Introduction

Tofacit XR 11 is used to treat moderate to severe rheumatoid arthritis. It helps decrease pain, tenderness and swelling in the joints by reducing inflammation. It also helps slow the progression of bone and joint damage. Tofacit XR 11 may be prescribed by itself or in combination with another medicine. The tablets can be taken with or without food and it is best to take them at the same time each day. Your dose will depend on your condition and what other medicines you are taking. You should use it as your doctor tells you to. Do not stop taking this medicine unless your doctor tells you to, because your condition could get worse. The most common side effects of Tofacit XR 11 include throat and nose infections, nausea and viral infection. You may also get cold sores, feel sick or have symptoms of a cold like stuffy nose, sneezing and sore throat. There are other less common side effects, some of them serious, including blood clots and tears in the stomach or intestine wall. These need urgent medical attention. If you have any worries about side effects, talk to your doctor. You may need blood tests before you are given this medicine and you should not start taking it if you have any kind of infection. Make sure you talk to your doctor before starting treatment if you have, or have ever had, tuberculosis, shingles, kidney or liver disease, hepatitis B or C, or blood clots in your legs or lungs. Tofacit XR 11 can make you more likely to get infections or may worsen any current infections so avoid contact with people who have things you might catch (such as chickenpox, measles, flu). This medicine is not suitable for children under 18 years old and you should not use it if you are pregnant or breastfeeding, unless your doctor feels the benefit is greater than the risk. Your doctor may need to examine you on a regular basis.

Uses of Tofacit XR 11

• Rheumatoid arthritis

Side effects of Tofacit XR 11

• Diarrhea
• Headache
• High blood pressure
• Nasal congestion (stuffy nose)
• Runny nose
• Sore throat
• Upper respiratory tract infection

How to use Tofacit XR 11

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Tofacit XR 11 may be taken with or without food, but it is better to take it at a fixed time.

How Tofacit XR 11 works

Tofacit XR 11 is an Janus kinase inhibitor. It works by blocking the action of the enzyme, Janus kinase. This decreases inflammation and joint damage in rheumatoid arthritis.

Indication

Rheumatoid Arthritis, Tofacitinib is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).

Administration

May be taken with or without food.

Adult Dose

Rheumatoid Arthritis Indicated as second-line treatment for moderate-to-severe active rheumatoid arthritis in patients with an inadequate response or intolerance to methotrexate; may be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs Adult: Recommended Dose: 5 mg twice daily. Hepatic impairment Mild: No dosage adjustment required Moderate: Not to exceed 5 mg qDay Severe: Not recommended

Child Dose

Safety and efficacy not established

Renal Dose

Renal impairment Mild: No dosage adjustment required Moderate-to-severe: Not to exceed 5 mg qDay

Contraindication

Hypersensitivity to the active substance or to any of the excipients.

Mode of Action

Janus kinases (JAKs) pathways inhibitor; JAK consists of a group of intracellular tyrosine kinases that transmit signals from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoieses and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression; tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. These signals are essential in maintaining the inflammatory condition in rheumatoid arthritis (RA); inhibition of JAKs reduces production of and modulates proinflammatory cytokines central to RA.

Precaution

Serious Infections – Do not administer Tofacitinib during an active infection, including localized infections. If a serious infection develops, interrupt Tofacitinib until the infection is controlled. Lymphomas and other malignancies have been reported in patients treated with Tofacitinib Gastrointestinal Perforations – Use with caution in patients that may be at increased risk. Laboratory monitoring –Recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids. Immunizations –Live vaccines should not be given concurrently with Tofacitinib Do not initiate therapy in patients w/ an active infection including localized infections, chronic or recurrent infections, or those who have been exposed to TB, history of a serious or an opportunistic infection, resided or travelled in areas of endemic TB or endemic mycoses; underlying conditions that may predispose to infection. Evaluate & test patients for latent or active infection prior to administration. Monitor for signs & symptoms of TB. Perform screening for viral hepatitis before starting therapy. Malignancy & lymphoproliferative disorder excluding nonmelanoma skin cancer. Periodic skin exam for patients who are at increased risk of skin cancer. Patients who may be at increased risk for GI perforation (eg, history of diverticulitis). Monitor lymphocyte at baseline & every 3 mth thereafter; neutrophils & Hb at baseline & after 4-8 wk of treatment & every 3 mth thereafter. Discontinue if Hb levels <8>2 g/dL while on treatment. Assess lipid parameters approx 4-8 wk following initiation of therapy. Not recommended to be given w/ concurrent live vaccines. Moderate or severe renal impairment. Severe hepatic impairment. Avoid use in RA patients in combination w/ biological DMARDs. Pregnancy & lactation. Childn <18 yr. Elderly ≥65 yr.

Side Effect

>10% Overall infections (20-22%) 1-10% URTI (4.5%),Headache (4.3%),Diarrhea (4%),Nasopharyngitis (3.8%),UTI (2%),Hypertension (1.6%) <1% ANC <500/mm³ (0.07%),Lymphocytes <500/mm³ (0.04%) Frequency Not Defined Serious infections: 1.7 events per 100 patient-years Malignancies: 0.3 events per 100 patient-years

Pregnancy Category Note

Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women during pregnancy; patients can call the toll free number 1-877-311-8972 There are no adequate and well-controlled studies therapy in pregnant women In the tofacitinib clinical development programs, birth defects and miscarriages were reported Animal data Based on animal studies, tofacitinib has the potential to affect a developing fetus Based on findings in rats, females of reproductive potential taking tofacitinib may result in reduced fertility Contraception Advise females of reproductive potential to use effective contraception during treatment and for >4 weeks after the last dose Advise females to inform their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment Lactation It is not known whether the drug is excreted in human milk There are no data to assess effects of drug on breastfed child; drug is excreted in rat milk at concentrations higher than in maternal serum Women should not breastfeed while treated; a decision should be made whether to discontinue breastfeeding or to discontinue therapy

Interaction

Increased exposure w/ potent CYP3A4 inhibitors (eg, ketoconazole), moderate CYP3A4 inhibitors & potent CYP2C19 inhibitors (eg, fluconazole). Decreased exposure w/ potent CYP inducers (eg, rifampin). Increased AUC & decreased Cmax w/ tacrolimus & cyclosporine. Decreased AUC & Cmax of MTX.