Drug Safety Information

  • Discard outdated tetracyclines as degradation products may be toxic.
  • Not recommended in pregnancy and in children under 8 years of age as permanent enamel hyperplasia, discoloration of teeth, and inhibition of fetal skeletal growth may occur.
  • Should be taken with water to reduce risk of gastrointestinal and esophageal irritation.

Adverse Effects

    • 13.6% of 700 patients showed side effects.

[BJD 1996; 134:693-95]

    • Vestibular
    • Candida
    • GI
    • Skin
    • Benign Intracranial hypertension
  • Cutaneous effects may include photosensitivity, pigmentation of the skin and mucous membranes, fungal overgrowth and hypertrophy of lingual papillae.
  • Other skin side effects include urticaria, exfoliative dermatitis, Erythema multiforme fixed drug eruption, erythema nodosum, photo-onycholysis, Sweets, ANCA+vasculitis
  • Pigmentation
    • skin, gingival, mouth, sclera, permanent teeth and nails
    • 4% when the dose was 200mg a day and 0.4% when 100mg daily
    • occurred in all after a course of 8 months duration and a cumulative dose of 70grams
    • Localized pigment- in scars and sites of inflammation as well as lower shins. May be more common in rosacea as a result of greater blood flow in flushers
    • Generalized diffuse pigmentation rare under total dose of 50grams and most over 100grams and most had been on the drug for 3 years. Commoner in older individuals especially with photo damage
  • Gastrointestinal effects may include cramping, diarrhea, nausea, vomiting, hepatotoxicity and pancreatitis..
  • Central nervous system effects may include benign intracranial hypertension and CNS toxicity..
  • Other effects may include nephrogenic diabetes insipidus.
  • RARE but potentially SERIOUS adverse effects.

[Rev Med Interne 2003 May: 24(5):305-16]

  • Review of Cyclines and side effects in acne patients in the literature 1997-2001
  • 250 cases of adverse reports
  • 72-autoimmune-DIL,hepatitis, DHS,serum sickness
  • 24 Pseudo tumor cerebri
  • 123 pigmentation problems
  • Drug Hypersensitivity syndrome.
  • Drug induced Lupus.
  • Drug induced Hepatitis

Drug Hypersensitivity Syndrome

  • Tetracycline and Doxycycline does not have the amino acid group that initiates the reaction
  • Fever
  • Skin rash
  • Internal organ involvement
  • Most frequent during the first drug exposure usually in the first 2-6 weeks. It is not dose related
  • Fever 38-40C,malaise ,sore throat with possible neck nodes
  • 85% have an exanthema accompanying the fever
  • LFT elevated and if severe changes in PT and elevated bilirubin
  • Occasional renal, CNS and thyroid involvement
  • Therapy includes stopping the drug and possibly using systemic steroids
  • First degree relatives are at increased risk

Drug Induced Lupus

  • Musculo skeletal symptoms-arthritis of small and large joints
  • Fever
  • Weight loss
  • Pleuropulmonary involvement in over 50%
  • Renal,CNS and vasculitis rare
  • Most have no skin signs- urticaria,erythema, and vasculitis
  • WBC up or down, ESR up, LFT elevated, ANA+ may be up to 1: 1600. antiDNA absent, anti histone in 90% but non specific
  • Only a small % of those developing +ANA will go on to have DIL
  • May occur 1 year after starting on Minocycline. Average time is 2 years
  • Young women at risk
  • AVOID this drug in SLE as well as first degree relatives
  • Stop drug. Resolves in 4-6 weeks. ANA remain + for 6-12 months
  • NSAI and systemic steroids if severe

[Arch Derm 132: 934-939 1996, BMJ 312:169-172 1996, Pediatrics 926-928 1997, J Rheumatol 23;2160-2161 1996]

Drug Induced Hepatitis

  • Usually 3-12 weeks into therapy. More common if large dose used..
  • May occur alone or as part of a more generalized hypersensitivity mimicking an infectious, Mononucleosis like condition.
  • Can be fatal especially if the drug is not d/c.
  • LFT not recommended as routine on all patients. These tests as well as ANA must be done in those with suspicious symptoms

[BMJ 1993;306:555-6 Minocycline induced fulminant hepatitis 2 deaths and 1 liver transplant]

Bacterial Resistance Issues

  • Increasing resistance of P.acnes and Staph epidermidis to the commonly used anti-acne antibiotics
  • Bacterial resistance in different countries correlates with the varying prescribing habits in that more frequent resistance to the most commonly used antibiotic
  • Erythromycin is the commonest drug to be ineffective and frequent cross resistance is seen with clindamycin. Bacterial resistance is beginning to be seen to minocycline although much less common that to the other antibiotics. The problem of resistance increases the longer the duration of therapy. Dermatologists working in acne clinics much more frequently harbor resistant P.acnes on their skin than their colleagues. The use of long term antibiotics in the treatment of acne is becoming outdated
  • Adding topical Benzoyl peroxide to the treatment regimen reduces the frequency of bacterial resistance. Oral isotretinoin has also been seen to do the same.

[BJD 2003 March:148(3) 467-78 ), Med J Aust 1998 Sept 7;169(5):259-61, Ann Acad Med Singapore 2001 Jan;30(1):22-51, BJD 2001 Feb;144(2):339-46, SeminCutanMedSurg2001Sept;20(3):184-9, JEurAcadDermatolVenerol 2001:15suppl3 51-5]

FDA Pregnancy Category D (systemic) and B (topical)

  • Tetracyclines may cause permanent discoloration of the teeth, enamel hypoplasia, and inhibition of fetal skeletal growth. Tetracyclines are distributed into the breast milk and may cause adverse effects in the neonate. Topical tetracyclines have not shown adverse fetal effects in animal studies.

Major Drug Interactions

  • Concurrent therapy with antacids, calcium supplements, iron supplements, or magnesium salicylates, laxatives, colestipol, and cholestyramine may impair the absorption of tetracyclines; oral contraceptives, may be reduced in reliability, and increase breakthrough bleeding may occur; digoxin concentrations may be increased; penicillins may be reduced in efficacy; vitamin A may lead to benign intracranial hypertension; and phenytoin, carbamazepine, or barbiturates will induce metabolism of doxycycline reducing it’s effectiveness.
  • Concurrent topical therapy is not recommended with the drying, abrasive or medicated soaps and cleansers, alcohol-containing preparations, peeling agents, or medicated cosmetics, as increased skin irritation may occur.