What is Misenbo 62.5?
Misenbo 62.5 is used to treat the symptoms of pulmonary arterial hypertension. This is the high blood pressure that occurs in the main artery that carries blood from the right side of the heart (the ventricle) to the lungs. When the smaller blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump enough blood through the lungs. Misenbo 62.5 works by blocking a hormone (a naturally occurring substance), that is found in the blood and lungs in large quantities of the people with pulmonary arterial hypertension. Misenbo 62.5 helps by increasing the supply of blood to the lungs and reducing the workload of the heart.
This medicine is available only under a special restricted distribution program called the Misenbo 62.5 Access Program (T.A.P.).
Misenbo 62.5 indications
Oral
Pulmonary hypertension
Adult: >12 yr <40 kg: Initial and maintenance dose is 62.5 mg bid; ≥40 kg: Initially, 62.5 mg bid for 4 wk, then increased to a maintenance dose of 125 mg bid.
Elderly: No dosage adjustment needed.
Renal impairment: No dosage adjustment needed in renal impairment or dialysis patients.
Hepatic impairment: Mild: No dosage adjustment needed. Moderate and severe: Contraindicated.
Special Populations: Dosage adjustment for patients w/ confirmed LFT elevations. >3 and ≤5 x ULN: Reduce dose or discontinue therapy. Monitor LFT at least every 2 wk until LFT return to pre-treatment levels, continue or restart therapy as needed; >5 and ≤8 x ULN: Stop treatment and monitor LFT levels at least every 2 wk. Consider to restart therapy if LFT returns to pre-treatment levels; >8 x ULN: Stop treatment and Misenbo 62.5 should not be restarted.
How should I use Misenbo 62.5?
Use Misenbo 62.5 as directed by your doctor. Check the label on the medicine for exact dosing instructions.
- Misenbo 62.5 comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Misenbo 62.5 refilled.
- Take Misenbo 62.5 by mouth with or without food.
- Do not suddenly stop taking Misenbo 62.5 without checking with your doctor. Your condition may become worse if Misenbo 62.5 is suddenly stopped. If you need to stop Misenbo 62.5, your doctor may gradually lower your dose.
- Take Misenbo 62.5 on a regular schedule to get the most benefit from it. Taking Misenbo 62.5 at the same times each day will help you to remember to take it.
- Continue to take Misenbo 62.5 even if you feel well. Do not miss any doses.
- If you miss a dose of Misenbo 62.5, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.
Ask your health care provider any questions you may have about how to use Misenbo 62.5.
Uses of Misenbo 62.5 in details
Use: Labeled Indications
Pulmonary arterial hypertension: Treatment of pulmonary artery hypertension (PAH) (WHO Group I) in adults with WHO-FC II, III, or IV symptoms to improve exercise ability and to decrease clinical deterioration; treatment of PAH (WHO Group 1) in pediatric patients ≥3 years with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), resulting in an improvement in exercise ability.
Off Label Uses
Digital ulcers in systemic sclerosis
Based on small controlled trials, Misenbo 62.5 may be effective for patients with digital ulcers caused by systemic sclerosis. Misenbo 62.5 has been found to decrease the number of new ulcers but has not been found to improve healing of existing ulcers.
Misenbo 62.5 description
Misenbo 62.5 is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Misenbo 62.5®. Misenbo 62.5 is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.
Misenbo 62.5 dosage
Misenbo 62.5 Dosage
Generic name: Misenbo 62.5 62.5mg
Dosage form: tablet, film coated
The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.
Healthcare professionals who prescribe Misenbo 62.5 must enroll in the Misenbo 62.5 REMS Program and must comply with the required monitoring to minimize the risks associated with Misenbo 62.5.
Adult Dosage
Initiate treatment at 62.5 mg twice daily for 4 weeks and then increase to the maintenance dose of 125 mg twice daily. Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of hepatotoxicity.
Misenbo 62.5 should be administered in the morning and evening with or without food.
Dosage Adjustments for Patients Developing Aminotransferase Elevations
Measure liver aminotransferase levels prior to initiation of treatment and then monthly. If aminotransferase levels increase, revise the monitoring and treatment plan. The table below summarizes the dosage adjustment and monitoring recommendations for patients who develop aminotransferase elevations >3 × ULN during therapy with Misenbo 62.5. Discontinue Misenbo 62.5 if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 × ULN. There is no experience with the reintroduction of Misenbo 62.5 in these circumstances.
| ALT/AST levels | Treatment and monitoring recommendations |
|---|---|
| |
| > 3 and ≤ 5 × ULN | Confirm by another aminotransferase test; if confirmed, reduce the daily dose to 62.5 mg twice daily or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks. If the aminotransferase levels return to pretreatment values, continue or reintroduce the treatment as appropriate*. |
| > 5 and ≤ 8 × ULN | Confirm by another aminotransferase test; if confirmed, stop treatment and monitor aminotransferase levels at least every 2 weeks. Once the aminotransferase levels return to pretreatment values, consider reintroduction of the treatment*. |
| > 8 × ULN | Treatment should be stopped and reintroduction of Misenbo 62.5 should not be considered. There is no experience with reintroduction of Misenbo 62.5 in these circumstances. |
Pregnancy Testing in Females of Reproductive Potential
Initiate treatment with Misenbo 62.5 in females of reproductive potential only after a negative pregnancy test. Obtain monthly pregnancy test during treatment.
Patients with Low Body Weight
In patients with a body weight below 40 kg but who are over 12 years of age, the recommended initial and maintenance dose is 62.5 mg twice daily. There is limited information about the safety and efficacy of Misenbo 62.5 in children between the ages of 12 and 18 years.
Use with Ritonavir
Coadministration of Misenbo 62.5 in Patients on Ritonavir
In patients who have been receiving ritonavir for at least 10 days, start Misenbo 62.5 at 62.5 mg once daily or every other day based upon individual tolerability.
Coadministration of Ritonavir in Patients on Misenbo 62.5
Discontinue use of Misenbo 62.5 at least 36 hours prior to initiation of ritonavir. After at least 10 days following the initiation of ritonavir, resume Misenbo 62.5 at 62.5 mg once daily or every other day based upon individual tolerability.
Use in Patients with Pre-existing Hepatic Impairment
Misenbo 62.5 should generally be avoided in patients with moderate or severe liver impairment. Initiation of Misenbo 62.5 should generally be avoided in patients with elevated aminotransferases >3 × ULN. No dose adjustment is required in patients with mildly impaired liver function.
Treatment Discontinuation
There is limited experience with abrupt discontinuation of Misenbo 62.5. No evidence for acute rebound has been observed. Nevertheless, to avoid the potential for clinical deterioration, gradual dose reduction (62.5 mg twice daily for 3 to 7 days) should be considered.
More about Misenbo 62.5 (Misenbo 62.5)
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Consumer resources
- Misenbo 62.5
- Misenbo 62.5 (Advanced Reading)
Professional resources
- Misenbo 62.5 (AHFS Monograph)
- Misenbo 62.5 (FDA)
Related treatment guides
- Pulmonary Hypertension
Misenbo 62.5 interactions
See also:
What other drugs will affect Misenbo 62.5?
Cytochrome P450 Summary
Misenbo 62.5 is metabolized by CYP2C9 and CYP3A. Inhibition of these enzymes may increase the plasma concentration of Misenbo 62.5. Concomitant administration of both a CYP2C9 inhibitor (such as fluconazole or amiodarone) and a strong CYP3A inhibitor (e.g., ketoconazole, itraconazole) or a moderate CYP3A inhibitor (e.g., amprenavir, erythromycin, fluconazole, diltiazem) with Misenbo 62.5 will likely lead to large increases in plasma concentrations of Misenbo 62.5. Co-administration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with Misenbo 62.5 is not recommended.
Misenbo 62.5 is an inducer of CYP3A and CYP2C9. Consequently plasma concentrations of drugs metabolized by these two isozymes will be decreased when Misenbo 62.5 is co-administered. Misenbo 62.5 had no relevant inhibitory effect on any CYP isozyme in vitro (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A). Consequently, Misenbo 62.5 is not expected to increase the plasma concentrations of drugs metabolized by these enzymes.
Hormonal Contraceptives
Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when Misenbo 62.5 is co-administered. Females should practice additional methods of contraception and not rely on hormonal contraception alone when taking Misenbo 62.5.
An interaction study demonstrated that co-administration of Misenbo 62.5 and a combination oral hormonal contraceptive produced average decreases of norethindrone and ethinyl estradiol levels of 14% and 31%, respectively. However, decreases in exposure were as much as 56% and 66%, respectively, in individual subjects.
Cyclosporine A
The concomitant administration of Misenbo 62.5 and cyclosporine A is contraindicated.
During the first day of concomitant administration, trough concentrations of Misenbo 62.5 were increased by about 30-fold. The mechanism of this interaction is most likely inhibition of transport protein-mediated uptake of Misenbo 62.5 into hepatocytes by cyclosporine. Steady-state Misenbo 62.5 plasma concentrations were 3- to 4-fold higher than in the absence of cyclosporine A. Co-administration of Misenbo 62.5 decreased the plasma concentrations of cyclosporine A (a CYP3A substrate) by approximately 50%.
Glyburide
An increased risk of elevated liver aminotransferases was observed in patients receiving concomitant therapy with glyburide. Therefore, the concomitant administration of Misenbo 62.5 and glyburide is contraindicated, and alternative hypoglycemic agents should be considered.
Co-administration of Misenbo 62.5 decreased the plasma concentrations of glyburide by approximately 40%. The plasma concentrations of Misenbo 62.5 were also decreased by approximately 30%. Misenbo 62.5 is also expected to reduce plasma concentrations of other oral hypoglycemic agents that are predominantly metabolized by CYP2C9 or CYP3A. The possibility of worsened glucose control in patients using these agents should be considered.
Lopinavir/Ritonavir or Other Ritonavir-containing HIV Regimens
In vitro data indicate that Misenbo 62.5 is a substrate of the Organic Anion Transport Protein (OATP), CYP3A and CYP2C9. Ritonavir inhibits OATP and inhibits and induces CYP3A. However, the impact of ritonavir on the pharmacokinetics of Misenbo 62.5 may largely result from its effect on OATP.
In normal volunteers, co-administration of Misenbo 62.5 125 mg twice daily and lopinavir/ritonavir 400/100 mg twice daily increased the trough concentrations of Misenbo 62.5 on Days 4 and 10 approximately 48-fold and 5-fold, respectively, compared with those measured after Misenbo 62.5 administered alone. Therefore, adjust the dose of Misenbo 62.5 when initiating lopinavir/ritonavir.
Co-administration of Misenbo 62.5 125 mg twice daily had no substantial impact on the pharmacokinetics of lopinavir/ritonavir 400/100 mg twice daily.
Simvastatin and Other Statins
Co-administration of Misenbo 62.5 decreased the plasma concentrations of simvastatin (a CYP3A substrate), and its active P-hydroxy acid metabolite, by approximately 50%. The plasma concentrations of Misenbo 62.5 were not affected. Misenbo 62.5 is also expected to reduce plasma concentrations of other statins that are significantly metabolized by CYP3A, such as lovastatin and atorvastatin. The possibility of reduced statin efficacy should be considered. Patients using CYP3A-metabolized statins should have cholesterol levels monitored after Misenbo 62.5 is initiated to see whether the statin dose needs adjustment.
Rifampin
Co-administration of Misenbo 62.5 and rifampin in normal volunteers resulted in a mean 6-fold increase in Misenbo 62.5 trough levels after the first concomitant dose (likely due to inhibition of OATP by rifampin), but about a 60% decrease in Misenbo 62.5 levels at steady-state. The effect of Misenbo 62.5 on rifampin levels has not been assessed. When consideration of the potential benefits and known and unknown risks leads to concomitant use, measure liver function weekly for the first 4 weeks before reverting to normal monitoring.
Tacrolimus
Co-administration of tacrolimus and Misenbo 62.5 has not been studied in humans. Coadministration of tacrolimus and Misenbo 62.5 resulted in markedly increased plasma concentrations of Misenbo 62.5 in animals. Caution should be exercised if tacrolimus and Misenbo 62.5 are used together.
Ketoconazole
Co-administration of Misenbo 62.5 125 mg twice daily and ketoconazole, a potent CYP3A inhibitor, increased the plasma concentrations of Misenbo 62.5 by approximately 2-fold in normal volunteers. No dose adjustment of Misenbo 62.5 is necessary, but increased effects of Misenbo 62.5 should be considered.
Warfarin
Co-administration of Misenbo 62.5 500 mg twice daily for 6 days in normal volunteers, decreased the plasma concentrations of both S-warfarin (a CYP2C9 substrate) and R-warfarin (a CYP3A substrate) by 29 and 38%, respectively. Clinical experience with concomitant administration of Misenbo 62.5 and warfarin in patients with pulmonary arterial hypertension did not show clinically relevant changes in INR or warfarin dose (baseline vs. end of the clinical studies), and the need to change the warfarin dose during the trials due to changes in INR or due to adverse events was similar among Misenbo 62.5- and placebo-treated patients.
Digoxin, Nimodipine, and Losartan
Misenbo 62.5 has no significant pharmacokinetic interactions with digoxin and nimodipine, and losartan has no significant effect on plasma levels of Misenbo 62.5.
Sildenafil
In normal volunteers, co-administration of multiple doses of 125 mg twice daily Misenbo 62.5 and 80 mg three times daily sildenafil resulted in a reduction of sildenafil plasma concentrations by 63% and increased Misenbo 62.5 plasma concentrations by 50%. The changes in plasma concentrations were not considered clinically relevant and dose adjustments are not necessary. This recommendation holds true when sildenafil is used for the treatment of pulmonary arterial hypertension or erectile dysfunction.
Iloprost
In a small, randomized, double-blind, placebo-controlled study, 34 patients treated with Misenbo 62.5 125 mg twice daily for at least 16 weeks tolerated the addition of inhaled iloprost (up to 5 mcg 6 to 9 times per day during waking hours). The mean daily inhaled dose was 27 mcg and the mean number of inhalations per day was 5.6.
Misenbo 62.5 side effects
See also:
What are the possible side effects of Misenbo 62.5?
The following important adverse reactions are described elsewhere in the labeling:
•Potential liver injury
•Fluid retention
Clinical Studies Experience
Safety data on Misenbo 62.5 were obtained from 13 clinical studies (9 placebo-controlled and 4 open-label) in 870 patients with pulmonary arterial hypertension and other diseases. Doses up to 8 times the currently recommended clinical dose (125 mg twice daily) were administered for a variety of durations. The exposure to Misenbo 62.5 in these trials ranged from 1 day to 4.1 years (N=94 for 1 year; N=61 for 1.5 years and N=39 for more than 2 years). Exposure of pulmonary arterial hypertension patients (N=328) to Misenbo 62.5 ranged from 1 day to 1.7 years (N=174 more than 6 months and N=28 more than 12 months).
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Treatment discontinuations due to adverse events other than those related to pulmonary hypertension during the clinical trials in patients with pulmonary arterial hypertension were more frequent on Misenbo 62.5 (6%; 15/258 patients) than on placebo (3%; 5/172 patients). In this database the only cause of discontinuations > 1% and occurring more often on Misenbo 62.5 was abnormal liver function.
The adverse drug events that occurred in ? 3% of the Misenbo 62.5-treated patients and were more common on Misenbo 62.5 in placebo-controlled trials in pulmonary arterial hypertension at doses of 125 or 250 mg twice daily are shown in Table 2:
Table 2: Adverse events
Respiratory Tract Infection 56 22% 30 17%
Headache 39 15% 25 14%
Edema
Chest Pain
Syncope
Flushing
Hypotension
Sinusitis
Arthralgia
Liver Function Test Abnormal
Palpitations
Anemia
Postmarketing Experience
There have been several post-marketing reports of angioedema associated with the use of Misenbo 62.5. The onset of the reported cases occurred within a range of 8 hours to 21 days after starting therapy. Some patients were treated with an antihistamine and their signs of angioedema resolved without discontinuing Misenbo 62.5.
The following additional adverse reactions have been reported during the post approval use of Misenbo 62.5. Because these adverse reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Misenbo 62.5 exposure:
Unexplained hepatic cirrhosis
Liver failure
Hypersensitivity
Thrombocytopenia
Rash
Jaundice
Anemia requiring transfusion
Neutropenia and leukopenia
Misenbo 62.5 contraindications
See also:
What is the most important information I should know about Misenbo 62.5?
Use of Misenbo 62.5 is contraindicated in females who are or may become pregnant. While there are no adequate and well controlled studies in pregnant females, animal studies show that Misenbo 62.5 is likely to cause major birth defects when administered during pregnancy. In animal studies, Misenbo 62.5 caused teratogenic effects including malformations of the head, mouth, face, and large blood vessels. Therefore, pregnancy must be excluded before the start of treatment with Misenbo 62.5. Throughout treatment and for one month after stopping Misenbo 62.5, females of child bearing potential must use two reliable methods of contraception unless the patient has a tubal sterilization or Copper T 380A IUD or LNg 20 IUS inserted, in which case no other contraception is needed. Monthly pregnancy tests should also be obtained. If this drug is used during pregnancy or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Use with Cyclosporine A
Co-administration of cyclosporine A and Misenbo 62.5 resulted in markedly increased plasma concentrations of Misenbo 62.5. Therefore, concomitant use of Misenbo 62.5 and cyclosporine A is contraindicated.
Use with Glyburide
An increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with Misenbo 62.5. Therefore co-administration of glyburide and Misenbo 62.5 is contraindicated.
Hypersensitivity
Misenbo 62.5 is contraindicated in patients who are hypersensitive to Misenbo 62.5 or any component of the product. Observed reactions include rash and angioedema.
Active ingredient matches for Misenbo 62.5:
Bosentan in Vietnam.
List of Misenbo 62.5 substitutes (brand and generic names) | Sort by popularity |
| Unit description / dosage (Manufacturer) | Price, USD |
| Misenbo 125 (Vietnam) | |
| Mylan-Bosentan (Canada) | |
| Mylan-bosentan tablet 125.0 mg (Mylan Pharmaceuticals Ulc (Canada)) | |
| Mylan-bosentan tablet 62.5 mg (Mylan Pharmaceuticals Ulc (Canada)) | |
| Pahsentan (South Korea) | |
| PMS-Bosentan (Canada, New Zealand) | |
| PMS-bosentan tablet 62.5 mg (Pharmascience Inc (Canada)) | |
| PMS-bosentan tablet 125 mg (Pharmascience Inc (Canada)) | |
| Pulmohyperta (Bulgaria) | |
| Sandoz Bosentan (Canada) | |
| Sandoz Bosentan tablet 125 mg (Sandoz Canada Incorporated (Canada)) | |
| Sandoz Bosentan tablet 62.5 mg (Sandoz Canada Incorporated (Canada)) | |
| Sentoba (Estonia) | |
| Stayveer (Poland, Slovenia) | |
| Stayveer Film-coated tablet 62.5 mg (Marklas Nederlands Bv (EU)) | |
| Stayveer Film-coated tablet 125 mg (Marklas Nederlands Bv (EU)) | |
| Stayveer 125mg (Austria, Hungary) | |
| Stayveer 62.5mg (Austria, Hungary) | |
| Tansnura (Netherlands) | |
| Tracleer (Australia, Austria, Belgium, Canada, China, Croatia (Hrvatska), Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Luxembourg, Malaysia, Netherlands, New Zealand, Norway, Romania, Serbia, Singapore, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States) | |
| Tablet, Film-Coated; Oral; Bosentan Monohydrate 62.5 mg (Actelion) | |
| Tablet, Film-Coated; Oral; Bosentan Monohydrate 125 mg (Actelion) | |
| Tablet; Oral; Bosentan Monohydrate 62.5 mg (Actelion) | |
| Tablet; Oral; Bosentan Monohydrate 125 mg (Actelion) | |
| Tracleer 62.5 mg x 60's (Actelion) | |
| Tracleer 125 mg x 60's (Actelion) | |
| Tracleer FC tab 125 mg 60's (Actelion) | |
| Tracleer FC tab 62.5 mg 60's (Actelion) | |
| Tracleer film-coated tab 125 mg 60's (Actelion) | |
| Tracleer tab 125 mg 60's (Actelion) | |
| Tracleer tablet, film coated 62.5 mg/1 (Actelion) | |
| Tracleer Film-coated tablet 62.5 mg (Actelion) | |
| Tracleer tablet, film coated 125 mg/1 (Actelion) | |
| Tracleer Film-coated tablet 125 mg (Actelion) | |
| Tracleer tablet 62.5 mg (Actelion) | |
| Tracleer tablet 125 mg (Actelion) | |
| Tracleer Dispersible Tablet 32 mg (Actelion) | |
| Tracleer (bosentan) 125mg film-coated tablets (United Kingdom) | |
| Tracleer (bosentan) 62.5mg film-coated tablets (United Kingdom) | |
| Tracleer 125 mg (Hungary) | |
| Tracleer 125mg (Austria, Germany, Israel, Luxembourg, Switzerland) | |
| Tracleer 32mg (Austria, Germany, Switzerland) | |
| Tracleer 62,5mg (Austria, Germany, Israel, Luxembourg, Switzerland) | |
| Tracleer 62.5 mg (Hungary) | |
| Tractan (Turkey) | |
| Trasentan 125 (Israel) | |
| Trasentan 62.5 (Israel) | |
See 131 substitutes for Misenbo 62.5 | |
References
- DailyMed. "BOSENTAN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- PubChem. "Bosentan". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
- DrugBank. "Bosentan". http://www.drugbank.ca/drugs/DB00559 (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Misenbo 62.5 are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Misenbo 62.5. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
