AMZ-002

Guidance Supports Use of Tirosint®-SOL In Pediatric Population PARSIPPANY, N.J., Jan. 12, 2023 /PRNewswire/ -- The American Academy of Pediatrics (AAP), the Pediatric Endocrine Society (PES) and the American Thyroid Association (ATA) have published new guidelines for the treatment of congenital hypothyroidism (CH). For the first time, these leading medical societies cite levothyroxine oral solution as an option for managing patients with CH. Congenital hypothyroidism is a condition affecting up to 1 in every 2,000-4,000 live births in the United States annually. It is a leading cause of intellectual deficiency among infants.1 CH is typically treated with levothyroxine, a synthetic thyroid hormone that is administered daily to restore thyroid hormones to normal levels. Tirosint-SOL (levothyroxine sodium) oral solution is the leading FDA-approved levothyroxine oral solution currently available in the US. New Treatment Guidelines for Congenital Hypothyroidism Published Mention Levothyroxine Oral Solution The newly published treatment guidelines reinforce the use of Tirosint-SOL in the pediatric population. A randomized clinical study published in the journal Hormone Research in Pediatrics examined the efficacy and safety of treating infants newly diagnosed with CH with levothyroxine oral solution in lieu of traditional levothyroxine tablet formulations. In total, 78 infants with congenital hypothyroidism (CH) were studied.2 The study's authors concluded that levothyroxine oral solution was able to successfully treat CH patients to their therapeutic goals. Equally important, no study subject experienced cranial stenosis, a serious adverse effect experienced by infants who are exposed to excessive doses of levothyroxine. "The mention of levothyroxine oral solution in newly published guidelines is an acknowledgement of the utility of drugs like Tirosint-SOL for treating infants with congenital hypothyroidism" stated Susan Rose, Professor Emeritus of the University of Cincinnati College of Medicine, and Cincinnati Children's Hospital Medical Center. "However, liquid formulations like Tirosint-SOL are more easily absorbed than traditional tablet formulations, the current standard of care. Clinicians wishing to prescribe it should take this into consideration." Rose went on to add that "the availability of FDA-approved levothyroxine oral solutions makes it critical to avoid the use of extemporaneously compounded liquid levothyroxine preparations which have been demonstrated to be pharmacologically inconsistent. Clinicians wishing to prescribe liquid levothyroxine for children now have an FDA-approved oral solution." The new treatment guidelines for congenital hypothyroidism were developed jointly by the American Academy of Pediatrics (AAP), the Pediatric Endocrine Society (PES) and the American Thyroid Association (ATA). The new guidelines were published in Pediatrics, the Journal of the American Academy of Pediatrics. The journal is available in print and online. Commenting on the publication of the new guidelines, IBSA Pharma Chief Business and Medical Officer Dr. Carolyn Kong stated that "congenital hypothyroidism is a serious condition with significant public health implications. Traditional levothyroxine tablet formulations have been used for years to treat this population. These formulations require caregivers to crush a child's medication into powder and then to mix it into water before administration. The availability of a levothyroxine oral solutions like Tirosint®-SOL, which has been demonstrated to be effective and safe for infants with CH, now provides patients and healthcare practitioners with a simple, consistent, and convenient option for treating CH." Tirosint®-SOL is the only FDA-approved levothyroxine oral solution available in monodose packaging for convenience and dosing precision. It does not contain gluten, dyes, colorants, lactose, and other ingredients that can cause tolerability and absorption problems. Its unique formulation consists of only three ingredients – levothyroxine, glycerol, and water – which is packaged in patented monodose ampules for precision and convenience. Tirosint®-SOL is indicated to treat the full spectrum of hypothyroid patients regardless of age. It can be administered by pouring the contents of the monodose ampule directly into the mouth or using a spoon or mixing it with water. It is currently available in 15 dosage strengths including unique 13, 37.5, 44 and 62.5 microgram dosing options, giving it the widest dosing range of any levothyroxine therapy available. To help provide patients with cost-effective access to Tirosint®-SOL, IBSA recently enhanced the Tirosint®-SOL Copay Savings Coupon Program. With the new program, eligible patients with commercial insurance can pay as little as $4 for a one-month supply of Tirosint®-SOL or $0 for a 3-month supply. Additional information, including money-saving options for patients without commercial insurance or with high copays or deductibles, can be found at . About Congenital Hypothyroidism (CH) Congenital hypothyroidism (CH) is an endocrine disorder present in up to 1 in every 2,000 - 4,000 live births in the United States each year. It is the result of inadequate thyroid function which results in low or inexistent levels of thyroid hormones. Thyroid hormones are key to the development of human infants. Untreated, or sub-optimally treated, CH is a leading cause of intellectual disability.¹ Levothyroxine is the current standard for treating CH. It is a synthetic thyroid hormone that is administered daily and is available in intravenous and oral formulations. Oral tablets are the most popular form of levothyroxine and must be crushed and added to water before administration to infants. Levothyroxine therapy for CH, once started, continues for three years to life depending on the severity of the disease. Levothyroxine is available by prescription only. About IBSA Pharma Inc. IBSA Pharma is part of IBSA Group which is headquartered in Lugano, Switzerland. IBSA Pharma currently markets Tirosint® (levothyroxine sodium) capsules and Tirosint®-SOL (levothyroxine sodium) oral solution for the treatment of hypothyroidism and Licart® (diclofenac epolamine) topical system 1.3% and Flector® (diclofenac epolamine) topical system 1.3% for the treatment of acute pain due to strains, sprains, and contusions. IBSA Institut Biochimique SA IBSA (Institut Biochimique SA) is a Swiss multinational pharmaceutical Company, founded in 1945 in Lugano. Today, its products are present in over 90 Countries on 5 continents, through the Company's 17 subsidiaries located in Europe, China, and the United States. The company has a consolidated turnover of 800 million CHF, and employs over 2,000 people between headquarters, subsidiaries and production sites. IBSA holds 90 families of approved patents, plus others under development, as well as a vast portfolio of products, covering 10 therapeutic areas: reproductive medicine, endocrinology, pain and inflammation, osteoarticular, aesthetic medicine, dermatology, uro-gynaecology, cardiometabolic, respiratory, consumer health. It is also one of the largest operators worldwide in the area of reproductive medicine, and one of the world's leaders in hyaluronic acid-based products. IBSA has based its philosophy on four pillars: Person, Innovation, Quality and Responsibility. To report SUSPECTED ADVERSE REACTIONS, contact IBSA Pharma Inc. at 1-800-587-3513 or FDA at 1-800- FDA-1088 For more information about IBSA, visit . For full prescribing information, visit . References 1 Rastogi V et al, "Congenital hypothyroidism", Orphanet Journal of Rare Diseases, 2010; 5:17 2 Peroni et al, "Congenital hypothyroidism treatment in infants: a comparative study between liquid and tablet formulations of levothyroxine", Hormone Res Paediatrics, 2014: (81) 50 -54 IMPORTANT SAFETY INFORMATION WARNING: NOT FOR THE TREATMENT OF OBESITY OR FOR WEIGHT LOSS. See full prescribing information for complete boxed warning Thyroid hormones, including TIROSINT-SOL, should not be used for the treatment of obesity or for weight loss. Doses beyond the range of daily hormonal requirements may produce serious or even life-threatening manifestations of toxicity CONTRAINDICATIONS Hypersensitivity to glycerol Uncorrected adrenal insufficiency WARNINGS AND PRECAUTIONS Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate TIROSINT-SOL at less than the full replacement dose because of the increased risk of cardiac adverse reactions, including atrial fibrillation Myxedema coma: Do not use oral thyroid hormone drug products to treat myxedema coma Acute adrenal crisis in patients with concomitant adrenal insufficiency: Treat with replacement glucocorticoids prior to initiation of TIROSINT-SOL treatment Prevention of hyperthyroidism or incomplete treatment of hypothyroidism: Proper dose titration and careful monitoring is critical to prevent the persistence of hypothyroidism or the development of hyperthyroidism Worsening of diabetic control: Therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing, or discontinuing thyroid hormone therapy Decreased bone mineral density associated with thyroid hormone over-replacement. Over-replacement can increase bone reabsorption and decrease bone mineral density. Give the lowest effective dose Limitations of Use Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients Not indicated for treatment of transient hypothyroidism during the recovery phase of subacute thyroiditis Adverse Reactions Adverse reactions with TIROSINT-SOL are primarily those of hyperthyroidism due to therapeutic overdosage including arrhythmias, myocardial infarction, dyspnea, muscle spasm, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash PM 01-22-0102

One aspect of hormonal contraceptives' effect on the teenage body remains a mystery -- whether and how they modify the developing brain. New research in young rats links synthetic hormones found in birth control pills, patches and injections with disordered signal transmission between cells in the prefrontal cortex, an area of the brain that continues to develop throughout adolescence. Reproductive health experts consider hormonal contraceptives good choices for adolescents because they're safe and highly effective at preventing pregnancy, but one aspect of their effect on the teenage body remains a mystery -- whether and how they modify the developing brain. New research in young rats links the synthetic hormones found in birth control pills, patches and injections with disordered signal transmission between cells in the prefrontal cortex, an area of the brain that continues to develop throughout adolescence. Compared to control rats, the animals receiving hormonal contraceptives also produced higher levels of the stress hormone corticosterone, which is similar to cortisol in humans. The Ohio State University scientists launched this line of study in the prefrontal cortex, a region where mood is regulated, because some previous research has associated early adolescent use of hormonal contraceptives with risk for depression in adulthood. But what's most important, the researchers said, is learning how birth control affects the developing brain so individuals can weigh the risks and benefits of their reproductive health choices. "Birth control has had a major positive impact for women's health and autonomy -- so it's not that we're suggesting adolescents should not take hormonal contraceptives," said senior study author Benedetta Leuner, associate professor of psychology at Ohio State. "What we need is to be informed about what synthetic hormones are doing in the brain so we can make informed decisions -- and if there are any risks, then that's something that needs to be monitored. Then if you decide to use hormonal birth control, you would pay more attention to warning signs if you knew of any possible mood-related side effects." The research poster was presented today (Tuesday, Nov. 15, 2022) at Neuroscience 2022, the annual meeting of the Society for Neuroscience. An estimated 2 in 5 teenage girls in the United States have sexual intercourse between age 15 and 19, and the vast majority use a contraceptive -- condoms in particular. Of those using birth control, almost 5% use hormonal contraceptives, also known as long-acting reversible contraceptives. These products are also prescribed to treat acne and heavy periods. Despite their popularity, "there isn't a lot known about how hormonal birth control influences the teen brain and behavior," said co-author Kathryn Lenz, associate professor of psychology at Ohio State. "Adolescence is a crucially under-investigated period of dramatic brain change and dramatic hormonal change that we really haven't understood." The researchers gave a combination of synthetic estrogen and progesterone typically found in hormonal contraceptives to female rats for three weeks beginning about a month after they were born, an age equivalent to early adolescence in humans. Researchers confirmed the drugs disrupted the animals' reproductive cycling -- these birth control products work by stopping ovaries from producing hormones at levels necessary to generate eggs and making the uterine lining inhospitable for an egg to implant. Blood samples showed the treated rats were producing more corticosterone than untreated animals, a sign that they were stressed. And after being subjected to and recovering from an experimental stressor, the treated rats' corticosterone level remained high. Their adrenal glands were also larger, suggesting their stress hormone production was consistently higher than that of control animals. An analysis of gene activation markers in the animals' prefrontal cortex showed a decrease in excitatory synapses in that region of treated rats' brains compared to controls, but no change to inhibitory synapses -- a phenomenon that could set up an imbalance of normal signaling patterns and result in altered behavior. The loss of only excitatory synapses in the prefrontal cortex has been linked to exposure to chronic stress and depression in previous research. "What this means for the function of particular circuits, we don't know yet. But this gives us a clue of where to look next in terms of what the functional outcomes might be," Lenz said. The researchers are moving forward with additional studies targeting hormonal contraceptive effects on the brain between puberty and late adolescence -- a tricky time to study the developing brain because it is undergoing constant change, Leuner said. The reasons behind the drugs' effects are an open question, as well. "These are synthetic hormones, so are they affecting the brain because of their synthetic properties, or are they affecting the brain because they're blocking the naturally produced hormones?" she said. "It's a difficult question to answer, but an important one." First author Rachel Gilfarb, a graduate student in Leuner's lab, presented the poster. Additional Ohio State co-authors include Meredith Stewart, Abhishek Rajesh, Sanjana Ranade and Courtney Dye. Further information: