Neurocirculatory Asthenia

We still don’t fully understand why the SARS-CoV-2 virus is so transmissible and causes severe disease in some people but not others. But Dr. Philip Adamson, chief medical officer of Abbott’s heart failure business, said he’s amazed by how quickly we’re learning about COVID-19, building off our prior knowledge of coronaviruses and other viral pathogens. “We have more of a handle on the mechanisms, and that’s where I think we are beginning to have hope for clarity,” he said. “In just about every disease that we are able to treat, we develop those treatments because we understand the fundamental mechanism of the disease.” Adamson warned of increasing rates of heart and lung failure due to COVID-19 when Medical Design & Outsourcing interviewed him last year. We’ve checked in for an update on the latest about COVID-19’s cardiovascular impact and how medical devices can keep patients alive. The following conversation has been lightly edited for space and clarity. MDO: What have you learned about COVID-19 since we last spoke? Adamson: The receptor that this virus utilizes to get into the cell is part of the system we call the renin-angiotensin-aldosterone system. It’s the angiotensin II receptor. That’s really all over the body, but mostly expressed in the lungs, so that’s why it focuses on lung damage when it sets up an infection. But the process, we’ve now learned, is there are both direct and indirect effects on the heart and blood vessels. We talked a lot about the indirect effects of the cytokine storm and the intense inflammation that occurs typically in some people with this disease and syndrome. That is well defined now through multiple different inflammatory mediators that actually could be targets for therapy in the future. But that inflammatory mediation is maybe more exaggerated in people with preexisting cardiovascular inflammatory states like metabolic syndrome or other syndromes that would cause this underlying, low-burn inflammatory state that we’re aware of. Clearly, those that have cardiovascular disease seem to have a higher chance to have severe disease when they get COVID-19. What we were worried about early on is that we can fairly commonly see and detect injury to the heart during a severe COVID infection. When patients are having COVID and feeling bad but not going to the hospital, nobody tests those folks for heart inflammation as a result. But when the moderate to severe disease that lends itself to hospitalization occurs, the cardiac community has been interested to see how that’s mediated, how many people get it, is it only found in moderate to severe disease? We typically make inferred diagnoses in cardiovascular disease. So if we measure a blood component that is a biomarker like troponin that is only in the bloodstream measurably when the heart’s damaged, or we measure a protein called B-type natriuretic protein — which really is only in the circulation in higher levels when the heart has stress on its filling — we then take those essential measurements and make diagnoses or inferred diagnoses from that. We find that troponin I — which is a significant marker of myocardial injury or heart muscle injury — is elevated in many people with moderate or severe disease. We thought that the total inflammation plus the direct effect on the heart might cause a marked increase in myocarditis, which is a global inflammation of the heart muscle itself, and it is associated with other viral infections. That’s not been what we see in these infections. But there’s clear evidence that in about 20% of people there’s an elevation in troponin, which would be a diagnostic criterion for a myocardial injury or myocardial infarction. And that then leads to a higher risk of death. It’s pretty clear actuarially that if a moderate or severe COVID syndrome is associated with an elevation of troponin then the prognosis is much poorer. It is associated with higher risk of death through a variety of blood vessel and heart muscle abnormalities that can cause cardiovascular disability as well as death. MDO: Anything new on lasting cardiovascular effects from mild COVID-19 cases? Adamson: I am still concerned that any kind of inflammation or any kind of direct injury to the heart muscle — we know this from other diseases and other situations — sets up this potential for long-term myocardial damage and nonischemic cardiomyopathy. It’s just too soon. That takes years. It is theoretically possible and certainly there’s a lot of evidence to suggest that could happen. The data is still accumulating about how severe the heart is involved in mild to moderate nonhospitalized cases. There are studies that would suggest that there is some probable inflammatory injury. But I don’t think that we have enough definitive information to make a conclusion yet. MDO: We initially thought of COVID-19 as a respiratory disease, but is it more helpful to think of it as a vascular disease in that it touches everything the vascular system touches down to the smallest capillaries? Adamson: That’s a great question, and it turns out that it can be better understood when you understand the angiotensin receptor that’s involved in the transmission of this disease. The virus binds to this natural receptor to get into the cell, and in that process gets into the membrane and then it sets up all the inflammation, etc. And the lung, alveolar cells are really studded with these receptors, so that’s where the virus finds the opportunity into the cell. It makes sense then that most of the symptoms and developments as a result of COVID-19 syndrome are focused on the lungs. That being said, the angiotensin system is one of the most important regulatory systems for the cardiovascular system, both the heart and the blood vessels. Those receptors are everywhere, and they’re available when you inhale the virus. When it becomes systemic, then you do get direct effects on the blood vessels, on the heart, on the coagulation sequencing in the blood vessels, primarily probably stimulated by disruptions in the endothelial cells that line the inside of the blood vessels. The body doesn’t like disruptions in that. When it sees those kinds of breaks in the endothelium, it has to fix them and it starts that fix with the coagulation system. That can deplete the system of its first responders, which then causes this concept of disseminated intervascular coagulation in which you get this cascade of coagulation. And that’s most apparent in the smaller blood vessels, especially those that are going from the heart to the lungs, the capillaries in the pulmonary circulation, and that just obstructs the ability to get oxygen then into the bloodstream. Then the oxygen level drops, acid-base levels change, electrolytes change, and now you have not only systemic inflammation, but you have all the substrate for injury to the heart. That would include direct muscle injury, direct production of arrhythmias, blood clots in small vessels, deep vein thrombosis and pulmonary emboli are very common. It’s a cascading effect, a combination of both direct effects on the heart and the blood vessels, and an indirect effect of this massive inflammation that can occur along with the oxygenation, etc. It is complex, but on the other hand, it kind of makes sense if you think of it as starting with this receptor that is found in a lot of places, and every place it’s found has a potential of being impacted by the disease. And so far it’s shown great success in doing that. MDO: The coagulation in the smallest capillaries, is that what’s referred to as COVID-19 microclotting? Adamson: Exactly, and we all do this because our blood vessels are constantly under stress. When there’s a break in them we have this system that surveils and repairs those vessels all the time. And when that cascading of blood clotting gets out of control, then the blood clot obstructs the blood vessel. These tiny vessels where the exchange of oxygen and carbon dioxide occur are not too much bigger than a red blood cell itself, so it doesn’t take much to get a clot that destroys or blocks up those vessels. Then it doesn’t matter how much oxygen you breathe in, you can’t get it across the membrane into the bloodstream if that happens in a large enough load on the lung. MDO: Are there tests to detect microclotting? Adamson: You can’t really look at the tiny blood vessels, but you can see the effects of it in some of this ground glass appearance on CT scans of the lungs. Oxygenation’s a big deal in this disease. And that’s why extracorporeal membrane oxygenation has become a lifesaving intervention. Essentially it’s a bypass for the lungs. You take away that function until it can recannulate and it eventually will if given enough time. But unfortunately, the host can’t survive if it doesn’t have an operating lung system. Larger clots are fairly common and we can directly image them either with ultrasound or venography. In the veins of the leg, many times those clots break off and can go to other parts of the circulation. Most commonly, they go back into the lungs. These are big clots that can obstruct the blood flow in general to a whole segment of the lung. Pulmonary embolism can range from not even knowing you have it to death — sudden death. That component is well described with the coagulation abnormalities that occur with COVID-19. MDO: What role can medical devices play to tackle COVID-19, both in prevention and treatment? Adamson: The most important are supportive devices when severe disease occurs. It is absolute in my mind, it is very clear that extracorporeal membrane oxygenation is the most effective way to save a life. Early on, it was thought that when ECMO was applied, people tended to die. What we learned is that there was too much time before it was applied. It was applied too late. ECMO was this sort of temporizing medical device intervention that saves lives. We now have seen that we really have to have a broader availability of providing that therapy. And I think everybody now recognizes that we’re going to have to have that if people are going to survive this disease. Related: Dexcom focuses on early diabetes diagnosis as COVID links emerge

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

FARMVILLE, N.C., Oct. 24, 2022 /PRNewswire/ -- CMP Pharma announced today that Tadliq ® (Tadalafil) Oral Suspension, 20 mg/5 mL, the first and only FDA-approved oral liquid suspension of tadalafil, is now available. Tadliq is the first and only FDA-approved liquid oral suspension of tadalafil for adult patients with difficulty swallowing. Tadliq is indicated for the treatment of pulmonary arterial hypertension and ensures consistent dosing. FDA-approved Tadliq addresses the inconsistencies that come from unapproved crushed or compounded tablets and removes the need for complex preparation of powder formulations. Tadliq has a mild peppermint flavor and is available in 150 mL bottles with a 24-month shelf life. "Tadliq is for patients who need treatment but have difficulty swallowing tablets. This product is a nice addition to our portfolio of cardiovascular liquids for this specific patient population which is often ignored", said Gerald Sakowski, CEO of CMP Pharma, Inc. Tadliq is available through three preferred specialty pharmacies and selected wholesalers. CMP Pharma also supports physicians and patients through the CMP Support Services program. Support service representatives are available Monday through Friday from 8 AM to 5 PM EST by contacting the program at 1-844-267-0001. Tadliq (Tadalafil) Oral Suspension is now available. For more information, contact CMP Pharma at 252-753-7111 or visit tadliq.com. About Tadliq Tadliq is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%). Tadliq is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. About CMP Pharma, Inc. CMP Pharma is a specialty pharmaceutical company that addresses critical needs for niche markets by developing and manufacturing a portfolio of high value pharmaceutical products, including oral liquids and semi-solids. CMP Pharma combines decades of experience in pharmaceutical development and manufacturing to provide medicines to fill the unmet medical needs of many patients. Important Safety Information Indications and Usage TADLIQ® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%). Contraindications Concomitant organic nitrates Concomitant Guanylate Cyclase (GC) Stimulators History of known serious hypersensitivity reaction to TADLIQ, ADCIRCA® or CIALIS® Warnings and Precautions Hypotension: Carefully consider whether patients with certain underlying cardiovascular disease could be adversely affected by vasodilatory effects of TADLIQ. Not recommended in patients with pulmonary veno-occlusive disease. Effects on the eye: Sudden loss of vision could be a sign of non-arteritic ischemic optic neuropathy (NAION) and may be permanent. Hearing impairment: Cases of sudden decrease or loss of hearing have been reported with tadalafil. Concomitant PDE5 inhibitors: Avoid use with CIALIS, ADCIRCA or other PDE5 inhibitors. Prolonged erection: Advise patients to seek emergency treatment if an erection lasts >4 hours. To report SUSPECTED ADVERSE REACTIONS, contact CMP Pharma, Inc. at 1-844-321-1443 or FDA at 1-800-FDA-1088 or . Drug Interactions Nitrates: Administration of nitrates within 48 hours after the last dose of TADLIQ is contraindicated Alpha-Blockers: PDE5 inhibitors, including TADLIQ, and alpha-adrenergic blocking agents are both vasodilators with blood- pressure-lowering effects. Antihypertensives: PDE5 inhibitors, including TADLIQ, are mild systemic vasodilators. Alcohol: Both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. CYP3A Inhibitors/Inducers: Ritonavir, Potent Inhibitors of CYP3A, Potent Inducers of CYP3A Dosage and Administration The recommended dose of TADLIQ is 40 mg (10 mL) taken once daily with or without food. Please click link for full Prescribing Information: TAD-00030 SOURCE CMP Pharma