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STALEVO (carbidopa, levodopa and entacapone) tablets,
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use STALEVO safely and effectively. See full prescribing information for STALEVO.
STALEVO ® (carbidopa, levodopa and entacapone) tablets, for oral use
Initial U.S. Approval: 2003
INDICATIONS AND USAGE
Stalevo, a combination drug consisting of levodopa (aromatic amino acid), carbidopa (aromatic amino acid decarboxylation inhibitor), and entacapone (catechol-O-methyltransferase (COMT) inhibitor) is indicated for the treatment of Parkinson's disease. Stalevo is to be used:
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To substitute (with equivalent strengths of each of the three components) for carbidopa/levodopa and entacapone previously administered as individual products (1)
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To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose "wearing-off" and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias (1)
DOSAGE AND ADMINISTRATION
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The optimum daily dosage of Stalevo must be determined by careful titration in each patient (2.1)
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Individual tablets should not be split or fractionated. Administer only one tablet at each dosing interval (2.6)
DOSAGE FORMS AND STRENGTHS
Each Stalevo tablet contains a 1:4 ratio of carbidopa to levodopa and 200 mg of entacapone (mg of carbidopa per mg of levodopa per mg of entacapone) (3)
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Stalevo 50 (12.5 mg per 50 mg per 200 mg)
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Stalevo 75 (18.75 mg per 75 mg per 200 mg)
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Stalevo 100 (25 mg per 100 mg per 200 mg)
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Stalevo 125 (31.25 mg per 125 mg per 200 mg)
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Stalevo 150 (37.5 mg per 150 mg per 200 mg)
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Stalevo 200 (50 mg per 200 mg per 200 mg)
CONTRAINDICATIONS
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Concomitant use of nonselective monoamine oxidase (MAO) inhibitors (4)
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Narrow-angle glaucoma (4)
WARNINGS AND PRECAUTIONS
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May cause falling asleep during activities of daily living without apparent warning, and daytime drowsiness and somnolence (5.1)
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May cause syncope and hypotension/orthostatic hypotension (5.2)
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May cause or exacerbate dyskinesia (5.3)
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May cause depression and suicidality (5.4)
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May cause hallucinations and/or other psychotic-like behavior (5.5)
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May cause problems with impulse control and compulsive behaviors (5.6)
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Abrupt discontinuation may cause hyperpyrexia and confusion (5.7)
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May cause diarrhea and/or drug-induced colitis (5.8)
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May cause rhabdomyolysis (5.9)
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Increased risk of melanoma (5.10)
ADVERSE REACTIONS
The most common adverse reactions (incidence 3% or higher than placebo incidence) are dyskinesias, urine discoloration, diarrhea, nausea, abdominal pain, vomiting, and dry mouth (6)
To report SUSPECTED ADVERSE REACTIONS, contact NOVARTIS PHARMACEUTICAL CORPORATION at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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Drugs metabolized by COMT: use with caution (5.11,7.2)
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Anti-hypertensive agents: dose adjustment may be required (7.3)
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Tricyclic antidepressants: risk of hypertension and dyskinesia reported during concomitant use with carbidopa/levodopa (7.4)
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Dopamine D2 receptor antagonists, isoniazid, phenytoin, papaverine and iron salts: may reduce efficacy of Stalevo (7.5, 7.6, 7.7, 7.8, 7.9)
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Drugs that interfere with biliary excretion, glucuronidation and intestinal beta-glucuronidase: dose adjustment of Stalevo may be required (7.10)
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Drugs metabolized by CYP2C9 (e.g., coumadin): dose adjustment of Stalevo may be required; monitor INR when initiating Stalevo in patients on coumadin (7.11)
USE IN SPECIFIC POPULATIONS
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Pregnancy: based on animal data, may cause fetal harm (8.1)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 7/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
Stalevo, a combination drug consisting of levodopa, carbidopa (dopa decarboxylase inhibitor), and entacapone (catechol-O-methyltransferase-COMT inhibitor) is indicated for the treatment of Parkinson's disease.
Stalevo can be used:
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To substitute (with equivalent strengths of each of the three components) carbidopa/levodopa and entacapone previously administered as individual products.
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To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose "wearing-off" and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias.
2 DOSAGE AND ADMINISTRATION
Stalevo should be used as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. However, some patients who have been stabilized on a given dose of carbidopa/levodopa may be treated with Stalevo if a decision has been made to add entacapone (see below). Therapy should be individualized and adjusted according to the desired therapeutic response.
2.1 Dosing Information
The optimum daily dosage of Stalevo must be determined by careful titration in each patient.
Clinical experience with daily doses above 1,600 mg of entacapone is limited. The maximum recommended daily dose of Stalevo depends on the strength used. The maximum number of tablets to be used in a 24-hour period is less with the highest strength (Stalevo 200) than with lower strengths (see Table 1). Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 mg per day to 100 mg per day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.
2.2 Converting Patients from Carbidopa, Levodopa, and Entacapone to Stalevo
Patients currently treated with entacapone 200 mg with each dose of non-extended release carbidopa/levodopa tablet, can switch to the corresponding strength of Stalevo containing the same amounts of levodopa and carbidopa. For example, patients receiving one tablet of carbidopa/levodopa 25 mg/100 mg and one tablet of entacapone 200 mg at each administration can switch to a single Stalevo 100 tablet (containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone).
2.3 Converting Patients from Carbidopa and Levodopa Products to Stalevo
There is no experience in transferring patients currently treated with extended release formulations of carbidopa/levodopa, or carbidopa/levodopa products that are not combined in a 1:4 ratio of carbidopa to levodopa.
Patients with a history of moderate or severe dyskinesias or taking more than 600 mg of the levodopa component per day are likely to require a reduction in their daily levodopa dose when entacapone is added. Because dose adjustment of the individual carbidopa or levodopa component is not possible with fixed-dose products, initially titrate patients to a dose that is tolerated and that meets their individual therapeutic need using a separate carbidopa/levodopa tablet (1:4 ratio) plus an entacapone tablet. Once the patient's individual dose of carbidopa/levodopa plus entacapone dose has been established using two separate tablets; switch the patient to a corresponding single tablet of Stalevo.
When less levodopa is required, reduce the total daily dosage of carbidopa/levodopa either by decreasing the strength of Stalevo at each administration or by decreasing the frequency of administration by extending the time between doses.
2.4 Concomitant Use with Other Anti-Parkinson's Disease Drugs
Anticholinergic agents, dopamine agonists, monoamine oxidase (MAO) - B inhibitors, amantadine, and other standard drugs for Parkinson's disease may be used concomitantly while Stalevo is being administered; however, dosage adjustments of the concomitant medication or Stalevo may be required.
2.5 Decrease or Interruption of Dosing
Avoid interruption of Stalevo dosing because hyperpyrexia has been reported in patients who suddenly discontinue or reduce their use of levodopa [see Warnings and Precautions (5.7)].
2.6 Important Administration Instructions
Do not split, crush or chew Stalevo tablets. Administer only one tablet at each dosing interval. All strengths of Stalevo contain 200 mg of entacapone. Combining multiple tablets or portions of tablets to achieve a higher levodopa dose may lead to an overdose of entacapone.
Administer Stalevo with or without food. However, a high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hours [see Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
Each Stalevo tablet, provided in 6 single-dose strengths, contains carbidopa and levodopa in a 1:4 ratio and a 200 mg dose of entacapone. Stalevo (carbidopa, levodopa and entacapone) is supplied as film-coated tablets for oral administration in the following 6 strengths:
Stalevo 50 film-coated tablets containing 12.5 mg of carbidopa, 50 mg of levodopa and 200 mg of entacapone. The round, bi-convex shaped tablets are brownish- or greyish-red, unscored, and embossed "LCE 50" on one side.
Stalevo 75 film-coated tablets containing 18.75 mg of carbidopa, 75 mg of levodopa and 200 mg of entacapone. The oval-shaped tablets are light brownish red, unscored and embossed with code "LCE 75" on one side.
Stalevo 100 film-coated tablets containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone. The oval-shaped tablets are brownish- or greyish-red, unscored, and embossed "LCE 100" on one side.
Stalevo 125 film-coated tablets containing 31.25 mg of carbidopa, 125 mg of levodopa and 200 mg of entacapone. The oval-shaped tablets are light brownish red, unscored and embossed with code "LCE 125" on one side.
Stalevo 150 film-coated tablets containing 37.5 mg of carbidopa, 150 mg of levodopa and 200 mg of entacapone. The elongated-ellipse shaped tablets are brownish- or greyish-red, unscored, and embossed "LCE 150" on one side.
Stalevo 200 film-coated tablets containing 50 mg of carbidopa, 200 mg of levodopa and 200 mg of entacapone. The oval shaped tablets are dark brownish red, unscored, and embossed "LCE 200" on one side.
4 CONTRAINDICATIONS
Stalevo is contraindicated in patients:
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Taking nonselective monoamine oxidase (MAO) inhibitors (e.g., phenelzine and tranylcypromine). These nonselective MAO inhibitors must be discontinued at least two weeks prior to initiating therapy with Stalevo.
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With narrow-angle glaucoma.
5 WARNINGS AND PRECAUTIONS
The following adverse reactions described in this section are related to at least one of the components of Stalevo (i.e., levodopa, carbidopa, and/or entacapone) based upon the safety experience in clinical trials (especially pivotal trials) or in postmarketing reports.
5.1 Falling Asleep During Activities of Daily Living and Somnolence
Patients with Parkinson's disease treated with Stalevo or other carbidopa/levodopa products have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (including the operation of motor vehicles). Some of these episodes resulted in accidents. Although many of these patients reported somnolence while taking entacapone, some did not perceive warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported to occur up to one year after initiation of treatment.
Somnolence was reported in 2% of patients taking entacapone and 0% in placebo in controlled trials. It is reported that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients who have already experienced somnolence and/or an episode of sudden sleep onset should not participate in these activities during treatment with Stalevo.
Before initiating treatment with Stalevo, |
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