carbidopa/levodopa (Sinemet, Parcopa, Atamet)
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Introduction
Sinemet for sin + emesis (without emesis)
Indications
symptomatic treatment of Parkinson's disease
Contraindications
Dosage
- start 1 tab PO TID (25/100)
- increase 1/2 tab/dose as needed every several days
- higher doses generally divided QID
- even more frequent dosing may be needed
- doses of 600-1000 mg of L-dopa suggests addition of another agent such as selegiline may be indicated
- give on an empty stomach
Tabs: 10/100, 25/100, 25/250 mg carbidopa/levodopa.
Tabs: 50/200 mg carbidopa/levodopa.
65 or 105 mg of carbidopa with 75, 100, 125, or 150 mg of levodopa[8]
- IPXO66 (experimental) extends "on" time by about 1 hour[8]
Parcopa: dissolves on the tongue
Tabs: 10/100, 25/100, 25/250 mg carbidopa/levodopa.
Pharmacokinetics
- good oral bioavailability
- dietary protein (neutral amino acids) may interfere with absorption
- H pylori may interfere with absorption, eradication may improve absorption, effectiveness[7]
- peak serum levels 1-2 hours after oral administration
- 1/2 life 1.5-2 hours, longer with the extended release product
- carbidopa does not cross the blood brain barrier, thus does not interfere with CNS conversion of L-dopa to dopamine
- elimination: liver
Adverse effects
- common (> 10%)
- less common (1-10%)
- eyelid spasms, anorexia, diarrhea, dry mouth, headache, muscle twitching, discoloration of urine/sweat
- uncommon (< 1%)
- other
- cardiac arrhythmias are rare with inclusion of carbidopa which blocks decarboxylation of L-dopa
- orthostatic hypotension: usually transient
- GI complaints: nausea/vomiting
- psychosis
- hallucinations
- confusion
- nightmares
- clozapine may be useful for L-dopa induced psychosis
- dark color of body fluids
- see dopamine receptor agonist for general adverse effects
- see levodopa for on-off effect
- management of motor fluctuations, & dyskinesias (wearing off effect)
- usually choreiform movements
- effect is dose dependent
- generally occurs after prolonged therapy
- minimized by giving smaller doses more frequently
- amantadine (Gocovri) for treatment of Sinemet-induced dyskinesias[10]
- abrupt withdrawal can result in neuroleptic malignant syndrome[3]
* minimized by giving smaller doses of levpdopa more frequently[3]
* prescribe higher dose of carbidopa (carbidopa/levodopa 25/100)[3]
Drug interactions
- pyridoxine:
- rapid reversal of L-dopa's effects when not used in combination with carbidopa
- cofactor in catabolism of L-dopa
- hydantoins decrease effect of L-dopa
- hypertensive reactions with concurrent administration of MAO inhibitors
- increased dietary protein (> 1 g/kg body weight) decreases L-dopa absorption due to intestinal transport saturation mechanisms
- dopamine antagonists block effects of L-dopa
- selegiline inhibits dopamine catabolism, thus effects may be additive with sinemet
- meperidine used in combination may cause lethal seizures
- benzodiazepines
- reserpine
- methyldopa
- antihypertensive agents
- antacids
Mechanism of action
- combination dopamine precursor & dopa-decarboxylase inhibitor used in the treatment of Parkinson's disease
- unlike dopamine, L-dopa (levodopa) crosses the blood brain barrier
- within the central nervous system, L-dopa is decarboxylated to form dopamine
- Carbidopa inhibits decarboxylation of L-dopa so that adequate amounts may gain access to the CNS & diminishes vomiting caused by action of dopamine on area postrema
- does levodopa/carbopa influence progression of disease?
More general terms
Additional terms
Components
- carbidopa (Lodosyn)
- levodopa; L-3-hydroxytyrosine; L-3,4-dihydroxyphenylalanine; L-dopa (Dopar, Larodopa, Inbrija)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Prescriber's Letter 11(11): 2004 Parcopa (Carbidopa-Levodopa Orally Disintegrating Tablets) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201113&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Journal Watch 25(1):11, 2005 Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K; Parkinson Study Group. Levodopa and the progression of Parkinson's disease. N Engl J Med. 2004 Dec 9;351(24):2498-508. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15590952
- ↑ 7.0 7.1 Pierantozzi M et al, Helicobacter pylori eradication and L-dopa absorption in patients with PD and motor fluctuations. Neurology 2006, 66:1824 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16801644
- ↑ 8.0 8.1 8.2 Hauser RA et al. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: A phase 3 randomised, double-blind trial. Lancet Neurol 2013 Apr; 12:346. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23485610
- ↑ Trenkwalder C et al. Increased dose of carbidopa with levodopa and entacapone improves "off" time in a randomized trial. Neurology 2019 Mar 26; 92:e1487 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30824559
- ↑ 10.0 10.1 Brooks M FDA Clears First Drug for Parkinson's Dyskinesia Medscape - Aug 25, 2017. http://www.medscape.com/viewarticle/884697