Tofacitinib

Tofacitinib was first approved by the FDA on November 6, 2012, for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients with inadequate or intolerant response to methotrexate therapy.

In China, Tofacitinib was approved for market on March 15, 2017. The drug specification produced by Lucius is 5mg*30 tablets.

Tofacitinib is a JAK inhibitor that reduces cytokine signaling, cytokine induced gene expression, and cell activation by inhibiting the JAK pathway, thereby reducing various chronic inflammatory responses.

1.Main components

Tofacitinib

2.Adapt to the population

Tofacitinib is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more TNF blockers.

3.Medication for special populations

3.1Pregnancy

Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis or ulcerative colitis. Adverse  pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight  (less than 2500 g) infants, and small for gestational age at birth.

3.2Lactation

Based on published data, tofacitinib is present in human milk. Data on the effects of tofacitinib  on the breastfed infant is limited to a small number of cases with no reported adverse effects. There are no data on the effects on milk production. Given the serious adverse reactions seen in  patients treated with Tofacitinib Oral Solution, such as increased risk  of serious infections, advise patients that breastfeeding is not recommended during treatment and  for at least 18 hours after the last dose of Tofacitinib Oral Solution or 36 hours after the last dose of Tofacitinib (approximately 6 elimination half-lives).

3.3Females and Males of Reproductive Potential

There is uncertainty as to how these animal findings relate to females of reproductive potential  treated with the recommended clinical dose. Consider pregnancy planning and prevention for  females of reproductive potential.

Based on findings in rats, treatment with Tofacitinib Oral Solution may result in reduced fertility in females of reproductive potential. It is not known if this effect is  reversible.

3.4Pediatric Use

The safety and effectiveness of Tofacitinib Oral Solution for the treatment of active  pcJIA have been established in patients 2 years to 17 years of age.

Safety and efficacy of Tofacitinib Oral Solution in pediatric patients for indications  other than pcJIA have not been established.  

The safety and effectiveness of Tofacitinib in pediatric patients have not been established.

3.5Geriatric Use

As there is a higher incidence of infections in the elderly population in general, caution should be  used when treating the elderly.

3.6Use in Diabetics

As there is a higher incidence of infection in diabetic population in general, caution should be  used when treating patients with diabetes.

3.7Renal Impairment

Dosage adjustment of Tofacitinib Oral Solution is recommended in  patients with moderate or severe renal impairment (including but not limited to those with severe  insufficiency who are undergoing hemodialysis).

No dosage adjustment is required in patients with mild renal impairment.

4.Drug overdose

There is no specific antidote for overdose with Tofacitinib Oral  Solution. In case of an overdose, it is recommended that the patient be monitored for signs and  symptoms of adverse reactions.

5.Drug storage

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between  59°F and 86°F).

6.Pharmacokinetics

The absolute oral bioavailability of Tofacitinib is 74%. Coadministration of Tofacitinib with a  high-fat meal resulted in no changes in AUC while Cmax was reduced by 32%. In clinical trials, Tofacitinib was administered without regard to meals.

from FDA，2024.09