Drugs List

Therapeutic Indications

Uses

Parkinson's disease

For the treatment of advanced levodopa-responsive Parkinson's disease with severe motor fluctuations and hyperkinesia or dyskinesia when other medicinal products have not been successful.

Administration

For long term administration, the gel should be administered using a portable pump directly into the duodenum or upper jejunum by a permanent tube via percutaneous endoscopic gastrostomy with an outer transabdominal tube and an inner intestinal tube. If this is not suitable for any reason, then a radiological gastrojejunostomy may be considered as an alternative.

A positive test of the clinical response to this co-careldopa formulation administered via a temporary nasoduodenal tube is required before a permanent tube is inserted.

Treatment may be discontinued at any time by withdrawing the tube and letting the wound heal. Treatment should then be continued with oral formulations.

For administration of co-careldopa intestinal gel, only the CADD-legacy pump (CE0473) should be used. A manual with instructions for using the portable pump is delivered together with the pump.

Contraindications

Children under 18 years
Suspected malignant melanoma
Within 2 weeks of discontinuing MAOIs
Acute phase of cerebrovascular accident
Breastfeeding
Cushing's disease
History of malignant melanoma
Hyperthyroidism
Malignant melanoma
Narrow angle glaucoma
Phaeochromocytoma
Pregnancy
Serious cardiac arrhythmias
Severe cardiac failure
Severe psychiatric disorder

Precautions and Warnings

General anaesthesia
Predisposition to narrow angle glaucoma
Predisposition to peripheral neuropathy
Asthma
Diabetes mellitus
Endocrine disease
History of myocardial infarction
History of peptic ulcer
History of postural hypotension
History of psychosis
History of seizures
Open angle glaucoma
Osteomalacia
Polyneuropathy
Psychiatric disorder
Psychosis
Pulmonary disease
Severe cardiovascular disorder
Severe hepatic impairment
Severe renal impairment
Supraventricular arrhythmias
Ventricular arrhythmias

Advise patient/carer risk of dopamine dysregulation syndrome (DDS)
Not recommended for treatment of drug induced extrapyramidal reactions
Advise patient somnolence may affect ability to drive or operate machinery
Advise patient that sudden onset sleep episodes may affect ability to drive
Exacerbation of bradykinesia may indicate tube blockage needing correction
If a sudden deterioration in response occurs confirm correct tube placement
Monitor closely patient with a history of myocardial infarction
Monitor for melanoma regularly
Monitor for mental changes, suicidal depression and antisocial behaviour
Monitor for polyneuropathy before and periodically during treatment
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor patients for impulse control disorders
Monitor renal, hepatic and haematological parameters
Response to treatment should be assessed using a nasoduodenal tube first
Review treatment if impulse control disorders symptoms occur
Contains hydrazine, a degradation product
May cause postural hypotension
Reduce dose if dyskinesia occurs
May affect results of some laboratory tests
May colour urine red
Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
Reduce dose or discontinue if sudden onset of sleep during daily activities
Advise patient/carer about symptoms of impulse control disorders

Pregnancy and Lactation

Pregnancy

Co-careldopa is contraindicated in pregnancy.
Manufacturer advises that should not be used unless benefits to the mother outweigh risks to the foetus.

Animal studies have shown teratogenicity. Both levodopa and combinations of levodopa and carbidopa have caused visceral and skeletal malformations in rabbits. No adverse outcomes associated with this drug have been observed in a limited number of human pregnancies though. Data published in 1995 describes the two pregnancies which were terminated at 8 weeks and 10 weeks by a women with juvenile Parkinson's disease who had been taking 200/800 mg/day of carbidopa/ levodopa. The relatively high concentrations of dopamine in foetal peripheral organs and neural tissue implied that the foetuses had metabolised levodopa. Because neurotransmitters were known to alter early neural development in animals and cultured cells, the investigators cautioned that the increased amounts of dopamine found in this study suggested that chronic use of levodopa during gestation could induce long term damage. Because of this potential risk to the foetus, co-careldopa should not be used during pregnancy.

Schaefer (2007) states that inadvertent use of a Parkinson drug not belonging to the broadly used ergotamine derivatives is not grounds for termination of pregnancy or grounds for invasive diagnostic procedures, although advises that detailed foetal ultrasonography may be considered in the first trimester.

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

Co-careldopa is contraindicated in breastfeeding.

Levodopa is excreted into human breast milk but it is unknown whether carbidopa is excreted. A study in 1974 provided clinical evidence that levodopa inhibits lactation. Doses of 500 to 3500 mg/day of levodopa were given orally to ten female patients with a history of inappropriate galactorrhoea. Partial to complete suppression of lactation was observed but when the treatment was stopped, lactation returned to normal. Briggs (2011) classifies levodopa and carbidopa separately as probably being compatible with breastfeeding. However, Hale (2010) puts levodopa in a risk category of possibly hazardous because there is positive evidence of risk to a breastfed infant or to breast milk production. Because of the potential for adverse effects in the newborn and the suppression of lactation, co-careldopa should not be administered to lactating women.

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

Abscess
Activation of latent Horner's syndrome
Aggression
Agitation
Agranulocytosis
Anaemia
Angioedema
Anorexia
Anxiety
Arrhythmias
Ataxia
Bitter taste
Blepharospasm
Blurred vision
Bradykinesia
Bruxism
Burning tongue
Chest pain
Choreiform movement
Complications associated with the administration device
Confusion
Constipation
Convulsions
Dementia
Depression
Discolouration of body fluids
Disorientation
Dizziness
Dopamine dysregulation syndrome
Double vision
Dry mouth
Duodenal ulcer
Dyskinesia
Dyspepsia
Dysphagia
Dyspnoea
Dystonia
Euphoria
Exanthema
Falls
Fatigue
Fear
Fine tremor (usually hands)
Flushing
Gait abnormality
Gastro-intestinal symptoms
Gastrointestinal bleeding
Haemolytic anaemia
Hair loss
Hallucinations
Headache
Henoch-Schonlein purpura
Hiccups
Hoarseness
Hypersexuality
Hypertension
Increased libido
Insomnia
Leucopenia
Loss of mental acuity
Malaise
Malignant melanoma
Muscle spasm
Narrow angle glaucoma
Nausea
Neuroleptic malignant syndrome
Nightmares
Numbness
Oculogyric crisis
Oedema
On/off episodes
Orthostatic hypotension
Palpitations
Paraesthesia
Pathological gambling
Perspiration
Phlebitis
Pneumonia
Polyneuropathy
Possible alteration of laboratory tests
Priapism
Pruritus
Psychotic episodes
Pupillary dilatation
Sense of stimulation
Sepsis
Sialorrhoea
Somnolence
Sudden sleep onset episodes
Suicidal tendencies
Syncope
Thrombocytopenia
Trismus
Unusual breathing patterns
Urinary incontinence
Urinary retention
Urticaria
Vomiting
Weakness
Weight changes

Presentation

Gel formulation for continuous intestinal administration containing carbidopa and levodopa.

Drugs List

Therapeutic Indications

Uses

Parkinson's disease

For the treatment of advanced levodopa-responsive Parkinson's disease with severe motor fluctuations and hyperkinesia or dyskinesia when other medicinal products have not been successful.

Dosage

A temporary nasoduodenal/nasojejunal tube should be considered to determine if the patient responds favourably to this method of treatment before a permanent percutaneous endoscopic gastrostomy with jejunal tube (PEG J) is placed. In cases where the physician considers this assessment is not necessary, the nasojejunal test phase may be waived and treatment initiated directly with placement of the PEG-J.

The drug cassettes are for single use only and should be used for a maximum of 16 hours and not then re-used.

The dose should be adjusted to an optimal clinical response for the individual patient, which means maximising the functional ON-time during the day by minimising the OFF episodes and the time OFF (bradykinesia) and minimising ON-time with disabling dyskinesia.

Adults

Elderly

Administration

For long term administration, the gel should be administered using a portable pump directly into the duodenum or upper jejunum by a permanent tube via percutaneous endoscopic gastrostomy with an outer transabdominal tube and an inner intestinal tube. If this is not suitable for any reason, then a radiological gastrojejunostomy may be considered as an alternative.

A positive test of the clinical response to this co-careldopa formulation administered via a temporary nasoduodenal tube is required before a permanent tube is inserted.

Treatment may be discontinued at any time by withdrawing the tube and letting the wound heal. Treatment should then be continued with oral formulations.

For administration of co-careldopa intestinal gel, only the CADD-legacy pump (CE0473) should be used. A manual with instructions for using the portable pump is delivered together with the pump.

Contraindications

Children under 18 years
Suspected malignant melanoma
Within 2 weeks of discontinuing MAOIs
Acute phase of cerebrovascular accident
Breastfeeding
Cushing's disease
History of malignant melanoma
Hyperthyroidism
Malignant melanoma
Narrow angle glaucoma
Phaeochromocytoma
Pregnancy
Serious cardiac arrhythmias
Severe cardiac failure
Severe psychiatric disorder

Precautions and Warnings

General anaesthesia
Predisposition to narrow angle glaucoma
Predisposition to peripheral neuropathy
Asthma
Diabetes mellitus
Endocrine disease
History of myocardial infarction
History of peptic ulcer
History of postural hypotension
History of psychosis
History of seizures
Open angle glaucoma
Osteomalacia
Polyneuropathy
Psychiatric disorder
Psychosis
Pulmonary disease
Severe cardiovascular disorder
Severe hepatic impairment
Severe renal impairment
Supraventricular arrhythmias
Ventricular arrhythmias

Advise patient/carer risk of dopamine dysregulation syndrome (DDS)
Not recommended for treatment of drug induced extrapyramidal reactions
Advise patient somnolence may affect ability to drive or operate machinery
Advise patient that sudden onset sleep episodes may affect ability to drive
Exacerbation of bradykinesia may indicate tube blockage needing correction
If a sudden deterioration in response occurs confirm correct tube placement
Monitor closely patient with a history of myocardial infarction
Monitor for melanoma regularly
Monitor for mental changes, suicidal depression and antisocial behaviour
Monitor for polyneuropathy before and periodically during treatment
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor patients for impulse control disorders
Monitor renal, hepatic and haematological parameters
Response to treatment should be assessed using a nasoduodenal tube first
Review treatment if impulse control disorders symptoms occur
Contains hydrazine, a degradation product
May cause postural hypotension
Reduce dose if dyskinesia occurs
May affect results of some laboratory tests
May colour urine red
Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
Reduce dose or discontinue if sudden onset of sleep during daily activities
Advise patient/carer about symptoms of impulse control disorders

Pregnancy and Lactation

Pregnancy

Co-careldopa is contraindicated in pregnancy.
Manufacturer advises that should not be used unless benefits to the mother outweigh risks to the foetus.

Animal studies have shown teratogenicity. Both levodopa and combinations of levodopa and carbidopa have caused visceral and skeletal malformations in rabbits. No adverse outcomes associated with this drug have been observed in a limited number of human pregnancies though. Data published in 1995 describes the two pregnancies which were terminated at 8 weeks and 10 weeks by a women with juvenile Parkinson's disease who had been taking 200/800 mg/day of carbidopa/ levodopa. The relatively high concentrations of dopamine in foetal peripheral organs and neural tissue implied that the foetuses had metabolised levodopa. Because neurotransmitters were known to alter early neural development in animals and cultured cells, the investigators cautioned that the increased amounts of dopamine found in this study suggested that chronic use of levodopa during gestation could induce long term damage. Because of this potential risk to the foetus, co-careldopa should not be used during pregnancy.

Schaefer (2007) states that inadvertent use of a Parkinson drug not belonging to the broadly used ergotamine derivatives is not grounds for termination of pregnancy or grounds for invasive diagnostic procedures, although advises that detailed foetal ultrasonography may be considered in the first trimester.

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

Co-careldopa is contraindicated in breastfeeding.

Levodopa is excreted into human breast milk but it is unknown whether carbidopa is excreted. A study in 1974 provided clinical evidence that levodopa inhibits lactation. Doses of 500 to 3500 mg/day of levodopa were given orally to ten female patients with a history of inappropriate galactorrhoea. Partial to complete suppression of lactation was observed but when the treatment was stopped, lactation returned to normal. Briggs (2011) classifies levodopa and carbidopa separately as probably being compatible with breastfeeding. However, Hale (2010) puts levodopa in a risk category of possibly hazardous because there is positive evidence of risk to a breastfed infant or to breast milk production. Because of the potential for adverse effects in the newborn and the suppression of lactation, co-careldopa should not be administered to lactating women.

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

Abscess
Activation of latent Horner's syndrome
Aggression
Agitation
Agranulocytosis
Anaemia
Angioedema
Anorexia
Anxiety
Arrhythmias
Ataxia
Bitter taste
Blepharospasm
Blurred vision
Bradykinesia
Bruxism
Burning tongue
Chest pain
Choreiform movement
Complications associated with the administration device
Confusion
Constipation
Convulsions
Dementia
Depression
Discolouration of body fluids
Disorientation
Dizziness
Dopamine dysregulation syndrome
Double vision
Dry mouth
Duodenal ulcer
Dyskinesia
Dyspepsia
Dysphagia
Dyspnoea
Dystonia
Euphoria
Exanthema
Falls
Fatigue
Fear
Fine tremor (usually hands)
Flushing
Gait abnormality
Gastro-intestinal symptoms
Gastrointestinal bleeding
Haemolytic anaemia
Hair loss
Hallucinations
Headache
Henoch-Schonlein purpura
Hiccups
Hoarseness
Hypersexuality
Hypertension
Increased libido
Insomnia
Leucopenia
Loss of mental acuity
Malaise
Malignant melanoma
Muscle spasm
Narrow angle glaucoma
Nausea
Neuroleptic malignant syndrome
Nightmares
Numbness
Oculogyric crisis
Oedema
On/off episodes
Orthostatic hypotension
Palpitations
Paraesthesia
Pathological gambling
Perspiration
Phlebitis
Pneumonia
Polyneuropathy
Possible alteration of laboratory tests
Priapism
Pruritus
Psychotic episodes
Pupillary dilatation
Sense of stimulation
Sepsis
Sialorrhoea
Somnolence
Sudden sleep onset episodes
Suicidal tendencies
Syncope
Thrombocytopenia
Trismus
Unusual breathing patterns
Urinary incontinence
Urinary retention
Urticaria
Vomiting
Weakness
Weight changes

Effects on Laboratory Tests

Positive Coombs' tests have been reported.

Co-careldopa may cause a false positive result when a dipstick test for urinary ketone is performed, and this is not altered by boiling the urine. The use of glucose oxidase methods may give false negative results for glycosuria.

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: January 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on July 04, 2014.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Duodopa intestinal gel. Abbvie Ltd. Revised November 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 January 2018