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Recall Alert: Drug Product; Zolan 200mg/5ml Suspension (Batch # L-083) by Swat Pharmaceuticals, Swat

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DRAP Alert NoNo II/S/10-23-35
Action Date4th Oct, 2023
Target Audience·  Pharmacists and Chemists at Distribution, Pharmacies and Medical Stores
·  Healthcare Professionals- Physicians, Pharmacists, and Nurses at hospital and clinics etc.
· General Public
Problem / Issue Federal Government Analyst, CDL Karachi has declared the Batch No. L083 of product “Zolan suspension” as of substandard quality.

Therapeutic Good(s) Affected: –

Product NamesCompositionBatch No Manufacturer
Zolan 200mg/5mL Suspension
 
Reg.No  027683

Metronidazole benzoateBatch No L-083
 
Mfg. Date: May 2023
Exp. Date: Apr 2025		Ms. Swat Pharmaceuticals,
Saidu Sharif Swat.
Risk Statement:Metronidazole benzoate oral suspension is commonly used to treat bacterial infections and intestinal parasites. Inaccurate use of the product may lead to common side effects like nausea, vomiting, diarrhea, and abdominal discomfort; more severe reactions, such as convulsive seizures and peripheral neuropathy, may also occur.
 
The impact of the use of substandard products on the basis of noncomplying pH may significantly alter the stability, and solubility of the product and may interfere with its absorption which could lead to sub-optimal therapeutic effect.
Action Initiated-The manufacturer has been directed to immediately recall the defective 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 quarantined and returned to the supplier/ company. The regulatory field force of all federating units (DRAP and Provincial Health Departments) has increase surveillance in the market to ensure the effective recall of defective products(s).

-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 ProfessionalsDRAP 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 this 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.

    Recall Alert: Drug Product; Kemodryl Cough Syrup (Batch # K-1068) by Alkemy Pharmaceutical (Pvt) Ltd., Hyderabad

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    DRAP Alert NoNo II/S/09-23-38
    Action Date16th Oct, 2023
    Target Audience·  Pharmacists and Chemists at Distribution, Pharmacies and Medical Stores
    ·  Healthcare Professionals- Physicians, Pharmacists, and Nurses at hospital and clinics etc.
    · General Public
    Problem / Issue Federal Government Analyst, CDL Karachi has declared the Batch No. L083 of product “Kemodryl Cough Syrup” as of substandard quality.

    Therapeutic Good(s) Affected: –

    Product NamesCompositionBatch No Manufacturer
    Kemodryl Cough Syrup
     
    Reg.No 007069

    		Chlorpheniramine
    Maleate 4mg:
    Ammonium
    Chloride 125mg :
    Sodium Citrate 55mg    		Batch No K-1068
     
    Mfg. Date: Aug 2023
    Exp. Date: July 2025    		Ms. Alkemy
    Pharmaceutical
    Laboratories (Pvt) Ltd.,
    Hyderabad.
    Risk Statement:Kemodryl Cough Syrup is a combination of Chlorpheniramine Maleate + Ammonium Chloride + Sodium Citrate which relieves cough. Chlorpheniramine is an anti-allergic which relieves allergy symptoms like runny nose, watery eyes and sneezing. Ammonium chloride can be used as an expectorant due to its irritative action on the bronchial mucosa. Sodium citrate is a mucolytic.
     
    Inaccurate use of the product may lead to common side effects like Stomach pain/epigastric pain, Allergic reaction, sleepiness, thickened respiratory tract secretions and impaired coordination.
     
    The impact of the use of substandard products on the basis of a higher limit of assay tests may cause adverse reactions on therapeutic doses.
    Action Initiated-The manufacturer has been directed to immediately recall the defective 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 quarantined and returned to the supplier/ company. The regulatory field force of all federating units (DRAP and Provincial Health Departments) has increase surveillance in the market to ensure the effective recall of defective products(s).

    -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 ProfessionalsDRAP 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 this 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.

      Drug Safety Alert: Risk of Serious Renal and Gastrointestinal Harms with Codeine plus Ibuprofen Drug Combination.

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      Drug Safety Alert

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

      Date:20 October, 2023
      Target Audience:·         Manufacturers and importers of drug combinations containing codeine with ibuprofen;
      ·         Healthcare professionals; and
      ·         Patients, consumers or caregivers.
      Background:The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) in September 2022 recommended a change to the product information for codeine with ibuprofen combination medicines to include a warning of serious harms, including death, particularly when taken for prolonged periods at higher than recommended doses.
      The PRAC reviewed several cases of renal, gastrointestinal and metabolic toxicities that have been reported in association with cases of abuse of and dependence on codeine with ibuprofen combinations, some of which have been fatal. The PRAC found that, when taken at higher than recommended doses or for a prolonged period of time, codeine with ibuprofen can cause damage to the kidneys, preventing them from removing acids properly from the blood into the urine (renal tubular acidosis). Kidney malfunction can also cause hypokalaemia, which in turn may cause symptoms such as muscle weakness and light-headedness. Therefore, renal tubular acidosis and hypokalaemia will be added to the product information as new adverse effects. The PRAC noted that medicines containing a combination of codeine and ibuprofen are authorized at the national level and in some countries these medicines are available without medical prescription. The PRAC considered that prescription-only medicine status would be the most effective risk minimization measure to mitigate the harm associated with abuse and dependence of these products.
      Therapeutic Good(s) Affected:Codeine with ibuprofen is a combination of opioid (codeine) and anti-inflammatory (ibuprofen), which is used to treat pain. Repeated use of codeine with ibuprofen may lead to dependence and abuse due to the codeine component.
      Action in PakistanThe case was discussed in the 3rd meeting of PRAEC, held on the 8th of September, 2023, which decided as per Rule 10(1)(h)(iv) of Pharmacovigilance Rules, 2022 that registration holders of Codeine with Ibuprofen combination should include information about serious harms (renal, gastrointestinal and metabolic toxicities) including death, particularly when taken for prolonged periods at higher than recommended doses in the warning and precaution section, and to add renal tubular acidosis and hypokalemia as adverse drug reactions in the prescribing information/ label of codeine with ibuprofen combination.
       
      Advice for healthcare professionals:Healthcare professionals are informed that severe hypokalemia and renal tubular acidosis have been reported due to prolonged use of ibuprofen at higher-than-recommended doses. This risk is
       
      increased with the use of codeine/ibuprofen as patients may become dependent on the codeine component. Presenting signs and symptoms included a reduced level of consciousness and generalized weakness. Ibuprofen-induced renal tubular acidosis should be considered in patients with unexplained hypokalemia and metabolic acidosis.
      Advice for patients:Medicine containing codeine with ibuprofen should be used for the duration as recommended by doctors as it may lead to dependence, abuse and addiction, which may result in a life-threatening overdose. If you are taking for longer than the recommended time or at higher than recommended doses you are at risk of serious harm. These include serious harm to the stomach/gut and kidneys, as well as very low levels of potassium in your blood. These can be fatal.
      If you experience any of the following signs whilst taking these medicines talk to your doctor or
      pharmacist as it could be an indication that you are dependent or addicted.
      •      You need to take this medicine for longer than advised
      •      You need to take more than the recommended dose
      •      You are using this medicine for reasons other than medical reasons, for instance, ‘to stay calm’ or to ‘help you sleep’
      •      You have made repeated, unsuccessful attempts to quit or control the use of this medicine
      •      When you stop taking this medicine you feel unwell, and you feel better once you take this medicine again (‘withdrawal effects’)
      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 3rd meeting of Pharmacovigilance Risk Assessment Expert Committee.
      ·         EMA-Europe: Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 26-29 September 2022.
      ·    EMA-Europe: New product information wording – Extracts from PRAC recommendations on signals
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      Drug Safety Alert: Risk of Respiratory Failure and Sepsis with Terlipressin.

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

      Date:20 October, 2023
      Target Audience:·         Manufacturers and importers of terlipressin products
      ·         Healthcare professionals; and
      ·         Patients, consumers or caregivers.
      Background:The Medicines and Healthcare Products Regulatory Agency (MHRA) of the United Kingdom (UK) in March 2023 announced that the Pharmacovigilance Expert Advisory Group of the UK’s Commission on Human Medicines agreed with the recommendations made as a result of EMA’s review which was triggered by the CONFIRM trial findings that new measures were required to reduce the risk of respiratory failure and sepsis when terlipressin is used in patients with type 1 hepatorenal syndrome. The clinical trial found that in patients with type 1 hepatorenal syndrome, terlipressin may cause serious or fatal respiratory failure at a frequency higher than previously known and that terlipressin increases the risk of sepsis and septic shock.
       
      Previously, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) in September 2022 recommended new measures to reduce the risk of respiratory failure and sepsis when using terlipressin in people with type 1 hepatorenal syndrome (HRS-1), which is a serious kidney problem in people with advanced liver disease. The recommendations follow the PRAC’s review of available data, including results from the CONFIRM clinical trial that included patients with HRS-1. Results of the trial suggested that patients who were treated with terlipressin were more likely to experience and die from respiratory disorders within 90 days after the first dose than those who were given a placebo. Although respiratory failure is a known adverse effect of terlipressin, the frequency of respiratory failure seen in the study was higher (11%) than previously reported in the product information. In addition, the study reported sepsis in 7% of patients in the terlipressin arm compared with none in the placebo group. The new measures include adding a warning to avoid terlipressin in patients with advanced acute-on-  
       
      chronic liver disease or advanced kidney failure, to the product information along with necessary recommendations to the patient. The PRAC recommendations were sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) which endorsed them and adopted its position on 10 November 2022. Furthermore, the label of Terlipressin  (TERLIVAZ)- US-FDA also contains a Boxed Warning about respiratory failure.
      Therapeutic Good(s) Affected:Terlipressin is a synthetic pituitary hormone indicated for the treatment of bleeding from dilated veins in the food pipe leading to the stomach (bleeding oesophageal varices) and for emergency treatment of type 1 hepatorenal syndrome (rapidly progressive renal failure in patients with liver cirrhosis (scarring of the liver) and ascites (fluid accumulation in the abdomen)). The advice is not relevant to the use of terlipressin for bleeding oesophageal varices.
      Action in PakistanThe case was discussed in the 3rd meeting of PRAEC, held on the 8th of September, 2023, which
      decided as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 registration holders should include information about strict monitoring of respiratory failure and sepsis when using terlipressin in people with type 1 hepatorenal syndrome (HRS-1) in the warning and precaution section. Adding a warning to avoid terlipressin in patients with advanced acute-on-chronic liver disease or advanced kidney failure and information that patients with breathing problems should receive treatment to manage their condition before starting terlipressin-containing medicines in the prescribing information/ label of terlipressin when used in people with type 1 hepatorenal syndrome (HRS-1). Furthermore, registration holders were also advised to create a boxed warning regarding this risk.
      Advice for healthcare professionals:Healthcare professionals were advised to consider the individual benefits and risks for patients with type 1 hepatorenal syndrome when initiating terlipressin treatment, especially for those with severe renal or hepatic impairment and monitor all patients closely during terlipressin treatment. The advice is not relevant to the use of terlipressin for bleeding oesophageal varices. Patients with breathing problems should receive treatment to manage their condition before starting terlipressin. During and after treatment, patients should be monitored for signs and symptoms of respiratory failure and infection. In addition, healthcare professionals can consider giving terlipressin-containing medicines as a continuous infusion (drip) into the vein as an alternative to giving it by bolus injection (full dose injected in one go) as this may reduce the risk of severe side effects.
      Advice for patients:Patients are informed that a higher than previously known risk of respiratory failure (severe breathing difficulty that may be life-threatening) has been reported when using terlipressin-containing medicines for the treatment of type 1 hepatorenal syndrome (HRS-1) (kidney problems in people with advanced liver disease). In addition, a new risk of sepsis (when bacteria and their toxins circulate in the blood leading to organ damage) has also been identified when terlipressin is used for treating this disease. Patients who have any questions or concerns should speak to their healthcare professionals.
      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 3rd meeting of Pharmacovigilance Risk Assessment Expert Committee.
      ·         MHRA-UK: Terlipressin: new recommendations to reduce risks of respiratory failure and septic shock in patients with type 1 hepatorenal syndrome.
      ·         EMA-Europe: New recommendations for terlipressin-containing medicines in the treatment of hepatorenal syndrome
      EMA-Europe: Terlipressin-containing medicinal products indicated in the treatment of hepatorenal syndrome
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        Drug Safety Alert: Risk of Tendon Disorders with Third-Generation Aromatase inhibitors

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

        Date:20 October, 2023
        Target Audience:·         Manufacturers and importers of third-generation aromatase inhibitors (anastrozole, exemestane and letrozole);
        ·         Healthcare professionals; and
        ·         Patients, consumers or caregivers.
        Background:Health Canada in January, 2023 announced that the product safety information for third-generation aromatase inhibitors (anastrozole, exemestane and letrozole) will be updated to include the risk of tendon disorders. The review was triggered by an update including the risks of tendonitis and tendon rupture by the EMA to letrozole product safety information. It was informed that Health Canada is working with the manufacturers of third-generation aromatase inhibitors to update the Candian Product Monographs to include these risks. Tendon disorders include tendon inflammation (tendonitis), inflammation of the tendon sheath (tenosynovitis) and tendon tears (tendon rupture).

        Health Canada reviewed reports of events of tendonitis and tenosynovitis and their potential relation to tendon rupture in five randomized controlled trials (RCTs). The agency also reviewed 25 case reports (2 domestic and 23 international) of tendon rupture (10 cases) and tendonitis (15 cases), where a link between the risk of tendon rupture and tendonitis with the use of a third-generation aromatase inhibitor could not be ruled out. However, these case reports included other medications and/or conditions that could have contributed to the reported adverse events. The review concluded that there is likely a link between the use of third-generation aromatase inhibitors and the risks of tendonitis and tenosynovitis. Also, a link with tendon rupture could not be ruled out.
        Therapeutic Good(s) Affected:Third-generation aromatase inhibitors (anastrozole, exemestane and letrozole) are prescription drugs authorized for the treatment of breast cancer in women who have reached menopause (post-menopausal breast cancer).
        Action in PakistanThe case was discussed in the 3rd meeting of PRAEC, held on the 8th of September, 2023, which decided as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 that registration holders of third-generation aromatase inhibitors (anastrozole, exemestane and letrozole) should update their prescribing information by including information about tendon disorders (tendonitis, tendon rupture and tenosynovitis etc.) in the warning and precaution section and list these in adverse drugs reaction section.
        Advice for healthcare professionals:The use of third-generation aromatase inhibitors was found to be associated with tendonitis and tenosynovitis as reported in randomized controlled trials. Tendon rupture was found to be a potential risk. Tendonitis and tenosynovitis were estimated to be of uncommon occurrence, and tendon rupture was of rare occurrence. Treating physicians should monitor patients for these adverse drug reactions.
        Advice for patients:Patients are advised to promptly notify their healthcare professional if they experience symptoms such as pain, swelling and difficulty moving their joints while they are on treatment with third-generation aromatase inhibitors (anastrozole, exemestane and letrozole).
        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 3rd meeting of Pharmacovigilance Risk Assessment Expert Committee.
        ·Health Canada: Summary Safety Review – Third Generation Aromatase Inhibitors (anastrozole, exemestane, letrozole) – ·Assessing the Potential Risk of Tendon Disorders.

          Drug Safety Alert: Risk of Seizures with Cephalosporins

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

          Date:20 October, 2023
          Target Audience:·         Manufacturers and importers of Fluorouracil and Capecitabine;
          ·         Healthcare professionals; and
          ·         Patients, consumers or caregivers.
          Background:Health Canada in January, 2023 announced that the product safety information for cephalosporins will be updated to include the risk of seizures in all the cephalosporins. As the risk of seizures was already included for some cephalosporins, this update was applied to cephalosporins that did not include the risk. The review was triggered by a US Food and Drug Administration update to the product safety information for cefazolin to include the risk of seizures. Accordingly, Health Canada reviewed the available information from searches of the Canada Vigilance database, international databases, as well as medical and scientific literature. Health Canada reviewed 84 cases (7 domestic and 77 international) of seizures in patients taking cephalosporins. Of the 84 cases, 13 cases (all international) were found to be probably linked to the use of cephalosporins, and 62 cases (4 domestic and 58 international) were found to be possibly linked. Three cases (all international) were unlikely to be linked to the use of cephalosporins. Six cases (3 domestic and 3 international) could not be assessed. The review concluded that there may be a link between the use of cephalosporins and the risk of seizures and therefore the agency informed that it would work with manufacturers to update the Canadian Product Monographs for the cephalosporins that did not already include the risk.
          The New Zealand Medicines and Medical Devices Safety Authority (Medsafe) in its publication dated 2nd March, 2023 informed that the risk of neurotoxicity with cephalosporins was discussed at the December 2022 Medicines Adverse Reaction Committee (MARC) meeting wherein the committee recommended that all cephalosporin data sheets should include consistent messaging on the risk of neurotoxicity. Cephalosporin-induced neurotoxicity may present in a range of conditions which are mainly characterized by encephalopathy, myoclonus and/or seizures. Seizures associated with cephalosporins may present as either convulsive or non-convulsive. Symptoms of neurotoxicity have been reported to develop within several days after starting treatment and to resolve following discontinuation. In patients with renal impairment, accumulation can occur, especially when doses are not adjusted appropriately, potentially leading to toxic effects. Additional risk factors for cephalosporin-induced neurotoxicity include older age groups, underlying central nervous system (CNS) disorders and high doses of cephalosporins administered by intravenous injection.
          Therapeutic Good(s) Affected:Cephalosporins are a group of prescription antibiotic medicines (cephalexin, cefazolin, cefadroxil, cefuroxime, cefprozil, cefotaxime, ceftazidime, ceftriaxone, cefixime and cefepime) and are indicated for the treatment of a wide range of bacterial infections including urinary and respiratory tract infections.
          Action in PakistanThe case was discussed in the 3rd meeting of PRAEC, held on the 8th of September, 2023, which decided as per Rule 10(1)(h)(iv) of the Pharmacovigilance Rules, 2022 that the registration holders of all cephalosporins should include information on the risk of seizures/ neurotoxicity in the warning and precaution section and also list in adverse drug reaction section in the prescribing information/label of all cephalosporins.
          Advice for healthcare professionals:Seizures may occur with the administration of Cefazolin for Injection, particularly in patients with renal impairment when the dosage is not reduced appropriately. Additional risk factors for cephalosporin-induced neurotoxicity include older age groups, underlying central nervous system (CNS) disorders and high doses of cephalosporins administered by intravenous injection. Discontinue the cephalosporin antibiotic if seizures occur or make the appropriate dosage adjustments in patients with renal impairment. Anticonvulsant therapy should be continued in patients with known Seizure disorders.
          Advice for patients:Patients are advised to take their antibiotic for the recommended duration and indication and promptly notify their healthcare professional about any signs of seizures/ neurotoxicity they experience.
          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 3rd meeting of Pharmacovigilance Risk Assessment Expert Committee.
          ·         Health Canada: Summary Safety Review – Cephalosporins – Assessing the Potential Risk of Seizures.
          ·   Medsafe-New Zealand: Risk Of Neurotoxicity With Cephalosporins.
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          Drug Safety Alert: Risk of Kidney Damage with Oral Anticoagulants

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          Drug Safety Alert

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

          Date:20 October, 2023
          Target Audience:·         Manufacturers and importers of Fluorouracil and Capecitabine;
          ·         Healthcare professionals; and
          ·         Patients, consumers or caregivers.
          Background:The Therapeutic Goods Administration (TGA) of Australia in June 2023 announced that a warning about serious kidney damage has been added to the prescribing information for all oral anticoagulants given through the oral route. Anticoagulant-related nephropathy (ARN) is a rare but serious adverse event resulting from profuse glomerular bleeding and has the potential to cause irreversible kidney damage and death.  The TGA investigated the safety signal based on reports of ARN in patients taking oral anticoagulants, mainly from overseas and sought a piece of advice from the Advisory Committee on Medicines (ACM). The committee noted that this adverse event is now well documented in the medical literature with warfarin and there is growing evidence for other oral anticoagulants. The ACM supported a class-wide warning being added to the Product Information for all oral anticoagulants. The ACM does not consider a warning for parenteral anticoagulants to be needed at this stage. This is because they are mainly used in hospitals and for a shorter duration.
          Therapeutic Good(s) Affected:Oral anticoagulants are widely used to prevent and treat thromboembolic conditions and include apixaban, rivaroxaban and warfarin etc. Anticoagulants, sometimes called blood thinners, reduce the blood’s natural ability to clot. This alert does not apply to parenteral anticoagulants.
          Action in PakistanThe case was discussed in the 3rd meeting of PRAEC, held on the 8th of September, 2023, which decided as per Rule 10(1)(h)(iv) of the Pharmacovigilance Rules, 2022 that registration holders should include information about Anticoagulant-related nephropathy (ARN) and its monitoring and evaluation in the warning and precaution section and to list ARN as an adverse drug reaction of unknown frequency in the prescribing information/label for oral anticoagulants.
          Advice for healthcare professionals:Healthcare professionals are informed that early detection and intervention of ARN is critical to reducing permanent kidney damage and death. Although anticoagulant-related nephropathy is rare, it is likely underdiagnosed as kidney biopsy is required for a definitive diagnosis but is rarely performed in people taking anticoagulants, and patients who develop ARN have comorbidities that may explain their acute kidney injury presentation. Therefore, healthcare professionals are advised that while treating patients who are taking oral anticoagulants, talk to them about the risk of anticoagulant-related nephropathy. Close monitoring, including renal testing, is recommended for those with excessive anticoagulation (or supratherapeutic INR for those on warfarin) and hematuria.
          Advice for patients:If you are taking an oral anticoagulant and have any questions or concerns about your treatment, speak to your doctor. Do not stop taking these medicines without discussing it with your doctor first. Contact your doctor immediately if you experience any of the following signs and symptoms: high blood pressure; decreased amount of urine; blood in urine; and swelling in legs, ankles, and around the eyes, which may indicate your kidneys aren’t working properly.
          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 3rd meeting of Pharmacovigilance Risk Assessment Expert Committee.
          ·         TGA: Oral Anticoagulants Can Cause Serious Kidney Damage in Rare circumstances.
          · TGA:  Risk Of Kidney Damage with Oral Anticoagulants.
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          Drug Safety Alert:Risk of Potentially Life-threatening Toxicity with Fluorouracil and Capecitabine in Di-hydropyrimidine Dehydrogenase (DPD) Deficient Patients.

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          Drug Safety Alert

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

          Date:26 October, 2023
          Target Audience:·         Manufacturers and importers of Fluorouracil and Capecitabine;
          ·         Healthcare professionals; and
          ·         Patients, consumers or caregivers.
          Background:The Therapeutic Goods Administration (TGA) of Australia in Sep-2022 and the Medicine and Health Product Agency (MHRA) in October, 2020 issued updates regarding the use of fluorouracil, capecitabine and flucytosine. These updates included a new warning about the potential for severe and life-threatening toxicity in patients with a partial di-hydropyrimidine dehydrogenase (DPD) deficiency. Previously, these medications were contraindicated for patients with known complete DPD deficiency. Reports of adverse events suggested a link between DPD deficiency and toxicities, although DPD deficiency testing was often not performed in affected patients. Healthcare professionals were advised to consider DPD deficiency testing before initiating therapy and to reduce the starting dose if partial DPD deficiency is detected. Similar recommendations were made by the MHRA, referencing a European safety review, which emphasized the importance of DPD deficiency testing prior to treatment initiation. Testing is not required for topical fluorouracil formulations due to minimal systemic absorption. The PRAC of the EMA in March 2020 also recommended pre-treatment testing for DPD deficiency before administering fluorouracil via injection or infusion. Lack of DPD enzyme can lead to the accumulation of fluorouracil in the blood, resulting in severe and life-threatening adverse reactions. Patients with complete DPD deficiency should not be given these medications, and a reduced starting dose is recommended for patients with partial DPD deficiency.
          Therapeutic Good(s) Affected:Fluorouracil and Capecitabine

          Fluorouracil is indicated alone or in combination with other medicines to treat various cancers such as malignant tumours, particularly of the breast, colon or rectum. Also, it is applied to the skin for actinic keratosis and dermal warts. The recommendations are related to system fluorouracil not topical.

          Capecitabine is indicated for the treatment of certain types of colon, colorectal, oesophagogastric and breast cancer.
          Action in PakistanThe case was discussed in the 2nd meeting of PRAEC-DRAP wherein it was decided to Co-opt experts in Oncology as per Rule 9 (5) of the Pharmacovigilance Rules, 2022 to assess the case of testing of DPD deficiency in patients before initiation of treatment with Fluorouracil and Capecitabine and submit their reports in the next meeting of PRAEC. Two expert members of oncology were selected from the leading hospitals in Pakistan.
           
          Accordingly, the PRAEC in its 3rd meeting held on the 8th of September, 2023 decided as per Rule 10(1)(h)(ii) of the Pharmacovigilance Rules, 2022 and in light of comments of co-opted experts to update contraindications in patients with known complete absence of di-hydro pyrimidine dehydrogenase (DPD) activity. Likewise, the PRAEC as per Rule 10(1)(h)(iv) of the Pharmacovigilance Rules, 2022 decided to update the warning and precaution section of prescribing information by including information about the importance of testing for DPD deficiency before initiation of the treatment with Fluorouracil and Capecitabine. Include information about the reduced starting dose in partial DPD deficiency, followed by enhanced monitoring for toxicities.
          Advice for healthcare professionals:Healthcare professionals are informed that patients with complete or partial DPD deficiency are at increased risk of severe and fatal toxicity during treatment with medicines containing 5-fluorouracil (intravenous) and capecitabin. Therefore, healthcare professionals are advised not to treat patients with known complete DPD deficiency with these medicines. Likewise, in patients with partial DPD deficiency, a reduced starting dose should be considered.  All patients need to be monitored for toxicity particularly during the first cycle of treatment or after a dose increase.
          Advice for patients:Patients should inform healthcare professionals if he/she or their family members have a history of complete or partial DPD deficiency. Patients should also promptly notify healthcare professionals about fluoropyrimidines-related toxicity, including for example stomatitis, diarrhoea, mucosal inflammation, neutropenia, and neurotoxicity.
          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 3rd meeting of Pharmacovigilance Risk Assessment Expert Committee.
          ·         Fluorouracil and capecitabine – DPD deficiency of TGA website.
          ·         5-Fluorouracil (intravenous), capecitabine, tegafur: MHR-UK recommended DPD testing before initiation to identify patients at increased risk of severe and fatal toxicity.
          ·         PRAC-EMA recommendation.
          Download

          Recall Alert: Medical Devices; Trifecta Family of Valves by M/s ST. Jude Medical, USA

          Asad Ullah Recall Alerts

          Recall Alert

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          DRAP Alert NoNo II/S/09-23-37
          Action Date10th October, 2023
          Target Audience• Healthcare Professionals particularly working in the critical care areas of hospitals including Physicians, Cardiologists, Pharmacists, and Nurses.
          • People implanted with affected Trifecta Family Valves.
          • Procurement Officers at Hospitals and Healthcare Institutions.
          • Pharmacists and Chemists at Distribution, Pharmacies and Medical Stores.
          Problem / Issue Abbot Structural Heart (St.Jude Medical, USA) has initiated a market withdrawal for the Trifecta family of valves (TrifectaTM Valve and TrifectaTM Valve with Glide Technology see table below) and will be removing the limited remaining inventory from the field due to potential for early Structural Valve Deterioration (SVD). Accordingly, the manufacturing company is recalling all the defective products from the international market including Pakistan. The Medical Device Board has already suspended the product registration in its 61st Meeting and further course of action for deregistration is in process under the Medical Device Rules 2017.

          Therapeutic Goods Affected:-

          Brand Names and DescriptionModel NoGTN/UDI Manufacturer and Distributor
          TrifectaTM Valve 19mm
          TrifectaTM Valve 21mm
          TrifectaTM Valve 23mm
          TrifectaTM Valve 25mm
          TrifectaTM Valve 27mm
          TrifectaTM Valve 29mm
          TrifectaTM Valve with Glide Technology 19mm
          TrifectaTM Valve with Glide Technology 21mm
          TrifectaTM Valve with Glide Technology 23mm
          TrifectaTM Valve with Glide Technology 25mm
          TrifectaTM Valve with Glide Technology 27mm
          TrifectaTM Valve with Glide Technology 29mm          		TF-19A
          TF-21A
          TF-23A
          TF-25A
          TF-27A
          TF-29A
          TFGT-19A
          TFGT-21A
          TFGT-23A
          TFGT-25A
          TFGT-27A
          TFGT-29A          		05414734052016
          05414734052023
          05414734052030
          05414734052047
          05414734052054
          05414734052061
          05415067018205
          05415067018212
          05415067018229
          05415067018236
          05415067018243
          05415067018250          		M/s St. Jude Medical 11 county road b e saint paul, mn USA 55117
          Distributor in Pakistan:
          M/s Verizon, 60-D, F.C.C Zahoor Elahi Road, Gulberg-IV, Lahore.
           
          Products registration no.    MDIR -0003639.
          MDIR -0000233.
          (Names and Models of defective products being recalled from market. For More Information please click here)
          Risk Statement:The valves are intended to maximize valve opening and improve hemodynamic performance. Therefore, defective trifecta family heart valves pose a risk of patient harm which will compromise the hemodynamic performance of the valve and can lead to cardiac arrest, other serious injuries.
          Action Initiated-The manufacturing company has initiated a recall of the affected lots of defective products from the market where it was distributed.

          -All healthcare professionals working in critical care units of hospitals as well as pharmacists and chemists working at distributions and pharmacies should immediately check their stocks and stop supplying these lots of the product. The remaining stock should be quarantined and returned to the supplier/company.

          -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 ProfessionalsDRAP requests to enhance vigilance within the supply chains of institutions/pharmacies/healthcare facilities likely to be affected by these defective lots of the Medical Device. Patient using the affected device should immediately contact their doctors for further guidance. Furthermore, Abbott, USA provided patient management considerations for those patients implanted with the Trifecta and Trifecta GT valves. https://www.structuralheart.abbott/fileadmin/pdf/FINAL_Abbott_Letter_US_Trifecta_Abbott_Website_sig ned.pdf)

          Understanding that clinical decisions are shared between healthcare providers and patients, please consider the following post-implant:

          · Patients should be reminded to seek medical attention with new onset of symptoms such as shortness of breath or fatigue.
          · An initial post-procedural transthoracic echocardiogram (TTE) study is recommended for all patients within 1 to 3 months after the implant procedure to evaluate valve hemodynamics and ventricular function.
          · Schedule annual follow-up visits beginning 1-year post-implant for clinical evaluation, including TTE to assess transvalvular gradients and valvular regurgitation grade.
          · Patients presenting with changes in symptoms (e.g., shortness of breath or fatigue on exertion) or signs (e.g., murmur) indicative of potential SVD should undergo a TTE.
          · Patients with evidence of hemodynamically significant SVD should be considered, in consultation with a heart team, for a possible valve intervention with either surgical aortic valve replacement (SAVR) or a trans catheter valve-in-valve intervention depending on individual patient risks and benefits.
          · Patients being considered for a valve-in-valve intervention should undergo pre-procedure planning with imaging studies to ensure all potential procedure-related risks such as coronary obstruction are minimized. Additional information regarding future valve-in-valve considerations can be found in the Trifecta GT valve IFU. Please note that the titanium frame of the Trifecta GT valve cannot be fractured using a balloon. Actions Abbott is Asking You to Take:
          · Please consider this information in your practice and share with relevant health care professionals (e.g., cardiac surgeons, cardiologists, primary care physicians) involved in the care of patients implanted with the Trifecta family of valves in your institution.
          · Complete and return the provided Acknowledgement Form.
          · Report any product incidents, regardless of procedure or patient outcome, to Abbott.

          -Adverse reactions or quality problems experienced with 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 Model no and shall contact to their physician or healthcare provider if they have experienced any problems that may be related to using this Medical Device and report the incident to National Pharmacovigilance Centre of Drug Regulatory Authority of Pakistan, through MedSafety Mobile Application, or online at Med Vigilance E Reporting System.

          -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.

            Recall Alert: Drug Product; Albex 200mg Tablets (Batch#112) by M/s Swat Pharmaceuticals, Swat

            Asad Ullah Recall Alerts

            Recall Alert

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            DRAP Alert NoNo II/S/09-23-34
            Action Date22th Sep, 2023
            Target Audience· Healthcare Professionals particularly working in hospitals; Physicians, Pharmacists, and Nurses.
            · Procurement Officers at Hospitals and Healthcare Institutions.
            · Pharmacists and Chemists at Distribution, Pharmacies and Medical Stores.
            Problem / Issue

            Therapeutic Good(s) Affected: –

            Product NamesCompositionBatch No Manufacturer
            Albex 200mg Table
             
            Reg No. 020291

            		Albendazole 200mgBatch No 112
             
            Mfg date 04.2023
            Exp date 03.2025            		Ms. Swat Pharmaceutical,
            Swat.
            Risk Statement:Albendazole is an anthelminthic drug used to treat various parasitic worm infections. Substandard preparations of albendazole tablets may lead to treatment failure or suboptimal therapeutic effects, adverse effects, and increased antimicrobial resistance by exposing the parasitic worms to suboptimal concentrations of the drug.
            Action Initiated-The manufacturer has been directed to immediately recall the defective 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 quarantined and returned to the supplier/ company. The regulatory field force of all federating units (DRAP and Provincial Health Departments) has increase surveillance in the market to ensure the effective recall of defective products(s).

            -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 ProfessionalsDRAP 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 this 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.