Levodopa + Carbidopa + Entacapone interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Alcohol may potentiate some of the pharmacologic effects of levodopa. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

  What to do: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents. Until more data are available, it is advisable to avoid large fluctuations in daily protein intake and to monitor patients for altered effects of levodopa if the protein content of the diet is increased.

  1 source

  1. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

• alcohol

  Moderate

  Synergy

  Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

  What to do: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

  4 sources

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):

Conditions

Conditions in which Levodopa + Carbidopa + Entacapone needs care, as documented in this source.

• Glaucoma

  Major

  The use of levodopa is contraindicated in patients with acute closed-angle glaucoma. Levodopa (with or without carbidopa) may be used in patients with open-angle glaucoma who are receiving appropriate therapy.

  2 sources

  1. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  2. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):

• Glaucoma

  Major

  Carbidopa-levodopa products are contraindicated in patients with narrow-angle glaucoma.

  1 source

  1. "Product Information. Lodosyn (carbidopa)." DuPont Pharma (2001):

• Heart Diseases

  Major

  Cardiac irregularities occur infrequently in patients on dopamine agonists. The initial administration and titration is recommended to occur under close cardiac monitoring in a facility equipped for intensive cardiac care. Adverse cardiac affects may include palpitation, sinus tachycardia, ventricular tachycardia, extrasystole, atrial flutter or fibrillation, or block of AV conduction.

  6 sources

  1. Shah PK, Amin DK, Horn E "Adverse clinical and hemodynamic effects of oral levodopa in chronic congestive heart failure." Am Heart J 110 (1985): 488-9
  2. Benaim ME "Levodopa and arrhythmias." Br Med J 4 (1972): 50-1
  3. Broderick G, Rajfer SI "The use of levodopa, an oral dopamine precursor, in congestive heart failure." Basic Res Cardiol 84 (1989): 187-90
  4. Chamsi-Pasha H, Horsley M, Barnes PC "Levodopa and congestive cardiomyopathy." Br J Hosp Med 41 (1989): 489
  5. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  6. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):

• Hypotension

  Major

  Dopamine agonists may impair the systemic regulation of blood pressure, with resultant orthostatic hypotension, especially during dose escalation. Therapy with dopamine agonists should be monitored carefully in patients with Parkinson's disease since they may have an impaired ability to respond to an orthostatic challenge, and also in patients receiving antihypertensive drugs.

  11 sources

  1. Hoehn MM "Levodopa-induced postural hypotension. Treatment with fludrocortisone." Arch Neurol 32 (1975): 50-1
  2. Iwasaki S, Hamaguchi K, Iwasaki A, Takakusagi M, Narabayashi Y "Hypotensive effect of long-term levodopa in patients with Parkinson's disease." Eur Neurol 30 (1990): 194-9
  3. "Product Information. Dostinex (cabergoline)." Pharmacia and Upjohn (2001):
  4. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  5. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  6. "Product Information. Mirapex (pramipexole)." Boehringer Ingelheim (2001):
  7. "Product Information. Requip (ropinirole)." SmithKline Beecham (2001):
  8. "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals (2001):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  10. "Product Information. Neupro (rotigotine)." Schwarz Pharma (2007):
  11. "Product Information. Xadago (safinamide)." US WorldMeds LLC (2017):

• Hypotension

  Major

  Dopamine agonists may impair the systemic regulation of blood pressure, with resultant orthostatic hypotension, especially during dose escalation. Therapy with dopamine agonists should be monitored carefully in patients with Parkinson's disease since they may have an impaired ability to respond to an orthostatic challenge, and also in patients receiving antihypertensive drugs.

  11 sources

  1. Hoehn MM "Levodopa-induced postural hypotension. Treatment with fludrocortisone." Arch Neurol 32 (1975): 50-1
  2. Iwasaki S, Hamaguchi K, Iwasaki A, Takakusagi M, Narabayashi Y "Hypotensive effect of long-term levodopa in patients with Parkinson's disease." Eur Neurol 30 (1990): 194-9
  3. "Product Information. Dostinex (cabergoline)." Pharmacia and Upjohn (2001):
  4. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  5. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  6. "Product Information. Mirapex (pramipexole)." Boehringer Ingelheim (2001):
  7. "Product Information. Requip (ropinirole)." SmithKline Beecham (2001):
  8. "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals (2001):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  10. "Product Information. Neupro (rotigotine)." Schwarz Pharma (2007):
  11. "Product Information. Xadago (safinamide)." US WorldMeds LLC (2017):

• Hypotension

  Major

  Dopamine agonists may impair the systemic regulation of blood pressure, with resultant orthostatic hypotension, especially during dose escalation. Therapy with dopamine agonists should be monitored carefully in patients with Parkinson's disease since they may have an impaired ability to respond to an orthostatic challenge, and also in patients receiving antihypertensive drugs.

  11 sources

  1. Hoehn MM "Levodopa-induced postural hypotension. Treatment with fludrocortisone." Arch Neurol 32 (1975): 50-1
  2. Iwasaki S, Hamaguchi K, Iwasaki A, Takakusagi M, Narabayashi Y "Hypotensive effect of long-term levodopa in patients with Parkinson's disease." Eur Neurol 30 (1990): 194-9
  3. "Product Information. Dostinex (cabergoline)." Pharmacia and Upjohn (2001):
  4. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  5. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  6. "Product Information. Mirapex (pramipexole)." Boehringer Ingelheim (2001):
  7. "Product Information. Requip (ropinirole)." SmithKline Beecham (2001):
  8. "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals (2001):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  10. "Product Information. Neupro (rotigotine)." Schwarz Pharma (2007):
  11. "Product Information. Xadago (safinamide)." US WorldMeds LLC (2017):

• Liver Diseases

  Major

  The pharmacokinetics of levodopa have not been studied in patients with hepatic or renal impairment. Therapy with levodopa should be administered cautiously in patients with liver or disease. Periodic monitoring of hepatic and renal function is recommended during extended therapy.

  1 source

  1. "Product Information. Inbrija (levodopa)." Acorda Therapeutics (2019):

• Lung Diseases

  Major

  Because of the risk of bronchospasm, use of levodopa in patients with asthma, COPD, or other chronic underlying lung disease is not recommended.

  1 source

  1. "Product Information. Inbrija (levodopa)." Acorda Therapeutics (2019):

• Melanoma

  Major

  The use of levodopa is considered by manufacturers to be contraindicated in patients with a history of melanoma or in patients with suspicious, undiagnosed skin lesions. Levodopa reportedly may activate malignant melanoma, although some investigators have found a causal relationship to be tenuous.

  14 sources

  1. Kochar AS "Development of malignant melanoma after levodopa therapy for Parkinson's disease. Report of a case and review of the literature." Am J Med 79 (1985): 119-21
  2. Bernstein JE, Medenica M, Soltani K, Solomon A, Lorincz AL "Levodopa administration and multiple primary cutaneous melanomas." Arch Dermatol 116 (1980): 1041-44
  3. Robinson E, Wajsbort J, Hirshowitz B "Levodopa and malignant melanoma." Arch Pathol 95 (1973): 213
  4. Haider SA, Thaller VT "Lid melanoma and parkinsonism." Br J Ophthalmol 76 (1992): 246-7
  5. Gurney H, Coates A, Kefford R "The use of L-dopa and carbidopa in metastatic malignant melanoma." J Invest Dermatol 96 (1991): 85-7
  6. Abramson DH, Rubenfeld MR "Choroidal melanoma and levodopa" JAMA 252 (1984): 1011-2
  7. Fermaglich J, Delaney P "Levodopa and melanoma" JAMA 241 (1979): 883-4
  8. Sober AJ, Wick MM "Levodopa therapy and malignant melanoma." JAMA 240 (1978): 554-5

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  9. Rosin MA, Braun M, 3d Braun M "Malignant melanoma and levodopa." Cutis 33 (1984): 572-4
  10. Fermaglich J, Delaney P "Parkinson's disease, melanoma, and levodopa." J Neurol 215 (1977): 221-4
  11. Van Rens GH, De Jong PT, Demols EE, Brihaye-Van Geertruyden MF "Uveal malignant melanoma and levodopa therapy in Parkinson's disease." Ophthalmology 89 (1982): 1464-6
  12. Weiner WJ, Singer C, Sanchez-Ramos JR, Goldenberg JN "Levodopa, melanoma, and Parkinson's disease." Neurology 43 (1993): 674-7
  13. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  14. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):

• Neuroleptic Malignant Syndrome

  Major

  The use of dopamine agonists is contraindicated in patients with neuroleptic malignant syndrome (NMS). NMS is characterized by hyperthermia, muscle rigidity, altered mental status, irregular pulse or blood pressure, tachycardia, and diaphoresis. The syndrome may rarely be precipitated by abrupt discontinuation of the dopamine agonist.

  5 sources

  1. Friedman JH, Feinberg SS, Feldman RG "A neuroleptic malignantlike syndrome due to levodopa therapy withdrawal." JAMA 254 (1985): 2792-5
  2. Genis D "Neuroleptic malignant syndrome: impaired dopaminergic systems?" Neurology 35 (1985): 1806
  3. Rainer C, Scheinost NA, Lefeber EJ "Neuroleptic malignant syndrome. When levodopa withdrawal is the cause." Postgrad Med 89 (1991): 175-8,
  4. Gibb WR, Griffith DN "Levodopa withdrawal syndrome identical to neuroleptic malignant syndrome." Postgrad Med J 62 (1986): 59-60
  5. "Product Information. Mirapex (pramipexole)." Boehringer Ingelheim (2001):

• Psychotic Disorders

  Major

  The use of dopamine agonists has been associated with psychiatric effects such as hallucinations, psychosis, confusion, anxiety, mania, hypomania, depression, rapid mood cycling, nightmares, and hypersexuality. Therapy with dopamine agonists should be administered cautiously in psychotic patients and all patients should be carefully observed for development of depression and suicidal tendencies.

  11 sources

  1. Ko GN, Leckman JF, Heninger GR "Induction of rapid mood cycling during L-dopa treatment in a bipolar patient." Am J Psychiatry 138 (1981): 1624-5
  2. Ryback RS, Schwab RS "Manic response to levodopa therapy. Report of a case." N Engl J Med 285 (1971): 788-9
  3. Banerjee AK, Falkai PG, Savidge M "Visual hallucinations in the elderly associated with the use of levodopa." Postgrad Med J 65 (1989): 358-61
  4. Vazquez A, Jimenez-Jimenez FJ, Garcia-Ruiz P, Garcia-Urra D ""Panic attacks" in Parkinson's disease. A long-term complication of levodopa therapy." Acta Neurol Scand 87 (1993): 14-8
  5. Nausieda PA, Glantz R, Weber S, Baum R, Klawans HL "Psychiatric complications of levodopa therapy of Parkinson's disease." Adv Neurol 40 (1984): 271-7
  6. Glantz RH, Bieliauskas L, Paleologos N "Behavioral indicators of hallucinosis in levodopa-treated Parkinson's disease." Adv Neurol 45 (1987): 417-20
  7. Friedman JH "The management of the levodopa psychoses." Clin Neuropharmacol 14 (1991): 283-95
  8. Harsch HH, Miller M, Young LD "Induction of mania by L-dopa in a nonbipolar patient." J Clin Psychopharmacol 5 (1985): 338-9

  Show all 11 sourcesShow fewer sources

  9. Maricle RA, Nutt JG, Carter JH "Mood and anxiety fluctuation in parkinson's disease associated with levodopa infusion: preliminary findings." Mov Disord 10 (1995): 329-32
  10. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  11. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):

• Psychotic Disorders

  Major

  Ordinarily, patients with major psychotic disorder should not be treated with dopaminergic antiparkinson agents, because of the risk of exacerbating psychosis. Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of these drugs.

  8 sources

  1. "Product Information. Dostinex (cabergoline)." Pharmacia and Upjohn (2001):
  2. "Product Information. Mirapex (pramipexole)." Boehringer Ingelheim (2001):
  3. "Product Information. Requip (ropinirole)." SmithKline Beecham (2001):
  4. "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals (2001):
  5. "Product Information. Lodosyn (carbidopa)." DuPont Pharma (2001):
  6. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  7. "Product Information. Neupro (rotigotine)." Schwarz Pharma (2007):
  8. "Product Information. Xadago (safinamide)." US WorldMeds LLC (2017):

• Psychotic Disorders

  Major

  Ordinarily, patients with major psychotic disorder should not be treated with dopaminergic antiparkinson agents, because of the risk of exacerbating psychosis. Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of these drugs.

  8 sources

  1. "Product Information. Dostinex (cabergoline)." Pharmacia and Upjohn (2001):
  2. "Product Information. Mirapex (pramipexole)." Boehringer Ingelheim (2001):
  3. "Product Information. Requip (ropinirole)." SmithKline Beecham (2001):
  4. "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals (2001):
  5. "Product Information. Lodosyn (carbidopa)." DuPont Pharma (2001):
  6. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  7. "Product Information. Neupro (rotigotine)." Schwarz Pharma (2007):
  8. "Product Information. Xadago (safinamide)." US WorldMeds LLC (2017):

• Psychotic Disorders

  Major

  Ordinarily, patients with major psychotic disorder should not be treated with dopaminergic antiparkinson agents, because of the risk of exacerbating psychosis. Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of these drugs.

  8 sources

  1. "Product Information. Dostinex (cabergoline)." Pharmacia and Upjohn (2001):
  2. "Product Information. Mirapex (pramipexole)." Boehringer Ingelheim (2001):
  3. "Product Information. Requip (ropinirole)." SmithKline Beecham (2001):
  4. "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals (2001):
  5. "Product Information. Lodosyn (carbidopa)." DuPont Pharma (2001):
  6. "Product Information. Azilect (rasagiline)." Teva Pharmaceuticals USA (2006):
  7. "Product Information. Neupro (rotigotine)." Schwarz Pharma (2007):
  8. "Product Information. Xadago (safinamide)." US WorldMeds LLC (2017):

• Depressive Disorder

  Moderate

  Caution and observation is recommended when treating patients with carbidopa, as depression with concomitant suicidal tendencies may develop or be exacerbated.

  1 source

  1. "Product Information. Lodosyn (carbidopa)." DuPont Pharma (2001):

• Hepatic Insufficiency

  Moderate

  Entacapone should be used with caution in patients with hepatic impairment, as the AUC and Cmax of the drug approximately doubled in patients with documented liver disease compared to patients with normal liver function.

  1 source

  1. "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals (2001):

• Peptic Ulcer Hemorrhage

  Moderate

  The use of levodopa, especially in combinations with carbidopa, has been associated with an increase in the frequency of gastrointestinal hemorrhage. Therapy with levodopa should be administered cautiously in patients with a history of peptic ulcer disease or gastrointestinal hemorrhage.

  2 sources

  1. "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):
  2. "Product Information. Sinemet CR (carbidopa-levodopa)." DuPont Pharmaceuticals (2001):