Effect of overuse of the antimigraine combination of indomethacin, prochlorperazine and caffeine (IPC) on the disposition of its components in chronic headache patients

Ferrari, Anna; Savino, Gustavo; Gallesi, Daniela; Pinetti, Diego; Bertolini, Alfio; Sances, Grazia; Coccia, Ciro Pio Rosario; Pasciullo, G; Leone, Sheila; Loi, Marianna; Sternieri, E

doi:10.1016/j.phrs.2006.03.022

Cited by 12 publications

(15 citation statements)

References 43 publications

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“…combination of indomethacin, caffeine and perchlorperazine (aged 35–66 years, mean 51.8 ± 9.9). Mixtures are the most utilized self-medication for the treatment of migraine in Italy, so that several patients suffering from chronic headache overuse this symptomatic medication in the attempt to control their daily headache attacks [10]. Each group was matched for age, gender, MOH duration, days with headache per month, and about daily drug intake.…”

Section: Methodsmentioning

confidence: 99%

Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

et al. 2013

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BackgroundMedication-overuse headache (MOH) is a chronic headache condition that results from the overuse of analgesics drugs, triptans, or other antimigraine compounds. The epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity, particularly in chronic patients. The aim of this work was to confirm and extend the results obtained from a previous study, in which we analyzed the urinary proteome of 3 MOH patients groups: non-steroidal anti-inflammatory drugs (NSAIDs), triptans and mixtures abusers, in comparison with non-abusers individuals (controls).MethodsIn the present work we employed specialized proteomic techniques, namely two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS), and the innovative Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry (SELDI-TOF-MS), to discover characteristic proteomic profiles associated with MOH condition.ResultsBy 2-DE and MS analysis we identified 21 over-excreted proteins in MOH patients, particularly in NSAIDs abusers, and the majority of these proteins were involved in a variety of renal impairments, as resulted from a literature search. Urine protein profiles generated by SELDI-TOF-MS analysis showed different spectra among groups. Moreover, significantly higher number of total protein spots and protein peaks were detected in NSAIDs and mixtures abusers.ConclusionsThese findings confirm the presence of alterations in proteins excretion in MOH patients. Analysis of urinary proteins by powerful proteomic technologies could lead to the discovery of early candidate biomarkers, that might allow to identify MOH patients prone to develop potential drug overuse-induced nephrotoxicity.

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Section: Methodsmentioning

confidence: 99%

Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

et al. 2013

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“…Observations To avoid the risk of abuse, the use of combination analgesics should be limited to ≤10 days/month; abuse can lead to headache chronification [79–81]. Side effects and contraindications in combination analgesics are the same as those for each component.…”

Section: Migrainementioning

confidence: 99%

Italian guidelines for primary headaches: 2012 revised version

et al. 2012

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The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version.

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“…[7] Over 90% of indomethacin and 35% of caffeine are protein bound. [25,26] The active constituents of indomethacin/ prochlorperazine/caffeine are metabolized in the liver to inactive compounds (indomethacin), N-desmethyl prochlorperazine (prochlorperazine) and active metabolites (caffeine), [7,26] with paraxanthine the primary active metabolite of caffeine. [25,26] The active constituents of indomethacin/ prochlorperazine/caffeine are metabolized in the liver to inactive compounds (indomethacin), N-desmethyl prochlorperazine (prochlorperazine) and active metabolites (caffeine), [7,26] with paraxanthine the primary active metabolite of caffeine.…”

Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

“…[7] Indomethacin is predominately eliminated via the urine as a glucuronide derivative, with lesser amounts appearing in the faeces; prochlorperazine is eliminated in the urine and faeces as a number of metabolites; and caffeine is rapidly eliminated via the urine as 1-methyluric acid and 1-methylxanthine. [25] Data regarding drug interactions between indomethacin/prochlorperazine/caffeine and other agents are not available. [25] Data regarding drug interactions between indomethacin/prochlorperazine/caffeine and other agents are not available.…”

Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

Indomethacin/Prochlorperazine/Caffeine

Hoy

Scott

2011

CNS Drugs

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The indomethacin/prochlorperazine/caffeine fixed combination (Difmetré®) combines the NSAID indomethacin with the phenothiazine antiemetic prochlorperazine and caffeine. It is currently available as two oral (effervescent tablet and coated tablet) and two rectal (suppository and low-dose suppository) formulations. Oral and rectal formulations of indomethacin/prochlorperazine/caffeine were effective and generally well tolerated in the treatment of migraine and episodic tension-type headache (TTH) in adult patients participating in randomized, multicentre, active-comparator controlled studies. For the most part, the efficacy of oral indomethacin/prochlorperazine/caffeine did not significantly differ from that of oral sumatriptan in patients with migraine and oral nimesulide in patients with episodic TTH. With rectal administration, indomethacin/prochlorperazine/caffeine was, in general, significantly more effective than sumatriptan in patients with migraine. Thus, oral and rectal formulations of indomethacin/prochlorperazine/caffeine provide a further option in the acute treatment of migraine and in the treatment of episodic TTH in adult patients.

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Effect of overuse of the antimigraine combination of indomethacin, prochlorperazine and caffeine (IPC) on the disposition of its components in chronic headache patients

Cited by 12 publications

References 43 publications

Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

Italian guidelines for primary headaches: 2012 revised version

Indomethacin/Prochlorperazine/Caffeine

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