In all both highdose intravenous and intrathecal methotrexate is used. Its most common use is in the treatment of airway obstruction from asthma or copd. Aminophylline, aminophylline iv uses, dose, side effects. Folate antagonists were among the first antineoplastic agents to be developed. Learn about drug interactions between aminophylline oral and methotrexate sodium inj and use the rxlist drug interaction checker to check drug combinations. An average 96% range 75 to 105% of an uncoated theophylline tablet is. Dose should be determined by theophylline serum level monitoring. Aminophylline is a methylxanthine and derivative of theophylline.
Child with acute methotrexate related neurotoxicity. Check with your doctor or nurse immediately if any of the following side effects occur while taking aminophylline. A case of methotrexate neurotoxicity presented as status. Adult intravenous aminophylline protocol for use by. Aminophylline for methotrexate induced neurotoxicity.
Aminophylline relaxes smooth muscles, particularly bronchial muscles. Aminophylline injection fda prescribing information, side. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Aminophylline and theophylline are medicines used to treat lung diseases such as asthma. Acute mtx toxicity often manifests as fluctuating neurologic symptoms with. It has also been reported that plasma homocysteine levels are increased acutely following methotrexate. Keywords aminophylline, fever, methotrexate, neurotoxicity, status epilepticus. Patients with compromised cardiac or circulatory function including congestive heart failure, angina pectoris or acute myocardial injury as myocardial stimulation. Nov 18, 2018 see use of methotrexate in the treatment of rheumatoid arthritis and therapeutic use and toxicity of highdose methotrexate. Csf adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased compared with control subjects mean values of 217 and 51 nmoll, median 175 and 52 nmoll. The toxicity was reversed after treatment with aminophylline. Methotrexate induced leukoencephalopathy has a very. Do not use it to treat or manage an actual overdose.
Aminophylline 100 mg tablets dear patient, please read. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate aminophylline is less potent and shorteracting than theophylline. Pdf methotrexateinduced leukoencephalopathy reversed by. Aminophylline for methotrexate induced leukoencephalopathy. Dbl aminophylline injection is also contraindicated in patients with bronchiolitis bronchopneumonia. Aminophylline relaxes and opens air passages in the lungs, making it easier to breathe. Mtx inhibits dihydrofolate reductase, an enzyme that reduces folic acid to tetrahydrofolic acid. Methotrexate induced acute toxic leukoencephalopathy includes various clinical manifestations. Learn about drug interactions between methotrexate sodium oral and theophylline oral and use the rxlist drug interaction checker to check drug combinations. Aminophylline comes as a tablet and syrup to take by mouth and a suppository to insert rectally. Although the anhydrous theophylline content varies greatly between products, there is similar excellent oral bioavailability. Methotrexate increased risk of toxicity with methotrexate.
Methotrexate induced acute encephalopathy is a serious complication of a common chemotherapy agent used in lymphoblastic leukemia. Mar 04, 1995 since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. Aminophylline belongs to a group of medicines known as bronchodilators. Aminophylline for methotrexateinduced neurotoxicity the lancet. Major side effects of lowdose methotrexate uptodate. Knowledge acquired of the kinetic disposition and effects of theophylline over the past 8 years has increased the clinical utility of the drug in the treatment of cardiorespiratory disorders. Find patient medical information for aminophylline intravenous on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Once in the body, theophylline is released and acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Methotrexaterelated neurotoxicity in the treatment of. Each 25 mgml, 2 ml vial contains methotrexate sodium equivalent to 50 mg methotrexate, 0. Methotrexate toxicitymethotrexate toxicity methotrexate mtx is a chemotherapeutic drug that is structurally similar to folic acid.
This xanthine most likely exerts its effect by inhibiting camp or cgmp phosphodiesterases, thereby increasing levels of the second messenger camp or cgmp intracellularly. Aminophylline is 80% theophylline 100 mg aminophylline 80 mg theophylline. Because of this variation in metabolism the use of aminophylline injection in children under 6 months of age is not recommended. This may occur as a result of confusion by patients with other daily medications or prescriptions being misinterpreted by nursing. Subacute methotrexate neurotoxicity may be mediated by adenosine and relieved by aminophylline. Mtx neurotoxicity is usually treated with aminophylline or leucoverin administration 33,34. Reversible encephalopathy induced by systemic high dose methotrexate dst lam, pl khong, aks chiang, sy ha. Methotrexate is an antimetabolite with an important role in the treatment of acute lymphoblastic leukaemia all. Learn about side effects, warnings, dosage, and more. Leukoencephalopathy reversed by aminophylline and highdose folinic acid. Aminophylline dissociates into theophylline, which is a xanthine derivative.
It is used as a bronchodilator and also as an antidote to dipyridamole toxicity. Mtx even after a previous episode of toxic leukoencephalopathy. Glucarpidase has recently been approved for the treatment of methotrexate toxicity. Although hdmtx is safely administered to most patients, it can cause significant toxicity, including acute kidney injury aki in 2%12% of patients. Uniphyllin phyllocontin nuelin sa slophyllin decision to commence documented by senior fy and above or nmp respiratory specialist nurse. This inhibition interferes with dna synthesis and cell reproduction. Aminophylline for methotrexateinduced neurotoxicity the. Aminophylline for methotrexateinduced neurotoxicity. May be administered via lumbar puncture or ommaya reservoir. Aminophylline injection is administered by slow intravenous injection or diluted and administered by intravenous infusion.
Clinical and radiological characteristics of methotrexateinduced. They help prevent and treat wheezing and other breathing problems, including respiratory distress associated with premature birth. Treating toxicity from methotrexate, nursing standard 10. Aminophylline definition of aminophylline by medical dictionary. Aminophylline is a compound of the bronchodilator theophylline with ethylenediamine in 2. Methotrexate induced leukoencephalopathy reversed by aminophylline and highdose folinic acid article pdf available in acta haematologica 1114. Administration may be oral, intramuscular, intravenous, or rectal. Methotrexate induced acute encephalopathyoccurrence on re. Adverse reactions associated with this drug are generally mild when theophylline concentrations are within the therapeutic range. Find patient medical information for aminophyllin oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Aminophylline or theophylline overdose occurs when someone takes more than the normal or recommended amount of these medicines. Methotrexateinduced leukoencephalopathy reversed by aminophylline and highdose folinic acid article pdf available in acta haematologica 1114.
Aminophylline injection aminophylline dihydrate dose. As this drug is considered vital for therapeutic success of leukemia therapy it is often rechallenged in these patients. Carbamazepine can stimulate the hepatic metabolism of aminophylline if used concurrently. A patient of acute lymphoblastic leukemia developed mild, transient hemiparesis after the 2nd dose of high dose methotrexate. Review aminophylline background the current th edition of the who model essential medicines list dated april 2003 includes aminophylline on the complementary list. Elimination of theophylline in children younger than 6 months of age, especially in neonates, appears to be reduced. Indication intravenous aminophylline may be used for acute exacerbation of chronic obstructive lung. Acute toxicity occurs with the ingestion of a high dose of theophylline while chronic toxicity occurs with the accumulation of the drug in the body 4. Pdf methotrexate is an antimetabolite with an important role in the. Aminophylline is used to prevent and treat wheezing, shortness of breath, and difficulty breathing caused by asthma, chronic bronchitis, emphysema, and other lung diseases.
Nov 01, 2019 aminophylline injection, usp is a sterile, nonpyrogenic solution of aminophylline in water for injection. Methotrexate is a major cause of treatmentrelated acute neurotoxicity in children with hematologic malignancies. The listing is as shown below together with the other respiratory tract medicines listed. Csf adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased. Methotrexate rasuvo, otrexup is a selfinjectable solution used to treat psoriasis and rheumatoid arthritis. In 1948, aminopterin was used to induce remission in childhood acute lymphoblastic leukemia all, and the related agent methotrexate mtx is still an important component of modern treatment for all as well as a number of other hematologic malignancies. A patient of acute lymphoblastic leukemia developed mild. However, it demonstrates several toxic effects such as mucositis. If you or someone you are with has an overdose, call your local emergency number such. Hematologic toxicity hematologic toxicity is a serious complication commonly observed with mtxhd 35. Mri scan revealing diffuse symmetric bilateral hyperintense t2 signal abnormality within the white matter. Aminophylline injection norphyl, phyllocontin, truphylline is a bronchodilator injection drug used for the management of acute worsening of asthma or copd. Loading dose should be decreased or eliminated if theophylline preparation has been used in pre ceding 24 hr. Learn about drug interactions between aminophylline iv and methotrexate sodium oral and use the rxlist drug interaction checker to check drug combinations.
Trexall methotrexate dose, indications, adverse effects. Although not all of these side effects may occur, if they do occur they may need medical attention. We report a case of severe mtx neurotoxicity in an adult presenting with. Intravenous aminophylline adults theophylline is a bronchial smooth muscle relaxant and bronchodilator.
Jun 12, 20 methotrexate induced acute encephalopathy is a serious complication of a common chemotherapy agent used in lymphoblastic leukemia. Clinical pharmacokinetics of theophylline springerlink. During therapy, patients should be monitored carefully for signs of toxicity. An overdose in theophylline prolongs the absorption of the drug and the take it takes for the body to excrete the drug from the body. Aminophylline is a drug combination that contains theophylline and ethylenediamine in a 2. Methotrexate induced leukoencephalopathy reversed by aminophylline and highdose folinic acid. The risk factors for methotrexate related toxicity include young age, highdose, intrathecal route and association with cranial radiation. Highdose folinic acid, in addition to standard folinic acid rescue, has been reported to relieve methotrexateinduced. Findings on diffusionweighted imaging and correlation with clinical outcome nancy rollins, naomi winick, robert bash, and timothy booth backgroundandpurpose. Similar to other theophyllines, aminophylline is indicated for the treatment of lung diseases such as asthma, chronic bronchitis, and copd. Symptoms and findings one or more of the following common toxicities associated with methotrexate mtx are seen in some form, at some time, in most patients. Aminophylline doses may need to be increased if carbamazepine is added. Because of this variation in metabolism the use of aminophylline injection in children under 6.
Acutelymphocyticleukemiaallisacommonmalignancy of childhood treated with methotrexate mtx, which is associated with acute neurotoxicity. Methotrexateinduced leukoencephalopathy acta haematol 2004. Leukoencephalopathy can occur acutely or as a chronic toxic effect. This explains why aminophylline, a reversible inhibitor of adenosine, can be used in treating methotrexate induced neurotoxicity 5,14,15. Aminophylline is less potent and shorteracting than theophylline.
Jun 06, 2016 folinic acid is indicated if a drug levels cannot be obtained within 24 hours, the patient is symptomatic, renal function is abnormal or drug levels are above the threshold for toxicity. The purpose of this study was to investigate whether diffusionweighted mr imaging dwi detects acute methotrexate white matter neurotoxicity in this patient population. But the mechanism by which it causes neurotoxicity is not understood. Sullivan, boston, suggested that his workwith intraarterial methotrexate showed that toxicity to this drug was not related to its concentration in the blood but to the time the tissues were exposed to it. The approach to the child with mtx neurotoxicity is not well established. Since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. In case of intake of high doses of this medication, inform your doctor at once and seek. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate.
In case of overdose, call the poison control helpline at 18002221222. Methotrexateinduced leukoencephalopathy reversed by. Intravenous iv theophylline is only available as aminophylline, which is a prodrug of theophylline. It is used for the treatment of pulmonary conditions, including asthma and chronic obstructive pulmonary disease copd. Aminophylline for methotrexateinduced neurotoxicity sciencedirect. Reversible encephalopathy induced by systemic high dose. Aminophylline, theophylline, nsaids increased risk of convulsions epilepsy can reduce seizure threshold. Diffusionweighted mr imaging of early methotrexate. Monitor closely for signs of methotrexate toxicity if coadministration cannot be avoided, including signs and symptoms of bone marrow toxicity immunosuppression sore throat, fever, reduced blood counts, unusual bruising or bleeding and liver toxicity, as examples. In this regard, the reversal of mtx neurotoxicity by aminophylline, presumably by displacement of adenosine from its receptor in the cns by aminophylline, has been suggested and should be studied further 31,32.
Aminophylline injection, usp is a sterile, nonpyrogenic solution of aminophylline in water for injection. Aminophylline dihydrate is approximately 79% of anhydrous theophylline by weight. Along with its needed effects, aminophylline may cause some unwanted effects. Extendedrelease controlledrelease, sustainedrelease products may be. As this drug is considered vital for therapeutic success of leukemia therapy it is often rechallenged in these. Methotrexate induced leukoencephalopathy acta haematol 2004. Successful therapeutic rechallenge after a severe episode of high. Methotrexateinduced leukoencephalopathy reversed by aminophylline and highdose folinic acid. Methotrexateinduced acute encephalopathy is a serious complication of a common chemotherapy agent used in lymphoblastic leukemia. Theophylline toxicity signs, symptoms, treatment, amount.
Do not exceed a dose of aminophylline 507 mgday equivalent to theophylline 400 mgday. Background methotrexate is a drug which is often unintentionally involved in medication misadventure. More importantly, serious aminophylline toxicity can result if carbamazepine is discontinued and the dose of aminophylline is not correspondingly decreased. Nov 01, 2019 theophylline 1,3dimethylxanthins can indirectly stimulate both. Reversible leukoencephalopathy following intrathecal. See use of methotrexate in the treatment of rheumatoid arthritis and therapeutic use and toxicity of highdose methotrexate. Reconstitute preservativefree methotrexate with preservativefree0.