General

Pronunciation:
rit-le-sye-ti-nib

Trade Name(s)

• Litfulo

Ther. Class.

none assigned

Pharm. Class.

kinase inhibitors

Indications

Severe alopecia areata.

Action

Irreversibly inhibits Janus kinase 3 and the tyrosine kinase expressed in the hepatocellular carcinoma (TEC) kinase family by blocking the adenosine triphosphate binding site, both of which may inhibit T cell activation.

Therapeutic Effect(s):

Reduction in scalp hair loss.

Pharmacokinetics

Absorption: 64% absorbed following oral administration.

Distribution: Unknown.

Metabolism and Excretion: Metabolized by multiple pathways, including glutathione S-transferase and several CYP450 enzymes (CYP3A, CYP2C8, CYP1A2, and CYP2C9). Primarily excreted as metabolites in the urine (66%), with 20% excreted in the feces.

Half-life: 1.3–2.3 hr.

TIME/ACTION PROFILE (reduction in scalp hair loss)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Active, serious infection;
• Severe hepatic impairment;
• Lactation:  Lactation.

Use Cautiously in:

• Chronic, recurrent infection;
• Previous exposure to tuberculosis (TB);
• History of serious or opportunistic infection;
• Lived or traveled in areas of endemic TB or mycoses;
• Predisposed to infection;
• >50 yr old with ≥1 cardiovascular risk factor (may ↑ risk of all-cause mortality, cardiovascular death, MI, stroke, and thrombosis);
• Current or past history of smoking (↑ risk of malignancy, cardiovascular death, MI, or stroke);
• Known malignancy (other than a successfully treated non-melanoma skin cancer or cervical cancer);
• OB:   Safety not established in pregnancy;
• Pedi:   Children <12 yr (safety and effectiveness not established);
• Geri:  Infection risk may be ↑ in older adults.

Adverse Reactions/Side Effects

CV: ARTERIAL THROMBOSIS, CARDIOVASCULAR DEATH, DEEP VEIN THROMBOSIS, MI

Derm: acne, atopic dermatitis, folliculitis, rash, urticaria

GI: diarrhea, ↑ liver enzymes, stomatitis

Hemat: anemia, lymphopenia, thrombocytopenia

MS: ↑ creatine kinase

Neuro: headache, dizziness, STROKE

Resp: PULMONARY EMBOLISM

Misc: fever, HYPERSENSITIVITY REACTIONS (including anaphylaxis), INFECTION (including TB, bacterial, invasive fungal, viral, and other infections due to opportunistic pathogens), MALIGNANCY

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• May ↑ risk of adverse reactions and ↓ antibody response to  live vaccines ; avoid concurrent use.
• May ↑ levels and risk of toxicity of  CYP3A substrates.
• May ↑ levels and risk of toxicity of  CYP1A2 substrates.
•  Strong CYP3A inducers, including  rifampin, may ↓ levels and effectiveness; concurrent use not recommended.

Route/Dosage

PO (Adults): 50 mg once daily.

Availability

Capsules: 50 mg

Assessment

• Assess scalp for hair regrowth periodically during therapy.
• Monitor for signs and symptoms of infection during and after therapy. If a patient develops a serious or opportunistic infection, interrupt ritlecitinib, promptly complete diagnostic testing appropriate for an immunocompromised patient, and start antimicrobial therapy. May resume ritlecitinib once the infection is controlled.
• Screen patient for TB before starting therapy. Do not administer ritlecitinib to patients with active TB. Start anti-TB therapy before starting ritlecitinib in patients with a new diagnosis of latent TB or previously untreated latent TB.
• May cause viral reactivation (herpes virus reactivation). If a patient develops herpes zoster, consider holding therapy until episode resolves.
• Screen for viral hepatitis before starting ritlecitinib.
• Monitor for signs and symptoms of a hypersensitivity reaction (dyspnea, feeling faint or dizzy, swelling of lips, tongue, or throat; urticaria, hives, rash) during therapy. Discontinue ritlecitinib if reaction occurs.

Lab Test Considerations:

Monitor absolute lymphocyte counts (ALC) and platelet counts before starting therapy, at 4 wk after start of therapy, then according to routine patient management. If ALC is <500/mm³ , hold doses; may be restarted once ALC returns to above this value. If platelet count is <50,000/mm³ , discontinue therapy.

• Monitor liver enzymes before starting and periodically during therapy. If increases in ALT or AST are observed and drug-induced liver injury is suspected, hold ritlecitinib until diagnosis is determined.
• May cause ↑ CK.

Implementation

• Verify that all vaccinations, including prophylactic herpes zoster, are current before starting therapy.
• PO Administer once daily without regard to food.  DNC: Swallow capsules whole; do not crush, split, or chew. 

Patient/Family Teaching

• Instruct patient to take ritlecitinib as directed. If a dose is missed, administer dose as soon as possible, unless it is <8 hr before next dose; then skip missed dose and resume dosing at the regular scheduled time. If therapy is held, a temporary interruption for <6 wk is not expected to result in significant loss of regrown scalp hair. Advise patient to read  Medication Information  before starting ritlecitinib and with each Rx refill in case of changes.
• Advise patient to notify health care professional if signs and symptoms of infections (fever; sweating; chills; muscle aches; cough or shortness of breath; blood in phlegm; weight loss; warm, red, or painful skin or sores on the body; diarrhea or stomach pain; burning on urination or urinating more often than usual; feeling very tired), heart attack or stroke (chest discomfort lasting more than a few minutes, or that goes away and comes back; severe tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw; pain or discomfort in arms, back, neck, jaw, or stomach; shortness of breath with or without chest discomfort; breaking out in a cold sweat; nausea or vomiting; light-headedness; weakness in one part or on one side of body; slurred speech), blood clots (swelling, pain or tenderness in one or both legs; sudden, unexplained chest or upper back pain; shortness of breath or difficulty breathing; changes in vision, especially in one eye only), or hypersensitivity reactions occur.
• Inform patient that ritlecitinib may increase risk of cancer (lymphoma, lung cancer). Advise patient to have periodic skin examinations and to tell health care professional if they have ever had any type of cancer.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to avoid live attenuated vaccines during or shortly before starting therapy.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy and for 14 hr after last dose. If patient becomes pregnant while receiving ritlecitinib, health care professional should report pregnancy exposure the Pregnancy Exposure Registry by calling 1-877-390-2940.

Evaluation/Desired Outcomes

Decrease in scalp hair loss.