In the JournalsPerspective

Flavored levofloxacin more easily accepted by kids with MDR-TB

An orange-peppermint flavored, dispersible levofloxacin tablet was reported to be more palatable and easier to prepare by caregivers of children with multidrug-resistant tuberculosis, according to research published in The Pediatric Infectious Disease Journal. The researchers said the new formulation may be more acceptable for young children and improve adherence.

Susan E. Purchase, MD, from the department of pediatrics and child health at Stellenbosch University and the Desmond Tutu TB Centre in South Africa, and colleagues said that both patient and medicinal characteristics determine whether a product is acceptable to use. These factors may include the taste of the drug, whether a patient is able to swallow it, and its appearance, dosing and mode of administration.

“Adult formulations of moxifloxacin and levofloxacin are not dispersible and are bitter when crushed,” Purchase and colleagues wrote. “Thus, there is an urgent need for child-friendly formulations of fluoroquinolones and for any new formulations to be appropriately assessed for acceptability in children prior to their use in clinical trials and routine care.”

Children aged younger than 5 years in Cape Town, South Africa, who were exposed to a household contact with MDR-TB were given standard care, which included an adult dose of levofloxacin (250 mg), ethambutol and high-dose isoniazid. When children enrolled in the study, the standard of care was interrupted, and the patients received a weight-balanced dose (15 mg/kg to 20 mg/kg) of the dispersible levofloxacin formulation.

The researchers evaluated the dispersible drug’s acceptability among children at follow-up visits 7 to 14 days after enrollment.

All 27 patients (median age, 1.9 years) were uninfected by HIV and clinically well at enrollment. Most children (85%) were able to take the full dose of the medication or swallowed it with only “minimal spillage,” the researchers said. The dose was refused by 12% of children, and 4% spat out the dose.

Most caregivers (93%) administered the medication dissolved in water at home, but one child swallowed the tablet whole and one child was administered the medication crushed into food.

Nearly all caregivers reported that the tablet size (82%) and volume of dispersion (93%) were acceptable. Additionally, caregivers reported that the flavor-masked medication was more palatable (69%) and easier to prepare (81%) than adult levofloxacin formulations.

“The much-improved acceptability of this dispersible formulation over existing adult tablets provides strong evidence for TB programs to take up this formulation for pediatric MDR-TB therapy, as it is now WHO prequalified and available from the Global Drug Facility,” the researchers wrote. – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

An orange-peppermint flavored, dispersible levofloxacin tablet was reported to be more palatable and easier to prepare by caregivers of children with multidrug-resistant tuberculosis, according to research published in The Pediatric Infectious Disease Journal. The researchers said the new formulation may be more acceptable for young children and improve adherence.

Susan E. Purchase, MD, from the department of pediatrics and child health at Stellenbosch University and the Desmond Tutu TB Centre in South Africa, and colleagues said that both patient and medicinal characteristics determine whether a product is acceptable to use. These factors may include the taste of the drug, whether a patient is able to swallow it, and its appearance, dosing and mode of administration.

“Adult formulations of moxifloxacin and levofloxacin are not dispersible and are bitter when crushed,” Purchase and colleagues wrote. “Thus, there is an urgent need for child-friendly formulations of fluoroquinolones and for any new formulations to be appropriately assessed for acceptability in children prior to their use in clinical trials and routine care.”

Children aged younger than 5 years in Cape Town, South Africa, who were exposed to a household contact with MDR-TB were given standard care, which included an adult dose of levofloxacin (250 mg), ethambutol and high-dose isoniazid. When children enrolled in the study, the standard of care was interrupted, and the patients received a weight-balanced dose (15 mg/kg to 20 mg/kg) of the dispersible levofloxacin formulation.

The researchers evaluated the dispersible drug’s acceptability among children at follow-up visits 7 to 14 days after enrollment.

All 27 patients (median age, 1.9 years) were uninfected by HIV and clinically well at enrollment. Most children (85%) were able to take the full dose of the medication or swallowed it with only “minimal spillage,” the researchers said. The dose was refused by 12% of children, and 4% spat out the dose.

Most caregivers (93%) administered the medication dissolved in water at home, but one child swallowed the tablet whole and one child was administered the medication crushed into food.

Nearly all caregivers reported that the tablet size (82%) and volume of dispersion (93%) were acceptable. Additionally, caregivers reported that the flavor-masked medication was more palatable (69%) and easier to prepare (81%) than adult levofloxacin formulations.

“The much-improved acceptability of this dispersible formulation over existing adult tablets provides strong evidence for TB programs to take up this formulation for pediatric MDR-TB therapy, as it is now WHO prequalified and available from the Global Drug Facility,” the researchers wrote. – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Jeffrey R. Starke

    Jeffrey R. Starke

    The treatment of TB infection and disease in children has been hampered significantly by the lack of child-friendly drug formulations for children. Because TB is considered an “orphan disease,” adequate pharmacokinetic (PK) studies in children and the development of pediatric formulations have not been required for TB drug licensing. As a result, children have been treated with pills and capsules that were designed for use in adults, which are often crushed or put into suspensions with unknown PK characteristics.

    Imagine having to administer four different kinds of anti-TB pills and capsules designed for adults to a 2-year-old child every day. I have always admired the families of my patients who have been able to successfully complete TB therapy for their children.

    In 2015, the TB Alliance and its partners developed child-friendly, dispersible, fixed-dose combination medications containing isoniazid, rifampicin and pyrazinamide for treating drug-susceptible TB. These formulations are being distributed all over the world and are having a large impact on treatment adherence and completion for children.

    A 2016 modelling study estimated that in 2014, 25,000 children developed MDR-TB and 1,200 developed extensively drug-resistant (XDR) TB. An estimated 2 million children have MDR-TB infection and 100,000 have XDR-TB infection worldwide.

    Levofloxacin is a particularly important drug to target for child-friendly formulations as it is part of the bulwark of treatment for MDR-TB disease and is the recommended drug for treatment of MDR-TB infection to prevent progression to disease, which is especially important for young children.

    This South African study showed a high rate of acceptance and acceptability of a dispersible formulation of levofloxacin among 27 children with a median age of 1.9 years. This study, along with the pre-marketing studies conducted by the TB Alliance, have established a standard for testing the acceptability of child-friendly TB drug formulations in children. It is critical that all manufacturers of anti-TB drugs developed in the future be required to provide child-friendly formulations that have undergone this type of evaluation.

    • Jeffrey R. Starke, MD
    • Professor of pediatrics
      Baylor College of Medicine
      Infectious Diseases in Children Editorial Board member

    Disclosures: Starke reports no relevant financial disclosures.