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Systematic (IUPAC) name
4,5-α-epoxy-3-hydroxy-17-methyl morphinan-6-one
CAS number 466-99-9
ATC code N02AA03
PubChem 5284570
DrugBank APRD01021
Chemical data
Formula C17H19NO3 
Mol. mass 285.338 g/mol
Pharmacokinetic data
Bioavailability Oral: 30–35%, Intranasal: 52–58%[1]
Protein binding 20%
Metabolism Hepatic
Half life 2–3 hours[2]
Excretion Renal
Therapeutic considerations
Pregnancy cat.


Legal status

Class A (UK),
DEA Schedule II (USA)

Dependence Liability High
Routes oral, intramuscular, intravenous, subcutaneous, intranasal, rectal, sublingual, transmucosal, buccal, transcutaneous (experimental)

Hydromorphone (Dilaudid®)is a potent centrally-acting analgesic drug of the opioid class; it is a derivative of morphine, specifically a hydrogenated ketone. This compound is therefore a semi-synthetic drug (i.e., both an opiate and a true narcotic). It is used in medicine as an alternative to morphine as indicated below. Hydromorphone was researched and developed in Germany in the early 20th Century, officially announced and patented in 1924, and introduced to the mass market by Knoll as Dilaudid beginning in 1926. Some authorities and publications use this name as a genericised brand name (e.g. like Kleenex, Xerox &c.) for hydromorphone and the name indicates its derivation and degree of similarity to morphine (by way of laudanum) -- Cf. Dicodid (hydrocodone), Dihydrin (dihydrocodeine) and Dinarkon (oxycodone). Hydromorphone is about eight times as potent as morphine by weight.

Hydromorphone is used to relieve moderate to severe pain and severe, painful dry coughing. As explored in detail below, hydromorphone is becoming more popular in the treatment of chronic pain in many countries, and it is used as a substitute for heroin and morphine where one or both of these drugs are not marketed. Hydromorphone is preferred even over morphine in many cases ranging from the emergency deparment to the operating suite to ongoing treatment of chronic pain syndromes on account of hydromorphone's superior solubility and speed of onset and less troublesome side effect profile and lower dependence liability as compared to morphine and heroin. Hydromorphone is also a good alternative to morphine when patients refuse morphine due to the stigma associated with it.

Hydromorphone's side effect profile, explored in greater detail in the section on side effects, is closer to that of dihydromorphine than that of morphine and importantly produces less nausea and vomiting and fewer histamine-related side effects than morphine as a result. In cases where significant doses are anticipated, hydromorphone may be easier to titrate to the needed dose for this and other related reasons. Like all other opioid analgesics, tolerance develops with repeated administration and there is no true maximum dose, although requirements for pain relief can often remain more or less constant for extended periods after initial titration and tolerance does indeed commonly follow a course of plateaus of this type interspersed with comparatively infrequent escalations of varying intensity and in some cases the opportunity to titrate downwards as well.

The above-mentioned properties account for hydromorphone being a useful agent for chronic pain. Many chronic pain patients find that hydromorphone has a spectrum of actions which suit them just as well as morphine, and better than synthetics like methadone, piritramide, fentanyl, or levorphanol in alleviating suffering, as contrasted with simple pain of equal objective intensity. Hydromorphone is a common alternative for those who tend to have hallucinations from fentanyl in the form of skin plasters and other dosage forms. Hydromorphone also lacks the toxic metabolites of many opioids related to pethidine and some of the methadone class.

Since, as noted below, there is not currently a hydromorphone analogue of MS-Contin or OxyContin on the market in the United States, the similarity in effects of hydromorphone and oxymorphone (which does come in an extended-release form, Opana®) is particularly important to note at this time since high-dose maintenance regimens of hydromorphone for chronic pain can present logistical problems for pharmacists and patients. Since there are two extended-release forms of hydromorphone available in other countries and the removal of them from the US market was the result of the drugs being used improperly, one could argue that reinstating this fourth option should be an important priority.

Furthermore, many authorities believe that the cross-tolerance between morphine and hydromorphone is incomplete, making alternating morphine and hydromorphone or adding the two drugs to a rotation of three or more agents a strategy worthy of consideration in a case of chronic pain or other afflictios requiring use of analgesics for an extended period. In addition, hydromorphone is similar to other opioids and semi-synthetics in particular as having its effectiveness possibly impacted by levels of liver enzymes, kidney issues, and other drugs being taken. This is especially the case when the drug is being given by mouth and careful titration which has control of pain as its objective is particularly important and it is quite possible that the amount of hydromorphone taken per 24 hours and single-dose quantities could vary significantly -- in either direction -- from the averages predicted by equianalgesic dose tables from one patient to the next.

Hydromorphone is also an important agent for use against moderate chronic pain, sub-chronic pain from severe injury, and acute pain requiring rapidly-escalatimg doses of narcotic anaglesics in countries where the majority or all of mid-level narcotic analgesics are mixed with paracetamol, aspirin, ibuprofen, naproxen, diclofenac and the like. The effects on the liver of paracetamol are particularly dangerous in such situations, and since hydrocodone and dihydrocodeine are not available for compunding prescriptions in the United States, for example, the choices left for these cases are oxycodone in pure form, morphine, levorphanol, possibly methadone, and hydromorphone. Of the above, the agents which cause intolerable side effects in the lowest percentage of users are levorphanol and hydromorphone. In such near borderline cases, the difficulty and/or time frame of titrating the available forms of fentanyl and mitigating side effects may make that agent a less than perfect choice as well.

In addition to the above, hydromorphone usually proves to be the first alternative of choice to morphine and fentanyl in severe chronic pain situations because the other commonly available agent in the United States, Canada, and various other countries is oxycodone, which a large percentage of chronic pain specialists do not rank high on the list of analgesics for maintenance treatment of most chronic pain syndromes (although a subgroup of patients do in fact respond particularly well to it, making its continued availabilty for this purpose very important nonetheless) for reasons ranging from stigma to regulatory and legal barriers limiting availability and/or willingness of physicians and pharmacists to deal with it, to the fact that many patients do have a very different reaction to oxycodone including a higher dependence and abuse liability than hydromorphone or most other opioids, a liability that some experts rate as uniquely combining the codeine, morphine, and cocaine types.


Brand Names & Dosage Forms

Hydromorphone is known in various countries around the world by the trade names Hydal, Sophidone, Hydrostat, Hydromorfan, Hydromorphan, Laudicon, Hymorphan, Palladone and others. An extended-release version of Palladone called Palladone SR was available for a short time in the United States before being voluntarily withdrawn from the market after an FDA advisory released in July 2005 warned of a high overdose potential when taken with alcohol; it is still available in the United Kingdom as of March 2007, and in most other European countries. Another extended-release version called Hydromorph Contin, manufactured as controlled release capsules, continues to be produced and distributed in Canada by Purdue Pharma Inc. in Pickering, Ontario.

Hydromorphone hydrochloride (anhydrous) is the salt used in virtually all hydromorphone products and in prescription compounding. The free base conversion ratio of this salt is 0.89. Some brands of hydromorphone tablets contain small amounts of sulphites. Hydromorphone's oral to intravenous effectiveness ratio is 5:1 and equinalgesia conversion ratio (hydromorphone HCl to anhydrous morphine sulphate, IV, SC, or IM) is 8:1 and is about 4:1 orally. This means that 30 mg of immediate-release morphine by mouth is similar in analgesic effect to 7.5 mg of hydromorphone by mouth, 10 mg of morphine by injection, and 1.5 mg of hydromorphone by injection. These doses also correspond to about 30 mg of hydrocodone, 24 mg of oxycodone, 200 mg of codeine, 135 mg of dihydrocodeine, 20 mg of dihydromorphine, 15 mg of nicomorphine, 12 mg of heroin, 34 mg of piritramide, circa or about 18 mg of ketobemidone, and 8 mg of dextromoramide by the default routes of administration and 60 mg of extended-release morphine via the oral route. These figures which can vary from person to person, especially with oral administration, on account of such things as relative and absolute levels of some liver enzymes, system pH, and others. This is especially the case with methadone, levomethadone and phenadoxone, which require extra steps in the conversion and titration process.

At this point in time, the tablets and capsules with the highest immediate-release dose of hydromorphone are 8 mg tablets; however, 16 mg (quarter-grain), 32 mg (half-grain) and 64 mg (one grain) tablets were available at least through the late 1950s in some countries, and 24, 36, and 48 mg tablets less commonly. As was the case with many other medications in the past including most of the centrally-acting analgesics, hypodermic tablets for preparing injections were made in the past as well and the tablets for oral administration were in fact low- or zero-residue multi-purpose tablets which could replace the "Solvets", as the hypodermic tablets were called, in times of emergency. In western countries, inexpensive ampoules of sterile solution for injection have largely replaced the hypodermic tablets that were so common in past decades.

The 32 mg extended-release Palladone SR® capsule, 500 mg (10 mg/ml * 50 ml) phial of Dilaudid HP® injection, and 5mg suppositories are the units with the largest doses in their respective categories at this time. The hydromorphone analogue of Roxanol® (liquid for oral, sublingual, or buccal administration via a calibrated dropper -- not to be confused with Dilaudid Cough Syrup, which is more dilute and contains a number of other ingredients including peach flavouring) of 1 mg per ml is available in 480 ml bottles, and the 250 mg phial of lipophilised powder for preparing injections with a 1000 mg phial available in the past.

Oral formulations of hydromorphone can also be administered under the tongue and between the lower jaw and cheek; these routes increase the effectiveness of the tablets by putting hydromorphone into the bloodstream prior to passing through the liver. A liquid formulation is commonly available and recommended specifically for these routes, and uncoated low-residue oral formulations are available in some countries to take advantage of this fact. However, all tablets potentially can be used in this fashion although they dissolve more slowly than purpose-made sublingual, buccal, and orally disintegrating tablets of other drugs like nitroglycerine, morphine, fentanyl, onadesentron, and others. Some tablets work better in this fashion if the coating on the tablet is first removed by sucking on it for a short time.

As with many other drugs, oral and soluble forms of hydromorphone such as the oral liquid, cough syrup, soluble tablets, &c., can be mixed with water or fruit juice if so desired; carbonated beverages and effervescent medications like Alka-Seltzer® have the added advantage of driving the medication through the stomach wall more rapidly.

Hydromorphone is generally believed to be the second most common agent, after morphine, used in Patient-Controlled Analgesia (PCA) units worldwide.

Some of the hydromorphone products said to be in development at various places as of December 2007 are nasal sprays and a skin plaster, possibly with an electronic component to aid delivery and possibly allow for rescue doses for breakthrough pain.

Available Forms

  • Tablets - 0.5mg, 1mg, 2mg, 3mg, 4mg, 8mg
  • Capsules (Palladone) - 1.3mg, 2.6mg
  • Modified Release capsules (Palladone SR) - 2mg, 4mg, 8mg, 16mg, 24mg, 30mg, 32mg
  • Controlled Release capsules (Hydromorph Contin) - 3mg, 6mg, 12mg, 18mg, 24mg, 30mg
  • Suppository - 3mg, 5mg
  • Powder for injection - 250 mg (hydromorphone HCl)
  • Oral liquid (HCl) - 1 mg/mL (480 mL)
  • Cough Syrup - 1 mg/5 ml
  • Injection (HCl) - 1 mg/mL (1 mL), 2 mg/mL (1 mL, 20 mL), 4 mg/mL (1 mL),
  • Dilaudid-HP - 10 mg/ml (1 mL, 5mL, 50mL)



Hydromorphone, a semi-synthetic μ-opioid agonist, is a hydrogenated ketone of morphine and shares the pharmacologic properties typical of opioid analgesics. Hydromorphone and related opioids produce their major effects on the central nervous system and gastrointestinal tract. These include analgesia, drowsiness, mental clouding, changes in mood, euphoria or dysphoria, respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increased biliary pressure, pinpoint constriction of the pupils, increased parasympathetic activity and transient hyperglycemia.

CNS depressants, such as other opioids, anesthetics, sedatives, hypnotics, barbiturates, phenothiazines, chloral hydrate and glutethimide may enhance the depressant effects of hydromorphone. MAO inhibitors (including procarbazine), first-generation antihistamines (brompheniramine, promethazine, diphenhydramine, chlorpheniramine), beta-blockers and alcohol may also enhance the depressant effect of hydromorphone. When combined therapy is contemplated, the dose of one or both agents should be reduced.


Patients with kidney problems must exercise caution when dosing hydromorphone. In those with renal impairment, the half-life of hydromorphone can increase to as much as 40 hours. This could cause an excess buildup of the drug in the body, and result in fatality. The typical half-life of intravenous hydromorphone is 2.3 hours.[3] Peak plasma levels usually occur between 30 and 60 minutes after oral dosing.[4]

Side effects

Adverse effects of hydromorphone are similar to those of other opioid analgesics, and represent an extension of pharmacological effects of the drug class. The major hazards of hydromorphone include respiratory and CNS depression. To a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest have occurred. The most frequently observed adverse effects are sedation, nausea, vomiting, constipation, lightheadedness, dizziness and sweating. These effects can be exaggerated by dose dumping if the medication is taken with alcohol.[5]

A common side effect associated with taking slightly higher doses of hydromorphone is extreme euphoria. This effect makes hydromorphone quite desirable to the opioid abusing community, more so opioid-tolerant users due to its high potency. An intra-nasal or intra-venous R.O.A. is preferred due to significantly higher bioavailabilities. For a non-tolerant user, a dose of approx. 4 to 6 mgs is ideal for achieving an overwhelming euphoria and powerful nod. Many opioid users do not take drugs intra-venously, and may prefer to snort their hydromorphone. Dilaudid brand is an excellent candidate for abusing, because it can be crushed and powdered almost effort free. In addition to this, Dilaudid contains no anti-abuse mechanisms, and the fewest binders and fillers compared to other brands of hydromorphone, so it can be injected fairly safely. Use about 8 units of water per mg of hydromorphone in the spoon for maximum potency for injection.

Hydromorphone, like all opioids, can be potentiated by taking a medicinal dose of a number of drugs about 20-40 minutes before dosing. A typical potentiation dose to enhance the effect of an opioid high can include approx. 100-200mgs Dimenhydrinate, 25-50 mgs Diphenhydramine, a decent amount of grapefruit juice, 1oz. of liquor, Hydroxyzine, or Cetirizine.


Commercially, hydromorphone is made from morphine either by direct re-arrangement (made by reflux heating of alcoholic or acidic aqueous solution of morphine in the presence of platinum or palladium catalyst), or reduction to dihydromorphine (usually via catalytic hydrogenation), followed by oxidation with benzophenone in presence of potassium tert butoxide or aluminium tert butoxide (Oppenauer oxidation). The 6 ketone group can be replaced with a methylene group via the Wittig reaction to produce 6-methylene-desomorphine which is 80x stronger than morphine.[6]

Changing morphine into hydromorphone increases its activity and therefore makes hydromorphone about eight times stronger than morphine on a weight basis, all other things being equal. Changed also is lipid solubility, contributing to hydromorphine having a more rapid onset of action and alterations to the overall Absorption, Distribution, Metabolism & Elimination profile as well as the side effect profile (generally less nausea and itching) versus that of morphine. The semi-synthetic opiates, of which hydromorphone and its codeine analogue hydrocodone are amongst the best-known and oldest, include a huge number of drugs of varying strengths and with differences amongst themselves both subtle and stark, allowing for many different options for treatment.

The human liver produces hydromorphone when processing hydrocodone using the cytochrome p450 II-D-6 enzyme pathway (CYP2D6). This is the same route that is used to convert many different opiate prodrugs into the active form. The proportion of drug that is converted into the stronger form is around 10% on average although this varies markedly between individuals. Drugs that are bioactivated in this way include codeine into morphine, nicocodeine to nicomorphine, oxycodone to oxymorphone and dihydrocodeine to dihydromorphine.

Some bacteria have been shown to be able to turn morphine into hydromorphone. As reported in the July 1993 issue of Applied Environmental Bacteriology, the bacterium Pseudomonas putida, serotype M10 produces a naturally occurring NADH-dependent morphinone reductase which can work on unsaturated 7,8 bonds -- with result that when these bacteria are living in an aqueous solution containing morphine, sigificant amounts of hydromophone form as it is an intermediary metabolite in this process; the same goes for codeine being turned into hydrocodone. At this time no information has been published indicating whether or not this process can change dihydromorphine into metopon or acetylated morphine derivatives into the respective ketones of the acetylmorphone series.

Exposure to light will cause solutions of hydromorphone to darken to an amber colour -- reportedly this does not effect the potency of the drug. Of course, any ampoules or phials containing sediment or cloudiness should be discarded.

See also


  • Hydromorphone Consumer Drug Information
  • Article Discussing Withdrawal of Extended-Release Hyrdromorphone from the U.S. Market
  • Pain Care and Patient Information about Opioid Analgesics
  • Dihydromorphinones From Morphine & Analogues


  1. ^ Coda BA, Rudy AC, Archer SM, Wermeling DP. "Pharmacokinetics and Bioavailability of Single-Dose Intranasal Hydromorphone Hydrochloride in Healthy Volunteers." Anesthesia Analgesia. 2003 Jul;97(1):117-23. PMID 12818953 Fulltext
  2. ^ Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL. "Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects." Journal of Clinical Pharmacology. 1981 Apr;21(4):152-6. PMID 6165742 Fulltext
  3. ^ That's Poppycock - Hydromorphone
  4. ^ Dilaudid Clinical Pharmacology
  5. ^ Palladone Pain Drug Pulled Off the Market.
  6. ^
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Hydromorphone". A list of authors is available in Wikipedia.
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