Experimental studies yield conflicting evidence. Several lists warn strictly against its use. The extent of hepatic exposure seems, however, insuffucient to give rise to clinical porphyrinogenic effects under normal therapeutic use. One case report describes safe use by a proven susceptible patient (who suffered a recent drug induced attack). It is unknown if any clinical attacks have been induced by clonidine.

Imidazoline derivative.

Imidazoline derivative with antihypertensive effect, also used as an adjuvant in the treatment of substance abuse.

The daily dose is well below 1 mg and plasmaconcentrations are well below 100nM.

Metabolized without first passage metabolism. 40 - 60% of the dose is excreted in unchanged form in urine. Main metabolite is p-hydroxyclonidine. No data pointing to CYP-interaction.

The effect of clonidine on the activity of delta-aminolevulinate synthase and on the formation of porphyrins and cytochrome P-450 were examined in the 18-day-old chick embryo liver in ovo. Clonidine was found to induce delta-aminolevulinate synthase in this system. The authors of the published experiment suggest that clonidin is avoided or used with caution in patients with acute porphyria (Andersson KE, et al. Biochim Biophys Acta 1978). Clonidine did not induce hepatic ALA-S or urinary excretion of ALA or PBG in normal as well as in DDC or AIA pretreated rats. Moreover the induction of P4501A1 (7-ethoxyresorufin-O-deethylase) by DDC was abolished by simultaneous application of clonidine. The authors of this publsihed experiment conclude that clonidine is a safe drug in human acute hepatic porphyria (Goerz G et al. Arzneimittel-Forschung 1997) No changes in the activity of ALA-S and in the hepatic and urinary porphyrin, ALA and PBG contents were observed during administration of different doses of clonidine in female rats. An increase in the activities of the P450 dependent isoenzymes aminopyrine-N-demethylase (ADM) in the short and median term application of clonidine and of 7-ERO-D in the long term application was detected. It is concluded from these findings that clonidine has no effect on the porphyrin biosynthesis, but has an influence on the activities of P450 dependent isoenzymes ADM or 7-ethoxyresorufin-O-deethylase (Goerz G et al. Arzneimittel-Forschung 1993).

Peters 2004: Suggests PRP

A male hypertensive patient (age 28) is treated with clonidine. After withdrawal because of non-compliance the patient is treated acutely for severe hypertension with methyldopa and hydralazine. Blood pressure gets normal, but continuous upper abdominal pain, constipation, red urine, and a strongly positive PBG (Walter-Schwartz test) arise upon this treatment. The patient improves on withdrawal of methyldopa and hydralazine, and administration of glucose. Afterwards the patient was safely treated with clonidine, nifedipine and vitamin K (Bhadoria). This proven susceptible patient tolerates clonidine and nifedipine.