The following immune-related adverse reactions were reported in less than 1% of patients treated with nivolumab monotherapy or nivolumab in combination with ipilimumab in clinical trials across doses and tumour types: pancreatitis, uveitis, demyelination, autoimmune neuropathy (including facial and abducens nerve paresis), Guillain-Barr syndrome, myasthenia gravis, myasthenic syndrome, aseptic meningitis, encephalitis, gastritis, sarcoidosis, duodenitis, myositis, myocarditis, and rhabdomyolysis. Frequent urination. Baseline characteristics were generally balanced across treatment groups. Median time to onset was 10.6 weeks (range: 1.1-68.3). Tumour assessments were performed at baseline, within 14 days of surgery, every 12 weeks after surgery for 2 years, then every 6 months for 3 years, and every year for 5 years until disease recurrence or progression. Patients with active brain metastases, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded from the study. Minimize risk of AKI in patients at risk by maintaining normal fluid balance, avoiding nephrotoxins (including iodinated intravenous contrast agents) when possible, and taking precautions such as giving fluids or drugs when contrast or cytolytic therapy is necessary. Figure 26: Kaplan-Meier curves of OS in patients with PD-L1 CPS 5 (CA209649), Figure 27: Kaplan-Meier curves of PFS in patients with PD-L1 CPS 5 (CA209649). In a small number of cases, the plug will be composed of matrix alone if no crystals are present. Its acidity by pH level is typically around 6.0, but value reflects dietary protein (higher pH) or vegetarian diet (higher alkaline levels). Data from SCCHN, adjuvant melanoma, and adjuvant OC or GEJC patients 75 years of age or older are too limited to draw conclusions on this population (see section 5.1). b Musculoskeletal pain is a composite term which includes back pain, bone pain, musculoskeletal chest pain, myalgia, neck pain, pain in extremity, spinal pain, and musculoskeletal discomfort. Medical management guidelines for both medicines should be followed (see section 4.2 and refer to the SmPC for cabozantinib). Tables 10 and 11 present the percentage for immune-related adverse reactions who were permanently discontinued from treatment by dosing regimen. Results of repeat urinalysis after 48 to 72 hours should be negative in patients with this condition.30. Nivolumab in combination with ipilimumab in MPM. However, the role of this biomarker (tumour PD-L1 expression) has not been fully elucidated. Organisms such as Chlamydia and Ureaplasma urealyticum should be considered in patients with pyuria and negative cultures. Tests may include: Some bladder stones wont show up on X-rays, so your vet may recommend an ultrasound as well. Overview of Intrarenal Acute Kidney Injury. Secondary endpoints per the pre-specified hierarchical testing were OS in patients with PD-L1 CPS 1 and in all randomised patients; further endpoints included ORR (BICR) in PD-L1 CPS 5 and all randomised patients. Abdominal x-rays without radiopaque contrast agents may be done to check for positioning of ureteral stents read more can establish the site of obstruction and guide therapy. The study included patients (18 years or older) with histologically confirmed non-squamous or squamous Stage IV or recurrent NSCLC (per the 7th International Association for the Study of Lung Cancer classification), ECOG performance status 0 or 1, and no prior anticancer therapy (including EGFR and ALK inhibitors). a Six patients (4%) randomised to docetaxel crossed over at any time to receive nivolumab treatment. Avoid using iodinated IV contrast in imaging studies. The safety and efficacy of nivolumab 240 mg in combination with cabozantinib 40 mg for the first-line treatment of advanced/metastatic RCC was evaluated in a phase 3, randomised, open-label study (CA2099ER). Grade 2 and Grade 3 hypopituitarism occurred in 0.4% (2/448) and 0.7% (3/448) of patients, respectively. Forty-nine (47.6%) responders had ongoing responses with a duration ranging from 0.0-27.6+ months. Chemotherapy consisted of cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 or carboplatin 5 AUC and pemetrexed 500 mg/m2. Even after the cat is unblocked, the underlying inflammatory syndrome will continue for some days at home (particularly since the catheter itself will have irritated the urethra). The safety and efficacy of nivolumab 3 mg/kg for the treatment of advanced (unresectable or metastatic) melanoma were evaluated in a phase 3, randomised, double-blind study (CA209066). In patients treated with nivolumab 360 mg every 3 weeks in combination with ipilimumab 1 mg/kg every 6 weeks and chemotherapy in NSCLC, the incidence of rash was 37.7% (135/358). They can also develop as a sign of an underlying medical problem. ","acceptedAnswer":{"@type":"Answer","text":"Yes, some cat foods can unbalance urine pH, causing crystals to develop. This study included patients regardless of their tumour PD-L1 status. To view the changes to a medicine you must sign up and log in. the total volume of infusion must not exceed 160 mL. False-positive and false-negative results are not unusual in dipstick urinalysis (Table 2). Median time to onset was 6.6 weeks (range: 0.1-97.4). D-mannose (which is also anti-inflammatory) is also used by some pet owners as a natural alternative to antibiotic treatment although this may be less targeted and specific than prescribed antibiotics following a urine culture. Renal causes of AKI involve intrinsic kidney disease or damage. The primary efficacy outcome measures were PFS (by BICR) and OS in patients with tumour cell PD-L1 expression 1%. Grade 2 and Grade 3 thyroid disorders were reported in 15.3% (102/666) and 1.7% (11/666) of patients, respectively. Bladder stones form due to a buildup of crystals in a cats bladder. Nephrolithiasis is not associated with an increase in the rate of progression of feline kidney injury, and cats with nephrolithiasis are generally managed without surgery. Severe rash has been observed with nivolumab in combination with ipilimumab and, less commonly, with nivolumab as monotherapy (see section 4.8). Since feline idiopathic cystitis is commonly known to reoccur, ongoing precautions need to be taken to avoid relapse. One vial of 4 mL contains 40 mg of nivolumab. To find similar products you must sign up and log in. b 25/100 (25%) of the patients in CA209205 Cohort C presented B-Symptoms at baseline. Grade 3 diarrhoea or colitis observed with nivolumab in combination with ipilimumab requires permanent discontinuation of treatment and initiation of corticosteroids at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents. The median age was 63 years (range: 39-85) with 44% 65 years of age and 11% 75 years of age. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Flare-ups of FIC generally begin as non-obstructive incidents involving acute inflammation of the lower urinary tract but where the cat is still able to urinate. A small stone may pass without causing symptoms. [1], Despite the shared terminology, cases of feline idiopathic cystitis, as opposed to human cystitis episodes, are sterile. Table 7: Adverse reactions with nivolumab in combination with ipilimumab, Nivolumab 1 mg/kg in combination with ipilimumab 3 mg/kg in melanoma, Nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC and dMMR or MSI-H CRC, Nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in OSCC and MPM, pneumonia, upper respiratory tract infection, lymphopaeniab, leucopoeniab, neutropaeniab, thrombocytopaeniab, anaemiab,j, lymphopaeniab, leucopoeniab, neutropaeniab,c, thrombocytopaeniab, anaemiab,j, anaemiab,c,j, lymphopaeniab, thrombocytopaeniab, infusion related reaction, hypersensitivity, infusion-related reaction, hypersensitivity, adrenal insufficiency, hypopituitarism, hypophysitis, hyperthyroidism, thyroiditis, adrenal insufficiencyc, hypophysitisc, thyroiditis, diabetes mellitusc, hyperthyroidism, adrenal insufficiencyc, hypopituitarism, hypophysitis, diabetes mellitus, thyroiditis, diabetic ketoacidosisc, diabetes mellitusc, Guillain-Barr syndrome, polyneuropathy, neuritis, peroneal nerve palsy, autoimmune neuropathy (including facial and abducens nerve paresis), encephalitisc, polyneuropathy, autoimmune neuropathy (including facial and abducens nerve paresis), myasthenia gravisc, encephalitis, arrhythmia (including ventricular arrhythmia)a, atrial fibrillation, myocarditisa,e, arrhythmia (including ventricular arrhythmia), myocarditisc, pneumonitisa,c, pulmonary embolisma, cough, colitisa, diarrhoea, vomiting, nausea, abdominal pain, stomatitis, pancreatitis, constipation, dry mouth, colitis, stomatitis, pancreatitis, dry mouth, gastritis, intestinal perforationa, gastritis, duodenitis, Stevens-Johnson syndrome, vitiligo, erythema multiforme, psoriasis, toxic epidermal necrolysisa,e, Stevens-Johnson syndromee, arthritis, muscle spasms, muscular weakness, spondyloarthropathy, Sjogren's syndrome, arthritis, myopathy, myositis (including polymyositis)a,d, rhabdomyolysisa,e, polymyalgia rheumatica, myositis (including polymyositis), rhabdomyolysis, renal failure (including acute kidney injury)c, renal failure (including acute kidney injury), fatigue, pyrexia, oedema (including peripheral oedema), oedema (including peripheral oedema), pain, increased AST, increased ALT, increased total bilirubin, increased alkaline phosphatase, increased lipase, increased amylase, increased creatinine, hypocalcaemia, hyperkalaemia, hypokalaemia, hypomagnesaemia, hyponatraemia, increased AST, increased ALT, increased total bilirubin, increased alkaline phosphatase, increased lipase, increased amylase, increased creatinine, hypercalcaemia, hypocalcaemia, hyperkalaemia, hypokalaemia, hypomagnesaemia, hyponatraemia, hyponatraemiac, increased AST, increased ALT, increased alkaline phosphatase, hypocalcaemia, hyperkalaemia, hypomagnesaemia, increased creatinine, hypokalaemia, hypercalcaemia, increased total bilirubin, increased lipase, increased amylase, hypercalcaemia, hypermagnesaemia, hypernatraemia. The best toothpaste for dogs, according to vets, White specks in dog poop: Heres what to do. DFS was defined as the time between the date of randomisation and the date of the first documented recurrence assessed by investigator (local urothelial tract, local non-urothelial tract or distant), or death (from any cause), whichever occurred first. Patients with treated brain metastases were eligible if neurologically returned to baseline at least 2 weeks prior to enrolment, and either off corticosteroids, or on a stable or decreasing dose of < 10 mg daily prednisone equivalents. The primary efficacy population included those intermediate/poor risk patients with at least 1 or more of 6 prognostic risk factors as per the International Metastatic RCC Database Consortium (IMDC) criteria (less than one year from time of initial renal cell carcinoma diagnosis to randomisation, Karnofsky performance status <80%, haemoglobin less than the lower limit of normal, corrected calcium of greater than 10 mg/dL, platelet count greater than the upper limit of normal, and absolute neutrophil count greater than the upper limit of normal). Patients with active autoimmune disease, symptomatic interstitial lung disease, or active brain metastases were excluded from the study. Cystine crystals are colorless, have a hexagonal shape, and are present in acidic urine, which is diagnostic of cystinuria. They could have developed a urinary blockage, which is a life-threatening medical emergency. Heres what happened. 1.1. Secondary efficacy outcome measures included overall survival (OS). Adopting unusual postures to cope with the pain. Grade 2, Grade 3, and Grade 4 cases were reported in 2.2% (8/358), 0.3% (1/358), and 0.3% (1/358) of patients, respectively. Enter search terms to find related medical topics, multimedia and more. The principal read more is initiated when, Severe electrolyte abnormalities cannot otherwise be controlled (eg, potassium > 6 mmol/L), Pulmonary edema persists despite drug treatment, Metabolic acidosis is unresponsive to treatment, Uremic symptoms occur (eg, vomiting thought to be due to uremia, asterixis, encephalopathy, pericarditis, seizures). The study excluded patients with active, known or suspected autoimmune disease, patients who had treatment with any chemotherapy, radiation therapy, biologics for cancer, intravesical therapy, or investigational therapy within 28 days of first administration of study treatment. A total of 821 patients were randomised to receive either nivolumab 3 mg/kg (n = 410) administered intravenously over 60 minutes every 2 weeks or everolimus (n = 411) 10 mg daily, administered orally. Although weight gain indicates excess fluid, water intake is not decreased if serum sodium remains normal; instead, dietary sodium is restricted. Schedule regular urinary checkups Monitor your cats urinary health with regular checks of their urine to make sure new crystals havent formed. Numerically more patients in the nivolumab in combination with chemotherapy arm (83%) had definitive surgery compared to patients in the chemotherapy arm (75%). Patients with active autoimmune disease, medical conditions requiring immunosuppression, recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, salivary gland or non-squamous histologies (e.g., mucosal melanoma), or active brain or leptomeningeal metastases were excluded from the study. Treatment could continue beyond disease progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. Randomisation was stratified by tumour PD-L1 status and M stage (M0/M1a/M1b versus M1c). The ORR was 35.4% (95% CI: 28.0, 43.4) for nivolumab plus ipilimumab vs. 19.7% (95% CI: 13.8, 26.8) for chemotherapy. Eight percent of patients were Asian, 23.2% and 76.5% of patients had a baseline KPS of 70 to 80% and 90 to 100%, respectively. patients treated with prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways). The recommended dose is 360 mg nivolumab administered intravenously over 30 minutes in combination with platinum-based chemotherapy every 3 weeks for 3 cycles (see section 5.1). Grade 2 and Grade 3 cases were reported in 25.6% (82/320) and 6.3% (20/320) of patients, respectively. Tumour assessments were continued after treatment discontinuation in patients who discontinued treatment for reasons other than progression. When nivolumab is given with cabozantinib, higher frequencies of Grades 3 and 4 ALT and AST elevations have been reported relative to nivolumab monotherapy in patients with advanced RCC (see section 4.8). Severe pneumonitis or interstitial lung disease, including fatal cases, has been observed with nivolumab monotherapy or nivolumab in combination with ipilimumab (see section 4.8). d Musculoskeletal pain is a composite term which includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity, spinal pain. Physicians should consider the delayed onset of nivolumab effect before initiating treatment in patients with OSCC. The study included patients (18 years or older) with previously untreated, advanced or metastatic renal cell carcinoma with a clear-cell component. The study included adult patients (18 years or older) with confirmed, treatment-naive, Stage III or IV BRAF wild-type melanoma and an ECOG performance-status score of 0 or 1. Nivolumab in combination with chemotherapy in OSCC. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. a Rash is a composite term which includes maculopapular rash, rash erythematous, rash pruritic, rash macular, rash morbilliform, rash papular, rash generalised, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis bullous, drug eruption, and exfoliative rash, nodular rash, rash vesicular. The website Trans4mind.com notes that meats test as alkaline before digestion, however, once metabolized by your body, meat forms acids. Baseline characteristics were generally balanced between the two groups. Small amounts of urine. Water intake can be further restricted for hyponatremia or increased for hypernatremia. However they can be a risk factor for cats suffering from urinary disease. However, sensitivity for obstruction is only 80 to 85% when ultrasonography is used because the collecting system is not always dilated, especially when the condition is acute, the ureter is encased (eg, in retroperitoneal fibrosis or neoplasm), or the patient has concomitant hypovolemia. Steroids were used in four patients and three patients responded to steroids. Resolution occurred in 34 patients (70.8%) with a median time to resolution of 7.1 weeks (range: 0.1+-149.3+). If a cat repeatedly has a large number of crystals in a freshly collected urine sample and improper sample handling has been ruled out, then treatment for crystalluria is recommended. If required, urine alkalinization can be achieved by administering NaHCO3, 1 g ( tsp)/5 kg, PO, tid, with food. It can affect both males and females of any breed of cat. This information is intended for use by health professionals. The safety and efficacy of nivolumab monotherapy for the adjuvant treatment of oesophageal or gastro-oesophageal junction cancer was evaluated in a phase 3 multicentre, randomised, placebo-controlled, double-blinded study (CA209577). In the subgroup of patients with tumour cell PD-L1 expression 1% who did not receive prior cisplatin in the neoadjuvant setting (n = 164), the DFS HR was 0.69 (95% CI: 0.44, 1.08) with median DFS of 29.67 and 11.37 months for the nivolumab and placebo arms, respectively. Grade 2, Grade 3, and Grade 4 cases were reported in 14.7% (47/320), 10.3% (33/320), and 0.6% (2/320) of patients, respectively. In the absence of data, nivolumab in combination with ipilimumab or chemotherapy should be used with caution in these populations after careful consideration of the potential benefit/risk on an individual basis. It is more commonly found in female cats; however, when males do exhibit cystitis, it is usually more dangerous. Yowling while urinating. Burmese, Himalayan, Tonkinese, Devon Rex, Persian, and Siamese cats appear to be genetically predisposed to developing calcium oxalate stones. Comparable to the overall population, median duration of response was increased with nivolumab vs. docetaxel for patients with no PD-L1 expression (18.3 months vs. 5.6 months) and for patients with PD-L1 expression (16.0 months vs. 5.6 months). Complications of allogeneic HSCT in classical Hodgkin lymphoma. The majority of patients were male (73.9%) and white (81.9%). Nivolumab or nivolumab in combination with ipilimumab may have a minor influence on the ability to drive and use machines. Detailed guidelines for the management of immune-related adverse reactions are described in section 4.4. Once the urinary tract is free of stones, prevention strategies are much more likely to be successful. A HR of 1.36 (95% CI: 0.74, 2.52) in OS and a HR of 1.12 (95% CI: 0.64, 1.96) in PFS was observed for nivolumab in combination with ipilimumab and chemotherapy vs. chemotherapy within this study subgroup. Despite excessive urinary loss of cystine in cystinuric dogs, plasma cystine levels remain the same as in healthy dogs; in fact, the only morbidity or mortality associated with the inherited defect of cystine reabsorption is urolith formation. The PD-1 receptor is a negative regulator of T-cell activity that has been shown to be involved in the control of T-cell immune responses. Randomised phase 3 study of nivolumab in combination with ipilimumab or nivolumab as monotherapy vs. ipilimumab as monotherapy (CA209067). Figure 22: Kaplan-Meier curves of OS in patients with tumour cell PD-L1 1% (CA209648), Nivolumab in combination with chemotherapy vs. chemotherapy. Patients in the chemotherapy arm received platinum-based chemotherapy administered every 3 weeks for up to 3 cycles. My cat had PU surgery. When nivolumab is administered in combination, refer to the SmPC of the other combination therapy agents prior to initiation of treatment. The observed PFS results at 18 months of follow-up and ORR and OS results at 28 months of follow-up were consistently demonstrated across subgroups of patients including baseline ECOG performance status, BRAF status, M stage, age, history of brain metastases, and baseline LDH level. Monitoring of thyroid function should continue to ensure appropriate hormone replacement is utilised. It also reflects the concentrating ability of the kidneys. While the use of urinary acidification to reduce urine pH to <6 and other individualized dietary maneuvers may prove effective, a few commercially available diets that are generally nutritionally balanced promote struvite stone dissolution. The median age was 66 years (range: 38 to 90) with 55% 65 years of age and 14% 75 years of age. The majority of adverse reactions were mild to moderate (Grade 1 or 2). The median age was 60 years (range: 28-83) with 31% 65 years of age and 5% 75 years of age, 83% were male, and 83% were white. No clear cut off for PD-L1 expression can reliably be established when considering the relevant endpoints of tumour response and PFS and OS. after diluting according to the following instructions: the final infusion concentration should range between 1 and 10 mg/mL. Grade 2 and Grade 3 thyroid disorders were reported in /8.0% (50/622) and 0.5% (3/622) of patients, respectively. Use to remove results with certain terms The ORR was 53.2% (95% CI: 45.1, 61.1) for nivolumab plus chemotherapy vs. 19.7% (95% CI: 13.8, 26.8) for chemotherapy. Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Median PFS was 7.69 months (95% CI: 7.03, 9.17) for nivolumab in combination with chemotherapy vs. 6.05 months (95% CI: 5.55, 6.90) for chemotherapy (HR = 0.68; 98% CI: 0.56, 0.81; p-value <0.0001). Another difference between the two crystal types is that calcium oxalate crystals are rarely seen in the urine of cats with a calcium oxalate stone. No sudden disruption to routine or changes in a cats environment. Interstitial Cystitis (IC) or also known as Painful Bladder Syndrome (PBS) creates a chronic pain related to the lower urinary tract, more specifically, the bladder. If clinically indicated, then group II gadolinium agents should be used preferentially due to lower risk of nephrogenic systemic fibrosis (2 Diagnosis references Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine read more ). Nivolumab as monotherapy (see section 4.2). The majority of patients were white (92%) and male (55%). Median time to onset was 9.6 weeks (range: 0.7-60.7). The 62 patients had a median follow-up from subsequent allogeneic HSCT of 38.5 months (range: 0-68 months). Efficacy results are shown in Table 41. Such symptoms include. If fresh urine is alkaline, a urinalysis and culture should be done, with the dog treated appropriately if an infection is present. The key to prevention of recurrence in animals with a struvite stone associated with infection is to achieve and maintain sterile urine. It allows continued monitoring of the benefit/risk balance of the medicinal product. Were reader-supported. For instructions on the preparation and handling of the medicinal product before administration, see section 6.6. Treatment must be initiated and supervised by physicians experienced in the treatment of cancer. Additional efficacy endpoints were PFS, ORR, and duration of response as assessed by BICR. Study CA209171 was a single-arm, open label study of nivolumab monotherapy in patients with previously treated advanced or metastatic squamous NSCLC. The primary efficacy outcome measure was OS. In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in OSCC and gastric, GEJ or oesophageal adenocarcinoma, or resectable NSCLC, the incidence of nephritis or renal dysfunction was 8.8% (112/1268). The safety and tolerability of nivolumab were investigated in a phase 1, open-label dose-escalation study in various tumour types, including malignant melanoma. The normal odor of urine is described as urinoid; this odor can be strong in concentrated specimens but does not imply infection. Struvite crystals can also be present in the urine of healthy cats. It also can alert the physician to the presence of systemic disease affecting the kidneys. Disorders may involve the blood vessels, glomeruli, tubules, or interstitium. 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