Dihydrocodeine

Third line weak opioid

Mechanism of action:  mu-opioid agonist. Very similar in structure to codeine.

Presentation: tablet, oral solution, modified-release tablet.

Suggested dose:  30-60mg orally four times a day for adults over 50kg with normal hepatic and renal function, reduce in frailty

Co-prescribe Naloxone

Oral absorption:  bioavailability is low, approx. 20%, with peak plasma levels reached at 90-110 mins

Protein binding:  not available

Metabolism: Metabolized in the liver by CYP2D6 into an active metabolite, dihydromorphine, which has activity comparable to that of morphine, and by CYP3A4 into the secondary metabolite nordihydrocodeine. Other metabolites include dihydrocodeine-6-glucuronide, dihydromorphine-3-glucuronide and dihydromorphine-6-glucuronide. Dihydromorphine and dihydromorphine-6-glucuronide have mu-opioid receptor affinities 70 times great than dihydrocodeine [Schmidt 2003].

Despite the importance of CYP2D6 in producing active metabolites, the CYP2D6 phenotype appears to have no major impact on the clinical effects of dihydrocodeine [Schmidt 2002, Wilder-Smith], unlike Codeine 

Elimination:  excreted by the kidneys

Half-life:  approx. 4 hours

 

Further prescribing information (side effects, contraindications, interactions):

BNF-Dihydrocodeine

References

Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician 2008; 11:S133-S153

Zhou SF.  Polymorphism of human cytochrome P450 2D6 and its clinical significance.  Clin Pharmacokinet 2009; 48:689–723.

Schmidt H, Vormfelde SV, Walchner-Bonjean M, et al. The role of active metabolites in dihydrocodeine effects. Int J Clin Pharmacol Ther. 2003 Mar;41(3):95-106. doi: 10.5414/cpp41095.

Schmidt H, Vormfelde Sv, Klinder K, et al. Affinities of dihydrocodeine and its metabolites to opioid receptors. Pharmacol Toxicol. 2002 Aug;91(2):57-63. doi: 10.1034/j.1600-0773.2002.910203.x

Wilder-Smith CH, Hufschmid E, Thormann W. The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. Br J Clin Pharmacol. 1998 Jun;45(6):575-81. doi: 10.1046/j.1365-2125.1998.00727.x