USP
USP Uses, Dosage, Side Effects, Food Interaction and all others data.
USP is a synthetic pyrimidine nucleoside and cytarabine analogue which is metabolised intracellularly to active diphosphate and triphosphate nucleosides. It inhibits DNA synthesis by inhibiting DNA polymerase and ribonucleotide reductase. It also induces apoptosis and is primarily active against cells in the S-phase, but may also arrest cells at the G1-S border.
USP is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis. More specifically, it blocks the progression of cells through the G1/S-phase boundary. USP demonstrated cytotoxic effects against a broad range of cancer cell lines in vitro. It displayed schedule-dependent antitumour activity in various animal models and xenografts from human non-small cell lung cancer (NSCLC) and pancreatic cancer. Therefore, the antineoplastic effects of gemcitabine are enhanced through prolonged infusion time rather than higher dosage. USP inhibited the growth of human xenografts from carcinoma of the lung, pancreas, ovaries, head and neck, and breast. In mice, gemcitabine inhibited the growth of human tumour xenografts from the breast, colon, lung or pancreas by 69 to 99%. In clinical trials of advanced NSCLC, gemcitabine monotherapy produced objective response rates ranging from 18 to 26%, with a median duration of response ranging from 3.3 to 12.7 months. Overall median survival time was 6.2 to 12.3 months. The combined use of cisplatin and gemcitabine produced better objective response rates compared to monotherapy. In patients with advanced pancreatic cancer, objective response rates in patients ranged from 5.to 12%, with a median survival duration of 3.9 to 6.3 months. In Phase II trials involving patients with metastatic breast cancer, treatment with gemcitabine alone or with adjuvant chemotherapies resulted in response rate ranging from 13 to 42% and median survival duration ranging from 11.5 to 17.8 months. In metastatic bladder cancer, gemcitabine has a response rate 20 to 28%. In Phase II trials of advanced ovarian cancer, patients treated with gemcitabine had response rate of 57.1%, with progression free survival of 13.4 months and median survival of 24 months.
USP causes dose-limiting myelosuppression, such as anemia, leukopenia, neutropenia, and thrombocytopenia; however, events leading to discontinuation tend to occur less than 1% of the patients. USP can elevate ALT, AST and alkaline phosphatase levels.
| Trade Name | USP |
| Availability | Prescription only |
| Generic | Gemcitabine |
| Gemcitabine Other Names | Gemcitabin, Gemcitabina, Gemcitabine, Gemcitabinum |
| Related Drugs | Opdivo, methotrexate, Keytruda, Arimidex, carboplatin, pembrolizumab, fluorouracil, doxorubicin, cisplatin, paclitaxel |
| Type | Ointment |
| Formula | C9H11F2N3O4 |
| Weight | Average: 263.1981 Monoisotopic: 263.071762265 |
| Protein binding | Gemcitabine plasma protein binding is less than 10%. |
| Groups | Approved |
| Therapeutic Class | Cytotoxic Chemotherapy |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ovarian Cancer: USP in combination with carboplatin is used for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.
Breast Cancer: USP in combination with paclitaxel is used for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraused.
Non-Small Cell Lung Cancer: USP is used for combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer.
Pancreatic Cancer: USP is used for first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. USP is used for patients previously treated with 5-FU.
USP is also used to associated treatment for these conditions: Advanced Ovarian Cancer, Bladder Transitional Cell Carcinoma Stage IV, Cervical Cancers, Cutaneous T-Cell Lymphoma (CTCL), Head and Neck Carcinoma, Hodgkins Disease (HD), Locally Advanced Pancreatic Adenocarcinoma, Mesothelioma, Metastatic Breast Cancer, Non-Small Cell Lung Cancer Stage IIIB, Non-small Cell Lung Cancer (NSCLC), Stage IV, Non-small Cell Lung Cancer Stage IIIA, Small Cell Lung Cancer (SCLC), Stage 4 Pancreatic adenocarcinoma
How USP works
USP is a potent and specific deoxycytidine analog. After uptake into malignant cells, gemcitabine is phosphorylated by deoxycytidine kinase to form gemcitabine monophosphate, which is then converted to the active compounds, gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). These active metabolites are nucleosides that mediate antitumour effects. dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, thereby competitively inhibiting DNA chain elongation. The non-terminal position of dFdCTP in the DNA chain prevents detection of dFdCTP in the chain and repair by proof-reading 3′5′-exonuclease: this process is referred to as "masked DNA chain termination." Incorporation of dFdCTP into the DNA chain ultimately leads to chain termination, DNA fragmentation, and apoptotic cell death of malignant cells.
USP has self-potentiating pharmacological actions that can increase the probability of successful incorporation of gemcitabine triphosphate into the DNA chain: dFdCDP inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate dCTP for DNA synthesis. Since dFdCDP reduces the levels of dCTP, there is less competition for gemcitabine triphosphate for incorporation into DNA. USP can also reduce metabolism and elimination of active metabolites from the target ce1l, prolonging high intracellular concentrations of the active metabolites. Such self-potentiating effects are not present with cytarabine.
Dosage
USP dosage
Intravenous (Adult)-
- Advanced non-small cell lung cancer: 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle; or 1250 mg/m2 on days 1 and 8 of each 21-day cycle.
- Pancreatic carcinoma: 1000 mg/m2 once wkly for up to 7 wk followed by 1 wk of rest. Continue thereafter with once wkly infusions for 3 consecutive wk out of 4.
- Ovarian carcinoma: To be given before carboplatin: 1000 mg/m2 on days 1 and 8 of each 21-day cycle.
- Breast cancer: Usually in combination with a taxane such as paclitaxel: 1250 mg/m2 on days 1 and 8 of each 21-day cycle.
- Bladder cancer: To be given before cisplatin. 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle.
Side Effects
Bone marrow suppression as manifested by leukopenia, thrombocytopenia, anaemia and myelosuppression. Mild GI effects; rashes; renal impairment, pulmonary toxicity, influenza-like symptoms; interstitial pneumonia, pulmonary oedema. Proteinuria, haematuria and haemolytic uraemic syndrome. Elevation of serum transaminase.
Toxicity
The oral LD50 is 333 mg/kg in mice and >500 mg/kg in rats. The dermal LD50 in rabbits is >1000 mg/kg.
There is no known antidote for gemcitabine overdose. In a dose-escalation study, patients were administered a single dose of gemcitabine as high as 5700 mg/m2
Precaution
Children, hepatic and renal impairment. May impair ability to drive or operate machinery. Discontinue on 1st sign of microangiopathic haemolytic anaemia. Prolonged infusion time (>60 minutes) and more frequent than wkly dosing may increase toxicity. Monitor CBC before every dose. Increased risk of haemolytic uraemic syndrome and/or thrombocytcpenic purpura which may lead to irreversible renal failure.
Interaction
May increase the anticoagulant effect of warfarin when used together.
Food Interaction
No interactions found.USP Hypertension interaction
[Major] Cardiovascular events such as myocardial infarction, arrhythmia, and hypertension have been reported during gemcitabine therapy.
Therapy with gemcitabine should be administered cautiously in patients with cardiovascular dysfunction.
USP Drug Interaction
Moderate: paclitaxel protein-bound, paclitaxel protein-boundMinor: ciprofloxacin, ciprofloxacinUnknown: lorazepam, lorazepam, diphenhydramine, diphenhydramine, pancrelipase, pancrelipase, hydromorphone, hydromorphone, acetaminophen, acetaminophen, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, ondansetron, ondansetron
Volume of Distribution
In patients with various solid tumours, the volume of distribution increased with infusion length. The volume of distribution of gemcitabine was 50 L/m2 following infusions lasting less than 70 minutes. For long infusions, the volume of distribution rose to 370 L/m2.
USP triphosphate, the active metabolite of gemcitabine, accumulates and retains in solid tumour cells in vitro and in vivo. It is not extensively distributed to tissues after short infusions that last less than 70 minutes. It is not known whether gemcitabine crosses the blood-brain barrier, but gemcitabine is widely distributed into tissues, including ascitic fluid. In rats, placental and lacteal transfer occurred rapidly at five to 15 minutes following drug administration.
Elimination Route
Peak plasma concentrations of gemcitabine range from 10 to 40 mg/L following a 30-minute intravenous infusion, and are reached at 15 to 30 minutes. One study showed that steady-state concentrations of gemcitabine showed a linear relationship to dose over the dose range 53 to 1000 mg/m2. USP triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. In one study, the Cmax of gemcitabine triphosphate in peripheral blood mononuclear cells occurred within 30 minutes of the end of the infusion period and increased increased proportionally with gemcitabine doses of up to 350 mg/m2.
Half Life
Following intravenous infusions lasting less than 70 minutes, the terminal half-life ranged from 0.7 to 1.6 hours. Following infusions ranging from 70 to 285 minutes, the terminal half-life ranged from 4.1 to 10.6 hours. Females tend to have longer half-lives than male patients. USP triphosphate, the active metabolite of gemcitabine, can accumulate in circulating peripheral blood mononuclear cells. The terminal half-life of gemcitabine triphosphate, the active metabolite, from mononuclear cells ranges from 1.7 to 19.4 hours.
Clearance
Following intravenous infusions lasting less than 70 minutes, clearance ranged from 41 to 92 L/h/m2 in males and ranged from 31 to 69 L/h/m2 in females. Clearance decreases with age. Females have about 30% lower clearance than male patients.
Elimination Route
USP mainly undergoes renal excretion. Within a week following administration of a single dose of 1000 mg/m infused over 30 minutes, about 92-98% of the dose was recovered in urine where 89% of the recovered dose was excreted as difluorodeoxyuridine (dFdU) and less than 10% as gemcitabine. Monophosphate, diphosphate, or triphosphate metabolites of gemcitabine are not detectable in urine. In a single-dose study, about 1% of the administered dose was recovered in the feces.
Pregnancy & Breastfeeding use
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Contraindication
Concurrent radical radiotherapy; pregnancy, lactation; hypersensitivity
Storage Condition
Store at 25° C.
Innovators Monograph
You find simplified version here USP
FAQ
What is USP used for?
USP treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer.
How safe is USP?
The safety profile of USP is unusually mild for such an active agent in solid tumours. USP is well tolerated and has a mild toxicity profile.
How does USP work?
USP kills cancer cells undergoing DNA synthesis. It inhibits ribonucleotide reductase, an enzyme important to DNA synthesis.
What are the common side effects of USP?
USP often causes nausea and vomiting. It can also cause flu-like symptoms such as chills, fever, general feeling of illness, headache, muscle pain, and weakness. It is very important that you continue to receive the medicine even if it makes you feel ill.
Is USP safe during pregnancy?
Based on animal data and its mechanism of action, this USP can cause fetal harm when administered to a pregnant woman. This USP can harm a developing fetus.
Is USP safe during breastfeeding?
Use is contraindicated. This USP may harm a nursing infant. The manufacturer recommends a breastfeeding abstinence period of 1 week after the last dose.
Can I drink alcohol with USP?
The drinking of alcohol does not appear to affect the safety or usefulness of USP. USP may damage sperm and may harm the baby if used during pregnancy. It is best to use birth control while being treated with USP.
Can I drive after taking USP?
You may experience drowsiness or dizziness; avoid driving or engaging in tasks that require alertness until your response to USP is known.
When should be taken of USP?
USP is usually given on certain days every 3 weeks. When USP is used to treat lung cancer, it is usually given on certain days every 3 or 4 weeks.
Can I drink alcohol with USP?
Some chemo should be taken on an empty stomach. You may need to stop eating certain foods while you take chemo. Some foods may prevent chemo from working correctly.
How long does USP take to work?
USP generally takes about 48 to 72 hours for your body to break down and/or get rid of most chemo drug.
How long can I stay on USP ?
Usually a cycle of USP is over 3 to 4 weeks (21 to 28 days). You usually have USP once a week for 2 or 3 weeks and then a week with no treatment. You have USP on its own or in combination with other cancer drugs.
Who should not take USP?
If you are a woman, do not use USP if you are pregnant. You may need to have a negative pregnancy test before starting this treatment. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 6 months after your last dose.
What happens if I miss a dose?
Call your doctor for instructions if you miss an appointment for your USP injection.
Can I overdose on USP?
USP overdose occurs when a patient has a severe toxic reaction to certain chemotherapy drugs, or in some cases, is unintentionally given an excessive dose. Both possibilities are extremely rare.
What happen If I stop taking USP?
If you decide to stop chemotherapy, be sure you're still getting relief from symptoms such as pain, constipation, and nausea. This is called palliative care, and it's meant to improve your quality of life.
Can USP affect my kidneys?
No significant cumulative effects of USP on renal function could be detected, although 3 patients, treated with multiple cycles of USP, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.
Can USP affects my heart ?
USP alone has been shown to have few cardiac effects, including stroke, arrhythmias and hypertension.
Can USP affects my liver?
The clinically apparent liver injury described with USP therapy tends to be severe and several fatal instances have been described.
