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HANIXOL is a brand name for Mercaptopurine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Hanixol 50 mg tablets is indicated for the treatment of APL (acute promyelocytic leukaemia) and AML M3 (acute myeloid leukaemia M3) in adults, adolescents and children. Indicated for maintenance of remission in moderate to severe inflammatory bowel disease (IBD) (Ulcerative Colitis or Crohn’s disease) in adults.
Verbatim from this product's MHRA label. Tap a section to expand.
Posology 6-mercaptopurine monohydrate treatment should be initiated and supervised by a doctor or other healthcare professional experienced in the management of patients with acute leukemia or IBD. Method of Administration 6-mercaptopurine monohydrate may be taken with food or on an empty stomach, but patients should standardise the method of administration.
5). 6- mercaptopurine monohydrate should be taken at least 1 hour before or 2 hours after ingestion of milk or dairy products. 6-mercaptopurine displays diurnal variation in pharmacokinetics and efficacy. Administration in the evening compared to morning administration may lower the risk of relapse.
Therefore the daily dose of mercaptopurine should be taken in the evening. Haxinol 50mg tablets can be split in half to give 25mg dose increments. A pill cutter, only to be used with Haxinol, should be utilised for this task. Patients should be recommended to perform this task themselves if possible and to wash their hands once this is completed.
Populations The dose is governed by cautiously monitored haematotoxicity and the dose should be carefully adjusted to suit the individual patient in accordance with the employed treatment protocol. 4). 5 mg/kg bodyweight per day, or 50 to 75 mg/m2 body surface area per day, but the dose and duration of administration depend on the nature and dosage of other cytotoxic agents given in conjunction with 6- mercaptopurine monohydrate.
The dosage should be carefully adjusted to suit the individual patient. 4, and the 25mg increments for dosing available with tablet splitting would mean that a normal rounding up and down methodology would be suitable. Dosing could then be adjusted depending on the monitoring results, adverse events and other factors.
6-mercaptopurine monohydrate has been used in various combination therapy schedules for acute leukaemia and the literature and current treatment guidelines should be consulted for details. Studies carried out in children with acute lymphoblastic leukaemia suggested that administration of 6-mercaptopurine monohydrate in the evening lowered the risk of relapse compared with morning administration.
25 mg/kg daily for patients with normal thiopurine S-methyltransferase (TPMT) activity. 5 mg/kg. For most adult patients this would correspond to 50 mg daily, or 25mg if TPMT is low. 5 mg/kg/day. Elderly It is advisable to monitor renal and hepatic function in these patients, and if there is any impairment, consideration should be given to reducing the 6-mercaptopurine monohydrate dosage.
). The majority of reported cases were in children under the age of six or with a low body mass index. Macrophage activation syndrome Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with autoimmune conditions, in particular with inflammatory bowel disease (IBD), and there could potentially be an increased susceptibility for developing the condition with the use of 6-mercaptopurine monohydrate.
If MAS occurs, or is suspected, evaluation and treatment should be started as early as possible, and treatment with 6-mercaptopurine monohydrate should be discontinued. Physicians should be attentive to symptoms of infection such as EBV and cytomegalovirus (CMV), as these are known triggers for MAS.
Metabolism and nutrition disorders Purine analogues (azathioprine and mercaptopurine) may interfere with the niacin pathway, potentially leading to nicotinic acid deficiency (pellagra). Cases of pellagra have been reported with the use of purine analogues, particularly in patients with chronic inflammatory bowel disease.
The diagnosis of pellagra should be considered in patients with a localised pigmented rash (dermatitis), gastroenteritis, or neurological deficits including cognitive deterioration. Appropriate medical care with niacin/nicotinamide supplementation must be initiated.
Lesch-Nyhan syndrome Limited evidence suggests that neither the 6-mercaptopurine monohydrate nor its pro- drug azathioprine are effective in patients with the rare inherited disease associated with complete hypoxanthine-guanine-phosphoribosyltransferase deficiency (Lesch- Nyhan syndrome).
The use of 6-mercaptopurine monohydrate or azathioprine is not recommended in these patients. Progressive Multifocal Leukoencephalopathy (PML) PML, an opportunistic infection caused by the JC virus, has been reported in patients receiving azathioprine, a precursor to 6-mercaptopurine, with other immunosuppressive agents.
6-mercaptopurine monohydrate is an active cytotoxic agent for use only under the direction of physician experienced in the administration of such agents. 6). If cholestasis of pregnancy occurs, case by case assessment is necessary considering the risk-benefit profile of the product (potential withdrawal/dose reduction).
Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended. In all cases, patients in remission should not receive live organism vaccines until the patient is deemed to be able to respond to the vaccine.
The interval between discontinuation of chemotherapy and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medications used, the underlying disease, and other factors.
Co-administration of ribavirin and 6-mercaptopurine monohydrate is not advised. 5). 6. Monitoring Since 6- mercaptopurine monohydrate is strongly myelosuppressive full blood counts must be taken daily during remission induction in acute myelogenous leukaemia.
Patients must be carefully monitored during therapy. It is recommended that on commencement of treatment with Haxinol for IBD, that FBS, U&E and LFTs are monitored at weeks 2, 4, 8 and 12 and then at least 3- monthly following. In patients where non-adherence to therapy or adverse events outside of those expected at the given dose, it is recommended that the thiopurine metabolites TGN and/or MeMP are checked where possible to allow for adjustment in treatment.
Cytotoxicity and haematological monitoring Treatment with 6-mercaptopurine monohydrate causes bone marrow suppression leading to leukopenia and thrombocytopenia and, less frequently, anaemia. Monitoring of haematological parameters should be conducted during therapy.
1. 5).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Special Populations Renal impairment Since 6-mercaptopurine pharmacokinetics has not been formally studied in renal impairment, no specific dose recommendations can be given. Since impaired renal function may result in slower elimination of mercaptopurine and its metabolites and therefore a greater cumulative effect, consideration should be given to reduced starting doses in patients with impaired renal function.
Patients should be closely monitored for dose related adverse reactions. Hepatic impairment Since 6-mercaptopurine pharmacokinetics has not been formally studied in hepatic impairment, no specific dose recommendations can be given. Since there is a potential for reduced elimination of mercaptopurine, consideration should be given to reduced starting doses in patients with impaired hepatic function.
2) Switching between tablet and oral suspension and vice versa An oral suspension of 6-mercaptopurine is also available. 2). Combination with xanthine oxidase inhibitors When xanthine oxidase inhibitors, such as allopurinol, oxipurinol or thiopurinol and 6- mercaptopurine monohydrate are administered concomitantly, it is essential that only 25 % of the usual dose of 6-mercaptopurine monohydrate is given since allopurinol decreases the rate of catabolism of 6-mercaptopurine monohydrate.
5). Patients on concomitant xanthine oxidase inhibitors should not be given Hanixol for IBD. TPMT deficient patients 6-Mercaptopurine is metabolised by the polymorphic TPMT enzyme. Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe 6-mercaptopurine monohydrate toxicity from conventional doses of 6- mercaptopurine monohydrate and generally require substantial dose reduction.
2). TPMT testing cannot substitute for haematological monitoring in patients receiving mercaptopurine. ). Patients with NUDT15 variant Patients with inherited mutated NUDT15 gene are at increased risk for severe 6- mercaptopurine toxicity (see […]
Immunosuppressive therapy should be withheld at the first sign or symptoms suggestive of PML and appropriate evaluation undertaken to establish a diagnosis. Neuromuscular agents Special care is necessary when 6-mercaptopurine is given concomitantly with neuromuscular acting agents like tubocurarine or succinylcholine.
5). Patients should be advised. UV exposure Patients treated with 6-mercaptopurine monohydrate is more sensitive to sunlight. Exposure to sunlight and UV light should be limited, and patients should be advised to wear protective clothing and use sunscreen with a high protection factor.
Lactose Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine. 5) Anticoagulants Inhibition of the anticoagulant effect of warfarin and acenocoumarol has been reported when co-administered with 6-mercaptopurine monohydrate ; therefore higher doses of the anticoagulant may be needed.
It is recommended that coagulation tests are closely monitored when anticoagulants are concurrently administered with 6- mercaptopurine monohydrate. 5) Patients with NUDT15 variant Patients with inherited mutated NUDT15 gene are at increased risk for severe 6- mercaptopurine toxicity, such as early leukopenia and alopecia, from conventional doses of thiopurine therapy.
2). 2% in Europeans and 0% in Africans. In any case, close monitoring of blood counts is necessary. 3) Taking 6-mercaptopurine monohydrate with food may decrease systemic exposure slightly. 6-mercaptopurine monohydrate can be taken with food or on an empty stomach, but patients should use a standard method of administration to avoid large variations in exposure.
The dose must not be taken with milk or dairy products since they contain xanthine oxidase, an enzyme that metabolizes 6-mercaptopurine monohydrate and therefore may lead to reduced plasma concentrations of 6- mercaptopurine monohydrate.
Effect of concomitant medicinal products on 6-mercaptopurine monohydrate:
Ribavirin Ribavirin inhibits the enzyme, inosine monophosphate dehydrogenase (IMPDH), leading to a lower production of the active 6-thioguanine nucleotides. 2). 4). Allopurinol / oxipurinol / thiopurinol and other xanthine oxidase inhibitors Xanthine oxidase activity is inhibited by allopurinol, oxipurinol and thiopurinol, which results in reduced […]
The leucocyte and platelet counts continue to fall after treatment is stopped, so at the first sign of an abnormally large fall in the counts, treatment should be interrupted immediately. Bone marrow suppression is reversible if 6-mercaptopurine monohydrate is withdrawn early enough.
During remission induction in acute myelogenous leukaemia the patient may frequently have to survive a period of relative bone marrow aplasia and it is important that adequate supportive facilities are available. 5). Increased haematological monitoring of the patient is advised when switching between different pharmaceutical formulations of 6- mercaptopurine monohydrate.
Hepatotoxicity 6-mercaptopurine monohydrate is hepatotoxic and liver function tests should be monitored weekly during treatment. The level of gamma glutamyl transferase (GGT) in plasma will be especially important to determine if discontinuation is necessary due to hepatotoxicity.
More frequent monitoring may be advisable in those with pre- existing liver disease or receiving other potentially hepatotoxic therapy. The patient should be instructed to discontinue 6-mercaptopurine monohydrate immediately if jaundice becomes apparent.
Renal Toxicity During remission induction when rapid cell lysis is occurring, uric acid levels in blood and urine should be monitored as hyperuricaemia and/or hyperuricosuria may develop, with the risk of uric acid nephropathy. Hydration and urine alkalinisation may minimize potential renal complications.
TPMT deficiency There are individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) who may be unusually sensitive to the myelosuppressive effect of 6-mercaptopurine monohydrate and prone to developing rapid bone marrow depression following the initiation of treatment with 6-mercaptopurine monohydrate.
This problem could be exacerbated by co-administration with drugs that inhibit TPMT, such as olsalazine, mesalazine or sulfazalazine. 8). 3% (1: 300) of patients have low or no detectable enzyme activity. Approximately 10% of patients with low or intermediate TPMT activity, and 90% of patients have normal TPMT activity.
There may also be a group of around 2% with a very high TPMT activity. Some laboratories offer testing for TPMT deficiency, although these tests have not been shown to identify all patients at risk of severe toxicity. Therefore, close monitoring of blood counts is still necessary.
Cross resistance Cross resistance usually exists between 6-mercaptopurine monohydrate and 6- tioguanine. Hypersensitivity Patients suspected of having suffered a hypersensitivity reaction to 6-mercaptopurine monohydrate should not be recommended to use its pro-drug azathioprine, unless the patient has been confirmed to be hypersensitive to 6-mercaptopurine monohydrate by allergological tests, and tested negative for azathioprine.
As azathioprine is a pro-drug of 6-mercaptopurine monohydrate, patients with a previous history of hypersensitivity to azathioprine must be assessed for hypersensitivity to 6-mercapopurine monohydrate prior to initiating treatment.
Renal and/or hepatic impairment:
Caution is advised during the administration of 6-mercaptopurine monohydrate in patients with renal impairment and/or hepatic impairment. 2 […]