Seretra Tablets

Seratrodast uncoated tablet

Each uncoated tablet contains: Seratrodast 80 mg

Uncoated tablet 80 mg

4.1 Therapeutic indications

Seretra is indicated in prophylactic management of mild to moderate asthma.

4.2 Posology and method of administration

• Adults: The recommended dose of Seretra is 80 mg once daily. Seretra 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 40mg/day.
• Pediatric Use (< 18 years of age): The safety and efficacy of Seretra has not been established in children and should not be used in this age group.

4.3 Contraindications

• Hypersensitivity to Seretra or any of the ingredients.
• Patients with hepatic failure.

4.4 Special warnings and precautions for use

Seretra may lead to an elevation in the levels of the hepatic enzymes. Therefore, it has to be administered with caution in patients with hepatic impairment.

4.5 Interaction with other medicinal products and other forms of interaction

• Use cautiously with other anti-inflammatory analgesics, cephalosporin antibiotics and drugs that have been reported to cause hemolytic anemia.
• As aspirin can compete for serum protein binding, it may increase the concentration of unbound drug (seratrodast) by 26%.

4.6 Pregnancy and lactation

Pregnancy and Lactation: There are no adequate and well controlled studies in pregnant women. Seretra should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Seretra should be avoided during lactation.

4.7 Effects on ability to drive and use machines

Seretra is not expected to affect a patient's ability to drive a car or operate machinery.

4.8 Undesirable effects

Adverse reactions are generally rare, but if present, range from mild to moderate in severity.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to:medico@zuventus.com

Website: http://www.zuventus.co.in/safety.aspx

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

There have been no reports of overdosage with Seretra. In cases of overdosage, the stomach should be emptied by aspiration and gastric lavage. Vital parameters should be managed symptomatically.

5.1 Pharmacodynamic properties

Seratrodast is a potent, long-acting, stereospecific thromboxane A2/prostaglandin endoperoxide receptor antagonist. The R-(+)-enantiomer of Seratrodast is the pharmacologically active moiety. Seratrodast appears to exert its anti-inflammatory effects through antagonism of the thromboxane A2 receptor (TP receptor). In addition, seratrodast blocks the broncho-constrictor effect of PGF2α, PGD2 and 9α, 11β-PGF2 mediated through activation of TP receptor.

5.2 Pharmacokinetic properties

Following single and repeated oral administration, seratrodast is rapidly and dose- dependently absorbed. The peak plasma concentrations of seratrodast increase proportionally with dose reaching steady-state concentration within 7 days of administration. Following once daily doses of 80mg for 15 days in patients with mild to moderate asthma, the peak plasma concentration of Seratrodast is 8.80 µg/ml with an average Tmax of 2.4 hours. The area under the plasma concentration-time curve (AUC) for Seratrodast is 22.96 µg.hr/ml and the average apparent volume of distribution is 33 liters.

Seratrodast has high protein binding capacity (more than 99%). It is metabolized to 5- methylhydroxyseratrodast and 4-hydroxyseratrodast by cytochrome P450 (CYP) isoenzymes. It is also partially (35%) glucuronidated in plasma and may be subjected to enterohepatic recycling. Following oral administration of 40 to 120 mg/day in healthy subjects the renal clearance of seratrodast ranges from 5.10 to 8.94 ml/hr (average 7.0 ml/hr) after a single dose and at steady-state respectively. The percentage of the dose excreted as unchanged drug in the urine ranges from 0.42% to 1.37% (average 0.83%) after a single dose and at steady-state. The plasma concentrations decline bi-exponentially with an average half-life of 20 and 36 hours after single and multiple administrations, respectively.

6.1 Animal Toxicology or Pharmacology

Acute Toxicity

The acute toxicity of seratrodast was assessed in mice and rats via oral, subcutaneous, and intraperitoneal administration at doses from 625 to 5000 mg/kg/d. Mortality was linked to lung congestion, as shown by necropsy. Surviving animals exhibited various pathological changes: spleen enlargement in subcutaneously treated rats, liver enlargement and interlobular adhesion in intraperitoneally treated animals, and visceral organ adhesion with white coating on the spleen in some mice. The LD50 values for oral gavage ranged from 1620 mg/kg/d in male mice to about 5000 mg/kg/d in female rats.

Chronic Toxicity

Seratrodast was administered to rats at various doses for 13 weeks by oral gavage (0, 4, 20, 100, or 500 mg/kg/d) and for 52 weeks in the diet (0, 3, 10, 30, or 100 mg/kg/d). No deaths or significant changes in clinical signs, ophthalmoscopy, or urine composition were observed. At high doses (100 and 500 mg/kg/d), weight gain was reduced, and erythrocyte numbers, hemoglobin, and hematocrit values decreased. Additionally, increased kidney, liver, and spleen weights, along with histopathological changes such as increased hematopoiesis and hepatocyte hypertrophy, were noted. The study concluded that seratrodast is toxic at high doses, with a nontoxic dose level between 10-20 mg/kg/d.

Mutagenicity, Reproductivity, Teratogenicity and Antigenicity

The mutagenic potential of seratrodast was assessed using the micronucleus test in male mice and the reversion test in various bacterial strains, with results indicating that seratrodast was not mutagenic and was not metabolized into mutagenic substances. Additionally, at doses up to 100 mg/kg/d, seratrodast showed no adverse effects on fertility, reproductive performance, or F1 generation development in rats, nor did it cause teratogenic or lethal effects in rabbits. Furthermore, seratrodast was found to be non-antigenic in guinea pigs and mice, whether administered alone or as a conjugate with human serum albumin.

Seratrodast is an orally active quinone derivative and a potent Thromboxane A2 (TXA2) receptor antagonist used in the prophylactic management of asthma.

Chemical name: (±) 7-phenyl-7-(2, 4, 5-trimethyl-3, 6-dioxocyclohexa-1, 4-dien-1-yl) heptanoic acid

Molecular formula: C₂₂ H₂₆ O₄

Molecular weight : 354.44

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on pack

8.3 Packaging information

1 Blister strip of 10 tablets

8.4 Storage and handing instructions

Store below 30°C. Protect from light & moisture. Keep out of reach of children.

• Inform your doctor if you are suffering from liver diseases as seratrodast treatment can lead to an elevation in the levels of liver enzymes.
• Tell your doctor if you are or planning to become pregnant. Seratrodast should be avoided during breastfeeding.
• Do not take any anti-inflammatory analgesics (painkiller), cephalosporin antibiotics and drugs that have been reported to cause hemolytic anemia, along with seratrodast.

03.09.2022