Celiprolol 200mg tablets

Fruit juice-antihypertensive drug interactions can lead to subtherapeutic or supratherapeutic outcomes. This systematic review and meta-analysis assesses such interactions and their potential clinical relevance. PubMed, Scopus, and Science Direct databases were searched from their inception through June 2024. Eligible studies were those that investigated the effects of fruit juice on the pharmacokinetics of antihypertensive drugs. I 2 was used to determine heterogeneity among studies, and a random effect model was employed for meta-analysis. This review adhered to PRISMA guidelines and was registered in PROSPERO (CRD42022340159). Fifty-one studies were included. Most of them were open-label crossover trials. Grapefruit juice (GFJ), an inhibitor of organic-anion-transporting polypeptide (OATP) transporters and cytochrome P450 (CYP) 3A4, significantly decreased the AUC and C max of aliskiren and celiprolol by approximately 80–90 %. Conversely, the AUC and C max of calcium channel blockers decreased with variable degrees when co-administered with GFJ. Apple and orange juices have comparable effects on certain medications. Most studies had small sample sizes and were of moderate quality. Hemodynamic effects were not assessed in most studies; thus, the clinical significance of these interactions remains uncertain and should be further investigated. Co-administration of fruit juice with antihypertensive drugs can result in an increase or decrease in drugs’ bioavailability, depending on the drugs’ metabolism route and the involvement of transporters. Though further studies are needed to confirm clinical relevance in hypertensive patients, it is advised to avoid co-consumption of fruit juice with drugs showing significant changes in pharmacokinetic parameters to prevent subtherapeutic or supratherapeutic effects. • Grapefruit juice decreased AUC and C max of aliskiren, celiprolol, and calcium channel blockers. • Orange juice and apple juice also decreased C max and AUC of certain antihypertensive drugs such as aliskiren and atenolol. • The clinical relevance of fruit juice-antihypertensive drug interactions remains unexplored in hypertensive patients.

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OBJECTIVES: Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders characterized by mutations affecting collagen and extracellular matrix proteins. Vascular EDS (vEDS) stands out for its severe prognosis due to the heightened risk of arterial and organ rupture which significantly increase mortality rates. Limited strategies for treating vEDS are prompting exploration for alternatives such as celiprolol, a cardioselective beta-blocker with potential to reduce vascular stress and improve collagen integrity. This review aims to evaluate current evidence on the impact of celiprolol in managing vEDS. METHODS: A comprehensive literature search was conducted across scientific databases for studies comparing celiprolol with placebo or other treatments, focusing on relevant outcomes. RESULTS: A total of 323 participants were included across studies published from 2010 to 2023, primarily conducted in European settings. Celiprolol administration, starting at 100 mg daily and titrated up to 400 mg, significantly reduced the incidence of major vascular events such as arterial dissections and ruptures. Most studies reported improved survival rates and fewer hospitalizations due to acute arterial events. Variations in treatment response and side effects such as dizziness and hypotension were noted across studies, occasionally leading to treatment. CONCLUSIONS: Celiprolol appears to be a promising treatment for reducing vascular events in vEDS patients, potentially improving quality of life and mitigating the substantial morbidity and mortality associated with vEDS. Future research should focus on refining treatment protocols, exploring mechanisms of action, and establishing comprehensive clinical guidelines to optimize patient outcomes.

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ObjectiveVascular Ehlers-Danlos syndrome (vEDS) is a rare monogenetic disease caused by pathogenic variants in procollagen 3A1. Arterial rupture is the most serious clinical manifestation. A randomised controlled trial, the Beta-Blockers in Ehlers-Danlos Syndrome Treatment (BBEST) trial, reported a significant protective effect of the beta blocker celiprolol. The aim was to study the outcome of celiprolol treatment in a cohort of Swedish patients with vEDS.MethodsUppsala is a national referral centre for patients with vEDS. They are assessed by vascular surgeons, angiologists, and clinical geneticists. Family history, previous and future clinical events, medication, and side effects are registered. Celiprolol was administered twice daily and titrated up to a maximum dose of 400 mg daily. Logistic regression was used to analyse predictors of vascular events.ResultsForty patients with pathogenic sequence variants in COL3A1 were offered treatment with celiprolol in the period 2011–2019. The median follow up was 22 months (range 1–98 months); total follow up was 106 patient years. In two patients, uptitration of the dose is ongoing. Of the remaining 38, 26 (65%) patients reached the target dose of 400 mg daily. Dose uptitration was unsuccessful in six patients because of side effects; one died before reaching the maximum dose, and five terminated the treatment. Five major vascular events occurred; four were fatal (ruptured ascending aorta; aortic rupture after type B dissection; ruptured cerebral aneurysm; and ruptured pulmonary artery). One bled from a branch of the internal iliac artery, which was successfully coiled endovascularly. The annual risk of a major vascular event was 4.7% (n = 5/106), similar to the treatment arm of the BBEST trial (5%) and lower than in the control arm of the same trial (12%). No significant predictor of vascular events was identified.ConclusionTreatment with celiprolol is tolerated in most patients with vEDS. Despite fatal vascular events, these observations suggest that celiprolol may have a protective effect in vEDS. Vascular Ehlers-Danlos syndrome (vEDS) is a rare monogenetic disease caused by pathogenic variants in procollagen 3A1. Arterial rupture is the most serious clinical manifestation. A randomised controlled trial, the Beta-Blockers in Ehlers-Danlos Syndrome Treatment (BBEST) trial, reported a significant protective effect of the beta blocker celiprolol. The aim was to study the outcome of celiprolol treatment in a cohort of Swedish patients with vEDS. Uppsala is a national referral centre for patients with vEDS. They are assessed by vascular surgeons, angiologists, and clinical geneticists. Family history, previous and future clinical events, medication, and side effects are registered. Celiprolol was administered twice daily and titrated up to a maximum dose of 400 mg daily. Logistic regression was used to analyse predictors of vascular events. Forty patients with pathogenic sequence variants in COL3A1 were offered treatment with celiprolol in the period 2011–2019. The median follow up was 22 months (range 1–98 months); total follow up was 106 patient years. In two patients, uptitration of the dose is ongoing. Of the remaining 38, 26 (65%) patients reached the target dose of 400 mg daily. Dose uptitration was unsuccessful in six patients because of side effects; one died before reaching the maximum dose, and five terminated the treatment. Five major vascular events occurred; four were fatal (ruptured ascending aorta; aortic rupture after type B dissection; ruptured cerebral aneurysm; and ruptured pulmonary artery). One bled from a branch of the internal iliac artery, which was successfully coiled endovascularly. The annual risk of a major vascular event was 4.7% (n = 5/106), similar to the treatment arm of the BBEST trial (5%) and lower than in the control arm of the same trial (12%). No significant predictor of vascular events was identified. Treatment with celiprolol is tolerated in most patients with vEDS. Despite fatal vascular events, these observations suggest that celiprolol may have a protective effect in vEDS.

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BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol has been suggested to significantly reduce rates of vascular events in this setting, though real-world evidence is limited. The aim of this study was to report our experience with celiprolol therapy in vEDS management. METHODS: Patients with a genetically confirmed diagnosis of vEDS who were referred for outpatient consultation at the Brescia University Hospital between January 2011 and July 2023 were included. At each visit, patients' medical history, results of vascular imaging, and office blood pressure measurements were recorded. Celiprolol therapy was progressively titrated to the maximum tolerated dose of up to 400 mg daily, according to the patients' tolerance. RESULTS: Overall, 26 patients were included. Female sex was prevalent (62%). Mean (SD) age was 37 (16) years. Follow-up duration was 72 (41) months. At the last follow-up visit, all patients were on celiprolol therapy, 80% of whom were taking the maximum recommended dose. The yearly risk of symptomatic vascular events was 8.8%, the majority of which occurred after reaching the maximum recommended dose of celiprolol. No significant predictor of symptomatic vascular events was identified among patients' clinical characteristics. CONCLUSION: In our cohort, rates of celiprolol use were high and the drug was well tolerated overall. Nonetheless, the risk of symptomatic vascular events remained nonnegligible. Future studies should identify reliable predictors of major adverse events and explore additional therapeutic strategies that could further lower the risk of life-threatening events in this population.

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) gene, encoding type III procollagen. Patients with vEDS present with severe tissue fragility that can result in arterial aneurysm, dissection, or rupture, especially of medium-caliber vessels. Although early reports have indicated a very high mortality rate in affected patients, with an estimated median survival of around 50 years, recent times have seen a remarkable improvement in outcomes in this population. This shift could be related to greater awareness of the disease among patients and physicians, with improved management both in terms of follow-up and treatment of complications. Increasing use of drugs acting on the cardiovascular system may also have contributed to this improvement. In particular, celiprolol, a β1 cardio-selective blocker with a β2-agonist vasodilator effect, has been shown to reduce rates of vascular events in patients with vEDS. However, the evidence on the true benefits and possible mechanisms responsible for the protective effect of celiprolol in this specific setting remains limited. Drugs targeting the extracellular matrix organization and autophagy-lysosome pathways are currently under investigation and could play a role in the future. This narrative review aims to summarize current evidence and future perspectives on vEDS medical treatment, with a specific focus on vascular prevention.

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Pritelivir is a novel viral helicase-primase inhibitor active against herpes simplex virus. In vitro drug-drug interaction studies indicated that pritelivir has the potential for clinically relevant interactions on the cytochrome P450 (CYP) enzymes 2C8, 2C9, 3A4, and 2B6, and intestinal uptake transporter organic anion transporting polypeptide (OATP) 2B1 and efflux transporter breast cancer resistance protein (BCRP). This was evaluated in 2 clinical trials. In 1 trial the substrates flurbiprofen (CYP2C9), bupropion (CYP2B6), and midazolam (CYP3A4) were administered simultaneously as part of the Geneva cocktail, while the substrate celiprolol (OAPT2B1) was administered separately. In another trial, the substrates repaglinide (CYP2C8) and rosuvastatin (BCRP) were administered separately. Exposure parameters of the substrates and their metabolites (flurbiprofen and bupropion only) were compared after administration with or without pritelivir under therapeutic concentrations. The results of these trials indicated that pritelivir has no clinically relevant effect on the exposure of substrates for the intestinal uptake transporter OATP2B1 and the CYP enzymes 3A4, 2B6, 2C9, and 2C8, and has a weak inhibitory effect on the intestinal efflux transporter BCRP. In summary, the results suggest that pritelivir has a low drug-drug interaction potential.

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