Does clonidine interact with methadone? Is clonidine addictive?/nA 30-year-old woman is treated wit

Fråga: Does clonidine interact with methadone? Is clonidine addictive?

A 30-year-old woman is treated with methadone because of opiate dependence, and sertraline and mirtazapine as antidepressants. She has also, on her own initiative, been taking clonidine because of profuse sweating, which is considered a side-effect of methadone.

Sammanfattning: There is no evidence of an interaction between clonidine and methadone. Clonidine is not addictive, but may cause prominent withdrawal symtoms. Clonidine has also been reported to interact with antidepressants, such as mirtazapine, resulting in hypertension.

Svar: Clonidine is a partial alpha-2-receptor agonist, used in the treatment of hypertension, and for alleviation of acute opiate withdrawal symtoms (1). Approximately 2/3 of the drug is excreted unchanged in the urine, whilst one third is metabolised to inactive metabolites (2, 3). The enzymes involved in this metabolism has not been identified.

Methadone has a complex elimination that includes both renal excretion and metabolism via several different cytochrome P450 enzymes (1).

We have found no indications in the literature of any adverse interactions between methadone and clonidine, and there is no apparent theoretical basis to suspect such in interaction.

As for the patients other medications, there are two case reports describing an interaction between clonidine and mirtazapine, leading to severe hypertension. Clonidine exerts its antihypertensive effects by activating central alfa-2-receptors, thereby causing a reduction in endogenous release of norephinephrine. Mirtazapine acts as an antagonist at the same receptor (4).

Furthermore, one study indicates that sertraline may inhibit the metabolism of mirtazapine, leading to a doubling of the concentration/dose ratio of the latter drug (5). Both these drugs are partly metabolised by the same enzymes; CYP3A4 and CYP2D6.

We have found no data supporting the idea that clonidine should be addictive. However, prominent withdrawal symtoms (headache, flushing, sweating, insomnia, agitation, emotional lability, tremor, nausea, and vomiting) have been described after sudden cessation of chronic clonidine administration, especially after high doses and in patients also treated with beta blockers (1).

In the present patient, sweating may possibly be worsened by sertraline. Selective serotonine reuptake inhibitors has been reported to cause sweating in approximately 10 percent of treated patients. Interestingly, mirtazapine has been suggested as an antidote to drug-induced sweating (6). A treatment option in this patient may be to stop sertraline and, if feasible, increase the dose of mirtazapine instead. Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999 Lowenthal DT. Pharmacokinetics of clonidine. J Cardiovasc Pharmacol 1980;2(suppl 1):S29-S37 Arndts D, Doevendans J, Kirsten R, Heintz B. New asspects of the pharmacokinetics and pharmacodynamics of clonidine in man. Eur J Clin Pharmacol 1983;24:21-30 SFINX (Swedish, Finnish INteraction X-referencing) Shams M, Hiemke C, Härtter S. Therapeutic drug monitoring of the antidepressant mirtazapine and its N-demethylated metabolite in human serum. Ther Drug Monit 2004;26:78-84. Buecking A, Vandeleur CL, Khazaal Y, Zullino DF. Mirtazapine in drug-induced excessive sweating. Eur J Clin Pharmacol 2005;61:543-44