Oxycodone Hydrochloride

Registered South African indications:

• Pain - moderate to severe

Contraindications

South African recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding (srt, cap)
• Severe renal impairment
  - CrCl<10ml/min (cap, srt)
  - CrCl<30ml/min (inj)
• Moderate to severe hepatic impairment
• Respiratory depression (inj)
• Respiratory depression with hypoxia and/or hypercapnia (srt)
• Severe respiratory depression with hypoxia and/or hypercapnia (cap)
• Head injury
• Paralytic ileus
• Acute abdomen
• Delayed gastric emptying
• Chronic obstructive lung disease (srt, inj)
• Severe chronic obstructive lung disease (cap)
• Cor pulmonale
• Chronic bronchial asthma
• Hypercarbia (inj)
• Chronic constipation
• Pre-operative use or for the first 12-24hrs post-operatively (srt)
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use
• Galactose intolerance, e.g., galactosaemia (srt)
• Lapp lactase deficiency (srt)
• Glucose-galactose malabsorption (srt)

Recommendations in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Moderate to severe hepatic impairment (cap)
• Paralytic ileus
• Severe respiratory depression with hypoxia
  - Hypercapnia (srt)
• Acute abdomen (cap, inj)
• Delayed gastric emptying (cap)
• Severe chronic obstructive pulmonary disease
• Cor pulmonale
• Severe bronchial asthma
• Chronic constipation (cap, inj)
• Elevated carbon dioxide levels in the blood (cap, inj)

Cautions

South African recommendations

• Breastfeeding (inj)
• Mild to moderate renal impairment
• Mild hepatic impairment
• Debilitated elderly and infirm patients
• Disease of the biliary tract
• Severe impaired pulmonary function (cap)
  - Severe pulmonary disease (srt)
• Parenteral administration of oral dosage forms (cap, srt)
  (Potentially fatal outcomes)
• Hypothyroidism
• Signs and symptoms of respiratory depression
• Sleep apnoea
• Pre-existing sleep apnoea
  - Central sleep apnoea
• Sleep-related hypoxaemia
• Risk of tolerance and physical dependence
• Abrupt withdrawal
• Psychological dependence (addiction)
• Opioid dependence
• History of substance and/or alcohol abuse
• Prolonged use
• Raised intracranial pressure
• Reduced level of consciousness of uncertain origin (cap,inj)
• Hypotension
• Hypovolaemia
• Toxic psychosis
• Pancreatitis
• Inflammatory bowel disorders
• Prostatic hypertrophy
• Adrenocortical insufficiency
• Addison’s disease
• Myxoedema
• Possibility of paralytic ileus occrring
• Cordotomy or other pain relieving surgical procedures (cap, srt)
  - 6 hours before or within the first 12-24 hours post-operatively (cap)
• Post abdominal surgery (cap)
• Underlying gastrointestinal disorders such as oesophageal cancer or colon cancer with a small gastrointestinal lumen (srt)
• Predisposing factors for bowel obstruction (srt)
• Those who have difficulty swallowing (srt)
• Alcoholism
• Delirium tremens
• Use of 80mg dosage in opioid naïve patients (srt)
  (Potentially fatal outcomes)
• Coadministration with benzodiazepines, or other CNS depressants
• May impair ability to drive and operate machinery

Recommendations in other jurisdictions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment (inj,srt)
• Debilitated elderly
• Opioid-dependent patients
• Those at risk of tolerance
• Those at risk of physical dependence
• Psychological dependence
• Severely impaired pulmonary (respiratory) function
• Myxoedema
• Hypothyroidism
• Addison’s disease
• Toxic psychosis
• Prostatic hypertrophy
• Adrenocortical insufficiency (cap,inj)
• Alcoholism
• Delirium tremens
• Diseases of the biliary tract
• Pancreatitis
• Possibility of paralytic ileus occrring
• Pre-operatively and within the first 12-24 hours post-operatively (cap,inj)
• Post abdominal surgery (inj,cap)
• Additional pain-relieving procedures (e.g., surgery, plexus blockade) and for 6 hours prior to the intervention (cap)
• Inflammatory bowel disorders (cap,inj)
• Obstructive and inflammatory intestinal diseases (srt)
• Hypotension
• Hypovolaemia
• Raised intracranial pressure
• Intracranial lesions
• Head injury
• Reduced level of consciousness of uncertain origin
• Risk of respiratory depression
  - Sleep related breathing disorders
  - Central sleep apnoea
  - Sleep-related hypoxemia
  - Sleep apnoea
• Personal or a family history (parents or siblings) of substance use disorders
  - Including alcohol use disorder
  - Current tobacco users
• Personal history of other mental health disorders
  - Major depression
  - Anxiety
  - Personality disorders
• Drug-seeking behaviour (e.g. too early requests for refills)
• Prolonged use
• Abrupt withdrawal
• Coadministration of sedative agents such as benzodiazepines or related agents
• Coadministration of monoamine oxidase inhibitors
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrose-isomaltase insufficiency
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap, srt, inj

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Pain - moderate to severe
- In those with cancer
- Post-operative pain after gastrointestinal function has returned
Pain requiring the use of a strong opioid analgesic - severe
- Opioid naïve patients
- Pain not controlled by weaker opioids

• Oral (cap): Initial: 5mg, 4-6hrly; Titrate carefully as frequently as once a day, if necessary, to achieve pain relief; Max: 400mg/24hrs

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The majority of patients will not require a daily dose greater than 400mg. However, a few patients may require higher doses

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• Oral (srt): Initial: 5-10mg, 12hrly; Titrate carefully as frequently as once a day, in 25-50% increments, if necessary, to achieve pain relief (unless unmanageable adverse drug reactions prevent this); Maintenance: 5-80mg, 12hrly either alone or in combination to achieve pain relief; Max: 200mg, 12hrly

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For the majority of patients, the maximum dose is 200mg, 12hrly. However, a few patients may require higher doses. Doses in excess of 1000mg daily have been recorded

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• IV: Bolus: 1-10mg, slowly over 1-2min, no less than 4hrly; Titrate gradually if analgesia is inadequate or if pain severity increases
  OR
• IV: Infusion: Initial: 2mg/hr; Titrate gradually if analgesia is inadequate or if pain severity increases
  OR
• IV: PCA: Bolus: 0.03mg/kg, administered with a minimum lock-out time of 5min

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Increasing severity of pain will require an increased dose of oxycodone capsules and prolonged release tablets. The need for escape medication more than twice a day indicates that the dosage of oxycodone prolonged-release tablets should be increased

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Oxycodone capsules and prolonged release tablets should be swallowed whole and not chewed

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IV: Dilute to 1mg/ml in 0.9% saline, 5% dextrose or water for injections

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The dose should be adjusted according to the severity of pain, the total condition of the patient and previous or concurrent medication

---

When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal

---

See additional prescribing points for transferring patients between oral and parenteral oxycodone; and conversion from morphine

---

Indications and dosages registered in other jurisdictions

Pain - moderate to severe
- In those with cancer
- Post-operative pain
Pain requiring the use of a strong opioid analgesic - severe

• Oral (cap): Initial: 5mg, 4-6hrly; Titrate carefully as frequently as once a day, if necessary, to achieve pain relief (unless unmanageable adverse drug reactions prevent this)
• IV: Bolus: 1-10mg, slowly over 1-2min, no less than 4hrly; Titrate gradually if analgesia is inadequate or if pain severity increases
  OR
• IV: Infusion: Initial: 2mg/hr; Titrate gradually if analgesia is inadequate or if pain severity increases
  OR
• IV: PCA: Bolus: 0.03mg/kg, administered with a minimum lock-out time of 5min
  OR
• SC: Bolus: Initial: 5mg, 4hrly as required; Titrate gradually if analgesia is inadequate or if pain severity increases

- Opioid naïve patients

• Oral (cap): Initial: 5mg, 4-6hrly; Titrate carefully as frequently as once a day, if necessary, to achieve pain relief (unless unmanageable adverse drug reactions prevent this)
• SC: Infusion: Initial: 7.5mg/day; Titrate gradually according to symptom control

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The dosage is dependent on the severity of the pain, and the patient's previous history of analgesic requirements

---

Prior to starting treatment with opioids (oral), a discussion should be held with patients to put in place a strategy for ending treatment with oxycodone in order to minimise the risk of addiction and drug withdrawal syndrome

---

Dilute to 1mg/ml in 0.9% saline, 5% dextrose or water for injections for IV bolus, infusion and PCA, as well as SC infusion dosages; Use as 10mg/ml concentration for SC bolus dosage

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Pain - severe
- Which can be adequately managed only with opioid analgesics
- Opioid naïve patients or those whose pain is not controlled by weaker opioids

• Oral (srt): Initial: 10mg, 12hrly; Titrate up to 20mg, 12hrly according to the intensity of pain and the patient's individual susceptibility, adjusting dosage in steps of approximately one third of the daily dose until the desired effect is obtained

- Non-malignant pain

• Oral (srt): 40mg/day is generally sufficient; Titrating up to higher dosages may be necessary

- Cancer-related pain

• Oral (srt): 80-120mg/day; May be increased up to 400mg/day; Higher doses should be decided individually, balancing efficacy with the tolerance and risk of undesirable effects

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Patients already receiving opioids may start treatment with higher dosages taking into account their experience with former opioid therapies, see additional prescribing points

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Oxycodone prolonged-release tablets should not be taken longer than necessary. If long-term treatment is necessary due to the type and severity of the illness, careful and regular monitoring is required to determine whether and to what extent treatment should be continued

---

When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal

---

Patients already receiving opioids may start treatment with higher dosages of oxycodone prolonged-release tablets, taking into account their experience with former opioid therapies

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Some patients who receive oxycodone prolonged-release tablets following a fixed schedule additionally need rapid release analgesics as rescue medication in order to control breakthrough pain. Oxycodone prolonged-release tablets are not indicated for the treatment of breakthrough pain. The single dose of the rescue medication should amount to 1/4 of the equianalgesic daily dose of oxycodone prolonged-release tablets and can be administered every 6 hours. Use of the rescue medication more than twice daily indicates that the dose of oxycodone prolonged-release tablets needs to be increased. The dose should not be adjusted more often than once every 1-2 days until a stable 12-hour dose is reached. The aim is a patient-specific 12 hourly dose maintaining adequate analgesia with tolerable undesirable effects and as little rescue medication as possible for as long as pain control is needed.

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See additional prescribing points for transferring patients between oral and parenteral oxycodone; and conversion from morphine

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Not established for use in children below 18 years

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Indications and dosages registered in other jurisdictions

Not established for use in children below 18 years (inj, cap)

Pain - severe
- Which can be adequately managed only with opioid analgesics
- Opioid naïve patients or those whose pain is not controlled by weaker opioids
- Non-malignant pain
- Cancer-related pain

Younger than 12 years

• Oral (srt): Not established for use

Older than 12 years

• Oral (srt): See adult dosages

Pregnancy

South African recommendations

• Contraindicated
• Oxycodone is not recommended for the use in pregnancy nor during labour
• Infants born to mothers who have received opioids during pregnancy should be monitored for respiratory depression
• Prolonged use of oxycodone during pregnancy can result in neonatal opioid withdrawal syndrome

Recommendations in other jurisdictions

• Caution; not recommended
  Capsules
• Oxycodone capsules are not recommended for use in pregnancy nor during labour
• There are limited data from the use of oxycodone in pregnant women
• Regular use in pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate
• If opioid use is required for a prolonged period in pregnant women, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
• Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available
  Slow release tablets
• Use of this agent should be avoided to the extent possible in patients who are pregnant
• If women take this drug during pregnancy, there is a risk that their new-born infants will experience neonatal withdrawal syndrome
• Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate
• If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
• Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available
  Injection
• Oxycodone injection is not recommended for use in pregnancy nor during labour
• There are limited data from the use of oxycodone in pregnant women
• Infants born to mothers who have received opioids during the last 3-4 weeks before giving birth pregnancy should be monitored for respiratory depression
• Withdrawal symptoms may be observed in the newborn of mothers undergoing treatment with oxycodone
• No studies on fertility or the post-natal effects of intrauterine exposure have been carried out. However, studies in rats and rabbits with oral doses of oxycodone equivalent to 3 and 47 times an adult dose of 160mg/day, respectively, did not reveal evidence of harm to the foetus due to oxycodone

Breastfeeding

South African recommendations

• Contraindicated (srt, cap) 
• Caution; not recommended (inj)
• Oxycodone may be secreted in breast milk and may cause respiratory depression in the newborn. Oxycodone should therefore not be used by breastfeeding mothers

Recommendations in other jurisdictions

• Caution; not recommended 
• Administration to breastfeeding women is not recommended as oxycodone may be secreted in breast milk and may cause respiratory depression in the infant

Fertility

South African recommendations

• No human data on the effect of oxycodone on fertility are available. In rats, there was no effect on mating or fertility with oxycodone treatment

Recommendations in other jurisdictions

• No human data on the effect of oxycodone on fertility are available. In rats, there was no effect on mating or fertility with oxycodone treatment (srt)
• No studies on fertility or the post-natal effects of intrauterine exposure have been carried out (inj)
• No information available (cap)

Renal Impairment

South African recommendations

• Mild to moderate: Caution; dose adjustment recommended 
  Opioid naïve patients
  - Oral (cap): Initial: 5mg, 6hrly
  - Oral (srt): Initial: 5mg, 12hrly titrated to pain relief
  - IV: Starting dose should be reduced by 50% and each patient should be titrated to adequate pain control according to their clinical situation
• Severe: CrCl<10ml/min (cap, srt): Contraindicated 
• Severe: CrCl<30ml/min (inj): Contraindicated 

Recommendations in other jurisdictions

• Caution; dose adjustment recommended 
  Starting dose should be reduced by 50% in opioid naïve patients, and each patient should be titrated to adequate pain control according to their clinical situation

Hepatic Impairment

South African recommendations

• Mild: Caution; dose adjustment recommended 
  Opioid naïve patients
  - Oral (cap): Initial: 5mg, 6hrly
  - Oral (srt): Initial: 5mg, 12hrly titrated to pain relief
  - IV: Starting dose should be reduced by 50% and each patient should be titrated to adequate pain control according to their clinical situation
• Moderate to severe: Contraindicated 

Recommendations in other jurisdictions

• Caution; dose adjustment recommended  
  Starting dose should be reduced by 50% in opioid naïve patients, and each patient should be titrated to adequate pain control according to their clinical situation
• Moderate to severe: Contraindicated (cap)

Elderly

• Caution; no dose adjustment recommended 
  Elderly patients should be treated with caution. The lowest dose should be administered with careful titration to pain control (inj)

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

•  Prohibited - In competition

Central Nervous System Disorders

• Headache
• Dizziness
• Sedation
• Somnolence up to a depressed level of consciousness
• Syncope
• Paraesthesia
• Impaired concentration
• Migraine
• Dysgeusia
• Hypermyotonia
• Tremor
• Involuntary muscle contractions
• Hypoaesthesia
• Abnormal coordination
• Convulsions 
• Amnesia
• Speech disorder
• Altered mood and personality change
• Decreased activity
• Restlessness
• Psychomotor hyperactivity
• Agitation
• Nervousness
• Insomnia
• Abnormal thinking
• Abnormal dreams
• Confusion
• Perception disturbances 
• Reduced libido
• Drug dependence
• Asthenia
• Disorientation
• Dysphoria
• Aggression

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Hypotension
• Vasodilation 

Respiratory Disorders

• Dyspnoea
• Cough

Gastrointestinal Disorders

• Constipation
• Nausea and vomiting
• Abdominal pain
• Diarrhoea
• Dry mouth
• Hiccups
• Dyspepsia
• Mouth ulceration
• Stomatitis
• Flatulence
• Melaena
• Tooth disorder
• Gingival bleeding
• Dysphagia
• Ileus 

Hepatobiliary System

• Biliary colic
• Increased hepatic enzymes 

Genitourinary System

• Urinary retention
• Dysuria
• Micturition urgency
• Erectile dysfunction
• Amenorrhoea

Endocrine and Metabolic Systems

• Decreased appetite
• Dehydration
• Increased appetite

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Skin reactions

Immune, Blood and Lymphatic System Disorder

• Hypersensitivity
• Anaphylactic reaction

Sensory Disorders

• Visual disturbances
• Hearing impairment

Others

• Physical dependence with drug withdrawal syndrome

• Central nervous system depressant agents
• Anticholinergic agents
• Monoamine oxidase inhibitors  
• Alcohol
• CYP3A4 inhibitors
• CYP3A4 inducers
• CYP2D6 inhibitors

None routine. Specific cases may require 

• Liver function
• Renal function
• Respiratory function

Switching from morphine to oxycodone therapy

South African recommendations

• Patients receiving oral morphine before oxycodone capsules or prolonged-release tablets should have their daily dose based on the following ratio: 10mg of oral oxycodone is equivalent to 20mg of oral morphine
• It must be emphasised that this is a guide to the dose of oxycodone capsules or prolonged-release tablets required
• Inter-patient variability requires that each patient is carefully titrated to the appropriate dose

Recommendations in other jurisdictions

CAP

• Patients receiving oral morphine before oxycodone capsules or prolonged-release tablets should have their daily dose based on the following ratio: 10mg of oral oxycodone is equivalent to 20mg of oral morphine
• It must be emphasised that this is a guide to the dose of oxycodone capsules or prolonged-release tablets required
• Inter-patient variability requires that each patient is carefully titrated to the appropriate dose

SRT

• The inter-patient variability requires that each patient be carefully adjusted to the dose that is appropriate for them
• At the beginning of the change, a dose that is lower than the dose equivalent may be recommended
• Patients who have received oral morphine prior to oxycodone therapy should receive their daily dose based on the following ratio: 10mg oral oxycodone is equivalent to 20mg oral morphine
• Because of individual differences in sensitivity for different opioids, it is recommended that patients should start conservatively with oxycodone hydrochloride prolonged-release tablets after conversion from other opioids, with 50-75% of the calculated oxycodone dose

INJ

• Patients switching from parenteral morphine to parenteral oxycodone therapy should do so on the basis of a one to one dose ratio
• It must be emphasised that this is a guide to the dose of oxycodone injection required
• Inter-patient variability requires that each patient is carefully titrated to the appropriate dose

Transferring patients between oral and parenteral oxycodone

• The dose should be based on the following ratio: 2mg of oral oxycodone is approximately equivalent to 1mg of parenteral oxycodone
• It must be emphasised that this is a guide to the dose required
• Inter-patient variability requires that each patient is carefully titrated to the appropriate dose

Use in non-malignant pain

• Opioids are not first-line therapy for chronic non-malignant pain, nor are they recommended as the only treatment
• Types of chronic pain which have been shown to be alleviated by strong opioids include chronic osteoarthritic pain and intervertebral disc disease
• The need for continued treatment in non-malignant pain should be assessed at regular intervals

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Dependance and addiction

The use of strong opioids in chronic non-cancer pain for prolonged periods requires screening for risk of abuse and requires regular assessment in order to quantify benefit ie: return to function. Prescriptions for the management of acute (eg. post-operative) pain should not exceed 5-7 days, and a follow-up examination, assessing pain reduction, sleep, mood, return to work, physical function and social function should be performed, and/or specialist guidance sought before considering extending the course.

Full opioid agonist at kappa, mu & delta opiate receptors in the brain & spinal cord

Tablet SR 5mg

• Oxycontin (Mundipharma) originator

Tablet SR 10mg 

• Oxycontin (Mundipharma) originator

Tablet SR 20mg

• Oxycontin (Mundipharma) originator

Tablet SR 40mg

• Oxycontin (Mundipharma) originator

Tablet SR 80mg

• Oxycontin (Mundipharma) originator

Capsule 5mg

• Oxycorrell (Camox)
• Oxynorm (Mundipharma) originator

Capsule 10mg

• Oxycorrell (Camox)
• Oxynorm (Mundipharma) originator

Capsule 20mg

• Oxycorrell (Camox)  
• Oxynorm (Mundipharma) originator

Injection (per ml) 10mg

• Oxynorm (Mundipharma) originator

Injection (per 2ml) 20mg

• Oxynorm (Mundipharma) originator

COMBINATION PREPARATIONS

Oxycodone/ Naloxone 

Tablet SRT 5/2,5mg 

• Targinact (Mundipharma) originator

Tablet SRT 10/5mg 

• Targinact (Mundipharma) originator

Tablet SRT 20/10mg 

• Targinact (Mundipharma) originator

Tablet SRT 40/20mg

• Targinact (Mundipharma) originator