Clin Transl Oncol (2007) 9:298-307
REVIEW
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
agonist activity on mu, kappa and delta receptors.
Equivalence with regard to morphine is 1:2. Its effect
commences one hour after administration and lasts for
12 h in the controlled-release formulation. Plasma half-
life is 3–5 h (half that of morphine) and stable plasma
levels are reached within 24 h (2–7 days for morphine).
Oral bioavailability ranges from 60 to 87%, and plasma
protein binding is 45%. Most of the drug is metabolised
in the liver, while the rest is excreted by the kidney
along with its metabolites. The two main metabolites are
oxymorphone – which is also a very potent analgesic –
and noroxycodone, a weak analgesic. Oxycodone me-
tabolism is more predictable than that of morphine, and
therefore titration is easier. Oxycodone has the same
mechanism of action as other opioids: binding to a re-
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-
ment of cancer pain. Long-term administration may be
associated with less toxicity in comparison with mor-
phine. In the future, both opioids could be used simulta-
neously at low doses to reduce toxicity. It does not ap-
pear that there are any differences between immediate
and slow-release oxycodone, except their half-life is 3–4
h, and 12 h, respectively. In Spain, controlled-release
oxycodone (OxyContin®) is marketed as 10-, 20-, 40-
or 80-mg tablets for b.i.d. administration. Tablets must
be taken whole and must not be broken, chewed or
A. Ordóñez Gallego (쾷)
Medical Oncology Service
“La Paz” University Hospital Madrid
Cátedra de Oncología y Medicina Paliativa
Universidad Autónoma de Madrid
Madrid, Spain
E-mail: amalio2@hotmail.com
Received 18 July 2006 / Accepted 8 February 2007
DOI 10.1007/s12094-007-0057-9
crushed. There is no food interference. The initial dose
is 10 mg b.i.d. for new treatments and no dose reduction
is needed in the elderly or in cases of moderate hepatic
or renal failure. Immediate-release oxycodone
(OxyNorm®) is also available in capsules and oral solu-
tion. Side effects are those common to opioids: mainly
nausea, constipation and drowsiness. Vomiting, pruritus
and dizziness are less common. The intensity of these
side effects tends to decrease over the course of time.
Oxycodone causes somewhat less nausea, hallucinations
and pruritus than morphine.
Key words Oxycodone • Opioid • Pain
Ordóñez Gallego A, González Barón M, Espinosa Arranz E
(2007) Oxycodone: a pharmacological and clinical review.
Clin Transl Oncol 9:298-307
Introduction
It is estimated that 70–90% of patients with advanced
cancer will suffer significant pain (moderate to severe)
in its different forms: acute or chronic, somatic or vis-
ceral, nociceptive or neuropathic, etc. In the majority of
cases, the pain is chronic, nociceptive and somatic [1,
2]. Some tumours inevitably present with pain through-
out the process (digestive, bone and genitourinary tu-
mours), while other types, the minority, may develop for
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].
Pain should not be viewed as an isolated symptom,
as it is the cause of functional disabilities, changing per-
sonal relationships and emotional disorders, all of which
have a marked negative effect on the quality of life of
these patients.
When treating pain it is essential to follow certain
general principles. However, these principles are not re-
spected in the majority of cases, and it can be confirmed
A. Ordóñez Gallego et al.: Oxycodone
Table 1 General principles of analgesia
01. Choose a drug from each step and get to know it in depth.
02. Drug potency must match pain intensity.
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.
07. Side effects must be prevented and treated.
08. Never forget to use coadjuvant drugs.
09. Provide clear, written instructions.
10. Treatment efficacy must be assessed continuously.
that nowadays many oncologists and Primary Health
Care doctors do not achieve adequate analgesia in these
patients. Some of these principles are explained in Table
1. It should also be noted that pain is underevaluated on-
ly too often in patients, and the use of placebos is not
indicated.
According to the WHO pain ladder, opioids are clas-
sified on the second and third steps. Within the opioid
group, oxycodone is a drug that has been available in
Spain since 2004 (although this molecule has been pres-
ent in other countries since 1917) [4].
Much of the information in this article, which we are
devoting to oxycodone, comes from an excellent review
conducted by Domínguez et al., published in the journal
Medicina Paliativa [5].
It should also be mentioned that in the last few years
in our department we have been very interested in using
Fig. 1 Structural formula of oxycodone
299
major opioids from WHO step 2, following NSAID ad-
ministration, prescribing doses in accordance with the
visual analogue scale (VAS) [6–8].
General remarks
Oxycodone (14-hydroxy-7,8-dihydrocodeinone) is a
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.
Its structural formula is shown in Fig. 1. The struc-
tural differences between oxycodone and morphine
mean that oxycodone initially undergoes less metabo-
lism in comparison with morphine and therefore it has
greater bioavailability (60–87%) [9]. Also, the differ-
ences from morphine’s molecules mean that there is less
immunodepression than in other opioids [10].
There are various experimental findings that suggest
that oxycodone’s intrinsic antinociceptive effect is mediat-
ed by the kappa and mu receptors alike, unlike morphine,
which mainly acts through the mu receptors [11, 12].
In the USA, medical use of opioids increased 400%
between 1996 and 2000. At present, 86% of the market
consists of four opioids: (1) controlled-release hydro-
morphone, (2) controlled-release morphine, (3) con-
trolled-release oxycodone (CRO) and (4) transdermal
fentanyl [13].
300
Table 2 Some characteristics of the ideal opioid
Short half-life
Long-lasting action
Predictable pharmacokinetics
Absence of active metabolites
No ceiling effect
Few adverse effects
The first article on oxycodone was published in Ger-
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
formulations in Europe for seven years: controlled-re-
lease tablets, immediate release capsules, liquid and
parenteral preparations. In Spain, CRO tablets appeared
in 2004, immediate-release capsules appeared in 2005
and a liquid formulation of the immediate-release ver-
sion has been available on the market since the begin-
ning of 2006.
WHO classifies oxycodone as a step 2 drug when
used with a NSAID adjuvant, which means that it has a
ceiling effect, but it should be remembered that oxy-
codone is actually a major opioid drug to be used in se-
vere cancer pain; it is not a codeine-like substance for
mild or moderate pain [15].
It is accepted that the ratio for opioid conversion re-
garding oxycodone and morphine is 1:2, although clini-
cal studies reviewed suggested an equivalence ranging
from 1/1.4 to 1/1.8. Clinical analgesia commences with-
in one hour and in the controlled-release formulation
analgesia lasts for 12 h.
CRO has certain characteristics that near the defini-
tion of an ideal opioid: short half-life, long-lasting ac-
tion, absence of active metabolites, easy to titrate, no
ceiling effect and tolerable adverse effects (Table 2) [16,
17], with a possible further addition of reasonable cost-
effectiveness.
Pharmacokinetics and metabolism
Bioavailability
Oxycodone is a low-molecular-weight opioid that is
more lipophilic than morphine. Its oral bioavailability is
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
at least twice as great as that of morphine (60–87%).
The high correlation between dose, plasma concentra-
tion and pharmacological effects makes its pharmacoki-
netics more predictable [9].
This high bioavailability may be due to the methyl
group at position 3, which prevents the liver stage of
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
[19].
Absorption and metabolism
The CRO formulation consists of two acrylic polymers
that mean that release and absorption occur in two phas-
es. In the first phase, the gastrointestinal secretions
erode the tablet surface in order to permit a fast release
of oxycodone and dissolution of the same. Its action
commences within one hour, and its half-life is 0.6 h,
affecting 38% of the dose. Then there is a second phase
of sustained release that can last 12 h, with a half-life of
6.9 h, and this phase affects the remaining 62% of the
dose [20].
Liver metabolism then takes place, with the produc-
tion of two metabolites: oxymorphone (resulting from
O-demethylation), which is a potent analgesic in mini-
mum concentrations, and noroxycodone (resulting from
N-demethylation), which circulates in high concentra-
tions and has a mild analgesic action. These metabolites
are excreted through the kidneys.
The O-demethylation that occurs in the liver to pro-
duce the oxymorphone is a reaction that is catalysed by
the isoenzyme CYP2D6 of the P450 cytochrome. It also
causes 6-cytoreduction (6-oxycodol) and conjugation
with glucuronic acid [21].
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-
ter 24 h (2–7 days in the case of morphine). Plasma con-
centrations are slightly higher in women because elimi-
nation is slower.
The high analgesic potency of oxymorphone has led
some investigators to suggest that this metabolism is re-
sponsible for the analgesia afforded by oxycodone, but
A. Ordóñez Gallego et al.: Oxycodone
Table 4 Main oxycodone studies
Author No. of patients
Hagen (1997) 44 patients
Heiskanen (1997) 45 patients
Citron (1998) 87 patients
Mucci-Le Russo (1998) 100 patients
Bruera (1998) 32 patients
Kaplan (1998) 164 patients
Parris (1998) 111 patients
Salzman (1999) 48 patients
Stambaugh (2001) 30 patients
several other studies support the idea that it is oxy-
codone itself that produces the analgesic and pharmaco-
dynamic effects of the opioid [23].
Distribution and elimination
Oxycodone penetrates easily into the interstitial space
and inside cells because of its relatively low molecular
weight and its lipophilia. A high percentage of the drug
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.
This property is not dose-dependent [24].
Oxycodone and its metabolites are essentially elimi-
nated by the kidneys. Clearance is affected by liver and
kidney dysfunction, although to a much lesser extent
than in the case of morphine, which is why an improved
toxicity profile has been demonstrated when morphine
is replaced by oxycodone.
After 24 h, 8–14% of free and conjugated oxy-
codone has been excreted. Noroxycodone is almost all
excreted without conjugation and oxycodone is mainly
excreted as a conjugate [25]. Table 3 summarises some
of the pharmacokinetic characteristics of oxycodone.
Mechanism of action
As oxycodone is an opioid agonist, it binds to the mu,
kappa and delta receptors that are coupled to the G pro-
teins which are distributed by the central, peripheral and
autonomous nervous systems. Oxycodone’s affinity
with the receptors is 1/10 to 1/40 in comparison with
morphine. This union triggers a series of intracellular
effects (second messenger) that lead to the hyperpolari-
sation of the nerve cell. The adenylyl cyclase system is
inhibited, and there is a fall in the AMPc, and of ionic
calcium entering the cell, and an increase in potassium
ion flow. There is also a reduction in the release of neu-
rotransmitters, and therefore reduced transmission of
nerve stimulation [26, 27].
These mechanisms are also involved in the develop-
ment of tolerance and physical dependence.
301
Active substances
CRO vs. hydromorphone
CRO vs. morphine CR
CRO
CRO vs. morphine CR
CRO vs. morphine CR
CRO vs. IRO
CRO vs. IRO
CRO vs. IRO
CRO vs. IRO
Indications
Oxycodone is indicated in the treatment of pain caused
by different pathologies: neoplasia, infection, postopera-
tive pain, neuralgia (herpes zoster, trigeminal neuralgia,
diabetic neuropathy), rheumatological processes, etc.
[28–30]. In addition to its analgesic effect, it causes re-
laxation and anxiolysis, as do the majority of opioids.
Efficacy in cancer pain
With regard to chronic cancer pain, it should be men-
tioned that nine major studies have been published since
1997, six of which were double-blind, on the efficacy
and toxicity of oxycodone, with a total of 611 patients
[31–39] (Tables 4 and 5). The results of these studies
can be summarised in the following points:
1. Oral oxycodone has equivalent analgesic efficacy
to oral morphine, with a ratio of 1/1.5–2 in these
patient cohorts.
2. There are also similar efficacy and adverse ef-
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
CRO appears to have a better analgesic effect.
4. In the majority of studies, oxycodone has shown
less incidence of adverse effects than morphine,
particularly in the case of long-term treatment.
Also, in a study that compared the combination of
CRO and IR morphine with standard morphine in pa-
tients with advanced cancer, there is less use of mor-
phine as rescue medication (38%) in the oxycodone
group [40].
In a long-term study on the use of CRO in the treat-
ment of cancer pain, it was demonstrated that the drug
can be successfully used to manage cancer pain for peri-
ods of more than 12 weeks [33].
It should be stressed that the type of pain under dis-
cussion here is severe or moderate cancer pain. It is also
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
Fig. 2 Mechanism of action of oxycodone
ing undertaken with the association of morphine and
oxycodone at low doses. With reference to analgesic ef-
fect, synergy has been demonstrated between morphine
(pure mu agonist) and oxycodone (mu, kappa and delta
agonist), and a greater analgesic effect has been found
in combination than in morphine alone, with a lower in-
cidence of vomiting [40–42].
In the treatment of cancer pain, morphine is nor-
mally used as the drug of choice, although the reasons
for this are not based on strict criteria regarding clini-
cal efficacy, but on parameters such as costs, availabil-
ity, etc. It has been demonstrated that morphine is not
effective in at least 20% of patients, and treatment is
required with other opioids in order to optimise an ap-
propriate balance between pain relief and adverse ef-
fects. In a recent study, patients who did not respond to
morphine or showed intolerance to it were shown to
achieve pain control with minimum adverse effects in
96% of cases when treatment was changed to oxy-
codone CR [43].
Efficacy in neuropathic pain
Neuropathic pain is an important issue because the ma-
jority of patients with cancer pain suffer neuropathic
pain due to nerve compression from the tumour, or
mixed pain (nociceptive+neuropathic). The efficacy of
oxycodone in neuropathic pain has been well estab-
303
lished, with studies that have found that this drug pro-
vides greater pain relief and improved quality of life
than a placebo [28, 44, 45].
The number of patients needed to treat (NNT) is a
specific treatment measurement that is used to compare
the relative efficacy of drugs. NNT compound values
are evaluated in comparison with a placebo. With regard
to neuropathic pain, a recent assessment of NNT has
been conducted in the most commonly used drugs [46].
NNT was 3.3 for tricyclic antidepressants, 4.2 for anti-
convulsants such as gabapentin and carbamazepine, 7.6
for NMDA antagonists and 2.5 for opioids. Specifically,
the NNT for oxycodone was 2.6.
It has been demonstrated that oxycodone is effective
in post-herpetic neuralgia [28] and in diabetic neuropa-
thy [44, 45]. In these pathologies, it is unsatisfactory for
many patients. Oxycodone shows evidence of efficacy
in polyneuropathy, as demonstrated in the case report of
a German patient with polyneuropathy caused by inter-
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
the patient’s quality of life [47].
Efficacy in somatic pain
Oxycodone’s effectiveness in improving somatic pain
has been well documented, with proven evidence pro-
304
vided by studies conducted on osteoarthritis, back pain
and pre- and post-operative pain.
Osteoarthritic pain
Different studies have confirmed that in the treatment of
pain in osteoarthritic patients, oxycodone is more effective
than placebo and comparable with the use of oxycodone
IR. Furthermore, these studies not only evaluated improved
pain relief, but also improved sleep, mood and in general
how pain interferes in the patient’s quality of life [48–53].
Back pain
Several studies have been published on the use of oxy-
codone CR vs. oxycodone IR in the treatment of back
pain [29], and also using the combination of oxycodone
and acetaminophen [54]. Recently, two observational
studies demonstrated that oxycodone CR is more effec-
tive than standard analgesics [55, 56] and also that pa-
tients on oxycodone CR had improved rehabilitation.
Post-operative pain
Oxycodone CR is not recommended during the first 24
h post-operatively, although oxycodone can be used i.v.
during this period.
However, there are studies that report the efficacy of
oxycodone CR in post-operative pain, with less seda-
tion, sleep alterations or vomiting following the opera-
tion, in patients who had undergone cruciate ligament
surgery [57]. Oxycodone CR achieves effective analge-
sia during rehabilitation following knee arthroplasty
[58]. The efficacy of oxycodone CR and tramadol fol-
lowing trauma surgery has been compared [59]. Oxy-
codone for post-operative pain has also been compared
with standard analgesia, including epidural anaesthesia
[60, 61]. The patients treated with oxycodone spent less
days in hospital, and were mobilised before those treat-
ed with epidural anaesthesia.
Efficacy in visceral pain
The need to improve recognition and treatment of vis-
ceral pain has brought about the development of experi-
mental pain models, which offer the possibility of ex-
ploring pain under controlled conditions [62].
In an experimental model evoking cutaneous,
muscular and visceral pain, the analgesic effects of
oxycodone, morphine and placebo were compared in
patients with chronic pancreatitis [63]. It was demon-
strated that oxycodone was more effective than mor-
phine and the placebo in mechanical muscular pain, me-
chanical and heat cutaneous pain, and thermal pain in
the oesophagus. In another study conducted on healthy
volunteers, oxycodone and morphine afforded better
analgesia than the placebo in all tissues [64].
Oxycodone’s enhanced efficacy in visceral pain is
due to its activity as a κ receptor agonist.
A. Ordóñez Gallego et al.: Oxycodone
Presentation and dosage
Leaving aside presentations that were used in the past,
and in fact are still used in some countries (parenteral,
rectal, nasal presentations), it is clear that the great ma-
jority of studies are conducted with oral oxycodone in
tablets or capsules, with or without associated NSAIDs.
At present, there are just two types of oral presentation:
immediate release and slow release. Both are already
available in Spain [4].
In Spain, oxycodone hydrochloride is marketed un-
der the name OxyContin®, in 10-, 20-, 40- and 80-mg
tablets, to be taken every 12 h.
CRO tablets should be taken whole and never be
broken, chewed or crushed because this could lead to a
rapid release and absorption of the opioid, and increased
toxicity. There is no interference with foods, unlike the
IRO presentation [65]. Furthermore, release does not
appear to be dependent on gastric pH.
Generally, the dose is commenced at 10 mg/12 h
when used as the first opioid. The therapeutic protocol
should be identical in all patients, including the elderly
and patients with moderate liver or kidney impairment.
In paediatric patients, the FDA has only approved oxy-
codone in its CRO presentation, and only in children
over the age of 12.
Oxycodone does not have a ceiling effect and the
dose can be increased gradually, provided that adverse
effects are monitored. Immediate release oxycodone is
marketed in Spain under the name of OxyNorm® and is
presented in 5-, 10- and 20-mg capsules, and in a con-
centrated oral solution of 10 mg/ml. Breakthrough pain
should be treated with immediate release oxycodone.
Opioid rotation
Opioid rotation refers to replacing one opioid with an-
other with the aim of increasing analgesic efficacy and
reducing toxicity. When rotation is done due to intolera-
ble toxicity, the theoretical conversion dose must be re-
duced by 25–30%. If it is done for insufficient pain con-
trol, then 100% of the theoretical conversion dose
should be prescribed [66].
To calculate the dose, the following steps should be
followed:
1. Calculate the total dose of opioid that the patient
is taking over 24 h, including extra doses for
breakthrough pain.
2. Obtain the conversion dose of the new opioid us-
ing a conversion table (this provides an approxi-
mate figure).
3. In general, reduce the dose obtained by 25% to
make allowance for incomplete cross tolerance
(except when changing from morphine to trans-
A. Ordóñez Gallego et al.: Oxycodone 305

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

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