Ojjaara Drug Information

OJJAARA is indicated for the treatment of intermediate or high‑risk myelofibrosis (MF), including primary MF or secondary MF, in adults with anemia.

Recommended Dosage

The recommended dosage of OJJAARA is 200 mg orally once daily. OJJAARA may be taken with or without food. Swallow OJJAARA tablets whole.

Do not cut, crush, or chew tablets. If a dose of OJJAARA is missed, the next scheduled dose should be taken the following day.

Laboratory Monitoring for Safety Obtain the following blood tests prior to starting treatment with OJJAARA, periodically during treatment, and as clinically indicated: • Complete blood count (CBC) with platelets • Hepatic panel

Dosage Modification for Hepatic Impairment

The recommended starting dosage in patients with severe hepatic impairment (Child‑Pugh Class C) is 150 mg orally once daily. No dose adjustment is recommended for patients with mild or moderate hepatic impairment.

Dosage Modification for Adverse Reactions

Manage hematologic and non‑hematologic adverse reactions as described in Table 1. Table 1: Dose Modifications for OJJAARA-Related Adverse Reactions Discontinue OJJAARA in patients unable to tolerate 100 mg once daily.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OJJAARA was evaluated in 215 patients in 2 clinical trials (MOMENTUM and SIMPLIFY‑1 anemic subgroup ). MOMENTUM Patients in the MOMENTUM trial had been previously treated with a JAK inhibitor and were randomly assigned 2:1 to receive double‑blind OJJAARA 200 mg orally once daily (n = 130) or danazol 300 mg orally twice daily (n = 65) for 24 weeks, after which they were eligible to receive open‑label OJJAARA in an extended treatment phase.

Fatal adverse reactions occurred in 12% of patients who received OJJAARA; the most common (≥2%) fatal adverse reaction was viral infection (5%). Permanent discontinuation of OJJAARA due to an adverse reaction occurred in 18% of patients during the randomized treatment period of the MOMENTUM trial. Adverse reactions that resulted in permanent discontinuation (≥2%) included viral infection (2%) and thrombocytopenia (2%).

Dosage reduction or treatment interruption due to an adverse reaction occurred in 34% of patients. Among the 130 patients treated with OJJAARA during the randomized treatment period of MOMENTUM, the most common adverse reactions (≥20%) were thrombocytopenia, diarrhea, hemorrhage, and fatigue ( Table 2 ). Upon completion of the double‑blind treatment phase, all patients were eligible to receive OJJAARA during the open‑label phase.

The safety of OJJAARA was evaluated in the population of patients with MF who were anemic at study entry. SIMPLIFY‑1 enrolled 180 anemic patients who received OJJAARA (n = 85) or ruxolitinib (n = 95). A fatal adverse reaction (bacterial infection) occurred in 1 patient who received OJJAARA.

Dosage reductions or treatment interruptions of OJJAARA due to an adverse reaction occurred in 21% of patients. Among the 85 anemic patients treated with OJJAARA during the randomized treatment period of SIMPLIFY‑1, the most common adverse reactions (≥20%) were dizziness, fatigue, bacterial infection, hemorrhage, thrombocytopenia, diarrhea, and nausea ( Table 3 ). Table 3: Adverse Reactions Occurring in ≥5% of Anemic Patients Receiving OJJAARA during Randomized Treatment in SIMPLIFY-1 Clinically relevant adverse reactions occurring in <5% of anemic patients in the MOMENTUM and SIMPLIFY‑1 studies include: Eye Disorders: Blurred vision.

Infections and Infestations: Fungal infection (excludes opportunistic infections). Musculoskeletal and Connective Tissue Disorders: Arthralgia. Nervous System Disorders: Neuralgia, peripheral neuropathy, peripheral motor neuropathy, polyneuropathy, syncope.

Vascular Disorders: Flushing.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of OJJAARA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Hypersensitivity.

Metabolism and Nutrition Disorders: Hypoglycemia. Skin and Subcutaneous Tissue Disorders: Erythema multiforme, toxic epidermal necrolysis (TEN).

Effect of Other Drugs on OJJAARA Organic Anion Transporting Polypeptide (OATP)1B1/B3 Inhibitors Momelotinib is an OATP1B1/B3 substrate. Concomitant use with an OATP1B1/B3 inhibitor increases momelotinib maximal concentrations (C max ) and area under the concentration‑time curve (AUC), which may increase the risk of adverse reactions with OJJAARA. Monitor patients concomitantly receiving an OATP1B1/B3 inhibitor for adverse reactions and consider OJJAARA dose modifications.

Effect of OJJAARA on Other Drugs Breast Cancer Resistance Protein (BCRP) Substrates Momelotinib is a BCRP inhibitor. OJJAARA may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. When administered concomitantly with OJJAARA, initiate rosuvastatin (BCRP substrate) at 5 mg and do not increase to more than 10 mg once daily.

Dose adjustment of other BCRP substrates may also be needed. Follow approved product information recommendations for other BCRP substrates.

Pregnancy Risk Summary Available data on the use of OJJAARA in pregnant women are insufficient to determine whether there is a drug‑associated risk for major birth defects or miscarriage. Based on animal reproduction studies conducted in rats and rabbits, momelotinib may cause embryo‑fetal toxicity at exposures lower than the expected exposure in patients receiving 200 mg once daily (see Data). OJJAARA should only be used during pregnancy if the expected benefits to the mother outweigh the potential risks to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Embryo‑fetal toxicity (embryonic death, soft tissue anomalies, skeletal variations, and lower mean fetal body weights) was observed at 12 mg/kg (in the presence of maternal toxicity). Skeletal variations were observed (in the absence of maternal toxicity) at 6 mg/kg/day at exposures 3.5 times the exposure at the recommended human dose of 200 mg daily based on combined momelotinib and M21 (a major human metabolite) AUC. No developmental toxicity was observed at 2 mg/kg/day at exposures equivalent to the recommended dose (based on combined momelotinib and M21 AUC).

Momelotinib was associated with maternal toxicity at 60 mg/kg/day, which resulted in reduced mean fetal weight, delayed bone ossification, and an abortion at less than the exposure at the recommended dose (based on combined momelotinib and M21 AUC). No developmental toxicity was observed at lower doses tested in rabbits. Decreased pup body weights and embryo‑lethality were observed in the dams administered 6 and 12 mg/kg/day.

Pup survival was significantly reduced in the 12 mg/kg/day group from birth to Day 4 of lactation. Momelotinib exposure in dams at 12 mg/kg and 6 mg/kg were approximately 2 times the exposure at the recommended dose (based on combined momelotinib and M21 AUC). The exposure in dams at the No Observed Adverse Effect Level (NOAEL) dose of 2 mg/kg was less than the exposure at the recommended dose (based on combined momelotinib and M21 AUC).

Pediatric Use The safety and effectiveness of OJJAARA in pediatric patients have not been established.

There is no known antidote for overdose with OJJAARA. If overdose is suspected, the patient should be monitored for signs or symptoms of adverse reactions or effects, and appropriate supportive treatment should be instituted immediately. Further management should be as clinically indicated.

Hemodialysis is not expected to enhance the elimination of momelotinib. Consider contacting the Poison Help line (1‑800‑222‑1222) or a medical toxicologist for additional overdose management recommendations.