Year: 2024
Visiting hours of DRAP
Expressions of Interest (EOI) for pool of expert members of central licensing board of DRAP
Drug Safety Alert: Risk of Posterior Reversible Encephalopathy Syndrome (PRES) and Reversible Cerebral Vasoconstriction Syndrome (RCVS) with Pseudoephedrine Containing Medicines.
Drug Safety Alert
Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan
| Date: | 27th of April, 2024 |
| Target Audience: | · Manufacturers and importers of pseudoephedrine-containing medicines; · Healthcare Professionals; and · Patients, Consumers or Caregivers. |
| Background: | The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicine Agency (EMA) in its meeting held on 27-30th November 2023 recommended new measures for medicines containing pseudoephedrine to minimize the risks of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) and informed that product information for all pseudoephedrine-containing medicines will be updated to include the risks. The recommendations follow a review of all available evidence, including post-marketing safety data, which concluded that pseudoephedrine is associated with risks of PRES and RCVS. During the review, PRAC sought advice from an expert group of general practitioners, otorhinolaryngologists (specialists in diseases of the ear, nose, throat, head and neck), allergologists (specialists in the treatment of allergies) and a patient representative. PRAC also considered information submitted by a third party representing healthcare professionals. It was recommended that medicines containing pseudoephedrine are not to be used in patients with high blood pressure that is severe or uncontrolled (not being treated or resistant to treatment), or with severe acute (sudden) or chronic (long-term) kidney disease or failure. In addition, as part of its advice on safety-related aspects to other EMA committees, the PRAC discussed a direct healthcare professional communication (DHPC) with important information on pseudoephedrine-containing products which was also forwarded to EMA’s human medicines committee (CHMP). RES and RCVS are rare conditions that can involve reduced blood supply to the brain, potentially causing serious, life-threatening complications. With prompt diagnosis and treatment, symptoms of PRES and RCVS usually resolve. Healthcare professionals should advise patients to stop using these medicines immediately and seek treatment if they develop symptoms of PRES or RCVS, such as severe headache with a sudden onset, feeling sick, vomiting, confusion, seizures and visual disturbances. On 25 January 2024, EMA’s Committee for Medicinal Products for Human Use (CHMP) endorsed the measures recommended by the PRAC to minimise the risks of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) for medicines containing pseudoephedrine. CHMP confirmed that medicines containing pseudoephedrine are not to be used in patients with high blood pressure that is severe or uncontrolled (not being treated or resistant to treatment) or in patients with severe acute (sudden) or chronic (long-term) kidney disease or failure. The CHMP opinion has been sent to the European Commission, which will issue a legally binding decision across the EU. |
| Therapeutic Good(s) Affected: | Pseudoephedrine is a stimulant that is often used as a decongestant in people who have a cold or allergies. |
| Action in Pakistan | The case was discussed in the 4th meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the DRAP held on 26th of February, 2024 which decided the case as per Rule 10 (1) (h) (iv) of the Pharmacovigilance Rules, 2022 that registration holders should update the warning and precaution section of the prescribing information/label of pseudoephedrine-containing medicines by including information about the risks of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) along with advise that medicines containing pseudoephedrine are not to be used in patients with high blood pressure that is severe or uncontrolled (not being treated or resistant to treatment), or with severe acute (sudden) or chronic (long-term) kidney disease or failure. Similarly, as per Rules 10 (1) (h) (vi) registration holders were advised to issue direct healthcare professionals communication by highlighting the risk. |
| Advice for healthcare professionals: | Healthcare professionals are informed that a review has found that pseudoephedrine-containing medicines are associated with risks of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), a serious condition affecting the cerebral blood vessels. This follows an evaluation of all available data including a few reported cases of these conditions. There were no fatal cases of PRES or RCVS reported internationally, and most of the cases were resolved following discontinuation of the medicine and appropriate treatment. Healthcare professionals are advised that pseudoephedrine-containing medicines must not be used in patients with severe or uncontrolled hypertension or severe acute or chronic kidney disease or renal failure, as these are risk factors for developing PRES or RCVS. Patients should be advised to discontinue treatment and seek immediate medical assistance if they develop symptoms of PRES or RCVS such as sudden, severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. The risks of PRES and RCVS should be considered alongside other risks associated with pseudoephedrine-containing medicines, including cardiovascular or ischaemic events. |
| Advice for patients: | Patients are advised not to take pseudoephedrine-containing medicines if they have high blood pressure that is severe or uncontrolled (not being treated or resistant to treatment) or if they have severe acute (sudden) or chronic (long-term) kidney disease or failure, as these are risk factors for developing PRES or RCVS. Patients are also advised to stop using pseudoephedrine-containing medicines immediately and seek urgent medical assistance if they develop symptoms of PRES or RCVS such as a severe headache with a sudden onset, feeling sick, vomiting, confusion, seizures and changes in vision. |
| Guidelines for reporting Adverse Drug Reactions (ADRs): | Both healthcare professionals and patients are requested to report any suspected Adverse Drug Reaction (ADR) to National Pharmacovigilance Centre, Drug Regulatory Authority of Pakistan through Med Vigilance E-Reporting system available on DRAP website. Similarly, ADRs can also be reported through MedSafety App that is available for download from App store (for iOS devices) and Google Play (for Android devices). |
| References: | · Minutes of the 4th meeting of the Pharmacovigilance Risk Assessment Expert Committee. · Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 27-30 November 2023. · Pseudoephedrine-containing medicinal products – referral, EMA. |
Drug Safety Alert: Risk of Haemophagocytic Lymphohistiocytosis (HLH) with Sulfamethoxazole and Trimethoprim combination.
Drug Safety Alert
Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan
| Date: | 27th of April, 2024 |
| Target Audience: | · Manufacturers and importers of Sulfamethoxazole and Trimethoprim combination; · Healthcare Professionals; and · Patients, Consumers or Caregivers. |
| Background: | Health Canada in May 2023 announced that the product safety information for combination sulfamethoxazole and trimethoprim-containing products will be updated to include the risk of haemophagocytic lymphohistiocytosis (HLH). Triggered by a labelling update for these products by the EMA, Health Canada reviewed the available information from the Canadian and international databases, and the scientific literature. Of the ten cases assessed, one case was found to be probably linked to the use of the medicine, eight were found to be possibly linked (including one fatal case) and one (another fatal case) was unlikely to be linked. The review found a possible link between the use of the medicine and the risk of HLH. HLH is a life-threatening syndrome of pathologic immune activation characterised by clinical signs and symptoms of extreme systemic inflammation (e.g. fever, hepatosplenomegaly, hypertriglyceridaemia, hypofibrinogenaemia, high serum ferritin, cytopenias and haemophagocytosis) and is associated with high mortality rates if not recognised early and treated. Healthcare professionals were advised to immediately evaluate patients who develop early manifestations of pathologic immune activation. If HLH is diagnosed, discontinue sulfamethoxazole-trimethoprim treatment. Previously, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicine Agency in its meeting from 03-06 May 2021 considered the available evidence in EudraVigilance, the literature, and the data submitted by Roche/ Eumedica, Aspen Pharma and Teva regarding the risk of Haemophagocytic lymphohistiocytosis (HLH) with sulfamethoxazole/trimethoprim in combination and agreed that the available information is considered sufficient to support a warning statement in the product information of the drug combination. |
| Therapeutic Good(s) Affected: | Sulfamethoxazole plus Trimethoprim is a prescription antibiotic medicine indicated for the treatment of various bacterial infections, such as urinary tract infections, respiratory tract infections, and gastrointestinal infections. |
| Action in Pakistan | The case was discussed in the 4th meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the DRAP held on 26th of February, 2024 which decided the case as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 to update the warning and precaution section of the prescribing information/label of the drug combination of sulfamethoxazole and trimethoprim by including information about the risk of haemophagocytic lymphohistiocytosis (HLH). |
| Advice for healthcare professionals: | Healthcare professionals are informed that cases of HLH have been reported very rarely in patients treated with co-trimoxazole (Sulfamethoxazole+Trimethoprim). HLH is a life-threatening syndrome of pathologic immune activation characterised by clinical signs and symptoms of excessive systemic inflammation (e.g. fever, hepatosplenomegaly, hypertriglyceridaemia, hypofibrinogenaemia, high serum ferritin, cytopenias and haemophagocytosis). Patients who develop early manifestations of pathologic immune activation should be evaluated immediately. If a diagnosis of HLH is established, cotrimoxazole treatment should be discontinued. |
| Advice for patients: | Patients are informed not to stop the medication without the advice of their healthcare professional and to immediately consult their healthcare professional if they experience any symptoms of HLH during treatment with sulfamethoxazole+trimethoprim. |
| Guidelines for reporting Adverse Drug Reactions (ADRs): | Both healthcare professionals and patients are requested to report any suspected Adverse Drug Reaction (ADR) to National Pharmacovigilance Centre, Drug Regulatory Authority of Pakistan through Med Vigilance E-Reporting system available on DRAP website. Similarly, ADRs can also be reported through MedSafety App that is available for download from App store (for iOS devices) and Google Play (for Android devices). |
| References: | · Minutes of the 4th meeting of the Pharmacovigilance Risk Assessment Expert Committee. · Summary Safety Review – Combination Sulfamethoxazole and Trimethoprim – Assessing the Potential Risk of Hemophagocytic Lymphohistiocytosis. Health Canada. · EMA-PRAC recommendations on signals adopted on the 3-6th May 2021 meeting. |
Drug Safety Alert: Risk of Myasthenia Gravis and Ocular Myasthenia with Statins.
Drug Safety Alert
Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan
| Date: | 27th of April, 2024 |
| Target Audience: | · Manufacturers and Importers of statins; · Healthcare Professionals; and · Patients, Consumers or Caregivers. |
| Background: | The Pharmacovigilance Risk Assessment Committee (PRAC) of EMA in February, 2023 has recommended a change to the product information for statins to include potential risks of myasthenia gravis and ocular myasthenia. In a few cases, statins have been reported to induce de novo or aggravate pre-existing myasthenia gravis or ocular myasthenia. Treatment with statins should be discontinued in case of aggravation of symptoms. Recurrences when the same or a different statin was (re-) administered have been reported. The MHRA-UK in September 2023 informed the healthcare professional and patient about the European’s review recommendation related to new warnings on the risk of new-onset or aggravation of pre-existing myasthenia gravis with multiple statins. The findings of the European review were considered by the Pharmacovigilance Expert Advisory Committee (PEAG) of the Commission on Human Medicines (CHM), which agreed with the recommendations. It was informed that the product information of all statins is being updated to list myasthenia gravis and ocular myasthenia gravis as adverse drug reactions with a frequency ‘not known’. New warnings will also be added to the Summaries of Product Characteristics and Patient Information Leaflets. |
| Therapeutic Good(s) Affected: | Statins are HMG-CoA reductase inhibitors and include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Statins are an acceptably safe and effective group of medicines that help lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Statins play an important role in the treatment of atherosclerotic cardiovascular disease. |
| Action in Pakistan | The case was discussed in the 4th meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the DRAP held on 26th of February, 2024 which decided the case as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022, that registration holders of statins (HMG-CoA reductase inhibitors) should update the warning and precaution section about the risk of myasthenia gravis and ocular myasthenia gravis and list as adverse drug reactions with a frequency ‘not known’ in the adverse drug reaction section. |
| Advice for healthcare professionals: | Healthcare professionals are advised to refer patients presenting with suspected new-onset myasthenia gravis after starting statin therapy to a neurology specialist – it could be necessary to discontinue statin treatment depending on the assessment of the individual benefits and risks. Likewise, healthcare professionals should advise patients with pre-existing myasthenia gravis to be alert to the aggravation of symptoms while taking a statin. |
| Advice for patients: | Patients are informed that many people who take statins do not experience side effects and, where this does happen, these are typically mild – but it is important to read the Patient Information Leaflet that comes with their medicine and talk to a healthcare professional if they are experiencing problems. Patients are also advised not to stop their statin treatment without first discussing this with their doctor. Before taking a statin, inform your doctor if you have a history of myasthenia gravis or ocular myasthenia. Talk to your doctor if you experience weakness in your arms or legs that worsens after periods of activity, double vision or drooping of your eyelids, difficulty swallowing, or shortness of breath. Seek medical help immediately if you develop severe breathing or swallowing problems. |
| Guidelines for reporting Adverse Drug Reactions (ADRs): | Both healthcare professionals and patients are requested to report any suspected Adverse Drug Reaction (ADR) to National Pharmacovigilance Centre, Drug Regulatory Authority of Pakistan through Med Vigilance E-Reporting system available on DRAP website. Similarly, ADRs can also be reported through MedSafety App that is available for download from App store (for iOS devices) and Google Play (for Android devices). |
| References: | · Minutes of the 4th meeting of the Pharmacovigilance Risk Assessment Expert Committee. · Statins: very infrequent reports of myasthenia gravis report of MHRA-UK. · Product Information safety updates – October 2023 of TGA- Australia. |
Schedule of Meetings of Clinical Studies Committee (CSC) for the Year 2024
The Clinical Studies Committee (CSC) of Drug Regulatory Authority of Pakistan (DRAP) is mandated under Bio Study Rules 2017 for the regulatory oversight of clinical trials and clinical studies related to therapeutic goods in the country. The CSC reviews and approves clinical study protocols, ensuring they adhere to ethical and scientific standards. It also monitors ongoing clinical trials to assess participant safety and efficacy, makes informed decisions regarding study design, and collaborates with researchers, sponsors, and other stakeholders to ensure quality clinical research and safety of the participants.
The Committee has decided that the CSC meetings will be convened after every 45 days and an annual CSC meeting schedule for 2024 (tentative) has been issued with the aims to enhance transparency, efficiency, and collaboration.
| S. No. | CSC Meeting | Proposed Dates |
| 01 | 49th CSC Meeting | 2nd week of May, 2024 |
| 02 | 50th CSC Meeting | 4th week of June, 2024 |
| 03 | 51st CSC Meeting | 2nd week of August, 2024 |
| 04 | 52nd CSC Meeting | 4th week of September, 2024 |
| 05 | 53rd CSC Meeting | 2nd week of November 2024 |
| 06 | 54th CSC Meeting | 4th week of December, 2024 |
Change in Manufacturing Unit of M/s Sois Life Sciences to Site at G-77. S.I.T.E. Super Highway, Phase-II, Karachi.
The Enlistment Evaluation Committee (EEC) in 120th meeting has considered the request of M/s Sois Life Sciences for change in manufacturing facility for their products from A-84, SITE, Super Highway, Phase-I, Karachi to their manufacturing site situated at G-77, S.I.T.E, Super Highway, Phase-II, Karachi. The EEC acceded the request of the firm and revoked the Enlistment Certificate No 01304.
Henceforth, all the product of M/s Sios Sois Life Sciences will be manufactured G-77, S.I.T.E, Super Highway, Phase-II, Karachi viz-a-viz Enlistment No. 0090. Therefore, manufacturing of Alternative medicines and health products by M/s Sois Life Sciences at A-84, S.I.T.E, Super Highway, Phase-I is prohibited and punishable offence under Rule 11 of the SRO 412 (I) /2014 read with Schedule II and III of the DRAP Act, 2012. Accordingly Notifications have been issued for strict compliance.
Minutes of 296th Meeting of Central Licensing Board held on 2nd April, 2024
Recall Alert; Drug Products: Mebzole 100mg/5mL Suspension and Bioris 1mg/ml Oral Solution by M/s Biolabs Pvt., Ltd., Islamabad
Recall Alert
| DRAP Alert No | No I/S/04-24-18 |
| Action Date | 29th April 2024 |
| Target Audience | – National Regulatory Field Force. – Pharmacists and Chemists at Distribution, Pharmacies and Medical Stores – Healthcare Professionals- Physicians, Pharmacists, and Nurses at hospital and clinics – General Public |
| Problem / Issue | The Federal Government Analyst, CDL Karachi has declared the following batches of oral liquid preparations manufactured by M/s Biolab Pvt Ltd, Islamabad as of “Sub-standard” quality based on the presence of Ethylene Glycol impurity at an unacceptable level. |
Therapeutic Good(s) Affected: –
| Product Names | Composition | Batch No | Manufactured by |
|---|---|---|---|
| Mebzole 100mg/5mL Suspension Reg No. 046308 | Mebendazole | Batch No. 22J022(F), 22J022(B) Mfg. Date: 09-22 Exp. date: 08-24 | M/s. Biolabs (Private.) Limited., Islamabad. |
| Bioris 1mg/ml Oral Solution Reg No. 069917 | Risperidone | Batch No. 23B061 Mfg. Date: 02-23 Exp. date: 01-25 | M/s. Biolabs (Private.) Limited., Islamabad. |
| Risk Statement: | The presence of Ethylene Glycol (EG) in oral liquid preparations poses serious health risks due to its toxicity as small amounts of EG can be fatal, especially for children. When ingested, both diethylene glycol (DEG) and EG are metabolized into toxic compounds that can adversely affect the central nervous system, heart, and kidneys. |
| Action Initiated | –The manufacturer has been directed to immediately recall the defective batches of affected products from the market. All pharmacists and chemists working at distributions and pharmacies should immediately check their stocks and stop supplying these batches of products. –Distributors and pharmacies are advised to be vigilant and report any suspected batch of the product(s) in the supply chain to the DRAP using the online form, or through phone at +92 51 910 73 17, or by Email at gsms∂dra.gov.pk. –Regulatory field force of all federating units (DRAP, Provincial Health Departments, and States) has also increased the surveillance in the market to ensure the effective recall of defective product(s). |
| Advice for Healthcare Professionals | DRAP requests to enhance vigilance within the supply chains of institutions/pharmacies/healthcare facilities likely to be affected by this defective batch of the product. -Adverse reactions or quality problems experienced with this product may be reported to the National Pharmacovigilance Centre(NPC), DRAP using the Adverse Event Reporting Form or online through this link. -Please click here for further information on problem reporting to DRAP. |
| Advice for Consumers | -Consumers should stop using these product bearing the affected batch number(s). They shall contact their physician or healthcare provider(s) if they have experienced any problem that may be related to using this product. -All therapeutic products must be obtained from authorized licensed pharmacies /outlets. Their authenticity and condition should be carefully checked. If you have any doubts, please seek advice from your pharmacist. |