CLASSESAnti-Parkinson Agents, Dopamine Precursors Show
DESCRIPTIONCombination product of dopamine precursor (levodopa) with a decarboxylase inhibitor (carbidopa) COMMON BRAND NAMESAtamet, Dhivy, Duopa, Parcopa, Rytary, SINEMET, SINEMET CR HOW SUPPLIEDAtamet/Carbidopa, Levodopa/Dhivy/SINEMET Oral Tab: 10-100mg, 25-100mg, 25-250mg DOSAGE & INDICATIONSFor the treatment of idiopathic Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication. For the treatment of motor fluctuations in patients with advanced Parkinson's disease. Enteral suspension dosage (naso-jejunal tube for short-term administration or PEG-J for long-term administration) Adults Prior to initiating the enteral suspension on Day 1, convert patients from all other forms of levodopa to oral immediate-release carbidopa; levodopa (1:4 ratio). Patients should remain on a stable dose
of their concomitant medications taken for the treatment of Parkinson's disease before initiation of the carbidopa; levodopa suspension via enteral pump. Ensure patients take their oral Parkinson's disease medications the morning of the PEG-J procedure. The daily enteral suspension dose can be titrated as needed, based on response and tolerability after Day 1 and until a stable daily dose is maintained. Adjustments to concomitant Parkinson's disease medications may be needed. Once no further
adjustments are required to the morning dose, continuous dose, or extra dose, this dosing regimen should be administered daily over 16 hours. Additional dose adjustments may be necessary over time based on the level of activity of the patient and disease progression. The maximum recommended daily dose of Duopa enteral suspension is 2,000 mg of the levodopa component (i.e., 1 cassette per day) administered over 16 hours. At the end of each daily 16-hour infusion, the patient will disconnect the
pump from the PEG-J and take their night-time dose of oral immediate-release carbidopa-levodopa. DAY 1 MORNING DOSING: Determine the total amount of levodopa in milligrams (mg) in the first dose of oral immediate-release carbidopa; levodopa that was taken by the patient on the previous day. Convert the oral levodopa dose from milligrams (mg) to milliliters (mL) by multiplying the oral dose by 0.8 and then dividing by 20 mg/mL. This calculation will provide the morning dose of carbidopa; levodopa
suspension in mL. Add 3 mL to the morning dose to fill (prime) the intestinal tube to obtain the total morning dose. Program the pump to deliver the total morning dose, which is usually administered over 10 to 30 minutes. DAY 1 CONTINUOUS DOSING: Determine the amount of oral immediate-release levodopa that the patient received from oral immediate-release carbidopa-levodopa doses throughout the previous day (16 waking hours), in milligrams (mg). Do not include the doses of oral immediate-release
carbidopa-levodopa taken at night when calculating the levodopa amount. Subtract the first oral levodopa dose in milligrams (mg) taken by the patient on the previous day from the total oral levodopa dose in milligrams (mg) taken over 16 waking hours. Divide the result by 20 mg/mL. This is the dose of carbidopa; levodopa suspension administered as a continuous dose (in mL) over 16 hours. The hourly infusion rate (mL/hour) is obtained by dividing the continuous dose by 16 (hours). The hourly
infusion rate will be programmed into the pump as the continuous rate. If persistent or numerous "off" periods occur during the 16-hour infusion, consider increasing the continuous dose or using the extra dose function. If dyskinesia or levodopa-related adverse reactions (ADRs) occur, consider decreasing the continuous dose or stopping the infusion until the ADRs subside. MORNING DOSE ADJUSTMENTS: If there was an inadequate response within 1 hour of the morning dose on the prior day, adjust the
morning dose (excluding the 3 mL to fill the tube) as follows: If the morning dose on the prior day was 6 mL or less, increase the morning dose by 1 mL. If the morning dose on the preceding day was greater than 6 mL, increase the morning dose by 2 mL. If the patient experienced dyskinesias or levodopa-related ADRs within 1 hour of the morning dose on the prior day, decrease the morning dose by 1 mL. CONTINUOUS DOSE ADJUSTMENTS: Consider increasing the continuous dose based on the number and
volume of extra doses of carbidopa; levodopa (i.e., total amount of levodopa component) that was needed for the previous day and clinical response. Consider decreasing the continuous dose if the patient experienced troublesome dyskinesia, or other troublesome treatment-related ADRs on the preceding day as follows: For troublesome ADRs lasting 1 hour or more, decrease the continuous dose by 0.3 mL/hour. For troublesome ADRs lasting for 2 or more periods of 1 hour or more, decrease the continuous
dose by 0.6 mL/hour. EXTRA DOSES: The enteral infusion pump has an extra dose function that can be used to manage acute "off" symptoms that are not controlled by the morning dose and the continuous dose administered over 16 hours. The extra dose function should be set at 1 mL (20 mg of levodopa) when starting the enteral suspension. If the amount of the extra dose needs to be adjusted, it is typically done in 0.2 mL increments. Limit the extra dose frequency to 1 extra dose every 2 hours.
Administration of frequent extra doses may cause or worsen dyskinesias. TREATMENT DISCONTINUATION: Avoid sudden discontinuation or rapid dose reduction. If discontinuation is needed, the dose should be tapered or patients should be switched to oral immediate-release carbidopa; levodopa. When using a PEG-J tube, the drug can be discontinued by withdrawing the tube and letting the stoma heal. The removal of the tube should only be performed by a qualified healthcare provider. Oral dosage (immediate-release tablets; e.g., Sinemet) Adults INITIAL TREATMENT: The usual initial dose for patients who have not previously received levodopa is 1 carbidopa 25 mg/levodopa 100 mg tablet PO 3 times per day. The dosage may be increased by 1 tablet every day or every other day up to a maximum of 8 tablets per day. If carbidopa 10 mg/levodopa 100 mg is used, the dosage may be started with 1 tablet 3 or 4 times a day.
However, this may not provide an adequate amount of carbidopa for many patients. Therefore, the dosage may be increased by 1 tablet every day or every other day up to a total of 8 tablets (i.e., 2 tablets PO 4 times a day). MAINTENANCE TREATMENT: Individualize and adjust dosing regimen according response and tolerability. At least 70 mg to 100 mg of carbidopa per day should be provided. When a greater proportion of carbidopa is required, 1 tablet of carbidopa 25 mg/levodopa 100 mg may be
substituted for each carbidopa 10 mg/levodopa 100 mg tablet. When more levodopa is required, carbidopa 25 mg/levodopa 250 mg should be substituted for carbidopa 25 mg/levodopa 100 mg or carbidopa 10 mg/levodopa 100 mg. If necessary, the dosage of carbidopa 25 mg/levodopa 250 mg may be increased by one-half or 1 tablet every day or every other day to a maximum of 8 tablets daily. For patients requiring smaller dose adjustments, carbidopa/levodopa tablets that are functionally scored (Dhivy) may
be used to adjust doses in increments of 6.25 mg/25 mg. Experience with total daily doses of carbidopa greater than 200 mg is limited. Because both therapeutic and adverse responses (e.g., involuntary movements) occur more rapidly with carbidopa-levodopa than with levodopa alone, patients should be monitored closely during the dose adjustment period, and changes made accordingly. Blepharospasm may be a useful early sign of excess dosage in some patients. CONVERTING PATIENTS FROM LEVODOPA TO
CARBIDOPA-LEVODOPA: Levodopa must be discontinued at least 12 hours before starting carbidopa-levodopa. A daily dosage of carbidopa-levodopa should be chosen that will provide approximately 25% of the previous levodopa dosage. Patients who are taking less than 1500 mg of levodopa a day should be started on 1 tablet of carbidopa 25 mg/levodopa 100 mg PO 3 or 4 times a day. The suggested starting dosage for most patients taking more than 1500 mg of levodopa is 1 tablet of carbidopa 25 mg/levodopa
250 mg PO 3 or 4 times a day. Oral dosage (extended-release tablets; e.g., Sinemet CR) Adults INITIAL TREATMENT: The usual initial dose is Sinemet CR 1 carbidopa 50 mg/levodopa 200 mg tablet PO twice daily. Most patients have been adequately treated with the extended-release tablets in doses that provide 400 mg to 1,600 mg of levodopa per day. The dosing intervals should be 4 to 8 hours apart during the waking day.
Dosage adjustments should generally be made at 3-day intervals. Doses 2,400 mg or more per day levodopa or shorter intervals (less than 4 hours) have been used, but are usually not recommended. Dosage adjustments may be necessary when other antiparkinson medication is added. A dose of regular-release carbidopa-levodopa (one-half or 1 tablet) can be added to the dosage regimen of the extended-release formulation in selected patients with advanced disease who need additional immediate-release
levodopa for brief times during the daytime. CONVERTING PATIENTS FROM LEVODOPA TO CARBIDOPA-LEVODOPA: Initiate therapy at approximately 25% of the previous dosage of levodopa alone. In patients with mild to moderate disease, the usual initial dosage is 1 carbidopa 50 mg/levodopa 200 mg extended-release tablet twice daily. CONVERTING PATIENTS FROM IMMEDIATE-RELEASE CARBIDOPA-LEVODOPA TO EXTENDED-RELEASE CARBIDOPA-LEVODOPA: Substitute extended-release tablets at a dosage that provides
approximately 10% more levodopa per day than the immediate-release tablets, although this may need to be increased to a dosage that provides up to 30% more levodopa per day. The dosing intervals should be 4 to 8 hours apart during the waking day. The following general guidelines may be used to initiate therapy. For patients receiving 300 mg/day to 400 mg/day of levodopa as immediate-release carbidopa-levodopa, the suggested starting regimen of Sinemet CR is carbidopa 50 mg/levodopa 200 mg twice
daily. For patients receiving 500 mg/day to 600 mg/day of levodopa as immediate-release carbidopa-levodopa, the suggested starting regimen of Sinemet CR is carbidopa 50 mg/levodopa 200 mg 3 times daily or a total of 300 mg levodopa twice daily. For patients receiving 700 mg/day to 800 mg/day of levodopa as immediate-release carbidopa-levodopa, the suggested starting regimen of Sinemet CR is a total of 800 mg levodopa in 3 divided doses (e.g., 300 mg in the morning, 300 mg in the afternoon, and
200 mg in the evening). For patients receiving 900 mg/day to 1,000 mg/day of levodopa as immediate-release carbidopa-levodopa, the suggested starting regimen of Sinemet CR is a total of 1,000 mg levodopa in 3 divided doses (e.g., 400 mg in the morning, 400 mg in the afternoon, and 200 mg in the evening). Oral dosage (extended-release capsules; e.g., Rytary) Adults INITIAL TREATMENT: Rytary 23.75 mg/95 mg PO three
times a day for the first 3 days. On Day 4, may increase the dose to 36.25 mg/145 mg three times a day. Based on response and tolerability, the dose may be further increased up to a maximum dose of 97.5 mg/390 mg three times a day. The dosing frequency may be changed from three times a day up to a maximum of five times a day if more frequent dosing is needed and is tolerated. The maximum recommended daily dose is 612.5 mg/2,450 mg. CONVERTING PATIENTS FROM IMMEDIATE-RELEASE CARBIDOPA-LEVODOPA TO
EXTENDED-RELEASE CARBIDOPA-LEVODOPA: Dosages of other carbidopa and levodopa products are not interchangeable with carbidopa; levodopa extended-release capsules; therefore, the following conversions are recommended. For patients receiving 400 mg to 549 mg levodopa as immediate-release carbidopa-levodopa, the suggested starting dose of Rytary is 3 capsules (23.75 mg/95 mg each capsule) 3 times daily (total 855 mg of levodopa daily). For patients receiving 550 mg to 749 mg levodopa as
immediate-release carbidopa-levodopa, the suggested starting dose of Rytary is 4 capsules (23.75 mg/95 mg each capsule) 3 times daily (total 1,140 mg of levodopa daily). For patients receiving 750 mg to 949 mg levodopa as immediate-release carbidopa-levodopa, the suggested starting dose of Rytary is 3 capsules (36.25 mg/145 mg each capsule) 3 times daily (total 1,305 mg of levodopa daily). For patients receiving 950 mg to 1,249 mg levodopa as immediate-release carbidopa-levodopa, the suggested
starting dose of Rytary is 3 capsules (48.75 mg/195 mg each capsule) 3 times daily (total 1,755 mg of levodopa daily). For patients receiving 1,250 mg or more levodopa as immediate-release carbidopa-levodopa, the suggested starting dose of Rytary is 4 capsules (48.75 mg/195 mg each capsule) 3 times daily (total 2,340 mg of levodopa daily) OR 3 capsules (61.25 mg/245 mg each capsule) 3 times daily (total 2,205 mg of levodopa daily). The dosage frequency may be changed from 3 times a day up
to 5 times a day based on efficacy and tolerability. For conversion from carbidopa; levodopa; entacapone, the recommended conversions may need to be increased. NOTE: Avoid sudden discontinuation or rapid dose reduction. Tapering is recommended when treatment is being discontinued. For the treatment of restless legs syndrome (RLS)†. Oral dosage Adults A bedtime dose of immediate-release
carbidopa-levodopa starting at 25 mg/100 mg has been suggested. Levodopa dosages as high as 600 mg/day in divided doses have been employed. Dosages may be increased rapidly based on individual response and are usually given prior to bedtime in most studies. A rebound phenomenon has been described in some patients receiving Sinemet 25/100 at bedtime during prolonged use (several weeks) of regular and sustained-release Sinemet. These patients experienced morning symptoms of RLS. The authors
claimed that the morning symptoms could be controlled with daytime administration of the sustained-release product, but could not exclude the possibility of returned symptoms of RLS later in the day. (Morning symptoms disappeared when the dosage was changed to 2 doses of Sinemet CR 50/100 in the evening and 1 dose of 25/100 in the morning.) The reason for this phenomenon has not been determined, but should be considered when using levodopa for RLS. For the treatment of amblyopia†. Oral dosage (immediate-release products) Children 4 years and older and Adolescents Various doses have been studied including levodopa-carbidopa 1.02/0.25 mg/kg PO 3 times daily, or 0.5 mg levodopa (with a 25% fixed-dose combination of carbidopa) PO 3 times daily; some studies compared the drug with patching or occlusion while others added the drug to patching/occlusion. Limited data indicate that there may
be some benefit to combining levodopa/carbidopa with occlusion therapy. A single-dose study of 20 children (4 to 14 years) with amblyopia all undergoing occlusion therapy, compared levodopa-carbidopa 25/6.25 mg or 50/12.5 mg to placebo. Significant improvement of 1 line in visual acuity was observed at both levodopa/carbidopa dosages whereas no significant improvement in visual acuity was noted with use of placebo. In a 7-week study, 13 amblyopic children (7 to 12 years) who no longer responded
to occlusion or penalization therapy were randomized to treatment with levodopa/carbidopa 1.02/0.25 mg/kg 3 times daily with or without occlusion (occlusion was used for 3 hours/day). A significantly greater improvement in visual acuity of the amblyopic eye was observed in the occlusion group compared to the non-occlusion group (2.1 lines vs. 0.8 lines, p = 0.002). In addition, the occlusion group maintained a greater improvement in the visual acuity of the amblyopic eye 4 weeks after study
termination. No statistically significant difference was noted in the visual acuity of the dominant eye 4 weeks after study termination. In another 7-week study, amblyopic patients (4 to 22 years) were randomized to receive treatment with levodopa alone (0.5 mg/kg with a 25% fixed-dose combination of carbidopa 3 times daily), levodopa with part-time occlusion (3 hours/day), or levodopa with full-time occlusion (during all waking hours). None of the patients 15 years or older responded to
therapy. An improvement in visual acuity occurred in 74% of the patients (n = 53), regardless of occlusion therapy. Forty-four of the responders were followed up 1 year after cessation of levodopa-carbidopa therapy. Improvement in visual acuity was maintained in approximately 50% of these patients. Although the addition of occlusion (part-time or full-time) did not facilitate recovery of vision, improvement in visual acuity was maintained for a longer duration in the patients who received
full-time occlusion than in those receiving levodopa-carbidopa alone or with part-time occlusion. †Indicates off-label use MAXIMUM DOSAGEAdults NOTE: Experience with daily dosages of carbidopa greater than 200 mg/day PO is limited. Geriatric NOTE: Experience with daily dosages of carbidopa greater than 200 mg/day PO is limited. Adolescents Safety and efficacy have not been established. Children Safety and efficacy have not been established. Infants Not indicated. Neonates Not indicated. DOSING CONSIDERATIONSHepatic Impairment Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Renal Impairment Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. ADMINISTRATIONOral Administration Many products may be taken with or without food. Follow the directions of the product prescribed. Oral Solid Formulations Immediate-release tablets (e.g., Sinemet): Immediate-release tablets, functionally scored (Dhivy): Extended-release tablets (e.g., Sinemet CR): Extended-release capsules (Rytary): Orally disintegrating tablets (ODT, e.g., Parcopa): Extemporaneous Compounding-Oral Extemporaneous compounding instructions for liquid formulation: Other Administration Route(s) Intrajejunal Route Carbidopa and Levodopa enteral suspension (Duopa): Duopa Cassettes: Recommended Tubing Sets for Long-Term PEG-J Administration: Enteral infusion interruption or discontinuation: Pharmacy Thawing and Storage instructions for Duopa: STORAGEAtamet: CONTRAINDICATIONS / PRECAUTIONSGeneral Information The administration of carbidopa; levodopa is contraindicated in any patient who has demonstrated a hypersensitivity to carbidopa, levodopa, or any inactive ingredients in the formulations. Dyskinesia Carbidopa; levodopa therapy can cause dyskinesias that may require a dosage reduction of the product used or a dosage reduction of other medications used for the treatment of Parkinson's disease. Because carbidopa permits more levodopa to reach the brain and more dopamine to be formed, dyskinesias (involuntary movements), may occur at lower dosages
and sooner with carbidopa; levodopa than with levodopa alone. Abrupt discontinuation, hyperthermia, mental status changes, surgery Avoid abrupt discontinuation of carbidopa; levodopa therapy. Sporadic cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have been associated with dose reductions and withdrawal of carbidopa, levodopa or other medications with dopaminergic properties, and may be life-threatening. Hyperpyrexia and confusion
are uncommon but they may be life-threatening with a variety of features, including hyperthermia/fever/hyperpyrexia, muscle rigidity, involuntary movements, altered consciousness/mental status changes, delirium, autonomic dysfunction, tachycardia, tachypnea, sweating, hypo- or hypertension, and abnormal laboratory findings (e.g., creatine phosphokinase (CPK) elevation, leukocytosis, myoglobinuria, and increased serum myoglobin). The early diagnosis of this condition is important for the
appropriate management of these patients, which includes intensive medical monitoring and management. This may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include anticholinergic toxicity, heat stroke, drug fever, or a primary central nervous system (CNS) pathology. If a patient needs to discontinue or reduce
their daily dose of this product, the dose should be decreased slowly, with supervision from a health care provider, especially if the patient is also receiving neuroleptics. If a patient requires general anesthesia for surgery, carbidopa; levodopa may be continued as long as the patient is permitted to take fluids and medication by mouth. Cases of neuroleptic malignant syndrome have been reported post-surgery so close monitoring is warranted; re-institute carbidopa; levodopa therapy as soon as
possible after the procedure. In addition, some patients receiving levodopa have experienced postoperative bleeding episodes, so hematological studies are recommended for all patients who undergo surgery while receiving this drug. MAOI therapy The administration of non-selective monoamine oxidase inhibitor therapy (MAOI therapy) is contraindicated with carbidopa; levodopa. Concomitant use of non-selective MAOIs with carbidopa-levodopa combinations can result in
hypertensive crisis. Nonselective MAO inhibitors must be discontinued at least 2 weeks prior to initiating therapy with levodopa; carbidopa. Selective MAO-B inhibitors and other standard drugs for Parkinson's disease may be used concomitantly with carbidopa; levodopa; however, dosage adjustments of therapies may be required. Cardiac arrhythmias, cardiac disease, hypotension, myocardial infarction, orthostatic hypotension, syncope Caution should be exercised
when prescribing carbidopa; levodopa to Parkinson's patients who are prone to hypotension or orthostatic hypotension. Syncope and/or orthostatic hypotension have been reported with drugs that increase dopaminergic tone, including levodopa; carbidopa. Reports of syncope are generally more frequent in patients who have experienced prior episodes of documented hypotension. Monitor for orthostatic hypotension, especially after initiation of treatment or after increasing the carbidopa; levodopa dose.
Cardiac monitoring in a facility with provisions for intensive cardiac care is recommended during initial titration of carbidopa-levodopa in Parkinson's patients with significant cardiac disease, including patients a history of myocardial infarction who have residual cardiac arrhythmias (i.e., atrial, nodal, or ventricular arrhythmias). Behavioral changes, depression, psychosis, suicidal ideation All patients receiving carbidopa; levodopa should be monitored
closely for changes in thought processes, moods, or behaviors. Carbidopa; levodopa may cause mental status and behavioral changes, which may be severe, including psychotic-like behavior, during treatment. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies or suicidal ideation. Patients with past or current psychosis should be treated with caution. Dopaminergic therapy in patients with Parkinson's disease has been associated with
hallucinations and may lead to drug withdrawal or patient hospitalization in rare instances. These reactions are thought to be due to increased brain dopamine following administration of levodopa. Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion, narcolepsy, sleep apnea, sudden sleep onset Carbidopa; levodopa has the potential to cause drowsiness or somnolence. There have been postmarketing reports of patients who
have experienced sudden sleep onset during daily activities when taking dopaminergic agents. In some cases, excessive drowsiness has resulted in automobile accidents or other harmful events in the course of daily living. Patients should be advised of this effect and be instructed to use extreme caution when driving or operating machinery or performing other tasks that require alertness while receiving carbidopa; levodopa. Reassessment for drowsiness or oversedation is necessary throughout
therapy. Sleep disorders (e.g., narcolepsy, sleep apnea), coadministration with other CNS depressants, or interacting medications may increase the risk of suddenly falling asleep while on this medication. Patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Advise patients to speak with their health care prescriber before ethanol ingestion, taking sedating medications, or before taking other CNS depressant
medications because of the possible additive effects in combination with carbidopa; levodopa. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), this drug product should ordinarily be discontinued. If a decision is made to continue treatment, patients should be advised to avoid driving or other potentially dangerous activities. There is insufficient data to establish if dose
reduction will eliminate sudden episodes of falling asleep. Impulse control symptoms Some patients receiving medications that increase dopaminergic tone have reported intense and uncontrollable impulse control symptoms, such as urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, or other intense urges. Advise patients that they may experience impulsive and/or compulsive behaviors while taking 1 or more of the medications used
for the treatment of Parkinson's disease. Ask patients about the development of new or increased gambling urges, sexual urges, urges for uncontrolled spending, or other intense urges while being treated with carbidopa; levodopa. Advise patients to inform their physician or health care provider if they experience new or increased symptoms of this type while taking this medication. Consider dose reduction or discontinuation if a patient develops these symptoms during treatment. Closed-angle glaucoma Carbidopa; levodopa is generally contraindicated for use in patients with closed-angle glaucoma. Levodopa therapy can cause mydriasis which can increase intraocular pressure. Patients with other types of glaucoma may be treated cautiously with carbidopa; levodopa if intraocular pressure is controlled and monitored. GI bleeding, GI obstruction, GI perforation, intussusception, peptic ulcer disease Carbidopa; levodopa combinations may
increase the risk of upper GI bleeding in patients with a history of active peptic ulcer disease, so it should be used with extreme caution in such patients. Because the enteral suspension (i.e., Duopa) is administered into the jejunum using a PEG-J or naso-jejunal tube (NJ tube), intestinal complications can occur. These complications include bezoar, ileus, implant site erosion/ulcer, intestinal hemorrhage, intestinal ischemia, intestinal obstruction, intestinal perforation, intussusception,
pancreatitis, peritonitis, pneumoperitoneum, and post-operative wound infection. It may be prudent to use the enteral suspension formulation with caution in patients with a history of GI perforation or GI obstruction or risk factors for these events. These complications may result in serious outcomes, such as death or the need for surgery. Patients should be instructed to notify their healthcare provider immediately if they experience abdominal pain, prolonged constipation, nausea, vomiting,
fever, or melanotic stool while receiving carbidopa; levodopa enteral suspension. Diabetes mellitus Use carbidopa; levodopa with caution during the interpretation of certain urine tests in patients with diabetes mellitus. When a test tape is used for determination of ketonuria in patients taking carbidopa; levodopa, a false-positive urinary ketone test may result. This reaction will not be altered by boiling the urine specimen. Additionally, false-negative tests
may result with the use of glucose-oxidase methods of testing for glucosuria. Melanoma Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma skin cancer than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. Patients and providers are advised to
monitor for melanomas frequently and on a regular basis when using levodopa; carbidopa. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists). The carbidopa-levodopa extended-release capsules and the enteral suspension no longer carry this precaution in their product labels. Laboratory test interference, pheochromocytoma Rarely, falsely diagnosed pheochromocytoma has been reported in patients
receiving levodopa due to a laboratory test interference. Caution should be exercised when interpreting the plasma and urine levels of catecholamines and their metabolites in patients on carbidopa; levodopa therapy. Asthma, pulmonary disease, pulmonary fibrosis, retroperitoneal fibrosis Carbidopa; levodopa should be administered cautiously to patients with severe pulmonary disease or bronchial asthma. Use caution when combining carbidopa; levodopa with other
dopaminergic treatments. Cases of retroperitoneal fibrosis, pulmonary fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening have been reported in some patients treated with ergot-derived dopaminergic agents. These complications may resolve when the drug is discontinued, but complete resolution does not always occur. Although these adverse reactions may be related to the ergoline structure of these compounds, a possible causal role of non-ergot drugs (e.g., levodopa), which
increase dopaminergic activity, has also been considered. The rate of such complications is very low. Peripheral neuropathy Patients should be evaluated for signs and symptoms of peripheral neuropathy before starting carbidopa; levodopa enteral suspension. In addition, patients should be monitored periodically for signs of neuropathy during treatment with the enteral suspension, particularly those with pre-existing neuropathy or who have a medical condition that
may be associated with a risk for neuropathy (e.g., diabetes mellitus, Guillain-Barre syndrome, vitamin B12 deficiency, thiamine deficiency, alcoholism, systemic lupus erythematosus (SLE), acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis). Also use caution in patients who are receiving medications associated with a potential risk for neuropathy (e.g., "statins", metronidazole, some medications for HIV infection, fluoroquinolones, certain chemotherapy agents, or excessive dose of
pyridoxine). During clinical trials, 5% of patients treated with the enteral suspension developed a generalized polyneuropathy, most often characterized as sensory or sensorimotor. Electrodiagnostic results were primarily consistent with an axonal polyneuropathy in those patients who underwent the testing (15/16). There was insufficient information to determine the potential role of vitamin deficiencies in the etiology of neuropathy associated with carbidopa; levodopa enteral suspension. Hepatic disease, renal disease There is a very general precaution that carbidopa; levodopa combinations should be administered with caution to patients with renal disease or hepatic disease. No dosage adjustments are recommended based on renal or hepatic impairment; titration occurs to clinical response. Geriatric Although no overall meaningful differences in safety or effectiveness were observed between geriatric and younger adults in
clinical trials of carbidopa; levodopa, a greater sensitivity of some geriatric patients to the products cannot be ruled out. Therefore, careful monitoring is advisable. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, antiparkinson medications may cause significant confusion, restlessness, delirium, dyskinesia, nausea, dizziness, hallucinations, and agitation. In addition, there is an
increased risk of postural hypotension and falls, particularly during concurrent use of antihypertensive medications. Pregnancy There are no adequate or well-controlled studies of carbidopa; levodopa during pregnancy. Because the pregnancy outcome data are too limited to be conclusive, carbidopa; levodopa should be used in pregnancy only if the potential benefit outweighs the potential risk to the fetus. It has been reported from individual cases that levodopa
crosses the human placental barrier, enters the fetus, and is metabolized. Instruct female patients to notify their physicians if they become pregnant or intend to become pregnant during carbidopa; levodopa therapy. Limited data suggest that carbidopa crosses the placenta in humans in low concentrations. Levodopa crosses the placenta and reaches levels in the fetus comparable to maternal blood, although pregnancy outcomes have been primarily unremarkable. Two miscarriages were reported in the
first trimester during use of carbidopa-levodopa, and 1 infant exposed to levodopa in utero was reported to have osteomalacia. Maternal complications reported in 3 pregnancies during use of carbidiopa-levodopa included first trimester vaginal bleeding, third trimester nausea and vomiting, depression, and preeclampsia. In animals, administration of carbidopa-levodopa during pregnancy was associated with developmental toxicity, including increased incidences of fetal malformations. Visceral and
skeletal malformations were observed in rabbits at all doses and ratios of carbidopa-levodopa tested. In rats, there was a decrease in live births. The effects of carbidopa; levodopa in labor and delivery are unknown. Breast-feeding Caution should be exercised when carbidopa; levodopa is administered to a woman who is breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately
treated condition. It is not known whether carbidopa is excreted in human milk. Levodopa has been detected in human milk; however, there are no adequate data on the effects of levodopa or carbidopa on the breastfed infant, or the effects of milk production. In a case report of a breast-feeding mother with Parkinson's disease receiving sustained-release (SR) carbidopa/levodopa 50/200 mg 4 times daily, peak levels of levodopa in milk occurred 3 hours after a dose and returned to baseline after 6
hours. After receiving the same dose of the immediate-release (IR) formulation, similar results were observed, with the exception of a higher milk:plasma ratio with the IR product (0.32 vs. 0.28). The infant ingested 0.127 mg and 0.181 mg of levodopa after maternal intake of the SR and IR products, respectively. It was estimated that the infant received an average of 0.3% of the maternal weight-adjusted dosage of the SR product and 0.5% of the maternal weight-adjusted dose of the IR product.
Levodopa did not inhibit lactation. No adverse effects were observed in her infant, whose development was normal at 2 years of age. The authors suggest that nursing or pumping milk at times of lower levodopa breast milk levels may help minimize the amount of levodopa received by an infant. Because levodopa can inhibit prolactin secretion, interference with lactation is possible. Partial to complete suppression of lactation has been observed in female patients given levodopa for galactorrhea. If
carbidopa; levodopa must be administered during breast-feeding, the breast-fed infant should be monitored for commonly encountered adverse effects associated with dopaminergic therapy including dyskinesias, insomnia, sedation, nausea, and constipation. Children, infants Carbidopa; levodopa combinations have not been adequately studied for safety and efficacy in children and adolescents less than 18 years of age. This drug combination is not indicated in
infants. Juvenile onset Parkinson's disease is very rare. Phenylketonuria Patients with phenylketonuria patients should be informed that carbidopa; levodopa orally disintegrating tablets (ODT) contain aspartame, a source of phenylalanine. For example, the Parcopa product contains phenylalanine 3.4 mg per 25/100 ODT, 3.4 mg per 10/100 ODT, and 8.4 mg per 25/250 ODT. ADVERSE REACTIONSSevere akinesia /
Delayed / Incidence not known Moderate orthostatic hypotension / Delayed / 0-73.0 Mild nausea / Early / 3.0-30.0 DRUG INTERACTIONSAlfentanil: (Major) Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications. The patient should be observed for symptoms resembling neuroleptic malignant syndrome, and the usual
regimen should be administered as soon as the patient is able to take oral medication. PREGNANCY AND LACTATIONPregnancy There are no adequate or well-controlled studies of carbidopa; levodopa during pregnancy. Because the pregnancy outcome data are too limited to be conclusive, carbidopa; levodopa should be
used in pregnancy only if the potential benefit outweighs the potential risk to the fetus. It has been reported from individual cases that levodopa crosses the human placental barrier, enters the fetus, and is metabolized. Instruct female patients to notify their physicians if they become pregnant or intend to become pregnant during carbidopa; levodopa therapy. Limited data suggest that carbidopa crosses the placenta in humans in low concentrations. Levodopa crosses the placenta and reaches
levels in the fetus comparable to maternal blood, although pregnancy outcomes have been primarily unremarkable. Two miscarriages were reported in the first trimester during use of carbidopa-levodopa, and 1 infant exposed to levodopa in utero was reported to have osteomalacia. Maternal complications reported in 3 pregnancies during use of carbidiopa-levodopa included first trimester vaginal bleeding, third trimester nausea and vomiting, depression, and preeclampsia. In animals, administration of
carbidopa-levodopa during pregnancy was associated with developmental toxicity, including increased incidences of fetal malformations. Visceral and skeletal malformations were observed in rabbits at all doses and ratios of carbidopa-levodopa tested. In rats, there was a decrease in live births. The effects of carbidopa; levodopa in labor and delivery are unknown. Caution should be exercised when carbidopa; levodopa is administered to a woman who is breast-feeding. Consider the
benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. It is not known whether carbidopa is excreted in human milk. Levodopa has been detected in human milk; however, there are no adequate data on the effects of levodopa or carbidopa on the breastfed infant, or the effects of milk production. In a case report of a breast-feeding mother with Parkinson's disease receiving sustained-release (SR) carbidopa/levodopa
50/200 mg 4 times daily, peak levels of levodopa in milk occurred 3 hours after a dose and returned to baseline after 6 hours. After receiving the same dose of the immediate-release (IR) formulation, similar results were observed, with the exception of a higher milk:plasma ratio with the IR product (0.32 vs. 0.28). The infant ingested 0.127 mg and 0.181 mg of levodopa after maternal intake of the SR and IR products, respectively. It was estimated that the infant received an average of 0.3% of
the maternal weight-adjusted dosage of the SR product and 0.5% of the maternal weight-adjusted dose of the IR product. Levodopa did not inhibit lactation. No adverse effects were observed in her infant, whose development was normal at 2 years of age. The authors suggest that nursing or pumping milk at times of lower levodopa breast milk levels may help minimize the amount of levodopa received by an infant. Because levodopa can inhibit prolactin secretion, interference with lactation is possible.
Partial to complete suppression of lactation has been observed in female patients given levodopa for galactorrhea. If carbidopa; levodopa must be administered during breast-feeding, the breast-fed infant should be monitored for commonly encountered adverse effects associated with dopaminergic therapy including dyskinesias, insomnia, sedation, nausea, and constipation. MECHANISM OF ACTIONThe combination of levodopa with carbidopa is used for the treatment of
Parkinson's disease. Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson's disease because it does not cross the blood-brain barrier. The administration of these drugs increases dopamine levels within the corpus striatum. PHARMACOKINETICSThe combination of carbidopa-levodopa is administered orally as regular-release tablets, extended-release tablets, and extended-release capsules, and as an enteral suspension delivered into the jejunum via a programmable enteral infusion pump. Carbidopa-levodopa distributes throughout the body. Plasma protein binding of carbidopa and levodopa are clinically insignificant. Less than 1% of levodopa would reach the CNS if given without carbidopa. Carbidopa reduces the dosage of levodopa required to produce a given effect in the CNS by about 75%. Carbidopa does not penetrate the CNS. When administered with levodopa, carbidopa inhibits the peripheral metabolism of levodopa resulting in increases in both plasma levels and the plasma half-life of levodopa and decreases levels of dopamine and homavanillic acid in the plasma and urine. Carbidopa allows a larger percentage of the levodopa dose to enter the CNS where it is metabolized to dopamine by L-aromatic amino acid decarboxylase and 3-O-methyldopa. Peripheral dopa-decarboxylase may be saturated by carbidopa in other carbidopa/levodopa products at 70—100 mg/day, which produces equivalent exposure to 140—200 mg of carbidopa in the extended-release capsules. The two metabolites of carbidopa are primarily eliminated in the urine unchanged or as a glucuronide. Unchanged carbidopa accounts for 30% of the total urinary elimination. The plasma half-life of levodopa in the presence of carbidopa is roughly 1—2 hours. The half-life of carbidopa is about 2 hours. Carbidopa; levodopa is eliminated renally as dopamine metabolites and small amounts of unchanged drug. The full therapeutic effects of conventional carbidopa-levodopa dosage forms at any given dosage can be observed 2—3 weeks after therapy is first initiated, but some patients require up to 6 months before maximal response to a given dosage is seen. Affected cytochrome P450 (CYP450) enzymes and drug transporters: None. Oral Route After oral administration, amino acid transport mechanisms carry levodopa across the membrane of the GI tract, with approximately 30—50% of the drug entering the circulation. As a result, it is thought that high concentrations of amino acids in the GI tract (i.e., a high-protein diet) can interfere with absorption of levodopa. There is evidence, however, to suggest that amino acid-levodopa transport competition is more likely to occur during levodopa active transport across
the blood-brain barrier. Other Route(s) Intrajejunal Route (Duopa) What are the contraindications of carbidopa levodopa?Who should not take Carbidopa-levodopa?. malignant melanoma, a type of skin cancer.. diabetes.. mental problems from taking the drug.. psychotic disorder.. suicidal thoughts.. signs or symptoms of neurosis.. depression.. wide-angle glaucoma.. Which is contraindicated for a patient with Parkinson's disease who is on levodopa?In patients on levodopa therapy, mono amino oxide (MAO) inhibitors are contraindicated and sympathomimetics should be used with caution as these can cause an acute rise in blood pressure.
What are the contraindications of co Careldopa?have had an allergic reaction to co-careldopa, levodopa, carbidopa or any other medicines in the past.. have glaucoma.. have ever had a mental health condition, including depression or psychosis.. What are the complications of carbidopa levodopa?Levodopa and carbidopa may cause side effects.. dizziness.. loss of appetite.. diarrhea.. dry mouth.. mouth and throat pain.. constipation.. change in sense of taste.. forgetfulness or confusion.. |