Carbidopa Levodopa

Brand names: CARBIDOPA, CARBIDOPA AND LEVODOPA, CARBIDOPA, LEVODOPA AND ENTACAPONE, Carbidopa, Carbidopa Tablets, 25 mg, Carbidopa and Levodopa, Carbidopa and levodopa, Carbidopa, Levodopa and Entacapone, Carbidopa, Levodopa, and Entacapone, Carbidopa, levodopa and entacapone, LODOSYN, Lodosyn, Parcopa, RYTARY, SINEMET, Stalevo, carbidopa, levodopa and entacapone, Dhivy

Warnings

No boxed warning. The label warns that patients "have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living." It also notes "seizures associated with vitamin B6 deficiency have been reported," sporadic cases of a symptom complex "resembling neuroleptic malignant syndrome (NMS)" with dose reduction or withdrawal, and impulse control problems including "intense urge to gamble, increased sexual urges...binge eating."

Contraindications

4 CONTRAINDICATIONS DHIVY is contraindicated in patients Currently taking a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine, linezolid, and tranylcypromine) or have recently (within 2 weeks) taken a nonselective MAO inhibitor. Hypertension can occur if these drugs are used concurrently [see Drug Interactions ( 7.1 )] . With known hypersensitivity to any component of DHIVY [see Adverse Reactions (6 )]. Nonselective MAO inhibitors ( 4 ) With known hypersensitivity to any component of DHIVY ( 4 )

Overdose

10 OVERDOSAGE Based on the limited available information, the acute symptoms of levodopa/dopa decarboxylase inhibitor overdosage can be expected to arise from dopaminergic overstimulation. Doses of a few grams may result in CNS disturbances, with an increasing likelihood of cardiovascular disturbance (e.g., hypotension, tachycardia) and more severe psychiatric problems at higher doses. An isolated report of rhabdomyolysis and another of transient renal insufficiency suggest that levodopa overdosage may give rise to systemic complications, secondary to dopaminergic overstimulation. Monitor patients and provide supportive care. Patients should receive electrocardiographic monitoring for the development of arrhythmias; if needed, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs, increasing the risk of drug interactions (especially catechol-structured drugs) should be taken into consideration.

Drug interactions

7 DRUG INTERACTIONS Iron salts and dopamine D2 antagonists including metoclopramide: May reduce the effectiveness of DHIVY ( 7.2 , 7.3 ) 7.1 Monoamine Oxidase (MAO) Inhibitors The use of nonselective MAO inhibitors with DHIVY is contraindicated [see Contraindications ( 4 ) ] . Discontinue use of any nonselective MAO inhibitors at least two weeks prior to initiating DHIVY. DHIVY may be administered concomitantly with the manufacturer's recommended dose of selective MAO-B inhibitors (e.g., rasagiline or selegiline HCl). Concomitant therapy with selegiline and carbidopa/levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa/levodopa alone. 7.2 Dopamine D 2 Receptor Antagonists and Isoniazid Dopamine D 2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the effectiveness of levodopa. Monitor patients taking these drugs with DHIVY for worsening Parkinson’s symptoms. 7.3 Iron Salts Iron salts or multivitamins containing iron salts can form chelates with levodopa and carbidopa and can cause a reduction in the bioavailability of DHIVY. If iron salts or multivitamins containing iron salts are co-administered with DHIVY, monitor patients for worsening Parkinson’s symptoms. 7.4 Antihypertensive Drugs Symptomatic postural hypotension occurred when carbidopa/levodopa was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with DHIVY is started, dosage adjustment of the antihypertensive drug may be required. 7.5 Dopamine-Depleting Agents Use of DHIVY with dopamine-depleting agents (e.g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended. 7.6 Metoclopramide Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also reduce effectiveness of levodopa by its dopamine receptor antagonistic properties.

Uses

SINEMET is indicated in the treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Dosage forms & strengths

Capsule, Extended Release Tablet Tablet, Extended Release Tablet, Film Coated Tablet, Orally Disintegrating TABLET

CARBIDOPA 10 mg CARBIDOPA 10 mg / LEVODOPA 100 mg LEVODOPA 100 mg CARBIDOPA 12.5 mg ENTACAPONE 200 mg LEVODOPA 50 mg CARBIDOPA 18.75 mg LEVODOPA 75 mg CARBIDOPA 25 mg CARBIDOPA 25 mg / LEVODOPA 100 mg CARBIDOPA 25 mg / LEVODOPA 250 mg LEVODOPA 250 mg CARBIDOPA 31.25 mg LEVODOPA 125 mg CARBIDOPA 37.5 mg LEVODOPA 150 mg CARBIDOPA 50 mg LEVODOPA 200 mg CARBIDOPA ANHYDROUS 25 mg / LEVODOPA 100 mg Carbidopa 10 mg Levodopa 100 mg levodopa 100 mg Carbidopa 25 mg Levodopa 250 mg Carbidopa 50 mg / Levodopa 200 mg LEVODOPA 145 mg CARBIDOPA 36.25 mg LEVODOPA 195 mg CARBIDOPA 48.75 mg LEVODOPA 245 mg CARBIDOPA 61.25 mg LEVODOPA 95 mg CARBIDOPA 23.75 mg carbidopa 10 mg / levodopa 100 mg carbidopa 12.5 mg levodopa 50 mg entacapone 200 mg carbidopa 18.75 mg levodopa 75 mg carbidopa 25 mg carbidopa 25 mg / levodopa 100 mg carbidopa 25 mg / levodopa 250 mg levodopa 250 mg carbidopa 31.25 mg levodopa 125 mg carbidopa 37.5 mg levodopa 150 mg carbidopa 50 mg / levodopa 200 mg carbidopa 50 mg levodopa 200 mg CARBIDOPA HYDRATE 25 mg/1 LEVODOPA 100 mg/1

2 DOSAGE AND ADMINISTRATION Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. ( 2.1 ) The recommended starting dosage of DHIVY is one 25 mg /100 mg tablet taken orally three times a day. ( 2.2 ) Dosage may be increased by up to one whole tablet every day or every other day, as needed, until a maximum dosage of eight whole tablets of DHIVY a day is reached. ( 2.2 ) Swallow DHIVY with or without food. ( 2.4 ) 2.1 Management of Vitamin B6 Levels Evaluate vitamin B6 levels prior to initiating treatment with carbidopa-levodopa therapies including DHIVY, periodically during treatment, and as clinically indicated [see Warnings and Precautions ( 5.7 )] . If vitamin B6 levels are low, supplement to sufficient levels per standard of care. Patients may initiate and continue treatment with DHIVY while supplementing vitamin B6. 2.2 Initial Dosage and Maintenance of Therapy The recommended starting dosage of DHIVY is one 25 mg / 100 mg tablet taken orally three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by up to one whole tablet every day or every other day, as needed to a maximum daily dosage of eight whole tablets. Dosing with DHIVY should be individualized and adjusted according to clinical response and tolerability. The tablet is functionally scored to facilitate dose adjustment. At least 70 mg to 100 mg of carbidopa per day should be provided. Experience with total daily dosages of carbidopa greater than 200 mg is limited. Monitor patients closely during the dose adjustment period. Specifically, involuntary movements may occur with DHIVY, which may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients. Maintain patients on the lowest dosage required to achieve symptomatic control and to minimize adverse reactions, such as dyskinesia and nausea. 2.3 Discontinuation of DHIVY Avoid sudden discontinuation or rapid dose reduction of DHIVY. The daily dosage of DHIVY should be tapered at the time of treatment discontinuation [see Warnings and Precautions ( 5.2 ) ] . If general anesthesia is required, DHIVY may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling neuroleptic malignant syndrome, and the usual daily dosage may be administered as soon as the patient is able to take oral medication. 2.4 Administration Information Swallow DHIVY with or without food. The patient should be advised that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. If the patient has difficulty swallowing the tablet due to its size, the tablet can be broken at the score lines.