Using Aceclofenac, Paracetamol and Serratiopeptidase Combination Following Dental Implant Placement: Review and Indian Experience

Three surgical techniques have been employed for dental implants: the two-stage method involving implant placement under soft tissue followed by abutment attachment after bone healing; the one-stage approach with simultaneous implant and abutment placement; and the immediate-loading method where both implant and prosthetic abutment are inserted in the initial surgery, often followed by transitional restoration. [1] Dental implant procedures trigger inflammation causing postoperative pain, the intensity of which may vary based on patient characteristics and surgical factors. Optimal pain management is crucial for patient comfort, healing, and overall implant success. Pain medications are administered to alleviate discomfort, and reduce inflammation, ensuring a smooth recovery and favorable treatment outcomes [2]

Inflammation & Pain Management: Practical Goals for Post-Dental Implant Care

Following dental implant surgery, patients commonly experience postoperative discomfort including pain and swelling, attributed to the release of inflammatory mediators. Various factors related to the surgery itself (e.g., type, duration, and extent) and patient characteristics (e.g., stress, blood pressure, heart rate, and anxiety) can influence the severity of these symptoms. Implant placement, especially near the inferior alveolar nerve, could lead to neuropathic pain if nerve integrity is compromised. Heat generation during implant placement, combined with potential nerve injury, can also contribute to postoperative pain. [3,4]

Dental implant procedural interventions induce inflammation that leads to postoperative pain, lasting for days. Surgical aspects such as grafting techniques, number and location of implants, flap size, cooling during drilling, flap management, and implant torque could influence post-operative pain. This necessitates effective inflammation & pain management after dental implant placement to ensure patient comfort, promote successful healing, and optimize overall treatment outcomes. Thus, treatment goals are aimed to minimize inflammation, reducing patient discomfort and complications; allowing for a smooth recovery. [2,5]. Implant procedures incite inflammatory pain due to tissue trauma. Pain medications are effective by depressing the nociceptive system. Currently, the medications given postoperatively after dental implant placement to reduce pain include non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, opioids, and corticosteroids. A combination of NSAIDs has also shown better pain control than single agents. The combined use of aceclofenac and paracetamol has been found to have a more sustained effect in reducing post-implant surgery pain among Indian patients [2,6]

Rationale for Considering Aceclofenac, Paracetamol, And Serratiopeptidase Combination

Aceclofenac categorized as an NSAID, is orally absorbed with a bioavailability of approximately 60-70%. With a primary COX-2 inhibition, it acts as an anti-inflammatory, potent analgesic for dental pain and an antipyretic agent. [7] Paracetamol is well-accepted for its analgesic properties for reducing dental pain, along with its antipyretic properties. It effectively inhibits COX-1 and COX-2 via peroxidase functions, making it a standard choice for pain, fever, and inflammation relief across all age groups.[8] Serratiopeptidase is a proteolytic enzyme that possesses anti-inflammatory and analgesic properties, along with supporting the wound healing process. Serratiopeptidase functions as an anti-inflammatory by regulating cytokines and cell adhesion molecules, effectively curbing inflammation. It relieves dental pain by hydrolyzing histamine, serotonin, and bradykinin. Serratiopeptidase aids in reducing inflammation by promoting interstitial fluid thinning and drainage, leading to diminished swelling and pain. Its distinctive ability to dissolve deceased tissue at the inflammation site without harming live tissue accelerates healing, while also improving microcirculation to support the healing process.[9]

The synergistic effect of combining NSAIDs such as aceclofenac and paracetamol with serratiopeptidase is effective in managing postoperative dental pain, making it an appropriate consideration for addressing severe post-implant discomfort. In the context of dental implantation, serratiopeptidase finds potential clinical utility in treating inflammation around peri-implants, complemented by its anti-inflammatory and antipyretic properties. [2,8,9,10]

• Serratiopeptidase Reduces Postoperative Pain and Swelling after Surgical Intervention: Khateeb AL et al conducted an intraindividual, retrospective, double-blind, cross-over study to analyze the efficacy of serratiopeptidase in reducing postoperative pain and swelling which included 24 patients undergoing surgical intervention. All the patients were administered either serratiopeptidase 5 mg or placebo. Pain intensity was measured using a numerical scale on the 1st, 2nd, 3rd, and 7th postoperative days. It was observed that the group receiving serratiopeptidase exhibited a reduction in postoperative pain and swelling (p<0.05). This concludes that serratiopeptidase is effective in reducing postoperative dental pain. [14]
• Aceclofenac Effective for Postoperative Dental Pain Reduction: Jyothsna K et al conducted a randomized comparative study assessing Aceclofenac 100 mg twice a day vs. Diclofenac Sodium 50 mg three times a day in 100 Indian patients (18-60 years) post dental surgery. Aceclofenac demonstrated a 40% (p<0.05) pain reduction vs. 27% with diclofenac after 8h, and on day 5, aceclofenac achieved 100% pain reduction compared to 95% with diclofenac. This study concluded aceclofenac's rapid onset and sustained analgesic effect for effective dental pain management.[11]
• Aceclofenac Paracetamol Serratiopeptidase Combination: Widely Accepted by Indian Dentists for Postoperative Pain Management Following Implant Placement: Karthikeyan M et al conducted a retrospective study among 200 Indian patients who underwent implant surgery to assess the analgesics and anti-inflammatory drugs that are given following implant placement. Among 200 patients, 87% received Aceclofenac (100 mg), Paracetamol (325 mg), and Serratiopeptidase (15 mg), while 10% received Paracetamol (650 mg), and 3% received Piroxicam (20 mg) for postoperative pain after implant placement. The study showed that the combination of aceclofenac (100 mg), paracetamol (325 mg), and serratiopeptidase (15 mg) was the most commonly prescribed analgesic in postoperative pain management following implant placement. [13]

Benefits and Dosage of Combination Treatment

• Serratiopeptidase has a novel action of attenuating pain by restraining bradykinin release from inflamed tissues. It also reduces tissue swelling by draining fluid and aids wound healing by breaking down abnormal proteins at the inflammation site.[9]
• Aceclofenac inhibits COX enzymes (COX-1 and COX-2), reducing inflammation and pain by hindering prostaglandin production, vital for wound healing and platelet functions.[7]
• Paracetamol offers analgesia by blocking pain-inducing brain messengers and exhibits antipyretic effects by influencing the brain's temperature control system.[8]
• The combination of Aceclofenac, Paracetamol, and Serratiopeptidase offers a comprehensive approach to pain and inflammation control and is well-accepted among Indian dentists for use in post-implant pain relief.[13] Through unique complementary mechanisms of action, the combination provides synergistic activity and a broader spectrum of clinical benefits. [2,8,9,10]
• The recommended dosage of the combination is Aceclofenac (100 mg), Paracetamol (325 mg) and Serratiopeptidase (15 mg) can be up to two times daily. (15)

• Dental implants offer advantages over conventional dentures, providing stable support and reducing adjacent teeth complications while promoting bone preservation.[1]
• Dental implant surgery induces postoperative discomfort, influenced by patient and surgical factors.[2,3,4]
• Medications like NSAIDs, paracetamol, opioids, and corticosteroids are used to manage postoperative pain and inflammation.[2,6]
• The combination of Aceclofenac, Paracetamol, and Serratiopeptidase plays a crucial role in addressing inflammation, alleviating pain, and promoting the healing process of surgically induced wounds, making it an effective therapeutic option.[7,8,9]
• Combination therapy of aceclofenac, paracetamol, and serratiopeptidase offers synergistic effects for pain and inflammation control. Clinical studies underscore the efficacy of Aceclofenac, Paracetamol, and Serratiopeptidase in effectively alleviating dental pain.[2,8,9,10,14]
• The combination therapy addresses multiple facets of inflammation, pain, and wound healing; enhancing patient comfort and recovery after dental implant placement.[2,8,9,10]

References:

1. Ranjan Gupta; Neha Gupta; Kurt K. Weber. Dental Implants. StatPearls Publishing. 2022. https://www.ncbi.nlm.nih.gov/books/NBK470448/

2. G. Bryce, D. I. Bomfim, and G. S. Bassi. Pre- and post-operative management of dental implant placement. Part 1: management of post-operative pain. British Dental Journal 2014; 217: 123-127. https://doi.org/10.1038/sj.bdj.2014.650

3. Matteo Melini, Andrea Forni, Francesco Cavallin, Matteo Parotto and Gastone Zanette. Matteo Melini 1 *, Andrea Forni 2 , Francesco Cavallin3 , Matteo Parotto4 and Gastone Zanette. 2021;Front. Pharmacol. 11:634963.https://doi.org/10.3389/fphar.2020.634963

4. Diane Isabel Selvido, Bishwa Prakash Bhattarai, Dinesh Rokaya, Nattisa Niyomtham, Natthamet Wongsirichat. Pain in Oral and Maxillofacial Surgery and Implant Dentistry: Types and Management. 2021;15:588–598. https://doi.org/10.1055/s-0041-1725212

5. Alaa W. AlQutub. Pain Experience after Dental Implant Placement Compared to Tooth Extraction. International Journal of Dentistry 2021, 4134932,1-5. https://doi.org/10.1155/2021/4134932

6. Sundaram Surendran, Sahana Selvaganesh, Thiyaneswaran Nesappan, Vishnu Priya Veeraraghavan & Rajalakshmanan Eswaramoorthy. Post-operative pain management using two drugs following dental implant surgery among Indians. Bioinformation 2023;19(4): 476-478https://doi.org/10.6026/97320630019476

7. Rabia Bushra, Muhammad Harris Shoaib, Muhammad Iyad Naeem, Nousheen Aslam. ACECLOFENAC: A NEW EFFECTIVE AND SAFE NSAID. IJDDT 2013;4(1);34-42. https://www.researchgate.net/publication/236646093_Aceclofenac_A_New_Effective_and_Safe_NSAID

8. Garry G. Graham • Michael J. Davies • Richard O. Day • Anthoulla Mohamudally • Kieran F. Scott. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity, and recent pharmacological findings. Inflammopharmacol (2013) 21:201–232. https://doi.org/10.1007/s10787-013-0172-x

9. Swati B. Jadhava, Neha Shahb , Ankit Rathia , Vic Rathia , Abhijit Rathi.Serratiopeptidase: Insights into the therapeutic applications. Biotechnology Reports 2020; e00544 https://doi.org/10.1016/j.btre.2020.e00544

10. Nair, S. R., & Devi., S. Serratiopeptidase: An integrated View of Multifaceted Therapeutic Enzyme. Biomolecules,2022,12(10), 1468. https://doi.org/10.3390/biom12101468

11. Kudaravalli Jyothsna, Narayan Deshpande and Gali Vijayalakshmi. Efficacy and Safety of Diclofenac Sodium and Aceclofenac in Controlling Post Extraction Dental Pain: A Randomised, Open Label Comparative Study. Journal Of Pharmacology And Toxicology 6(5): 541-547,2011. DOI: 10.3923/jpt.2011.541.547

12. Dodson, T. Paracetamol is an effective drug to use for pain following oral surgery: Is paracetamol (acetaminophen) effective in controlling pain after oral surgery? Evidence-Based Dentistry 2007;8(3), 79–80. https://doi.org/10.1038/sj.ebd.6400510

13. Karthikeyan Murthykumar, Arvina Rajasekar, & Gurumoorthy Kaarthikeyan. Analgesics/Anti-Inflammatory Drugs Preferred Following Implant Placement: A Retrospective Study. Journal of Long-Term Effects of Medical Implants, 2022;32(1):1–6 https://www.dl.begellhouse.com/download/article/0aedd6266f065d60/JLT-37302.pdf

14. Al-Khateeb, T. H., & Nusair, Y. Effect of the proteolytic enzyme serrapeptase on swelling, pain, and trismus after surgical extraction of mandibular third molars. International Journal of Oral and Maxillofacial Surgery,2008;37(3), 264–268. https://doi.org/10.1016/j.ijom.2007.11.011

15. Acleclofenac, Paracetamol and Serratiopeptidase tablets. Taj Life Sciences. Retrieved on 25th August 2023 from https://tajlifesciences.com/portfolio/aceclofenac-paracetamol-and-serratiopeptidase-tablets-100mg325mg15mg-2/