A prospective, single-arm, open-label, multi-centric to determine the safety and effectiveness of Anafortan –N. Fixed-dose combination of Camylofin Dihydrochloride 50mg and Nimesulide 100mg in patients with acute colicky abdominal pain in India

Acute colicky abdominal pain is caused by thedistention, obstruction, or inflammation of intra-abdominal visceral organs andis 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 extremelyintense and persistent. The prevalence of colicky abdominal pain ranges from 10%to 46% and up to 75% in women irrespective of age groups, ethnicities, andgeographic regions.2,3 Antispasmodics, analgesics, antacids, anti-diarrheals,and laxatives are the main medications used for the relieving of upper andlower abdominal pain symptoms.4,5

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

The spasmolytic action of CamylofinDihydrochloride has been demonstrated in several clinical studies.9,10,11,12Camylofin Dihydrochloride at a dose of 25mg administered either intramuscularlyor intravenously is used as a potent and safe antispasmodic in cases ofbiliary, renal, and ureteric colic; dysmenorrhea; peptic ulcer; and chronicenterocolitis.6 Antispasmodics are effective in the management ofnon-specific colicky abdominal pain both in adults and children.3, 4 Astudy in the Indian population demonstrated the antispasmodic effect of CamylofinDihydrochloride when used intravenously along with an non- steroidal anti-inflammatorydrugs (NSAID) analgesic.13

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

Nimesulide was one of the drugs showing oneof 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 severalcommonly used NSAIDs such as piroxicam, ketoprofen, and ketorolac.17 However,Arfè et al reported a dose-dependent increased risk of hospitalization forheart failure associated with nimesulide.18 In a review of literature,nimesulide was found to have a suitable safety profile and gastrointestinaltolerability compared with other NSAIDs in osteoarthritis patients.19

Clinical studies have established theanalgesic tolerability and effectiveness of orally administered nimesulide inthe treatment ofvarious painful and inflammatory conditions such as renalcolic, osteoarthritis, cancer, thrombophlebitis, oral surgery, dysmenorrhea, andgeneral surgery.16 Nimensulide is particularly well-tolerated bymost aspirin-(acetylsalicylic acid) and/or NSAID-intolerant patients and inpatients with asthma.15

Clinical studies on the combination of an antispasmodic(hyoscine) and an analgesic (paracetamol) in abdominal pain have demonstratedstatistically significant improvement in abdominal pain intensity in comparisonwith placebo.20, 21 The development of fixed dose combinations(FDCs) is becoming increasingly common either to improve compliance or to benefitfrom the added effects of the 2 or more active drugs given together. Between1961 and 2013, the Central Drugs Standard Control Organization approved 1,125oral FDCs including 67 NSAIDs FCD formulations (of which 52 were originalformulations and 15 were variants).22 Although, FDCs will providesynergetic effectiveness, their safety needs to be established in a real-worldscenario as there is a possibility of increase in safety concerns as a result becauseof combinations.

Anafortan-N®, the FDC of camylofindihydrochloride 50 mg and nimesulide 100 mg, is routinely used in clinicalpractice to provide synergistic benefits in terms of increased pain relief.However, data on the combination of Camylofin Dihydrochloride and nimesulide inthe treatment of acute colicky abdominal pain in adults in literature arescarce. We aim to study the safety and effectiveness of Anafortan-N®tablets in adults with acute colicky abdominal pain. The primary safetyconcerns 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 aswell as based on laboratory parameters. Treatment effectiveness will beassessed with the help of patient-reported outcomes (PROs) including a visualanalogue scale (VAS) for pain and physician’s assessment of efficacy. The studywill generate real‑world‑settings, pan-India data, which can provide latestevidence on the  safety, tolerability andeffectiveness and of Anafortan-N® tablets, and can be used by physicians in regular clinicalpractice.