Tofacitinibum
Tofacitinibum Uses, Dosage, Side Effects, Food Interaction and all others data.
Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.
Tofacitinibum is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinibum works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.
Tofacitinibum targets inflammation present in rheumatoid arthritis by inhibiting the janus kinases involved in the inflammatory response pathway.
In placebo controlled trials of rheumatoid arthritis patients receiving 5mg or 10mg of tofacitinib twice daily, higher ACR20 responses were observed within 2 weeks in some patients (with ACR20 being defined as a minimum 20% reduction in joint pain or tenderness and 20% reduction in arthritis pain, patient disability, inflammatory markers, or global assessments of arthritis by patients or by doctors, according to the American College of Rheumatology (ACR) response criteria list), and improvements in physical functioning greater than placebo were also noted.
Common known adverse effects of tofacitinib include headaches, diarrhea, nausea, nasopharyngitis and upper respiratory tract infection. More serious immunologic and hematological adverse effects have also been noted resulting in lymphopenia, neutropenia, anemia, and increased risk of cancer and infection.
| Trade Name | Tofacitinibum |
| Availability | Prescription only |
| Generic | Tofacitinib |
| Tofacitinib Other Names | Tasocitinib, Tofacitinib, Tofacitinibum |
| Related Drugs | Entyvio, Humira, Cosentyx, Zeposia, Colazal, prednisone, naproxen, methotrexate, dexamethasone, hydrocortisone |
| Type | |
| Formula | C16H20N6O |
| Weight | Average: 312.3696 Monoisotopic: 312.169859292 |
| Protein binding | 40%, mostly bound to albumin. |
| Groups | Approved, Investigational |
| Therapeutic Class | Immunosuppressant |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Rheumatoid Arthritis: Tofacitinibum is used 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).
Psoriatic Arthritis: Tofacitinibum is used for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).
Ulcerative Colitis: Tofacitinibum is used for the treatment of adult patients with moderately to severely active ulcerative colitis (UC).
Tofacitinibum is also used to associated treatment for these conditions: Polyarticular-course Juvenile Idiopathic Arthritis (JIA), Moderate Rheumatoid arthritis, Severe Rheumatoid arthritis
How Tofacitinibum works
Rheumatoid arthritis is an autoimmune disease characterized by a dysregulation of pro-inflammatory cytokines including IL7, IL15, IL21, IL6, IFN-alpha, and IFN-beta. (3) Cytokines signalling results in tissue inflammation and joint damage by stimulating the recruitment and activation of immune cells via the janus kinase signalling pathway.
Tofacitinibum is a partial and reversible janus kinase (JAK) inihibitor that will prevent the body from responding to cytokine signals. By inhibiting JAKs, tofacitinib prevents the phosphorylation and activation of STATs. The JAK-STAT signalling pathway is involved in the transcription of cells involved in hematopoiesis, and immune cell function. Tofacitinibum works therapeutically by inhibiting the JAK-STAT pathway to decrease the inflammatory response. However, there is evidence to suggest that it may also achieve efficacy via other pathways as well.
Dosage
Tofacitinibum dosage
Do not initiate Tofacitinibumif absolute lymphocyte count <500 cells/mm3, an absolute neutrophil count (ANC) <1000 cells/mm3 or hemoglobin <9 gm/dL.
Rheumatoid Arthritis: Tofacitinibum 5 mg twice daily or Tofacitinibum 11 mg once daily.Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinibum 5 mg once daily.
Psoriatic Arthritis (in combination with nonbiologic DMARDs): Tofacitinibum 5 mg twice daily or Tofacitinibum 11 mg once daily. Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinibum 5 mg once daily.
Ulcerative Colitis:
- Tofacitinibum 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Discontinue after 16 weeks of 10 mg twice daily, if adequate therapeutic benefit is not achieved. Use the lowest effective dose to maintain response.
- Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment: half the total daily dosage recommended for patients with normal renal and hepatic function.
Side Effects
The most commonly reported adverse reactions during the first 3 months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with Tofacitinibum monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea and nasopharyngitis.
Toxicity
Minimum lethal dose in rat: 500 mg/kg. Maximum asymptomatic dose in non human primate: 40 mg/kg.
Lymphatic, immune system, bone marrow and erythroid cell toxicity was seen in animal studies involving rate and monkeys. Doses used in these studies ranged from 1mg/kg/day to 10mg/kg/day, over a duration of 6 weeks to 6 months. Lymphopenia, neutropenia, and anemia is seen in human subjects and may call for an interruption or discontinuation of therapy if severe.
Reduced female fertility in rats was seen at exposures 17 times the maximum recommended human dose. Fertility may be impaired in human females and harm may be caused to unborn child. Carcinogenic potential is seen, however evidence for dose dependency is lacking.
Because the janus kinase pathway plays a role in stimulating the production of red blood cells and is involved in immune cell function, inhibition of this pathway leads to increased risk of anemia, neutropenia, lymphopenia, cancer and infection.
Lymphopenia, neutropenia, and anemia in human subjects may call for an interruption or discontinuation of therapy if severe.
Role of JAK inhibition in the development of gastrointestinal perforation is not known.
Precaution
Serious Infections: Avoid use of Tofacitinibum during an active serious infection, including localized infections.
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: Avoid use with Tofacitinibum.
Interaction
Potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., Ketoconazole)
Recommended dose is Tofacitinibum 5 mg once daily: One or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole)
Recommended dose is Tofacitinibum 5 mg once daily Potent CYP inducers (e.g.Rifampin): May result in loss of or reduced clinical response.
Food Interaction
- Avoid grapefruit products. Dose adjustments are required when administering CYP3A4 inhibitors (grapefruit) and CYP2C19 inhibitors with tofacitinib.
- Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of tofacitinib and may reduce its serum concentration.
- Take with or without food.
Tofacitinibum Cholesterol interaction
[Moderate] Hyperlipidemia has been observed in patients receiving tofacitinib.
Patients with preexisting hyperlipidemia may require close monitoring during therapy, and adjustments made accordingly in their lipid-lowering regimen.
Tofacitinibum therapy should be administered with caution in these patients.
Tofacitinibum Drug Interaction
Major: mycophenolate mofetil, adalimumabModerate: aspirin, oxycodone, omeprazole, bifidobacterium infantis / lactobacillus acidophilus, tramadolUnknown: amoxicillin / clavulanate, celecoxib, ubiquinone, dexlansoprazole, ethanol, ipratropium, escitalopram, pregabalin, rimegepant, acetaminophen, tiotropium, levothyroxine, cholecalciferol
Tofacitinibum Disease Interaction
Major: cardiovascular risk, malignancy, thrombosis, viral reactivation, GI perforation, hepatic disorder, infections, renal disease, tuberculosisModerate: cytopenias, diabetes, GI obstruction, hyperlipidemia
Volume of Distribution
Vd= 87L after intravenous administration. Distribution is equal between red blood cells and plasma.
Elimination Route
74% oral absorption (absolute bioavailability), with peak plasma concentrations (T max) achieved in 0.5-1 hour.
Administration with fatty meals does not alter AUC but reduces Cmax by 32%.
Half Life
~3 hours
Elimination Route
70% metabolized in the liver by CYP3A4 (major) and CYP2C19 (minor). Metabolites produced are inactive. 30% renally eliminated as unchanged drug.
Pregnancy & Breastfeeding use
Pregnancy Category C. There are no adequate and well controlled studies in pregnant women. Tofacitinibum should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Tofacitinibum is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Tofacitinibum, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug for the mother
Contraindication
None
Special Warning
Pediatric Use: The safety and effectiveness of Tofacitinibum in pediatric patients have not been established.
Geriatric Use: The frequency of serious infection among Tofacitinibum-treated subjects 65 years of age and older was higher than among those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.
Storage Condition
Store at 20°C to 25°C
Innovators Monograph
You find simplified version here Tofacitinibum
Tofacitinibum contains Tofacitinib see full prescribing information from innovator Tofacitinibum Monograph, Tofacitinibum MSDS, Tofacitinibum FDA label
FAQ
What is Tofacitinibum used for?
Tofacitinibum is used to treat psoriatic arthritis and rheumatoid arthritis. It helps to decrease pain/tenderness/swelling in the joints.Tofacitinibum is also used to treat a certain bowel disease (ulcerative colitis). It helps to reduce symptoms of ulcerative colitis such as diarrhea, rectal bleeding, and stomach pain.
How safe is Tofacitinibum?
Tofacitinibum safety clinical trial show an increased risk of serious heart-related problems and cancer with the arthritis and ulcerative colitis Tofacitinibum compared to another type of medicine.
What are the common side effects of Tofacitinibum?
Common side effects may include:
- skin rash, shingles;
- increased blood pressure;
- abnormal blood tests;
- fever;
- headache;
- nausea, vomiting, diarrhea; or.
- cold symptoms such as stuffy nose, sneezing, sore throat.
How long I stay on Tofacitinibum?
Tofacitinibum daily can be continued for a total of 16 weeks, depending on response.
Does Tofacitinibum cause weight gain?
Tofacitinibum don't lead to weight gain or weight loss.
Is Tofacitinibum is safe during pregnancy?
There are currently no adequate or well-controlled studies of tofacitinib or any disease-modifying antirheumatic drug in pregnant women.
Does Tofacitinibum cause infertility?
Tofacitinibum had no effects on male fertility.
Is Tofacitinibum is safe during breastfeeding?
Tofacitinibum has not been well studied for use during breastfeeding.The manufacturer and an expert panel recommend that breastfeeding be stopped while using Tofacitinibum and for 18 hours after the last dose.
Can I drink alcohol with Tofacitinibum?
You should not drink excessive amounts of alcohol while you are taking Tofacitinibum because both are metabolized by the liver and can cause liver damage.
How long does it take for Tofacitinibum to work?
If Tofacitinibum works for you, you'll usually see an improvement within eight weeks. But some people may find that they begin to feel better as soon as three days after starting treatment.
What time of day should I take Tofacitinibum?
Tofacitinibum is taken as tablets that can be taken with or without food. The usual dose is two tablets a day – one in the morning and one in the evening.
When should I stop taking Tofacitinibum?
It is recommended to stop Tofacitinibum at least seven days prior to surgery because the drug is known to increase the risk of serious infection even in patients not undergoing surgery.
Does Tofacitinibum cause hair loss?
Hair loss is not a side effect of Tofacitinibum.
What happen if I stop Tofacitinibum suddenly?
Sudden shortness of breath or difficulty breathing. Chest pain. Swelling of the leg or arm. Leg tenderness or pain.
Does Tofacitinibum cause blood clots?
Tofacitinibum could increase the risk of blood clots in the lungs and in deep veins in patients who are already at high risk.
How is Tofacitinibum taken?
Take Tofacitinibum exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Swallow the extended-release tablets whole; do not split, chew, or crush them. Always use the oral dosing syringe that comes with Tofacitinibum solution to measure your dose.
What happen If I missed Tofacitinibum?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
Can Tofacitinibum stop working?
Tofacitinibum stops working because Tofacitinibum is a small molecule, antibodies to the drug are not likely to form. This means that tofacitinib is less likely than biologics to stop working over time.
