Ojjaara
(momelotinib)Dosage & Administration
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Ojjaara Prescribing Information
OJJAARA is indicated for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [post-polycythemia vera (PV) and post-essential thrombocythemia (ET)], 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:
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- Complete blood count (CBC) with platelets [see Warnings and Precautions ]
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- Hepatic panel [see Warnings and Precautions ]
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 [see Use in Specific Populations ]. 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.
| ALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal. | ||
| a Reinitiate or escalate treatment up to starting dosage as clinically appropriate. | ||
| b May reinitiate treatment at 100 mg if previously dosed at 100 mg. | ||
| c If baseline >2 × ULN. | ||
| d If baseline >1.5 × ULN. | ||
| e Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events per (CTCAE). | ||
Thrombocytopenia | Dose Modificationa | |
Baseline Platelet Count | Platelet Count | |
≥100 × 109/L | 20 × 109/L to <50 × 109/L | Reduce daily dose by 50 mg from the last given dose. |
<20 × 109/L | Interrupt treatment until platelets recover to 50 × 109/L. Restart OJJAARA at a daily dose of 50 mg below the last given doseb. | |
≥50 × 109/L to <100 × 109/L | <20 × 109/L | Interrupt treatment until platelets recover to 50 × 109/L. Restart OJJAARA at a daily dose of 50 mg below the last given doseb. |
<50 × 109/L | <20 × 109/L | Interrupt treatment until platelets recover to baseline. Restart OJJAARA at a daily dose of 50 mg below the last given doseb. |
Neutropenia | Dose Modificationa | |
Absolute neutrophil count (ANC) <0.5 × 109/L | Interrupt treatment until ANC ≥0.75 × 109/L. Restart OJJAARA at a daily dose of 50 mg below the last given doseb. | |
Hepatotoxicity (unless other apparent causes) | Dose Modificationa | |
ALT and/or AST >5 × ULN (or >5 × baseline, if baseline is abnormal) and/or total bilirubin >2 × ULN (or >2 × baseline, if baseline is abnormal) | Interrupt treatment until AST and ALT ≤2 × ULN or baselinec and total bilirubin ≤1.5 × ULN or baselined. Restart OJJAARA at a daily dose of 50 mg below the last given doseb. If reoccurrence of ALT or AST elevations >5 × ULN, permanently discontinue OJJAARA. | |
Other Non-Hematologic | Dose Modificationa | |
Grade 3 or highere | Interrupt treatment until the toxicity resolves to Grade 1 or lower (or baseline). Restart OJJAARA at a daily dose of 50 mg below the last given doseb. | |
Discontinue OJJAARA in patients unable to tolerate 100 mg once daily.
100 mg round tablet – brown with an underlined “M” debossed on one side and “100” on the other side.
150 mg triangular tablet – brown with an underlined “M” debossed on one side and “150” on the other side.
200 mg capsule-shaped tablet – brown with an underlined “M” debossed on one side and “200” on the other side.
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 2% to 4% and 15% to 20%, respectively.
Data
Animal Data: In an embryofetal development study, pregnant rats received momelotinib 2, 6 or 12 mg/kg/day orally, during the period of organogenesis (Gestation Day 6 to 17). 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).
In an embryofetal developmental study, pregnant rabbits received momelotinib at 7.5, 30 or 60 mg/kg/day orally during the period of organogenesis (Gestation Day 7 to 20). 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.
In a pre- and post-natal development study, pregnant rats received momelotinib 2, 6 or 12 mg/kg/day orally from organogenesis through lactation (Gestation Day 6 to lactation Day 20). 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).
Lactation
Risk Summary
There are no data on the presence of momelotinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. It is not known whether OJJAARA is excreted in human milk. Momelotinib was present in rat pups following nursing from treated dams with adverse effects observed in the offspring. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential for serious adverse reactions in a breastfed child, patients should not breastfeed during treatment with OJJAARA, and for at least 1 week after the last dose of OJJAARA.
Data
Animal Data: In a pre- and postnatal development study, momelotinib was administered orally to rats during the lactation period; the drug was detected in plasma of nursing pups, which adversely affected pup survival.
Females and Males of Reproductive Potential
Contraception
Advise females of reproductive potential who are not pregnant to use highly effective contraception during therapy and for at least 1 week after the last dose of OJJAARA.
Pediatric Use
The safety and effectiveness of OJJAARA in pediatric patients have not been established.
Geriatric Use
There were 275 patients aged 65 years and older in the clinical studies for MF [see Clinical Studies ]. Of the total number of OJJAARA-treated patients in these studies, 163/216 (75%) were aged 65 years and older, and 63/216 (29%) were aged 75 years and older. No overall differences in safety or effectiveness of OJJAARA have been observed between patients aged 65 years and older and younger adult patients.
Hepatic Impairment
The recommended starting dose of OJJAARA in patients with severe hepatic impairment (Child-Pugh C) is 150 mg orally once daily [see Dosage and Administration ]. No dose modification is recommended for patients with mild hepatic impairment (Child-Pugh A) or moderate hepatic impairment (Child-Pugh B).
Momelotinib is extensively metabolized [see Clinical Pharmacology ]. Momelotinib exposure increased with severe hepatic impairment (Child-Pugh C). No clinically significant changes in momelotinib exposure were observed in subjects with mild hepatic impairment (Child-Pugh A) or moderate hepatic impairment (Child-Pugh B) [see Clinical Pharmacology ].
None.
Risk of Infections
Serious (including fatal) infections (e.g., bacterial and viral, including COVID-19) occurred in 13% of patients treated with OJJAARA. Infections regardless of grade occurred in 38% of patients treated with OJJAARA [see Adverse Reactions ]. Delay starting therapy with OJJAARA until active infections have resolved. Monitor patients receiving OJJAARA for signs and symptoms of infection and initiate appropriate treatment promptly.
Hepatitis B Reactivation
Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine transaminase (ALT) or aspartate transaminase (AST), have been reported in patients with chronic hepatitis B virus (HBV) infection taking Janus Kinase (JAK) inhibitors, including OJJAARA. The effect of OJJAARA on viral replication in patients with chronic HBV infection is unknown. In patients with HBV infections, check hepatitis B serologies prior to starting OJJAARA. If HBsAg and/or anti-HBc antibody is positive, consider consultation with a hepatologist regarding monitoring for reactivation versus prophylactic hepatitis B therapy. Patients with chronic HBV infection who receive OJJAARA should have their chronic HBV infection treated and monitored according to clinical HBV guidelines.
Thrombocytopenia and Neutropenia
OJJAARA can cause thrombocytopenia and neutropenia [see Adverse Reactions ].
New or worsening thrombocytopenia, with platelet count less than 50 × 109/L, was observed in 20% of patients treated with OJJAARA. Eight percent of patients treated with OJJAARA had baseline platelet counts less than 50 × 109/L.
Severe neutropenia, absolute neutrophil count (ANC) less than 0.5 × 109/L, was observed in 2% of patients treated with OJJAARA.
Assess complete blood counts (CBC), including platelet and neutrophil counts, before initiating treatment and periodically during treatment as clinically indicated. Interrupt dosing or reduce the dose for thrombocytopenia or neutropenia [see Dosage and Administration ].
Hepatotoxicity
Two of the 993 patients with MF who received at least one dose of OJJAARA in clinical trials experienced reversible drug-induced liver injury. Overall, new or worsening elevations of ALT and AST (all grades) occurred in 23% and 24%, respectively, of patients treated with OJJAARA; Grade 3 and 4 transaminase elevations occurred in 1% and 0.5% of patients, respectively. New or worsening elevations of total bilirubin occurred in 16% of patients treated with OJJAARA. All total bilirubin elevations were Grades 1-2. The median time to onset of any grade transaminase elevation was 2 months, with 75% of cases occurring within 4 months.
Delay starting therapy in patients presenting with uncontrolled acute and chronic liver disease until apparent causes have been investigated and treated as clinically indicated. When initiating OJJAARA, refer to dosing in patients with hepatic impairment [see Dosage and Administration ].
Monitor liver tests at baseline, every month for 6 months during treatment, then periodically as clinically indicated. If increases in ALT, AST or bilirubin related to treatment are suspected, modify OJJAARA dosage based upon Table 1 [see Dosage and Administration ].
5.4 Severe Cutaneous Adverse Reactions (SCARs)
Severe cutaneous adverse reactions, including toxic epidermal necrolysis (TEN), have been observed in some patients treated with OJJAARA.
If signs or symptoms of severe cutaneous reactions occur, interrupt OJJAARA until the etiology of the reaction has been determined. Consider early consultation with a dermatologist for evaluation and management.
If etiology is considered to be associated with OJJAARA, permanently discontinue and do not reintroduce OJJAARA in patients who have experienced SCARs or other life-threatening cutaneous reactions during OJJAARA treatment.
Major Adverse Cardiovascular Events (MACE)
Another JAK inhibitor increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke [compared with those treated with tumor necrosis factor (TNF) blockers] in patients with rheumatoid arthritis, a condition for which OJJAARA is not indicated.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OJJAARA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Inform patients receiving OJJAARA of the symptoms of serious cardiovascular events and the steps to take if they occur.
Thrombosis
Another JAK inhibitor increased the risk of thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis (compared with those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which OJJAARA is not indicated.
Evaluate patients with symptoms of thrombosis and treat appropriately.
Malignancies
Another JAK inhibitor increased the risk of lymphoma and other malignancies excluding nonmelanoma skin cancer (NMSC) (compared with those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which OJJAARA is not indicated. Current or past smokers were at increased risk.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OJJAARA, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.