during the first 3 months of exposure in the controlled clinical trials are summarized below:
•Mean LDL cholesterol increased by 15% in the XELJANZ 5 mg twice daily arm and 19% in the XELJANZ 10 mg twice daily arm.
•Mean HDL cholesterol increased by 10% in the XELJANZ 5 mg twice daily arm and 12% in the XELJANZ 10 mg twice daily arm.
•Mean LDL/HDL ratios were essentially unchanged in XELJANZ-treated patients.
In a controlled clinical trial, elevations in LDL cholesterol and ApoB decreased to pretreatment levels in response to statin therapy.
In the long-term safety population, elevations in lipid parameters remained consistent with what was seen in the controlled clinical trials.
Serum Creatinine
In the controlled clinical trials, dose-related elevations in serum creatinine were observed with XELJANZ treatment. The mean increase in serum creatinine was <0.1 mg/dL in the 12-month pooled safety analysis; however with increasing duration of exposure in the long-term extensions, up to 2% of patients were discontinued from XELJANZ treatment due to the protocol-specified discontinuation criterion of an increase in creatinine by more than 50% of baseline. The clinical significance of the observed serum creatinine elevations is unknown.
Other Adverse Reactions
Adverse reactions occurring in 2% or more of patients on 5 mg twice daily or 10 mg twice daily XELJANZ and at least 1% greater than that observed in patients on placebo with or without DMARD are summarized in Table 4.
Table 4: Adverse Reactions Occurring in at Least 2% or More of Patients on 5 or 10 mg Twice Daily XELJANZ With or Without DMARD (0–3 months) and at Least 1% Greater Than That Observed in Patients on Placebo
XELJANZ
5 mg Twice Daily
XELJANZ
10 mg Twice Daily
Placebo
Preferred Term
N = 1336
(%)
N = 1349
(%)
N = 809
(%)
N reflects randomized and treated patients from the seven clinical trials
Diarrhea
4.0
2.9
2.3
Nasopharyngitis
3.8
2.8
2.8
Upper respiratory tract infection
4.5
3.8
3.3
Headache
4.3
3.4
2.1
Hypertension
1.6
2.3
1.1
Other adverse reactions occurring in controlled and open-label extension studies included:
Blood and lymphatic system disorders: Anemia
Metabolism and nutrition disorders: Dehydration
Psychiatric disorders: Insomnia
Nervous system disorders: Paresthesia
Respiratory, thoracic and mediastinal disorders: Dyspnea, cough, sinus congestion
Gastrointestinal disorders: Abdominal pain, dyspepsia, vomiting, gastritis, nausea
Hepatobiliary disorders: Hepatic steatosis
Skin and subcutaneous tissue disorders: Rash, erythema, pruritus
Musculoskeletal, connective tissue and bone disorders: Musculoskeletal pain, arthralgia, tendonitis, joint swelling
General disorders and administration site conditions: Pyrexia, fatigue, peripheral edema
7 DRUG INTERACTIONS
7.1 Potent CYP3A4 Inhibitors
Tofacitinib exposure is increased when XELJANZ is coadministered with potent inhibitors of cytochrome P450 (CYP) 3A4 (e.g., ketoconazole) [see Dosage and Administration (2.1) and Figure 3].
7.2 Moderate CYP3A4 and Potent CYP2C19 Inhibitors
Tofacitinib exposure is increased when XELJANZ is coadministered with medications that result in both moderate inhib
