Information Letter-Notice

Levofloxacin (Novox®), Ofloxacin (Ofor®)

Information letter-notice to healthcare professionals – reminder of restrictions on use (risk of persistent serious adverse reactions)

Dear Healthcare Professionals,

Organosyn Ltd., Ukraine, the authorized representative of the applicant Organosyn Lifesciences (FZC), UAE, the marketing authorization holder for the antibacterial medicinal products of the quinolone group – Novox®, infusion solution 0.5%, Novox®-500, Novox®-750, film-coated tablets 500 mg or 750 mg (active substance: levofloxacin), and Ofor®, film-coated tablets (active substances: ofloxacin and ornidazole) – in agreement with the European Medicines Agency (EMA) and the State Expert Center of the Ministry of Health of Ukraine, hereby informs you of the following:

Summary:

• Recent studies indicate that antibacterial agents belonging to the fluoroquinolone class continue to be prescribed outside the recommended indications.

• Fluoroquinolones for systemic and inhalation use should NOT be prescribed:

  • to patients with a history of serious adverse reactions associated with quinolone or fluoroquinolone antibacterial agents;

  • for mild or self-limiting infections (such as pharyngitis, tonsillitis, and acute bronchitis);

  • for infections of mild to moderate severity (including uncomplicated cystitis, exacerbation of chronic bronchitis and chronic obstructive pulmonary disease (COPD), acute bacterial rhinosinusitis, and acute otitis media), except when other antibacterial agents commonly recommended for these infections are deemed inappropriate;

  • for non-bacterial infections, e.g., non-bacterial (chronic) prostatitis;

  • for prophylaxis of traveler’s diarrhea or recurrent lower urinary tract infections.

• Fluoroquinolones for systemic and inhalation use are associated with very rare, but serious, disabling, long-lasting, and potentially irreversible adverse reactions. These agents should be prescribed only for approved indications and after careful benefit–risk assessment for each patient.

Background of the safety issue

The European Medicines Agency (EMA) strongly recommends limiting the use of systemic and inhaled fluoroquinolones based on a European-wide review conducted in 2018 to assess the risk of serious, long-term (lasting months or years), disabling, and potentially irreversible adverse reactions, mainly affecting the musculoskeletal and nervous systems. As a result of the EMA review, the use of fluoroquinolones was significantly restricted in 2019.

These serious adverse reactions may include tendinitis, tendon rupture, arthralgia, limb pain, gait disturbances, neuropathies associated with paresthesia, depression, fatigue, memory impairment, hallucinations, psychosis, sleep disorders, and sensory impairments (hearing, vision, taste, and smell). Tendon damage (especially to the Achilles tendon, though other tendons may be affected) can occur within 48 hours of treatment initiation or may appear several months after treatment has been discontinued.

An EMA-funded study [“Impact of changes in labelling of fluoroquinolone-containing antibacterial agents for systemic and inhalation use in the European Union” (EUPAS37856)], based on data from six European healthcare databases (Belgium, France, Germany, the Netherlands, Spain, and the UK), suggests that fluoroquinolones may still be prescribed outside the approved indications. However, due to study limitations, definitive conclusions cannot be drawn.

• Healthcare professionals should advise patients:

  • about the risk of serious adverse reactions;

  • about the potentially long-term and serious nature of such reactions;

  • about the need to seek immediate medical advice at the first signs of serious adverse reactions before continuing treatment.

• Special caution should be exercised in patients taking corticosteroids, elderly patients, patients with renal impairment, and those who have undergone solid organ transplantation, as the risk of tendinitis and tendon rupture due to fluoroquinolones may be increased in these groups.

Call for reporting

In accordance with the requirements of the Pharmacovigilance Procedure approved by the Order of the Ministry of Health of Ukraine No. 898 of December 27, 2006, registered with the Ministry of Justice of Ukraine on January 29, 2007 under No. 73/13340, all suspected adverse reactions should be reported to the State Expert Center of the Ministry of Health of Ukraine at:

https://aisf.dec.gov.ua/

You may also report adverse reactions to the official representative of the applicant of these medicinal products in Ukraine – Organosyn Ltd. by phone: +38 (050)444-70-26 or by email: vigilance@organosyn.com.ua

Link to the letter: [view]