Drugs List

Therapeutic Indications

Uses

Parkinson's disease - adjunct to levodopa + dopa-decarboxylase inhibitor

Indicated as an adjunct to standard preparations of levodopa/benserazide or levodopa/carbidopa for use in patients with Parkinson's disease and end-of-dose motor fluctuations, who cannot be stabilised on those combinations.

Contraindications

Children under 18 years
Breastfeeding
Hepatic impairment
History of neuroleptic malignant syndrome
History of non-traumatic rhabdomyolysis
Phaeochromocytoma
Pregnancy

Precautions and Warnings

Ischaemic heart disease
Renal dialysis

Consider increasing dose interval for dialysis patients
Advise ability to drive/operate machinery may be affected by side effects
Advise patient that sudden onset sleep episodes may affect ability to drive
Some products contain arachis (peanut) oil, soya or soya derivative
Take at a different time from iron supplement
Monitor patient's weight
Monitor patients for impulse control disorders
Monitor weight loss if side effect of diarrhoea occurs and is tolerated
Review treatment if impulse control disorders symptoms occur
Advise patient that postural hypotension may occur
Lower dose of levodopa initially to reduce dopaminergic side effects
Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
Advise patient urine may be coloured reddish brown
Advise patient/carer about symptoms of impulse control disorders

Isolated cases of Neuroleptic Malignant Syndrome have been reported, especially following abrupt reduction or discontinuation of entacapone and other dopaminergic medications. When necessary, withdrawal of entacapone and other dopaminergic treatment should proceed slowly, and if signs and/or symptoms occur despite a slow withdrawal, an increase in levodopa dosage may be necessary.

The doses of other antiparkinsonian medications may need to be adjusted when entacapone treatment is initiated.

Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide combinations slightly (5 to 10%) more than from standard levodopa/carbidopa ones. Therefore on initiation of entacapone, patients taking a levodopa/benserazide combination may need a larger reduction in the levodopa dose.

For patients who experience progressive anorexia, asthenia and weight decrease within a relatively short period of time, a general medical evaluation including liver function should be considered.

Pregnancy and Lactation

Pregnancy

Entacapone is contraindicated in pregnancy.

Animal studies have shown entacapone was teratogenic in rats at plasma levels of entacapone close to those observed in humans. Although no teratogenic effect was seen in rabbits (Briggs, 2011).

There is no experience in pregnant women. Schafer (2007) concludes that the inadvertent use of entacapone is not grounds for termination of pregnancy or for invasive diagnostic procedures. A detailed ultrasonography may be considered.

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

Entacapone is contraindicated in breastfeeding.

At the time of writing no reports describing the use of entacapone during human breastfeeding have been located. The molecular weight (about 305) is low enough that excretion into milk should be expected, but the relatively short elimination half-life should limit the amount in milk (Briggs, 2011).

In animal studies entacapone was excreted in milk. The safety of entacapone in infants is unknown.

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
Agitation
Altered liver function tests
Angina pectoris
Anorexia
Cholestatic hepatitis
Colitis
Confusion
Constipation
Darkening of urine
Diarrhoea
Discolouration of hair
Discolouration of nails (temporary)
Discolouration of urine
Dizziness
Dream abnormalities
Dry mouth
Dyskinesia
Dystonia
Erythematous rash
Falls
Fatigue
Hallucinations
Hyperkinesia
Hypersexuality
Increased libido
Increased sweating
Insomnia
Maculopapular rash
Myocardial infarction
Nausea
Neuroleptic malignant syndrome
Orthostatic hypotension
Paranoia
Pathological gambling
Rhabdomyolysis
Skin discolouration
Somnolence
Sudden sleep onset episodes
Urticaria
Vomiting
Weight loss
Worsening of Parkinson's disease

Presentation

Tablets containing entacapone

Drugs List

Therapeutic Indications

Uses

Parkinson's disease - adjunct to levodopa + dopa-decarboxylase inhibitor

Indicated as an adjunct to standard preparations of levodopa/benserazide or levodopa/carbidopa for use in patients with Parkinson's disease and end-of-dose motor fluctuations, who cannot be stabilised on those combinations.

Dosage

Adults

Elderly

Patients with Renal Impairment

Contraindications

Children under 18 years
Breastfeeding
Hepatic impairment
History of neuroleptic malignant syndrome
History of non-traumatic rhabdomyolysis
Phaeochromocytoma
Pregnancy

Precautions and Warnings

Ischaemic heart disease
Renal dialysis

Consider increasing dose interval for dialysis patients
Advise ability to drive/operate machinery may be affected by side effects
Advise patient that sudden onset sleep episodes may affect ability to drive
Some products contain arachis (peanut) oil, soya or soya derivative
Take at a different time from iron supplement
Monitor patient's weight
Monitor patients for impulse control disorders
Monitor weight loss if side effect of diarrhoea occurs and is tolerated
Review treatment if impulse control disorders symptoms occur
Advise patient that postural hypotension may occur
Lower dose of levodopa initially to reduce dopaminergic side effects
Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
Advise patient urine may be coloured reddish brown
Advise patient/carer about symptoms of impulse control disorders

Isolated cases of Neuroleptic Malignant Syndrome have been reported, especially following abrupt reduction or discontinuation of entacapone and other dopaminergic medications. When necessary, withdrawal of entacapone and other dopaminergic treatment should proceed slowly, and if signs and/or symptoms occur despite a slow withdrawal, an increase in levodopa dosage may be necessary.

The doses of other antiparkinsonian medications may need to be adjusted when entacapone treatment is initiated.

Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide combinations slightly (5 to 10%) more than from standard levodopa/carbidopa ones. Therefore on initiation of entacapone, patients taking a levodopa/benserazide combination may need a larger reduction in the levodopa dose.

For patients who experience progressive anorexia, asthenia and weight decrease within a relatively short period of time, a general medical evaluation including liver function should be considered.

Pregnancy and Lactation

Pregnancy

Entacapone is contraindicated in pregnancy.

Animal studies have shown entacapone was teratogenic in rats at plasma levels of entacapone close to those observed in humans. Although no teratogenic effect was seen in rabbits (Briggs, 2011).

There is no experience in pregnant women. Schafer (2007) concludes that the inadvertent use of entacapone is not grounds for termination of pregnancy or for invasive diagnostic procedures. A detailed ultrasonography may be considered.

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

Entacapone is contraindicated in breastfeeding.

At the time of writing no reports describing the use of entacapone during human breastfeeding have been located. The molecular weight (about 305) is low enough that excretion into milk should be expected, but the relatively short elimination half-life should limit the amount in milk (Briggs, 2011).

In animal studies entacapone was excreted in milk. The safety of entacapone in infants is unknown.

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
Agitation
Altered liver function tests
Angina pectoris
Anorexia
Cholestatic hepatitis
Colitis
Confusion
Constipation
Darkening of urine
Diarrhoea
Discolouration of hair
Discolouration of nails (temporary)
Discolouration of urine
Dizziness
Dream abnormalities
Dry mouth
Dyskinesia
Dystonia
Erythematous rash
Falls
Fatigue
Hallucinations
Hyperkinesia
Hypersexuality
Increased libido
Increased sweating
Insomnia
Maculopapular rash
Myocardial infarction
Nausea
Neuroleptic malignant syndrome
Orthostatic hypotension
Paranoia
Pathological gambling
Rhabdomyolysis
Skin discolouration
Somnolence
Sudden sleep onset episodes
Urticaria
Vomiting
Weight loss
Worsening of Parkinson's disease

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: March 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 [March 12, 2014]].

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

Summary of Product Characteristics: Comtess 200mg film-coated tablets. Orion Pharma (UK) Ltd. Revised August 2013.

Summary of Product Characteristics: Entacapone 200mg film-coated tablets. Wockhardt UK Ltd. Revised February 2013.