Acute colicky abdominal pain is caused by the distention, obstruction, or inflammation of intra-abdominal visceral organs and is one of the most common reasons for people to seek medical care.¹ Colic can be of intestinal, renal, gynecological, or hepatic origin and the associated pain is extremely intense and persistent. The prevalence of colicky abdominal pain ranges from 10% to 46% and up to 75% in women irrespective of age groups, ethnicities, and geographic regions.^2,3 Antispasmodics, analgesics, antacids, anti-diarrheals, and laxatives are the main medications used for the relieving of upper and lower abdominal pain symptoms.^4,5

Treatment with antispasmodics relieves the spasm of the smooth muscles and thereby alleviates pain. Camylofin dihydrochloride is been used as an antispasmodic agent that exerts dual antispasmodic action, direct spasmolytic action (musculotropic) on the smooth muscles and a mild atropine-like anticholinergic (neurotropic) action, making it one of the most potent antispasmodic agents.⁶ In pre-clinical settings, the anticholinergic adverse effects (AE) of camylofin, such as the dryness of mouth, dilatation of pupils, paralysis of accommodation and palpitations were observed to be are negligible.⁷ The relaxing effect extends to other smooth muscles and therefore Camylofin Dihydrochloride is indicated in the treatment of spasms of the uterus, bronchi, bile duct, and the uterine smooth muscles.⁸

The spasmolytic action of Camylofin Dihydrochloride has been demonstrated in several clinical studies.^9,10,11,12 Camylofin Dihydrochloride at a dose of 25mg administered either intramuscularly or intravenously is used as a potent and safe antispasmodic in cases of biliary, renal, and ureteric colic; dysmenorrhea; peptic ulcer; and chronic enterocolitis.⁶ Antispasmodics are effective in the management of non-specific colicky abdominal pain both in adults and children.^{3, 4} A study in the Indian population demonstrated the antispasmodic effect of Camylofin Dihydrochloride when used intravenously along with an non- steroidal anti-inflammatory drugs (NSAID) analgesic.¹³

NSAIDs have been used in the treatment of pain secondary to smooth muscle spasms^. The therapeutic effects of NSAIDs are largely because of their ability to inhibit prostaglandin synthesis through the inhibition of the 2 cyclooxygenase enzymes (COX-1 and COX-2).¹⁴ Nimesulide is an NSAID of the sulfonanilide class and is a preferential COX-2 inhibitor with 5-16 fold selectivity for COX-2.¹⁵ It has a rapid onset of action and provides symptomatic pain relief. It is particularly indicated for the treatment of acute pain, where inflammation is also a major component.^{14, 15} The consensus report group on nimesulide concluded that nimesulide remains an effective and safe therapeutic choice for the treatment of various painful inflammatory conditions, with a rapid onset of analgesic activity and an overall positive benefit/risk profile.¹⁶

Nimesulide was one of the drugs showing one of the lowest risks for upper gastrointestinal bleeding (3.2, 95% CI 1.9, 5.6), which was comparable with ibuprofen, and much lower than risks shown by several commonly used NSAIDs such as piroxicam, ketoprofen, and ketorolac.¹⁷ However, Arfè et al reported a dose-dependent increased risk of hospitalization for heart failure associated with nimesulide.¹⁸ In a review of literature, nimesulide was found to have a suitable safety profile and gastrointestinal tolerability compared with other NSAIDs in osteoarthritis patients.¹⁹

Clinical studies have established the analgesic tolerability and effectiveness of orally administered nimesulide in the treatment ofvarious painful and inflammatory conditions such as renal colic, osteoarthritis, cancer, thrombophlebitis, oral surgery, dysmenorrhea, and general surgery.¹⁶ Nimensulide is particularly well-tolerated by most aspirin-(acetylsalicylic acid) and/or NSAID-intolerant patients and in patients with asthma.¹⁵

Clinical studies on the combination of an antispasmodic (hyoscine) and an analgesic (paracetamol) in abdominal pain have demonstrated statistically significant improvement in abdominal pain intensity in comparison with placebo.^{20, 21} The development of fixed dose combinations (FDCs) is becoming increasingly common either to improve compliance or to benefit from the added effects of the 2 or more active drugs given together. Between 1961 and 2013, the Central Drugs Standard Control Organization approved 1,125 oral FDCs including 67 NSAIDs FCD formulations (of which 52 were original formulations and 15 were variants).²² Although, FDCs will provide synergetic effectiveness, their safety needs to be established in a real-world scenario as there is a possibility of increase in safety concerns as a result because of combinations.

Anafortan-N^®, the FDC of camylofin dihydrochloride 50 mg and nimesulide 100 mg, is routinely used in clinical practice to provide synergistic benefits in terms of increased pain relief. However, data on the combination of Camylofin Dihydrochloride and nimesulide in the treatment of acute colicky abdominal pain in adults in literature are scarce. We aim to study the safety and effectiveness of Anafortan-N^® tablets in adults with acute colicky abdominal pain. The primary safety concerns planned to be assessed in the study include nausea, vomiting, dry mouth, drowsiness, epigastric pain, heartburn, diarrhea, vomiting, skin rash, headache, hepatotoxicities given the fast oral absorption, and hepatic metabolism of the drug. The safety will be assessed on clinical as well as based on laboratory parameters. Treatment effectiveness will be assessed with the help of patient-reported outcomes (PROs) including a visual analogue scale (VAS) for pain and physician’s assessment of efficacy. The study will generate real‑world‑settings, pan-India data, which can provide latest evidence on the  safety, tolerability and effectiveness and of Anafortan-N^® tablets, and can be used by physicians in regular clinical practice.