Interactions between Levodopa and Rozerem
1 drug interaction and 21 additional warnings found for the following 2 drugs:
- levodopa
- Rozerem (ramelteon)
Drug interactions
Moderate drug interactions
Moderate:
levodopa ramelteon
Applies to: levodopa and Rozerem (ramelteon)
Monitor
Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.
Management
During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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 (36)
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- (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
- Ferslew KE, Hagardorn AN, McCormick WF (1990) "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci, 35, p. 477-82
- Plushner SL (2000) "Valerian: valeriana officinalis." Am J Health Syst Pharm, 57, p. 328-35
- (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
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- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
levodopa Food/Lifestyle
Applies to: 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)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- 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
- (2022) "Product Information. Duopa (carbidopa-levodopa)." AbbVie US LLC
- (2021) "Product Information. Duodopa (carbidopa-levodopa)." AbbVie Pty Ltd, 18
- (2023) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie Corporation
- (2022) "Product Information. Dhivy (carbidopa-levodopa)." Avion Pharmaceuticals
- (2024) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie US LLC
Moderate:
ramelteon Food/Lifestyle
Applies to: Rozerem (ramelteon)
Generally avoid
Alcohol may potentiate some of the pharmacologic effects of ramelteon. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
Adjust dosing interval
Administration of ramelteon with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In study subjects, administration of a 16 mg dose of ramelteon with a high-fat meal decreased the peak plasma drug concentration (Cmax) by 22% and delayed the median time to reach peak plasma drug concentration (Tmax) by approximately 45 minutes compared to administration in a fasted state.
Management
Patients receiving ramelteon should be advised to avoid the consumption of alcohol. For faster sleep onset, ramelteon should not be administered with or immediately after a high-fat/heavy meal.
References (1)
- (2005) "Product Information. Rozerem (ramelteon)." Takeda Pharmaceuticals America
Moderate:
levodopa multivitamins with minerals
Applies to: 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)
- Campbell NR, Hasinoff B (1989) "Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism." Clin Pharmacol Ther, 45, p. 220-5
- Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
- 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
- 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
18 potential interactions Applies to: 14 conditions, including Depression, Asthma, COPD, Sleep Apnea, and Hypotension.
Asthma
Major:
levodopa
Levodopa 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.
Cardiovascular Conditions and Disorders
Major:
levodopa
Levodopa 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:
levodopa
Levodopa 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.
Depression
Major:
Rozerem
The ramelteon in Rozerem has a major potential interaction with Depression.
A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of most anxiolytics, sedatives and hypnotics. Some of these changes include decreased inhibition, aggressiveness, agitation, and hallucinations. These drugs can cause or exacerbate mental depression and cause suicidal behavior and ideation. Therapy with these drugs should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Gastrointestinal Hemorrhage
Moderate:
levodopa
Levodopa 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:
levodopa
Levodopa 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.
Moderate:
Rozerem
The ramelteon in Rozerem has a moderate potential interaction with Glaucoma/Intraocular Hypertension.
Some hypnotic drugs can have an anticholinergic effect and should be used with caution in patients with glaucoma, and trouble urinating due to retention or enlarged prostate.
Hypotension
Moderate:
levodopa
Levodopa 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:
levodopa
Levodopa 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.
Moderate:
Rozerem
The ramelteon in Rozerem has a moderate potential interaction with Liver Disease.
In general, anxiolytics, sedatives and hypnotics are extensively metabolized by the liver. Their plasma clearance may be decreased and their half-life prolonged in patients with impaired hepatic function. Therapy with these drugs should be administered cautiously in patients with liver disease (some are not recommended in severe liver impairment), and the dosage should be adjusted accordingly. Laboratory testing is recommended prior and during treatment.
Psychosis
Major:
levodopa
Levodopa 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:
levodopa
Levodopa 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.
Renal Dysfunction
Major:
levodopa
Levodopa 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.
Major:
Rozerem
The ramelteon in Rozerem has a major potential interaction with Renal Dysfunction.
Some anxiolytic, sedative and hypnotic drugs have not been studied in patients with severe renal impairment and should not be used on these patients.
Skin Cancer
Major:
levodopa
Levodopa 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 Apnea
Major:
Rozerem
The ramelteon in Rozerem has a major potential interaction with Sleep Apnea.
The use of ramelteon could exacerbate symptoms of sleep apnea, and has not been studied in patients with severe sleep apnea. Ramelteon is not recommended in patients with severe sleep apnea.
Sleep Disorders
Moderate:
levodopa
Levodopa 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.
Urinary Retention
Moderate:
Rozerem
The ramelteon in Rozerem has a moderate potential interaction with Urinary Retention.
Some hypnotic drugs can have an anticholinergic effect and should be used with caution in patients with glaucoma, and trouble urinating due to retention or enlarged prostate.
More resources
levodopa
A total of 532 drugs are known to interact with levodopa.
- Levodopa is in the drug class dopaminergic antiparkinsonism agents.
- Levodopa is used to treat the following conditions:
Rozerem
A total of 444 drugs are known to interact with Rozerem.
- Rozerem is in the drug class miscellaneous anxiolytics, sedatives and hypnotics.
- Rozerem is used to treat Insomnia.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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