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Q: Levodopa/Carbidopy ( Answered 5 out of 5 stars,   1 Comment )
Subject: Levodopa/Carbidopy
Category: Health > Medicine
Asked by: doctordoris-ga
List Price: $12.00
Posted: 12 Mar 2003 07:14 PST
Expires: 11 Apr 2003 08:14 PDT
Question ID: 175084
I want the most authoritative and  up-to-date information about the
drug levodopa/carbidopa, including common side-effects and drug
interactions.  A manufacturer's product monograph would be ideal,
and/or one or two (or three) other detailed information sources.  (If
it makes a difference to your answer, I am particularly interested in
the 100mg/25mg
combination, and in the form that is not controlled release.)
Subject: Re: Levodopa/Carbidopy
Answered By: kevinmd-ga on 12 Mar 2003 08:03 PST
Rated:5 out of 5 stars
Hello - thanks for asking your question.  

The following is taken from the Drug Information Handbook.  This is
the most recent information and closest in form to a monograph that I
could find.  I do not think it is available on-line, or else I would
have just given you the link.  Here is more information on the source:
"The Drug Information Handbook, Pocket contains up to 20 fields of
information for over 1,280 drug monographs. The handbook is
alphabetically organized by both trade and generic drug name and is
fully cross-referenced by page number.

The Appendix information includes extracted information from the full
handbook version and includes comparative drug charts, therapy
recommendations and other important information on a variety of
clinical topics."

"U.S. BRAND NAMES — Sinemet®; Sinemet® CR

SYNONYMS — Carbidopa and Levodopa


CANADIAN BRAND NAMES — Apo®-Levocarb; Endo®-Levodopa/Carbidopa;
Nu-Levocarb; Sinemet®; Sinemet® CR

PHARMACOLOGIC CATEGORY Anti-Parkinson's Agent, Dopamine Agonist 

USE — Idiopathic Parkinson's disease; postencephalitic parkinsonism;
symptomatic parkinsonism

USE - UNLABELED / INVESTIGATIONAL — Restless leg syndrome


LACTATION — Excretion in breast milk unknown

CONTRAINDICATIONS — Hypersensitivity to levodopa, carbidopa, or any
component of the formulation; narrow-angle glaucoma; use of MAO
inhibitors within prior 14 days (however may be administered
concomitantly with the manufacturer's recommended dose of an MAO
inhibitor with selectivity for MAO type B); history of melanoma or
undiagnosed skin lesions

WARNINGS / PRECAUTIONS — Use with caution in patients with history of
cardiovascular disease (including myocardial infarction and
arrhythmias); pulmonary diseases such as asthma, psychosis, wide-angle
glaucoma, peptic ulcer disease; as well as in renal, hepatic, or
endocrine disease. Sudden discontinuation of levodopa may cause a
worsening of Parkinson's disease. Elderly may be more sensitive to CNS
effects of levodopa. May cause or exacerbate dyskinesias. May cause
orthostatic hypotension; Parkinson's disease patients appear to have
an impaired capacity to respond to a postural challenge; use with
caution in patients at risk of hypotension (such as those receiving
antihypertensive drugs) or where transient hypotensive episodes would
be poorly tolerated (cardiovascular disease or cerebrovascular
disease). Observe patients closely for development of depression with
concomitant suicidal tendencies. Some products may contain tartrazine.
Has been associated with a syndrome resembling neuroleptic malignant
syndrome on withdrawal or significant dosage reduction after long-term
use. Toxic reactions have occurred with dextromethorphan. Protein in
the diet should be distributed throughout the day to avoid
fluctuations in levodopa absorption.

ADVERSE REACTIONS — Frequency not defined. 

Cardiovascular: Orthostatic hypotension, arrhythmias, chest pain,
hypertension, syncope, palpitations, phlebitis

Central nervous system: Dizziness, anxiety, confusion, nightmares,
headache, hallucinations, on-off phenomenon, decreased mental acuity,
memory impairment, disorientation, delusions, euphoria, agitation,
somnolence, insomnia, gait abnormalities, nervousness, ataxia, EPS,
falling, psychosis, peripheral neuropathy, seizures (causal
relationship not established)

Dermatologic: Rash, alopecia, malignant melanoma, hypersensitivity
(angioedema, urticaria, pruritus, bullous lesions, Henoch-Schönlein

Endocrine & metabolic: Increased libido 

Gastrointestinal: Anorexia, nausea, vomiting, constipation, GI
bleeding, duodenal ulcer, diarrhea, dyspepsia, taste alterations,
sialorrhea, heartburn

Genitourinary: Discoloration of urine, urinary frequency 

Hematologic: Hemolytic anemia, agranulocytosis, thrombocytopenia,
leukopenia; decreased hemoglobin and hematocrit; abnormalities in AST
and ALT, LDH, bilirubin, BUN, Coombs' test

Neuromuscular & skeletal: Choreiform and involuntary movements,
paresthesia, bone pain, shoulder pain, muscle cramps, weakness

Ocular: Blepharospasm, oculogyric crises (may be associated with acute
dystonic reactions)

Renal: Difficult urination 

Respiratory: Dyspnea, cough 

Miscellaneous: Hiccups, discoloration of sweat, diaphoresis

OVERDOSAGE / TOXICOLOGY — Symptoms of overdose include palpitations,
arrhythmias, spasms; may cause hypertension or hypotension. Treatment
is supportive. EKG monitoring is warranted. May precipitate a variety
of arrhythmias.

DRUG INTERACTIONS Antacids: Levodopa absorption may be increased;

Anticholinergics: May reduce the efficacy of levodopa, possibly due to
reduced gastrointestinal absorption (also see tricyclic
antidepressants); limited evidence of clinical significance; monitor

Antipsychotics: May inhibit the antiparkinsonian effects of levodopa
via dopamine receptor blockade; use antipsychotics with low dopamine
blockade (clozapine, olanzapine, quetiapine)

Benzodiazepines: May inhibit the antiparkinsonian effects of levodopa;
monitor for reduced effect

Clonidine: May reduce the efficacy of levodopa; monitor 

Dextromethorphan: Toxic reactions have occurred with dextromethorphan

Furazolidone: May increase the effect/toxicity of levodopa;
hypertensive episodes have been reported; monitor

Iron salts: Binds levodopa and reduces its bioavailability; separate
doses of iron and levodopa

Linezolid: Due to MAO inhibition (see note on MAO inhibitors), this
agent is best avoided

MAO inhibitors: Concurrent use of levodopa with nonselective MAO
inhibitors may result in hypertensive reactions via an increased
storage and release of dopamine, norepinephrine, or both; use with
carbidopa to minimize reactions if combination is necessary, otherwise
avoid combination.

L-methionine: May inhibit levodopa's antiparkinsonian effects; monitor
for reduced effect

Metoclopramide: May increase the absorption/effect of levodopa;
hypertensive episodes have been reported. Levodopa antagonizes
metoclopramide's effects on lower esophageal sphincter pressure. Avoid
use of metoclopramide for reflux, monitor response to levodopa
carefully if used.

Methyldopa: May potentiate the effects of levodopa; levodopa may
increase the hypotensive response to methyldopa; monitor

Papaverine: May decrease the efficacy of levodopa; includes other
similar agents (ethaverine); monitor

Penicillamine: May increase serum concentrations of levodopa; monitor
for increased effect

Phenytoin: May inhibit levodopa's antiparkinsonian effects; monitor
for reduced effect

Pyridoxine: May inhibit levodopa's antiparkinsonian effects; monitor
for reduced effect (pyridoxine in doses >10-25 mg for levodopa alone,
higher doses >200 mg/day may be a problem for levodopa/carbidopa)

Spiramycin: May inhibit levodopa's antiparkinsonian effects; monitor
for reduced effect

Tacrine: May inhibit the effects of levodopa via enhanced cholinergic
activity; monitor for reduced effect

Tricyclic antidepressants: May decrease the absorption
(bioavailability) of levodopa; rare hypertensive episodes have also
been attributed to this combination

ETHANOL / NUTRITION/HERB INTERACTIONS Ethanol: Avoid ethanol (due to
CNS depression).

Food: Avoid high protein diets and high intakes of vitamin B6. 

Herb/Nutraceutical: Avoid kava kava (may decrease effects). Pyridoxine
in doses >10-25 mg (for levodopa alone) or higher doses >200 mg/day
(for levodopa/carbidopa) may decrease efficacy.

MECHANISM OF ACTION — Parkinson's symptoms are due to a lack of
striatal dopamine; levodopa circulates in the plasma to the
blood-brain-barrier (BBB), where it crosses, to be converted by
striatal enzymes to dopamine; carbidopa inhibits the peripheral plasma
breakdown of levodopa by inhibiting its decarboxylation, and thereby
increases available levodopa at the BBB

PHARMACODYNAMICS / KINETICS Duration: Variable, 6-12 hours; longer
with sustained release forms

See individual agents.

DOSAGE — Oral: 

Adults: Initial: Carbidopa 25 mg/levodopa 100 mg 2-4 times/day,
increase as necessary to a maximum of carbidopa 200 mg/levodopa 2000
mg per day Restless leg syndrome (unlabeled use): Carbidopa 25
mg/levodopa 100 mg given 30-60 minutes before bedtime; may repeat dose

Elderly: Initial: Carbidopa 25 mg/levodopa 100 mg twice daily,
increase as necessary

Conversion from Sinemet® to Sinemet® CR (50 / 200): (Sinemet® [total
daily dose of levodopa] / Sinemet® CR) 300-400 mg / 1 tablet twice
daily 500-600 mg / 11/2 tablets twice daily or one 3 times/day 700-800
mg / 4 tablets in 3 or more divided doses 900-1000 mg / 5 tablets in 3
or more divided doses

Intervals between doses of Sinemet® CR should be 4-8 hours while awake

ADMINISTRATION — Administer with meals to decrease GI upset

MONITORING PARAMETERS — Blood pressure, standing and sitting/supine;
symptoms of parkinsonism, dyskinesias, mental status

TEST INTERACTIONS — False-positive reaction for urinary glucose with
Clinitest®; false-negative reaction using Clinistix®; false-positive
urine ketones with Acetest®, Ketostix®, Labstix®

DIETARY CONSIDERATIONS — Levodopa peak serum concentrations may be
decreased if taken with food. High protein diets (>2 g/kg) may
decrease the efficacy of levodopa via competition with amino acids in
crossing the blood-brain barrier.

PATIENT EDUCATION — Take exactly as directed; do not change dosage or
discontinue without consulting prescriber. Do not crush sustained
release form. Therapeutic effects may take several weeks or months to
achieve and you may need frequent monitoring during first weeks of
therapy. Take with meals if GI upset occurs, before meals if dry mouth
occurs, after eating if drooling or if nausea occurs. Take at the same
time each day. Maintain adequate hydration (2-3 L/day of fluids unless
instructed to restrict fluid intake); void before taking medication.
Do not use alcohol and prescription or OTC sedatives or CNS
depressants without consulting prescriber. Urine or perspiration may
appear darker. You may experience drowsiness, dizziness, confusion, or
vision changes (use caution when driving, climbing stairs, or engaging
in tasks requiring alertness until response to drug is known);
orthostatic hypotension (use caution when changing position - rising
to standing from sitting or lying); increased susceptibility to heat
stroke, decreased perspiration (use caution in hot weather - maintain
adequate fluids and reduce exercise activity); constipation (increased
exercise, fluids, or dietary fruit and fiber may help); dry skin or
nasal passages (consult prescriber for appropriate relief); nausea,
vomiting, loss of appetite, or stomach discomfort (small frequent
meals, frequent mouth care, chewing gum, or sucking lozenges may
help). Report unresolved constipation or vomiting; chest pain or
irregular heartbeat; difficulty breathing; acute headache or
dizziness; CNS changes (hallucination, loss of memory, nervousness,
etc); painful or difficult urination; abdominal pain or blood in
stool; increased muscle spasticity or rigidity; skin rash; or
significant worsening of condition. Pregnancy/breast-feeding
precautions: Inform prescriber if you are or intend to be pregnant.
Consult prescriber if breast-feeding.

NURSING IMPLICATIONS — Space doses evenly over the waking hours;
sustained release product should not be crushed

ADDITIONAL INFORMATION — 50-100 mg/day of carbidopa is needed to block
the peripheral conversion of levodopa to dopamine. "On-off" (a
clinical syndrome characterized by sudden periods of drug
activity/inactivity), can be managed by giving smaller, more frequent
doses of Sinemet® or adding a dopamine agonist or selegiline; when
adding a new agent, doses of Sinemet® can usually be decreased.
Protein in the diet should be distributed throughout the day to avoid
fluctuations in levodopa absorption. Levodopa is the drug of choice
when rigidity is the predominant presenting symptom.

Consider use of alternative therapies before attempting to use
levodopa containing products.

50-100 mg/day of carbidopa is needed to block the peripheral
conversion of levodopa to dopamine. "On-off" (a clinical syndrome
characterized by sudden periods of drug activity/inactivity), can be
managed by giving smaller, more frequent doses of Sinemet® or adding a
dopamine agonist or selegiline; when adding a new agent, doses of
Sinemet® can usually be decreased. Protein in the diet should be
distributed throughout the day to avoid fluctuations in levodopa
absorption. Levodopa is the drug of choice when rigidity is the
predominant presenting symptom.

Parkinson's disease (ie, treatment with levodopa and carbidopa
combination) is associated with orthostatic hypotension. Patients
medicated with this drug combination should be carefully assisted from
the chair and observed for signs of orthostatic hypotension.

information available to require special precautions

DOSAGE FORMS Tablet: 10/100: Carbidopa 10 mg and levodopa 100 mg
25/100: Carbidopa 25 mg and levodopa 100 mg 25/250: Carbidopa 25 mg
and levodopa 250 mg

Tablet, sustained release: Carbidopa 25 mg and levodopa 100 mg
Carbidopa 50 mg and levodopa 200 mg" (1)

Please use any answer clarification before rating this answer. I will
be happy to explain or expand on any issue you may have.    
Kevin, M.D.    
Search strategy:   
No internet search engine was used in this answer.  All sources are  
from physician-written and peer-reviewed sources.  
1) Lacy.  Sinemet.  Drug Information Handbook: Lexi-comp, Inc. 2002.

Other sources:
RX List - Sinemet:

International Antiaging Systems - Sinemet:

Request for Answer Clarification by doctordoris-ga on 14 Mar 2003 05:30 PST
Superbly helpful answer.  My only question is how precisely does
protein need to be distributed through the day.   Does this require
major changes in what the patient eats at each meal?  Or just don't
eat  a huge steak and a lot of cheese at a single meal, washed down
with a huge glass of milk?

Clarification of Answer by kevinmd-ga on 14 Mar 2003 18:56 PST
I asked a neurologist about this question.  There is no precise way of
distributing protein.  It is a general statement - take protein in
moderation and don't have large protein binges during the day or else
it may interfere with levodopa absorption.

Kevin, M.D.
doctordoris-ga rated this answer:5 out of 5 stars and gave an additional tip of: $2.00
Superbly helpful answer.  Much appreciated!

Subject: Re: Levodopa/Carbidopy
From: kevinmd-ga on 15 Mar 2003 20:24 PST
Thanks for the generous rating and tip.

Kevin, M.D.

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