Levodopa with carbidopa and entacapone oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Tablets containing levodopa, carbidopa and entacapone
Drugs List
Therapeutic Indications
Uses
Parkinson's disease
Parkinson's. Motor fluctuations inadequately controlled by dopaminergics
Dosage
The optimum daily dosage should be determined individually by careful titration of levodopa.
Patients should only take one tablet for each dose.
Usually these formulations are to be used in patients who have already been receiving treatment with corresponding doses of standard release levodopa/dopa decarboxylase (DDC) inhibitor and entacapone.
Adults
Transferring patients from levodopa/DDC inhibitor (carbidopa or benserazide) preparations and entacapone
Patients who are currently treated with entacapone and with standard release levodopa/carbidopa in doses equal to the strength of the combined formulation can be transferred directly onto the corresponding combined tablets.
In patients where their current dosing regimen doses do not correspond to the strength of the combined formulation, the dosage should be carefully titrated for optimal clinical response. At initiation, the combined formulation dosage should be adjusted to correspond as closely as possible to the total daily dose of levodopa currently used.
When initiating the combined formulation in patients currently treated with entacapone and a standard release formulation of levodopa/benserazide, the previous dosing schedule should be discontinued on the night prior to starting the new combined formulation, beginning with a dosage that will provide either the same amount or slightly (5 to 10%) more.
Transferring patients not currently treated with entacapone
Initiation of the combined formulation may be considered at corresponding doses to current treatment in some patients who are not stabilised on their current levodopa/DDC inhibitor treatment. However, a direct switch is not recommended for patients that have dyskinesias or whose daily levodopa dose is above 800 mg. In these patients it is recommended that entacapone is introduced as a separate medication, and the levodopa dose adjusted accordingly, before switching to the combined formulation.
Entacapone enhances the effects of levodopa, and so it may be necessary, particularly in patients with dyskinesia, to reduce levodopa dosage by 10 to 30% within the first few days to weeks after initiating treatment with the combined formulation. The daily dose of levodopa can be reduced by extending the dosing intervals and/or by reducing the amount of levodopa per dose, according to the clinical condition of the patient.
Dosage adjustment during the course of treatment
In situations where a greater dose of levodopa is required, an increase in the frequency of doses and/or the use of an alternative strength of the combined formulation should be considered, adhering to the maximum number of combined formulation tablets per day.
When less levodopa is required, the total daily dosage should be reduced either by decreasing the frequency of administration by extending the time between doses, or by decreasing the strength of the combined tablets at an administration.
If other levodopa products are used concomitantly with a combined formulation product, the maximum dosage recommendations should be followed.
Maximum dosage of each strength
The maximum dosage is 10 tablets per day (each dose being one tablet) for the 50/12.5/200 mg tablets, 75/18.75/200 mg tablets, 100/25/200 mg tablets, 125/31.25/200 mg tablets and 150/37.5/200 mg tablets.
The maximum recommended daily dose of 175/43.75/200 mg tablets is 8 per day.
The maximum recommended daily dose of 200/50/200 mg tablets is 7 per day.
Elderly
(See Dosage; Adult)
Additional Dosage Information
Discontinuing therapy:
If combined treatment (levodopa/carbidopa/entacapone) is discontinued and the patient is transferred to levodopa/DDC inhibitor therapy without entacapone, it is necessary to adjust the dosing of other antiparkinsonian treatments, especially levodopa, to achieve a sufficient level of symptom control.
Where abrupt dosage reduction or withdrawal is unavoidable, patients must be carefully observed for rhabdomyolysis and neuroleptic malignant syndrome (NMS).
Patients who receive less than 70 to 100 mg of carbidopa a day are more likely to experience nausea and vomiting.
Contraindications
Children under 18 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding
History of malignant melanoma
History of neuroleptic malignant syndrome
History of non-traumatic rhabdomyolysis
Malignant melanoma
Narrow angle glaucoma
Phaeochromocytoma
Pregnancy
Severe hepatic impairment
Severe psychiatric disorder
Precautions and Warnings
Asthma
Cardiac arrhythmias
Cushing's disease
Diabetes mellitus
Endocrine disease
Galactosaemia
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of myocardial infarction
History of peptic ulcer
History of postural hypotension
History of psychosis
History of seizures
Hyperthyroidism
Ischaemic heart disease
Lactose intolerance
Mild hepatic impairment
Open angle glaucoma
Osteomalacia
Psychosis
Pulmonary disease
Renal dialysis
Severe cardiovascular disorder
Severe renal impairment
Advise patient/carer risk of dopamine dysregulation syndrome (DDS)
Consider increasing dose interval for dialysis patients
Not recommended for treatment of drug induced extrapyramidal reactions
Advise patient that sudden onset sleep episodes may affect ability to drive
May contain polysorbate
Some formulations contain lactose
Some formulations contain sucrose
Some products may contain soya or soya derivative
Take at a different time from iron supplement
Haematological monitoring required in long term use
Monitor cardiovascular function
Monitor for melanoma regularly
Monitor for mental changes, suicidal depression and antisocial behaviour
Monitor hepatic function
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor patients for impulse control disorders
Monitor renal function
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
Reduce dose if dyskinesia occurs
May affect results of some laboratory tests
Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
Discontinue if severe and persistent diarrhoea develops
Consider dose reduction in hepatic impairment
Absorption of drug may be impaired by a high protein diet
Advise patient urine may be coloured reddish brown
Advise patient/carer about symptoms of impulse control disorders
Advise patients that hallucinations can occur
In patients due to receive a general anaesthetic, the product may continue to be taken as long as oral fluids and medicinal products are permitted. As soon as the nil-by-mouth restriction is lifted after the anaesthetic it is possible to re-start the treatment.
Consider a general medical examination, including liver function, in patients who experience progressive anorexia, asthenia and loss of weight within a short period of time.
Pregnancy and Lactation
Pregnancy
Levodopa with carbidopa and entacapone is contraindicated in pregnancy.
The potential risk for humans is unknown as there are no adequate data from the use of this combination in pregnant women, however, animal studies have shown reproductive toxicity of the separate compounds. Entacapone has been associated with decreased foetal weight and slightly delayed bone development in rabbits. Levodopa and combinations of levodopa and carbidopa have been associated with visceral and skeletal malformations in rabbits.
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
Levodopa with carbidopa and entacapone is contraindicated in breastfeeding.
Levodopa is excreted in human breast milk, and there is evidence that lactation is suppressed during treatment with levodopa. Carbidopa and entacapone are excreted in the milk of animals but it is not known whether they are excreted in human breast milk. The safety of levodopa, carbidopa or entacapone in the infant is not known.
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
Abnormal liver function tests
Activation of latent Horner's syndrome
Agitation
Angioedema
Anorexia
Anxiety
Arthralgia
Asthenia
Ataxia
Bitter taste
Blepharospasm
Blood disorders
Blood dyscrasias
Blurred vision
Bruxism
Chest pain
Cholestatic hepatitis
Chromaturia
Cognitive impairment
Compulsive disorders
Confusion
Constipation
Convulsions
Dark sweat
Darkening of urine
Decreased appetite
Delusions
Depression
Diplopia
Discolouration of hair
Dizziness
Dream abnormalities
Dry mouth
Duodenal ulcer
Dyskinesia
Dyspepsia
Dysphagia
Dyspnoea
Dysrhythmia
Erythematous rash
Euphoria
Faintness
Falls
Fatigue
Flatulence
Flushing
Gait abnormality
Gastro-intestinal disturbances
Gastro-intestinal haemorrhage
Gastrointestinal bleeding
Glaucoma (closed angle)
Hair loss
Hallucinations
Headache
Hiccups
Hoarseness
Hyperkinesia
Hypersexuality
Hypertension
Increased libido
Increased sweating
Insomnia
Malaise
Malignant melanoma
Mental status changes
Movement disturbances
Muscle pain
Muscular cramps
Neuroleptic malignant syndrome
Nightmares
Numbness
Oculogyric crisis
Oedema
Orthostatic hypotension
Paraesthesia
Paranoia
Pathological gambling
Phlebitis
Possible alteration of laboratory tests
Priapism
Pruritus
Psychotic episodes
Pupillary dilatation
Rash
Rhabdomyolysis
Sense of stimulation
Sialorrhoea
Skin discolouration
Somnolence
Suicidal tendencies
Tremor
Trismus
Unusual breathing patterns
Urinary incontinence
Urinary retention
Urticaria
Weakness
Weight changes
Worsening of Parkinson's disease
Effects on Laboratory Tests
False positive for urinary dipstick tests for ketone.
False negative for glycosuria if glucose oxidase methods are used.
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 2015
Reference Sources
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 (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on 12 March, 2015.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Summary of Product Characteristics: Sastravi 50/12.5/200mg. Actavis (UK) Ltd. Revised September 2014.
Summary of Product Characteristics: Sastravi 75/18.75/200mg. Actavis (UK) Ltd. Revised September 2014.
Summary of Product Characteristics: Sastravi 100/25/200mg. Actavis (UK) Ltd. Revised September 2014.
Summary of Product Characteristics: Sastravi 125/31.25/200mg. Actavis (UK) Ltd. Revised September 2014.
Summary of Product Characteristics: Sastravi 150/37.5/200mg. Actavis (UK) Ltd. Revised September 2014.
Summary of Product Characteristics: Sastravi 175/43.75/200mg. Actavis (UK) Ltd. Revised September 2014.
Summary of Product Characteristics: Sastravi 200/50/200mg. Actavis (UK) Ltd. Revised September 2014.
Summary of Product Characteristics: Stalevo 50/12.5/200mg. Orion Pharma (UK) Ltd. Revised July 2019.
Summary of Product Characteristics: Stalevo 75/18.75/200mg. Orion Pharma (UK) Ltd. Revised July 2019.
Summary of Product Characteristics: Stalevo 100/25/200mg. Orion Pharma (UK) Ltd. Revised July 2019.
Summary of Product Characteristics: Stalevo 125/31.25/200mg. Orion Pharma (UK) Ltd. Revised July 2019.
Summary of Product Characteristics: Stalevo 150/37.5/200mg. Orion Pharma (UK) Ltd. Revised July 2019..
Summary of Product Characteristics: Stalevo 175/43.75/200mg. Orion Pharma (UK) Ltd. Revised July 2019.
Summary of Product Characteristics: Stalevo 200/50/200mg. Orion Pharma (UK) Ltd. Revised July 2019.
Summary of Product Characteristics: Stanek 50/12.5/200mg. Teva UK Limited. Revised January 2015.
Summary of Product Characteristics: Stanek 75/18.75/200mg. Teva UK Limited. Revised January 2015.
Summary of Product Characteristics: Stanek 100/25/200mg. Teva UK Limited. Revised January 2015.
Summary of Product Characteristics: Stanek 125/31.25/200mg. Teva UK Limited. Revised January 2015.
Summary of Product Characteristics: Stanek 150/37.5/200mg. Teva UK Limited. Revised January 2015.
Summary of Product Characteristics: Stanek 175/43.75/200mg. Teva UK Limited. Revised January 2015.
Summary of Product Characteristics: Stanek 200/50/200mg. Teva UK Limited. Revised January 2015.
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