Litfulo (ritlecitinib) is an oral, once-daily prescription treatment for severe alopecia areata in adults and adolescents aged 12 and older.

Alopecia areata is an autoimmune disease characterized by patchy hair loss, usually on the scalp but occasionally on the face (eyebrows, eyelashes, beard) and other body areas. It is caused by the body’s immune system attacking healthy hair follicles, which causes the hair to fall out.

Litfulo works by selectively and irreversibly inhibiting Janus kinase 3 (JAK3), and other tyrosine kinases, and inhibits cytokine-induced STAT phosphorylation mediated by JAK3-dependent receptors. In addition, it inhibits the signaling of immune receptors dependent on TEC kinase family members. Alopecia areata is characterized by the deregulation of JAK/STAT activity, and the actions of Lifulo are thought to inhibit the function of signaling molecules and immune cells associated with hair loss in alopecia areata.

Litfulo was approved on June 23, 2023, and was the first treatment to be approved for adolescents as well as adults with alopecia areata. It belongs to the class of medicines known as covalent kinase inhibitors.

Litfulo is associated with an increased risk of serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death, including tuberculosis (TB). Litfulo should not be started in those with active TB or a serious infection. Investigations for latent TB should be undertaken before and during therapy and treatment started and the infection cleared before starting Litfulo. All patients should be monitored for signs and symptoms of infection, including TB, during and after treatment.

Janus kinase inhibitors, such as Litfulo are associated with a higher rate of all-cause mortality, including sudden cardiovascular death, myocardial infarction, and stroke, compared to other medications, such as TNF blockers. Thrombosis has occurred in patients treated with Litfulo and there is a higher risk of pulmonary embolism, and venous and arterial thrombosis with JAK inhibitors versus other medications.

Higher rates of malignancies, including non-melanoma skin cancer (NMSC), and lymphoma have been observed in clinical trials of Litfulo, compared to those treated with other medications. Higher rates of lung cancer and all types of malignancies were observed in current or past smokers treated with Litfulo. Consider the risks and benefits of treatment with ritlecitinib in those with a known malignancy other than a successfully treated NMSC or cervical cancer. Periodic skin examinations are recommended for patients who are at increased risk for skin cancer.

Should not be used in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants.

Not recommended in severe liver disease.

You should not use Litfulo if you are allergic to ritlecitinib or any of the inactive ingredients in the capsule. Discontinue if a clinically significant hypersensitivity reaction occurs.

Taking Litfulo can increase your risk of life-threatening medical problems, including serious infections, a heart attack or stroke, blood clots, or cancer. Tell your doctor if you've had:

• a weak immune system or chronic infection (such as tuberculosis, shingles, HIV, or hepatitis)
• any type of cancer
• chronic lung disease
• heart problems
• a heart attack, stroke, or blood clot
• liver disease
• if you've ever smoked
• if you are scheduled to receive any vaccine.

Tell your doctor if you've been sick with signs of infection, such as fever, chills, muscle aches, cough, trouble breathing, skin sores, diarrhea, or painful urination.

Tell your doctor if you've had or been exposed to tuberculosis, or if you recently traveled. Some infections are more common in certain parts of the world, and you may have been exposed during travel.

Your doctor will order some blood tests before starting Litfulo to check for any laboratory abnormalities. Your treatment may be interrupted or discontinued if any of these occur, such as significant decreases in lymphocyte or platelet counts occur.

Using this medicine may increase your risk of developing certain cancers, such as lymphoma or lung cancer. Ask your doctor about this risk.

Children

The safety of Litfulo in children under 12 years of age has not been established.

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. It is not known if this medicine will harm an unborn baby. If you inadvertently become pregnant ask your healthcare providers to ring 1-877-390-2940.

Breastfeeding

Tell your doctor if you are breastfeeding or plan to breastfeed. Breastfeeding is not recommended during treatment with Litfulo and for approximately 14 hours after the last dose.

How do I take Litfulo?

The recommended dose of Litfulo is one 50mg capsule taken once a day by mouth.

May be taken with or without food.

Swallow capsules whole. Do not crush, split, or chew.

Take the missed dose as soon as you remember. Skip the missed dose if it is less than 8 hours before the next dose. Do not use extra medicine to make up for the missed dose.

Temporary treatment interruptions for less than 6 weeks are not expected to result in significant loss of regrown scalp hair.

Litfulo is not expected to be toxic in overdose. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid receiving a "live" vaccine. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles).

The most common side effects are:

• headache
• diarrhea
• acne
• rash
• urticaria
• folliculitis
• fever
• atopic dermatitis
• dizziness
• increases in laboratory values of creatine phosphokinase and decreases in red blood cell counts
• mouth ulcers.

Tell your doctor about all your other medicines, especially:

• CYP3A substrates (such as acetaminophen, codeine, ciclosporin, diazepam, and erythromycin)
• CYP3A inducers (such as rifampicin)
• CYP1A2 substrates, such as caffeine, clozapine, tacrine, propranolol, and mexiletine.

Should not be used in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants.

This list is not complete. Other drugs may affect Litfulo, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.