ritlecitinib

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 (↓ in scalp hair loss)

ROUTEONSETPEAKDURATION
PO6–8 wkunknown≥24 wk

Contraindication/Precautions

Contraindicated in:

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

Use Cautiously in:

  • Black Box:  Chronic, recurrent infection;
  • Black Box:  Previous exposure to tuberculosis (TB);
  • Black Box:  History of serious or opportunistic infection;
  • Black Box:  Lived or traveled in areas of endemic TB or mycoses;
  • Black Box:  Predisposed to infection;
  • Black Box:  >50 yr old with ≥1 cardiovascular risk factor (may ↑ risk of all-cause mortality, cardiovascular death, MI, stroke, and thrombosis);
  • Black Box:  Current or past history of smoking (↑ risk of malignancy, cardiovascular death, MI, or stroke);
  • Black Box:  Known malignancy (other than a successfully treated nonmelanoma 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 (DVT), MI

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

GI: diarrhea, ↑ liver enzymes, stomatitis

Hemat: anemia, lymphopenia, thrombocytopenia

MS: ↑ CK

Neuro: headache, dizziness, STROKE

Resp: PULMONARY EMBOLISM (PE)

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 latent 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.
  • 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.  If hypersensitivity reaction occurs,  discontinue ritlecitinib.
  • Monitor for thrombosis, including PE, DVT, and arterial thrombi.  If signs/symptoms of thrombosis occur,  permanently discontinue ritlecitinib.
  • Perform periodic skin examination in ↑ risk patients of skin cancer.

Lab Test Considerations:

  • Monitor absolute lymphocyte counts (ALC) and platelet counts before starting therapy, at 4 wk after start of therapy, and then according to routine patient management. If ALC <500 cells/mm3  or platelet count <100,000 cells/mm3 , hold ritlecitinib; may be restarted once levels return to above this value. If platelet count <50,000 cells/mm3 , discontinue ritlecitinib.
  • Screen for viral hepatitis at baseline. Initiation is not recommended in patients with hepatitis B or C.
  • Monitor liver enzymes before starting and periodically during therapy.  If ↑ in ALT or AST are observed and drug-induced liver injury is suspected,  hold ritlecitinib until diagnosis determined.
  • May ↑ CK.

Implementation

  • Verify that all vaccinations, including prophylactic herpes zoster, are current before starting therapy. Avoid use of live-attenuated vaccines during treatment or shortly before starting therapy.
  • PO Administer once daily without regard to food.  DNC: Swallow capsules whole; do not crush, split, or chew. 

Patient/Family Teaching

  • Explain the purpose and side effects of ritlecitinib. Instruct patient to take 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 patients and family to call 911 and seek urgent treatment for signs and symptoms of hypersensitivity reactions (difficulty breathing; chest tightness; hives; rash; feeling light-headed; itching; swelling of the face, lips, tongue, or throat).
  • Advise patients and family to call 911 and seek urgent treatment if signs and symptoms of MI or stroke (chest pain, dizziness, nausea, weakness, slurred speech, confusion, trouble breathing); or 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) occur.
  • Advise patient to notify health care provider 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).
  • Inform patient that ritlecitinib may ↑ risk of cancer (lymphoma, lung cancer). Advise patient to have periodic skin examinations and to tell health care provider if they have ever had any type of cancer.
  • Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
  • Advise patient to avoid live attenuated vaccines during or shortly before starting therapy.
  • Rep:  Advise women of reproductive potential to notify health care provider 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 provider should report pregnancy exposure to Pregnancy Exposure Registry by calling 1-877-390-2940.

Evaluation/Desired Outcomes

Decrease in scalp hair loss.