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  • Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies.

Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies.

The journal of headache and pain (2014-11-20)
Hans-Christoph Diener, Morris Gold, Martina Hagen
ABSTRACT

Most patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints. Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were 'all headache episodes' and those with 'severe pain at baseline'. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities. 6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p < 0.0001), and similarly for those severe at baseline (20.2% vs. 12.1% and 10.8%; p ≤ 0.0003). A similar pattern of superiority was observed for secondary endpoints. The triple combination was generally well tolerated. The combination of acetylsalicylic acid, acetaminophen and caffeine is effective and well tolerated in episodic tension-type headache, and significantly superior to acetaminophen with regard to being pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Caffeine, powder, ReagentPlus®
Supelco
Caffeine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Acetaminophen, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Caffeine, anhydrous, 99%, FCC, FG
Sigma-Aldrich
Acetaminophen, BioXtra, ≥99.0%
Sigma-Aldrich
Acetaminophen, meets USP testing specifications, 98.0-102.0%, powder
Sigma-Aldrich
Caffeine, Sigma Reference Standard, vial of 250 mg
Supelco
Caffeine Melting Point Standard, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Melting point standard 235-237°C, analytical standard
Sigma-Aldrich
Acetaminophen, analytical standard
Paracetamol, European Pharmacopoeia (EP) Reference Standard
Supelco
Caffeine, certified reference material, TraceCERT®
USP
Acetaminophen, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Caffeine, anhydrous, tested according to Ph. Eur.
Supelco
Mettler-Toledo Calibration substance ME 18872, Caffeine, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC)
Sigma-Aldrich
Caffeine, meets USP testing specifications, anhydrous
USP
Caffeine, United States Pharmacopeia (USP) Reference Standard
USP
Caffeine melting point standard, United States Pharmacopeia (USP) Reference Standard
Supelco
Acetaminophen solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Caffeine for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Caffeine, BioXtra
Caffeine, European Pharmacopoeia (EP) Reference Standard