Frequently Asked Questions

What is Seratrodast?

Seratrodast is a thromboxane A₂ (TXA₂) receptor (TP receptor) antagonist used primarily in the treatment of asthma. It is the first thromboxane receptor antagonist that has been developed as an anti-asthmatic drug and has received marketing approval in Japan, China and India. Seratrodast inhibits bronchoconstriction induced by the TXA₂ and has been reported to inhibit both immediate and late asthmatic responses in asthma.

Seratrodast has been clinically used as controller medication in treatment of bronchial asthma, symptomatic treatment of allergic rhinitis and treatment of cough in COPD.

What is the role of TXA₂ in Asthma?

TXA₂ is a biologically potent arachidonic acid metabolite derived from the cyclo-oxygenase pathway. It is implicated in the pathophysiology of asthma through airway smooth-muscle contraction, development of mucosal oedema, increase in airway hyper-responsiveness, airway plasma exudation and increase in mucosal secretions which leads to the blocking of the airways. TXA₂ also leads to the proliferation of human airway smooth muscle cells.

For additional information on thromboxane A₂, please click here.

What are Thromboxane Modulators?

Thrombaxane modulators refer to thromboxane synthase inhibitors and thromboxane A₂ receptor antagonists. The effects of TXA₂ in asthma can be blocked by either inhibiting synthesis of TXA₂ through thromboxane synthase inhibition (e.g. Ozagrel) or directly blocking the action of TXA₂ on TP receptors (e.g. Seratrodast).

What are Reliever and Controller medications?

Reliever medications are usually bronchodilators that quickly relieve bronchospasm and are taken on demand. They include short acting β₂-agonist like albuterol and anticholinergic bronchodilator like ipratropium bromide. These medications generally do not treat the underlying inflammatory process of asthma.

Controller medications are taken daily on a long-term basis for the prophylactic and preventive purpose. These agents are primarily directed at the underlying inflammatory mechanism of asthma that leads to chronic symptoms and possibly permanent airway damage. They include inhaled corticosteroids, cysteinyl-leukotriene receptor inhibitors, TXA₂ receptor antagonists, Th2 cytokine inhibitor, mast cell stabilizer etc.

What are the Indications of Seratrodast?

Seratrodast is indicated in Adults (18 years and above) for the prophylactic management of asthma. It is also effective in the treatment of allergic rhinitis and COPD.

What is the dosage and administration of Seratrodast?

In the prophylactic management of bronchial asthma, a dose of 80 mg once daily is recommended. Seratrodast has been shown to be well-tolerated following repeated once daily oral doses of up to a maximum of 320 mg.

In elderly patients the treatment should be started with a lower dose of 40 mg/day.

What is the safety profile of Seratrodast?

Seratrodast is well tolerated and has not been associated with clinically significant adverse events. In a post-marketing study conducted in over 4000 patients, the most frequently observed adverse reactions (occurrence 0.1 to 5%) with the use of seratrodast are elevated levels of liver enzymes, nausea, loss of appetite, stomach discomfort, abdominal pain, diarrhea, constipation, dry mouth, taste disturbance, drowsiness, headache, dizziness, palpitations and malaise. All the adverse reactions reported are of mild to moderate severity.

In clinical studies with Seratrodast, including the one conducted on Indian patients, no significant difference was observed in the incidence of adverse events when compared with Montelukast.

What is the maximum duration for which seratrodast has been safely given?

Seratrodast has been safely given as 80 mg once daily for 2 years in bronchial asthma patients.

What is the efficacy of Seratrodast in Asthma?

In various clinical studies, seratrodast improved lung function parameters such as FEV₁, FVC and PEF, and clinical symptoms of asthma such as wheezing, shortness of breath, cough, expectoration and chest tightness. The improvement in PEF with seratrodast (80 mg o.d. for 28 days) was found to be significantly greater than Montelukast (10 mg o.d. for 28 days). With respect to the levels of various biochemical parameters of sputum, seratrodast showed significant reduction in sputum fucose, eosinophil cationic protein (ECP) and albumin levels. The decrease in sputum ECP and albumin levels with seratrodast was found to be better than Montelukast.

In a 6-week comparative clinical study with zafirlukast 20 mg, seratrodast was observed to have a better control over asthma compared to zafirlukast (71.68% vs. 62.62%).

What are the drug interactions with Seratrodast?

Seratrodast should be used cautiously with other anti-inflammatory analgesics, antipyretics, cephalosporins and drugs that have been reported to cause hemolytic anemia. Aspirin can compete with seratrodast for serum protein binding which may increase the concentration of unbound drug (seratrodast) by 26%.

What are the contraindications to Seratrodast?

Seratrodast is contraindicated in patients who are hypersensitive to the drug and in patients with hepatic failure.

Is Seratrodast safe in Pregnancy and Lactation?

There are no adequate and well controlled studies in pregnant women. Seratrodast should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Seratrodast should be avoided during lactation.

If a woman of childbearing age plans for pregnancy, when should she stop taking Seratrodast?

The half-life of Seratrodast is 22 hours. As it normally takes around 5 half-lives for over 95% of any drug to get eliminated from the body, a woman of childbearing age should stop taking Seratrodast around 5 to 7 days before planning for pregnancy.

Is Seratrodast safe in Hepatic and Renal Impairment?

While Seratrodast is contraindicated in patients with hepatic failure, it can be very well given in patients with renal impairment.

What is the status of Seratrodast in elderly population?

The area under the plasma concentration-time curve (AUC), the time to peak concentration, and the half-life of seratrodast are increased to nearly two-fold in elderly patients. Therefore the treatment should be started with a lower dose of 40 mg/day in elderly patients.

Can Seratrodast be given to Children?

The safety and efficacy of Seratrodast has not been established in children and should not be used in this age group (< 18 years of age).

Can Seratrodast lead to bleeding?

Bleeding tendency is one of the possible adverse effects of anti-TXA₂ agents due to suppression of platelet aggregation. This is much more pronounced with Thromboxane synthase inhibitors viz. Ozagrel because PGI₂ production, which has anti-platelet aggregation activity, is enhanced by pathway blockade of PGH₂ to TXA₂ by Thromboxane synthase inhibitors.

The dose of seratrodast at which bleeding may occur is 10 times the therapeutic dose i.e. 800mg/day. As seen in preclinical studies, seratrodast did not affect the platelet activating factor (PAF) or adenosine-5’-diphosphate (ADP)-induced aggregation. Seratrodast did not induce shape change or platelet aggregation. In addition, seratrodast in therapeutic dosage has no effect on prothrombin time and activated partial thromboplastin time, thus ruling out any action on blood coagulation cascade.

The results of previously conducted clinical studies indicated that seratrodast does not possess any inhibitory effect on either clotting-induced production of TXB₂, leukocyte production of LTB₄, or platelet aggregation in response to PAF.

Furthermore, clinical trials conducted on Indian patients did not show any bleeding tendency with the use of seratrodast. The reason behind this may be attributed to the differential activity of seratrodast on TP-receptor-mediated events in platelets and smooth muscle.

Is seratrodast available in US?

Seratrodast is not available in US because of patent conflict and financial disputes of Japanese originator with American pharmaceutical partner organizations. Therefore no clinical trials were conducted in America and the matter was not pursued with the US FDA.

Are there any clinical trials in Indian Population?

Seratrodast has been tried in Indian patients (n=205) in a multicentric, double blind, double dummy, comparative clinical trial with montelukast and it was found to be better than montelukast. Seratrodast was well tolerated and similar to montelukast in safety.