The question concerns a middle-aged male treated with doxycycline in ordinary doses. Four days afte

Fråga: The question concerns a middle-aged male treated with doxycycline in ordinary doses. Four days after the start of treatment, the patient developed nephrogenic diabetes insipidus-like symptoms. Could doxycycline have this side-effect?

Sammanfattning: We have found no documentation of nephrogenic diabetes insipidus after treatment with doxycycline. However, there are a few observations of a nephrogenic diabetes-insipidus-like syndrome reported after treatment with demeclocycline and some reported cases of polyuria after treatment with doxycycline.

Therefore, it is not excluded that the diabetes insipidus like event observed in the actual patient could have a casual relationship to doxycycline administration.

Svar: No documentation could be found on doxycycline and the occurrence of nephrogenic diabetes insipidus. Tetracycline antibiotics such as doxycycline are known to have a nephrotoxic effect. The mechanism is uncertain but may be in part related to antianabolic effect of tetracyclines as well as a direct dose related toxic effect (1). Nephrotoxicity is initially reflected by polyuria, tubular proteinuria and increased enzymuria followed by cylinderuria and reduced glomerular filtration. Tubular regeneration usually occurs within 15 to 30 days (2). For demeclocycline (demetylchlortetracyclinehydrochloride) (no longer registered in Sweden) there have been a few observations of a nephrogenic diabetes insipidus like syndrome (1,3,4,5). This effect is dose-dependent and occurs with daily doses in excess of 1200 mg. The mechanism is unknown, but the resistance to exogenous vasopressin suggests an impairment of renal concentration function due to tubular damage. The drug may also be acting as an aldosterone agonist (3). The Swedish Adverse Drug Reactions Advisory Committee (SADRAC) has received one report of polyuria where demeclocycline (Ledermycin) has been judged to be a probable cause of polyuria (6). One case of renal insufficiency was judged as possible resulting from doxycycline. In the WHO database, there are five cases of polyuria and two cases of hyponatremia reported in connection with doxycycline (7).

We recommend that this case be reported to the regional centre at Huddinge Hospital of the Swedish Adverse Drug Reactions Advisory Committee. 1 Lambert & O´Grady, Antibiotic and chemotherapy. 1992; 6th ed: 282-284

2 Morin JP, Fillastre JP, Olier B: Antibiotic nephrotoxicity. Chemioterapia 1984; 3: 33-40
3 Meyler´s, Side effects of drugs. Ed by MNG Dukes, Elsevier, Amsterdam. 1992; 12: 638
4 Hayek A, Ramirez J: Demeclocycline-induced diabetes insipidus. JAMA 1974; 229: 676-677

5 Maxon HR 3d, Rutsky EA: Vasopressin-resistant diabetes insipidus associated with short-term demethylchlortetracycline (declomycin) therapy. Mil Med 1973; 138: 500-501 6 Swedis 7 WHO, INTDIS, Uppsala