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Drug Safety Alert: Risk of dental problems with orally dissolved Buprenorphine

Asad Ullah Safety Alerts

Drug Safety Alert

Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan

Date:10th of April, 2023
Target Audience:• Manufacturers and importers of Buprenorphine medicines;
• Healthcare Professionals; and
• Patients, consumers or caregivers.
Background:The United States Food and Drug Administration (US-FDA) on 12th of January, 2022 through a drug safety communication warned that dental problems have been reported with medicines containing buprenorphine that are dissolved in the mouth. Dental problems, including tooth decay, cavities, oral infections, and loss of teeth have been reported, even in patients with no prior history of dental issues. The buprenorphine medicines that are associated with dental problems are tablets and films that are dissolved under the tongue or placed against the inside of the cheek. There are also buprenorphine products for pain and opioid use disorder (OUD) delivered by other routes such as a skin patch and injection, but FDA has not identified a concern for dental health related to these other forms.
Therapeutic Good(s) Affected:Name: Buprenorphine medicines that are orally dissolved.

Buprenorphine is an opioid used to treat opioid use disorder (misuse of prescribed opioid medications) and pain. The comprehensive approach of buprenorphine combined with counselling and other behavioural therapies is often one of the most effective ways to treat OUD. At proper doses, buprenorphine also decreases the pleasurable effects of other opioids, making misuse of them less appealing.
Action in PakistanAccordingly, the case of risk of dental problems with orally dissolved Buprenorphine was discussed in the 2nd  meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the National Pharmacovigilance Centre (NPC), Division of Pharmacy Services, Drug Regulatory Authority of Pakistan (DRAP) which after detailed deliberation and discussion decided
 
 
as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 to update the prescribing information/safety specification of buprenorphine medicines that are dissolved in the mouth by including information related to the risk of dental issues, pre-prescribing assessment of patients and guidelines of taking extra steps after use in the warning and precaution sections.
Advice for healthcare professionals:Healthcare professionals are advised to be aware that the benefits of buprenorphine medicines still clearly outweigh the risks in treating OUD patients and should ask patients about their oral health history before prescribing treatment with the transmucosal/oral buprenorphine medicines. Healthcare professionals should also counsel patients about the potential for dental problems and the importance of taking extra steps after the medicine has completely dissolved, including to gently rinse their teeth and gums with water and then swallow and to wait at least 1 hour before brushing their teeth.
Advice for patients:Patients are advised to continue taking buprenorphine medicine as prescribed and not to stop it suddenly as it could lead to serious consequences including withdrawal symptoms. Patients are also advised to take extra steps to reduce the risk of serious dental problems such as rinsing their mouth with water and waiting at least 1 hour before brushing their teeth after buprenorphine medicines are dissolved to avoid damage to their teeth.
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 2nd meeting of Pharmacovigilance Risk Assessment Expert Committee.
    31-Safety-Alert-Risk-of-dental-problems-orally-dissolved-BuprenorphineDownload
    Minutes of 2nd Meeting of Pharmacovigilance Risk Assessment Expert Committee (PRAEC) held on March 07, 2023

    Drug Safety Alert: Risk of Hypersensitivity Reactions with Pegaspargase (Peg L Asparaginase)

    Asad Ullah Safety Alerts

    Drug Safety Alert

    Update from Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of Pakistan

    Date:10th of April, 2023
    Target Audience:• Manufacturers and importers of Peg L Asparaginase;
    • Healthcare Professionals; and
    • Patients, consumers or caregivers.
    Background:The National Pharmacovigilance Centre (NPC), Division of Pharmacy Services, Drug Regulatory Authority of Pakistan (DRAP) received six cases of hypersensitivity reactions from Indus Hospital Karachi with Pegaspargase (Peg L Asparaginase) with different batches having the same importer i.e. M/S Lab Diagnostic System and same manufacture i.e. Jiangsu Hengrui Medicine Co Ltd, China. The drug was prescribed for Acute Lymphoid Leukemia/ Leukemia with a dose of 2500 IU/m2 in children. The events of hypersensitivity reactions including swelling of lips, nausea, rash, vomiting, swelling of the tongue, itching all over the body, shivering, red eyes and abdominal pain were noted in the six cases after administration of Pegaspargase (Peg L Asparaginase) 3750IU. The time to onset of reactions was one day. The Pegaspargase was withdrawn in all cases except one case where the status is unknown and the patients recovered in all those cases. The causality assessment of all six cases was performed by the Causality Assessment Group of the National Pharmacovigilance Centre (NPC) and classified all six cases to have a possible relationship with drug intake.
     
    Further assessment was carried out at the National Pharmacovigilance Centre (NPC), Drug Regulatory Authority of Pakistan (DRAP), where the signal was confirmed from the approved label of Peg L Asparaginase of United States Food and Drugs Administration (US-FDA) and Summary of Product Characteristics (SmPC) of Medicine and Health Products Agency (MHRA) and from the published research articles of hypersensitivity reactions with the drug. There was also significant disproportionality and potential association of hypersensitivity with Pegaspargase as per statistical tool available in VigiLyze of the Uppsala Monitoring Centre, Sweden.
     
     The case was therefore discussed in the 2nd meeting of the Pharmacovigilance Risk Assessment
    Expert Committee (PRAEC) of the NPC, DRAP which after detailed deliberation, decided to update the prescribing information/ safety specification/ label of Pegaspargase injection with the inclusion of information related to hypersensitivity reactions and its monitoring in the warning and precaution section and information on treatment modification as per the grade of hypersensitivity reactions in dosage and administration sections. Registration holder was also directed to introduce an educational training programme for healthcare professionals on proper preparation, administration and monitoring of Pegaspargase and to ensure that resuscitation equipment are available at the treatment sites.
    Therapeutic Good(s) Affected:Name: Pegaspargase (Peg L Asparaginase)

    Pegaspargase is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of pediatric and adult patients with Acute Lymphoid Leukaemia (ALL) and hypersensitivity to native forms of L-asparaginase.
    Advice for healthcare professionals:Healthcare professionals are informed that hypersensitivity reactions to Pegaspargase, including life-threatening anaphylaxis, can occur during therapy, including in patients with known hypersensitivity to E. coli-derived asparaginase formulations. Other hypersensitivity reactions can include angioedema, lip swelling, eye-swelling, erythema, decreased blood pressure, bronchospasm, dyspnoea, pruritus and rash. Premedicate patients 30-60 minutes before administration of pegaspargase. As a routine precautionary measure, the patient should be monitored for an hour after administration and resuscitation equipment and other appropriate means for the treatment of anaphylaxis such as epinephrine, oxygen, intravenous steroids, etc should be available at the treatment sites. Pegaspargase should be discontinued in patients with serious hypersensitivity reactions. Monitoring of patients and modification of treatment is recommended as per the following schedule: reduce the infusion rate by 50% in case of Grade 1 hypersensitivity reaction; interrupt the infusion, treat the symptoms, when symptoms resolved, resume the infusion and reduce the infusion rate by 50% in case of Grade 2 hypersensitivity reaction; and for Grade 3 to 4 hypersensitivity reactions permanently discontinue the pegaspargase.
    Advice for patients:Patients are informed that hypersensitivity reactions with Pegaspargase injection can occur during chemotherapy of Acute Lymphoid Leukaemia (ALL). Talk to your doctor if you have a history of hypersensitivity with conventional asparaginase formulations.
    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 2nd meeting of Pharmacovigilance Risk Assessment Expert Committee.
      30-Safety-Alert-of-Hypersensitivity-Reactions-with-Pegaspargase-Peg-L-Asparaginase.Download

      Recall Alert: Drug Product; Micogen-B Cream (Batch#MB-012/22) by M/s. Delux Chemical Industries, Karachi

      Asad Ullah Recall Alerts

      Recall Alert

      DRAP Alert NoNoII/S/03-23-17
      Action Date27th March 2023
      Target Audience1. Pharmacists and Chemists at Distributions, Pharmacies and Medical Stores
      2. Healthcare Professionals- Physicians, Pharmacists, and Nurses at Hospitals, Clinics and Healthcare Providing Institutions
      3. General Public
      Product(s) Affected Micogen-B Cream
      Composition: Gentamicin, Miconazole and Betamethasone
      Manufactured by: M/s. Delux Chemical Industries, Karachi
      Batch No. MB-012/22
      Manufacturing Date: 11-2022
      Expiry Date: 11-2024
      Problem / Issue Federal Government Analyst, CDL Karachi has declared the Batch No. MB-012/22 of the product “Micogen-B Cream” as of substandard quality.
      Risk StatementDrug Product contains multiple ingredients including Betamethasone, Gentamicin & Miconazole, is indicated for treatment of fungal and bacterial infections of the skin. Impact of use of substandard product on basis of Bio Assay test may leads to sub optimal to no therapeutic effect and may intensify/ flare the existing bacterial and fungal infection.
      Action Initiated-The manufacturing company / registration holder has been directed to immediately recall the defected batch of product from the market.

      -All Pharmacists and chemists working at distributions and Pharmacies should immediately check their stocks and stop supplying this batch of product. The remaining stock should be quarantine and return to the supplier / company.

      -Distributors and pharmacies are advised to be vigilant and report any suspected batch of product(s) in the supply chain to the DRAP using online form, or through phone at +92 51 910 73 17, or 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 increase vigilance within the supply chains of healthcare institutions and hospital pharmacies to identify and return the defective batch(es) of this product to the importer / company.

      -Adverse reactions or quality problems experienced with the use of this product may be reported to the National Pharmacovigilance Centre(NPC), DRAP using 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 this product bearing the affected batch number(s) and shall contact to their physician or healthcare provider(s) if they have had experienced any problem that may be related to taking or using this product.

      -All drug products must be obtained from the authorized licensed pharmacies /outlets. Their authenticity and condition should be carefully checked. If you have any doubt, please seek advice from your pharmacist.
        Micogen-B-Cream-Batch-MB-012-22Download

        Recall Alert: Drug Product; Mefco 50mg/5ml Suspension (Batch# 2J041) by M/s. Eros Pharmaceuticals (Pvt) Ltd., Karachi

        Asad Ullah Recall Alerts

        Recall Alert

        DRAP Alert NoNoII/S/03-23-19
        Action Date29th March 2023
        Target Audience1. Pharmacists and Chemists at Distributions, Pharmacies and Medical Stores
        2. Healthcare Professionals- Physicians, Pharmacists, and Nurses at Hospitals, Clinics and Healthcare Providing Institutions
        3. General Public
        Product(s) Affected Mefco 50mg/5ml Suspension
        Composition: Mefenamic Acid
        Manufactured by: M/s. Eros Pharmaceutical (Pvt) Ltd., Karachi
        Batch No. 2J041
        Manufacturing Date: 10-2022
        Expiry Date: 10-2024
        Problem / Issue Federal Government Analyst, CDL Karachi has declared the Batch No. 2J041 of the product “Mefco 50mg/5ml Suspension” as of substandard quality.
        Risk StatementMefenamic acid is used to treat mild to moderate pain. Impact of use of substandard product on basis of pH test may significantly altered the solubility and interfere with its absorption.
        Action Initiated-The manufacturing company / registration holder has been directed to immediately recall the defected batch of product from the market.

        -All Pharmacists and chemists working at distributions and Pharmacies should immediately check their stocks and stop supplying this batch of product. The remaining stock should be quarantine and return to the supplier / company.

        -Distributors and pharmacies are advised to be vigilant and report any suspected batch of product(s) in the supply chain to the DRAP using online form, or through phone at +92 51 910 73 17, or 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 increase vigilance within the supply chains of healthcare institutions and hospital pharmacies to identify and return the defective batch(es) of this product to the importer / company.

        -Adverse reactions or quality problems experienced with the use of this product may be reported to the National Pharmacovigilance Centre(NPC), DRAP using 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 this product bearing the affected batch number(s) and shall contact to their physician or healthcare provider(s) if they have had experienced any problem that may be related to taking or using this product.

        -All drug products must be obtained from the authorized licensed pharmacies /outlets. Their authenticity and condition should be carefully checked. If you have any doubt, please seek advice from your pharmacist.
          Mefco-50mg-Suspension-batch-2J041-Eros-PharmaDownload

          Decisions of 56th Meeting of Medical Device Board (Deficiency letter for Medical Devices Applications)

          Asad Ullah Medical Devices, Medical Devices Board

          The Medical Device Board (MDB) of Drug Regulatory Authority of Pakistan in its 56th meeting has deferred the following applications of registration of medical devices due to various deficiencies / shortcomings in the applications dossiers. These applicants are requested to furnish the requisite information / documentations as directed by the Medical Device Board. The detail is provided in the below attachment.

          Applications for Local Manufacturing

          Defered-Letter-of-56th-Meeting-of-MDB-LocalDownload

          Applications for Import

          Defered-Letter-of-56th-Meeting-of-MDB-ImportDownload

          Stakeholders Comments are invited on the Draft Guidelines for Good Cold Chain Management Practices for Temperature-Sensitive Drug Products

          Asad Ullah Drugs, General , , ,

          The supply chain of Time and Temperature Sensitive Drug Products (TTSDPs) requires constant maintenance of temperature so that the cold chain remains integral to ensure that the product quality is not compromised. Registration holders of TTSDPs including manufacturers, Importers and exporters along with their authorized distributors, are required to provide suitable storage conditions throughout the life cycle of the product under the Drugs (Licensing, Registering & Advertising) Rules, 1976. Similarly, Pharmacies, Medical stores and other authorized sale outlets, and healthcare institutions are also required to provide suitable storage and distribution while dispensing TTSDPs under relevant provincial drug sale rules.

          DRAP has drafted this guidelines to set out the principal requirements for the safe storage and distribution of time- and temperature-sensitive pharmaceutical products (TTSDPs). These guidelines intended to emphasize the increased importance of pharmaceutical cold chain management as a result of changing product environment, the requirements for Good Storage and Distribution Practices, current regulatory trends, quality management, risk assessment factors, and temperature monitoring system.

          This draft guideline is uploaded on the official website of DRAP dated on 27th March, 2023, for seeking comments and suggestions from stakeholders on the draft document. Stakeholders can submit their comments and suggestions within 15 days of uploading this document using prescribed format. For further guidelines on how to submit comments visit DRAP website or click here. Comments and suggestions can be forwarded via email to ajmal.sohail∂dra.gov.pk, copying at akbar.ali∂dra.gov.pk, or can be posted at mailing address, Director, Quality Assurance & Lab Testing, Drug Regulatory Authority of Pakistan, 3rd floor TF Complex, 7th Mauve Area, G-9/4, Islamabad.

          Draft_Guidance_on_Cold_Chain_Practices_FormattedDownload

          Decisions of 55th Meeting of Medical Device Board (Deficiency letter for Medical Devices Applications)

          Asad Ullah Medical Devices, Medical Devices Board

          The Medical Device Board (MDB) of Drug Regulatory Authority of Pakistan in its 55th meeting has deferred the following applications of registration of medical devices due to various deficiencies / shortcomings in the applications dossiers. These applicants are requested to furnish the requisite information / documentations as directed by the Medical Device Board. The detail is provided in the below attachment.

          Applications for Registration of Medical Devices for Local Manufacturing

          Deffered-letters-M-55-LocalDownload

          Applications for Registration of Medical Devices for Import

          Deffered-letters-M-55-ImportDownload

          Decisions of 54th Meeting of Medical Device Board (Deficiency letter for Medical Devices Applications)

          Asad Ullah Medical Devices, Medical Devices Board

          The Medical Device Board (MDB) of Drug Regulatory Authority of Pakistan in its 54th meeting has deferred the following applications of registration of medical devices due to various deficiencies / shortcomings in the applications dossiers. These applicants are requested to furnish the requisite information / documentations as directed by the Medical Device Board. The detail is provided in the below attachment.

          Deferred-MDB-54Download