Stalevo

Stalevo

carbidopa + levodopa + entacapone

Manufacturer:

Orion

Distributor:

Harn Thai

Marketer:

Orion Pharma Thai
Full Prescribing Info
Contents
Levodopa, carbidopa, entacapone.
Description
Each 100/25/200 mg tablet contains of levodopa 100 mg, carbidopa 25 mg and entacapone 200 mg.
Each 150/37.5/200 mg tablet contains levodopa 150 mg, carbidopa 37.5 mg and entacapone 200 mg.
Each tablet also contains the following excipients: Tablet core: Croscarmellose sodium, magnesium stearate, maize starch, mannitol and povidone K30; film-coating: Glycerol 85%, hypromellose, magnesium stearate, polysorbate 80, red iron oxide (E172), sucrose, titanium dioxide (E171) and yellow iron oxide (E172).
Action
Antiparkinsonian dopaminergic drug.
Pharmacology: Pharmacodynamics: According to current understanding, the symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Dopamine does not cross the blood-brain barrier. Levodopa, the precursor of dopamine, crosses the blood-brain barrier and relieves the symptoms of the disease. As levodopa is extensively metabolised in the periphery, only a small portion of a given dose reaches the central nervous system when levodopa is administered without metabolic enzyme inhibitors.
Carbidopa and benserazide are peripheral dopa decarboxylase (DDC) inhibitors which reduce the peripheral metabolism of levodopa to dopamine, resulting in an increase in the amount of levodopa available to the brain. When decarboxylation of levodopa is reduced with the co-administration of a DDC inhibitor, a lower dose of levodopa can be used and the incidence of undesirable effects eg, nausea is reduced.
With the inhibition of the decarboxylase by a DDC inhibitor, catechol O-methyltransferase (COMT) becomes the major peripheral metabolic pathway catalyzing the conversion of levodopa to 3-O-methyldopa (3-OMD), a potentially harmful metabolite of levodopa. Entacapone is a reversible, specific and mainly peripherally acting COMT inhibitor designed for concomitant administration with levodopa. Entacapone slows the clearance of levodopa from the bloodstream resulting in an increased area under the curve (AUC) in the pharmacokinetic profile of levodopa. Consequently the clinical response to each dose of levodopa is enhanced and prolonged.
The evidence of the therapeutic effects of Stalevo is based on 2 phase III double-blind studies, in which 376 Parkinson's disease patients with end-of-dose motor fluctuations received either entacapone or placebo with each levodopa/DDC inhibitor dose. Daily ON time with and without entacapone was recorded in home-diaries by patients. In the 1st study, entacapone increased the mean daily ON time by 1 hr 20 min (CI95% 45 min, 1 hr 56 min) from baseline. This corresponded to an 8.3% increase in the proportion of daily ON time. Correspondingly, the decrease in daily OFF time was 24% in the entacapone group and 0% in the placebo group. In the 2nd study, the mean proportion of daily ON time increased by 4.5% (CI95% 0.93%, 7.97%) from baseline. This is translated to a mean increase of 35 min in the daily ON time. Correspondingly, the daily OFF time decreased by 18% on entacapone and by 5% on placebo. Because the effects of Stalevo tablets are equivalent with entacapone 200-mg tab administered concomitantly with the commercially available standard release carbidopa/levodopa preparations in corresponding doses these results are applicable to describe the effects of Stalevo as well.
Pharmacokinetics: General Characteristics of the Active Substances: Absorption/Distribution: There are substantial inter- and intraindividual variations in the absorption of levodopa, carbidopa and entacapone. Both levodopa and entacapone are rapidly absorbed and eliminated. Carbidopa is absorbed and eliminated slightly more slowly than levodopa. When given separately without the other 2 active substances, the bioavailability of levodopa is 15-33%, that of carbidopa 40-70% and that of entacapone 35% after a 200-mg oral dose. Meals rich in large neutral amino acids may delay and reduce the absorption of levodopa. Food does not significantly affect the absorption of entacapone. The distribution volume of both levodopa (Vd 0.36-1.6 L/kg) and entacapone (Vdss 0.27 L/kg) is moderately small; no data are available for carbidopa.
Levodopa is bound to plasma proteins only to a minor extent (about 10-30%), while carbidopa is bound approximately 36%, and while entacapone is extensively bound (about 98%), mainly to serum albumin. At therapeutic concentrations, entacapone does not displace other extensively bound active substances (eg, warfarin, salicylic acid, phenylbutazone or diazepam), nor is it displaced to any significant extent by any of these substances at therapeutic or higher concentrations.
Metabolism and Elimination: Levodopa is extensively metabolised to various metabolites, decarboxylation by DDC and O-methylation by catechol-O-methyltransferase (COMT) being the most important pathways.
Carbidopa is metabolised to 2 main metabolites which are excreted in the urine as glucuronides and unconjugated compounds. Unchanged carbidopa accounts for 30% of the total urinary excretion.
Entacapone is almost completely metabolised prior to excretion via urine (10-20%) and bile/faeces (80-90%). The main metabolic pathway is glucuronidation of entacapone and its active metabolite, the cis-isomer, which accounts for about 5% of the total amount in plasma.
Total clearance of levodopa is in the range of 0.55-1.38 L/kg/hr and that of entacapone is in the range of 0.7 L/kg/hr. The elimination-half life (t½) is 0.6-1.3 hrs for levodopa, 2-3 hrs for carbidopa and 0.4-0.7 hrs for entacapone, each given separately.
Due to short elimination half-lives, no true accumulation of levodopa or entacapone occurs on repeated administration.
Data from in vitro studies using human liver microsomal preparations indicate that entacapone inhibits cytochrome P-450 2C9 (IC50~4 micromole). Entacapone showed little or no inhibition of other types of P-450 isoenzymes (CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A and CYP2C19) (see Interactions).
Toxicology: Preclinical Safety Data: Preclinical data for levodopa, carbidopa and entacapone tested alone or in combination revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. In repeated dose toxicity studies with entacapone, anaemia, most probably due to iron chelating properties of entacapone, was observed. Regarding reproduction toxicity of entacapone, decreased foetal weight and a slightly delayed bone development were noticed in rabbits treated at systemic exposure levels in the therapeutic range. Both levodopa and combinations of carbidopa and levodopa have caused visceral and skeletal malformations in rabbits.
Indications/Uses
Treatment of patients with Parkinson's disease and end-of-dose motor fluctuations not stabilised on levodopa/DDC inhibitor treatment.
Dosage/Direction for Use
Each tablet is to be taken orally either with or without food (see Pharmacokinetics). One tablet contains 1 treatment dose. The tablets should always be swallowed whole.
The optimum daily dosage must be determined by careful titration of levodopa in each patient. The daily dose should preferably be optimised using 1 of the 3 available tablet strengths (100/25/200 mg or 150/37.5/200 mg levodopa/carbidopa/entacapone).
Patients should be instructed to take only 1 Stalevo tab/dose administration. Patients receiving <70-100 mg carbidopa a day are more likely to experience nausea and vomiting. While the experience with total daily dosage >200 mg carbidopa is limited, the maximum recommended daily dose of entacapone is 2000 mg and therefore the maximum Stalevo dose is 10 tabs/day.
Usually Stalevo is intended for use in patients already receiving treatment with corresponding doses of standard-release levodopa/DDC inhibitor and entacapone.
Starting Stalevo Therapy: As with levodopa/carbidopa, nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with Stalevo. These inhibitors must be discontinued at least 2 weeks prior to initiating therapy with Stalevo. Stalevo may be administered concomitantly with the manufacturer's recommended dose of MAO inhibitors with selectivity for MAO type B (eg, selegiline HCl).
Switching from Levodopa/DDC Inhibitor (Carbidopa or Benserazide) Preparations and Entacapone to Stalevo:
a. Patients who are currently receiving treatment with entacapone and standard-release levodopa/carbidopa in doses equal to Stalevo tablet strengths can be directly switched to the corresponding Stalevo tablets. For example, patients taking 1 tab of 100/25 mg levodopa/carbidopa with 1 tab of entacapone 200 mg 4 times daily can be switched to one 100/25/200 mg Stalevo tablet 4 times daily.
b. When initiating Stalevo therapy in patients currently receiving treatment with entacapone and levodopa/carbidopa in doses not equal to the available Stalevo tablet strengths (100/25/200 or 150/37.5/200 mg), Stalevo dosing should be carefully titrated for optimal clinical response. At the start of therapy, Stalevo should be adjusted to correspond as closely as possible to the total daily dose of levodopa currently used.
c. When initiating Stalevo in patients currently treated with entacapone and levodopa/benserazide in a standard-release formulation, treatment should be stopped for 1 night and Stalevo therapy started the next morning. The therapy should begin with a dosage of Stalevo that will provide either the same amount of levodopa or slightly (5-10%) more.
Switching in Patients not Currently Treated with Entacapone to Stalevo: Initiation of Stalevo at a dosage corresponding to current treatment may be considered in some patients with Parkinson's disease and end-of-dose motor fluctuations who are not stabilised on their current standard-release levodopa/DDC inhibitor treatment. However, a direct switch from levodopa/DDC inhibitor to Stalevo is not recommended for patients who have dyskinesias or whose daily levodopa dose is >800 mg. In such patients it is advisable to introduce entacapone treatment as a separate medication (entacapone tablets) and adjust the levodopa dose if necessary, before switching to Stalevo.
Entacapone enhances the effects of levodopa. It may therefore be necessary, particularly in patients with dyskinesia, to reduce levodopa dosage by 10-30% within the 1st days to 1st weeks after initiating Stalevo treatment. 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 the Treatment: When more levodopa is required, an increase in the frequency of doses and/or the use of an alternative strength of Stalevo should be considered, within the dosage recommendations.
When less levodopa is required, the total daily dosage of Stalevo should be reduced either by decreasing the frequency of administration by extending the time between doses, or by decreasing the strength of Stalevo at an administration.
If other levodopa products are used concomitantly with a Stalevo tablet, the maximum dosage recommendations should be followed.
Discontinuation of Stalevo Therapy: If Stalevo treatment (levodopa/carbidopa/entacapone) is discontinued and the patient is switched 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 control of the parkinsonian symptoms (see Rhabdomyolysis under Precautions).
Children and Adolescents: The safety and efficacy of Stalevo in patients <18 years have not been established. Therefore, the use of Stalevo in patients <18 years cannot be recommended.
Elderly: No adjustment of Stalevo dosage is necessary in elderly patients.
Hepatic Impairment: Caution is recommended when administering Stalevo to patients with mild to moderate hepatic impairment. Dose reduction may be necessary.
Renal Insufficiency: Renal insufficiency does not affect the pharmacokinetics of entacapone. No specific studies are reported on the pharmacokinetics of levodopa and carbidopa in patients with renal insufficiency, and Stalevo should therefore be administered with caution in patients with severe renal impairment including those receiving dialysis therapy.
Overdosage
No case of overdose has been reported.
Management of acute overdosage with Stalevo is similar to acute overdosage with levodopa. Hospitalisation is advised and general supportive measures should be employed with immediate gastric lavage and repeated doses of charcoal over time. This may hasten the elimination of entacapone in particular by decreasing its absorption/reabsorption from the gastrointestinal tract. The adequacy of the respiratory, circulatory and renal systems should be carefully monitored and appropriate supportive measures employed. ECG monitoring should be started and the patient carefully monitored for the possible development of arrhythmias. If required, appropriate antiarrhythmic therapy should be given. The possibility that the patient has taken other active substances in addition to Stalevo should be taken into consideration. The value of dialysis in the treatment of overdosage is not known.
Contraindications
Known hypersensitivity to the active substances or to any of the excipients of Stalevo. Severe hepatic impairment. Narrow-angle glaucoma. Pheochromocytoma.
Concomitant use of a nonselective monoamine oxidase (MAO-A and MAO-B) inhibitor (eg, phenelzine, tranylcypromine).
Concomitant use of a selective MAO-A inhibitor and a selective MAO-B inhibitor (see Starting Stalevo Therapy under Dosage & Administration and Other Antiparkinsonian Medicinal Products under Interactions).
A history of neuroleptic malignant syndrome (NMS) and/or nontraumatic rhabdomyolysis.
Special Precautions
Stalevo is not recommended for the treatment of drug-induced extrapyramidal reactions.
Stalevo therapy should be administered with caution to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or convulsions.
In patients with a history of myocardial infarction who have residual atrial nodal or ventricular arrhythmias, cardiac function should be monitored with particular care during the period of initial dosage adjustments.
All patients treated with Stalevo should be monitored carefully for the development of mental changes (eg, hallucinoses and psychoses), depression with suicidal tendencies and serious antisocial behaviour. Patients with past or current psychosis should be treated with caution.
Concomitant administration of antipsychotics with dopamine receptor-blocking properties, particularly D2-receptor antagonists, should be carried out with caution and the patient carefully observed for loss of antiparkinsonian effect or worsening of parkinsonian symptoms.
Patients with chronic wide-angle glaucoma may be treated with Stalevo with caution, provided the intraocular pressure is well controlled and the patient is monitored carefully for changes in intraocular pressure.
Stalevo may induce orthostatic hypotension. Therefore, caution is necessary when giving Stalevo to patients who are taking other medicinal products which may cause orthostatic hypotension.
Entacapone in combination with levodopa has been associated with somnolence and episodes of sudden sleep onset in patients with Parkinson's disease and caution should therefore be exercised when driving or operating machines (see also Effects on the Ability to Drive or Operate Machinery as follows).
In clinical studies, undesirable dopaminergic effects eg, dyskinesia, were more common in patients who received entacapone and dopamine agonists (eg, bromocriptine), selegiline or amantadine compared to those who received placebo with this combination. The doses of other antiparkinsonian medicinal products may need to be adjusted when Stalevo is introduced in a patient not previously treated with entacapone.
Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson's disease. Close monitoring is therefore necessary in an event of abrupt dosage reductions or withdrawal of levodopa, particularly in patients who are also receiving neuroleptics. NMS, including rhabdomyolysis and hyperthermia, is characterised by motor symptoms (rigidity, myoclonus, tremor), mental status changes (eg, agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase. In individual cases, only some of these symptoms and/or findings may be evident. Early diagnosis is important for the appropriate management of NMS. A syndrome resembling NMS including muscular rigidity, elevated body temperature, mental changes and increased serum creatine phosphokinase has been reported with the abrupt withdrawal of antiparkinsonian agents. Neither NMS nor rhabdomyolysis was reported in association with entacapone treatment in controlled trials in which entacapone was discontinued abruptly. Since the introduction of entacapone into the market, cases with some similar signs and symptoms have been rarely reported. Prescribers should exercise caution when switching patients from Stalevo to levodopa/DDC inhibitor therapy without entacapone. When considered necessary, the replacement of Stalevo with levodopa and DDC inhibitor without entacapone should proceed slowly and an increase in levodopa dosage may be necessary.
If general anaesthesia is required, therapy with Stalevo may be continued for as long as the patient is permitted to take fluids and medication by mouth. If therapy has to be stopped temporarily, Stalevo may be restarted as soon as oral medication can be taken at the same daily dosage as before.
Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with Stalevo.
For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease.
Effects on the Ability to Drive or Operate Machinery: Levodopa, carbidopa and entacapone together may cause dizziness and symptomatic orthostatism. Therefore, caution should be exercised when driving or using machines.
Patients being treated with Stalevo and presenting with somnolence and/or sudden sleep onset episodes must be instructed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (eg, operating machines) until such recurrent episodes have resolved (see also Precautions).
Use in Pregnancy: There are no adequate data from the use of the combination of levodopa/carbidopa/entacapone in pregnant women. Studies in animals have shown reproductive toxicity of the separate compounds (see Toxicology: Preclinical Safety Data under Actions). The potential risk for humans is unknown. Stalevo should not be used during pregnancy.
Use in Lactation: Levodopa is excreted in human breast milk. There is evidence that lactation is suppressed during treatment with levodopa. Carbidopa and entacapone were excreted in milk in 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. Women should not breastfeed during treatment with Stalevo.
Use In Pregnancy & Lactation
Use in Pregnancy: There are no adequate data from the use of the combination of levodopa/carbidopa/entacapone in pregnant women. Studies in animals have shown reproductive toxicity of the separate compounds (see Toxicology: Preclinical Safety Data under Actions). The potential risk for humans is unknown. Stalevo should not be used during pregnancy.
Use in Lactation: Levodopa is excreted in human breast milk. There is evidence that lactation is suppressed during treatment with levodopa. Carbidopa and entacapone were excreted in milk in 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. Women should not breastfeed during treatment with Stalevo.
Adverse Reactions
The following section describes the undesirable effects reported for levodopa/carbidopa and for entacapone used in combination with levodopa/DDC inhibitor.
Levodopa/Carbidopa: Undesirable effects that occur frequently with levodopa/carbidopa are those due to the central neuropharmacological activity of dopamine. These reactions can usually be diminished by levodopa dosage reduction. The most common undesirable effects are dyskinesias including choreiform, dystonic and other involuntary movements. Muscle twitching and blepharospasm may be taken as early signs to consider levodopa dosage reduction. Nausea, also related to enhanced central dopaminergic activity, is a common adverse effect of levodopa/carbidopa.
Other undesirable effects associated with levodopa/carbidopa therapy are mental changes, including paranoid ideation and psychotic episodes; depression, with or without development of suicidal tendencies; and cognitive dysfunction. Adding of entacapone to levodopa/DDC inhibitor therapy (carbidopa or benserazide) ie, initiation of Stalevo treatment in an entacapone-naive patient, may aggravate some of these mental changes (see table, Psychiatric Disorders).
Less frequent undesirable effects of levodopa/carbidopa therapy are irregular heart rhythm and/or palpitations, orthostatic hypotensive episodes, bradykinetic episodes (the 'on-off' phenomenon), anorexia, vomiting, dizziness and somnolence.
Gastrointestinal bleeding, development of duodenal ulcer, hypertension, phlebitis, leucopenia, haemolytic and nonhaemolytic anaemia, thrombocytopenia, agranulocytosis, chest pain, dyspnoea and paraesthesia have occurred rarely with levodopa/carbidopa.
Convulsions have occurred rarely with levodopa/carbidopa; however a causal relationship to levodopa/carbidopa therapy has not been established.
Other undesirable effects that have been reported with levodopa and may, therefore, also be potential undesirable effects of Stalevo, include:
Metabolism and Nutrition Disorders: Weight gain or loss, oedema.
Psychiatric Disorders: Confusion, insomnia, nightmares, hallucinations, delusions, agitation, anxiety, euphoria.
Nervous System Disorders: Ataxia, numbness, increased hand tremor, muscle twitching, muscle cramp, trismus, activation of latent Horner's syndrome. Falling and gait abnormalities are also potential undesirable effects.
Eye Disorders: Diplopia, blurred vision, dilated pupils, oculogyric crises.
Gastrointestinal Disorders: Dry mouth, bitter taste, sialorrhoea, dysphagia, bruxism, hiccups, abdominal pain and distress, constipation, diarrhoea, flatulence, burning sensation of the tongue.
Skin and Subcutaneous Tissue Disorders: Flushing, increased sweating, dark sweat, rash, hair loss.
Renal and Urinary Disorders: Urinary retention, urinary incontinence, dark urine, priapism.
Miscellaneous: Weakness, faintness, fatigue, headache, hoarseness, malaise, hot flushes, sense of stimulation, bizarre breathing patterns, NMS, malignant melanoma.
Entacapone: The most frequent adverse reactions caused by entacapone relate to the increased dopaminergic activity and occur most commonly at the beginning of the treatment. Reduction of levodopa dosage decreases the severity and frequency of the reactions. The other major class of adverse reactions are gastrointestinal symptoms eg, nausea, vomiting, abdominal pain, constipations and diarrhoea. Urine may be discoloured reddish-brown by entacapone, but this is a harmless phenomenon.
The following adverse reactions, listed in the following table, have been accumulated both from clinical studies with entacapone as an adjunct to levodopa/DDC inhibitor and since the introduction of entacapone into the market for the combination use of entacapone with levodopa/DDC inhibitor.
Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000), including isolated reports. Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. (See table.)

Click on icon to see table/diagram/image

Entacapone used in combination with levodopa has been associated with isolated cases of excessive daytime somnolence and sudden sleep onset episodes (see Effects on the Ability to Drive or Operate Machinery under Precautions).
Laboratory Tests: The following laboratory abnormalities have been reported with levodopa/carbidopa treatment and should, therefore, be borne in mind when treating patients with Stalevo:
Commonly, levels of BUN, creatinine and uric acid are lower during administration of levodopa/carbidopa than with levodopa alone. Transient abnormalities include elevated values of blood urea, AST (SGOT), ALT (SGPT), LDH, bilirubin and alkaline phosphatase.
Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.
Positive Coombs' tests have been reported, both for levodopa/carbidopa and for levodopa alone, but haemolytic anaemia is extremely rare.
Levodopa/carbidopa may cause false-positive result when a dipstick is used to test for urinary ketone; this reaction is not altered by boiling the urine sample. The use of glucose oxidase methods may give false-negative results for glycosuria.
Drug Interactions
Other Antiparkinsonian Medicinal Products: To date there has been no indication of interactions that would preclude concurrent use of standard antiparkinsonian medicinal products with Stalevo therapy. Entacapone in high doses may affect the absorption of carbidopa. However, no interaction with carbidopa has been observed with the recommended treatment schedule (200 mg of entacapone up to 10 times daily). Interactions between entacapone and selegiline have been investigated in repeated dose studies in Parkinson's disease patients treated with levodopa/DDC inhibitor and no interaction was observed. When used with Stalevo, the daily dose of selegiline should not exceed 10 mg.
Because Stalevo contains entacapone, it should not be used concurrently with Comtan (entacapone).
Caution should be exercised when the following active substances are administered concomitantly with levodopa therapy.
Antihypertensives: Symptomatic postural hypotension may occur when levodopa is initiated in patients already receiving antihypertensives. Dosage adjustment of the antihypertensive agent may be required.
Antidepressants: Rarely, reactions including hypertension and dyskinesia have been reported with the concomitant use of tricyclic antidepressants and levodopa/carbidopa. Interactions between entacapone and imipramine and between entacapone and moclobemide have been investigated in single-dose studies in healthy volunteers. No pharmacodynamic interactions were observed. A significant number of Parkinson's disease patients have been treated with the combination of levodopa, carbidopa and entacapone with several active substances including MAO-A inhibitors, tricyclic antidepressants, noradrenaline reuptake inhibitors eg, desipramine, maprotiline and venlafaxine and medicinal products that are metabolised by COMT (eg, catechol-structured compounds: Rimiterol, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, α-methyldopa, apomorphine and paroxetine). No pharmacodynamic interactions have been observed. However, caution should be exercised when these medicinal products are used concomitantly with Stalevo (see also Contraindications and Precautions).
Other Active Substances: Dopamine receptor antagonists (eg, some antipsychotics and antiemetics), phenytoin and papaverine may reduce the therapeutic effect of levodopa. Patients taking these medicinal products with Stalevo should be carefully observed for loss of therapeutic response.
Due to entacapone's affinity to cytochrome P-450 2C9 in vitro (see Pharmacokinetics), Stalevo may potentially interfere with active substances whose metabolism is dependent on this isoenzyme eg, S-warfarin. However, in an interaction study with healthy volunteers, entacapone did not change the plasma levels of S-warfarin, while the AUC for R-warfarin increased on average by 18% (CI90 11-26%). The INR values increased on average by 13% (CI90 6-19%). Thus, a control of INR is recommended when Stalevo is initiated in patients receiving warfarin.
Other Forms of Interactions: Since levodopa competes with certain amino acids, the absorption of Stalevo may be impaired in some patients on a high-protein diet.
Levodopa and entacapone may form chelates with iron in the gastrointestinal tract. Therefore, Stalevo and iron preparations should be taken at least 2-3 hrs apart (see Adverse Reactions).
Stalevo may be given to patients with Parkinson's disease who are taking vitamin preparations that contain pyridoxine HCl (vitamin B6).
Incompatibilities: Not applicable.
Storage
Do not store above 30°C.
ATC Classification
N04BA03 - levodopa, decarboxylase inhibitor and COMT inhibitor ; Belongs to the class of dopa and dopa derivative dopaminergic agents. Used in the management of Parkinson's disease.
Presentation/Packing
FC tab 50/12.5/200 mg x 100's. 100/25/200 mg x 100's. 150/37.5/200 mg x 100's. 200/50/200 mg x 100's.
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