Dihydrocodeine

Dihydrocodeine is a semisynthetic opioid receptor agonist that belongs to the group of antitussives, or weakly acting opioid analgesics. Chemically, it is closely related to codeine. Dihydrocodeine is administered orally, approximately as a sustained-release tablet (containing 60, 90, or 120 mg of the active ingredient). Dihydrocodeine is not subject to the BTMV.

Dihydrocodeine is a partial opioid receptor agonist, with significantly weaker analgesic effects than morphine. 60 mg DHC correspond to 10 mg morphine. The partial agonist effect results in a ceiling effect (above a certain dose, a higher analgesic effect can no longer be achieved by increasing the dose). The potency of dihydrocodeine, as well as codeine and tramadol, is strongly influenced by the genotype of the cytochrome P450 isoenzyme CYP2D6, which varies greatly from person to person. This explains reports of over- or underdoses after administration of standard doses of the two drugs.

Dihydrocodeine) has a mild analgesic effect and is rapidly absorbed from the gastrointestinal tract, with a plasma half-life of about 3-4.5 hours. In the organism, the substance is converted into dihydromorphine, which is characterized by a comparatively high addictive potential. Elimination is predominantly extrarenal.

So-called weak opioid analgesics are often used to treat severe pain, or when paracetamol or a non-steroidal anti-inflammatory drug (NSAID) prove insufficient.

Dihydrocodeine should not be used during pregnancy as there is no experience on the safety of such use. For related agents there is evidence of malformations in humans, growth retardation in the fetus and shortening of the duration of pregnancy.

60.0-210.0mg p.o./day

Side effects consist of nausea, vomiting, drowsiness, mood swings. Contraction of smooth muscle may cause constipation, contraction of the ureter and inhibition of the micturition reflex.

Adverse reactions of the skin: rare. Single case reports refer to AGEP (Nakai N et al. 2014 and erythema multiforme (Matsuzawa Yet al. 2010). More common are pruritus, nonspecific erythema, and generalized dermatitis (Els C et al. 2017).

Overdose symptoms present as drowsiness, stupor or coma, slow respiratory rate, cyanosis, hypotension, and shock. Initially, there are pinhead-sized pupils, followed by increasing hypoxaemia, then pupillary dilatation, cessation of urine output, drop in body temperature, cold sweaty skin and decreased muscle tone.

MAO inhibitors: Dihydrocodeine should not be used during therapy or within 14 days after discontinuation of therapy with MAO inhibitors (e.g. tranylcypromine). Enhancement of central nervous effects or the occurrence of other adverse effects to an unpredictable degree may occur.

Central depressant drugs: Concomitant administration of dihydrocodeine and sedatives/hypnotics, psychotropic drugs (e.g. phenothiazines such as chlorpromazine, thioridazine or perphenazine;

antidepressants such as imipramine, opipramol, or amitryptiline) or sedating antihistamines (e.g., promethazine, meclozine) may potentiate sedative and respiratory depressant effects.

Alcohol: Dihydrocodeine together with alcohol reduces psychomotor performance more than the individual components. Therefore, alcohol should be avoided during treatment with DHC Mundipharma.

Partial opioid agonists/antagonists: The combination of partial opioid agonists/antagonists (e.g. buprenorphine, pentacozine) and dihydrocodeine may result in an attenuation of the effect of DHC Mundipharma.

Antitussives: The effect of antitussives may be increased with concomitant administration of DHC Mundipharma.

Expectorants or secretolytics: Due to the cough suppressant effect of DHC Mundipharma, secretion congestion may occur with concomitant administration of expectorants or secretolytics.

Sildenafil: Concomitant use of dihydrocodeine and sildenafil may in isolated cases cause erections that persist after sexual intercourse.

Cimetidine and other drugs affecting liver metabolism: Inhibition of morphine degradation has been observed during morphine treatment. This resulted in increased plasma concentrations of morphine. Such an interaction cannot be excluded for dihydrocodeine.

Contraindications to the prescription are extreme obesity and impaired lung function.

Monopreparations: Codidol® (A), Codicontin® (CH), DHC Mundipharma ^® (D), Dehace® (A), Dicodin® (F), Paracodin ^® (D, A, CH), Tiamon ^® (D).

Combination preparations: Escotussin ® (CH), Makatussin comp. ^® (CH)

Dihydrocodeine has a dependence potential similar to other potent opioid receptor agonists. Long-term use can lead to physical and psychological dependence as well as tolerance. Rapid relapse is to be expected in cases of pre-existing opioid dependence (including those in remission). Dihydrocodeine is considered a substitute by heroin addicts. Addicts of alcohol or sedatives also tend to abuse and become dependent on dihydrocodeine. Dihydrocodeine should be prescribed with special caution in cases of history or existing abuse of alcohol, drugs, or medications.

The treatment of cough and pain states must not be carried out with codeine or dihydrocodeine-containing drugs in opiate-dependent patients. Non-opiates among antitussives or other effective analgesics should be chosen. The treatment of pain conditions in opiate addicts requires considerable experience and specialized knowledge.

Dihydrocodeine can be detected in samples of whiskers as early as 1 day after oral ingestion. The maximum concentration can be measured 6 days after oral ingestion (Ramírez Fernández MDM et al. 2019).

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2. Estrada JL et al (2001) Generalized eczema due to codeine. Contact Dermatitis. 44:185.
3. Leppert W et al (2016) Dihydrocodeine: safety concerns. Expert Rev Clin Pharmacol 9:9-12.
4. Matsuzawa Yet al. (2010) Erythema multiforme major putatively induced by dihydrocodeine phosphate. Clin Exp Dermatol 35:673-674.
5. Nakai N et al (2014) Acute generalized exanthematous pustulosis caused by dihydrocodeine phosphate in a patient with psoriasis vulgaris and a heterozygous IL36RN mutation. JAMA Dermatol 151:311-315.
6. Ramírez Fernández MDM et al. (2019) Time course detection of dihydrocodeine in body hair after a single dose. Forensic Sci Int 302:109864.