Drug Interactions between IFE-Bimix 30/1 and levodopa
This report displays the potential drug interactions for the following 2 drugs:
- IFE-Bimix 30/1 (papaverine/phentolamine)
- levodopa
Interactions between your drugs
levodopa papaverine
Applies to: levodopa and IFE-Bimix 30 / 1 (papaverine / phentolamine)
MONITOR: Concomitant use of levodopa and papaverine may result in reduced efficacy of levodopa. The exact mechanism is unknown, though some animal studies have suggested that papaverine may be able to block dopamine receptors in the brain. Clinical data are conflicting. Five case reports were documented in the 1970s where patients with Parkinson's disease began therapy with papaverine in the dose range recommended at that time for treatment of cerebral arteriosclerosis (e.g., 100 mg daily). Reports indicated a gradual loss of therapeutic effect of levodopa over a period of several weeks with recovery of the lost response to levodopa occurring about 7 to 10 days after papaverine was stopped. However, a small study (n=9) did not demonstrate any difference in the neurological symptoms of Parkinson's disease (global, tremor, rigidity, or akinesia scores) when oral papaverine (150 mg) was added to a regimen of antiparkinsonian drugs (range of 100 to 750 mg levodopa plus decarboxylase inhibitor in 9 patients, which was combined with bromocriptine 40 mg in 2 patients or trihexyphenidyl 15 mg in 2 other patients) every day for 3 weeks either preceding or following placebo for 3 weeks. Data examining other formulations of papaverine (intracoronary or intracavernosal for example) are not available.
MANAGEMENT: Some authorities recommend close monitoring for the loss of therapeutic response of levodopa if it is used concomitantly with papaverine. The amount of papaverine absorbed systemically may affect the severity of this interaction.
References (7)
- Duvoisin RC (1975) "Antagonism of levodopa by papaverine." JAMA, 231, p. 845-6
- Montastruc JL, Rascol O, belin j, ane m, rascol a (1987) "Does papaverine interact with levodopa in Parkinson's disease?" Ann Neurol, 22, p. 558-9
- (2020) "Product Information. Carbidopa-Levodopa (carbidopa-levodopa)." Teva Pharmaceuticals USA
- (2020) "Product Information. Stalevo 50 (carbidopa/entacapone/levodopa)." Almatica Pharma Inc
- (2023) "Product Information. AA-Levocarb CR (carbidopa-levodopa)." AA Pharma Inc
- (2023) "Product Information. Lecado (co-careldopa)." Sandoz Ltd
- (2023) "Product Information. Lecigon (carbidopa/entacapone/levodopa)." Stada Pharmaceuticals Australia Pty Ltd
levodopa phentolamine
Applies to: levodopa and IFE-Bimix 30 / 1 (papaverine / phentolamine)
MONITOR: The hypotensive and central nervous system (CNS) depressant effects of levodopa or foslevodopa may be additive with antihypertensive agents or agents with both hypotensive properties and 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)
- (2003) "Product Information. Stalevo 150 (carbidopa/entacapone/levodopa)." Novartis Pharmaceuticals
- (2023) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie Corporation
- (2024) "Product Information. DUODOPA (foscarbidopa-foslevodopa)." ABBVIE SPAIN, S.L.U
- (2024) "Product Information. Produodopa (foscarbidopa-foslevodopa)." AbbVie Ltd
- (2024) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie US LLC
- (2024) "Product Information. Vyalev 2400/120 (foscarbidopa-foslevodopa)." AbbVie Pty Ltd, Version 1
papaverine phentolamine
Applies to: IFE-Bimix 30 / 1 (papaverine / phentolamine) and IFE-Bimix 30 / 1 (papaverine / phentolamine)
MONITOR: Concomitant use of multiple vasodilator drugs for the treatment of erectile dysfunction (ED) may increase the risk of additive adverse effects, including hypotension, dizziness, syncope, prolonged erection, or priapism. However, available data are conflicting. For example, approximately 4.9% and 7.1% of people in selected studies using single ingredient intracavernosal injections (ICIs) of papaverine reported experiencing painful/prolonged erections and priapism, respectively. Conversely, selected studies of people using ICIs containing papaverine and phentolamine reported an increase in the average rate of prolonged/painful erections to approximately 8.9%, but a reduction in the average rate of priapism to approximately 5.5%. Additionally, 1 case series reported an increase in dizziness and syncope when patients used both oral agents and ICIs to treat ED. Clinical data are not available for all possible combinations. The route of administration and amount of medication absorbed systemically may affect the clinical significance and severity of this interaction.
MANAGEMENT: Most clinical guidelines advise caution and closer clinical monitoring for patients on erectile dysfunction (ED) regimens that include multiple vasodilative agents due to the potential for additive adverse effects. Some drug manufacturers recommend avoiding combinations due to the potential risks and a lack of established data on safety. However, some of these medications are available as combinations (either commercially or via compounding) and some ED guidelines indicate that combination therapy may be appropriate in certain situations. Healthcare providers should refer to the product labeling and appropriate treatment guidelines for the most up to date information and recommendations; as well as, counsel patients on potential adverse effects and what to do should they occur.
References (14)
- (2021) "Product Information. Papaverine Hydrochloride (papaverine)." Oryza Pharmaceuticals Inc
- (2023) "Product Information. Invicorp (aviptadil-fentolamin)." Evolan Pharma AB
- (2023) "Product Information. Caverject (alprostadil)." Pfizer U.S. Pharmaceuticals Group
- (2021) "Product Information. Caverject (alprostadil)." Pfizer Ltd
- (2019) "Product Information. Caverject Impulse (alprostadil)." Pfizer Australia Pty Ltd, pfpcaviv10519
- (2018) "Product Information. Muse (alprostadil)." Meda Pharmaceuticals
- (2018) "Product Information. Muse (alprostadil)." Viatris UK Healthcare Ltd
- Dhir RR, Lin HC, Canfield SE, Wang R (2011) "Combination therapy for erectile dysfunction: an update review." Asian J Androl, 13, p. 382-90
- Al-Adl AM, Abdel-Wahab O, El-Karamany T, Aal AA (2011) "Combined intracavernous vasoactive drugs and sildenafil citrate in treatment of severe erectile dysfunction not responding to on-demand monotherapy." Arab J Urol, 9, p. 153-8
- Karakus S, Burnett AL (2024) The medical and surgical treatment of erectile dysfunction: a review and update. https://www.canjurol.com/abstract.php?ArticleID=&version=1.0&PMID=32876000
- Burnett AL, Nehra A, Breau RH, et al. (2018) "Erectile Dysfunction: AUA Guideline." J Urol, 200, p. 633-41
- Hackett G, Kirby M, Wylie K, et al. (2018) "British society for sexual medicine guidelines on the management of erectile dysfunction in men - 2017." J Sex Med, 15, p. 430-57
- Lowy M, Ramanathan V (2024) Erectile dysfunction: causes, assessment and management options. https://australianprescriber.tg.org.au/articles/erectile-dysfunction-causes-assessment-and-management-options.html
- Domes T, Najafabadi BT, Roberts M, et al. (2021) "Canadian urological association guideline: erectile dysfunction." Can Urol Assoc J, 10, p. 310-22
Drug and food interactions
levodopa food
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
papaverine food
Applies to: IFE-Bimix 30 / 1 (papaverine / phentolamine)
MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.
MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.
References (10)
- Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
- Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
- Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
- Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
- 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
- Cerner Multum, Inc. "Australian Product Information."
- Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
- Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
- (2023) "Product Information. Buprenorphine (buprenorphine)." G.L. Pharma UK Ltd
- (2023) "Product Information. Temgesic (buprenorphine)." Reckitt Benckiser Pty Ltd
phentolamine food
Applies to: IFE-Bimix 30 / 1 (papaverine / phentolamine)
MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.
MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.
References (10)
- Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
- Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
- Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
- Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
- 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
- Cerner Multum, Inc. "Australian Product Information."
- Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
- Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
- (2023) "Product Information. Buprenorphine (buprenorphine)." G.L. Pharma UK Ltd
- (2023) "Product Information. Temgesic (buprenorphine)." Reckitt Benckiser Pty Ltd
levodopa food
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
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.
See also
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. |
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