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Dihydrocodeine chemical structure

IUPAC name
CAS number
ATC code


Chemical formula {{{chemical_formula}}}
Molecular weight 301.38 g/mol
Bioavailability 20%[1]
Metabolism Mainly hepatic through CYP3A4 and CYP2D6
Elimination half-life 4 hours[1]
Pregnancy category C (US)
Legal status
Routes of administration Oral, IV, subcutaneous, rectal

Dihydrocodeine, also called DHC and Paracodeine and by the brand names of SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, and DF-118 amongst others, is a semi-synthetic opioid analgesic prescribed for postoperative pain, severe dyspnea, or as an antitussive. Dihydrocodeine tartrate is also present in co-dydramol. In some countries, controlled-release dihydrocodeine and/or the immediate release forumulations are used as an alternative to methadone in treatment of opioid dependency and addiction.

Commonly available as tablets, solutions, elixirs, and other oral forms, dihydrocodeine is also available in some countries as an injectable solution for deep subcutaneous and intra-muscular administration. Intravenous administration could be dangerous due to pulmonary oedema and the potential of anaphylaxis as it is with codeine. At one time in the past and possibly now, dihydrocodeine suppositories also existed.

Dihydrocodeine is used as an alternative to or incrementation on codeine for the above mentioned spectrum of situations. It is available as the following salts, in rough descending order of frequency of use: bitartrate, phosphate, hydrochloride, tartrate, hydroiodide, methyliodide, hydrobromide, and sulphate. The salt to free base conversion factors are 0,67 for the bitartrate, 0,73 for the phosphate, and 0,89 for the hydrochloride.

Dihydrocodeine was developed in Germany during the early 1900s during the great search for more effective antitussives, and is similar in chemical structure, pharmacological activity, and potency as codeine. Depending on individual metabolism, dihydrocodeine is 100 to 150 percent as strong as codeine. Although dihydrocodeine does have extremely active metabolites, in the form of dihydromorphine and dihydromorphine-6-glucuronide (one hundred times more potent), these metabolites are produced in such small amount that they do not have clinically important effects.[2]


Approved indication for dihydrocodeine is the management of moderate to moderately severe pain as well as coughing and shortness of breath. As is the case with other drugs in this group, the antitussive dose tends to be less than the analgesic dose, and dihydrocodeine is a powerful cough suppressant like all other members of the immediate codeine family (see below) and their cousins hydrocodone and ethylmorphine (a.k.a. dionine and codethyline)

For use against pain, dihydrocodeine is usually formulated as tablets containing a quarter grain (15 or 16 mg) and a half grain (30 or 32 mg) with or without other active ingredients such as aspirin, paracetamol, ibuprofen, or others. The usual dose is one tablet taken every 4-6 hours when necessary.

Controlled-release dihydrocodeine is available for both pain and coughing as indicated below as waxy tablets containing 60 to 120 mg of the drug, and some formulations intended for use against coughing and the like have other active ingredients such as antihistamines, decongestants and others. Generally, the starting dose would be 60 mg every 12 hours.

Injectable dihydrocodeine is most often given as a deep subcutaneous shot.

The above doses are typical starting doses for "opioid naïve" patients. Existing tolerance to opioids and more severe pain (up to about 6 or 7 on a 1 to 10 scale perhaps) call for higher doses; dihydrocodeine may be more like hydrocodone and oxycodone than codeine and ethylmorphine in lacking a theoretical analgesic ceiling, but toxicity of other ingredients (especially aspirin and paracetamol) and/or the side effects of the opioid itself -- especially vasodilation, itching, and other effects of the large quantities of histamine released in the body -- generally supervene and thus limit dihydrocodeine to the middle range of painkillers, viz. between ethylmorphine and nicocodeine on the continuum. Controlled-release dihydrocodeine is often taken every 8 hours and even 6 especially when titrating the dose in chronic pain cases and similar situations. Different authorities list the maximum daily dose for dihydrocodeine as being anywhere from 240 mg to 720 mg, all other things being equal.

Dihydrocodeine products which can be purchased over the counter in many European and Pacific Rim countries generally contain from 2 to 20 mg of dihydrocodeine per dosing unit combined with one or more other active ingredients such as paracetamol, aspirin, ibuprofen, antihistamines, decongestants, vitamins, medicinal herb preparations and other such ingredients. In a subset of these countries and foreign possessions, 30 mg tablets and 60 mg controlled-release tablets are available over the counter and chemists may very well be able to dispense the 90 and 120 mg strengths at their discretion.

In the United States, the most common analgesic brands with DHC are: DHC Plus (16 and 32 mg), Panlor SS (32 mg), ZerLor (32 mg), Panlor DC (16 mg) and Synalgos DC (16 mg). These combination products also include paracetamol (acetaminophen) and caffeine. Aspirin is used in the case of Synalgos DC.

The Panlor series is manufactured by Pan-American Laboratories of Covington, Louisiana, and they also market several dihydrocodeine-based prescription cough syrups in the United States.

Dihydrocodeine is sometimes marketed in combination preparations with paracetamol as co-dydramol (BAN) to provide greater pain relief than either agent used singly (q.v. drug synergy).

In the UK and other countries, 30-mg tablets containing only dihydrocodeine as the active ingredient (DF-118) are available.

The original dihydrocodeine product, Paracodin, is an elixir of dihydrocodeine hydroiodide also available as a Tussionex-style suspension in many European countries.

In many European countries and elsewhere in the world, the most commonly-found dihydrocodeine preparations are extended-release tablets made by encasing granules of the ingredient mixture, almost always using the bitartrate salt of dihydrocodeine, of four different sizes in a wax-based binder. The usual strengths are 60, 90, and 120 mg. These tablets are used in some countries, such as Austria, as an alternative to methadone (MS-Contin/MST-Continus type medications and buprenorphine are also used for this purpose) for management of opiate addiction. Common trade names for the extended-release tablets are Didor Continus, Codidol, Codi-Contin, Dicodin (made in France and the major product containing the tartrate salt) and DHC Continus.

Dihydrocodeine is available in Japan as tablets which contain 2½ mg of dihydrocodeine phosphate and caffeine, the decongestant d,l-methylephedrine HCl, and the antihistamine chlorpheniramine, and packets of granules which effervesce like Alka-Seltzer® with 10 mg of dihydrocodeine with lysozyme and chlorpheniramine, marketed for OTC sale as SS Bron. These two formulations may have once contained phenyltoloxamine citrate as the antihistamine component. The manufacturer of SS Bron, IsuIsu, also markets an ibuprofen with dihydrocodeine product called S.Tac EVE. Elsewhere in the Pacific Rim and elsewhere, Dicogesic in analogous to Glaxo/Smith-Kline's DF-118.

Dihydrocodeine is also the original member and chemical base of a number of similar semi-synthetic opiates such as acetyldihydrocodeine, dihydrocodeine enol acetate, dihydroisocodeine, nicocodeine, nicodicodeine, and thebacon.

Side effects

As with other opioids, tolerance and physical and psychological dependence develop with repeated dihydrocodeine use. All opioids can impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery if taken in large doses, but have the opposite effect in moderate doses.[3]

Itching and flushing and other effects of blood vessel dialation are also common side effects, due to histamine release in response to the drug using one or more types of receptors in the CNS and/or other responses elsewhere in the body. First-generation antihistamines such as tripelennamine (Pyrabenzamine®), clemastine (Tavist®), hydroxyzine (Atarax®), diphenhydramine (Benadryl®), cyproheptadine (Periactin®), brompheniramine (Dimetapp®), chlorpheniramine (Chlor-Trimeton®), doxylamine (NyQuil®) and phenyltoloxamine (Percogesic® Original Formula) not only combat the histamine-driven side effects, but are analgesic-sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan®) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol® and the like) by this and/or other unknown mechanisms.

Other side effects include giddiness and a sense of hyperactivity. Many patients and experts have pointed out that many opiates have the effect of generating empathy and improving interpersonal skills in a manner analogous to, but subjectively different from, MDMA, MDA, and many related amphetamine-variant entheogen/empathogen/hallucinogenics. Dihydrocodeine and hydrocodone seem to have this effect somewhat in excess of their theoretical analgesic potency as compared to other opioids.

As with all drugs, side effects depend on the person taking the medication. They can range in severity from mild to extreme, from headaches to difficulty breathing.

Constipation is the one side-effect of dihydrocodeine and almost all opioids which is near-universal. It results from the slowing of peristalsis in the gut and is a reason why dihydrocodeine, ethylmorphine, codeine, opium preparations, and morphine are used to stop diarrhoea and combat Irritable Bowel Syndrome (IBS) in its diarrhoeal and cyclical forms as well as other conditions causing hypermotility and/or intestinal cramping. The gut itself contains its own opioid receptors, which also allows opioids which do not enter the CNS at all or in appreciable quantites following oral administration such as the pethidine-related drugs loperamide, diphenoxylate, and difenoxin to work in the same fashion in a significant percentage of the population. These drugs also have direct anticholinergic effects which contribute to their action. The loperamide-like drugs, however, can exacerbate cyclical IBS and have little or no effect on the cramps associated with all major forms of IBS and exacerbate the constipation-predominant manifestation of this condition. As a result, the most effective opioids for this spectrum of GI complaints would be whole-opium preparations such as paregoric, laudanum, Dover's Powder, granulated opium, opium in pill form etc., with codeine and dihydrocodeine working very well also, especially on diarrhoeal and cyclical IBS. Whole opium contains not only morphine and codeine and other narcotic alkaloids but also the alkaloid papaverine, a smooth-muscle relaxant, and other alkaloids, oils, resins and waxes which can help with cramping and other symptoms. Preparations containing both paregoric and extract of belladonna were once available that were probably the strongest and most efficaceous of GI drugs.


In Hong Kong, Dihydrocodeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purporses. The substance can be given by pharmacists under a prescription. Anyone who supply the substance without presciption can be fined $10000(HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.

In the United Kingdom dihydrocodeine is a Class B drug; however, it is available over-the-counter in small amounts (less than 8 mg), when combined with paracetamol (see co-dydramol). Illegal possession of dihydrocodeine can result in up to 5 years in prison and/or an unlimited fine.

In the USA, it is a DEA Schedule II substance, although preparations containing small amounts of dihydrocodeine are classified as Schedule III or Schedule V, depending on the concentration of dihydrocodeine relative to other active constituents, such as paracetamol (acetaminophen). This scheduling is similar to codeine's. The DEA's Drug Code for dihydrocodeine free base and all salts is 9120.

International treaties and the controlled-substances laws of most countries, such as the German Betäubungsmittelgesetz, regulate dihydrocodeine at the same level as codeine. Dihydrocodeine-based pharmaceuticals are especially used where chronic pain patients are able to have essentially OTC access to them provided they are registered with the provincial or national government as such a patient.

Controlled-release dihydrocodeine is a non-prescription item in some places, especially the 60 mg strength. A report by the Ivo Šandor Organisation in 2004 listed Andorra, Spain, Gibraltar, and Austria as having varying degrees of access to these and other dihydrocodeine, nicocodeine, and codeine products.


Dihydrocodeine is the parent drug of a series of moderately strong narcotics including hydrocodone, nicocodeine, nicodicodeine, thebacon, acetyldihydrocodeine and others.

From the point of view of the organic chemist, the removal of the double bond makes the structure much more stable. It is more resistant to metabolic attack (hence a duration of action of 6 hours rather than 4 for codeine). It is also more stable in acidic, high-temperature environments. Whereas converting codeine to morphine is a difficult and unrewarding task, dihydrocodeine can be converted to dihydromorphine with very high yields (over 95%). Dihydromorphine is widely used in Japan. The dihydromorphine can be quantitativly converted to hydromorphone using potassium tert butoxide.


  1. 1.0 1.1 Rowell F, Seymour R, Rawlins M (1983). Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites.. Eur J Clin Pharmacol 25 (3): 419-24. PMID 6628531.
  2. Schmidt H, Vormfelde S, Walchner-Bonjean M, Klinder K, Freudenthaler S, Gleiter C, Gundert-Remy U, Skopp G, Aderjan R, Fuhr U (2003). The role of active metabolites in dihydrocodeine effects.. Int J Clin Pharmacol Ther 41 (3): 95-106. PMID 12665158.
  3. O'Neill W, Hanks G, Simpson P, Fallon M, Jenkins E, Wesnes K (2000). The cognitive and psychomotor effects of morphine in healthy subjects: a randomized controlled trial of repeated (four) oral doses of dextropropoxyphene, morphine, lorazepam and placebo.. Pain 85 (1-2): 209-15. PMID 10692620.

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