In accordance with paragraph 8 of Section IV of the Procedure for Expert Evaluation, the applicant must amend the instructions for medical use of the medicinal product upon receipt of new data, including bringing the instructions for medical use into line with the approved instructions for medical use of the original (reference) medicinal product, and ensure that the information on the medicinal product corresponds to current scientific knowledge.
The Pharmacovigilance Risk Assessment Committee (PRAC), based on the evaluation of periodic safety update reports (PSURs) for medicinal products containing phenylephrine / tropicamide, PSUSA/00010430/202511, reached the following conclusions.
In view of the available data on anaphylactic reaction and necrotizing enterocolitis in premature infants obtained from literature sources and spontaneous reports, including in individual cases a close temporal relationship, a positive reaction to withdrawal of the medicinal product (de-challenge) and/or a positive reaction to re-administration of the medicinal product (re-challenge), as well as in view of a plausible mechanism of action, the PRAC considers that a causal relationship between the use of phenylephrine / tropicamide and anaphylactic reaction and necrotizing enterocolitis in premature infants is at least reasonably possible. The PRAC concluded that the instructions for medical use of medicinal products containing phenylephrine / tropicamide should be amended accordingly.
Having considered the PRAC recommendations, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the overall conclusions of the PRAC and the grounds for the recommendations.
Based on the scientific conclusions on phenylephrine / tropicamide (phenylephrine / tropicamide), the CMDh considers that the benefit / risk balance of medicinal products containing phenylephrine / tropicamide (phenylephrine / tropicamide) remains unchanged, subject to the introduction of the proposed changes to the instructions for medical use.
Changes to be made to the relevant sections of the package insert (new text underlined and in bold, deleted text struck through).
“Special precautions for use” section
The following warning should be added:
Pediatric population
Use in children under 12 years of age is contraindicated because serious systemic adverse reactions have been reported with ophthalmic medicinal products containing phenylephrine and tropicamide, especially in the pediatric population, such as cardiovascular disorders with severe hypertension, changes in heart rate, and pulmonary edema and necrotizing enterocolitis in premature infants.
“Adverse reactions” section
The following adverse reaction should be added to the System Organ Class (SOC) “Immune system disorders” with the frequency “not known”:
Anaphylactic reaction
The following adverse reaction should be added to the tabular list of adverse reactions:
Pediatric population
[…]
– Gastrointestinal disorders:
Necrotizing enterocolitis in premature infants with the frequency “not known” (cannot be estimated from the available data).
Changes to the safety information of medicinal products containing phenylephrine / tropicamide (phenylephrine / tropicamide) following the meeting of the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) of 21 – 22 July 2026
Phenylephrine / tropicamide (phenylephrine / tropicamide) – PSUSA/00010430/202511
The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), having considered the Periodic Safety Update Reports (PSURs) on the basis of the recommendations and report of the Pharmacovigilance Risk Assessment Committee (PRAC), agreed by consensus to amend the registration materials / instructions for medical use of medicinal products containing phenylephrine / tropicamide.
Tropicamide is also registered as a single-component medicinal product. PRAC concluded that the risk of an anaphylactic reaction should also be taken into account for medicinal products containing tropicamide as the sole active substance, since several identified cases of anaphylactic reactions occurred during the use of eye drops containing tropicamide as the sole active substance.
A list of medicinal products containing phenylephrine / tropicamide (phenylephrine / tropicamide) and tropicamide (tropicamide) that are authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 15.09.2026). (12 KB) (Uploaded: 29.09.2026 06:59:42)
TO ANALYZE THE PUBLISHED INFORMATION AND SUBMIT THE RELEVANT APPLICATION FOR AMENDMENTS TO THE REGISTRATION MATERIALS, THE APPLICANT MUST USE THE ORIGINAL TEXT AVAILABLE AT THE FOLLOWING LINKS:
