Based on the evaluation of the analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing dorzolamide (dorzolamide), the Pharmacovigilance Risk Assessment Committee (PRAC) reached the following conclusions.
Tachycardia: of the 21 adverse reaction (hereinafter – ADR) reports received from the registration certificate holder (hereinafter – RCH), 3 were categorized as “serious” (led to hospitalization). There were also 18 reports in which the ADR was classified as non-serious. 1 report of a non-serious ADR was received from another RCH. Reports of some ADR cases were poorly documented, and others reported factors that prevent establishing a causal relationship. Finally, in 11 cases positive de-challenge tests were recorded, and in 10 – re-challenge tests. 3 ADR cases were recorded with the use of dorzolamide alone.
Hypertension: Of 37 adverse reaction (AR) reports received from the RCHs, 3 were deemed serious (2 – hospitalization, 1 – life-threatening). 51 reports of increased blood pressure were also received, including 3 serious ones (1 hospitalization). 9 reports (1 serious and 8 non-serious) were received from other RCHs. Based on the analysis of the cases provided by the RCHs, some cases were poorly documented and confusing, while others reported factors that prevent establishing a causal relationship. Finally, in 19 cases the causal relationship was assessed as “possible,” of which 17 had positive de-challenge tests, including 4 with re-challenge, with dorzolamide alone.
Taking into account the probable pharmacological mechanism, the absorption of dorzolamide into the systemic circulation after topical use, and the known adverse reactions with eye drops containing brinzolamide – another carbonic anhydrase inhibitor, PRAC recommends adding the adverse reactions “tachycardia” and “arterial hypertension” to the instructions for medical use of medicinal products containing dorzolamide.
In this connection, in accordance with the PhVWP recommendations of June 2011 on the risk of systemic adverse reactions of beta-blockers for ophthalmic use, a step of eye drop instillation should be added to the “Dosage and administration” section of the instructions for medical use, consisting of pressing on the inner corner of the eye for approximately two minutes after instillation to reduce the systemic exposure to dorzolamide. This information has been included in the instructions for medical use of the innovative product Trusopt® and should be implemented by all RCHs if similar wording has not yet been implemented.
The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the scientific conclusions drawn by the PRAC.
Based on the scientific conclusions, the CMDh considers that the benefit/risk balance of medicinal products containing dorzolamide remains unchanged, provided that the appropriate changes are made to the instructions for medical use.
Amendments to be included in the relevant sections of the instructions for medical use (new text underlined in bold, deleted text struck through).
Section "Posology and method of administration"
Method of administration
…
With nasolacrimal occlusion or closure of the eyelids for 2 minutes, systemic absorption is reduced. This may lead to a decrease in systemic side effects and an increase in local activity.
“Adverse reactions” section
Add the adverse reaction “tachycardia” with the frequency “not known” to the “Cardiac disorders” subsection.
Add to the subsection “Vascular disorders” the adverse reaction “hypertension” with the frequency “not known”.
By the decision of the Coordination Group for Mutual Recognition and Decentralized Procedures – Human (CMDh) held on October 11-13, 2022, clarifications were provided within the PSUSA procedure.
Within the PSUSA for medicinal products containing dorzolamide, the PRAC noted that dorzolamide is also authorized in fixed-dose combination medicinal products. The PRAC considered that the risks of tachycardia and hypertension and the need for nasolacrimal occlusion to limit the absorption of dorzolamide into the systemic circulation in patients with glaucoma are also appropriate to include for medicinal products containing dorzolamide in fixed-dose combinations.
List of medicinal products containing dorzolamide and authorized for medical use in the territory of Ukraine (according to the State Register of Medicinal Products as of 01.12.2022)
For the analysis of published information, the applicant must use the original text available at the link:
