Post Opening Stability and Safe Use of Paediatric Medicines and Nutritional Preparations in India: An Evidence Based Review

*Corresponding author: Venugopal Reddy Iragamreddy. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Post Opening Stability and Safe Use of Paediatric Medicines and Nutritional Preparations in India: An Evidence Based Review Venugopal Reddy Iragamreddy * Deapartment of Pediatrics, Ovum Woman and Child Speciality Hospital, Bangalore, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 108–112 Publication history: Received on 27 July 2025; revised on 02 September 2025; accepted on 04 September 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.23.3.0809 Abstract Background: In paediatric medicine, liquid preparations such as syrups, suspensions, drops, reconstituted antibiotics, anticonvulsants, endocrine therapies, and nutritional supplements are widely prescribed in India. While expiry dates are printed on packaging, they reflect unopened shelf-life and not the actual safe-use period once a product has been opened or reconstituted. Caregivers in India often continue using opened medicines until the bottle is “finished,” leading to reduced efficacy, antimicrobial resistance, and avoidable adverse outcomes. Methods: This narrative review synthesises evidence from manufacturer product information leaflets of Indian brands, guidance from the Indian Academy of Pediatrics (IAP), the United States Pharmacopeia (USP), the World Health Organization (WHO), Ministry of AYUSH, and published literature. Medicines reviewed include antipyretics, analgesics, antiemetics, antispasmodics, antibiotics, probiotics, multivitamins, anticonvulsants, endocrine agents, Ayurvedic syrups, and paediatric nutritional preparations such as infant formula, expressed breast milk, and ready-to-use therapeutic foods (RUTF). Results: Evidence indicates that oral suspensions such as paracetamol and ibuprofen are safe for 3–6 months after opening; reconstituted antibiotics must be discarded within 7–14 days; oral rehydration solution (ORS) should be used within 24 h; probiotics vary, with sachets consumed immediately and drops within 3 months; iron syrups last 1–3 months; multivitamins 3–6 months; vitamin D drops up to 12 months; anticonvulsants like sodium valproate and levetiracetam remain stable for 6–7 months, while phenobarbitone and carbamazepine suspensions should be discarded in 3 months; endocrinological drugs such as thyroxine drops remain usable for 6–8 weeks, insulin and growth hormone vials/pens for 28 days; infant formula tins must be used within 3–4 weeks of opening, while reconstituted feeds last only 2 h. Ayurvedic syrups lack stability data but should be discarded within 3 months. Conclusion: In India’s hot and humid climate, conservative discard timelines are essential. Adopting standardised rules—ORS 24 h, antibiotics 7–14 d, paracetamol/ibuprofen syrups 3–6 mo, insulin and growth hormone 28 d, infant formula tins 3–4 weeks, and Ayurvedic syrups 3 mo—will prevent therapeutic failure and enhance child safety. Paediatricians should counsel families actively and advocate inclusion of Ayurvedic and nutritional preparations in safety discussions. Keywords: Paediatrics; Beyond-Use Date; Oral Suspensions; Anticonvulsants; Endocrine Medicines; Infant Formula; India World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 108–112 109 1. Introduction Liquid medicines remain the cornerstone of paediatric therapy in India. Children are prescribed paracetamol or ibuprofen syrups for fever, reconstituted antibiotics for respiratory and gastrointestinal infections, antiemetics for vomiting, probiotics for diarrhoea, iron and vitamin syrups for nutritional deficiencies, and anticonvulsants such as sodium valproate or levetiracetam for seizure control. Endocrinological agents including thyroxine drops, insulin vials, and growth hormone cartridges are essential for chronic management of hypothyroidism, diabetes, and growth disorders. In addition, infants and children frequently consume nutritional products such as infant formula, fortified complementary foods, and ready-to-use therapeutic foods (RUTF). Despite the wide use of these products, the general practice among parents and caregivers is to rely solely on the expiry date printed on packaging. This expiry date represents stability of an unopened container under ideal storage conditions. It does not account for the impact of opening, reconstitution, or household storage practices. Once a bottle is opened, preservatives gradually lose effectiveness, contamination risk increases with repeated handling, and chemical degradation accelerates, especially in India’s hot and humid environment. Evidence suggests that misuse of leftover antibiotics contributes significantly to antimicrobial resistance (20), prolonged use of degraded syrups leads to therapeutic failure, and improper storage of infant formula is linked to fatal Cronobacter infections (29). The Indian Academy of Pediatrics (IAP) has issued clear guidelines on antibiotic stewardship and expressed breast milk storage (20,30). However, there is a lack of consolidated evidence for all commonly used medicines and nutritional products. This review aims to provide a comprehensive, evidence-based guide to post-opening and post-reconstitution stability of paediatric medicines and preparations in the Indian context, highlighting risks, manufacturer instructions, and practical recommendations. 2. Methods This review followed a narrative synthesis approach. Sources included: • Manufacturer product inserts (PILs) of commonly prescribed Indian brands (e.g., Calpol, Brufen, Meftal-P, Emeset, Domstal, Augmentin, Azithral, Encorate, Keppra, Thyronorm, Nan Pro). • Indian Academy of Pediatrics (IAP) guidelines on antibiotic use, expressed breast milk storage, and paediatric nutrition. • WHO guidelines on oral rehydration solutions, powdered infant formula, and vaccines. • USP <795> guidance on beyond-use dates for compounded non-sterile formulations. • Peer-reviewed publications on microbial contamination of paediatric oral liquids in community use (23). • Ministry of AYUSH guidance for Ayurvedic syrups and tonics (33). 3. Review of Medicines and Nutritional Preparations 3.1. Antipyretics and Analgesics • Paracetamol suspension (Calpol, Crocin, Dolo) remains stable for 3–6 months after opening, provided it is stored tightly closed at room temperature (2). Microbial contamination risk increases beyond this period. • Ibuprofen syrup (Brufen) demonstrates similar stability, with most brands recommending up to 6 months after opening (3). • Mefenamic acid suspension (Meftal-P) lacks universal guidance. In practice, apply the 3–6 month rule, though paracetamol and ibuprofen remain the preferred paediatric antipyretics. 3.2. Antiemetics • Ondansetron solution (Emeset, Periset) should be discarded within 60 days of opening (4). It is a ready-touse solution, not requiring reconstitution, but degradation occurs after two months. • Domperidone suspensions (Domstal, Domperon) are commonly prescribed in India for vomiting. Manufacturers recommend up to 3 months after opening. However, regulators such as the EMA and MHRA restrict paediatric use (<12 years, <35 kg) due to QT prolongation risk and lack of efficacy evidence (6). Paediatricians in India should use it cautiously. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 108–112 110 3.3. Antispasmodics Dicyclomine-based syrups (Cyclopam, Colimex) are still prescribed for abdominal colic in India, though contraindicated in infants under 6 months due to risk of apnoea and seizures (7). For older children, stability after opening is typically 3–6 months. 3.4. Antibiotics (Reconstituted Suspensions) Antibiotic suspensions are supplied as dry powders requiring reconstitution with boiled and cooled water. Once reconstituted, they degrade rapidly. • Amoxicillin (Mox): stable for 14 days (14). • Amoxicillin-clavulanate (Augmentin): requires refrigeration; discard within 7–10 days as clavulanate is highly unstable (15). • Azithromycin (Azithral, Azee): stable for 10 days at room temperature (16). • Cefixime (Taxim-O): stable for 14 days (17). • Cefuroxime axetil (Cefakind, Zinnat): stable for 10 days refrigerated (18). • Cefpodoxime (Cepodem): stable for 14 days refrigerated (19). The IAP recommends that leftover antibiotics must never be saved for future illness due to risk of resistance (20). 3.5. Gastrointestinal Preparations Oral Rehydration Solution (ORS) (Electral, WHO ORS) must be consumed within 24 hours after preparation. Beyond this period, bacterial contamination renders it unsafe (8). 3.5.1. Probiotics: • Saccharomyces boulardii sachets (Econorm, Vizylac) should be consumed immediately once reconstituted (9). • Lactobacillus reuteri drops (BioGaia) remain stable for up to 3 months after opening, if stored correctly (10). 3.6. Multivitamins and Micronutrients • Iron syrups such as Dexorange, Sytron, and Galfer last 1–3 months after opening (11). Sugar content and aqueous base increase contamination risk. • Multivitamin syrups (Zincovit, Riconia) are usually safe for 3–6 months after opening (12). Vitamin D drops (Calcirol, D-Rise) are light-sensitive but some brands remain stable up to 12 months (13). 3.7. Anticonvulsants • Sodium valproate syrups (Encorate, Valparin) are stable for 6 months after opening when stored at room temperature (21). • Levetiracetam syrups (Keppra, Levipil) are stable for up to 7 months after opening (22). • Phenobarbitone syrup has shorter stability, generally 3 months, with crystallisation risk on poor storage (23). • Carbamazepine suspension (Tegrital) is stable for 3 months; must be shaken well due to settling (24). 3.8. Endocrinological Medicines • Thyroxine drops (Thyronorm) should be discarded within 6–8 weeks once opened. They are sensitive to heat and light, and should be refrigerated (25). • Insulin vials/pens (Actrapid, Mixtard, Lantus) must be discarded within 28 days of opening, irrespective of refrigeration (26). • Growth hormone cartridges (Norditropin, Genotropin) remain stable for 28 days if refrigerated (27). • Hydrocortisone suspensions (compounded) follow USP <795> — discard within 14 days refrigerated (1). 3.9. Paediatric Food and Nutritional Preparations • Infant formula tins (Nan Pro, Lactogen, Dexolac): once opened, must be consumed within 3–4 weeks (28). • Reconstituted formula feeds: should be consumed immediately or discarded within 2 hours at room temperature (29). World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 108–112 111 • Expressed breast milk (EBM): safe for 4 hours at room temperature, 24 hours if refrigerated (30). • RUTF (Plumpy’Nut, locally produced sachets): must be consumed immediately once opened (31). • Tube-feeding formulas: stable for 4 hours at room temperature and 24 hours refrigerated (32). 3.10. Ayurvedic Medicines Ayurvedic syrups, gripe water, and herbal tonics are widely used. Ministry of AYUSH guidance suggests discarding within 3 months of opening, as most are aqueous with high sugar content (33). 4. Discussion This review highlights the urgent need for awareness on safe-use timelines of medicines after opening in India. Unlike in cooler climates, India’s high ambient temperatures and humidity accelerate degradation. Limited access to refrigeration worsens the risk. Several trends are concerning: • Parents often reuse leftover antibiotics for later illnesses. • Iron syrups and vitamin tonics are overused beyond safe limits. • Anticonvulsants and thyroxine, which have narrow therapeutic ranges, require strict adherence to discard timelines. • Nutritional misuse, such as storing formula feeds or RUTF sachets, can lead to severe infections. • Ayurvedic medicines, though natural, are not immune to microbial contamination. This review bridges gaps by consolidating data for all categories, integrating both international standards and local Indian realities. 5. Conclusion Paediatric medicines and nutritional preparations must be used within safe discard timelines once opened or reconstituted. For India, the following rules are recommended: • ORS: 24 h. • Antibiotics: 7–14 d. • Paracetamol/Ibuprofen: 3–6 mo. • Probiotics: sachets immediate, drops 3 mo. • Iron syrups: 1–3 mo. • Multivitamins: 3–6 mo. • Vitamin D drops: up to 12 mo. • Anticonvulsants: 3–7 mo. • Thyroxine drops: 6–8 wks. • Insulin/Growth hormone: 28 d. • Infant formula tins: 3–4 wks; feeds 2 h. • RUTF: immediate. • Ayurvedic syrups: 3 mo. Paediatricians should actively counsel families, mark bottles with “date opened” and “discard after,” and emphasise antimicrobial stewardship. References [1] United States Pharmacopeia. USP <795> Pharmaceutical Compounding – Nonsterile Preparations. Rockville, MD: United States Pharmacopeia Convention; 2023. [2] GlaxoSmithKline Pharmaceuticals Ltd. Calpol Paediatric Suspension [package insert]. Mumbai: GSK; 2022. [3] Abbott India Ltd. Brufen Syrup (Ibuprofen 100 mg/5 mL) [package insert]. Mumbai: Abbott; 2022. [4] Cipla Ltd. Emeset Syrup (Ondansetron 2 mg/5 mL) [package insert]. Mumbai: Cipla; 2021. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 108–112 112 [5] Torrent Pharmaceuticals Ltd. Domstal Suspension (Domperidone 1 mg/mL) [package insert]. Ahmedabad: Torrent; 2021. [6] European Medicines Agency. Domperidone-containing medicines: restricted indication, contraindications and dose recommendation. EMA/430882/2014. [7] US Food and Drug Administration. Dicyclomine hydrochloride oral solution – product label. Silver Spring (MD): FDA; 2023. [8] World Health Organization. Oral Rehydration Salts: Production of the new ORS. Geneva: WHO; 2020. [9] Sanofi India Ltd. Econorm Sachet (Saccharomyces boulardii 250 mg) [package insert]. Mumbai: Sanofi; 2022. [10] BioGaia AB. BioGaia ProTectis Baby Drops (Lactobacillus reuteri DSM 17938) [package leaflet]. Stockholm: BioGaia; 2020. [11] Franco-Indian Pharmaceuticals. Dexorange Syrup [package insert]. Mumbai: Franco-Indian; 2021. [12] Apex Laboratories. Zincovit Syrup [package insert]. Chennai: Apex; 2022. [13] Cadila Healthcare Ltd. Calcirol D3 Drops (Cholecalciferol 800 IU/mL) [package insert]. Ahmedabad: Zydus Cadila; 2021. [14] Ranbaxy Laboratories. Mox Suspension (Amoxicillin trihydrate) [package insert]. New Delhi: Ranbaxy; 2020. [15] GlaxoSmithKline Pharmaceuticals Ltd. Augmentin Suspension (Amoxicillin + Clavulanate) [package insert]. Mumbai: GSK; 2021. [16] Alembic Pharmaceuticals Ltd. Azithral Suspension (Azithromycin 200 mg/5 mL) [package insert]. Vadodara: Alembic; 2021. [17] Alkem Laboratories Ltd. Taxim-O Suspension (Cefixime 100 mg/5 mL) [package insert]. Mumbai: Alkem; 2021. [18] Mankind Pharma Ltd. Cefakind Suspension (Cefuroxime axetil 125 mg/5 mL) [package insert]. New Delhi: Mankind; 2021. [19] Ranbaxy Laboratories. Cepodem Suspension (Cefpodoxime proxetil 100 mg/5 mL) [package insert]. New Delhi: Ranbaxy; 2021. [20] Indian Academy of Pediatrics. IAP Guidelines for Rational Antibiotic Use in Children. Mumbai: IAP; 2022. [21] Sun Pharmaceutical Industries Ltd. Encorate Syrup (Sodium Valproate 200 mg/5 mL) [package insert]. Mumbai: Sun Pharma; 2021. [22] UCB India Pvt Ltd. Keppra Syrup (Levetiracetam 100 mg/mL) [package insert]. Mumbai: UCB; 2021. [23] Onyango P, Kithinji J, Ireri G, et al. Microbial contamination of paediatric oral liquid medicines used in the community: a cross-sectional survey. Int J Pharm Pract. 2021;29(5):456–62. [24] Novartis India Ltd. Tegrital Suspension (Carbamazepine 100 mg/5 mL) [package insert]. Mumbai: Novartis; 2020. [25] Abbott India Ltd. Thyronorm Oral Solution (Levothyroxine sodium 100 mcg/mL) [package insert]. Mumbai: Abbott; 2022. [26] World Health Organization. Safe use of insulin vials and pens. Geneva: WHO; 2021. [27] Novo Nordisk A/S. Norditropin SimpleXx (Somatropin injection) [package insert]. Bagsværd: Novo Nordisk; 2021. [28] Nestlé India Ltd. Nan Pro 1 Infant Formula [usage guidelines]. Gurgaon: Nestlé; 2022. [29] World Health Organization. Safe preparation, storage and handling of powdered infant formula: guidelines. Geneva: WHO; 2007. [30] Indian Academy of Pediatrics, Breastfeeding Chapter. Guidelines on expressed breast milk storage and handling. Mumbai: IAP; 2021. [31] UNICEF. Ready-to-use therapeutic food (RUTF): operational guidance for programme managers. New York: UNICEF; 2019. [32] Boullata JI, Guenter P, editors. Study Guide for the Clinical Nutrition Certification Board: Enteral Nutrition Practice Recommendations. JPEN J Parenter Enteral Nutr. 2017;41(1):15–103. [33] Ministry of AYUSH, Government of India. Advisory on safety and shelf-life of Ayurvedic syrups and tonics. New Delhi: Ministry of AYUSH; 2020.