Drug Safety Alert: Increased Risk of Cardiovascular Events with Co-administration and Interaction Between Hydroxychloroquine or Chloroquine, and Macrolide Antibiotics

Asad Ullah Safety Alerts November 29, 2022November 29, 2022

Drug Safety Alert

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

Date:	29^thof November, 2022
Target Audience:	• Manufacturers and importers of hydroxychloroquine or chloroquine, and systemic macrolide antibiotics; • Healthcare professionals; and • Patients, consumers or caregivers.
Background:	The MHRA on 15th February, 2022 announced that the product information for hydroxychloroquine, chloroquine and macrolide antibiotics (azithromycin, erythromycin or clarithromycin) will be revised to include the increased risk of cardiovascular events and cardiovascular mortality if hydroxychloroquine or chloroquine is taken with a macrolide-antibiotic. A review was conducted by the Pharmacovigilance Expert Advisory Group of the Commission on Human Medicines following the results of a retrospective observational study which shows that co-administration of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events (including angina or chest pain and heart failure) and cardiovascular mortality. It was recommended in the review that the product information for hydroxychloroquine and systemic azithromycin medicines should be amended to include new warnings and advice on these risks. Owing to the similar safety profiles, the risks with concurrent use of hydroxychloroquine and azithromycin were considered to apply to the concurrent use of hydroxychloroquine and other systemic macrolide antibiotics (clarithromycin or erythromycin) and to the use of chloroquine with systemic macrolide antibiotics. Therefore, the review recommended that similar warnings should also be added to the product information for chloroquine and for systemic clarithromycin or erythromycin. However, these warnings were not being introduced for topical macrolide products (which are indicated for conjunctivitis or acne). The MHRA also reminded the healthcare professionals that the product information for hydroxychloroquine and chloroquine already contains warnings about cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcomes. It was also informed that evidence suggests both hydroxychloroquine and chloroquine can prolong the QT interval, especially in overdose or when used in combination with other medicines with the potential to induce cardiac arrhythmias. Likewise, warnings are also in place across the product information for azithromycin, clarithromycin, and erythromycin to use caution in patients with a history of QT interval prolongation or in patients receiving a medicine known to cause QT prolongation. Although the mechanism of the observed effects was not examined in detail by the study, it was proposed that events could have been caused by cumulative effects of hydroxychloroquine and azithromycin on the QT interval, potentiating arrhythmias and cardiac death, or through other additive cardiotoxic effects more generally.
Therapeutic Good(s) Affected:	Name of Drugs: (i)Hydroxychloroquine, (ii) Chloroquine; and (iii) Systemic macrolide antibiotics (not topical). Hydroxychloroquine is indicated for the treatment of rheumatoid arthritis, systemic lupus erythematosus, and dermatological conditions aggravated by sunlight. Chloroquine is indicated for malaria prophylaxis or treatment and other indications. Macrolide antibiotics such as erythromycin, clarithromycin and azithromycin are used to manage and treat various bacterial infections like pneumonia, sinusitis, pharyngitis and tonsillitis etc.
Action in Pakistan	Accordingly, the case of risk of cardiovascular events with co-administration and interaction between hydroxychloroquine or chloroquine, and macrolide antibiotics was discussed in the 1st 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). The PRAEC-DRAP after discussion decided as per Rule 10 (1) (h) (iv) and (vi) of Pharmacovigilance Rules, 2022 (reliance mechanism) to update prescribing information (warning and interaction sections) of hydroxychloroquine, chloroquine and macrolide antibiotics (azithromycin, erythromycin or clarithromycin excluding topical macrolides) about the potential interaction of increased risk of cardiovascular events and cardiovascular mortality if hydroxychloroquine or chloroquine is taken with a macrolide-antibiotic.
Advice for healthcare professionals:	Healthcare professionals are informed that an observational study has shown that co-administration of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events (including angina or chest pain and heart failure) and cardiovascular mortality. Therefore, carefully consider the benefits and risks before prescribing systemic azithromycin or other systemic macrolide antibiotics (erythromycin or clarithromycin) to patients being treated with hydroxychloroquine or chloroquine. If there is a clinical need to prescribe systemic macrolide antibiotics with hydroxychloroquine or chloroquine, use caution in patients with risk factors for cardiac events.
Advice for patients:	Patients are informed that some antibiotics (known as macrolides) taken by mouth or given as an injection at the same as hydroxychloroquine or chloroquine have been associated with an increased risk of side effects that affect the heart. Seek urgent medical help if you have any signs of problems with your heart (for example, palpitation, fainting, chest pain, or unexplained breathlessness).
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 1st meeting of Pharmacovigilance Risk Assessment Expert Committee. MHRA update regarding Hydroxychloroquine, chloroquine: increased risk of cardiovascular events when used with macrolide antibiotics; reminder of psychiatric reactions.

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Date:	19_^th of November 2022
Target Audience:	• Manufacturers and importers of Iodinated contrast media (ICM) injections such as iohexol, iopromide and iodixanol etc; • Healthcare Professionals; and • Patients, consumers or caregivers.
Background:	On 30th March, 2022, the United States Food and Drug Administration (US-FDA) through a Drug Safety Communication informed that they have approved a new warning to the prescribing information for the entire class of iodinated contrast media (ICM) injections and monitoring recommendations for children 3 years or younger. The warning describes the risk of an underactive thyroid or a temporary decrease in thyroid hormone levels. These risks and recommendations pertain to ICM given as an injection through an artery or vein. Newborns, particularly those born premature, and children in their first 3 years with underlying conditions such as heart issues may be at higher risk for problems with the thyroid. It was informed that the agency first alerted the public about cases of underactive thyroid in infants receiving ICM back in 2015 and now six new research studies evaluating this risk have been published. The FDA has concluded based on their review of the published studies that there is compelling evidence of a significant risk for an underactive thyroid or a temporary decrease in thyroid hormone levels in newborns and children through 3 years after exposure to ICM. Back in December 2017, the Medicines and Medical Devices Safety Authority (Medsafe) of New Zealand also requested that data sheets for iodine-containing contrast agents (ICAs) to be updated with information on the risk of hypothyroidism, particularly in neonates and should include advice on thyroid monitoring.
Therapeutic Goods Affected:	Iodinated contrast media (ICM) injections such as iohexol, iopromide and iodixanol etc. ICM are drugs containing iodine that are given to patients to enhance the ability to see blood vessels, organs, and tissues on medical images such as X-rays or computed tomography (CT) scans, thus helping healthcare professionals to diagnose potential problems. Examples include iohexol (Omnipaque), iopromide (Ultravist 300, 370) and iodixanol (Visipaque 270, 320) etc. Common side effects associated with ICM include flushing in the face, nausea or vomiting, mild itchiness, and skin rash.
Action in Pakistan	Accordingly, the case of the risk of hypothyroidism in babies and young children with iodinated contrast media (ICM) injections was discussed in the 1st 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). The PRAEC after detailed deliberation and discussion decided as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 (reliance mechanism) to update the warning and precaution section of the prescribing information of the entire class of iodinated contrast media (ICM) that are used for radiological purposes to include risks of an underactive thyroid or a temporary decrease in thyroid hormone levels in children 3 years or younger i.e newborns, particularly those born premature, and children in their first 3 years with underlying conditions such as heart issues etc.
Advice for healthcare professionals:	Healthcare professionals are advised to perform appropriate monitoring of patients from birth through 3 years for the possibility of hypothyroidism or a temporary decrease in thyroid hormone levels following exposure to iodinated contrast media (ICM) injections. Healthcare professionals are also advised to consider evaluating thyroid function within 3 weeks, especially in term and preterm neonates and children with some underlying conditions. If thyroid dysfunction is detected, it should be properly treated and monitored as clinically needed to avoid future cognitive and other developmental disabilities. Increased-risk pediatric patients include those who are newborns or have very low birth weight, prematurity, or the presence of cardiac or other conditions such as those requiring care in neonatal or pediatric intensive care units. Patients with cardiac conditions may be at the greatest risk since they often require high doses of contrast during invasive cardiac procedures. These increased-risk pediatric patients require close monitoring.
Advice for patients:	Parents and caregivers of a child below 3 years and receiving ICM injections should talk with healthcare professionals for additional information. If the child is a newborn, has very low birth weight, was premature, has a heart condition, or was admitted to a neonatal or pediatric intensive care unit, they may be at higher risk of developing underactive thyroid or a temporary decrease in thyroid hormone levels. Babies & young children typically do not show any visible signs of thyroid problems & may need to be monitored by their healthcare professionals after receiving ICM.
Guidelines for reporting Adverse Drug Reactions (ADRs):	Both healthcare professionals and patients are requested to report any suspected adverse drug reaction (ADRs) 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 1st meeting of Pharmacovigilance Risk Assessment Expert Committee. Drug Safety Communication of the United States Food and Drug Administration (US-FDA) regarding Iodinated contrast media (ICM).

Date:	21^st of November 2022
Target Audience:	• Manufacturers and importers of Remdesivir; • Healthcare Professionals; and • Patients, consumers or caregivers.
Background	Health Canada in August, 2021 announced that it will work with the manufacturer of Remdesivir to update the product information to include a warning on the potential risk of sinus bradycardia. Health Canada assessed case reports of sinus bradycardia in patients receiving Remdesivir in their database and in the literature and concluded that a link between the use of Remdesivir and the risk of sinus bradycardia is possible. Previously, in June 2021, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicine Agency (EMA) recommended a change to the product information for Remdesivir (Veklury®) to include sinus bradycardia as an adverse drug reaction. The PRAC reviewed available data on rare reported cases of bradycardia in patients treated with Remdesivir as well as data from clinical trials and the scientific literature. The PRAC concluded that a causal relationship between the use of Remdesivir and the event is reasonably possible and recommended the revision of the product information. The majority of the events of sinus bradycardia resolved a few days after the treatment with Remdesivir was discontinued. Sinus bradycardia occurs when the heart beats slower than normal. Sinus bradycardia can very rarely cause symptoms, such as dizziness, tiredness, shortness of breath, and chest discomfort.
Action in Pakistan	Accordingly, the case of the risk of sinus bradycardia with Remdesivir was discussed in the 1st 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). The PRAEC after discussion decided as per Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 (reliance mechanism) to update the prescribing information (warning & adverse drug reactions sections) of Remdesivir to include the potential risk of sinus bradycardia.
Therapeutic Goods Affected:	Remdesivir injection Remdesivir is an antiviral medicine that is indicated to treat COVID-19 in adults and adolescents with pneumonia requiring supplemental oxygen. Remdesivir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleotide analog RNA polymerase inhibitor indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients (28 days of age and older and weighing at least 3 kg) with positive results of direct SARS-CoV-2 viral testing, who are: hospitalized, or not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death..
Advice / Directions for for Registration Holder	Registration holders of Remdesivir injection are hereby advised/directed to update the prescribing information/safety specification/ label of Remdesivir with the inclusion of information related to infusion-related hypersensitivity reactions and its monitoring in the warning and precaution sections. Furthermore, registration holders should also introduce educational training for healthcare professionals on proper preparation, administration and flow rate of Remdesivir, and monitoring of patients.
Advice for healthcare professionals:	Healthcare professionals are informed that the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the NPC-DRAP has decided to update the prescribing information (warning & adverse drug reactions sections) of Remdesivir to include the potential risk of sinus bradycardia. Therefore, healthcare professionals should monitor patients receiving Remdesivir for sinus bradycardia and accordingly treat the patients as appropriate.
Guidelines for reporting Adverse Drug Reactions (ADRs):	Both healthcare professionals and patients are requested to report any suspected adverse drug reaction (ADRs) 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 1st meeting of Pharmacovigilance Risk Assessment Expert Committee. Minutes of Meeting of PRAC of European Medicines Agency.

Date:	18_^th of November 2022
Target Audience:	• Manufacturers and importers of Remdesivir; • Healthcare Professionals; and • Patients, consumers or caregivers.
Problem or Issue:	The National Pharmacovigilance Centre (NPC), Division of Pharmacy Services, Drug Regulatory Authority of Pakistan (DRAP) received a cluster of three serious (life-threatening) adverse drug reaction reports from a hospital with Inj Remdesivir (100mg/20ml). The events of tachycardia, dyspnoea, chills and pyrexia were noted after the use of Remdesivir through an intravenous drip for COVID-19 Pneumonia, with a time to onset of 0 days. The causality assessment of all three cases was performed by the Causality Assessment Group of the NPC and classified that all three cases have a possible relationship with drug intake. However, at the same time, the NPC also carried out the quality testing of the suspected batch of Remdesivir, which was declared of standard quality with regard to the tests performed by the Central Drugs Laboratory, DRAP, Karachi. The NPC accordingly labelled it as a potential signal of infusion-related hypersensitivity reactions with the injection of Remdesivir. Further assessment was also carried out at NPC-DRAP, where the signal was confirmed from the approved label of the United States Food and Drugs Administration (US-FDA) and Summary of Product Characteristics (SmPC) of Medicine and Health Products Agency (MHRA) of the United Kingdom. There was also significant disproportionality and potential association of Remdesivir with infusion-related hypersensitivity reactions as per the statistical tools available in VigiLyze of the Uppsala Monitoring Centre. The case was discussed in the 1st meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the NPC, DRAP and decides as to update the prescribing information/ safety specification/ label of Remdesivir injection with the inclusion of information related to infusion-related hypersensitivity reactions and its monitoring in the warning and precaution sections. Furthermore, it was also decided that all registration holders should introduce educational training for healthcare professionals on proper preparation, administration and flow rate of Remdesivir, and monitoring of patients.
Therapeutic Goods Affected:	Remdesivir injection Remdesivir is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleotide analog RNA polymerase inhibitor indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients (28 days of age and older and weighing at least 3 kg) with positive results of direct SARS-CoV-2 viral testing, who are: hospitalized, or not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.
Advice / Directions for for Registration Holder	Registration holders of Remdesivir injection are hereby advised/directed to update the prescribing information/safety specification/ label of Remdesivir with the inclusion of information related to infusion-related hypersensitivity reactions and its monitoring in the warning and precaution sections. Furthermore, registration holders should also introduce educational training for healthcare professionals on proper preparation, administration and flow rate of Remdesivir, and monitoring of patients.
Advice for healthcare professionals:	Healthcare professionals are informed that the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the DRAP has recommended updating the prescribing information/ safety specification/ label of Remdesivir injection with the inclusion of information related to infusion-related hypersensitivity reactions and its monitoring in the warning and precaution sections, and is working with registration holders in this regard. Healthcare professionals are also informed that the signs and symptoms of infusion-related hypersensitivity reactions may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering, which have been observed during and following administration of Remdesivir injection which mostly occurred within one hour. Therefore, slower infusion rates with a maximum infusion time of up to 120 minutes should be considered to potentially prevent these signs and symptoms. Furthermore, monitor patients during infusion and observe patients for at least one hour after the infusion is completed for signs and symptoms of hypersensitivity as clinically appropriate. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue the administration of Remdesivir injection and initiate appropriate treatment.
Advice for patients:	Patients are informed that hypersensitivity reactions including infusion-related reactions have been observed during and following the administration of Remdesivir injection. Immediately call your doctor if you experience signs and symptoms such as hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering after administration of Remdesivir injection.
Guidelines for reporting Adverse Drug Reactions (ADRs):	Both healthcare professionals and patients are requested to report any suspected adverse drug reaction (ADRs) with Diclofenac Sodium 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 1st meeting of Pharmacovigilance Risk Assessment Expert Committee. Approved label of Veklury (Remdesivir) of US-FDA.

Date:	18_^th of November 2022
Target Audience:	• Manufacturers and importers of Clozapine; • Healthcare Professionals; and • Patients, consumers or caregivers.
Background	The Therapeutic Goods Administration (TGA) of Australia on 22nd, April 2022 through a safety advisory informed that Product Information (PI) and Consumer Medicine Information (CMI) for Clozapine have been updated to strengthen warnings about potential severe gastrointestinal side effects, including constipation. It was informed that Clozapine may also affect the bowels by slowing them down and can cause severe constipation, the condition known as clozapine-induced gastrointestinal hypomotility. If untreated, it can lead to serious problems. Consumers who were using clozapine were informed to look out for changes in their bowel function and to contact their health professionals if they develop any of the symptoms. On 14th January 2022, the United States Food and Drug Administration (US-FDA) through Drug Safety Podcast referred to the already issued communication dated 18th of February 2020 where the FDA strengthens the existing warning that untreated constipation caused by schizophrenia medicine clozapine (Clozaril®) can lead to serious bowel problems. It was informed that serious bowel complications can lead to hospitalization or even death if constipation is not diagnosed and treated quickly.
Action in Pakistan	Accordingly, the case of risk of serious bowel complications with Clozapine was discussed in the 1st 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 to update and strengthen the warning section of Clozapine with gastrointestinal side effects, including constipation and severe bowel problem in light of Rule 10 (1) (h) (iv) of Pharmacovigilance Rules, 2022 as a part of reliance mechanism on stringent regulatory authorities.
Therapeutic Goods Affected:	Clozapine Tablets Clozapine is a medicine that has been used for more than 40 years to treat schizophrenia in patients whose symptoms are not controlled with standard treatment
Advice for healthcare professionals:	Healthcare professionals are advised the following: to evaluate bowel function before starting a patient on clozapine and avoid co-prescribing clozapine with other anticholinergic medicines that can cause gastrointestinal hypomotility; advise patients frequently of the significant risk of constipation and life-threatening bowel issues and the need to stay hydrated to prevent constipation; advise patients to contact a healthcare professional right away if they have difficulty having a bowel movement or passing stools, do not have a bowel movement at least three times a week or less than their normal frequency.
Advice for patients:	Patients are advised to contact their healthcare professionals if they have symptoms that can be associated with serious bowel problems such as nausea, vomiting or stomach pain. To prevent constipation, they should eat more fruits, vegetables, and grains that are high in fibre; drink plenty of water and other liquids, and get enough exercise.
Guidelines for reporting Adverse Drug Reactions (ADRs):	Both healthcare professionals and patients are requested to report any suspected adverse drug reaction (ADRs) 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:	1-Minutes of 1st meeting of Pharmacovigilance Risk Assessment Expert Committee. 2-Safety Advisory- constipation: a potentially serious side effect issued by the Therapeutic Goods Administration of Australia. 3-Drug safety podcast of the United States Food and Drug Administration (US-FDA) regarding constipation caused by schizophrenia medicine clozapine.

Date:	10_^th of November 2022
Target Audience:	• Manufacturers and importers of Diclofenac Sodium. • Healthcare Professionals; and • Patients, consumers or caregiver
Problem or Issue:	The National Pharmacovigilance Centre (NPC), Division of Pharmacy Services, Drug Regulatory Authority of Pakistan (DRAP) through the Provincial Pharmacovigilance Centre (PPC), Directorate of Drugs Control Punjab received two serious cases of anaphylactic reactions upon STAT dose administration of injection Diclofenac Sodium 75mg/3ml intramuscular (IM). The cases were reported by Clinical Pharmacy and Pharmacovigilance Officers (CPPOs) of two public sector hospitals in the Punjab province. The diclofenac injection was used in these cases for the wound pain in the left leg and backache. One of the patients has a history of asthma. The symptoms noted were pruritus, erythema, sweating, apprehension and fainting due to a sudden drop in blood pressure, severe shortness of breath, wheezy chest, hypoxia and hypotension. The adverse drug reactions were assessed for causality using the WHO Causality Assessment Criteria and were categorized as “Possible” and “Probable” based on plausible time to onset (same day immediately after administration), positive dechallenge (recovered on withdrawing) and unable to explain from other drugs/ disease. The case were, therefore, discussed in the 1st meeting of the Pharmacovigilance Risk Assessment Expert Committee (PRAEC) of the NPC, DRAP which decided to update the warning, precaution & contraindication sections of the prescribing information / safety specification / label of Diclofenac Sodium injection about the occurrence of anaphylactic reaction/ anaphylactic shock and its contraindication in a patient with a history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
Therapeutic Goods Affected:	Diclofenac Sodium injection
Advice for healthcare professionals:	Healthcare professionals are informed that Pharmacovigilance Risk Assessment Expert Committee of the DRAP has recommended to update the warning, precaution & contraindication sections of the prescribing information/ safety specification/ label of Diclofenac Sodium injection about the occurrence of anaphylactic reaction/ anaphylactic shock and its contraindication in a patient with a history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Therefore, healthcare professionals should know that are rare chances that anaphylactic reactions may occur with diclofenac sodium injection in patients with the aspirin triad or in patients without prior exposure to diclofenac. Immediately discontinue the diclofenac injection if an anaphylactic reaction occurs. Likewise, Diclofenac is contraindicated in patients with a history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
Advice for patients:	Patients are informed that there are rare chances of the development of anaphylactic reaction/ anaphylactic shock with an injection of diclofenac sodium. Talk to your doctor if you have a history of asthma or urticaria, or if you had previously experienced an anaphylactic reaction/ allergic-type reaction with diclofenac sodium or after taking aspirin or other NSAIDs.
Guidelines for reporting Adverse Drug Reactions (ADRs):	Both healthcare professionals and patients are requested to report any suspected adverse drug reaction (ADRs) with Diclofenac Sodium 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 1st meeting of Pharmacovigilance Risk Assessment Expert Committee.

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