Alimta
Alimta: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Alimta
ATX code: L01BA04
Active ingredient: pemetrexed (Pemetrexed)
Producer: Eli Lilly and Company (USA), Lilly France (France)
Description and photo update: 2019-10-07
Prices in pharmacies: from 62,300 rubles.
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Alimta is an antineoplastic drug, an antimetabolite.
Release form and composition
Dosage form - lyophilisate for preparation of solution for infusion: from white to yellowish-green or yellowish color (in a cardboard box 1 bottle of 100 or 500 mg and instructions for use of Alimta).
Composition of 1 bottle of lyophilisate:
- active substance: pemetrexed (in the form of pemetrexed disodium heptahydrate) - 100 or 500 mg;
- additional components (100/500 mg): mannitol - 106.4 / 500 mg; 10% hydrochloric acid solution and / or 10% sodium hydroxide solution - in the amount necessary to achieve pH (added during production).
Pharmacological properties
Pharmacodynamics
Pemetrexed, an active component of Alimta, is one of the antagonists of folic acid that affect many targets of its metabolism and inhibit TS (thymidylate synthase), DHFR (dihydrofolate reductase), GARFT (glycinamide ribonucleotide formyltransferase). These are key folate-dependent enzymes in the biosynthesis of purine and thymidyl nucleotides.
The entry of pemetrexed into cells is mediated by protein folate-binding transport systems and a reduced folate transporter. After entering the cells, pemetrexed is effectively and quickly transformed into polyglutamate forms with the help of the enzyme folylpolyglutamate synthetase. The polyglutamate forms of pemetrexed are retained in the cells. They are more potent inhibitors of GARFT and TS.
Polyglutamination is a concentration and time dependent process. Found in tumor cells and, to a lesser extent, in normal tissues. For polyglutaminated metabolites, an increased T 1/2 (half-life) is characteristic, due to this, the effect of pemetrexed in tumor cells is increased.
According to the studies carried out, when combined with cisplatin, there is a synergistic antitumor effect.
Pharmacokinetics
The constant V d (volume of distribution) of pemetrexed is 9 l / m 2. Approximately 81% of the dose binds to plasma proteins. In patients with severe renal failure, binding is not impaired.
Pemetrexed is metabolized in the liver to a limited extent.
During the first 24 hours after administration, 70–90% of pemetrexed is excreted by the kidneys as an unchanged substance. The total plasma clearance of the substance is 92 ml / min, T 1/2 from plasma - 3.5 hours in patients with no renal dysfunction.
Indications for use
- locally advanced or metastatic non-squamous cell non-small cell lung cancer;
- malignant pleural mesothelioma.
Contraindications
Absolute:
- myelosuppression (with an absolute neutrophil count <1500 / μl, platelets <100,000 / μl);
- severe renal failure (in patients with creatinine clearance <45 ml / min);
- combined use with a vaccine to prevent yellow fever;
- pregnancy and the period of breastfeeding;
- age up to 18 years;
- the presence of hypersensitivity to the components of Alimta.
Relative (therapy is carried out with caution):
- hepatic dysfunction;
- diseases of the cardiovascular system in severe course, including cerebral circulation disorders and myocardial infarction.
Alimta, instructions for use: method and dosage
Alimta is injected intravenously over 10 minutes on the first day of each 21-day cycle at a dose of 500 mg / m 2.
When using Alimta in combination with cisplatin, the latter is administered against the background of hydration at a dose of 75 mg / m 2 approximately 30 minutes after the administration of pemetrexed.
The severity and frequency of skin reactions can be reduced by the use of dexamethasone (it can be replaced with its analogue) 2 times a day, 4 mg for three days, starting one day before the administration of Alimta.
In order to reduce the toxicity of pemetrexed, folic acid preparations or multivitamins with folic acid content in an amount that provide its daily requirement are prescribed.
Folic acid in the dose range of 0.35–1 mg (on average 0.4 mg) should be administered at least 5 days within a week before the first administration of pemetrexed, during the entire cycle of therapy and for three weeks after the last administration of Alimta.
Also, patients are injected intramuscularly 1 mg of vitamin B 12 once in a period of 7 days before the first injection of pemetrexed and then after the start of treatment every 3 cycles. Subsequent injections of vitamin B 12 in the same dose can be carried out on the day of Alimta administration.
Before each administration of Alimta, it is recommended to assess the patient's condition and conduct observation, including a general clinical blood test and determining the number of platelets and leukocyte count. To monitor the function of the liver and kidneys, a biochemical blood test is prescribed.
Before the start of each cycle of chemotherapy, ANC (absolute neutrophil count) should be ≥ 1500 cells / mm 3, platelet count - ≥ 100 000 cells / mm 3, total bilirubin concentration - ≤ 1.5 times the ULN (upper normal limit), alkaline concentration phosphatase, alanine and aspartic aminotransferases - ≤ 3 times from VGN, and in the presence of liver metastases - ≤ 5 times from VGN.
Based on the lowest of the hematological parameters or on the most pronounced non-hematological toxicity observed during the previous treatment cycle, dose adjustment is performed before repeated cycles. Treatment may be delayed to recover from toxicity.
As recovery progresses, treatment is continued in accordance with the recommendations (value from the previous dose of pemetrexed and cisplatin in%):
- 75%: with a minimum neutrophil count <500 / μl and platelets ≥ 50,000 / μl; with a minimum platelet count <50,000 / μl, regardless of the minimum neutrophil count;
- 50%: With a minimum platelet count <50,000 / μL with bleeding [meeting the NCI-CTC (National Cancer Institute) grade II bleeding definition for total toxicity] regardless of the minimum neutrophil count.
In patients who develop non-hematological toxicity (other than neurotoxicity) ≥ III degree, therapy is postponed until the indicators return to the values before treatment.
Then the treatment is continued in accordance with the recommendations below (value from the previous dose of pemetrexed and cisplatin in%):
- 75/75%: any grade III – IV toxicity other than mucosal inflammation; diarrhea III-IV degree, or diarrhea requiring hospitalization (regardless of the degree);
- 50/100%: III – IV degree inflammation of the mucous membrane.
In case of neurotoxicity of grade 0 – I, the dose of drugs is not adjusted, grade II - the dose of cisplatin should be reduced by 50%, grade III – IV - therapy is canceled.
The use of Alimta is discontinued in cases when, after two dose reductions, non-hematological and hematological grade III – IV toxicity is noted. With grade III – IV neurotoxicity, therapy should be discontinued immediately.
To prepare the solution, only 0.9% sodium chloride solution should be used.
To obtain an infusion solution, the contents of a 100 mg bottle are dissolved in 4.2 ml of a solvent, Alimta 500 mg - 20 ml. The resulting concentration is 25 mg / ml. The bottle is gently shaken until the lyophilisate is completely dissolved. The solution should be transparent, a permissible color change - from colorless to greenish-yellow or yellowish. Before administration, it is recommended to inspect the solution for discoloration and the presence of foreign particles.
The corresponding volume of the obtained Alimta solution should be additionally diluted with 0.9% sodium chloride solution to 100 ml.
After dissolution, the drug must be administered immediately or within 24 hours if it is stored at a temperature of 2–8 ° C. The unused volume of the solution must be destroyed.
Side effects
Assessment of the incidence of adverse reactions observed during the use of Alimta:> 10% - very often; > 1% and 0.1% and 0.01% and <0.1% - rarely.
Locally advanced or metastatic non-squamous cell non-small cell lung cancer
Monotherapy with the addition of folic acid and vitamin B 12:
- digestive organs: very often - diarrhea, nausea, anorexia, vomiting, pharyngitis / stomatitis; often - abdominal pain, constipation, increased activity of aspartate aminotransferase and alanine aminotransferase;
- hematopoietic system: very often - neutropenia, leukopenia, anemia; often - thrombocytopenia;
- nervous system: often - motor or sensory neuropathy;
- skin and skin appendages: very often - peeling / rash; often - alopecia, pruritus, erythema multiforme;
- cardiovascular system: infrequently - supraventricular arrhythmia;
- urinary system: often - an increase in the concentration of serum creatinine;
- others: very often - increased fatigue; often - allergic reactions, fever, febrile neutropenia, accession of secondary infections without neutropenia.
Combination therapy with cisplatin supplemented with folic acid and vitamin B 12:
- digestive organs: very often - pharyngitis / stomatitis, nausea, anorexia, vomiting, constipation, diarrhea; often - heartburn, dyspepsia, increased activity of alanine aminotransferase and aspartate aminotransferase; infrequently - increased activity of gamma-glutamyl transferase;
- respiratory organs: infrequently - chest pains;
- hematopoietic system: very often - thrombocytopenia, neutropenia, leukopenia, anemia;
- nervous system: often - taste disturbance, sensory neuropathy; infrequently - motor neuropathy;
- skin and skin appendages: very often - alopecia; often peeling / rash;
- cardiovascular system: infrequently - arrhythmia;
- urinary system: very often - an increase in the concentration of serum creatinine; often - renal failure, decreased creatinine clearance;
- others: very often - increased fatigue; often - febrile neutropenia, accession of secondary infections, dehydration, conjunctivitis, fever.
Monotherapy: maintenance treatment with the addition of folic acid and vitamin B 12 patients with no progression after first-line:
- digestive organs: very often - anorexia, nausea; often - constipation, diarrhea, vomiting, stomatitis / inflammation of the mucous membranes, increased activity of alanine aminotransferase and aspartate aminotransferase;
- hematopoietic system: very often - anemia; often - neutropenia, leukopenia, thrombocytopenia;
- nervous system: often - motor and sensory neuropathy;
- skin and skin appendages: often - peeling / rash, pruritus, alopecia; infrequently - erythema multiforme;
- cardiovascular system: infrequently - supraventricular arrhythmia;
- urinary system: often - renal failure, increased serum creatinine concentration, decreased glomerular filtration;
- others: very often - increased fatigue; often - increased lacrimation, pain syndrome, edema, dizziness, accession of secondary infections, febrile neutropenia, conjunctivitis, fever without neutropenia; infrequently - pulmonary embolism, allergic reactions.
Malignant pleural mesothelioma
Combination therapy with cisplatin supplemented with folic acid and vitamin B 12:
- digestive organs: very often - diarrhea, nausea, vomiting, pharyngitis / stomatitis, anorexia, constipation; often - dyspepsia, increased activity of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase;
- hematopoietic system: very often - anemia, leukopenia, thrombocytopenia, neutropenia;
- nervous system: very often - sensory neuropathy; often - taste disturbance; infrequently - motor neuropathy;
- skin and skin appendages: very often - alopecia, rash;
- urinary system: very often - a decrease in creatinine clearance, an increase in serum creatinine concentration; often renal failure;
- respiratory organs: often - chest pain;
- cardiovascular system: infrequently - arrhythmia;
- others: very often - increased fatigue; often - dehydration, conjunctivitis, accession of secondary infections, febrile neutropenia, urticaria, fever.
Use of pemetrexed in other clinical trials
When pemetrexed was used in combination with other anticancer drugs, the development of serious cardiovascular and cerebrovascular adverse events, including myocardial infarction, angina pectoris, stroke, transient cerebrovascular accident, was infrequently observed. These reactions were observed mainly in the presence of risk factors for cardiovascular disorders.
Other violations:
- infrequently: esophagitis / radiation esophagitis, pancytopenia; reported cases of colitis (including perforation of the intestinal wall, inflammation of the caecum, necrosis of the intestinal wall, rectal and intestinal bleeding, sometimes fatal) and interstitial pneumonitis in combination with respiratory failure (sometimes fatal);
- rarely: hepatitis of a potentially severe degree.
According to the results of clinical studies, approximately 1% of patients developed sepsis (in some cases, fatal).
Post-marketing data
Adverse events of Alimta registered during the post-marketing period:
- infrequently: acute renal failure, edema, radiation pneumonitis, ischemia of the extremities (in some cases with the development of necrosis);
- rarely: re-development of skin reactions, similar to radiation, in patients who previously received radiation therapy (anamnestic reactions to radiation), with the subsequent appointment of pemetrexed; bullous dermatitis, including toxic epidermal necrolysis and Stevens-Johnson syndrome (in some cases fatal), anaphylactic shock, immune-mediated hemolytic anemia.
Overdose
If there is a suspicion of an overdose of Alimta, it is necessary to regularly monitor the general blood test.
The main symptoms: depression of bone marrow function, which manifests itself in the form of neutropenia, thrombocytopenia and anemia. It is also possible to attach secondary infections, the development of diarrhea, rash, inflammation of the mucous membranes.
Therapy: symptomatic, including the immediate use of folinic acid or calcium folinate.
special instructions
Alimta therapy should be carried out under the supervision of a doctor who has experience in the use of antineoplastic agents.
Myelosuppression is the dose-limiting toxicity of the drug.
Before each dose of Alimta is administered, a general blood test should be performed, including the calculation of the leukocyte formula and the number of platelets.
A biochemical blood test should be performed periodically to assess liver and kidney function.
Required values before using Alimta: absolute neutrophil count - ≥ 1,500 per μl, platelets - ≥ 100,000 per μl.
During the period of use of the drug and for at least six months after the end of therapy, reliable methods of contraception must be used.
The effect of the presence of effusion in the serous cavities (pleurisy or ascites) on the effect of pemetrexed has not been conclusively established. In patients with serous effusion who are in a stable state, there were no differences in plasma concentrations of pemetrexed administered at a standard dose, or its clearance, compared with patients without such effusion. Therefore, before starting to use Alimta, you need to consider the possibility of draining the effusion, but this is not a prerequisite.
Influence on the ability to drive vehicles and complex mechanisms
Alimta can lead to increased fatigue, in such cases, one should refrain from driving vehicles and activities that require a quick psychomotor reaction and high concentration of attention.
Application during pregnancy and lactation
The use of Alimta during pregnancy / breastfeeding is contraindicated.
Pediatric use
Prescribing the drug to patients under 18 years of age is contraindicated.
With impaired renal function
Due to insufficient data on the use of Alimta in patients with creatinine clearance <45 ml / min, the use of the drug in this category of patients is not recommended.
For violations of liver function
In case of impaired hepatic function, Alimta should be used with caution.
Drug interactions
According to the results of the studies carried out, pemetrexed is actively secreted by OAT3 (human organic anion carrier type 3).
Pemetrexed interacts with drugs that are metabolized by isoenzymes CYP2D6, CYP3A, CYP2C9, CYP1A2, minimally.
Possible interactions:
- nephrotoxic drugs and / or substances excreted by the kidneys through tubular secretion (probenecid, loop diuretics, cyclosporine, aminoglycosides, platinum-containing drugs): a decrease in pemetrexed clearance may be observed against the background of combined use;
- oral anticoagulants: during the period of combined use, it is necessary to regularly monitor the INR (International Normalized Ratio);
- NSAIDs (non-steroidal anti-inflammatory drugs) in high doses (ibuprofen from 1600 mg per day or acetylsalicylic acid from 1300 mg per day): there may be a decrease in the clearance of pemetrexed and an increase in its side effects, even in the absence of impaired renal function.
In renal failure of mild to moderate severity (in patients with creatinine clearance of 45–79 ml / min), the use of NSAIDs with a short half-life is not recommended for a 5-day period, starting 2 days before pemetrexed therapy.
There is no information on a possible interaction between NSAIDs with a long half-life (piroxicam, rofecoxib) and pemetrexed. In this regard, patients with mild or moderate renal insufficiency receiving NSAIDs should be interrupted for a week, starting at least 5 days before the administration of pemetrexed and ending 2 days after the last administration of Alimta. If there is a need for combined use with NSAIDs, it is necessary to establish strict monitoring of toxicity, in particular myelosuppression and toxicity from the digestive system.
Pemetrexed is incompatible with Ringer's solutions and Ringer's lactate. The simultaneous use of Alimta with other drugs and solutions, except for 0.9% sodium chloride solution, has not been investigated, therefore it is not recommended.
With the combined use of Alimta with live attenuated vaccines, there may be an intensification of the replication of the vaccine virus, an increase in its side effects and / or a decrease in the production of antibodies in the patient's body in response to the vaccine administration.
Analogs
Alimta's analogs are: Pemetrexed, Pemetrexed-native, Pemetrexed disodium, Verotrexed, Pemjam, etc.
Terms and conditions of storage
Store at 15-25 ° C. Keep out of the reach of children.
The shelf life is 3 years.
The prepared solution can be stored at 2–8 ° С for up to 24 hours.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Alimta
Reviews about Alimta, evaluating the effectiveness, are mostly positive. The main disadvantage is the high cost of the drug.
Price for Alimta in pharmacies
The approximate price for Alimta 500 mg per bottle is 39,500–42,000 rubles.
Alimta: prices in online pharmacies
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Drug name Price Pharmacy |
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Alimta 500 mg lyophilisate for preparation of solution for infusion 1 pc. RUB 62300 Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
