Entacapone

Registered South African indications:

• Parkinson's disease

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hepatic impairment
• Phaeochromocytoma
• Previous history of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis
• Coadministration with non-selective monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, tranylcypromine)
• Coadministration with a selective MAO-A inhibitor plus a selective MAO-B inhibitor

Cautions

• Pregnancy
• Breastfeeding
• Abrupt withdrawal
• Ischaemic heart disease
• Risk factors for orthostatic hypertension
• Persistent or prolonged diarrhoea
• Anorexia
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• May affect ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Parkinson's disease (additional agent required)

• Oral (tab): 200mg, to be taken with each dose of levodopa/dopa carboxylase inhibitor; Max: 2000mg/24hrs

See Additional Prescribing Points 

Not established for use in children below 18 years

Pregnancy

• Caution; not recommended
• No overt teratogenic or primary foetotoxic effects were observed in animal studies in which the exposure levels of entacapone were markedly higher than the therapeutic exposure levels
• Although the near absence of human pregnancy experience prevents an assessment of the risk to the embryo-foetus, inadvertent exposure to entacapone during early gestation does not appear to present a significant risk
• Animal data suggest moderate risk
• As there is no experience in pregnant women, entacapone should not be used during pregnancy

Breastfeeding

• Caution; not recommended
• In animal studies, entacapone was excreted in milk. The safety of entacapone in infants is unknown
• Women should not breastfeed during treatment with entacapone
• Entacapone is usually given with levodopa/carbidopa. Even though levodopa inhibits prolactin release, normal lactation has been reported while women were being treated with the drug, and levodopa is excreted into breast milk. In addition, the effect of entacapone on levodopa metabolism will increase the amount of plasma levodpa available for transfer into milk. The use of carbidopa during lactation has also been described
• Therefore, a nursing infant will probably be exposed to all three drugs via the milk. The effects of this multiple exposure on a breastfeeding infant are unknown but warrant investigation

Renal Impairment

• No dose adjustment recommended
  A longer dosing interval may be considered for patients on dialysis

Hepatic Impairment

• Contraindicated 

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Insomnia
• Hallucinations
• Confusion
• Paroniria
• Agitation
• Dyskinesia
• Aggravated parkinsonism
• Dizziness
• Dystonia
• Hyperkinesia
• Fatigue
• Excessive daytime somnolence (in association with levodopa)
• Impulse control disorders (in association with levodopa)
  - Pathological gambling
  - Increased libido
  - Hypersexuality
  - Compulsive spending or buying
  - Binge eating
  - Compulsive eating

Cardiovascular Disorders

• Myocardial infarction
• Angina pectoris
• Ischaemic heart disease events

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Dry mouth
• Constipation
• Anorexia
• Colitis

Hepatobiliary Disorders

• Abnormal hepatic function tests
• Hepatitis with mainly choestatic features

Genitourinary Disorders

• Urine discoloration

Endocrine and Metabolic Disorders

• Decreased weight

Musculoskeletal Disorders

• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Erythematous or maculopapular rash
• Urticaria
• Skin, hair, beard and nail discolorations
• Increased sweating

Other

• Falling
• Neuroleptic malignant syndrome

• Monoamine oxidase inhibitors (MAO-A and MAO-B)
• Phenelzine
• Tranylcypromine
• Catechol-O-methyl transferase metabolites
• Rimiterol
• Isoprenaline
• Adrenaline
• Noradrenaline
• Dopamine
• Dobutamine
• Alpha-methyldopa
• Apomorphine
• Paroxetine
• Tricyclic antidepressants
• Noradrenaline reuptake inhibitors
• Desipramine
• Maprotiline
• Venlafaxine
• Iron preparations
• CYP2C9 substrates

• Mental status
• Hepatic function
• Blood pressure
• Dermatological examination

Specific cases may require

• Serum iron
• Weight

Coadministration with levodopa

• Entacapone is always given as an adjunct to levodopa treatment. Hence, the precautions valid for levodopa treatment should also be taken into account for entacapone treatment
• Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide preparations 5-10% more than from standard levodopa/carbidopa treatment
• To reduce levodopa-related dopaminergic adverse reactions, it is often necessary to adjust levodopa dosage within the first days to first weeks after initiating entacapone treatment, according to the clinical condition of the patient

Coadministration with other anti-Parkinsonian agents

• In clinical studies, adverse dopaminergic reactions e.g. dyskinesia, were more common in patients who received entacapone and dopamine agonists (such as bromocriptine), selegiline or amantadine compared to those who received placebo with this combination
• The doses of other anti-Parkinsonian medicinal products may need to be adjusted when entacapone treatment is initiated

Entacapone belongs to a new therapeutic class, catechol-O-methyl transferase (COMT) inhibitors. It is a reversible, specific, and mainly peripherally acting COMT inhibitor designed for concomitant administration with levodopa preparations. Entacapone decreases the metabolic loss of levodopa to 3-O-methyldopa (3-OMD) by inhibiting the COMT enzyme. This leads to a higher levodopa AUC. The amount of levodopa available to the brain is increased. Entacapone thus prolongs the clinical response to levodopa.

Tablet 200mg

• Comtan (Novartis) originator

COMBINATION PREPARATIONS

Carbidopa/ Entacapone/ Levodopa

Tablet 12.5mg/200mg/50mg

• Stalevo 50/2.5 (Novartis) originator

Tablet 25mg/200mg/100mg

• Stalevo 100/25 (Novartis) originator

Tablet 37.5mg/200mg/150mg

• Stalevo 150/37.5 (Novartis) originator