Pemirolast

Pregnancy Category C.

Pemirolast potassium caused an increased incidence of thymic remnant in the neck, interventricular septal defect, fetuses with wavy rib, splitting of thoracic vertebral body, and reduced numbers of ossified sternebrae, sacral and caudal vertebrae, and metatarsi when rats were given oral doses ≥250 mg/kg (approximately 20,000 fold the human dose at 2 drops/eye, 40 μL drop, QID for a 50 kg adult) during organogenesis.

Increased incidence of dilation of renal pelvis/ureter in the fetuses and neonates was also noted when rats were given an oral dose of 400 mg/kg pemirolast potassium (approximately 30,000 fold the human dose). Pemirolast potassium was not teratogenie in rabbits given oral doses up to 150 mg/kg (approximately 12,000 fold the human dose) during the same time period. There are no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, pemirolast ophthalmic solution should be used during pregnancy only if the benefit outweighs the risk.

Non-teratogenic effects

Pemirolast potassium produced increased pre- and post-implantation losses, reduced embryo/fetal and neonatal survival, decreased neonatal body weight, and delayed neonatal development in rats receiving an oral dose at 400 mg/kg (approximately 30,000 fold the human dose). Pemirolast potassium also caused a reduction in the number of corpus lutea, the number of implantations, and number of live fetuses in the F₁ generation in rats when F₀ dams Were given oral dosages ≥250 mg/kg (approximately 19,000 fold the human dose) during late gestation and the lactation period.

Pemirolast potassium is excreted in the milk of lactating rats at concentrations higher than those in plasma. It is not known whether pemirolast is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when pemirolast ophthalmic solution is administered to a nursing woman.

Pemirolast potassium was not mutagenic or clastogenic when tested in a series of bacterial and mammalian tests for gene mutation and chromosomal injury in vitro nor was it clastogenic when tested in vivo in rats.

Pemirolast potassium had no effect on mating and fertility in rats at oral doses up to 250 mg/kg (approximately 20,000 fold the human dose at 2 drops/eye, 40 μL/drop, QID for a 50 kg adult). A reduced fertility and pregnancy index occurred in the F₁ generation when F₀ dams were treated with 400 mg/kg pemirolast potassium during late pregnancy and lactation period (approximately 30,000 fold the human dose).

In clinical studies lasting up to 17 weeks with pemirolast ophthalmic solution, headache, thinitis, and cold/flu symptoms were reported at an incidence of 10-25%. The occurrence of these side effects was generally mild. Some of these events were similar to the underlying ocular disease being studied.

The following ocular and non-ocular adverse reactions were reported at an incidence of less than 5%:

Ocular: burning, dry eye, foreign body sensation, and ocular discomfort.

Non-Ocular: allergy, back pain, bronchitis, cough, dysmenorrhoea, fever, sinusitis, and sneezing/nasal congestion.