Stalevo 25 mg + 100 mg + 200 mg Tablets

Brand Name

This pharmaceutical product is marketed under the trade name Stalevo, a label widely recognized in the treatment of neurological movement disorders.

International Non-Proprietary Name

The active components are identified globally as levodopa, carbidopa, and entacapone, following the international nomenclature for medicinal substances.

Form of Release

The drug is available exclusively as film-coated tablets, designed for oral administration. It comes in multiple combination strengths: 50 milligrams levodopa with 12.5 milligrams carbidopa and 200 milligrams entacapone, 75 milligrams levodopa with 18.75 milligrams carbidopa and 200 milligrams entacapone, 100 milligrams levodopa with 25 milligrams carbidopa and 200 milligrams entacapone, 125 milligrams levodopa with 31.25 milligrams carbidopa and 200 milligrams entacapone, 150 milligrams levodopa with 37.5 milligrams carbidopa and 200 milligrams entacapone, and 200 milligrams levodopa with 50 milligrams carbidopa and 200 milligrams entacapone.

Composition

The medication contains three active ingredients: levodopa, the precursor to dopamine; carbidopa, a decarboxylase inhibitor; and entacapone, a COMT inhibitor, working together to enhance dopaminergic effects. The tablets include excipients such as microcrystalline cellulose, crospovidone, magnesium stearate, and hypromellose, ensuring stability and effective release. A film coating with titanium dioxide and iron oxides provides additional protection and identification.

Pharmacologic Properties

Pharmacodynamics

This treatment combines three complementary mechanisms to manage dopamine deficiency. Levodopa crosses the blood-brain barrier and converts into dopamine, replenishing levels in the brain to improve motor function. Carbidopa inhibits peripheral decarboxylation of levodopa, increasing its availability for central action and reducing peripheral side effects. Entacapone blocks catechol-O-methyltransferase (COMT), an enzyme that degrades levodopa, prolonging its duration of effect and stabilizing dopamine levels.

Clinical evidence shows this triple combination reduces motor fluctuations and enhances symptom control compared to levodopa alone. It targets the striatum, restoring dopaminergic signaling to alleviate rigidity, tremors, and bradykinesia. The synergy provides a smoother therapeutic response, particularly in advanced stages, without altering disease progression.

Pharmacokinetics

After oral intake, levodopa absorbs rapidly from the small intestine, reaching peak plasma levels in 0.5 to 2 hours, though food, especially protein-rich meals, may delay this. Carbidopa peaks in 2 to 3 hours, while entacapone achieves maximum concentration in 1 to 2 hours. Bioavailability varies: levodopa at 15 to 30 percent due to peripheral metabolism, carbidopa at 40 to 70 percent, and entacapone near 35 percent.

Levodopa distributes with a volume of 0.9 to 1.6 liters per kilogram, crossing into the brain, while carbidopa and entacapone remain largely peripheral, with volumes of 0.3 and 0.2 liters per kilogram, respectively. Levodopa binds to plasma proteins at 10 to 30 percent, carbidopa at 36 percent, and entacapone at 98 percent. Levodopa metabolizes via decarboxylation and COMT into dopamine and other metabolites, carbidopa undergoes minimal transformation, and entacapone is glucuronidated in the liver. Half-lives are approximately 1 to 3 hours for levodopa, 2 hours for carbidopa, and 0.4 to 0.7 hours for entacapone, though entacapone extends levodopa’s duration.

Excretion occurs primarily through urine: levodopa as metabolites (80 percent), carbidopa unchanged or conjugated (30 to 50 percent), and entacapone as glucuronides (90 percent). Renal clearance is significant for all, with hepatic function also influencing entacapone and levodopa elimination.

Indications for Use

Conditions and Disorders

The medication is prescribed for Parkinson’s disease in patients experiencing motor fluctuations despite levodopa-carbidopa therapy. It addresses “wearing-off” periods, where symptoms like tremors, stiffness, and slowness re-emerge before the next dose, providing smoother control and extended symptom relief. This combination is tailored for those needing enhanced dopaminergic support.

Stalevo simplifies management by consolidating three agents into one tablet, improving adherence and efficacy. Its use is specific to Parkinson’s with established levodopa response, with no approval for other conditions, though some clinicians may explore it in similar contexts pending further evidence.

Contraindications

Conditions Prohibiting Use

The drug is contraindicated in patients with hypersensitivity to levodopa, carbidopa, entacapone, or related components, as reactions could range from rashes to anaphylaxis. Narrow-angle glaucoma precludes its use due to potential intraocular pressure increases from levodopa. Severe hepatic impairment prohibits administration, given entacapone’s reliance on liver metabolism.

It should not be used with non-selective monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation, risking hypertensive crises. Conditions like pheochromocytoma, severe arrhythmias, or uncontrolled hypertension also restrict its use due to catecholamine-related risks. Active peptic ulcers or a history of neuroleptic malignant syndrome further contraindicate its application.

Method of Administration and Dosage

Administration Guidelines

The medication is taken orally, ideally on an empty stomach to optimize levodopa absorption, though it can be consumed with food to reduce nausea if needed. Tablets should be swallowed whole with water, not crushed or split, to maintain the combined effect. Dosing frequency varies based on individual needs, typically 3 to 8 times daily.

Dosage for Adults and Children

For adults with Parkinson’s, dosing is individualized, starting with a strength matching prior levodopa-carbidopa intake (e.g., 100/25 milligrams), plus 200 milligrams entacapone per dose. The total daily levodopa dose usually ranges from 200 to 800 milligrams, divided into multiple administrations, with a maximum of 8 tablets daily (e.g., 800/200/1600 milligrams). Pediatric use is not approved, as safety and efficacy in children remain unstudied.

Dose Adjustments for Specific Conditions

In moderate renal impairment (creatinine clearance 30 to 50 milliliters per minute), standard dosing is generally safe, but severe impairment (below 30 milliliters per minute) requires caution and possible reduction. Mild hepatic impairment allows use with monitoring, while severe liver dysfunction contraindicates it due to entacapone metabolism risks. Adjustments should reflect clinical response and organ function assessments.

Side Effects

Potential Adverse Reactions

Common effects include nausea, dyskinesia, and dizziness, often linked to levodopa’s dopaminergic action or dose initiation. Urine discoloration (orange-brown) from entacapone, diarrhea, and fatigue may occur, typically subsiding with time. Orthostatic hypotension and sleep disturbances are also frequent, reflecting combined neurological impacts.

Less common reactions involve hallucinations, confusion, or abdominal pain, potentially signaling sensitivity or disease progression. Rarely, severe outcomes like neuroleptic malignant syndrome, rhabdomyolysis, or compulsive behaviors emerge, requiring immediate attention. Persistent or intense symptoms, such as chest pain or allergic responses, warrant urgent medical review.

Overdose

Symptoms of Excessive Intake

Overdosing may lead to agitation, rapid heartbeat, and severe dyskinesia from levodopa excess, alongside hypotension or confusion. Entacapone could intensify gastrointestinal distress, while carbidopa may amplify peripheral effects. Severe cases might progress to coma, seizures, or respiratory failure, posing significant risks.

First Aid Measures

Stop the drug and seek emergency care promptly. Activated charcoal may limit absorption if given within an hour, provided the patient is conscious. Symptomatic treatment, such as fluids for hypotension or sedatives for agitation, supports stabilization. Professional oversight is essential to manage catecholamine surges or neurological complications.

Drug Interactions

Effects on Other Medications

The medication can enhance dopaminergic effects of other agents like pramipexole, increasing dyskinesia or hypotension risks. It may reduce efficacy of dopamine antagonists, such as antipsychotics, by opposing their action. COMT inhibitors like entacapone amplify levodopa levels, while MAO-B inhibitors (e.g., selegiline) risk excessive catecholamine activity if doses exceed recommendations.

Stalevo interacts with iron supplements, reducing absorption of both, and CYP2C9 inhibitors, like warfarin, potentially raising entacapone levels. Caution is needed with tricyclic antidepressants or sympathomimetics, as combined effects could elevate blood pressure or heart rate.

Compatibility with Alcohol and Food

Alcohol may worsen dizziness or sedation, so moderation is advised. High-protein meals can delay levodopa absorption, suggesting administration 1 hour before or 2 hours after eating for optimal effect, though light meals are generally tolerable. No strict dietary restrictions apply beyond protein timing.

Special Precautions

Use During Pregnancy and Breastfeeding

Limited data exist on pregnancy use, with no clear human evidence of safety or harm for the components. Animal studies suggest potential fetal risks from levodopa, so use should be restricted to cases where benefits outweigh uncertainties, under strict oversight. Levodopa and carbidopa may pass into breast milk, so nursing mothers should consult a doctor, possibly pausing lactation during therapy.

Impact on Driving and Machinery Operation

The medication may cause drowsiness, sudden sleep onset, or dizziness, particularly early in treatment or with dose changes. Patients should assess their tolerance before driving or operating machinery, avoiding these tasks if affected. Caregivers may need to supervise those at risk of abrupt sleep episodes.

Considerations for Elderly and Pediatric Patients

Elderly patients tolerate it well in most cases, though reduced renal or hepatic function may require cautious dosing in moderate to severe impairment. Stalevo is not approved for children, as its role in pediatric conditions lacks evidence, confining use to adults.