Ontruzant (trastuzumab-dttb)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Trastuzumab is a recombinant DNA-derived humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody and antineoplastic agent.
Trastuzumab and hyaluronidase-oysk is a fixed combination of trastuzumab (a recombinant DNA-derived humanized anti-HER2 monoclonal antibody) and hyaluronidase (an endoglycosidase); the hyaluronidase component is used to increase the absorption of trastuzumab.
Trastuzumab-anns (Kanjinti(R)), trastuzumab-dkst (Ogivri(R)), trastuzumab-dttb (Ontruzant(R)), trastuzumab-pkrb (Herzuma(R)), trastuzumab-qyyp (Trazimera(R)), and trastuzumab-strf (Hercessi(R)) are biosimilar to trastuzumab (Herceptin(R)). FDA defines a biosimilar as a biological product highly similar to an FDA-licensed reference biologic with the exception of minor differences in clinically inactive components, and for which there are no clinically meaningful differences in safety, purity, or potency. The claim of biosimilarity is based on a totality-of-evidence approach, which includes consideration of data from analytical, animal, and clinical studies (e.g., human pharmacokinetic and pharmacodynamic studies, clinical immunogenicity assessment, additional comparative clinical studies).
Therefore, biosimilarity may be established even when there are formulation or minor structural differences as long as these differences are not clinically meaningful. Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between the proposed biologic and the reference biological, but does not independently establish safety and effectiveness of the proposed biosimilar biological. In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product; these requirements include demonstrating the biological product can be expected to produce the same clinical results as the reference product in any given patient and, for a biological product administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is no greater than the risk of using the reference product without such alteration or switch.
Biosimilar products that are interchangeable can be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. None of the currently available trastuzumab biosimilars have interchangeable data at this time.
Trastuzumab, a recombinant DNA-derived humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is an antineoplastic agent. Trastuzumab inhibits proliferation of tumor cells that overexpress HER2. The HER2 proto-oncogene (also known as c-erbB2 or neu) encodes a 185-kd transmembrane tyrosine kinase receptor known as p185HER2 or HER2, which is structurally related to the epidermal growth factor receptor.
Trastuzumab, a recombinant humanized murine monoclonal antibody, binds specifically to the extracellular domain of the HER2 receptor or HER2/neu protein. Results from in vitroassays and animal studies have shown trastuzumab inhibits the proliferation of human tumor cells that overexpress HER2/neu protein. Trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) also has been demonstrated and, according to in vitro studies, occurs preferentially in cells that overexpress the HER2 protein compared with cells that do not.
Hyaluronidase, a component of trastuzumab/hyaluronidase-oysk, is a recombinant human endoglycosidase used to increase the dispersion and absorption of co-administered medications when administered subcutaneously. Hyaluronidase depolymerizes hyaluronan, a polysaccharide found in the extracellular matrix of subcutaneous tissue; this leads to increased permeability of subcutaneous tissues. Hyaluronidase acts transiently and locally; effects are reversible, and permeability of the subcutaneous tissue is restored within 24-48 hours.
Hyaluronidase was shown to increase absorption rate of a trastuzumab product in animal studies.
Trastuzumab is eliminated via parallel linear and non-linear elimination pathways; as a result, total trastuzumab clearance increases with decreasing concentrations. Although the average trastuzumab exposure was higher following the first cycle in breast cancer patients receiving the every-3-week schedule compared to the weekly schedule of IV trastuzumab, the average steady-state exposure was essentially the same at both dosages. The average trastuzumab exposure following the first cycle at steady state, as well as the time to steady state, was higher in breast cancer patients compared with metastatic gastric cancer patients at the same dosage; the reason for this difference is unclear.
Time to steady state with IV trastuzumab administration was approximately 12 weeks in breast cancer patients and 9 weeks in patients with metastatic gastric cancer. Following discontinuation of IV trastuzumab, trastuzumab concentrations will decrease to approximately 3% of the population predicted steady-state trough serum concentration (97% washout) by 7 months in most patients. Pharmacokinetics of IV trastuzumab are not significantly affected by age or race (Asian versus non-Asian evaluated in studies).
Trastuzumab exposure following subcutaneous administration of trastuzumab/hyaluronidase-oysk 600 mg/10,000 units every 3 weeks is comparable to that observed with a regimen of IV trastuzumab 8 mg/kg (loading dose) followed by 6 mg/kg every 3 weeks. In a pharmacokinetic study comparing trastuzumab/hyaluronidase-oysk to IV trastuzumab, the mean maximum plasma concentration of trastuzumab was 32% lower with trastuzumab/hyaluronidase-oysk, and the mean AUC following the cycle 7 dose and cycle 12 dose was approximately 10 and 20% higher, respectively. Following subcutaneous administration of trastuzumab/hyaluronidase-oysk, trastuzumab concentrations reached steady state after the cycle 7 dose, with a <15% increase in concentration up to cycle 13.
The absolute bioavailability of subcutaneous trastuzumab/hyaluronidase-oysk is 77%, and the time to maximum concentration is 3 days. Trastuzumab is estimated to reach concentrations <1 mcg/mL by 7 months after discontinuation in the majority of patients. In patients with body weight 50 kg and under, the mean steady state AUC of trastuzumab was approximately 80% higher with trastuzumab/hyaluronidase-oysk than with IV trastuzumab; in patients with body weight >90 kg, the AUC was approximately 20% lower with trastuzumab/hyaluronidase-oysk than with IV trastuzumab.
However, the manufacturer of trastuzumab/hyaluronidase-oysk does not recommend any dosage adjustments based on body weight at this time, as these changes in drug exposure are not thought to be clinically relevant.
Several trastuzumab biosimilars are available. Biosimilarity of these products has been demonstrated for the indications described in Table 1. Biosimilarity to originator trastuzumab is additionally supported by comparative clinical studies in patients with breast cancer (trastuzumab-anns, trastuzumab-dkst, trastuzumab-dttb, trastuzumab-pkrb, trastuzumab-qyyp, and trastuzumab-strf).
Generic name: trastuzumab-dttb
Pronunciation: (tras-TOOZ-ue-mab)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ontruzant
Indications
The following indications are listed for Ontruzant:
- Her2-Positive Adenocarcinoma Of Gastroesophageal Junction
- Her2-Positive Carcinoma Of Breast
- Her2-Positive Gastric Adenocarcinoma
Also known as: Her-2 Overexpressing Adenocarcinoma Of Gastroesophageal Junction, Her-2 Overexpressing Gastroesophageal Junction Adenocarcinoma, Her2-Overexpressing Gastric Adenocarcinoma, Her2-Positive Adenocarcinoma Of Stomach, Her2-Positive Gastroesophageal Junction Adenocarcinoma.
Dosing
No dosing information is available for this tab.
Trastuzumab and biosimilars are administered by IV infusion only. These products should not be administered by rapid IV injection, such as IV push or bolus, and should not be mixed with other medications.
Trastuzumab/hyaluronidase-oysk is administered by subcutaneous injection only and should not be administered IV.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
In patients receiving trastuzumab for adjuvant treatment of breast cancer, the most common adverse reactions (>=5%) were headache, diarrhea, nausea, and chills.
In patients receiving trastuzumab/hyaluronidase-oysk for adjuvant treatment of breast cancer, the most common adverse reactions (>=10%) were fatigue, arthralgia, diarrhea, injection site reaction, upper respiratory tract infection, rash, myalgia, nausea, headache, edema, flushing, pyrexia, cough, and pain in extremity.
In patients receiving trastuzumab for metastatic breast cancer, the most common adverse reactions (>=10%) were fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash.
In patients receiving trastuzumab for metastatic gastric cancer, the most common adverse reactions (>=10%) were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infection, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
The safety and efficacy of trastuzumab and trastuzumab/hyaluronidase-oysk have not been established in pediatric patients.
Trastuzumab and trastuzumab/hyaluronidase-oysk may cause fetal harm if administered to a pregnant females. In post-marketing reports and published literature, use of trastuzumab during pregnancy has been associated with cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In these case reports, oligohydramnios occurred in pregnant females who received trastuzumab either alone or in combination with chemotherapy. In most cases, amniotic fluid index increased after trastuzumab was stopped. In cases where trastuzumab was resumed after amniotic index improved, oligohydramnios recurred.
Verify the pregnancy status of females of reproductive potential prior to initiating trastuzumab or trastuzumab/hyaluronidase-oysk. Apprise patients of the potential risks to a fetus. If either product is administered during pregnancy, or if a patient becomes pregnant during or within 7 months following the last dose of trastuzumab or trastuzumab/hyaluronidase-oysk, healthcare providers and patients should immediately report the exposure to the manufacturer's pregnancy pharmacovigilance program at 1-888-835-2555. Monitor females who received trastuzumab or trastuzumab/hyaluronidase-oysk during pregnancy or within the 7 months prior to conception for oligohydramnios; if oligohydramnios occurs, perform fetal/neonatal testing as appropriate for gestational age and consistent with community standards of care.
Studies in Cynomolgus monkeys have shown that trastuzumab crosses the placenta during the early (gestation days 20-50) and late (gestation days 120-150) phases of gestation. Trastuzumab concentrations in fetal serum and amniotic fluid were approximately 33 and 25%, respectively, of those present in maternal serum but were not associated with adverse developmental effects. No evidence of teratogenicity was observed when subcutaneous recombinant human hyaluronidase was administered to pregnant mice during the period of organogenesis at doses >7,200 times the human dose.
There are no data regarding the presence of trastuzumab or hyaluronidase in human milk, the effects on the breast-fed infant, or effects on milk production. Data suggest human immunoglobulin G (IgG) is present in human milk but does not enter neonatal or infant circulation in substantial amounts. Trastuzumab is present in the milk of Cynomolgus monkeys but not associated with neonatal toxicity.
Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for trastuzumab or trastuzumab/hyaluronidase-oysk and any potential adverse effects on the breast-fed child from the medication or from the underlying maternal condition. This consideration should also take into account the 7-month washout period for trastuzumab and trastuzumab/hyaluronidase-oysk.
The manufacturers make no specific dosage recommendations for geriatric patients.
In clinical trials, trastuzumab was administered to 386 patients with breast cancer who were >=65 years of age (253 patients in the adjuvant treatment setting and 133 patients in the metastatic treatment setting). In studies of trastuzumab/hyaluronidase-oysk, 19% of patients were >=65 years of age, and 4.7% were >=75 years of age.
The risk of cardiac dysfunction is increased in geriatric patients compared with younger patients; however, limitations in data collection and differences in study design preclude a determination of whether the toxicity profile of trastuzumab in older patients is different from that observed in younger patients. Other differences in safety or efficacy were not observed between older patients and younger patients.
In a clinical trial of trastuzumab in patients with metastatic gastric cancer, 108 patients (37%) were >=65 years of age and 13 patients (4.4%) were >=75 years of age. No overall differences in safety and efficacy were observed in older patients compared with younger patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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