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Interactions between Inbrija and Methyldopa

1 drug interaction and 26 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

methyldopa levodopa

Applies to: methyldopa and Inbrija (levodopa)
Monitor

The hypotensive and central nervous system (CNS) depressant effects of levodopa or foslevodopa may be additive with antihypertensive agents or agents with hypotensive properties and/or CNS depressant effects. Postural hypotension may occur and/or the risk of sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

Management

Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Dose adjustments of the concomitant agent may be required. Patients should be advised to notify their doctor if they experience dizziness or syncope and/or sudden, excessive or prolonged CNS effects that interfere with their normal activities. Patients should also be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them.

References (6)
  1. (2003) "Product Information. Stalevo 150 (carbidopa/entacapone/levodopa)." Novartis Pharmaceuticals
  2. (2023) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie Corporation
  3. (2024) "Product Information. DUODOPA (foscarbidopa-foslevodopa)." ABBVIE SPAIN, S.L.U
  4. (2024) "Product Information. Produodopa (foscarbidopa-foslevodopa)." AbbVie Ltd
  5. (2024) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie US LLC
  6. (2024) "Product Information. Vyalev 2400/120 (foscarbidopa-foslevodopa)." AbbVie Pty Ltd, Version 1

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

levodopa Food/Lifestyle

Applies to: Inbrija (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 (7)
  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
  7. (2024) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie US LLC
Moderate:

methyldopa Alcohol (Ethanol)

Applies to: methyldopa
Monitor

Certain psychotherapeutic and other CNS-active agents may have blood pressure-lowering effects and may cause dizziness, orthostatic hypotension, or syncope. These effects may be more likely during treatment initiation, dose escalation, or treatment restart. Coadministration with antihypertensives or other agents with blood pressure-lowering properties, particularly vasodilators and alpha-adrenergic blockers, may result in additive hypotensive or orthostatic effects.

Management

Monitor blood pressure and clinical response during concomitant use, especially when starting or increasing the dose of either agent. Patients should be advised to rise slowly from a sitting or lying position and to report dizziness, lightheadedness, fainting, orthostasis, palpitations, or troublesome changes in pulse or heart rate. Patients should be cautioned that alcohol may enhance blood pressure-lowering effects during concomitant use with antihypertensives or other agents with hypotensive properties. Patients should avoid driving or operating hazardous machinery until they know how the medications affect them.

References (13)
  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  7. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
  8. (2023) "Product Information. Buprenorphine (buprenorphine)." G.L. Pharma UK Ltd
  9. (2023) "Product Information. Temgesic (buprenorphine)." Reckitt Benckiser Pty Ltd
  10. (2026) "Product Information. Urapidil (Carinopharm) (urapidil)." Imported (EU)
  11. (2020) "Product Information. URAPIDIL ACCORD (urapidil)." ACCORD HEALTHCARE LIMITED
  12. (2020) "Product Information. Ebrantil (urapidil)." CHEPLAPHARM ARZNEIMITTEL GMBH
  13. (2026) "Product Information. Urapidil (urapidil)." Imported (Switzerland)
Moderate:

methyldopa multivitamins with minerals

Applies to: methyldopa
Adjust dosing interval

The oral bioavailability and pharmacologic effects of methyldopa may be decreased during concurrent administration with iron-containing products. The proposed mechanism is chelation of methyldopa by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In one study, five hypertensive patients receiving chronic methyldopa therapy (250 mg to 1500 mg daily) all had elevated blood pressure following the addition of ferrous sulfate 325 mg three times daily for 2 weeks. The systolic pressure had increased by more than 15 mmHg in three of the patients and the diastolic pressure increased by more than 10 mmHg in two. Blood pressure returned to baseline within 7 days of discontinuing the iron. In 12 normal subjects, administration of methyldopa 500 mg with ferrous sulfate 325 mg or ferrous gluconate 600 mg resulted in an 88% and 79% reduction, respectively, in the renal excretion of unmetabolized, free methyldopa compared to administration of methyldopa alone. In another study, administration of ferrous sulfate simultaneously with methyldopa reduced the bioavailability of methyldopa by 83%, while administration one hour or two hours before methyldopa reduced its bioavailability by 55% and 42%, respectively.

Management

Until more information is available, patients receiving methyldopa in combination with iron-containing products should be advised to separate the times of administration by as much as possible. Patients should be monitored closely for altered hypertensive effect and methyldopa dosage increased as necessary. Selection of an alternative antihypertensive therapy may be necessary.

References (3)
  1. Campbell N, Paddock V, Sundaram R (1988) "Alteration of methyldopa absorption, metabolism, and blood pressure control caused by ferrous sulfate and ferrous gluconate." Clin Pharmacol Ther, 43, p. 381-6
  2. Campbell NR, Campbell RR, Hasinoff BB (1990) "Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism." Clin Invest Med, 6, p. 329-32
  3. Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
Moderate:

levodopa multivitamins with minerals

Applies to: Inbrija (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 (4)
  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

Disease interactions

22 potential interactions Applies to: 19 conditions, including Heart Failure, Asthma, COPD, Hypotension, and Anemia.

Anemia

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with Anemia.

Hemolytic anemia has occurred rarely during therapy with methyldopa and may be associated with a (+) direct Coombs. Therapy with methyldopa should be administered cautiously to patients with anemia or a predisposition to hemolytic syndromes. Clinical monitoring of hematopoietic function, including a baseline hematological profile, is recommended. If Coombs- positive hemolytic anemia occurs, the cause may be methyldopa and the drug should be discontinued

Asthma

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with Asthma.

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

Bleeding Disorder

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with Bleeding Disorder.

Hemolytic anemia has occurred rarely during therapy with methyldopa and may be associated with a (+) direct Coombs. Therapy with methyldopa should be administered cautiously to patients with anemia or a predisposition to hemolytic syndromes. Clinical monitoring of hematopoietic function, including a baseline hematological profile, is recommended. If Coombs- positive hemolytic anemia occurs, the cause may be methyldopa and the drug should be discontinued

Cardiovascular Conditions and Disorders

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with Cardiovascular Conditions and Disorders.

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.

COPD

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with COPD.

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

Fluid Retention

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with Fluid Retention.

Methyldopa may cause edema or weight gain associated with sodium retention. Therapy with methyldopa should be administered cautiously in patients adversely affected by sodium and water retention.

Gastrointestinal Hemorrhage

Moderate:

Inbrija

The levodopa in Inbrija has a moderate potential interaction with Gastrointestinal Hemorrhage.

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.

Glaucoma/Intraocular Hypertension

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with Glaucoma/Intraocular Hypertension.

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.

Heart Failure

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with Heart Failure.

Methyldopa may cause edema or weight gain associated with sodium retention. Therapy with methyldopa should be administered cautiously in patients adversely affected by sodium and water retention.

Hemodialysis

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with Hemodialysis.

Methyldopa is removed by dialysis. Patients receiving methyldopa and undergoing dialysis may occasionally become hypertensive.

History - Cerebrovascular Disease

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with History - Cerebrovascular Disease.

Rarely, involuntary choreoathetotic movements have been observed during therapy with methyldopa in patients with severe bilateral cerebrovascular disease. If these movements occur, therapy should be stopped.

Hypotension

Moderate:

Inbrija

The levodopa in Inbrija has a moderate potential interaction with Hypotension.

Dopamine agonists may impair the systemic regulation of blood pressure, with resultant orthostatic hypotension at any time, but especially during dose escalation. Additionally, patients with Parkinson's disease may have an impaired capacity to respond to an orthostatic challenge. For these reasons, patients with Parkinson's disease (or restless legs syndrome) who are being treated with dopaminergic agonists typically require careful monitoring for signs/symptoms of orthostatic hypotension, especially during dose escalation, and should be advised of this risk.

Liver Disease

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with Liver Disease.

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.

Major:

methyldopa

Methyldopa has a major potential interaction with Liver Disease.

The use of methyldopa is contraindicated in patients with active liver disease, such as active hepatitis or active cirrhosis, and in patients with previous methyldopa- associated liver disorders. Hepatotoxicity is an uncommon but toxic effect of methyldopa. Therapy with methyldopa should be administered cautiously in patients with a history of or predisposition to liver disease.

Neutropenia

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with Neutropenia.

Rare reports of reversible reduction in white blood cell count, primarily neutrophils, have been noted. White blood cell counts returned to normal with discontinuation of methyldopa. Therapy with methyldopa should be administered cautiously in patients with a history of or predisposition to decreased white blood cell or neutrophil counts. Clinical monitoring of hematopoietic function is recommended.

Pheochromocytoma

Moderate:

methyldopa

Methyldopa has a moderate potential interaction with Pheochromocytoma.

Methyldopa causes fluorescence in urine samples at the same wave lengths as catecholamines, falsely high levels of urinary catecholamines may be reported. This will interfere with the diagnosis of pheochromocytoma. It is important to recognize this phenomenon before a patient with a possible pheochromocytoma is subjected to surgery. Methyldopa is not recommended for the treatment of patients with pheochromocytoma.

Psychosis

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with Psychosis.

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.

Moderate:

Inbrija

The levodopa in Inbrija has a moderate potential interaction with Psychosis.

Ordinarily, patients with major psychotic disorder should not be treated with dopaminergic antiparkinsonian 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. The use of bromocriptine in patients with severe psychotic disorders is not recommended.

Minor:

methyldopa

Methyldopa has a minor potential interaction with Psychosis.

Rare symptoms of psychoses, such as hallucinations and delirium, and vivid dreams and nightmares have been reported during methyldopa therapy. Therapy with methyldopa should be administered cautiously to patients with a history of or predisposition to these conditions.

Renal Dysfunction

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with Renal Dysfunction.

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.

Skin Cancer

Major:

Inbrija

The levodopa in Inbrija has a major potential interaction with Skin Cancer.

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.

Sleep Disorders

Moderate:

Inbrija

The levodopa in Inbrija has a moderate potential interaction with Sleep Disorders.

Patients treated with products containing carbidopa and levodopa report excessive somnolence and falling asleep while engaged in daily activities, sometimes with no warning sign of drowsiness. Advise patients about the risks, especially those suffering from sleep disorders or using concomitant sedating medications.

More resources

Inbrija

A total of 532 drugs are known to interact with Inbrija.

methyldopa

A total of 352 drugs are known to interact with methyldopa.

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.