Drugs List

Therapeutic Indications

Uses

Treatment of opioid-induced constipation in patients with chronic pain
Treatment of opioid-induced constipation in terminally ill patients

Administration

For subcutaneous injection.

Can be injected without regard to food.

The upper legs, upper arms and the abdomen are recommended as the injection sites and these should be rotated regularly. Areas where the skin is tender, bruised, red, hard, has scars or stretch marks should be avoided.

Contraindications

Children under 18 years
Predisposition to gastrointestinal obstruction
Acute surgical abdomen
Breastfeeding
End stage renal disease
Mechanical gastrointestinal obstruction
Pregnancy
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Colostomy
Faecal impaction
Gastric mucosa lesion
Gastrointestinal diverticula
Renal impairment - creatinine clearance below 30 ml/minute

Reduce dose in patients with creatinine clearance below 30ml/min
Advise patient dizziness may affect ability to drive or operate machinery
Rotate injection sites to minimise the risk of lipoatrophy
May result in rapid onset of bowel movement
Discontinue if severe and persistent abdominal pain occurs
Discontinue if severe and persistent diarrhoea develops
Treatment should be limited to 4 months. No data for longer periods.

Should not be used to treat constipation unrelated to opioid use.

Methylnaltrexone bromide should be added to the usual laxative treatment in palliative care patients.

Cases of gastrointestinal perforation have been reported in patients using methylnaltrexone bromide. Although patients had medical conditions that may be associated with localised or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, pseudo obstruction, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases), the use of methylnaltrexone bromide may have contributed to these events. The overall risk-benefit profile should be taken into account when using methylnaltrexone bromide in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall e.g. Crohn's disease.

Symptoms consistent with opioid withdrawal (hyperhidrosis, chills, vomiting, abdominal pain, palpitations, blushing) have occurred with methylnaltrexone bromide. Patients with disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia.

Pregnancy and Lactation

Pregnancy

Methylnaltrexone bromide is contraindicated during pregnancy.

At the time of writing, there are no adequate data regarding the use of methylnaltrexone bromide during pregnancy and the potential risk to human pregnancies is unknown.

Data from animal studies have shown reproductive toxicity and reduced birth weights in rats at high doses. The clinical significance for humans is unknown and as such should only be used if clearly necessary.

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 to 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

Methylnaltrexone bromide is contraindicated during breastfeeding.

At the time of writing it is unknown whether methylnaltrexone bromide is excreted in human milk. Studies in animals have shown excretion of methylnaltrexone bromide in breast milk. The manufacturer advises that a decision as to whether to discontinue breastfeeding or whether to discontinue methylnaltrexone bromide while breastfeeding should be made.

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

Abdominal pain
Burning (injection site)
Chills
Diarrhoea
Dizziness
Flatulence
Gastro-intestinal perforation
Hot flushes
Hyperhidrosis
Injection site reactions
Local pain (injection site)
Nausea
Oedema (injection site)
Palpitations
Piloerection
Rhinorrhoea
Stinging (injection site)
Tremor
Vomiting

Presentation

Solution for injection containing methylnaltrexone bromide

Drugs List

Therapeutic Indications

Uses

Treatment of opioid-induced constipation in patients with chronic pain
Treatment of opioid-induced constipation in terminally ill patients

Dosage

Adults

Elderly

Patients with Renal Impairment

Administration

For subcutaneous injection.

Can be injected without regard to food.

The upper legs, upper arms and the abdomen are recommended as the injection sites and these should be rotated regularly. Areas where the skin is tender, bruised, red, hard, has scars or stretch marks should be avoided.

Contraindications

Children under 18 years
Predisposition to gastrointestinal obstruction
Acute surgical abdomen
Breastfeeding
End stage renal disease
Mechanical gastrointestinal obstruction
Pregnancy
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Colostomy
Faecal impaction
Gastric mucosa lesion
Gastrointestinal diverticula
Renal impairment - creatinine clearance below 30 ml/minute

Reduce dose in patients with creatinine clearance below 30ml/min
Advise patient dizziness may affect ability to drive or operate machinery
Rotate injection sites to minimise the risk of lipoatrophy
May result in rapid onset of bowel movement
Discontinue if severe and persistent abdominal pain occurs
Discontinue if severe and persistent diarrhoea develops
Treatment should be limited to 4 months. No data for longer periods.

Should not be used to treat constipation unrelated to opioid use.

Methylnaltrexone bromide should be added to the usual laxative treatment in palliative care patients.

Cases of gastrointestinal perforation have been reported in patients using methylnaltrexone bromide. Although patients had medical conditions that may be associated with localised or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, pseudo obstruction, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases), the use of methylnaltrexone bromide may have contributed to these events. The overall risk-benefit profile should be taken into account when using methylnaltrexone bromide in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall e.g. Crohn's disease.

Symptoms consistent with opioid withdrawal (hyperhidrosis, chills, vomiting, abdominal pain, palpitations, blushing) have occurred with methylnaltrexone bromide. Patients with disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia.

Pregnancy and Lactation

Pregnancy

Methylnaltrexone bromide is contraindicated during pregnancy.

At the time of writing, there are no adequate data regarding the use of methylnaltrexone bromide during pregnancy and the potential risk to human pregnancies is unknown.

Data from animal studies have shown reproductive toxicity and reduced birth weights in rats at high doses. The clinical significance for humans is unknown and as such should only be used if clearly necessary.

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 to 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

Methylnaltrexone bromide is contraindicated during breastfeeding.

At the time of writing it is unknown whether methylnaltrexone bromide is excreted in human milk. Studies in animals have shown excretion of methylnaltrexone bromide in breast milk. The manufacturer advises that a decision as to whether to discontinue breastfeeding or whether to discontinue methylnaltrexone bromide while breastfeeding should be made.

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

Counselling

Advise patients that rapid onset of a bowel movement can occur following treatment with methylnaltrexone bromide (within 30 to 60 minutes on average).

Advise patients that methylnaltrexone bromide may cause dizziness and as such may have an effect on driving and/or operating machinery.

Advise patients to promptly report severe, persistent or worsening symptoms.

Side Effects

Abdominal pain
Burning (injection site)
Chills
Diarrhoea
Dizziness
Flatulence
Gastro-intestinal perforation
Hot flushes
Hyperhidrosis
Injection site reactions
Local pain (injection site)
Nausea
Oedema (injection site)
Palpitations
Piloerection
Rhinorrhoea
Stinging (injection site)
Tremor
Vomiting

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 ).

Further Information

Last Full Review Date: September 2015

Reference Sources

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on 4 September 2015.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press Accessed on 4 September 2015.

Summary of Product Characteristics: Relistor 12mg/0.6ml solution for injection. Swedish Orphan Biovitrum Ltd. Revised January 2017.