hepatotoxicity may occur; if symptoms occur, measure LFTs and discontinue drug

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment

May increase BUN due to its anti-anabolic effects; use caution in patients with renal impairment

Consider drug serum level determinations in prolonged therapy

Tetracycline use during tooth development (last half of pregnancy through age 8 years) can cause permanent discoloration of teeth; use doxycycline in pediatric patients 8 years of age or less only when potential benefits expected to outweigh risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever); particularly when there are no alternative therapies

Fanconi-like syndrome may occur with outdated tetracyclines

Intracranial hypertension (pseudotumor cerebri) reported (rare) may occur; symptoms include headache, blurred vision, diplopia, and vision loss; papilledema can be found on funduscopy; women of childbearing age who are overweight or have a history of IH are at greater risk; possibility for permanent visual loss exists; if visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted; intracranial pressure can remain elevated for weeks after drug cessation; monitor patients until they stabilize

Doxycycline offers substantial but not complete suppression of asexual blood stages of Plasmodium strains; doxycycline does not suppress P. falciparum’s sexual blood stage gametocytes; subjects completing prophylactic regimen may still transmit infection to mosquitoes outside endemic areas

Prolonged use may result in superinfection

Overgrowth of non-susceptible organisms, including fungi, may occur; if such infections occur, discontinue use and institute appropriate therapy

May induce hyperpigmentation in many organs including skin, eyes, nails, thyroid and bone

If Clostridium difficile associated diarrhea suspected or confirmed, may need to discontinue ongoing antibacterial use not directed against C. difficile; may also need to institute appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation as clinically indicated

Use in pediatric patients 8 years of age or less only when potential benefits are expected to outweigh risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies

 

Pregnancy and lactation

Pregnancy category: d

Lactation: Enters breast milk; Not recommended

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Vibramycin, Monodox (doxycycline)

Mechanism of action

Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria; may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

 

Absorption

Oral: Almost complete; reduced 20% by food or milk

Peak serum time: 1.5-4 hr

Bioavailability: Reduced at high pH

 

Distribution

Protein bound: 90%

 

Metabolism

Liver

 

Elimination

Half-life: 15-25 hr

Excretion: Urine (23%); feces (30%)

 

Administration

 

Administration

Oral Administration

Absorption decreased when taken with food, particularly food containing calcium

Doryx MPC, delayed-release tablet

• Do not substitute on a mg-per-mg basis with other oral doxycyclines because of differing bioavailability
• Do not chew or crush tablets
• The recommended dosage, frequency of administration, and weight-based dosage recommendations differ from that of other doxycyclines; exceed the recommended dose may increase incidence of adverse effects
• Administer with adequate amount of fluid to was down the drug and reduce risk of esophageal irritation/ulceration
• Switching from Doryx to Doryx MPC
  • Doryx MPC 60 mg replaces Doryx 50 mg
  • Doryx MPC 120 mg replaces Doryx 100 mg

 

IV Incompatibilities

Additive: Meropenem (comp at 1 g/L mero and 200 mg/L doxy; incomp at 20 g/L and 200 mg/L doxy)

Y-site: Allopurinol, heparin, piperacillin/tazobactam

 

IV Compatibilities

Solution: D5W, Ns

Additive: Ranitidine

Syringe: Doxapram

Y-site (partial list): Acyclovir, amiodarone, aztreonam, hydromorphone, linezolid, MgSO4, meperidine, meropenem (comp at 1 mg/mL mero and 1 mg/mL doxy; incomp at 50 mg/mL mero and 1 mg/mL doxy), morphine SO4, propofol, remifentaniL

 

IV Preparation

For IV infusion dilute to a final concentration of 0.1-1 mg/mL w/ NS, D5W, LR, or D5/Lr

 

IV Administration

Administer by slow IV infusion, usually over 1-2 hr

Use central line if possible

Avoid rapid administration

Other parenteral routes not recommended