Drug Therapies for Sexually Transmitted Diseases

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Drug Therapies for Sexually Transmitted Diseases

• Daniel P. Healy, PharmD, FCCP, FIDSA
• Associate Professor
• University of Cincinnati College of Pharmacy

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Sources of Drug Information

• 2006 CDC STD Treatment Guidelines
• MMWR 200655(RR-11)1-94
• Clin Infect Dis 200744 (suppl 3) S1-S174
• http//www.cdc.gov
• Am Fam Physician 2007761827-32.
• Medical Letter Sept. 20075(61)81-88
• Mandells Principles and Practice of Infectious
  Diseases, 6th ed, 2005, Elsevier Inc.
• Primary Literature

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Treatment Guidelines

• Evidenced-based hierarchy
• Many important questions lack evidenced-based
  answers
• ADRs and Allergies
• Historical data chemistry, related drugs/classes
• Anecdotal reporting
• Limited comparative trials
• Many patients excluded from studies
• Minimum effective duration
• Safety in pregnancy

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Factors to Consider When Selecting Antimicrobials
for Treatment of STDs

• Population Demographics- age, sexual practices
• Evidence of infection- clinical, serological
• Organism susceptibility (in vitro activity),
  local resistance patterns
• Host Status age, allergies, renal/hepatic,
  concomitant drugs, diseases (HIV), host defenses,
  pregnancy, site of infection
• Mechanism of action cidal vs static
• PK/PD factors- dosing
• Drug of choice, alternatives- medical malpractice
• Duration of therapy
• Combination therapy needed?
• Adverse effects, drug interactions
• Monitoring
• Impact of Advertising, Direct-to-Consumer
  Marketing and CE
• Whos paying?

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Mechanisms of Action
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Selected Mechanisms of Resistance
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Pharmacokinetics L A D M E

• Liberation from Dose Form
• Erythromycin Dose Forms
• Depot IM Dosage Forms
• Absorption Into Blood/Tissue
• Extended Release Dose Forms
• Topicals Intact Skin?
• Distribution Delivery to Site of Infection
• Serum vs tissue protein binding, membrane
  penetration
• Caution CNS Disease, Joint Spaces
• Metabolism Primarily Liver
• Potential for Drug-Drug and Drug Disease
  Interactions
• Elimination from Body Primarily Liver/Kidney
• Effects of probenecid

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Pharmacodynamic Properties of Antimicrobials Used
for Treating STDs

• Concentration-dependent killing
• Fluoroquinolones, Aminoglycosides, metronidazole
• Correlation with outcome high peakMIC ratio and
  AUCMIC ratio
• Time-dependent killing (concentration-independent)
  
• ? lactams, macrolides, tetracyclines, azoles,
  vancomycin
• Correlation with outcome Time above the MIC
• Impact dosing considerations

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Antimicrobial Pharmacodynamics
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Adverse Reactions

• Gastrointestinal (n,v,d, altered/metallic taste)
• Tetracyclines, Macrolides, Clindamycin
  Metronidazole
• Hypersensitivity (including anaphylaxis)
• All, but especially ?-lactams, sulfonamides
• PCN- ?-lactam cross reactivity
• Jarisch-Herxheimer
• Endotoxin/treponeme release - NOT a Penicillin
  Effect
• Procaine Reactions- neurologic (bizarre
  sensations)
• Photosensitivity- tetracyclines, quinolones
• Mutagenicity- metronidazole
• Achilles tendon rupture-quinolones
• QT prolongation- macrolides, quinolones with
  antiarrhythmics

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Antibacterial Products

• Penicillins
• Cephalosporins
• Macrolides, Clindamycin
• Tetracyclines
• Sulfonamides
• Fluoroquinolones

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Penicillins

• Penicillin G Salts
• Aqueous Penicillin G Short Acting
• Procaine Penicillin G
• Benzathine Penicillin G
• Aminopenicillins
• Ampicillin
• Amoxicillin
• Enzyme Inhibitors
• Clavulanic Acid Amoxicillin
• Sulbactam Ampicillin ( Inj. only )

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Cephalosporins

• Cefoxitin - Mefoxin
• Cefotaxime - Claforan
• Ceftriaxone - Rocephin
• Ceftizoxime Cefizox
• Cefuroxime axetil - Ceftin
• Cefixime - Suprax
• Cefpodoxime proxetil - Vantin
• Cefprozil - Cefzil

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Tetracyclines

• Tetracycline
• Doxycycline - Vibramycin
• Minocycline - Minocin

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Sulfonamides

• Sulfisoxazole
• Trimethoprim/sulfamethoxazole - Bactrim / Septra

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Macrolides

• Erythromycins
• Erythromycin Base
• Erythromycin stearate
• Erythromycin ethylsuccinate
• Clarithromycin- Biaxin
• Azithromycin- Zithromax

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Fluoroquinolones

• Norfloxacin - Noroxin
• Ciprofloxacin - Cipro
• Ofloxacin - Floxin
• Levofloxacin Levaquin
• Moxifloxacin Avelox
• Gemifloxacin - Factive

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Spectinomycin

• Spectinomycin Trobicin
• Check with CDC for availability

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Anti-Herpes Virus Agents

• Acyclovir - Zovirax
• Famciclovir (penciclovir) - Famvir
• Valacyclovir (acyclovir) - Valtrex

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Anti-Louse

• Lindane Lotion, Shampoo - Rx
• Permethrin - Elimite, Acticin Rx/OTC
• Crotamiton Eurax Cream/Lotion - Rx
• Malathion Ovide Lotion Rx
• OTC pyrethrin combinations
• Tisit, Klout, A-200, Pronto, RID

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Summary of New CDC Recommendations (2006
Guidelines)

• Azithromycin (Zithromax) now 1st line for
  Chlamydia during pregnancy
• Quinolones no longer recommended for gonorrhea
• Provision of expedited partner treatment (EPT)
  for gonorrhea or chlamydia
• Tinidazole (Tindamax) for trichomoniasis

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Treatment of Chlamydia

• Men and Nonpregnant women
• Recommended
• Azithromycin (Zithromax) 1 gram PO once
• Doxycycline (Vibramycin) 100 mg PO BID x 7d
• Alternative
• Erythromycin base 500 mg PO QID x 7 days
• EES 800 mg PO QID x 7d
• Levofloxacin (Levaquin) 500 mg PO daily x 7d
• Rescreening or late retesting to detect
  reinfection for all adults at 3 months after
  treatment

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Treatment of Chlamydia

• Pregnant women- avoid quinolones, TCNs
• Recommended
• Azithromycin (Zithromax) 1 gram PO once
• Amoxicillin 500 mg PO TID x 7 days
• Alternative
• Erythromycin base 500 mg PO QID x 7 days or 250
  mg PO QID x 14 days (if GI intolerance)
• EES 800 mg PO QID x 7d or 400 mg QID x 14d (if GI
  intolerance)
• NOTE estolate form is contraindicated in
  pregnancy
• Treatment failure more common in pregnancy- early
  repeat testing recommended (3-4 weeks)

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Treatment of Chlamydia Causing Neonatal
Ophthalmia or Pneumonia

• Recommended
• Azithromycin 20 mg/kg PO once/day x 3 days
• Alternative
• Erythromycin 12.5 mg/kg PO QID x 14 days
• NOTE pyloric stenosis has been associated with
  use of erythromycin in newborns
• Note topical therapy of ophthalmic infections
  associated with treatment failure

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Lymphogranuloma Venereum (LGV)

• C. trachomatis serovars L1, L2, L3
• Usual self-limiting genital ulcer,
  inguinal/femoral adenopathy
• MSM acute proctitis, rectal ulceration, purulent
  anal d/c, fever, tenesmus, lower abdominal pain
• Presumptive Treatment
• Recommended Doxycycline 100mg PO BID x 21 days
• Alternate Erythromycin base 500 mg QID x 21 days

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Nongonococcal Nonchlamydial Urethritis (NGU) and
Cervicitis

• Mycoplasma genitalium (10-20), Ureaplasma
  urealyticum, Trichomonas vaginalis, HSV, others
• Recommended Treatments
• Azithromycin 1 gram x 1 dose
• Doxycycline 100mg PO BID x 7 days
• Persistent or Recurrent NGU
• Treat with azithromycin if doxycycline was used
  initially
• Some will add Metronidazole 2 g or Tinidazole 1 g
  PO x 1
• Alternatives
• Emycin base 500 mg or EES 800 mg PO QID x 7 days
• Levofloxacin 500 mg PO daily x 7 days

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Update on Resistant Gonorrhea

• Gonococcal Isolate Surveillance Project (GISP)
• Mid-1970s PPNG
• Mid-1980s CMRNG PPNG gt5 switch to Ceftriaxone
• 2002 CDC not to use quinolones in CA and HI
  0.9 QRNG in heterosexual men
• 2005 QRNG 29 MSM, 3.8 heterosexual men
• 2006 QRNG 38 , 6.7
• CDC has issued revised warnings No longer
  recommends the use of quinolones for NG
• See CDC website for updated information

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Treatment of Uncomplicated Gonococcal Infections

• Cervical, urethral, or rectal Infection
• First Line - Ceftriaxone 125mg IM x 1
• Parenteral Alternatives
• Cefoxitin 2 g IM x 1, Ceftizoxime 500 mg IM x 1,
  Cefotaxime 500 mg IM x 1, Cefotetan 1 g IM x 1
• Spectinomycin 2 g IM x 1 (check CDC website for
  availability)
• Oral Alternatives
• Cefixime (Suprax) 400mg PO x 1
• Cefpodoxime proxetil (Vantin) 200 mg PO x 1 (may
  change to 400 mg)
• Cefuroxime axetil (Ceftin) 1 g PO x 1
• Concomitant treatment for Chlamydia if not ruled
  out
• HIV/AIDS- same regimens

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Treatment of Uncomplicated Gonococcal Infections

• Pharyngeal Infection
• More difficult to detect and treat
• First Line - Ceftriaxone 125mg IM x 1
• Parenteral Alternatives
• Cefoxitin 2 g IM x 1, Ceftizoxime 500 mg IM x 1,
  Cefotaxime 500 mg IM x 1, Cefotetan 1 g IM x 1
• Oral Alternatives
• Cefixime (Suprax) 400mg PO x 1
• Cefpodoxime proxetil (Vantin)- less effective vs
  pharyngeal
• Azithromycin 2 g x 1 (limited data)- high GI ADR
  (35)
• Spectinomycin- NOT recommended for pharyngeal

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Treatment of Gonorrhea in Pregnancy

• First Line - Ceftriaxone 125mg IM x 1
• Alternatives
• Single-dose Cephalosporins
• Cefoxitin 2 g IM x 1, Ceftizoxime 500 mg IM x 1,
  Cefotaxime 500 mg IM x 1, Cefotetan 1 g IM x 1
• Spectinomycin- 2 mg IM x 1 (if available)
• Azithromycin 2 g (ADRs)
• Desensitize

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Disseminated Gonococcal Infections

• Ceftriaxone 1 g q24h
• Cefotaxime 1 g q8h IV
• Ceftizoxime 1g q8h IV
• Spectinomycin 2 g q12h IM
• PO Switch
• Cefixime 400mg PO BID

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Precautions with Ceftriaxone

• New Bolded Warning
• Calcium-ceftriaxone precipitates have formed in
  the lungs and kidneys of infants (fatal in some).
  As a result, calcium-containing solutions must
  not be mixed with, given at the same time as, or
  for up to 48 hours after ceftriaxone
  administration.
• Mainly an issue with hospitalized
  neonates/infants

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Pelvic Inflammatory Disease (PID)

• Polymicrobial mixed infection C. trachomatis, N.
  gonorrhoeae in 2/3 of cases with others (M.
  genitalium, M. hominis, anaerobes)
• Principles broad initial therapy followed by
  oral to complete approx 14 days
• Recommended Regimen A
• Cefoxitin 2 g iv Q6h or Cefotetan 2g iv Q12h
• Plus
• Doxycycline 100mg IV or PO Q12h
• Recommended Regimen B
• Clindamycin 900mg iv q8h
• plus
• Gentamicin 2 mg/kg LD, then 1.5 mg/kg q8h or ODA
  (5-7 mg/kg IV q24)- adjusted for renal function

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Pelvic Inflammatory Disease Alternative
Parenteral Regimens

• Levofloxcin 500mg IV daily Plus Metronidazole
  500mg IV Q8h
• Ofloxacin 400mg IV Q12h plus Metronidazole
  500mg IV Q8h
• Ampicillin/Sulbactam 3g IV Q6h plus Doxycycline
  100mg IV/PO Q12h
• Should not be used unless QRNG can be excluded

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Pelvic Inflammatory Disease Recommended Oral
Therapy

• Regimen A Outpatient
• Levofloxacin (500mg QD) or Ofloxacin (400 mg BID)
  with or without Metronidazole (500 mg BID) x 14
  Days
• Must rule out QRNG
• Regimen B Outpatient (more common as QRNG ?)
• Cephalosporin (e.g, Ceftriaxone 250 mg IM x 1 or
  others) plus Doxycycline (100mg BID) with or
  without Metronidazole (500mg BID) x 14 days

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Bacterial Vaginosis

• Metronidazole 500mg po BID x 7 d
• Gone - Metronidazole 2 g x 1 PO
• Tinidazole 2 g po QD x 2 d
• Metronidazole Gel QD x 5 d
• Gone - Metronidazole Gel BID x 5 days
• Clindamycin Vag Cream 2 QD x 7 d
• Alternative
• Tinidazole 1 g po QD x 5 d
• Metronidazole ER 750 mg po QD x 7 d
• Clindamycin 300mg po BID x 7 d
• Clindamycin Ovules 100mg Vag hs x 3 d

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Bacterial Vaginosis - Pregnancy

• Metronidazole 500mg BID x 7 days PO
• Metronidazole 250mg TID x 7 days PO
• Clindamycin 300mg BID x 7 days
• In pregnancy, topical preparations have not been
  effective in preventing premature delivery oral
  metronidazole has been effective in some studies
• Metronidazole now considered safe in all stages
  of pregnancy

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Trichomoniasis

• Metronidazole 2g PO x 1
• Tinidazole (Tindamax) 2g PO x 1 Alternative
  Regimen
• Metronidazole 500mg PO BID x 7 days
• Avoid alcohol for 24 hr after completion of
  metronidazole and for 72 hr after tinidazole
• Intravaginal tx with metro-gel not effective
• More data needed on optimal treatment during
  pregnancy

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Syphilis

• Primary, Secondary, Early Latent
• Benzathine Penicillin G 2.4 MU IM once
• Allergy-Doxycycline 100mg BID x 14 days
• Allergy and Pregnant Desensitize
• Allergy- limited data on use of ceftriaxone,
  azithromycin
• Late Latent, Unknown Duration, Tertiary
• Benzathine Penicillin G 2.4 MU IM qwk x 3
• Allergy- Doxycycline 100 mg po BID x 4 weeks
• Allergy Pregnant- desensitize

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Syphilis

• Neurosyphilis- no oral therapy
• Aqueous Penicillin G 18-24 MU daily for 10-14
  days (Not 12 days)
• Procaine Penicillin G 2.4 MU IM daily with
  probenecid 500mg PO QID for 10-14 days
• Allergy
• Ceftriaxone 2 g IV daily for 10-14 days
• Congenital
• Aq PCN G (50,000 U/kg IV q8-12h) or Procaine PCN
  G (50,000 U/kg Im QD) x 10-14 days

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Genital Herpes Simplex Virus (HSV)

• First Episode of Genital Herpes
• Acyclovir 400mg TID for 7-10 days
• Acyclovir 200mg 5 x day for 7-10 days
• Famciclovir 250mg TID for 7-10 days
• Valacyclovir 1g BID for 7-10 days

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Episodic Therapy for Recurrent HSV

• Recurrent Episodes
• Acyclovir 400 mg TID for 5 days
• Acyclovir 800 mg BID x 5 days
• New - Acyclovir 800 mg TID x 2 days
• Gone - Acyclovir 200 mg 5 x day for 5 days
• Famciclovir 125 mg BID for 5 days
• New - Famciclovir 1000 mg BID for 1 day
• Valacyclovir 500 mg BID for 3 days (not 3-5)
• Valacyclovir 1 g QD for 5 days (not 3-5 )

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Suppressive therapy for HSV

• Daily Suppressive Therapy
• Acyclovir 400mg BID
• Famciclovir 250mg BID
• Valacyclovir 500mg QD
• Valacyclovir 1g QD
• may be less effective in gt10 recurrence/yr
• Suppressive therapy with Val shown to reduce
  frequency of HSV transmission

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Genital Warts Human Papillomavirus (HPV)
Infection

• Patient Applied
• Podofilox 0.5 solution or gel BID x 3 d, 4 days
  off, then repeat up to 4 times- not in pregnancy
• Imiquimod Aldara Cream 5 - 3x/week x 16 weeks-
  not in pregnancy
• Provider Applied
• Cryotherapy with liquid nitrogen
• Trichloroacetic Acid
• Electrocautery or Electrodesiccation
• Laser
• Intralesional Interferon
• Vaccine females 9-26 yrs prevents HPV subtypes
  associated with cancer does NOT treat HPV

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Pediculosis Pubis

• Permethrin 1 Cream Rinse (Nix, others)- wash off
  after 10 min
• Pyrethrins with Piperonyl Butoxide
• Lindane 1 Shampoo- no longer recommended as 1st
  line due to neurotoxicity, aplastic anemia
  alternative (wash off after 4 min)
• Malathion can be used for treatment failure
  associated with resistance

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Scabies

• Permethrin 5 Cream- apply to whole body from
  neck down wash off after 8-14 h
• Lindane Lotion 1- no longer recommended as first
  line (neurotoxicity, aplastic anemia)
• Ivermectin 3 mg PO- not an FDA-approved
  indication 200-250 µg/kg as a single dose or 2
  doses separated by 1-2 weeks
• Others Malathion 0.5 otion, Benzyl benzoate,
  sulfur 6, Crotamiton 10- not FDA-approved

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When Treatment Fails, think

• Non-compliance
• Reinfection
• Drug Failure- resistance
• Drug Interactions
• Dose Form Failure

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Selecting a Product

• Concentration at Site of Infection
• Duration of Activity of Drug
• Tissue Distribution
• Multiple Pathogens
• Adverse reactions, drug interactions
• Pregnancy
• Dollars

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Drug Therapies for Sexually Transmitted Diseases

• For More Information
• Cincinnati STD/HIV
• Prevention Training Center
• 1-800-459-2820

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Drug Therapies for Sexually Transmitted Diseases

• Daniel P. Healy, PharmD, FCCP, FIDSA
• Associate Professor
• University of Cincinnati College of Pharmacy