Tetracycline

Aka: Tetracycline, Doxycycline, Minocycline, Minocin, Vibramycin, Monodox, Doryx, Nuzyra, Omadacycline, Minocycline-Induced Hyperpigmentation

1. Indications
   1. Skin disorders
      1. Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infections
      2. Acne Vulgaris
      3. Acne Rosacea
   2. Gastrointestinal disorders
      1. Helicobacter Pylori (part of quadruple therapy protocol)
   3. Tick-borne illness
      1. Lyme Disease
      2. Human Granulocytic Anaplasmosis (Human Granulocytic Ehrlichiosis)
      3. Rocky Mountain Spotted Fever
   4. Miscellaneous disorders
      1. Community Acquired Pneumonia
      2. Malaria Prophylaxis
   5. Sexually Transmitted Disease
      1. Chlamydia trachomatis
      2. Lymphogranuloma venereum
2. Contraindications
   1. Pregnancy
      1. Pregnancy category D
   2. Children under age 8 years old
      1. AAP now approves Doxycycline for ANY age up to 21 day duration
      2. Unlike Tetracycline, Doxycycline is unlikely to cause visible tooth staining
      3. For severe infections (e.g. Lyme Disease, Rocky Mountain Spotted Fever), Doxycycline is a first-line agent
3. Mechanism
   1. Tetracyclines are protein synthesis inhibitors, binding the 30S ribosomal subunit of susceptible Bacteria
4. Preparations
   1. Tetracycline
      1. Acne Vulgaris: 1 gram daily given in 2-4 divided doses
   2. Minocycline (Minocin)
      1. Acne Vulgaris: 50-200 mg/d in divided doses
   3. Nuzyra (Omadacycline)
      1. Load: 200 mg IV for one dose (or divided 100 mg IV every 12 hours for 2 doses)
      2. Maintenance: 100 mg IV once daily (or 300 mg orally once daily)
      3. Once daily agent indicated for Community Acquired Pneumonia and Skin Infections
      4. Released in 2018 at $400 per pill, and likely less effective than standard agents for CAP
      5. (2019) presc lett 26(1):4
   4. Doxycycline
      1. Typical dose: 100 mg orally twice daily
      2. Low doses, such as 50 mg daily, are often as effective for acne
      3. Avoid substituting low-dose Doxycycline (Periostat, Oracea) products for systemic infections
      4. May substitute other Doxycycline salts
         1. Doxycycline hyclate (Vibramycin, Doryx)
         2. Doxycycline monohydrate (Monodox)
         3. (2013) Presc Lett 20(5):26
      5. Other formulations
         1. Doxycyline Hyclate Delayed-Release (Doryx MPC)
            1. Expensive ($10/pill) formulated to by-pass the esophagus for less side effects
            2. Alternatively, take the doxycyline with 8 oz water and food
            3. (2016) Presc Lett 23(11)
5. Drug Interactions: Food Related
   1. Tetracycline
      1. Milk and calcium-rich food decrease absorption
      2. Take 1 hour before or 2 hours after a meal
   2. Doxycycline and Minocycline
      1. Can be taken with milk or food (unlike Tetracycline)
6. Precautions
   1. Use Sunscreen with these agents due to Drug-induced Photosensitivity
   2. Pill Esophagitis
      1. Take with a full glass of water
7. Adverse Effects
   1. Tetracycline
      1. Photosensitivity
      2. Interferes with OCP action
   2. Doxycycline
      1. Photosensitivity
      2. Abdominal Pain
      3. Diarrhea
      4. Pill Esophagitis (see above)
   3. Minocycline
      1. Generally well tolerated
      2. Does not generally cause photosensitivity
      3. Minocycline-Induced Hyperpigmentation
         1. Blue-gray or muddy brown Hyperpigmentation resulting from Minocycline-iron complex skin deposition
         2. Distribution: Face, arms, legs (esp. shins)
         3. Highest risk in long-term dosing for chronic infection or Rheumatoid Arthritis (risk increases with longer duration)
         4. Uncommon with low dose Acne Vulgaris use
         5. Hyperpigmentation often persists even after Minocycline is discontinued (limited therapies, e.g. laser)
         6. Jain (2019) Am Fam Physician 100(4): 239-240 [PubMed]
      4. Rare adverse effects
         1. Lupus-Like Syndrome (1:20,000)
         2. Vertigo
         3. Oral Mucosa pigmentation (blue-black pigmentation)
         4. Hypersensitivity Syndrome within 1-3 months
         5. Delayed Arthralgias or Polyarthritis
   4. Omadacycline (Nuzyra)
      1. Nausea and Vomiting are most common (>10% of patients)
8. References
   1. (2019) Tarascon Pharmacopeia, accessed 3/31/2019
   2. LoVecchio (2019) Crit Dec Emerg Med 33(3): 28