New drugs
MOTIXAFORTIDE
(Aphexda—BioLineRx)
Drug class: Aphexda is a hematopoietic stem cell mobilizer.
Indication: Aphexda is indicated in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.
Recommended dosage and administration: Initiate Aphexda treatment after filgrastim has been administered daily for 4 days. The recommended dosage is 1.25 mg/kg actual body weight by S.C. injection 10 to 14 hours prior to initiation of apheresis. A second dose of Aphexda can be administered 10 to 14 hours prior to a third apheresis.
Common adverse effects: The most common adverse reactions are injection site reactions, injection site pain, injection site erythema, injection site pruritus, flushing, and back pain.
Warnings and precautions: Aphexda is contraindicated in patients with a history of hypersensitivity reaction to Aphexda. Premedicate all patients with a combination of an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor prior to each Aphexda dose. Administer Aphexda in a setting where personnel and therapies are available for immediate treatment. Observe patients for signs and symptoms of anaphylaxis and manage promptly.
The addition of analgesic premedication is recommended for injection site reactions. Aphexda may mobilize leukemic cells and should not be used in leukemia patients. Increased circulating leukocytes have been observed. Monitor white blood cell counts during Aphexda use.
Tumor cells may be released from marrow during hematopoietic stem cell mobilization with Aphexda and filgrastim. The effect of reinfusion of tumor cells is unknown. Aphexda may cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. Advise patients not to breastfeed during treatment.
MOMELOTINIB
(Ojjaara—GlaxoSmithKline)
Drug class: Ojjaara is a kinase inhibitor.
Indication: 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 and administration: The recommended dosage is 200 mg orally once daily with or without food. In severe hepatic impairment, reduce the starting dose to 150 mg orally once daily.
Common adverse effects: The most common adverse reactions are thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
Warnings and precautions: Do not initiate Ojjaara in patients with an active infection. Monitor for signs and symptoms of infection, including reactivation of hepatitis B, and initiate appropriate treatment promptly. Manage thrombocytopenia and neutropenia by dose reduction or interruption. Obtain liver tests before initiation of and periodically throughout treatment with Ojjaara. Monitor for symptoms of major adverse cardiovascular events and evaluate and treat promptly. Evaluate and treat symptoms of thrombosis promptly. Monitor for development of secondary malignancies, particularly in current or past smokers. Monitor for adverse reactions when used concomitantly with organic anion transporting polypeptide (OATP)1B1/B3 inhibitors. If taken concomitantly with rosuvastatin, reduce rosuvastatin dosage. Follow approved product information recommendations if Ojjaara is taken concomitantly with other breast cancer resistant protein substrates. Ojjaara may cause fetal harm if used during pregnancy and patients should be advised not to breastfeed during treatment.
GEPIRONE
(Exxua—Fabe-Kramer Pharmaceuticals)
Drug class: The mechanism of the antidepressant effect of Exxua is not fully understood but it is thought to be related to its modulation of serotonergic activity in the central nervous system through selective agonist activity at 5HT1A receptors.
Indication: Exxua is indicated for the treatment of major depressive disorder in adults.
Recommended dosage and administration: Correct electrolyte abnormalities and perform an electrocardiogram (ECG) prior to initiating treatment with Exxua. Do not initiate therapy if the QTc is >450 msec. Perform ECGs during dosage titration and periodically during treatment. The recommended starting dose is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased to 36.3 mg once daily on day 4. Dosage may be further titrated to 54.5 mg once daily after day 7 and to 72.6 mg once daily after an additional week. In geriatric patients, the recommended starting dosage is 18.2 mg once daily and the dosage may be increased to 36.3 mg after 7 days. In patients with moderate hepatic impairment, dosage may be increased to 36.3 mg once daily after 7 days. Adjust Exxua dose by 50% when a moderate CYP3A4 inhibitor is administered.
Common adverse effects: The most common adverse reactions were dizziness, nausea, insomnia, abdominal pain, and dyspepsia.
Boxed warning: There is an increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Closely monitor for worsening and emergence of suicidal thoughts and behaviors. Exxua is not approved for use in pediatric patients.
Other warnings and precautions: Exxua is contraindicated in known hypersensitivity to gepirone or components of Exxua, prolonged QTc interval of >450 msec at baseline, congenital long QTc syndrome, concomitant use of strong CYP3A4 inhibitors, severe hepatic impairment, and use with an MAOI or within 14 days of stopping treatment with Exxua. Do not use Exxua within 14 days of discontinuing an MAOI.
Exxua prolongs the QTc interval. Correct electrolyte abnormalities. Perform ECGs prior to initiation, during dose titration, and periodically during treatment with Exxua. Monitor ECGs more frequently when Exxua is used concomitantly with drugs known to prolong the QTc interval, in patients who develop QTc intervals of ≥450 msec during treatment, or are at significant risk of developing torsade de pointes. Do not escalate dosage if QTc interval is >450 msec. There is an increased risk of serotonin syndrome when co-administered with other serotonergic agents. If serotonin syndrome occurs, discontinue Exxua and initiate supportive measures. Screen patients for bipolar disorder as activation of mania/hypomania can occur. Avoid concomitant use with strong CYP3A4 inducers as this reduces Exxua exposure. Use of Exxua in the third trimester may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (e.g., respiratory distress, temperature instability, feeding difficulty, hypotonia, irritability) in the neonate.
NEDOSIRAN
(Rivfloza—Novo Nordisk)
Drug class: Rivfloza is an LDHA-directed small interfering RNA.
Indication: Rivfloza is indicated to lower urinary oxalate levels in children 9 years and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function (eGFR ≥30 mL/min/1.73 m2).
Recommended dosage and administration: The recommended dosage in adults and adolescents 12 years and older weighing ≥50 kg is 160 mg once monthly. The recommended dosage in adults and adolescents 12 years and older weighing <50 kg is 128 mg once monthly. The recommended dosage in children between the ages of 9 years and 11 years ≥50 kg is 160 mg once monthly. The recommended dosage in children between the ages of 9 years and 11 years weighing <50 kg is 3.3 mg/kg once monthly, not to exceed 128 mg.
Common adverse effects: The most common adverse reaction is injection site reactions.
Warnings and precautions: There are none reported at this time.
New indications
TEMOZOLOMIDE
(Temodar—Merck Sharp & Dohme)
Drug class: Temodar is an alkylating drug.
Indication: Temodar is indicated for the treatment of adults with newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment, as an adjuvant treatment for adults with newly diagnosed anaplastic astrocytoma, and for the treatment of adults with refractory anaplastic syndrome.
Recommended dosage and administration: Temodar should be administered either orally or intravenously. For the treatment of newly diagnosed glioblastoma, the recommended dosage is 75 mg/m2 for 42 to 49 days concomitant with focal radiotherapy followed by initial maintenance dose of 150 mg/m2 once daily for days 1 to 5 of each 28-day cycle for 6 cycles. The maintenance dose may be increased to 200 mg/m2 on cycles 2 to 6 based on toxicity. Provide pneumocystis pneumonia (PCP) prophylaxis during concomitant phase and continue in patients who develop lymphopenia until resolution to Grade 1 or less.
For adjuvant treatment of newly diagnosed anaplastic astrocytoma, Temodar is administered orally beginning 4 weeks after the end of radiotherapy in a single dose on days 1 to 5 of a 28-day cycle for 12 cycles. The recommended dosage for cycle 1 is 150 mg/m2 per day and for cycles 2 to 12 is 200 mg/m2 if the patient experienced minimal or no toxicity in cycle 1. For the treatment of refractory anaplastic astrocytoma, the initial dose is 150 mg/m2 once daily on days 1 to 5 of each 28-day cycle.
Common adverse effects: The most common adverse reactions are alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, convulsions, decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes.
Warnings and precautions: Monitor absolute neutrophil count and platelet count prior to each cycle and during treatment. Geriatric patients and women have a higher risk of developing myelosuppression. Fatal and severe hepatotoxicity have been reported. Perform liver tests at baseline, midway through the first cycle, prior to each subsequent cycle, and approximately 2 to 4 weeks after the last dose of Temodar.
Closely monitor all patients, particularly those receiving steroids, for the development of lymphopenia and PCP. Myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed. Temodar can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. Temodar capsules should not be opened, chewed, or dissolved but should be swallowed whole with a glass of water. Patients should be advised not to breastfeed during treatment. ■
FDA approves cancer testing panel
In September 2023, FDA approved the first marketing authorization for the Invitae Common Hereditary Cancers Panel. This diagnostic test has the ability to test for hundreds of genetic variants that are associated with an elevated risk of developing certain cancers. Additionally, the test can be used to detect hereditary variants that are potentially associated with cancer in individuals who have already been diagnosed with cancer. The panel utilizes DNA extracted from a blood sample to identify variants in 47 different genes that are known to be associated with a higher risk of developing cancer. It is important that the results of the Invitae Common Hereditary Cancers Panel are reviewed with a health care professional to prevent patients from misunderstanding the results. Patients should be advised that this test is not intended to identify all known genes that are associated with a predisposition for cancer and that genetics are not the only factor in the development of cancer. ■