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Drug Interactions between ProvayBlue and Stalevo

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

levodopa methylene blue

Applies to: Stalevo (carbidopa / entacapone / levodopa) and ProvayBlue (methylene blue)

CONTRAINDICATED: Levodopa is the precursor of dopamine, which in turn is converted to norepinephrine. As such, levodopa may precipitate severe hypertensive reactions in patients treated with nonselective monoamine oxidase inhibitors (MAOIs). The mechanism is enhanced peripheral catecholamine availability due to decreased degradation (MAOI activity) and increased synthesis (levodopa effect) of dopamine and probably also norepinephrine.

MANAGEMENT: The concomitant administration of carbidopa has been reported to prevent or blunt the hypertensive response by inhibiting peripheral conversion of levodopa to dopamine. However, some clinicians maintain that, with or without carbidopa, levodopa should not be used concurrently with nonselective MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with levodopa.

References

  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  2. Goldberg LI (1964) "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA, 190, p. 456-62
  3. Sjoqvist F (1965) "Psychotropic drugs (2) interaction between monoamine oxidase (MAO) inhibitors and other substances." Proc R Soc Med, 58, p. 967-78
  4. Wright SP (1978) "Hazards with monoamine-oxidase inhibitors: a persistent problem." Lancet, 1, p. 284-5
  5. Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Pritchard BN (1973) "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J, 1, p. 311-5
  6. Schildkraut JJ, Klerman GL, Friend DG, Greenblatt M (1963) "Biochemical and pressor effects of oral d,l-dihydroxyphenylalanine in patients pretreated with antidepressant drugs." Ann N Y Acad Sci, 107, p. 1005-15
  7. Sharpe J, Marquez-Julio A, Ashby P (1972) "Idiopathic orthostatic hypotension treated with levodopa and MAO inhibitor: a preliminary report." Can Med Assoc J, 107, p. 296-300
  8. Teychenne PF, Calne DB, Lewis PJ, Findley LJ (1975) "Interactions of levodopa with inhibitors of monoamine oxidase and L-aromatic amino acid decarboxylase." Clin Pharmacol Ther, 18, p. 273-7
  9. Sjoerdsma A (1966) "Catecholamine-drug interactions in man." Pharmacol Rev, 18, p. 673-83
  10. Ban TA (1975) "Drug interactions with psychoactive drugs." Dis Nerv Syst, 36, p. 164-6
  11. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  12. De Vita VT, Hahn MA, Oliverio VT (1965) "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med, 120, p. 561-5
  13. Hunter KR, Boakes AJ, Laurence DR, Stern GM (1970) "Monoamine oxidase inhibitors and L-dopa." Br Med J, 3, p. 388
  14. (2001) "Product Information. Sinemet (carbidopa-levodopa)." DuPont Pharmaceuticals
  15. (2003) "Product Information. Stalevo 50 (carbidopa/entacapone/levodopa)." Novartis Pharmaceuticals
  16. (2004) "Product Information. Parcopa (carbidopa-levodopa)." Schwarz Pharma
  17. (2020) "Product Information. Carbidopa-Levodopa (carbidopa-levodopa)." Teva Pharmaceuticals USA
  18. (2020) "Product Information. Stalevo 50 (carbidopa/entacapone/levodopa)." Almatica Pharma Inc
  19. (2023) "Product Information. AA-Levocarb CR (carbidopa-levodopa)." AA Pharma Inc
  20. (2023) "Product Information. Lecado (co-careldopa)." Sandoz Ltd
  21. (2023) "Product Information. Lecigon (carbidopa/entacapone/levodopa)." Stada Pharmaceuticals Australia Pty Ltd
View all 21 references

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Major

methylene blue entacapone

Applies to: ProvayBlue (methylene blue) and Stalevo (carbidopa / entacapone / levodopa)

CONTRAINDICATED: Theoretically, coadministration of monoamine oxidase (MAO) inhibitors and catechol-O-methyltransferase (COMT) inhibitors may potentiate the risk of hypertensive crisis and serotonin syndrome, the latter of which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. MAO and COMT are the two major enzymatic pathways involved in the metabolism of catecholamines, thus inhibition of both systems may lead to excessive levels of norepinephrine and serotonin. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: In general, COMT inhibitors should not be used concurrently with nonselective MAO inhibitors or other agents that possess MAO inhibiting activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAO inhibitor therapy and initiation of treatment with COMT inhibitors.

References

  1. Pettinger WA, Soyangco FG, Oates JA (1968) "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther, 9, p. 442-7
  2. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  3. De Vita VT, Hahn MA, Oliverio VT (1965) "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med, 120, p. 561-5
  4. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  5. (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
  6. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
  7. (2001) "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals
  8. Wigen CL, Goetz MB (2002) "Serotonin syndrome and linezolid." Clin Infect Dis, 34, p. 1651-2
  9. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  10. Lavery S, Ravi H, McDaniel WW, Pushkin YR (2001) "Linezolid and serotonin syndrome." Psychosomatics, 42, p. 432-4
  11. (2020) "Product Information. Ongentys (opicapone)." Neurocrine Biosciences, Inc.
View all 11 references

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Moderate

levodopa entacapone

Applies to: Stalevo (carbidopa / entacapone / levodopa) and Stalevo (carbidopa / entacapone / levodopa)

MONITOR: When catechol-O-methyltransferase (COMT) inhibitors are administered together with levodopa/carbidopa, they may increase the relative bioavailability (AUC) of levodopa. This is due to a decrease in levodopa clearance resulting in a prolongation of the terminal elimination half-life of levodopa (from approximately 2 hours to 3.5 hours). Adverse effects such as dyskinesia, somnolence, and orthostatic hypotension may be potentiated. In the presence of the decarboxylase inhibitor carbidopa, COMT is the major metabolizing enzyme for levodopa. In clinical trials of COMT inhibitors administered concomitantly with levodopa, patients required a dosage reduction in levodopa if their daily dose of levodopa was greater than 600 mg with tolcapone or 800 mg with entacapone, or if they had moderate or severe dyskinesia before beginning COMT inhibitor treatment. In patients receiving once daily opicapone at bedtime with levodopa/carbidopa administered every three or four hours, levodopa peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 43% to 44% and 62% to 94%, respectively, compared to administration of levodopa/carbidopa alone.

MANAGEMENT: Although COMT inhibitors are intended for use with levodopa/carbidopa, clinicians should be aware that dose reduction of levodopa may be necessary during coadministration. This is especially true if the patient is experiencing dyskinesia induced by levodopa. Use with caution in patients with severe dyskinesia or dystonia. Likewise, when discontinuing a COMT inhibitor, monitor patients and consider adjustment of other dopaminergic therapies as needed. In addition, some authorities advise that opicapone should be administered as a once-daily dose at least one hour before or after combinations containing levodopa so as to avoid any interaction with the absorption of levodopa (AU, UK).

References

  1. (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
  2. Dingemanse J, Jorga K, Zurcher G, Schmitt M, Sedek G, Da Prada M, Van Brummelen P (1995) "Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa." Br J Clin Pharmacol, 40, p. 253-62
  3. Sedek G, Jorga K, Schmitt M, Burns RS, Leese P (1997) "Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers." Clin Neuropharmacol, 20, p. 531-41
  4. Baas H, Beiske AG, Ghika J, Jackson M, Oertel WH, Poewe W, Ransmayr G (1997) "Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuatin parkinsonian patients." J Neurol Neurosurg Psychiatry, 63, p. 421-8
  5. (2001) "Product Information. Comtan (entacapone)." Novartis Pharmaceuticals
  6. (2020) "Product Information. Ongentys (opicapone)." Neurocrine Biosciences, Inc.
  7. Svetel M, Tomic A, Kresojevic N, Kostic V (2018) "Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson’s disease." Expert Opin Drug Metab Toxicol, 14, p. 353-60
View all 7 references

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Drug and food interactions

Moderate

levodopa food

Applies to: Stalevo (carbidopa / entacapone / levodopa)

GENERALLY AVOID: 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.

MONITOR: Limited clinical data suggest that high protein content in the diet may reduce or cause fluctuations in the clinical response to oral and enteral formulations of levodopa in patients with Parkinson's disease. Proposed mechanisms include delayed gastric emptying, decreased levodopa absorption when taken with a protein rich diet, and competition with certain amino acids for transport across the gut wall and/or the blood brain barrier. Data have been conflicting. Clinical studies have variously reported no effect, reduced levodopa absorption with low-protein meals, reduced effects of oral and enteral formulations of levodopa with high daily protein intake, and no differences compared to fasting with high-protein meals. Neuroleptic malignant-like symptoms were reported in a patient with Parkinson's disease who was receiving pramipexole, entacapone, and immediate-release levodopa/carbidopa, after the protein content of his enteral feedings via nasogastric tube was increased from 0.88 g/kg/day to 1.8 g/kg/day; symptoms improved after the protein was reduced to 1 g/kg/day and bromocriptine was administered. Another patient receiving immediate-release carbidopa/levodopa, pramipexole, and entacapone experienced severe rigidity after initiation of continuous enteral nutrition via oral gastric tube containing 1.4 g/kg/day of protein; his Parkinsonian symptoms improved after the protein content was reduced to 0.9 g/kg/day, the feeding was changed to bolus feedings, and the levodopa was administered between boluses.

MANAGEMENT: 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 oral and enteral levodopa formulations if the protein content of the diet is increased.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67
  3. (2022) "Product Information. Duopa (carbidopa-levodopa)." AbbVie US LLC
  4. (2021) "Product Information. Duodopa (carbidopa-levodopa)." AbbVie Pty Ltd, 18
  5. (2023) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie Corporation
  6. (2022) "Product Information. Dhivy (carbidopa-levodopa)." Avion Pharmaceuticals
View all 6 references

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Moderate

entacapone food

Applies to: Stalevo (carbidopa / entacapone / levodopa)

GENERALLY AVOID: 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.

MANAGEMENT: 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.

References

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

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Moderate

levodopa food

Applies to: Stalevo (carbidopa / entacapone / levodopa)

ADJUST DOSING INTERVAL: The oral bioavailability and pharmacologic effects of levodopa and carbidopa may be decreased during concurrent administration with iron-containing products. The proposed mechanism is chelation of levodopa and carbidopa by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In nine patients with Parkinson's disease, administration of levodopa-carbidopa 100 mg-25 mg with ferrous sulfate 325 mg decreased levodopa peak plasma concentration (Cmax) and systemic exposure (AUC) by 47% and 30%, respectively, and carbidopa Cmax and AUC by 77% and 82%, respectively, compared to administration with placebo. There was also evidence of reduced efficacy of levodopa in some patients. In another study consisting of eight healthy subjects, coadministration of levodopa 250 mg with ferrous sulfate 325 mg resulted in greater than 50% reductions in the Cmax and AUC of levodopa compared to administration of levodopa alone. The magnitude of the interaction was the greatest in patients whose plasma levels of levodopa were the highest following administration of levodopa alone.

MANAGEMENT: Until more information is available, patients receiving levodopa and/or carbidopa in combination with iron-containing products should be advised to separate the times of administration by as much as possible. Patients should be monitored for reduced efficacy of levodopa, and the dosage adjusted as necessary.

References

  1. Campbell NR, Hasinoff B (1989) "Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism." Clin Pharmacol Ther, 45, p. 220-5
  2. Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
  3. Campbell NR, Rankine D, Goodridge AE, Hasinoff BB, Kara M (1990) "Sinemet-ferrous sulphate interaction in patients with Parkinson's disease." Br J Clin Pharmacol, 30, p. 599-605
  4. Greene RJ, Hall AD, Hider RC (1990) "The interaction of orally administered iron with levodopa and methyldopa therapy." J Pharm Pharmacol, 42, p. 502-4
View all 4 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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