Drugs List

Therapeutic Indications

Uses

Co-proxamol has been withdrawn from the market. Do not initiate treatment in new patients. Some presentations still remain available for individual patient supply.

Mild to moderate pain in adults where first line analgesics have proved ineffective or are inappropriate.

Administration

For oral administration

Contraindications

Patients with high suicide risk

Patients with a known propensity for drug dependence

Patients who are alcohol-dependent

Children under 18 years of age

Pregnancy (see Pregnancy)

Precautions and Warnings

Co-proxamol has been withdrawn from the market. Do not initiate treatment in new patients. Some presentations still remain available for individual patient supply.

Hepatic impairment (see Dosage - Hepatic impairment)

Renal impairment (see Dosage - Renal impairment )

Breastfeeding (see Lactation )

Elderly (see Dosage - Elderly )

History of alcohol abuse

Patients should be advised to avoid alcohol

Patients should be advised not to exceed the recommended dose

May impair the ability to drive and operate machinery

May cause dependence

May cause changes to ECG - prolonged QT, PR and QRS intervals.

Patients should be advised to seek urgent medical advice in the event of an overdose, even if they feel well. Fatalities within the first hour of overdose are not uncommon and can occur within 15 minutes. Compared to the general population the hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Patients should be advised not to take with any other paracetamol containing products.

Pregnancy and Lactation

Pregnancy

Safety in pregnancy has not been established. Withdrawal symptoms in neonates have been reported following use during pregnancy.

Single agent paracetamol is normally considered first line in pregnant women.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Both dextropropoxyphene and paracetamol are excreted in small amounts in breast milk.

Available published data do not contraindicate breast feeding. LactMed notes that low levels are found in the milk, recommends that the infant should be monitored for drowsiness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants. Maternal intake should be limited and analgesia supplemented with a non opioid analgesic if necessary. Contact a physician immediately if the infant shows increased signs of sleepiness, difficulty feeding, breathing difficulties or limpness.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Dizziness
Sedation
Nausea
Vomiting
Constipation
Abdominal pain
Rash
Lightheadedness
Headache
Weakness
Euphoria
Dysphoria
Hallucinations
Visual disturbances
Thrombocytopenia
Agranulocytosis
Abnormal liver function tests
Jaundice
Hepatic necrosis
Papillary necrosis
Myopathy
Toxic psychosis
Convulsions
ECG changes
Haemolysis
Haemolytic anaemia
Prolongation of QT interval
Deafness
Tinnitus
Hepatotoxicity

Presentation

Tablets containing 32.5mg dextropropoxyphene hydrochloride (equivalent to approximately 30mg dextropropoxyphene base) with 325mg paracetamol

Drugs List

Therapeutic Indications

Uses

Co-proxamol has been withdrawn from the market. Do not initiate treatment in new patients. Some presentations still remain available for individual patient supply.

Mild to moderate pain in adults where first line analgesics have proved ineffective or are inappropriate.

Dosage

Co-proxamol has been withdrawn from the market. Do not initiate treatment in new patients. Some presentations still remain available for individual patient supply.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For oral administration

Contraindications

Patients with high suicide risk

Patients with a known propensity for drug dependence

Patients who are alcohol-dependent

Children under 18 years of age

Pregnancy (see Pregnancy)

Precautions and Warnings

Co-proxamol has been withdrawn from the market. Do not initiate treatment in new patients. Some presentations still remain available for individual patient supply.

Hepatic impairment (see Dosage - Hepatic impairment)

Renal impairment (see Dosage - Renal impairment )

Breastfeeding (see Lactation )

Elderly (see Dosage - Elderly )

History of alcohol abuse

Patients should be advised to avoid alcohol

Patients should be advised not to exceed the recommended dose

May impair the ability to drive and operate machinery

May cause dependence

May cause changes to ECG - prolonged QT, PR and QRS intervals.

Patients should be advised to seek urgent medical advice in the event of an overdose, even if they feel well. Fatalities within the first hour of overdose are not uncommon and can occur within 15 minutes. Compared to the general population the hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Patients should be advised not to take with any other paracetamol containing products.

Pregnancy and Lactation

Pregnancy

Safety in pregnancy has not been established. Withdrawal symptoms in neonates have been reported following use during pregnancy.

Single agent paracetamol is normally considered first line in pregnant women.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Both dextropropoxyphene and paracetamol are excreted in small amounts in breast milk.

Available published data do not contraindicate breast feeding. LactMed notes that low levels are found in the milk, recommends that the infant should be monitored for drowsiness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants. Maternal intake should be limited and analgesia supplemented with a non opioid analgesic if necessary. Contact a physician immediately if the infant shows increased signs of sleepiness, difficulty feeding, breathing difficulties or limpness.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

Patients should be advised that co-proxamol may impair the ability to drive and operate machinery

Counselling

Patients should be advised that co-proxamol is to be withdrawn from the market, and to consult their doctor in order to find an alternative pain management system.

Patients should be advised to avoid alcohol

Patients should be advised not to exceed the recommended dose

Patients should be advised that co-proxamol may impair the ability to drive and operate machinery

Patients should be advised to seek urgent medical advice in the event of an overdose, even if they feel well

Patients should be advised that this medicine is for their use only, and that any unused medicine should be returned to the pharmacy

Patients should be advised not to take with any other paracetamol containing products.

Patients should be advised to report any signs or symptoms of arrhythmias.

Side Effects

Dizziness
Sedation
Nausea
Vomiting
Constipation
Abdominal pain
Rash
Lightheadedness
Headache
Weakness
Euphoria
Dysphoria
Hallucinations
Visual disturbances
Thrombocytopenia
Agranulocytosis
Abnormal liver function tests
Jaundice
Hepatic necrosis
Papillary necrosis
Myopathy
Toxic psychosis
Convulsions
ECG changes
Haemolysis
Haemolytic anaemia
Prolongation of QT interval
Deafness
Tinnitus
Hepatotoxicity

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

The MHRA have produced 'generic' overdose sections for the top ten drugs for which the NPIS received the greatest number of queries about management of overdose in 2002. This information is represented below:

The fatal dose of co-proxamol may be as little as 10-20 tablets for an adult, especially when CNS depressants such as alcohol, sedatives and tranquillisers have also been taken.

Liver damage is possible in patients who have taken 75mg/kg or more of paracetamol in less than an hour, and these patients should be referred to hospital. To avoid underestimating the potentially toxic paracetamol dose ingested by obese patients who weigh more than 110kg, a bodyweight of 110kg (rather than the actual bodyweight) should be used to calculate the total dose of paracetamol ingested in mg/kg.

Signs and Symptoms

Early features are due to the dextropropoxyphene (opioid) content and include coma, severe respiratory depression, convulsions, and cardiac arrest. These may occur within 30 minutes of ingestion, particularly if alcohol has also been ingested.

Cardiac arrhythmias including ventricular tachycardia may occur up to 12 hours after ingestion, particularly if features of CNS depression are also present.

In less severe cases, pallor, nausea and vomiting may persist for about 24 hours.
Psychotic reactions may occur.

Later features are due to the paracetamol content. After 1-3 days features of hepatic necrosis may appear with persistent nausea and vomiting, right subcostal pain and tenderness followed by jaundice. Loin pain, haematuria and proteinuria after the first 24 hours strongly suggest the development of renal tubular necrosis and the risk of acute renal failure.

Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Pancreatitis has been reported.

Treatment

This should include general symptomatic and supportive measures. Naloxone will reduce the respiratory depression and should be given intravenously if coma or respiratory depression is present. Consider activated charcoal if the patient presents within one hour of ingestion of a potentially toxic amount. Consider gastric lavage in adults within one hour of a potentially life-threatening overdose.

The ECG should be monitored and hypoxia, electrolyte abnormalities and acid base disturbance should be corrected.

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines.

Treatment with activated charcoal should be considered if the overdose in excess of 150mg/kg has been taken within 1 hour. Treatment with acetylcysteine is used up to, and possibly beyond, 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion, after which effectiveness declines. If required, the patient should be given intravenous acetylcysteine, in line with the established dosage schedule. Giving acetylcysteine by mouth (unlicensed route) is an alternative if intravenous access is not possible. Acetylcysteine can be given irrespective of the plasma paracetamol concentration:
in circumstances where the overdose is staggered or there is doubt over the time of paracetamol ingestion; or
in overdose with a timed plasma paracetamol concentration on or above a single treatment line joining points of 100mg/L at 4 hours and 15mg/L at 15 hours nomogram (https://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con184396.pdf), regardless of risk factors of hepatotoxicity.

Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentration are unreliable). If vomiting is not a problem, and overdose has been taken within 10-12 hours, oral methionine may be a suitable alternative for remote areas outside hospital. Management of patients who present beyond 24 hours from ingestion or with serious hepatic dysfunction should be discussed with the NPIS (https://www.npis.org/) or a liver unit.

Shelf Life and Storage

Not known.

Further Information

Last Full Review Date: May 2011

Reference Sources

Summary of Product Characteristics: Distalgesic. Meda Pharmaceuticals. Revised May 2007

British National Formulary, 61st Edition (2011) Pharmaceutical Press, London.

Martindale: The Complete Drug Reference, 36th edition (2009) ed. Sweetman, S. Pharmaceutical Press, London.

Drug safety update: Vol 1, Issue 4, November 2007
Co-proxamol withdrawal: reminder to prescribers
https://www.mhra.gov.uk/home/groups/pl-p/documents/publication/con2032917.pdf
Last accessed: May 12, 2011

Drug safety update: Vol 4, Issue 6, January 2011
(Dextro)propoxyphene: new studies confirm cardiac risks
https://www.mhra.gov.uk/home/groups/dsu/documents/publication/con105811.pdf
Last accessed: May 12, 2011

MHRA 19th September 2005
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/index.htm
Last accessed: May 9, 2011

MHRA 10th September 2012
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/Paracetamol/index.htm
Last accessed: September 20, 2012

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Propoxyphene. Record 382. Last revised: 3rd February 2009
Last accessed: May 12, 2011