official.ajinkya11@gmail.com -

After Second Liver Failure Death, Sarepta Therapeutics Halts Global Elevidys Dosing in Non-Ambulatory Duchenne Muscular Dystrophy Patients; Phase III ENVISION Trial Impacted

June 16, 2025

by official.ajinkya11@gmail.com with No Comment Disease & Drugs

Medically Written and Reviewed By:

Vikas Londhe, MPharm

On June 15, 2025, Sarepta Therapeutics announced the second death of a teenage male patient linked to acute liver failure (ALF) following its one-time gene therapy drug Elevidys in a non ambulatory Duchenne Muscular Dystrophy (DMD) patient, someone who is no longer able to walk due to this condition. The first fatality occurred in March 2025, when a 16-year-old boy succumbed to liver failure months after his treatment with Elevidys.

Official response

As soon as Sarepta was aware about adverse event, they suspended all commercial shipments of Elevidys to non‑ambulatory patients. Sarepta has completely paused dosing to non-ambulatory patient cohort in ENVISION Phase III trial which is going on in ambulatory and non-ambulatory older patient globally; as they are focusing on designing and enhancing more acceptable immunosuppressant regimen along with Elevidys.

Sarepta summon an independent panel of DMD and liver experts to evaluate alternate therapies like sirolimus in combination with corticosteroids to mitigate liver failure risk.

Alongside, Sarepta is continuously discussing with the FDA and other regulatory bodies their proposed plan for this event.

Roche, which is partnered with Sarepta and is responsible for Elevidys’ marketing outside the United States, has equally halted dosing and shipments of Elevidys for non‑ambulatory patients globally.

Sarepta has particularly reported that both fatalities were associated with non-ambulatory patients who were no longer able to walk, a subgroup with advanced DMD. Approximately 140 such patients have been treated, and now, with two ALF-related deaths, this is considered to be a serious safety signal.

However ambulatory patients (those still walking) can continue treatment under the current corticosteroid regimen, as company has not amended protocols for them.

Elevidys & liver risk

Elevidys (delandistrogene moxeparvovec) is an innovative gene therapy that uses an Adeno-Associated Virus (AAV) as a delivery system to transport a micro‑dystrophin genetic material into the body via a single IV infusion. AAV-based gene therapies are known to cause acute liver injury, which can lead to liver failure, though fatalities were rare.

The Elevidys’ previous FDA approval already requires corticosteroid administration one day before initiating treatment and continuing for 60 days post-administration, along with close monitoring for liver function, but those measures have not prevented these rare, severe outcomes. Sarepta is now working on an enhanced safety regimen, which may include the addition of the extra immunosuppressant drug sirolimus into the current corticosteroid regimen. This modification of treatment is held up by preclinical data, which demonstrated sirolimus’ effectiveness in suppressing certain liver enzymes, which may help to mitigate this potential safety signal.

Implications for patients and the market

The tragic loss of two non-ambulatory patients highlights the importance of carefully analyzing Elevidys’s further benefits against the serious risks of liver failure in this subgroup. The ENVISION trial will be amended to include stronger immunosuppressant protocols by the addition of sirolimus; however, this change must receive FDA clearance before dosing resumes. While the FDA has agreed to the pause and is reviewing emerging safety data, full restoration of the trial and treatment depends on how effectively Sarepta is mitigating liver risk in non-ambulatory patient populations.

Summary

Sarepta Therapeutics has reported a second death from acute liver failure in a non-ambulatory patient treated with its Duchenne Muscular Dystrophy gene therapy, Elevidys. Both fatalities occurred in patients who were no longer able to walk, prompting Sarepta and its partner Roche to suspend dosing and commercial shipments of Elevidys for this subgroup globally; however, treatment continues for ambulatory patients. For the time being, dosing to the non-ambulatory cohort group in the Phase III ENVISION trial is on hold pending regulatory review of enhanced immunosuppressant protocols, possibly for the addition of sirolimus into the regimen. The company is working with an independent panel of experts to evaluate stronger liver-protection strategies. These developments have deepened inspection of Elevidys’s safety profile, particularly in advanced-stage DMD. At the same time, it is raising questions about gene therapy risks.

References

Sarepta Community Letter: Safety Update regarding Elevidys in non-ambulatory individuals with Duchenne, Sarepta Therapeutics, June 15, 2025, https://www.parentprojectmd.org/wp-content/uploads/2025/06/Elevidys-Community-Letter-6.15.2025.pdf

Highlights of prescribing information, Elevidys, https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-ELEVIDYS_1.pdf

Sarepta Reports Second Death of Patient Using Its Gene Therapy, Bloomberg, https://www.bloomberg.com/news/articles/2025-06-15/sarepta-reports-second-death-of-patient-using-its-gene-therapy

Sarepta reports second case of liver failure death after its gene therapy treatment, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/sarepta-reports-second-case-liver-failure-death-after-its-gene-therapy-treatment-2025-06-15/

A safety update on Elevidys, June-2025, Parent Project Muscular Dystrophy, https://www.parentprojectmd.org/a-safety-update-on-elevidys-june-2025/?utm_source=chatgpt.com

Second DMD Patient Dies after Treatment with Sarepta Gene Therapy, https://www.genengnews.com/topics/genome-editing/second-dmd-patient-dies-after-treatment-with-sarepta-gene-therapy/

Sarepta Provides Safety Update for ELEVIDYS and Initiates Steps to Strengthen Safety in Non-Ambulatory Individuals with Duchenne, Sarepta Therapeutics, https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-provides-safety-update-elevidys-and-initiates-steps

freepik__the-style-is-candid-image-photography-with-natural__83723

The Essence of Panchakarma: The Fivefold Path to Healing and Inner Balance

June 15, 2025

by official.ajinkya11@gmail.com with No Comment Wellness

Written & Reviewed By:

Ayurvedacharya

Dr. Gaurav Pathare, BAMS

At the heart of Ayurveda lies a simple yet profound guiding principle:

“Swasthasya swasthya rakshanam, aturasya vikara prashamanam cha.”
(Charaka Samhita, Sutrasthana 30.26)

“To maintain the health of the healthy individual and to treat the disease of the sick”

This dual objective defines the true spirit of Ayurvedic medicine. Ayurveda, derived from the Sanskrit words “Ayu” (life) and “Veda” (knowledge), literally means “the knowledge of life science.” It is an eternal healing system practiced since ancient times to promote health, prevent disease, and ensure longevity. First documented in the Atharvaveda, Ayurveda is more than a medical system; it is a complete philosophy of life that harmonizes body, mind, and spirit with the rhythms of nature.

What Is Health According to Ayurveda?

In Ayurveda, health (Aarogya) is not just the absence of disease; it is a state of complete physical, mental, and spiritual harmony. Ayurveda clearly states that only a balanced condition of doshas, dhatus, and malas is Aarogya (Good health or disease-free condition), and their imbalance is the cause of ill health or disease.

समदोषा: समाग्नी: च समधातुमलक्रीय: |

प्रसन्न आत्म इंद्रियमना: स्वस्थ्य इति अभिधियते||

“Balanced doshas (biological energies), balanced Agni (digestive/metabolic fire), properly formed and functioning dhatus (body tissues), efficient elimination of malas (waste products), along with a pleasant state of the soul, senses, and mind—as per Ayurveda this is health.”

What is Panchakarma?

Clockwise: Vaman, Basti, Virechan, Raktamokshan, Nasya,

Source: Ayurdharmaclinic.com, shattayuayurveda.com

Panchakarma is a cornerstone of Ayurvedic therapy, which is designed to purify the body at the deepest cellular level. It focuses on detoxification (shodhana) and rejuvenation (rasayana), restoring balance to the body, mind, and consciousness.

The term “Panchakarma” comes from the Sanskrit:

“Pancha” = Five
“Karma” = Actions or therapeutic procedures

Together, it refers to a group of five therapeutic procedures for internal purification of the body, which aimed at cleansing the body, mind, and consciousness. This eliminates accumulated toxins (Ama), regulates Doshas (Vata, Pitta, Kapha), and rejuvenates the body from the inside out.

Objectives of Panchakarma

Panchakarma is not just a physical detoxification; it is a complete reset for your system. Its goals are

Detoxification of the Body: Removes deep toxins from tissues and organs.

Balancing the Doshas: Restores the natural harmony of Vata, Pitta, and Kapha, essential for health

Enhancing Immunity (Ojas): Strengthens the immune system and improves the body’s resistance to illness.

Promoting Longevity: Prevents the accumulation of disease-causing factors and supports graceful aging.

Rejuvenation and Vitality: Renews energy, improves clarity of mind, and promotes overall well-being.

The Five Main Panchakarma Therapies Procedure	Main Dosha Targeted	Purpose
Vaman	Kapha	Emesis therapy (vomiting)
Virechan	Pitta	Purgation therapy
Basti	Vata	Enema therapy
Nasya	Kapha (above shoulder)	Nasal administration of medicines
Raktamokshan	Raktadhatu	Bloodletting therapy

Vaman (Therapeutic Emesis)

Indicated for: Asthma, bronchitis, skin disorders, and obesity

Process: Use of emetic drugs to induce vomiting

Benefits: Clears the respiratory and digestive tract, removes excess Kapha

Virechan (Purgation Therapy)

Indicated for: Hyperacidity, skin disorders, liver issues

Process: Herbal laxatives are used to cleanse the intestines

Benefits: Eliminates excess Pitta, improves digestion and metabolism

Basti (Enema Therapy)

Indicated for: Arthritis, constipation, neurological disorders

Process: Medicated oil or decoction administered rectally

Benefits: Balances Vata, nourishes tissues, relieves pain

Nasya (Nasal Therapy)

Indicated for: Sinusitis, migraine, stress, memory issues

Process: Nasal administration of medicated oils/ghee

Benefits: Clears head channels, enhances brain function

Raktamokshan (Bloodletting)

Indicated for: Skin diseases, hypertension, varicose veins

Methods: Siravedha (venesection), Jalaukavacharan (leech therapy)

Benefits: Purifies blood, removes localized toxins

Pre-procedure of Panchakarma

Before undergoing the main Panchakarma therapies like Vaman (emesis), Virechana (purgation), and Basti (enema), preparatory steps are essential to loosen and mobilize the doshas (toxins).

Snehan (Oleation)

Definition: Application of medicated oils internally and/or externally to soften and mobilize toxins.

Method: External application of warm medicated oils through Abhyanga (massage).

Purpose:

Loosens accumulated doshas

Nourishes body tissues

Facilitates easier elimination during main Panchakarma therapy

Swedan (Sudation / Sweating)

Definition: Induction of sweating through steam or heat.

Method: Application of heat using medicated steam, hot bolus, or steam chambers.

Purpose:

Dilates body channels

Promotes sweating to liquefy toxins

Enhances absorption of Snehan

Sthanik Snehan & Swedana (Localized Oleation & Sudation)

Definition: Application of oil and heat to specific body parts.

Common Use: Especially done before Nasya Karma (nasal therapy) — typically on the face, head, and neck.

Purpose: Prepares the localized area for better absorption and effectiveness of the Nasya therapy.

Post-procedure of Panchakarma

After completion of the main Panchakarma therapies, the body needs gradual restoration to regular diet and lifestyle.

Sansarjan Karma (Dietary Regimen)

Definition: A structured post-Panchakarma diet plan.

Phases of Diet:

Peya – Thin rice gruel

Vilepi – Thick rice gruel

Kritakrita Yusha – Light vegetable soup

Kritakrita Mamsarasa – Light meat soup

Purpose: Gradually rekindles digestive fire (Agni), Prevents digestive shock, Helps sustain the therapeutic effects.

Dhumapana (Medicated Smoke Inhalation)

When: After Vamana (therapeutic emesis).

Purpose:

Clears residual Kapha from the upper respiratory tract

Prevents complications like cough, cold, or heaviness

Kavala (Gargling with Hot Water/Decoction)

When: After Nasya (nasal therapy)

Purpose:

Clears throat and oral cavity.

Removes residual oil or kapha

Maintains hygiene and promotes oral health

Benefits of Panchakarma

Enhances digestion, absorption, and assimilation at all levels (physical, mental, spiritual)

Improves sleep quality and provides deeper, more restful sleep

Detoxifies body and mind, eliminating toxins

Restores balance of Doshas and promotes holistic health

Strengthens the immune system and builds disease resistance

Promotes tissue rejuvenation and supports longevity

Normalizes menstrual cycles and supports hormonal balance

Boosts mental clarity, emotional stability, and overall awareness

Increases physical flexibility and mobility

Counters stress and slows the aging process

Induces deep relaxation and enhances a sense of well-being

Contraindications

Pregnancy

Extreme weakness or emaciation

Certain acute infections or emergencies

Children and elderly (need adapted versions)

Conclusion

Panchakarma is a powerful, time-tested method for detoxification and rejuvenation. Panchakarma empowers the body’s innate ability to heal and renew. It offers holistic healing by balancing mind, body, and spirit. Incorporating Panchakarma under expert supervision can lead to optimal health and well-being.

References

Charaka Samhita

Ashtanga Hridaya

Modern Ayurveda textbooks and journals

“UK’s Martha’s Rule: A Mother’s Fight That Sparked a National Reform and a Global Wake-Up Call on Patient Safety”

June 14, 2025

by official.ajinkya11@gmail.com with No Comment Health Tidings

Written by: Soniya Hajare, MPharm

Reviewed and Fact-Checked by: Vikas Londhe, MPharm

The UK government has recently introduced ‘Martha’s Rule,’ a new policy that allows patients and their families to directly request a rapid second medical opinion when someone’s condition is worsening or when there is disagreement about their care. This rule was created following the tragic death of Martha Mills, a a 13-year-old girl who tragically died of sepsis at King’s College Hospital in August 2021. Despite multiple warning signs—fever, rash, fluctuating vitals, and parents’ repeated concerns—the pediatric liver team failed to transfer her care to intensive support.

Martha’s Rule, implemented in NHS hospitals across England in April 2024, is a patient safety measure aimed at ensuring timely medical intervention when a patient’s condition worsens. It gives patients, their families, caregivers, or healthcare staff the right to request an urgent review by a critical care outreach team if they are worried about a patient’s health or feel their concerns are not being adequately addressed.

Martha’s Rule also serves as a cultural shift in healthcare, aiming to reduce hierarchical barriers, improve open communication, and empower patients and families to take an active role in medical decisions. Early reports from its initial rollout, shared in December 2024, suggest that the policy is already leading to better patient outcomes by preventing avoidable harm and deaths.

Background

In the summer of 2021, 13-year-old Martha Mills suffered a pancreatic injury after a bicycle accident during a family holiday in Wales, due to seriousness of injury she transferred to King’s College Hospital in London, a specialist centre for paediatric pancreatic trauma under the supervision of paediatric hepatology team. Although her health condition showed signs of worsening (high BPEWS score), she remained on a general paediatric ward and tragically succumbed to septic shock on 31 August 2021.

Investigations and Inquests

Following Martha’s death, a detailed internal investigation by King’s College Hospital found five missed opportunities to involve the intensive care unit, despite ICU beds being available at the time. In March 2022, the coroner concluded that Martha would likely have survived if she had been transferred to the intensive care ward earlier when worsening signs started appearing.

The inquest also highlighted systemic issues, such as the continued use of paper-based observation charts, poor communication between departments, and an absence of a well-defined ICU escalation protocol.

In May 2025, the General Medical Council (GMC) conducted a tribunal into the conduct of the senior consultant overseeing Martha’s care. He was found guilty of professional misconduct, including giving inaccurate and outdated information about Martha’s condition during a critical stage of her illness. Despite these findings, the tribunal decided not to impose any formal sanction, citing his long-standing career, previous good record, and the complexity of the situation.

The Five Missed Opportunities

Failure to escalate to high-dependency or ICU beds early enough
Ignoring early sepsis indicators
Communication breakdown and team culture issues
Misdiagnosis of rash on 29 August
Absence of senior consultant reviews during critical deterioration

Implementation

Martha’s mother, Merope Mills, a senior editor at The Guardian, used her platform not just to share her grief but to campaign for change. She didn’t seek blame; she wanted reform. Her stand was simple: families should have a formal right to escalate concerns if they believe something is wrong. This led to the creation and rollout of Martha’s Rule

After the heart-rending and preventable death of 13-year-old Martha Mills, a series of reforms and actions were taken in response to the findings of the investigation and public pressure from her family. The most significant and systemic change was the implementation of ‘Martha’s Rule’ across all NHS hospitals in England. Below is a detailed summary of the key implementations:

Introduction of “Martha’s Rule”

Martha’s Rule is a national policy designed to give patients and families direct access to a second clinical opinion or critical care review when they are concerned that a patient is deteriorating and not being properly heard.

Core Features

24/7 access for patients and families to request a rapid clinical review from a critical care team (separate from the patient’s current care team)

Hospitals must prominently display how and when to escalate concerns, including bedside posters and leaflets

Staff training to encourage listening to families, recognizing that they often detect subtle signs of deterioration early

Strengthening the early warning score systems and escalation pathways already in place, making them more transparent and family-accessible

Rollout of Martha’s Rule

The implementation of Martha’s Rule began as a phased rollout following strong public pressure and policy discussions initiated in late 2023. NHS England, working with patient safety experts and Martha Mills’s family, selected 143 NHS trusts to pilot the scheme in early 2024.

These pilot sites tested how effectively patients and families could escalate a rapid clinical review when they were concerned about a patient’s condition. Following positive evaluations, the NHS committed to nationwide implementation. By April 2025, Martha’s Rule was made mandatory across all acute hospitals in England, with dedicated resources, signage, and staff training provided to ensure uniform compliance.

Impact & Data from Pilot Evaluation

During the initial rollout across 143 NHS hospitals in England (September–October 2024), 573 calls were made by patients, families, carers, and staff concerning suspected deterioration. Of these:

286 calls (50%) led to an urgent clinical review by critical care outreach teams

Around 57 reviews (20%) resulted in a change in treatment; such as administration of antibiotics, oxygen, or other life-saving interventions. However the patient remained on their ward.

14 patients were urgently transferred to intensive care units (ICU) after the escalation, potentially prevention serious complications or death.

By March 2025

A total of over 2,000 escalations had been made under the Rule

More than 300 escalations were followed by documented improvements in care

Over 100 patients were transferred to ICU or its equivalent directly due to their concerns being flagged through Martha’s Rule

Additionally, about 75% of calls originated from family members, highlighting the vital role that caregivers play in recognising deterioration that might otherwise be missed

These figures clearly exemplify both the scale and effectiveness of Martha’s Rule: it is being used with meaningful results, not abused, and is saving lives. NHS England’s national medical director, Prof Sir Stephen Powis, described it as “one of the most significant changes in patient safety in recent years,” and England’s Patient Safety Commissioner, Dr Henrietta Hughes, confirmed it “improving safety and reducing harm”

Conclusion and Pharmacally’s Take

At Pharmacally, we believe that patient safety begins with patient empowerment and Martha’s Rule marks a powerful shift in that direction. Martha’s Rule is arises from the heartbreaking loss of 13-year-old Martha Mills, This reform is more than just a policy, It is a major step toward making sure that patients and families are listened, their concerns are taken seriously, and their role in care decisions is truly respected.

For a long time, when patients or families raised concerns, those warnings often got delayed or overlooked due to complicated hospital systems and strict hierarchies. Martha’s Rule changes that it gives patients and families the power to speak up and be taken seriously, not just with empathy, but with real action.

At Pharmacally, where our core mission is to translate cutting-edge medical insight into safer outcomes, we see Martha’s Rule as a milestone for all who believe that safety is a shared responsibility. It formalizes a patient’s right to speak up and be taken seriously, especially when every minute matters.

We urge our readers, patients, caregivers, clinicians, and health systems to view Martha’s Rule not just as a protocol, but as a cultural reset. A chance to build a health system that listens, learns, and acts faster. Patient Safety doesn’t start in the ICU it starts at the bedside, with a voice saying, “I think something is wrong.”

Martha’s Rule isn’t just Martha’s legacy. It’s a blueprint for a safer, smarter, more responsive healthcare system. And at Pharmacally, that’s exactly the kind of future we stand for

Stay Healthy This Monsoon: Ayurvedic Lifestyle Tips for Varsha Ritu

June 13, 2025

by official.ajinkya11@gmail.com with No Comment Lifestyle

Written and Reviewed By:

Ayurvedacharya Dr. Gaurav Pathare, BAMS

Period: Full Jyeshtha, Ashadha, and partly Shravana (approximately late June to mid-August)

In Ayurveda, the seasonal routine Ritucharya is an essential part of preventive healthcare. Each season affects the body and mind differently and calls for specific lifestyle and dietary adjustments. Varsha Ritu (Rainy Season) is one of the most sensitive periods for health due to the combined effects of heat accumulation from the previous season and the sudden coolness and moisture in the environment.

Seasonal Impact on the Body

Agni (digestive fire) becomes weak due to sudden cold and increased humidity.

Dosha Effects:

Vata becomes aggravated due to cold, dryness, and irregularity in weather.

Pitta increases due to natural acidity and internal heat built up during summer. Symptoms of Pitta may remain hidden initially due to the external coldness.

The body’s overall resistance is weakened, making it prone to infections, indigestion, and joint problems.

Dietary Regimen (Ahara Charya)

What to Eat

Light, warm, oily, and easily digestible foods

Old grains (1 year aged): Wheat, Jowar, Rice

Pulses: Moong dal, Tur dal, Lentils (in moderation)

Dishes: Moong (yellow split mung beans) Khichdi, Upma (Semolina pudding), Moong Varan-Bhat, Jowar (Sorghum) Bhakri

Fats: Moderate use of ghee and oils

Spices & Digestives

Asafoetida (Hing), Garlic, Ginger, Mint, Black Pepper, Cumin, Coriander, Cinnamon, Onion

Special Items

Buttermilk (with rock salt)

Honey (small quantity)

Amaranth laddus (Rajgira ladoo)

Roasted gram flour (Sattu)

Horse gram (Kulthi flour)

Soups

Hot chicken/mutton soup with garlic, ginger, and asafoetida (in moderation)

Water Intake

Boiled and medicated water using:

Nagarmotha, Cumin, Dry Ginger (Sunthi), Coriander

Avoid chilled water; prefer warm or lukewarm water

Foods to Avoid

Raw and heavy-to-digest foods: Tubers, potatoes, sweet potatoes, peas, lentils, chickpeas

New grains, fermented foods (e.g., pizza, cheese)

Leafy vegetables (due to risk of worms and bloating)

Cold and damp-inducing items: Cucumber, sugarcane juice, ice cream, soft drinks

Excess dairy: Curd at night, yogurt, excess milk with salt

Meat and seafood (especially fried or fermented)

Sweets, fried snacks, and overly oily foods

Lifestyle Guidelines (Vihara Charya)

Do’s

Use warm water for bathing and washing

Apply oil (Abhyanga) and take steam (Swedana) regularly

Practice Basti therapy (medicated enemas) as part of Panchakarma

Ensure proper clothing and bedding to avoid exposure to cold wind

Use aromatics and disinfectants in the home environment

Don’t

Avoid day sleeping, strenuous physical activity, and walking in the rain.

Refrain from cold exposure and excess sexual activity (maximum once a fortnight)

Do not eat without hunger or overeat

Avoid sleeping late, mental stress, and irregular routines

Panchakarma for Rainy Season

In Varsha Ritu, the body is susceptible to Vata aggravation, and the digestive system is weak. Therefore, Panchakarma therapies help maintain balance and remove accumulated Doshas

Snehana (Oleation)—Internal and external application of medicated oils

Swedana (Sudation Therapy)—Fomentation or sweating therapy to open body channels

Basti (Medicated Enema)—Most effective treatment for Vata disorders in this season

Conclusion

The rainy season is a vulnerable time for health in Ayurvedic understanding. Adopting a season-appropriate regimen helps maintain balance, supports immunity, and prevents common seasonal disorders such as indigestion, joint pains, and skin diseases. Through mindful dietary practices, lifestyle adjustments, and therapeutic Panchakarma treatments, one can harmonize with nature and stay healthy during Varsha Ritu.

Reference

Ashtang Hridaya Chapter 3

Moderna Launches mNEXSPIKE: New FDA-Approved COVID Vaccine for High-Risk Groups

June 13, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written By: Dewanshee Ingale, BPharm

In a landmark move, the FDA has granted approval to Moderna’s mNEXSPIKE, marking a new chapter in COVID-19 vaccine evolution. Approved on May 30, 2025, was a historic landmark towards the continuous development and evolution of messenger RNA (mRNA) technology based vaccines. The vaccine is such created that it acts as a next generation booster to improve the COVID-19 protection primarily focusing on the high-risk people. High risk populations include older adults from the age of 65 and above as well as smaller adults from the age of 12-24 with serious medical conditions defined by the Centres’ for Disease Control and Prevention (CDC) and that can increases the worsening of the outcomes if they are infected by virus. With the grand approval, Moderna now expects to provide mNEXSPIKE in addition to its original Spikevax® vaccine during this upcoming 2025-2026 respiratory virus season.

Present data and background

COVID-19 still serves as a major public health risk in the world. In 2024, the virus took more than 47,000 lives in America, which translates to a death every 11 minutes. Older adults usually experience very severe sickness, hospitalization, and death as compared to other groups. CDC surveillance data from October 2023 to April 2024 show that this older age group represented 70% of adult hospitalizations. Adults aged 65 and older comprised approximately 70% of all COVID-19-related hospitalizations among adults in the U.S. Among the adults who died in the hospital due to COVID-19, 80% were aged 65 and above.

The high prevalence of certain medical conditions further compounds this vulnerability. For example, obesity may increase the risk of severe COVID-19 outcomes by 1.4 times, diabetes by 1.8 times, and chronic lung diseases by as much as 3.2 times. These conditions significantly raise the likelihood of serious health complications. This data underscores the urgent need for effective and targeted vaccination strategies such as Moderna’s next-generation mNEXSPIKE vaccine to protect those most at risk, especially as the COVID-19 virus continues to evolve.

mNEXSPIKE is built upon Moderna’s mRNA-1273 (Spikevax) platform, but with an updated design, which primarily focusing on the key regions of the SARS-CoV-2 spike protein instead of targeting the whole structure. This invention, when combined with a lower dose (10 µg vs. Spikevax’s 50 µg), aims to improve efficiency while reducing reactogenicity. The development of mNEXSPIKE was guided by real-time data and advancements in prognostic analytics, reflecting Moderna’s commitment to continuous innovation and optimization.

A Novel Approach

Moderna’s mNEXSPIKE characterizes an important step ahead in COVID-19 vaccine. It is created on the basic foundation of mRNA technology but is designed in such a way that it is more efficient and can address present and future challenges as compared to previously present COVID-19 vaccines. mNEXSPIKE offers an enhanced mRNA technique that targets the specific region of the SARS-CoV-2 spike protein. This enables the human’s immune system to react strongly while it delivers a significantly low dose at 10 micrograms, which is one-fifth of the dose of Moderna’s original Spikevax vaccine.

The lowered-dose formulation is not only responsible for reducing the side effects but also for rationalizing manufacturing and distribution. mNEXSPIKE can be stored at regular refrigerator temperatures (2-8°C) for 90 days, overcoming the logistical difficulties of the prior existing mRNA vaccines and enabling use in a wide geographic area, particularly in areas where the facility of cold storage does not exist.

Individuals who have already received the COVID-19 vaccine are advised to use this vaccine as a booster vaccine to protect adults 65 years and above or 12-64 years old with other comorbidities. Clinical trials have established that this new vaccine offers more protection or equivalent protection in comparison to the previously existing vaccine. A stronger immune response is elicited against both the Omicron subvariants and the original virus strain.

With a designed antigen, reduced doses, and improved storage stability, mNEXSPIKE bears a very clever strategy for pandemic protection. This leads to increased efficiency, adaptability, and patient friendliness for those who are at risk.

Clinical trials and approval

Rigorous clinical trial data support the FDA approval of Moderna’s mNEXSPIKE COVID-19 vaccine, which represents efficacy and safety in different populations. The efficacy and safety of mNEXSPIKE were evaluated in a randomized, active-controlled NextCOVE clinical trial (NCT05815498) that was conducted in the United States, the United Kingdom, and Canada. The conducted large-scale evaluation included 11,417 individuals who were aged 12 years and above, with a median follow-up of 8.8 months.

The study population was distinct, with an average age of 56 years (range: 12-96 years). Demographically, the trial included

8.7% adolescents (12-17 years)

62.6% of adults (18-64 years)

28.7% older adults (65+ years)

The NextCOVE trial enrolled participants who were evenly divided between the mNEXSPIKE group (n = 5,706) and the comparator vaccine group (n = 5,711). Nearly all participants had received at least one prior COVID-19 vaccine dose, with an average interval of 9.8 months since their most recent vaccination. Notably, 74.3% of participants showed evidence of prior SARS-CoV-2 infection at baseline.

The mNEXSPIKE vaccine used in the study was a bivalent formulation, delivering a 10 microgram total dose comprising 5 µg targeting the original SARS-CoV-2 (Wuhan strain) and 5 µg targeting the Omicron variant. This represents a substantial dose reduction compared to the 50 µg dosage of the comparator vaccine. Participants received a single 0.2 mL intramuscular injection, administered at least three months after their previous COVID-19 vaccine dose.

Results

The primary endpoint of the NextCOVE Phase 3 trial (NCT05815498) was to evaluate the efficacy of Moderna’s mNEXSPIKE (mRNA-1283) vaccine in preventing symptomatic COVID-19, starting 14 days after a single booster dose, compared to the existing Spikevax (mRNA-1273) vaccine. The study enrolled over 11,400 participants aged 12 years and older, with nearly all having received at least one prior COVID-19 vaccination. The results demonstrated that mNEXSPIKE met the criteria for non-inferiority to Spikevax and showed a relative vaccine efficacy (rVE) of 9.3% in preventing symptomatic COVID-19 across all adults. Notably, in adults aged 65 and older, mNEXSPIKE showed an even higher rVE of 13.5%, indicating stronger protection in this high-risk group. The vaccine was also well tolerated, with a safety and reactogenicity profile comparable to or slightly improved over Spikevax, despite using a significantly lower dose of just 10 µg (versus 50 µg for Spikevax).

Safety profile

Moderna’s mNEXSPIKE has established a favorable safety profile across all age groups, with most side effects being mild to moderate and transient. Commonly reported adverse reactions included pain at the injection site, fatigue, headache, muscle pain, joint pain, chills, and nausea or vomiting, with slightly lower frequencies observed in adults aged 65 and older.

A key safety consideration is the rare risk of myocarditis and pericarditis, particularly in males aged 12–24 years, typically occurring within one week of vaccination. The estimated rates are approximately 8 cases per million doses in recipients under 64 years and 25 per million in males aged 12–25.

The vaccine is contraindicated in individuals with a history of severe allergic reactions (e.g., anaphylaxis) to any mNEXSPIKE component or prior Moderna COVID-19 vaccine dose. Syncope may also occur post-vaccination, as seen with other injectables.

Overall, the safety profile of mNEXSPIKE is consistent with other mRNA vaccines, and combined with its 9.3% higher relative vaccine efficacy, especially in older adults, it is a strong candidate for protecting high-risk populations during the ongoing COVID-19 threat.

Impact and future viewpoint

The sanction of Moderna’s mNEXSPIKE COVID-19 vaccine demonstrates an important invention in the pandemic protection, particularly for high risk groups like elderly people and those who have comorbidities. mNEXSPIKE offers an improved efficiency at a reduced dose and storage requirements, and is expected to increase the accessibility of vaccines and uptake, usually in areas with limited cold storage requirements. The vaccine’s improved safety and effectiveness characteristics are likely to reduce the total number of hospitalizations and deaths caused the COVID-19 which has taken thousands of lives in the U.S. over a year.

Looking at the future, mNEXSPIKE has undoubtedly set an entirely new standard for the upcoming next-generation vaccines, showcasing the potential for design and innovation that can protect the vulnerable population better. The approval also depicts the transformation toward personalized and adaptable vaccine planning strategies, which are of utmost importance due to the continuous evolution of the virus.

Overall, the newly created booster vaccine, Moderna’s mNEXSPIKE, is not only capable of strengthening the present pandemic preparedness but also lays the way for future innovation in mRNA vaccine technology and protection of public health.

References

mNEXSPIKE FDA Approval History https://www.drugs.com/history/mnexspike.html

Introducing mNEXSPIKE: Moderna’s New COVID-19 Vaccine https://www.modernatx.com/media-center/all-media/blogs/introducing-mnexspike-modernas-new-covid-19-vaccine

Moderna Receives U.S. FDA Approval for COVID-19 Vaccine mNEXSPIKE https://investors.modernatx.com/news/news-details/2025/Moderna-Receives-U-S–FDA-Approval-for-COVID-19-Vaccine-mNEXSPIKE/default.aspx

FDA approves Moderna’s new COVID-19 vaccine https://www.cidrap.umn.edu/covid-19/fda-approves-modernas-new-covid-19-vaccine

FDA Package Insert – MNEXSPIKE https://www.fda.gov/media/186738/download

Spyros Chalkias, Antionette Pragalos, Adebayo Akinsola, et al, Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain and N-Terminal Domain mRNA Vaccine, The Journal of Infectious Diseases, Volume 231, Issue 4, 15 April 2025, Pages e754–e763, https://doi.org/10.1093/infdis/jiaf022

A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 (NextCOVE), moderna clinical trials, https://trials.modernatx.com/study/?id=mRNA-1283-P301&Latitude=27.6648274&Longitude=-81.5157535&LocationName=Florida,%20USA&MileRadius=100

The article is reviewed and fact-checked by the editorial team of Pharmacally.com

The Hidden Pain Pathway: Paracetamol (Acetaminophen) Metabolite AM404 Blocks Peripheral Sodium Channels – A New Mechanism Uncovered

June 12, 2025

by official.ajinkya11@gmail.com with No Comment Research

Medically Written and Reviewed By: Vikas Londhe, M.Pharm, Pharmacology

For over a century, paracetamol (acetaminophen) has been one of the world’s most widely used analgesics and antipyretics. Despite its widespread use, its exact mechanism of action has remained unclear. It was long believed to work mainly by blocking certain enzymes called cyclooxygenases (COX), especially COX-2. These enzymes are responsible for producing prostaglandins, which are chemicals that promote pain, inflammation, and fever. By reducing prostaglandin production, paracetamol helps lower pain and fever without significantly reducing inflammation like other NSAIDs. However, it is believed that paracetamol is only effective in mild inflammations, like after tooth extraction, and it is not effective in severe inflammation that arises from rheumatoid arthritis and acute gout.

Another pathway involves the TRPV1 receptor, short for Transient Receptor Potential Vanilloid 1, which plays a role in sensing heat and pain. Some research suggests that an active metabolite of paracetamol, the fatty acid amide N-arachidonoylphenolamine (AM404), may activate TRPV1 in a way that leads to pain relief by desensitizing these pain-sensing receptors.

However, new research conducted at Hebrew University of Jerusalem and the findings are published in The Proceedings of the National Academy of Sciences (PNAS) has uncovered a previously unknown mechanism of paracetamol. The new research proposed that paracetamol acts directly at peripheral nerve endings. Its metabolite AM404 can block sodium channels in the nerves, which are essential for sending pain signals to the brain. This discovery adds a new dimension to our understanding of how paracetamol relieves pain: not just through the inhibition of certain enzymes and receptors, but also by directly inhibiting the body’s ability to send pain signals to the brain.

The Breakthrough Study

A team led by Professors Alexander Binshtok and Avi Priel from the Hebrew University of Jerusalem published these game-changing findings in the prestigious PNAS, titled “The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels”

The key findings of the Research Includes

Local production of AM404: After oral intake of paracetamol, the body converts it to p-aminophenol in the liver, which is subsequently transformed into AM404 by fatty acid amide hydrolase (FAAH) in primary sensory neurons, essentially at the nerve endings where pain signals originate.

Inhibition of nociceptive sodium channels: AM404 directly blocks voltage-gated sodium channels Na_V1.7 and Na_V1.8, both crucial for generating action potentials in pain-sensing neurons. The blockade occurs via the local anesthetic binding site.

Peripheral analgesia: Through this localized mechanism, AM404 prevents pain signals at their source, producing potent relief in both regular and inflammatory pain models in rodents.

Researchers found that AM404, a metabolite formed from paracetamol in the body, accumulates in peripheral sensory neurons where it directly inhibits voltage-gated sodium channels Na_V1.7 and Na_V1.8. These channels are critical for the initiation and conduction of pain signals at the site of injury or inflammation. By blocking these sodium channels, AM404 effectively diminishes nociceptive signal transmission at its source, preventing pain before it even reaches the spinal cord. This peripheral action represents a fundamental shift in our understanding of how paracetamol works. It positioned paracetamol not only as a central analgesic but also as a locally acting modulator of neuronal excitability.

Results

AM404 significantly reduced sodium current amplitude in isolated dorsal root ganglion (DRG) neurons in a dose-dependent manner. The greatest effect was observed on tetrodotoxin-resistant (TTX-R) sodium currents, which are characteristic of Nav1.8, a key player in chronic and inflammatory pain. AM404 had minimal effect on potassium and calcium currents, indicating a selective action on sodium channels.

In pharmacological profiling, AM404 showed the strongest inhibition of Nav1.7 and Nav1.8, both of which are highly expressed in nociceptive (pain-sensing) neurons. Other Nav subtypes, such as Nav1.5 (cardiac) and Nav1.6 (CNS), were minimally affected, suggesting a favorable safety profile by avoiding cardiac or CNS toxicity.

In formalin-induced inflammatory pain models, peripheral injection of AM404 significantly reduced both early (neurogenic) and late (inflammatory) phases of pain behaviors (licking, flinching). In the hot plate and tail flick thermal assays, AM404 increased latency to pain response, indicating effective thermal analgesia. Systemic or central (intrathecal) administration of AM404 had less prominent effects, highlighting that peripheral action is essential for its analgesic activity.

Computational docking predicted that AM404 binds to a hydrophobic fenestration site within the channel’s domain IV S6 segment, a region known to influence channel gating and drug binding.

Implications

This research challenges the traditional view of paracetamol as a centrally acting analgesic. It highlights that peripheral mechanisms, particularly in the context of inflammatory pain, are also crucial to its analgesic action. A key finding is the active pharmacological role of AM404, a metabolite of paracetamol, which is not just a metabolic byproduct but a potent modulator contributing to its pain-relieving effects. This adds to the recognition of the importance of drug metabolites in determining therapeutic efficacy. Moreover, the study strengthens the therapeutic relevance of targeting sodium channel subtype Na_V 1.7, positioning AM404 as a promising lead compound or molecular scaffold for the development of new, non-opioid analgesics.

Broader Impact: Beyond Paracetamol

This study opens exciting new avenues in the field of pain research. It triggers a re-evaluation of some metabolites that have been silent since their discovery and are also traditionally overlooked, but may possess key pharmacological actions, suggesting that other commonly used drugs could harbor unexplored therapeutic potential through their metabolites.

Additionally, the findings strengthen the scientific rationale for targeting peripheral sodium channels, particularly in managing chronic and inflammatory pain conditions. AM404, a paracetamol metabolite, exerts analgesic effects without causing sedation or respiratory depression, positioning it as a promising foundation for developing safer, non-addictive alternatives to opioids.

Conclusion

The discovery that AM404 blocks peripheral NaV channels redefines how we understand one of the worlds’s most commonly used analgesics. By uncovering this hidden peripheral pain pathway, researchers at the Hebrew University of Jerusalem have significantly advanced the field of analgesic pharmacology. This work not only deepens our molecular understanding of paracetamol but also opens up new possibilities for developing better pain medicines and emphasizing the vital role of peripheral targets in pain relief.

References

Y Maatuf, Y. Kushnir, A.Nemirovski, et al, The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels, Proc. Natl. Acad. Sci. U.S.A. 122 (23) e2413811122, https://doi.org/10.1073/pnas.2413811122

Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008 Oct; 18(10):915-21. Doi: 10.1111/j.1460-9592.2008.02764.x. PMID: 18811827

Israeli study finds acetaminophen drug works by first blocking pain in nerves, The Times of Israel, https://www.timesofisrael.com/israeli-study-finds-acetaminophen-drug-works-by-first-blocking-pain-in-nerves/

New discovery: Tylenol stops pain at the nerves, before it hits the brain, ScienceDaily, https://www.sciencedaily.com/releases/2025/06/250610074247.htm#:~:text=Summary%3A,channels%20in%20pain%2Dsensing%20nerves.

Mallet C, Desmeules J, Pegahi R, Eschalier A. An Updated Review on the Metabolite (AM404)-Mediated Central Mechanism of Action of Paracetamol (Acetaminophen): Experimental Evidence and Potential Clinical Impact. J Pain Res. 2023 Mar 29;16:1081-1094. Doi: 10.2147/JPR.S393809. PMID: 37016715; PMCID: PMC10066900.

Sharma CV, Long JH, Shah S, Rahman J, Perrett D, Ayoub SS, Mehta V, First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid. J Pain Res. 2017; 10:2703-2709 https://doi.org/10.2147/JPR.S143500

Wrong Blood, Lost Life: How a Blood Transfusion Error at SMS Hospital, Rajasthan Sparked a State-wide Medical Reckoning

June 11, 2025

by official.ajinkya11@gmail.com with No Comment Health Tidings

Written and Reviewed by Vikas Londhe M.Pharm (pharmacology)

Assisted By: Shakuntala Kawhale (M.Pharm pharmacology)

On May 20, 2025, a 23-year-old pregnant woman died in Jaipur’s prestigious Sawai Man Singh (SMS) Hospital, not from the illness she was fighting but from a blood transfusion mistake that was preventable and never should have happened.

A female patient from Tonk district, who was seven months pregnant, was admitted to SMS Hospital on May 12 with severe anaemia and miliary tuberculosis. Her pregnancy was already classified as high-risk. However, she was mistakenly given A+ blood, despite her actual blood type being B+.

The error was not caught until it was too late. By the time symptoms like fever, chills, hematuria, and rapid heart rate appeared, around 350 ml of incompatible blood had already been transfused. Patient succumbed to the reaction later that night.

Timeline of Errors

The tragedy was not the result of a single misstep but a chain of preventable lapses:

No dual verification between the blood samples sent from the ward and the patient’s records.
Incorrect blood group identification during ward-level preparation.
Failure to match identifiers (yellow tag, ABHA ID, blood bag barcode) at the point of transfusion.
Inadequate monitoring in the critical first 15–30 minutes post-transfusion, when early signs of reaction generally appear.
No immediate escalation occurred when the patient developed symptoms, delaying corrective measures.
Delayed and incomplete communication with her family, who were not immediately informed of the transfusion error.

This was the third transfusion-related death involving SMS and its affiliated hospitals in just over a year, highlighting a pattern of systemic failure.

What the Internal Inquiry Found and Why It Was Rejected

SMS Hospital conducted an internal investigation and acknowledged the transfusion error. However, the report controversially claimed that the mismatched blood was not the direct cause of death, pointing towards the patient’s tuberculosis and low haemoglobin levels.

This standpoint received immediate criticism from many levels. The Rajasthan government rejected the internal findings, labelled them unsatisfactory and ordered an independent, high-level investigation. Health Minister Gajendra Singh Khimsar announced the formation of a committee comprising senior doctors, administrative officials, and public health experts, tasked with submitting a report within three days.

The case also reached the Rajasthan State Human Rights Commission, which issued a notice demanding detailed reports by June 12.

Rajasthan Government’s Official Response: a Shift toward Safety

Under the public pressure and clear protocol violations, the Rajasthan government took immediate and serious action:

Key Policy Decisions Announced

Digital Blood Group mapping

All patients in state hospitals will now have their blood type linked to their Ayushman Bharat Health Account ID (ABHA ID), reducing room for clerical or manual entry errors.

Compulsory Admission—Time Blood Typing

Every patient must now undergo blood grouping at admission, with results entered into a centralized digital lab system.

Dual Verification at Blood Banks

Before releasing any blood unit, technicians must re-verify the patient’s blood type and documentation, independent of the ward-level grouping.

Detailed Chain of Custody Documentation

Blood request forms must now contain:

Name and mobile number of the requesting resident

Attending the duty doctor’s name

Name of the staff that collected the sample and the blood bag

Standardized Monitoring Protocol during Transfusion

Clinical staff must now:

Match the patient ID, yellow wristband, and blood label

Monitor vitals at 0, 5, 15, and 30 minutes during the transfusion

Record all observations in real time

Statewide SOP Enforcement across RMES Hospitals

SMS-level safety protocols are now mandatory across all government medical colleges and district hospitals under the Rajasthan Medical Education Society (RMES).

Patient Safety Lessons: When Systems Fail, People Pay the Price

The loss of life is a staggering reminder of how even routine clinical procedures can turn deadly without robust precaution. Blood transfusions are considered high-alert medical procedures, requiring multiple fail-safe mechanisms to prevent mismatches. When these mechanisms are skipped whether due to staff shortages, lack of training, or system fatigue the consequences are often fatal.

This case illustrates the urgent need for error-proof processes, accountability tracking, and a culture where speaking up about unsafe practices is encouraged.

Pharmacally’s Take: Reform Begins with Acknowledging the Risk

While the Rajasthan government’s response has been proactive and progressive, the real test lies in enforcement. Policies on paper must translate to practice on the ground. Frontline workers residents, nurses, lab techs must be trained, audited, and supported in following these updated protocols.

At Pharmacally.com, we advocate for healthcare systems that:

Prioritize patient safety
Embed digital tools to reduce human error.
Enforce chain-of-responsibility in critical procedures, and
Promote transparent investigations when outcomes go wrong.

Final Word: From Tragedy to Transformation

This patient should have gone home with her newborn in a few months. Instead, her death has exposed deep vulnerabilities in our public health system. If Rajasthan succeeds in turning this tragedy into a safety revolution, it could become a blueprint for the rest of India.

References:

Gandhi a, görlinger k, nair sc, kapoor pm, trikha a, mehta y, handoo a, karlekar a, kotwal j, john j, apte s. Patient blood management in india-review of current practices and feasibility of applying appropriate standard of care guidelines. A position paper by an interdisciplinary expert group. Journal of anaesthesiology clinical pharmacology. 2021 jan 1;37(1):3-13.

Bisht a, singh s, marwaha n. Hemovigilance program-india. Asian journal of transfusion science. 2013 jan 1;7(1):73-4.

Mammen jj, asirvatham es, sarman cj, ranjan v, charles b. A review of legal, regulatory, and policy aspects of blood transfusion services in india: issues, challenges, and opportunities. Asian journal of transfusion science. 2021 jul 1;15(2):204-11

Rajasthan to streamline blood transfusion system in all hospitals, News Arena India, https://newsarenaindia.com/nation/rajasthan-to-tighten-hospital-blood-transfusion-rules/45595

State Gov to tightens blood safety protocols after transfusion deaths, times of India, https://timesofindia.indiatimes.com/city/jaipur/state-govt-to-tighten-blood-safety-protocols-after-transfusion-death/articleshow/121421643.cms

Rajasthan hospital accused of fatal transfusion error after pregnant woman, 23, dies, The Economic Times, https://economictimes.indiatimes.com/news/india/rajasthan-hospital-accused-of-fatal-transfusion-error-after-pregnant-woman-23-dies/articleshow/121362945.cms?from=mdr

Mandukaparni (Centella asiatica): The Ayurvedic Herb That Rewires Your Brain & Rejuvenates Your Body

June 10, 2025

by official.ajinkya11@gmail.com with No Comment Wellness

Written By: Lavanya Chavhan, B.Pharm

Reviewed By: Ayurvedacharya Dr. Gaurav Pathare, BAMS

Mandukaparni (Gotu Kola) is an ancient Ayurvedic herb known for boosting memory, reducing anxiety, and healing the skin. Backed by clinical evidence and meta-analysis, learn how to use Mandukaparni effectively for optimal health

At Pharmacally, we believe that the best medicine combines ancient wisdom with modern science. One such powerful herb is Mandukaparni a small green leaf with big healing potential.

If you’re dealing with brain fog, skin problems, stress, or slow-healing wounds, Mandukaparni might be the natural support your body needs.

Known scientifically as Centella asiatica (CA), also known as Mandukaparni, Indian pennywort, or Gotu Kola, Mandukaparni has been a part of Ayurvedic medicine for centuries. In ancient texts, it’s described as a “Medhya Rasayana” an herb that nourishes and sharpens the mind. In Sanskrit Manduk means frog and Parni means leaves; which means shape of the leaves are resembled with the shape of feets of the frog, hence Mandukaparni.

Traditionally used in India and Southeast Asia, this herb is now being explored in modern clinical trials and meta-analyses, confirming many of its traditional uses. From boosting brain function to improving skin repair, Mandukaparni is gaining recognition as a truly holistic healer. It is mentioned in ancient texts like the Sushruta Samhita. The herb is also traditionally used in Java, Indonesia, and China, where it is considered a “miracle elixir of life.”

Active constituents involved in pharmacological action of a Mandukaparni

At the heart of its therapeutic power lies a complex array of phytochemicals, natural compounds that work in synergy to promote healing.

At the core of Mandukaparni’s healing power lies a unique group of compounds known as triterpenoid saponins. The most studied are asiaticoside and madecassoside. These compounds are primarily responsible for promoting wound healing by stimulating collagen synthesis and reducing inflammation.

In addition to triterpenoids, Mandukaparni contains significant amounts of flavonoids and polyphenols such as quercetin, kaempferol, and rutin. These compounds contribute to the herb’s potent antioxidant activity, helping to neutralize free radicals and protect brain cells from oxidative stress. Studies suggest that these flavonoids work in synergy with triterpenoids to enhance cognitive functions and delay age-related neurological decline.

Mandukaparni also yields a variety of essential oils, obtained through steam distillation of its leaves. Key volatile compounds include caryophyllene, pinene, and humulene, each of which exhibits antimicrobial, anti-inflammatory, and mood-stabilizing properties. These oils are often used in skin creams, ointments, and aromatherapy preparations for added therapeutic benefit, particularly in wound care. Further phytochemical screening reveals the presence of β-sitosterol, a plant sterol known for supporting cardiovascular health and cholesterol balance.

Health Benefits of Mandukaparni

Sharpens Memory & Boosts Mental Clarity

Mandukaparni is widely recognized as a natural brain tonic. It is believed to nourish the nervous system, support cognitive functions, and promote mental clarity. Regular use is said to enhance memory retention, sharpen focus, and reduce mental fatigue, making it a popular choice among students and individuals under high mental stress.

Reduces Stress & Calms the Mind

This herb is often used to soothe anxiety, restlessness, and irritability. In Ayurvedic texts, Mandukaparni is said to balance the “vata” dosha, which governs the nervous system. It promotes a calm, grounded mental state and helps reduce symptoms of stress-induced imbalances such as insomnia, overthinking, and emotional instability.

Revitalizes Skin Health

Mandukaparni has long been used to improve skin texture, tone, and elasticity. It is considered excellent for managing various skin disorders including dryness, discoloration, and minor wounds. Its regenerative properties support faster healing of cuts, scars, and burns while rejuvenating the skin from within.

Supports Cardiovascular and Circulatory Health

Centella asiatica is believed to strengthen blood vessels and promote better circulation. It may help relieve symptoms of varicose veins, swelling in the legs, and heaviness caused by poor venous return. By improving blood flow, it nourishes tissues and supports overall vascular health.

Supports Healthy Digestion

Mandukaparni is traditionally used to soothe and strengthen the digestive tract. It may reduce inflammation in the gut lining and improve digestion by calming excess heat and acidity. It’s also believed to promote better assimilation of nutrients and relieve minor digestive discomfort.

Promotes Longevity & Rejuvenation

In Ayurveda, Mandukaparni is regarded as a rasayana a substance that promotes longevity, vitality, and youthfulness. It is believed to rejuvenate tissues, slow down the aging process, and maintain balance in the body’s natural systems. Regular use is said to support energy levels, immunity, and overall well-being.

Improves Hair and Scalp Health

Applied externally or taken internally, Mandukaparni is beneficial for hair strength and scalp nourishment. It is traditionally used to reduce hair fall, promote hair growth, and combat dandruff. Its cooling nature helps soothe inflamed or itchy scalps, promoting a healthy hair environment.

Supports Joint Flexibility & Tissue Repair

The herb is believed to support flexibility and joint mobility. It helps nourish connective tissues, strengthen cartilage, and reduce stiffness, making it useful for people experiencing age-related wear and tear or joint discomfort.

How to Take Mandukaparni for Best Results

Form	Dosage	Usage
Capsules/Tablets	300–600 mg per day	With water after meals
Powder (Churna)	1–2 grams daily	Mix with warm water, honey, or ghee
Decoction (Kashayam)	30–50 ml	Once or twice daily
Tea	1–2 cups/day	Boil leaves for 10 minutes
Topical Creams	As directed	For wounds, scars, and skin rejuvenation

Note: Always consult your healthcare practitioner or Ayurvedic expert before starting any new herb, especially if you are pregnant, nursing, or taking medications.

Conclusion

Mandukaparni (Centella asiatica) stands as a timeless herbal treasure that gently nurtures the body, mind, and spirit. From sharpening memory to calming the nervous system, revitalizing the skin, supporting circulation, and rejuvenating the joints, its wide-reaching benefits are a testament to its revered status in Ayurveda as a medhya rasayana and rasayana a promoter of both intellect and longevity.

What gives Mandukaparni its unique healing potential is not just its traditional value, but also its rich phytochemical profile. It contains powerful bioactive compounds such as asiaticoside, madecassoside, asiatic acid, and madecassic acid. These triterpenoids are known to support tissue regeneration, enhance collagen synthesis, reduce inflammation, and promote neuroprotection at a cellular level. Additionally, the presence of flavonoids and saponins further enhances its antioxidant and adaptogenic properties.

In essence, Mandukaparni is more than a medicinal herb it is a holistic ally for modern wellness. Whether you’re seeking clarity of mind, youthful skin, restful sleep, or internal balance, this humble green leaf has something to offer.

References

Boju Sun, Lily Wu, You Wu et al, Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review, Front. Pharmacol, 04 September 2020 Sec. Ethnopharmacology Volume 11 – 2020 | https://doi.org/10.3389/fphar.2020.568032

Oluranti Mopelola Lawal, Fatima Wakel, Matthijs Dekker, Consumption of fresh Centella asiatica improves short term alertness and contentedness in healthy females, Journal of Functional Foods, Volume 77, 2021, 104337, https://doi.org/10.1016/j.jff.2020.104337.

Lokanathan Y, Omar N, Ahmad Puzi NN, Saim A, Hj Idrus R. Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica. Malays J Med Sci. 2016 Jan;23(1):4-14. PMID: 27540320; PMCID: PMC4975583.

Eduviere, A. T., Awhin, P. E., Edje, K. E., Otomewo, L. O., Adeoluwa, O. A., & Winter, J. E. (2021). Adaptogenic potential of Centella lujica supplement in sleep deprived mice. International Journal of Research in Medical Sciences, 9(11), 3269–3276. https://doi.org/10.18203/2320-6012.ijrms20214408

Jeevan Chandra, Himanshu Joshi, Pankaj Bahuguna, Anti-stress effect of Centella asiatica in rats, Sch. Acad. J. Biosci., 2015; 3(8):668-675, DOI : 10.36347/sajb.2015.v03i08.005

Gohil KJ, Patel JA, Gajjar AK. Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all. Indian J Pharm Sci. 2010 Sep;72(5):546-56. doi: 10.4103/0250-474X.78519. PMID: 21694984; PMCID: PMC3116297.

Health Benefits of Mandukaparni (Centella Asiatica), https://www.all-cures.com/cure/5451-Health-Benefits-of-Mandukaparni-(Centella-Asiatica)

Tan, S.C.; Bhattamisra, S.K.; Chellappan, D.K.; Candasamy, M. Actions and Therapeutic Potential of Madecassoside and Other Major Constituents of Centella asiatica: A Review. Appl. Sci. 2021, 11, 8475. https://doi.org/10.3390/app11188475

Razali NNM, Ng CT, Fong LY. Cardiovascular Protective Effects of Centella asiatica and Its Triterpenes: A Review. Planta Med. 2019 Nov;85(16):1203-1215. doi: 10.1055/a-1008-6138. Epub 2019 Sep 20. PMID: 31539918.

Dora Bhavna, Khatri Jyoti, Centella Asiatica: the elixir of life, International Journal of Research in Ayurveda & Pharmacy, 2(2), 2011 431-438

“Deadly Saline Killed 8: Neuromelioidosis Outbreak in Tamil Nadu Linked to Contaminated Dental Saline – What Went Wrong?”

June 9, 2025

by official.ajinkya11@gmail.com with No Comment Health Tidings

Written by: Dr. Arshada Fathin, PharmD (Coimbatore, Tamil Nadu)

Reviewed By: Dr. Seema Satbhai (BAMS, MPH, PhD, Public Health)

Neuromelioidosis, a central nervous system manifestation of melioidosis caused by Burkholderia pseudomallei, has emerged as a serious health concern in Vaniyambadi, Tirupattur district, Tamil Nadu, India. An unusual cluster of cases was identified between July 2022 and April 2023. Importantly, 10 out of 21 patients had undergone some dental procedure, most at the same dental clinic. Out of these 10 cases, 8 patients succumbed to death. This has raised critical questions regarding infection control practices in dental care settings. This article provides an overview of the outbreak, disease pathology, diagnostic considerations, and the role of procedural lapses in precipitating iatrogenic transmission.

Background of the Case

The outbreak of neuromelioidosis in Tamil Nadu centres on a cluster of 21 cases reported between July 2022 and April 2023. These included 11 sporadic infections and 10 distinct sub-cluster epidemiologically linked to a dental clinic in Vaniyambadi, Tirupattur district. The affected patients who visited the clinic presented with severe symptoms shortly after dental treatment.

About Neuromelioidosis

Neuromelioidosis results from infection of the central nervous system by Burkholderia pseudomallei, manifesting primarily as brainstem syndrome. Typical clinical features include facial pain, cranial nerve dysfunction, abscess formation, and necrotizing encephalitis. The infection often spreads along neuronal pathways, such as the trigeminal nerve, leading to rapid neurological decline. Adults within the age range of 26 to 44 years are predominantly affected in endemic regions. Diagnosis relies on isolation of the organism from blood, cerebrospinal fluid (CSF), or affected tissues through culture or polymerase chain reaction (PCR) assays. Molecular tools, including WGS and detection of virulence-associated genes such as bimA, aid in strain typing and epidemiological investigations. Management requires prompt initiation of intravenous antibiotics, commonly ceftazidime or meropenem, followed by prolonged oral eradication therapy, i.e., Co-Trimoxazole, for several months. Delay in recognition and treatment often results in poor clinical outcomes, sometimes death.

The Culprit: Burkholderia pseudomallei

This bacterium typically inhabits soil and water, but in this outbreak, it entered patients directly along nerve pathways by contact with mucous membranes in the mouth during dental treatments. This neurological route led to rapid brain infections rather than the more typical bloodstream spread.

Case Description and Microbiological Findings

The outbreak involved 21 patients with neuromelioidosis in Tamil Nadu, with a median age of 33 years, affecting both males and females. Clinical presentations include facial cellulitis, lymphadenopathy, brainstem involvement, and rapid neurological decline. Among the 10 patients with documented dental procedure exposure, 8 succumbed to the illness within a median period of 17 days post-exposure, indicating a higher fatality rate compared to sporadic cases. The high fatality of the outbreak is indicative of an iatrogenic source of infection. A high-level, authoritative investigation was warranted on an immediate basis.

Investigation by Researchers

It all started when a married couple presented at CMC Vellore with acute-onset fever followed by symptoms of brainstem syndrome. Radiological imaging revealed necrotizing brainstem encephalitis, a finding consistent with neuromelioidosis. The relative reported that both patients had undergone a dental procedure at the dental clinic in Vaniyambadi shortly before illness.

A highly authoritative investigation was carried out which led by researchers from CMC Vellore, ICMR-National Institute of Epidemiology, Chennai, and the Tamil Nadu Directorate of Public Health and Preventive Medicine. The primary objective of the investigation was to understand how the infection spread and confirm whether the source was iatrogenic. The outbreak investigation utilized clinical evaluation, microbiological cultures, environmental sampling and whole-genome sequencing (WGS) of bacterial strain to establish the transmission dynamics and identify the source of infection. The initial investigation pointed to the cases from Tirupattur district experiencing an outbreak after undergoing invasive dental procedures at a local dental clinic and suggested possible contamination during dental procedures.

Identified Deviations in Infection Control – Medication Error and Sterility Breach

Based on an interview with the dentist and investigation findings, the dental clinic involved in the outbreak provided a wide range of services, including fixation of partial dentures, full-mouth prophylaxis, root canal treatments, and tooth extraction. The clinic was staffed by a dentist, nursing personnel, and a receptionist; however, none of the staff had formal training in hospital infection control practices.

Normal saline was supplied in sterile 500 mL plastic bottles and used both for wound irrigation during surgical procedures and for dilution of local anesthetic for infiltration. It was observed that the sterile saline bottles were opened using a non-sterile periosteal elevator. These bottles were then loosely resealed and reused over several days until empty. There was no proper sterilization of equipment between patients.

Such practices deviated significantly from established infection control standards. The repeated use of opened saline bottles without proper aseptic technique, combined with the use of non-sterile instruments to open them, increased the risk of contamination. Indeed, an increase in failed dental procedures and complications was reported concurrent with the emergence of neuromelioidosis cases in the district.

Microbiological analysis supported these findings, as Burkholderia pseudomallei was isolated from one of the in-use saline bottles collected during environmental sampling at the clinic. These breaches in sterile technique and medication handling directly contributed to the iatrogenic transmission of the pathogen to patients during dental procedures.

Recommended Preventive Measures

Based on the outbreak findings, several corrective measures are essential to prevent similar incidents in the future:

Strict use of sterile supplies: Single-use sterile saline bottles should be opened aseptically and discarded after one use. The reuse of opened bottles must be avoided.

Adherence to aseptic technique: All dental procedures must be performed under sterile conditions, employing sterilized instruments and protective barriers such as sterile gloves.

Comprehensive staff training: Dental clinic personnel should receive ongoing training in infection prevention and control protocols, emphasizing proper handling of sterile supplies.

Environmental monitoring: Routine microbial testing of dental unit water lines and fluids should be conducted, particularly in regions endemic for B. pseudomallei.

Immediate investigation of infection clusters: Any unusual increase in post-procedural infections must prompt epidemiological investigation and suspension of implicated materials or practices.

Implementing these measures will reduce the risk of iatrogenic infection and ensure patient safety during dental procedures.

Conclusion: A Wake-Up Call for Infection Control in Outpatient Care

The tragic Neuromelioidosis outbreak in Tamil Nadu is more than just a public health incident. It is a warning about how single lapse in clinical hygiene, such as reusing a contaminated saline bottle, can escalate into a fatal outbreak of a rare and deadly infection. While melioidosis is typically associated with environmental exposure in endemic regions, this event underscores an alarming reality: modern medical settings are not immune to such threats when basic infection control protocols are neglected.

The Vaniyambadi dental clinic case highlights critical vulnerabilities in outpatient care, particularly in resource-limited settings where practices like reusing consumables or improper instrument handling may still occur. In this instance, the use of an unsterile periosteal elevator to repeatedly open a saline bottle facilitated the direct introduction of Burkholderia pseudomallei, a soil-dwelling microorganism, into the oral mucosa, bypassing traditional routes of transmission. The result was an outbreak of neuromelioidosis, a rare neurological manifestation with devastating consequences, including an 80% fatality rate among exposed patients.

The rapid identification of the outbreak source, coordinated by CMC Vellore, ICMR-NIE Chennai, and state health authorities, demonstrates the importance of multisectoral collaboration in outbreak investigation.

For healthcare systems across India and globally, this event serves as a wake-up call. It emphasizes the urgent need to:

Reinforce standard infection prevention protocols in dental and outpatient clinics

Mandate the single-use of consumables like saline bottles

Educate practitioners on rare but deadly infections like melioidosis

Improve clinical waste management and sterilization practices

Establish local microbiology networks for early pathogen detection

Ultimately, this outbreak is an earnest reminder that patient safety must never be compromised for convenience. The lives lost in Vaniyambadi are a tragic testament to what can go wrong, but also a call to action, urging the healthcare community to uphold the highest standards of hygiene, vigilance, and accountability.

This investigation and findings are published in the Lancet Regional Health – Southeast Asia

References

Angel Miraclin Thirugnanakumar, Prabu Rajkumar, Karthik Gunasekaran et al, Neuromelioidosis outbreak in Tamil Nadu, India: an investigation of transmission with genomic insights, The Lancet Regional Health – Southeast Asia 2025;37: 100602, https://doi.org/10.1016/j.lansea.2025.100602

Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med. 2012; 367(11):1035-44. Doi:10.1056/NEJMra1204699.

Kohn WG, Collins AS, Cleveland JL, Harte JA, Eklund KJ, Malvitz DM. Guidelines for infection control in dental health-care settings—2003. MMWR Recomm Rep. 2003;52(RR-17):1-61.

Meumann EM, Currie BJ. Approach to melioidosis. CMI Communications. 2024 Jun 6;100008.

White NJ. Melioidosis, Lancet, 2003 May 17;361(9370):1715-22

Chatterjee A, Saravu K, Mukhopadhyay C, Chandran V. Neurological melioidosis presenting as rhombencephalitis, optic neuritis, and scalp abscess with meningitis: a case series from Southern India. Neurol India. 2021 Mar-Apr;69(2):480-2. doi:10.4103/0028-3886.314590.

Wiersinga WJ, van der Poll T, White NJ, Day NP, Peacock SJ. Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei. Nat Rev Microbiol. 2006 Apr;4(4):272-82. doi:10.1038/nrmicro1385.

Enhancing Drug Safety: The Vital Role of Real-World Data (RWD) and Real-World Evidence (RWE) in Modern Pharmacovigilance

June 6, 2025

by official.ajinkya11@gmail.com with No Comment Health Tidings

Written By: Shital Doifode, M.Pharm Pharmacology

Reviewed and Fact-Checked By: Ashish Jaydeokar (Manager, Pharmacovigilance Operations, Germany)

Pharmacovigilance is the field of detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The field has undergone many evolutions in the 21st century, with the integration of artificial intelligence in recent times. Conventionally, it depends on randomized controlled trials (RCTs) and spontaneous adverse event reporting systems. However, these methods now fall short in capturing the complete safety profile of a drug, particularly in real-world use across diverse patient populations and disease profiles. This limitation has facilitated the integration of real-world data (RWD) and real-world evidence (RWE), active tools that offer a more inclusive, proactive approach to safety surveillance. By leveraging data from electronic health records, insurance claims, patient registries, digital health tools, and other routine clinical sources, pharmacovigilance systems can now monitor drug safety and effectiveness in real time throughout the entire life cycle of a pharmaceutical product. This shift will not only enhance signal detection and risk assessment but also support more informed regulatory and clinical decision-making in everyday healthcare practice.

What Are RWD and RWE?

Real-World Data (RWD): It refers to data related to patient health status collected from sources such as electronic health records (EHRs), insurance claims, patient registries, and even digital health tools like mobile health apps and also from social media.

Real-World Evidence (RWE) covers the clinical insights and evidence about the usage and potential safety and risk of medical products that are derived from the analysis of Real-World Data (RWD).

This change is crucial, as clinical trials during the establishment of efficacy and safety often involve highly selected populations and controlled environments, limiting their applicability to broader patient groups.

In contrast, RWD/RWE allows for the continuous and proactive assessment of medications across diverse populations, capturing long-term safety outcomes, rare adverse events, and drug performance in real-world scenarios.

Why RWD and RWE Matter in Pharmacovigilance

Clinical trials are conducted in controlled environments with carefully selected participants, generally excluding elderly patients, pregnant women, and those with multiple comorbidities. RWD and RWE help to fill these gaps by showing how drugs behave in the real world, including in these excluded populations. RWE helps to eliminate the potential bias caused in CTs. Biases are often described in 3 categories:

Selection bias, which derives from including or selectively following subsets of the population in the study in a way that distorts the relation between the exposure and the outcome.
Information bias, which derives from measurement errors.
Confounding bias: this derives from noncomparability of the intervention groups in the study (27 in ->11).

Early Detection of Adverse Drug Reactions (ADRs)

By continuously analyzing data from large and diverse patient populations, pharmacovigilance teams are able to detect rare, serious, or delayed adverse drug reactions much earlier; that would not be possible through traditional clinical trial methods alone. Traditional trials are typically limited in size, duration, and participant diversity, which can make it difficult to identify side effects that only occur infrequently or in specific subgroups. In contrast, real-world data sources such as electronic health records, insurance claims, patient registries, and post-marketing surveillance reports allow pharmacovigilance experts to monitor the safety of medications across millions of users in real time.

Improved Signal Detection and Risk Management

Real-World Evidence (RWE) enables more accurate signal detection by providing an all-inclusive view of how drugs perform across diverse, real-life patient populations. The broader dataset of RWE allows researchers and regulators to correlate adverse drug events (ADEs) not just with the drug itself, but with specific patient characteristics such as age, gender, genetic factors, or underlying co-morbidities like diabetes, hypertension, or renal impairment. RWE is generated according to a research plan and interpreted accordingly.

Furthermore, RWE supports the identification of risks associated with concurrent therapies. Many patients are on multiple medications simultaneously (polypharmacy), which can lead to drug-drug interactions that are difficult to study in traditional trials. RWE can detect patterns where certain drug combinations are consistently associated with adverse outcomes, enabling more precise risk stratification.

By uncovering these population-specific safety signals, RWE enhances pharmacovigilance efforts and allows healthcare providers and regulatory agencies to implement targeted risk management strategies.

RWE allows for more accurate signal detection by correlating adverse events with specific patient populations, comorbid conditions, or concurrent therapies. This enhances the ability to manage risks in a targeted manner.

Regulatory Decision Support

Health authorities like the FDA and EMA increasingly rely on RWE to support regulatory decisions, such as label updates, post-marketing requirements, and even new indications for existing drugs.

First-ever regulatory approval of label expansion of IBRANCE (palbociclib) for male breast cancer based on RWE, have brought in a new era in the applicability of RWE in healthcare.

Overseen by the Big Data Steering Group (BDSG), EMA and the European Medicines Regulatory Network (EMRN) are working to establish a sustainable framework to enable the use and establish the value of real-world evidence (RWE) across different regulatory use cases.

Approvals where RWE was considered:

A total of 30 FDA approvals were identified (EMA: 16).
The number of approvals is steadily increasing.
The approvals of new drugs only concern orphan drugs at both FDA and EMA; i.e. drugs against rare diseases.

Supporting Patient-Centred Outcomes

Real-World Data (RWD) captures the patient experience in a more holistic and meaningful way, as compare to traditional clinical trials. While randomized controlled trials (RCTs) focus primarily on efficacy under ideal conditions, RWD reflects how treatments perform in everyday clinical settings, where patients may have diverse backgrounds, health conditions, and behaviours.

One of the key advantages of RWD is its ability to provide insights into treatment adherence, how consistently patients follow prescribed therapies. Non-adherence is a major factor affecting treatment outcomes and safety, yet it’s often underreported in clinical trials. RWD can identify adherence patterns, uncover barriers (e.g., side effects, cost, complex regimens), and inform interventions to improve long-term medication use.

FDA recognizes the potential utility of using RWD in interventional studies; for example, to identify potential participants for a randomized controlled trial, to ascertain endpoints or outcomes (e.g., occurrence of stroke or other discrete events, hospitalization, survival) in a randomized controlled trial, or to serve as a comparator arm in an externally controlled trial, including historically controlled trials

Real-World Applications of RWD and RWE in Pharmacovigilance

Post-Marketing Surveillance: After a pharmaceutical product is approved and enters the market, continuous monitoring is essential to ensure its long-term safety and effectiveness. Companies now increasingly rely on electronic health records (EHRs) and insurance claims data to conduct this post-marketing surveillance. These real-world data sources enable the identification of safety trends, rare adverse events, and patterns of use that may not have emerged during clinical trials.

EHRs provide detailed clinical information, such as lab results, diagnoses, and physician notes, while claims data offer insights into medication usage, healthcare utilization, and treatment costs across large patient populations.

Risk Evaluation and Mitigation Strategies (REMS): Real-world evidence (RWE) plays a crucial role in both the design and assessment of REMS programs, which are mandated by regulatory agencies like the FDA to ensure that the benefits of certain high-risk medications outweigh their potential risks.

Adaptive Pharmacovigilance Systems: Advances in artificial intelligence (AI) and machine learning (ML), when applied to real-world data (RWD) such as electronic health records, claims databases, and patient-reported outcomes, are transforming traditional pharmacovigilance into a more dynamic, automated, and predictive system.

These technologies enable the development of adaptive pharmacovigilance systems, which can continuously analyze large and complex datasets to automatically detect safety signals such as unusual patterns of adverse events, drug interactions, or shifts in usage trends. Unlike traditional, passive reporting systems, these AI-driven tools can flag potential risks in near real-time, improving both the speed and sensitivity of signal detection.

Tools and Technologies Powering RWD and RWE

1. Electronic Health Records (EHR) Systems

EHRs are one of the primary sources of RWD. Tools like Allscripts collect detailed patient-level clinical information, including diagnoses, treatments, lab results, and adverse events. Integration of EHR data into pharmacovigilance platforms helps identify safety signals in near real-time.

2. Claims and Billing Databases

Administrative claims databases such as Optum offer large-scale, longitudinal patient information. These are particularly useful for tracking healthcare utilization, medication adherence, and long-term safety outcomes.

3. Patient Registries

Disease-specific and product-specific registries collect structured data over time from patients with defined characteristics. Tools like OpenClinica are commonly used to manage registry data. Registries help monitor rare adverse events and long-term safety in real-world populations.

4. Mobile Health (mHealth) and Wearables

Apps and devices like Fitbit, Apple Watch, and mobile symptom trackers generate real-time data on patient activity, heart rate, medication intake, and other health metrics. This type of continuous monitoring offers valuable insights into drug effects outside clinical settings.

5. Natural Language Processing (NLP) Tools

NLP tools can extract relevant information from unstructured data such as clinical notes, discharge summaries, and patient forums. Examples include Amazon Comprehend Medical NLP pipelines, which can help identify adverse drug reactions from text sources.

6. Artificial Intelligence and Machine Learning Platforms

AI-powered platforms like SAS, IBM Watson Health, and Google Cloud AI are used to detect patterns in large datasets, support predictive analytics, and improve the accuracy of signal detection. Machine learning algorithms can also classify and prioritize adverse events based on severity and novelty.

7. Data Integration and Analytics Platforms

Platforms like OMOP (Observational Medical Outcomes Partnership) and the Sentinel initiative by the FDA standardize and harmonize data from multiple sources. These tools enable scalable and reproducible analysis of RWD to support RWE generation.

8. Social Listening and Digital Epidemiology Tools

Mining social media and online patient communities through platforms like Brandwatch or MedWatcher Social can reveal emerging drug safety concerns from patients themselves, often before they are formally reported.

Conclusion

The integration of real-world data and real-world evidence into pharmacovigilance marks a more inclusive and responsive drug safety system. By bridging the gap between controlled clinical environments and the complexity of everyday healthcare, RWD and RWE enable a more nuanced, proactive, and patient-centric approach to monitoring drug safety. As regulatory frameworks and technological tools continue to evolve, their role in modern pharmacovigilance will only become more beneficial.

References

FDA (2018), Framework for FDA’s Real-World Evidence Program, U.S. Food and Drug Administration, https://www.fda.gov/media/120060/download

Makady, A., de Boer, A., Hillege, H., Klungel, O., & Goettsch, W. (2017). What is real-world data? A review of definitions based on literature and stakeholder interviews. Value in Health, 20(7), 858–865. https://doi.org/10.1016/j.jval.2017.03.008

Ghosh R, et al. (2022). Pharmacovigilance: A Review on Current Strategies and Future Directions. Therapeutic Advances in Drug Safety, 13, 20420986221093745

Vandenbroucke JP. (2008), Observational research, randomised trials, and two views of medical science, PLoS Medicine, 5(3), e67

Sherman RE, et al. (2016), Real-world evidence — what is it and what can it tell us? New England Journal of Medicine, 375(23), 2293–2297.

U.S. FDA, (2018), Framework for FDA’s Real-World Evidence Program, https://www.fda.gov/media/120060/download

European Medicines Agency (2021), EMA Regulatory Science to 2025 — Strategic Reflection, https://www.ema.europa.eu/en/documents/report/ema-regulatory-science-2025-strategic-reflection_en.pdf

Botsis T, et al. (2010). Secondary use of EHR: data quality issues and informatics opportunities. Summit on Translational Bioinformatics, 2010, 1–5.

Platt R, et al. (2018). The U.S. FDA’s Sentinel Initiative — A Comprehensive Approach to Medical Product Surveillance. Clinical Pharmacology & Therapeutics, 103(3), 219–222.

Hripcsak G, et al. (2015). Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers. Studies in Health Technology and Informatics, 216, 574–578.

FDA, (2018). Framework for FDA’s Real-World Evidence Program https://www.fda.gov/media/120060/download

EMA. (2022). Data Analysis and Real World Interrogation Network (DARWIN EU). https://www.ema.europa.eu/en/darwin-eu

Franklin JM, et al. (2021). Real-world evidence for regulatory decision-making: Challenges and opportunities. Clinical Pharmacology & Therapeutics, 109(4), 816–829.

Kakkar AK, et al. (2021). Direct oral anticoagulants: real-world evidence and clinical utility. Therapeutic Advances in Cardiovascular Disease, 15, 1753944720981525.

Schneeweiss S. (2019). Real-world evidence of treatment effects: the useful and the misleading. Clinical Pharmacology & Therapeutics, 106(1), 43–44.

Corrigan-Curay J, et al. (2018). Real-world evidence and real-world data for evaluating drug safety and effectiveness, JAMA, 320(9), 867–868.

Duke-Margolis Center for Health Policy. (2017). A Framework for Regulatory Use of Real-World Evidence. https://healthpolicy.duke.edu/sites/default/files/2020-11/rwe_white_paper_2017.09.13.pdf

Wedam S, Fashoyin-Aje L, Bloomquist E et al (2020) FDA approval summary: palbociclib for male patients with metastatic breast cancer. Clin Cancer Res 26(6):1208–1212. https://doi.org/10.1158/1078-0432.CCR-19-2580

FDA: Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products Guidance for Industry, U.S. Department of Health and Human Services Food and Drug Administration, August 2023

Marc L. Berger, Harold Sox, Richard J. Willke, et al, (2017), Good practices for real world data studies of treatment and/or comparative effectiveness: Recommendations from the joint ISPOR ISPE Special Task Force on real‐world evidence in health care decision making, Pharmacoepidemiol Drug Saf. 2017; 26:1033–1039, DOI:10.1002/pds.4297

EMA: Real-world evidence framework to support EU regulatory decision-making EMA/289699/2023), https://www.ema.europa.eu/en/documents/report/real-world-evidence-framework-support-eu-regulatory-decision-making-report-experience-gained-regulator-led-studies-september-2021-february-2023_en.pdf

All posts by : official.ajinkya11@gmail.com

After Second Liver Failure Death, Sarepta Therapeutics Halts Global Elevidys Dosing in Non-Ambulatory Duchenne Muscular Dystrophy Patients; Phase III ENVISION Trial Impacted

The Essence of Panchakarma: The Fivefold Path to Healing and Inner Balance

“UK’s Martha’s Rule: A Mother’s Fight That Sparked a National Reform and a Global Wake-Up Call on Patient Safety”

Stay Healthy This Monsoon: Ayurvedic Lifestyle Tips for Varsha Ritu

Moderna Launches mNEXSPIKE: New FDA-Approved COVID Vaccine for High-Risk Groups

The Hidden Pain Pathway: Paracetamol (Acetaminophen) Metabolite AM404 Blocks Peripheral Sodium Channels – A New Mechanism Uncovered

Wrong Blood, Lost Life: How a Blood Transfusion Error at SMS Hospital, Rajasthan Sparked a State-wide Medical Reckoning

Pharmacally’s Take: Reform Begins with Acknowledging the Risk

Mandukaparni (Centella asiatica): The Ayurvedic Herb That Rewires Your Brain & Rejuvenates Your Body

“Deadly Saline Killed 8: Neuromelioidosis Outbreak in Tamil Nadu Linked to Contaminated Dental Saline – What Went Wrong?”

Enhancing Drug Safety: The Vital Role of Real-World Data (RWD) and Real-World Evidence (RWE) in Modern Pharmacovigilance

Recent Posts

Recent Comments

Archives

Categories

Pharmacally a brand of

MedCognize Communications (OPC) Pvt. Ltd.

Gat No. 405, Plot No. 17, Post-Nighoje, Near Faith Automation,

Opp. Anjali T Precision, Chakan Industrial Area, Pune 410501

Maharashtra, India

Contact No. - +91 9960598036

Email - contactus@pharmacally.com

Follow Us -

Subscribe to Newsletter -

Follow Us -