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Clin Transl Oncol (2007) 9:298-307

REVIEW DOI 10.1007/s12094-007-0057-9

Oxycodone: a pharmacological and clinical review


A. Ordóñez Gallego, M. González Barón and E. Espinosa Arranz

Medical Oncology Service. “La Paz” University Hospital Madrid. Cátedra de Oncología y Medicina Paliativa.
Universidad Autónoma de Madrid. Madrid, Spain

Abstract Oxycodone is a semi-synthetic opioid with an crushed. There is no food interference. The initial dose
agonist activity on mu, kappa and delta receptors. is 10 mg b.i.d. for new treatments and no dose reduction
Equivalence with regard to morphine is 1:2. Its effect is needed in the elderly or in cases of moderate hepatic
commences one hour after administration and lasts for or renal failure. Immediate-release oxycodone
12 h in the controlled-release formulation. Plasma half- (OxyNorm®) is also available in capsules and oral solu-
life is 3–5 h (half that of morphine) and stable plasma tion. Side effects are those common to opioids: mainly
levels are reached within 24 h (2–7 days for morphine). nausea, constipation and drowsiness. Vomiting, pruritus
Oral bioavailability ranges from 60 to 87%, and plasma and dizziness are less common. The intensity of these
protein binding is 45%. Most of the drug is metabolised side effects tends to decrease over the course of time.
in the liver, while the rest is excreted by the kidney Oxycodone causes somewhat less nausea, hallucinations
along with its metabolites. The two main metabolites are and pruritus than morphine.
oxymorphone – which is also a very potent analgesic –
and noroxycodone, a weak analgesic. Oxycodone me- Key words Oxycodone • Opioid • Pain
tabolism is more predictable than that of morphine, and
therefore titration is easier. Oxycodone has the same Ordóñez Gallego A, González Barón M, Espinosa Arranz E
mechanism of action as other opioids: binding to a re- (2007) Oxycodone: a pharmacological and clinical review.
Clin Transl Oncol 9:298-307
ceptor, inhibition of adenylyl-cyclase and hyperpolarisa-
tion of neurons, and decreased excitability. These mech-
anisms also play a part in the onset of dependence and
tolerance. The clinical efficacy of oxycodone is similar
to that of morphine, with a ratio of 1/1.5–2 for the treat- Introduction
ment of cancer pain. Long-term administration may be
associated with less toxicity in comparison with mor- It is estimated that 70–90% of patients with advanced
phine. In the future, both opioids could be used simulta- cancer will suffer significant pain (moderate to severe)
neously at low doses to reduce toxicity. It does not ap- in its different forms: acute or chronic, somatic or vis-
pear that there are any differences between immediate ceral, nociceptive or neuropathic, etc. In the majority of
and slow-release oxycodone, except their half-life is 3–4 cases, the pain is chronic, nociceptive and somatic [1,
h, and 12 h, respectively. In Spain, controlled-release 2]. Some tumours inevitably present with pain through-
oxycodone (OxyContin®) is marketed as 10-, 20-, 40- out the process (digestive, bone and genitourinary tu-
or 80-mg tablets for b.i.d. administration. Tablets must mours), while other types, the minority, may develop for
be taken whole and must not be broken, chewed or a long time without any significant pain (leukaemias,
lymphomas).
Cancer patients’ pain may be due to multiple causes:
direct infiltration of the tumour into sensitive structures
(bone metastases, nerve compression, hollow organ ob-
struction), treatments (dysaesthesia from surgery, mu-
cositis and neuropathy from chemotherapy, fibrosis
from radiotherapy) and those very ill patients suffer
from (pressure sores, constipation, bed rest) [3].
A. Ordóñez Gallego (쾷) Pain should not be viewed as an isolated symptom,
Medical Oncology Service as it is the cause of functional disabilities, changing per-
“La Paz” University Hospital Madrid sonal relationships and emotional disorders, all of which
Cátedra de Oncología y Medicina Paliativa have a marked negative effect on the quality of life of
Universidad Autónoma de Madrid
Madrid, Spain
these patients.
E-mail: amalio2@hotmail.com When treating pain it is essential to follow certain
general principles. However, these principles are not re-
Received 18 July 2006 / Accepted 8 February 2007 spected in the majority of cases, and it can be confirmed
A. Ordóñez Gallego et al.: Oxycodone 299

Table 1 General principles of analgesia major opioids from WHO step 2, following NSAID ad-
ministration, prescribing doses in accordance with the
01. Choose a drug from each step and get to know it in depth.
02. Drug potency must match pain intensity.
visual analogue scale (VAS) [6–8].
03. Analgesics must be administrated around-the-clock and
not as needed.
04. Oral and subcutaneous routes are preferable.
05. Dosage must be individualised.
06. Always consider the presence of breakthrough pain. General remarks
07. Side effects must be prevented and treated.
08. Never forget to use coadjuvant drugs. Oxycodone (14-hydroxy-7,8-dihydrocodeinone) is a
09. Provide clear, written instructions.
10. Treatment efficacy must be assessed continuously. pure semi-synthetic opioid agonist derived from the-
baine with affinity for the kappa receptor, and to a less-
er degree for the mu receptor. It also acts on the delta
receptor.
that nowadays many oncologists and Primary Health Its structural formula is shown in Fig. 1. The struc-
Care doctors do not achieve adequate analgesia in these tural differences between oxycodone and morphine
patients. Some of these principles are explained in Table mean that oxycodone initially undergoes less metabo-
1. It should also be noted that pain is underevaluated on- lism in comparison with morphine and therefore it has
ly too often in patients, and the use of placebos is not greater bioavailability (60–87%) [9]. Also, the differ-
indicated. ences from morphine’s molecules mean that there is less
According to the WHO pain ladder, opioids are clas- immunodepression than in other opioids [10].
sified on the second and third steps. Within the opioid There are various experimental findings that suggest
group, oxycodone is a drug that has been available in that oxycodone’s intrinsic antinociceptive effect is mediat-
Spain since 2004 (although this molecule has been pres- ed by the kappa and mu receptors alike, unlike morphine,
ent in other countries since 1917) [4]. which mainly acts through the mu receptors [11, 12].
Much of the information in this article, which we are In the USA, medical use of opioids increased 400%
devoting to oxycodone, comes from an excellent review between 1996 and 2000. At present, 86% of the market
conducted by Domínguez et al., published in the journal consists of four opioids: (1) controlled-release hydro-
Medicina Paliativa [5]. morphone, (2) controlled-release morphine, (3) con-
It should also be mentioned that in the last few years trolled-release oxycodone (CRO) and (4) transdermal
in our department we have been very interested in using fentanyl [13].

Fig. 1 Structural formula of oxycodone


300 A. Ordóñez Gallego et al.: Oxycodone

Table 2 Some characteristics of the ideal opioid at least twice as great as that of morphine (60–87%).
The high correlation between dose, plasma concentra-
Short half-life
Long-lasting action
tion and pharmacological effects makes its pharmacoki-
Predictable pharmacokinetics netics more predictable [9].
Absence of active metabolites This high bioavailability may be due to the methyl
No ceiling effect group at position 3, which prevents the liver stage of
Few adverse effects glucuronidation. A lower degree of individual variation
in oxycodone makes it easier to titrate than morphine
[18]. Oxycodone has a bioavailability of 50–60% in
rectal administration, and 46% in nasal administration
The first article on oxycodone was published in Ger- [19].
many in 1917, and it has been used in the USA for over
80 years [14]. CRO has only been used in the USA for
the last 10 years, and it has been available in different Absorption and metabolism
formulations in Europe for seven years: controlled-re-
lease tablets, immediate release capsules, liquid and
parenteral preparations. In Spain, CRO tablets appeared The CRO formulation consists of two acrylic polymers
in 2004, immediate-release capsules appeared in 2005 that mean that release and absorption occur in two phas-
and a liquid formulation of the immediate-release ver- es. In the first phase, the gastrointestinal secretions
sion has been available on the market since the begin- erode the tablet surface in order to permit a fast release
ning of 2006. of oxycodone and dissolution of the same. Its action
WHO classifies oxycodone as a step 2 drug when commences within one hour, and its half-life is 0.6 h,
used with a NSAID adjuvant, which means that it has a affecting 38% of the dose. Then there is a second phase
ceiling effect, but it should be remembered that oxy- of sustained release that can last 12 h, with a half-life of
codone is actually a major opioid drug to be used in se- 6.9 h, and this phase affects the remaining 62% of the
vere cancer pain; it is not a codeine-like substance for dose [20].
mild or moderate pain [15]. Liver metabolism then takes place, with the produc-
It is accepted that the ratio for opioid conversion re- tion of two metabolites: oxymorphone (resulting from
garding oxycodone and morphine is 1:2, although clini- O-demethylation), which is a potent analgesic in mini-
cal studies reviewed suggested an equivalence ranging mum concentrations, and noroxycodone (resulting from
from 1/1.4 to 1/1.8. Clinical analgesia commences with- N-demethylation), which circulates in high concentra-
in one hour and in the controlled-release formulation tions and has a mild analgesic action. These metabolites
analgesia lasts for 12 h. are excreted through the kidneys.
CRO has certain characteristics that near the defini- The O-demethylation that occurs in the liver to pro-
tion of an ideal opioid: short half-life, long-lasting ac- duce the oxymorphone is a reaction that is catalysed by
tion, absence of active metabolites, easy to titrate, no the isoenzyme CYP2D6 of the P450 cytochrome. It also
ceiling effect and tolerable adverse effects (Table 2) [16, causes 6-cytoreduction (6-oxycodol) and conjugation
17], with a possible further addition of reasonable cost- with glucuronic acid [21].
effectiveness. The plasma half-life of oxycodone ranges from 3 to
5 h (almost half that of morphine). This half-life is not
influenced by the route of administration (intravenous,
rectal or oral) [22]. Stable plasma levels are attained af-
Pharmacokinetics and metabolism ter 24 h (2–7 days in the case of morphine). Plasma con-
centrations are slightly higher in women because elimi-
Bioavailability nation is slower.
The high analgesic potency of oxymorphone has led
Oxycodone is a low-molecular-weight opioid that is some investigators to suggest that this metabolism is re-
more lipophilic than morphine. Its oral bioavailability is sponsible for the analgesia afforded by oxycodone, but

Table 3 Pharmacokinetic properties of oxycodone

Oral bioavailability 60–87%


Two-phase release-absorption model:
Phase one half-life 0.6 h
Phase two half-life 7h
Plasma half-life 3–5 h (stable plasma levels after 24 h)
Renal elimination After 24 h, 8–14% of free and conjugated oxycodone has been eliminated
A. Ordóñez Gallego et al.: Oxycodone 301

Table 4 Main oxycodone studies

Author No. of patients Active substances

Hagen (1997) 44 patients CRO vs. hydromorphone


Heiskanen (1997) 45 patients CRO vs. morphine CR
Citron (1998) 87 patients CRO
Mucci-Le Russo (1998) 100 patients CRO vs. morphine CR
Bruera (1998) 32 patients CRO vs. morphine CR
Kaplan (1998) 164 patients CRO vs. IRO
Parris (1998) 111 patients CRO vs. IRO
Salzman (1999) 48 patients CRO vs. IRO
Stambaugh (2001) 30 patients CRO vs. IRO

several other studies support the idea that it is oxy-


codone itself that produces the analgesic and pharmaco- Indications
dynamic effects of the opioid [23].
Oxycodone is indicated in the treatment of pain caused
Distribution and elimination
by different pathologies: neoplasia, infection, postopera-
tive pain, neuralgia (herpes zoster, trigeminal neuralgia,
Oxycodone penetrates easily into the interstitial space
diabetic neuropathy), rheumatological processes, etc.
and inside cells because of its relatively low molecular
[28–30]. In addition to its analgesic effect, it causes re-
weight and its lipophilia. A high percentage of the drug
laxation and anxiolysis, as do the majority of opioids.
remains outside the vascular compartments and is not
eliminated by the kidneys or by the liver, which con-
tributes to its slow release. Almost 45% of oxycodone
binds to plasma proteins, predominantly to albumin. Efficacy in cancer pain
This property is not dose-dependent [24].
Oxycodone and its metabolites are essentially elimi- With regard to chronic cancer pain, it should be men-
nated by the kidneys. Clearance is affected by liver and tioned that nine major studies have been published since
kidney dysfunction, although to a much lesser extent 1997, six of which were double-blind, on the efficacy
than in the case of morphine, which is why an improved and toxicity of oxycodone, with a total of 611 patients
toxicity profile has been demonstrated when morphine [31–39] (Tables 4 and 5). The results of these studies
is replaced by oxycodone. can be summarised in the following points:
After 24 h, 8–14% of free and conjugated oxy- 1. Oral oxycodone has equivalent analgesic efficacy
codone has been excreted. Noroxycodone is almost all to oral morphine, with a ratio of 1/1.5–2 in these
excreted without conjugation and oxycodone is mainly patient cohorts.
excreted as a conjugate [25]. Table 3 summarises some 2. There are also similar efficacy and adverse ef-
of the pharmacokinetic characteristics of oxycodone. fects between oral immediate-release oxycodone
(IRO) (every 3–4 h) and oral CRO (every 12 h).
3. No significant differences have been observed ei-
ther between CRO and hydromorphone, although
Mechanism of action CRO appears to have a better analgesic effect.
4. In the majority of studies, oxycodone has shown
As oxycodone is an opioid agonist, it binds to the mu, less incidence of adverse effects than morphine,
kappa and delta receptors that are coupled to the G pro- particularly in the case of long-term treatment.
teins which are distributed by the central, peripheral and
autonomous nervous systems. Oxycodone’s affinity Also, in a study that compared the combination of
with the receptors is 1/10 to 1/40 in comparison with CRO and IR morphine with standard morphine in pa-
morphine. This union triggers a series of intracellular tients with advanced cancer, there is less use of mor-
effects (second messenger) that lead to the hyperpolari- phine as rescue medication (38%) in the oxycodone
sation of the nerve cell. The adenylyl cyclase system is group [40].
inhibited, and there is a fall in the AMPc, and of ionic In a long-term study on the use of CRO in the treat-
calcium entering the cell, and an increase in potassium ment of cancer pain, it was demonstrated that the drug
ion flow. There is also a reduction in the release of neu- can be successfully used to manage cancer pain for peri-
rotransmitters, and therefore reduced transmission of ods of more than 12 weeks [33].
nerve stimulation [26, 27]. It should be stressed that the type of pain under dis-
These mechanisms are also involved in the develop- cussion here is severe or moderate cancer pain. It is also
ment of tolerance and physical dependence. interesting to note the experimental studies that are be-
302 A. Ordóñez Gallego et al.: Oxycodone

Table 5 Main oxycodone studies. Development

Author, year, Treatment regime Principal


design, variable Results
no. of patients

Experimental Control Experimental group Complications/adverse

Kaplan R et al., Oxycodone Oxycodone Mean pain Daily mean of pain Less adverse effects were
1998, double-blind, CR IR intensity intensity was similar reported in relation to the
n=164 score in both treatment groups medication in the oxycodone
(mean of 1.3±0.1 for CR group (109) than in the
oxycodone CR and for oxycodone IR group (186)
oxycodone IR) (p=0.006)

Parris et al., Oxycodone Oxycodone Mean pain Daily mean of pain In patients treated with
1998, double-blind, CR IR intensity intensity was similar oxycodone CR it was
n=111 score in both treatment groups observed that there was a
(mean of 1.4±0.1 for trend towards less episodes
oxycodone CR and of of nausea, vomiting and
1.1±0.1 for oxycodone IR) sweating. Incidents of adverse
events in patients was similar
in both treatment groups.

Bruera et al., Oxycodone Morphine VAS and Intense pain was No differences were observed
1998, double-blind, CR CR categorical controlled. No in the intensity or frequency
n=32 pain intensity statistically significant of adverse events reported in
scale differences were observed the two treatment groups.
in the VAS and CAT pain
intensity scales between
oxycodone CR and
morphine CR.

Heiskanen et al., Oxycodone Morphine Mean pain Intense pain was Patients treated with morphine
1997, double-blind, CR CR intensity controlled. No statistically presented more episodes of
n=45 score significant differences nightmares and nausea.
were observed in the VRS The most common adverse
of pain intensity between events in both groups were
oxycodone CR and constipation and sedation.
morphine CR. Constipation was more
common with oxycodone.

Mucci-LoRusso Oxycodone Morphine VAS and Intense pain was The adverse effects reported
et al., 1998, CR CR categorical controlled. No in both groups were the same
double-blind, n=101 pain intensity statistically significant as described for opioid drugs.
scale differences were observed The safety profile for
in the VAS and the oxycodone CR and
categorical pain intensity morphine CR were very
scale between oxycodone similar.
CR and morphine CR.

Lauretti et al., Oxycodone Morphine Use of More breakthrough Patients treated with
2003, double-blind, CR CR rescue medication was used by controlled-release morphine
n=26 medication patients treated with presented more episodes of
(morphine controlled-release nausea and vomiting than
immediate morphine than in patients treated with
release) patients treated with oxycodone CR (p<0.05).
controlled-release Incidence of dry mouth,
oxycodone drowsiness, hallucinations,
constipation, pruritus,
headache, anorexia, dyspnoea
and degree of acceptance of
the study drugs was similar in
both treatment groups.
A. Ordóñez Gallego et al.: Oxycodone 303

Fig. 2 Mechanism of action of oxycodone

ing undertaken with the association of morphine and lished, with studies that have found that this drug pro-
oxycodone at low doses. With reference to analgesic ef- vides greater pain relief and improved quality of life
fect, synergy has been demonstrated between morphine than a placebo [28, 44, 45].
(pure mu agonist) and oxycodone (mu, kappa and delta The number of patients needed to treat (NNT) is a
agonist), and a greater analgesic effect has been found specific treatment measurement that is used to compare
in combination than in morphine alone, with a lower in- the relative efficacy of drugs. NNT compound values
cidence of vomiting [40–42]. are evaluated in comparison with a placebo. With regard
In the treatment of cancer pain, morphine is nor- to neuropathic pain, a recent assessment of NNT has
mally used as the drug of choice, although the reasons been conducted in the most commonly used drugs [46].
for this are not based on strict criteria regarding clini- NNT was 3.3 for tricyclic antidepressants, 4.2 for anti-
cal efficacy, but on parameters such as costs, availabil- convulsants such as gabapentin and carbamazepine, 7.6
ity, etc. It has been demonstrated that morphine is not for NMDA antagonists and 2.5 for opioids. Specifically,
effective in at least 20% of patients, and treatment is the NNT for oxycodone was 2.6.
required with other opioids in order to optimise an ap- It has been demonstrated that oxycodone is effective
propriate balance between pain relief and adverse ef- in post-herpetic neuralgia [28] and in diabetic neuropa-
fects. In a recent study, patients who did not respond to thy [44, 45]. In these pathologies, it is unsatisfactory for
morphine or showed intolerance to it were shown to many patients. Oxycodone shows evidence of efficacy
achieve pain control with minimum adverse effects in in polyneuropathy, as demonstrated in the case report of
96% of cases when treatment was changed to oxy- a German patient with polyneuropathy caused by inter-
codone CR [43]. feron-alpha. In this case, the patient’s pain score fell
from 8 to 2 (on a scale of 10) after three weeks of oxy-
codone CR therapy, with a significant improvement in
Efficacy in neuropathic pain the patient’s quality of life [47].

Neuropathic pain is an important issue because the ma-


jority of patients with cancer pain suffer neuropathic Efficacy in somatic pain
pain due to nerve compression from the tumour, or
mixed pain (nociceptive+neuropathic). The efficacy of Oxycodone’s effectiveness in improving somatic pain
oxycodone in neuropathic pain has been well estab- has been well documented, with proven evidence pro-
304 A. Ordóñez Gallego et al.: Oxycodone

vided by studies conducted on osteoarthritis, back pain


and pre- and post-operative pain. Presentation and dosage

Osteoarthritic pain Leaving aside presentations that were used in the past,
Different studies have confirmed that in the treatment of and in fact are still used in some countries (parenteral,
pain in osteoarthritic patients, oxycodone is more effective rectal, nasal presentations), it is clear that the great ma-
than placebo and comparable with the use of oxycodone jority of studies are conducted with oral oxycodone in
IR. Furthermore, these studies not only evaluated improved tablets or capsules, with or without associated NSAIDs.
pain relief, but also improved sleep, mood and in general At present, there are just two types of oral presentation:
how pain interferes in the patient’s quality of life [48–53]. immediate release and slow release. Both are already
available in Spain [4].
Back pain In Spain, oxycodone hydrochloride is marketed un-
Several studies have been published on the use of oxy- der the name OxyContin®, in 10-, 20-, 40- and 80-mg
codone CR vs. oxycodone IR in the treatment of back tablets, to be taken every 12 h.
pain [29], and also using the combination of oxycodone CRO tablets should be taken whole and never be
and acetaminophen [54]. Recently, two observational broken, chewed or crushed because this could lead to a
studies demonstrated that oxycodone CR is more effec- rapid release and absorption of the opioid, and increased
tive than standard analgesics [55, 56] and also that pa- toxicity. There is no interference with foods, unlike the
tients on oxycodone CR had improved rehabilitation. IRO presentation [65]. Furthermore, release does not
appear to be dependent on gastric pH.
Post-operative pain Generally, the dose is commenced at 10 mg/12 h
Oxycodone CR is not recommended during the first 24 when used as the first opioid. The therapeutic protocol
h post-operatively, although oxycodone can be used i.v. should be identical in all patients, including the elderly
during this period. and patients with moderate liver or kidney impairment.
However, there are studies that report the efficacy of In paediatric patients, the FDA has only approved oxy-
oxycodone CR in post-operative pain, with less seda- codone in its CRO presentation, and only in children
tion, sleep alterations or vomiting following the opera- over the age of 12.
tion, in patients who had undergone cruciate ligament Oxycodone does not have a ceiling effect and the
surgery [57]. Oxycodone CR achieves effective analge- dose can be increased gradually, provided that adverse
sia during rehabilitation following knee arthroplasty effects are monitored. Immediate release oxycodone is
[58]. The efficacy of oxycodone CR and tramadol fol- marketed in Spain under the name of OxyNorm® and is
lowing trauma surgery has been compared [59]. Oxy- presented in 5-, 10- and 20-mg capsules, and in a con-
codone for post-operative pain has also been compared centrated oral solution of 10 mg/ml. Breakthrough pain
with standard analgesia, including epidural anaesthesia should be treated with immediate release oxycodone.
[60, 61]. The patients treated with oxycodone spent less
days in hospital, and were mobilised before those treat-
ed with epidural anaesthesia.
Opioid rotation

Efficacy in visceral pain Opioid rotation refers to replacing one opioid with an-
other with the aim of increasing analgesic efficacy and
The need to improve recognition and treatment of vis- reducing toxicity. When rotation is done due to intolera-
ceral pain has brought about the development of experi- ble toxicity, the theoretical conversion dose must be re-
mental pain models, which offer the possibility of ex- duced by 25–30%. If it is done for insufficient pain con-
ploring pain under controlled conditions [62]. trol, then 100% of the theoretical conversion dose
In an experimental model evoking cutaneous, should be prescribed [66].
muscular and visceral pain, the analgesic effects of To calculate the dose, the following steps should be
oxycodone, morphine and placebo were compared in followed:
patients with chronic pancreatitis [63]. It was demon- 1. Calculate the total dose of opioid that the patient
strated that oxycodone was more effective than mor- is taking over 24 h, including extra doses for
phine and the placebo in mechanical muscular pain, me- breakthrough pain.
chanical and heat cutaneous pain, and thermal pain in 2. Obtain the conversion dose of the new opioid us-
the oesophagus. In another study conducted on healthy ing a conversion table (this provides an approxi-
volunteers, oxycodone and morphine afforded better mate figure).
analgesia than the placebo in all tissues [64]. 3. In general, reduce the dose obtained by 25% to
Oxycodone’s enhanced efficacy in visceral pain is make allowance for incomplete cross tolerance
due to its activity as a κ receptor agonist. (except when changing from morphine to trans-
A. Ordóñez Gallego et al.: Oxycodone 305

Table 6 Approximate equianalgesic doses of CRO in relation Table 7 Commonest adverse effects of oxycodone
to other opioids
Constipation 25–30%
Oxycodone 1 Nausea 25%
Codeine 7–20 Drowsiness 25%
Transdermal fentanyl 1 Dizziness 15%
Transdermal buprenorphine 0.6 Vomiting 10–15%
Hydromorphone 0.25 Pruritus 10–15%
Methadone 0.75
Morphine 2
Oxymorphone 0.5
less pruritus have been observed in oxycodone in com-
parison with morphine [70–72].
Doses of more than 60 mg/day should be gradually
dermal fentanyl). A 50% reduction should be cal- reduced because sudden withdrawal may trigger the on-
culated in the case of opioid-induced neurotoxici- set of abstinence syndrome. Oxycodone may also affect
ty, the elderly and in severe heart, liver or kidney cognitive skills and increase levels of serum prolactin.
disease. These are typical phenomena of agonist opioids [73].
4. Establish the maintenance dose. Cases of addiction are very rare.
5. Calculate the rescue dose, which should be
5–15% of the total dose [67].
Oxycodone is a very useful drug for use in opioid Conclusions
rotation. Although there are no studies that provide con-
clusive evidence, Table 6 shows a series of figures for 1. Oxycodone is a semi-synthetic opioid, with ago-
practical purposes. nist activity on the mu, kappa and delta receptors.
As mentioned earlier, the equianalgesic ratio of oxy- It is a step three analgesic and is therefore used to
codone and morphine is 1:1.5–2 [68]. With hydromor- treat moderate and severe cancer pain.
phone, a drug that is shortly to be introduced in Spain, 2. Some of its pharmacokinetic characteristics are:
the ratio is 1:4 [69]. oral bioavailability of 60–87%, two-phase re-
lease-absorption process, and plasma half-life of
3–5 h.
3. The mechanism of action follows the normal opi-
Adverse effects oid process: binding to a receptor, inhibition of
the adenylyl cyclase system and hyperpolarisa-
The adverse effects of oxycodone are those that are typ- tion of the nerve cell, with reduced excitability.
ically found in opioids: constipation, nausea and drowsi- Oxycodone is indicated for moderate to intense
ness are the three most common (Table 7). Constipation chronic pain in different types of pathologies, in-
occurs in 25–30% of patients and tends to be more cluding cancer and non-cancer pain.
marked than in morphine. Nausea is also observed in 4. Oral oxycodone has a similar efficacy to oral
25–30% of patients and drowsiness in 25%. Vomiting, morphine, with an opioid conversion ratio of
pruritus and dizziness are observed in 5–15% of pa- 1:1.5–2.
tients taking oxycodone. Other effects such as 5. In Spain oxycodone hydrochloride slow release
headaches, dry mouth, hallucinations and bronchospasm has recently been introduced for oral administra-
present in less than 5%. tion every 12 h. It is also available in capsules,
Incidence and intensity of these side effects tend to and in immediate release concentrated solution.
decrease in the course of time, as is the case of other 6. The side effects of oxycodone are the same as for
opioids. Incidence is generally similar to that observed all opioid substances. It appears that oxycodone
in morphine and hydromorphone, although in some may cause less nausea, vomiting, hallucinations
studies less nausea and vomiting, less hallucinations and and pruritus than morphine.

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