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Some cancer patients are most troubled by the fact that they have other diseases, such as hypertension, diabetes, hyperlipidemia, etc., combination medication is a common phenomenon, but the drugs "rush" between each other, always in the clouds, afraid of eating what problems without knowing it.
Don't worry, today we will make it clear, relatively long, can be collected, from time to time to look at.
Due to the interaction between drugs, or between drugs and the body, the original physicochemical properties of the drug, the sensitivity of metabolic processes or tissues in the body to the drug are changed, so that there are pharmacological effects or toxic effects that a single drug does not have, resulting in beneficial or undesirable effects. Drug interactions may occur in four aspects: absorption, distribution, metabolism, and excretion, of which the incidence is high in metabolic processes.
Drug interactions between some anti-cancer drugs, as well as with other commonly used drugs (such as hypertension treatment drugs, antibiotics, hypolipidemia drugs, nonsteroidal anti-inflammatory drugs, antihistamines, anti-rheumatism drugs, etc.), reduce the efficacy of anti-cancer drugs or increase their toxic side reactions, which is what we usually call drugs.
Clinically, according to different biochemical mechanisms, anti-tumor drugs are divided into the following 6 categories: cytotoxic drugs, hormone drugs, biological response regulators, targeted drugs (small molecule drugs, monoclonal antibody drugs), other drugs, auxiliary drugs, we will talk about the first 4 categories today.
01
Cytotoxic drugs
Cytotoxic drugs, as the name suggests, are drugs that have toxic effects on cells.
First, drugs that interfere with nucleic acid biosynthesis: they belong to antimetabolites. Drugs block the biosynthesis of nucleic acids in tumor cells in different links.
(1) Folic acid antagonists: inhibit dihydrofolate reductase.
Representative drug: methotrexate
Indications: Broad-spectrum antitumor activity. Treatment of breast cancer, gestational chorionic carcinoma, malignant mole or mole alone. In combination, it is used for the treatment of acute leukemia (especially acute lymphoblastic leukemia or acute myeloid leukemia), Burketts lymphoma, advanced lymphosarcoma (stage III and IV,Peter's stage system) and advanced fungal mycosis. High doses can be used to treat osteosarcoma, acute leukemia, bronchopulmonary cancer or head and neck epithelial cancer.
Adverse drug interactions:
1. It is common with salicylates, nonsteroidal anti-inflammatory drugs, sulfonamides, and phenytoin, and will produce potential drug toxic interactions. For example, when used together with salicylate, it can inhibit the renal excretion of methotrexate tablets, resulting in increased serum drug concentrations, which in turn increases toxicity.
2. Oral antibiotics. Tetracycline, chloramphenicol, and broad-spectrum antibiotics that are not absorbed may reduce intestinal absorption of methotrexate or interfere with the hepatic and intestinal circulation by inhibiting the intestinal flora or inhibiting drug metabolism by bacteria.
3. Methotrexate combined with some drugs will change the uptake rate of methotrexate by cells, so during the use of methotrexate, only other drugs agreed by oncologists can be used, including: penicillin, cephalosporin I., kanamycin, bleomycin, vincristine and vinblastine, hydrocortisone succinate, methylprednisolone, asparaginase.
4. When combined with probenecid, the blood concentration of methotrexate may increase and the toxicity increases (it should be carefully monitored, probenecid inhibits the transport function of the renal tubules).
5. When combined with lipid-lowering compounds (such as cholestyramine), its ability to bind methotrexate is greater than that of serum proteins.
6. Penicillin and sulfonamides may reduce the renal clearance of methotrexate, the serum concentration of methotrexate has been observed to increase and be accompanied by hematologic and gastrointestinal toxicity, methotrexate should be closely observed when combined with penicillin or sulfonamides.
7. The combination of leflunomide and methotrexate may lead to drug-induced interstitial pneumonia (ILD). Leflunomide is a commonly used drug for the treatment of rheumatoid arthritis (RA), causing interstitial pneumonia and even deaths reported gradually increasing. There is a history of methotrexate or drug-induced interstitial pneumonia, and mortality is higher.
(2) Pyrimidine antagonists:
Representative drug: fluorouracil (5-FU, inhibition of thymidine synthase)
Indications: Mainly used for digestive system adenocarcinoma, including esophageal cancer, stomach cancer, pancreatic cancer, intestinal cancer, biliary tract cancer, liver metastatic adenocarcinoma. or higher doses of fluorouracil for the treatment of chorioepithelial carcinoma. It is also commonly used to treat breast cancer, ovarian cancer, lung cancer, cervical cancer, bladder cancer and skin cancer.
Route of administration: oral absorption, but not as bioavailable as intravenous administration (blood concentration peak time is long, body fluid distribution and concentration are not constant)
Adverse drug interactions:
1. It has been reported that methotrexate, metronidazole and aldohydrofolate, tetrahydrofolate may affect the anti-cancer efficacy and toxicity of fluorouracil. In combination with methotrexate, methotrexate should be given 4 to 6 hours before fluorouracil, otherwise it will be ineffective. Tetrahydrofolate followed by fluorouracil can increase its efficacy.
2. It is not advisable to use aspirin drugs together to reduce the possibility of gastrointestinal bleeding.
3. Combined with ethanol (alcohol) or other central nervous system inhibitory drugs, the central inhibitory effect is enhanced.
4. Combined with amphetamine, the effect of the latter can be reduced.
5. When combined with phenobarbital or other anticonvulsants, it can change the seizure pattern of epilepsy and cannot increase the efficacy of anticonvulsants.
6. When combined with antihypertensive drugs, severe hypotension can occur.
7. When combined with anticholinergic drugs, it is possible to increase intraocular pressure.
8. Combined with epinephrine, due to the blockade of α receptors, the activity of β receptors is dominant, which can lead to a decrease in blood pressure.
9. When combined with lithium salts, attention should be paid to observing neurotoxicity and brain damage.
10. Combined with methyldopa, it can produce impaired consciousness, slow thinking, and disorientation.
11. Combined with carbamazepine, the blood concentration of this product can be reduced and the effect is weakened.
(3) DNA polymerase inhibitors
Representative drug: cytarabine
Indications: Induction of remission of leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia and erythropathy, as well as treatment and maintenance of meningeal leukemia and other meningal malignancies. Combination regimens containing cytarabine are effective in children with non-Hodgkin lymphoma.
Route of administration: oral inactive, cytarabine can be used subcutaneously or intravenously, bolus, continuous intravenous infusion, or intrathecal injection.
Adverse drug interactions:
1. Patients who have used L-aspartylase have reported acute pancreatitis after applying cytarabine injection.
2. Digoxin (cardiotonic agent, for hypertension, valvular heart disease, congenital heart disease and other acute and chronic cardiac insufficiency) combined with digoxin treatment, chemotherapy regimens containing cyclophosphamide, vincristine and prednisone, regardless of whether it includes cytarabine or methylbenzhydrazine, the steady-state plasma concentration of digoxin and renal glucose secretion are reversibly reduced. Therefore, to closely monitor the concentration of digoxin, consideration may be given to replacing digoxin with digitalis toxin.
3. The decrease in the sensitivity of gentamicin K. pneumonia strain to gentamicin is related to cytarabine. When gentamicin is used to treat K. pneumoniae infection, patients on cytarabine who do not rapidly develop therapeutic effects need to readjust the antimicrobial regimen.
4. The efficacy of flucytosine during the treatment of cytarabine is inhibited, possibly due to the absorption of flucytosine, which is competitively inhibited by cytarabine.
5. Methotrexate Intravenous cytarabine is combined with intrathecal methotrexate, which increases the risk of serious neurological adverse reactions, such as headache, paralysis, coma and stroke-like attacks.
(4) Purine antagonists: inhibition of purine nucleotide interaction.
Representative drug: mercaptopurine (6-mercaptopurine)
Indications: for chorioepithelial carcinoma, malignant mole, blast phase of chronic myelogenous leukemia, acute lymphoblastic leukemia and acute non-lymphoblastic leukemia.
Adverse drug interactions:
1. When used with allopurine, because the latter inhibits the metabolism of mercaptopurine, the efficacy and toxicity of mercaptopurine are significantly increased.
2. When used with drugs toxic to hepatocytes, there is an increased risk of hepatotoxicity;
3. When combined with other anti-tumor drugs or radiotherapy that inhibit bone marrow, the mercaptopurine effect will be enhanced, and the dose and course of mercaptopurine must be adjusted.
(5) Ribonucleotide reductase inhibitors:
Representative drug: hydroxyurea
Indications: accelerated and blast phases of treatment of chronic myelogenous leukemia (CML) (can be used for Malilan-resistant CML), polycythemia vera, multiple myeloma; Melanoma, head and neck squamous cell carcinoma, recurrent metastatic ovarian cancer, kidney cancer, etc.; Radiation sensitizers can increase the efficacy of head and neck squamous cell carcinoma and cervical squamous cell carcinoma.
Adverse drug interactions:
1. It is possible to increase the concentration of uric acid in the patient's blood. Therefore, when combined with allopurinol, colchicine, probenecid, etc. to treat gout, it is necessary to adjust the dose of the above anti-gout drugs.
2. When used in combination with drugs that can cause leukocytes or thrombocytopenia, or in combination with radiotherapy, the patient's blood picture should be observed and the dosage should be adjusted.
3. It has an inhibitory effect on the central nervous system and produces drowsiness. When using this product, be cautious about the use of barbiturates, tranquilizers, anesthetics, etc., such as with pentobarbital, methaquanone nizepam, anesthetics, phenol thiazides, tricyclic antidepressants and other combinations, after the additive effect, attention should be paid to adjusting the dose.
4. It has been reported that in patients with myelodysplastic abnormalities, there has been a cutaneous vascular toxicity reaction with the use of hydroxyurea, most of these patients have been or are receiving interferon therapy.
Drugs that interfere with nucleic acid transcription: selectively act on DNA templates, inhibit DNA-dependent RNA polymerases, and interfere with RNA synthesis.
Representative drug: actinomycin D
Indications: treatment of Hodgkin's disease (HD) and neuroblastoma, control of fever; The cure rate of chorionic carcinoma without metastases alone is 90% to 100%, which is similar to the effect of methotrexate alone; In combination with other drugs in the treatment of testicular cancer; Combination treatment with radiation therapy for nephroblastoma (Wilmsoma) improves survival and treats Juve sarcoma and rhabdomyosarcoma.
Adverse drug interactions
1. It can improve radiation sensitivity, and when used with radiotherapy, it may reduce radiotherapy leukocytes and aggravate the response to damage to local tissues.
2. May weaken the efficacy of vitamin K.
Drugs that disrupt the structure and function of DNA
(1) Alkylating agent:
Representative drug: cyclophosphamide
Indications: Broad-spectrum anticancer drugs that are effective for malignant lymphoma, acute or chronic lymphocytic leukemia, multiple myeloma, breast cancer, testicular tumor, ovarian cancer, lung cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, neuroblastoma, rhabdomyosarcoma and osteosarcoma.
Adverse drug interactions:
1. Reduce the pseudocholinesterase in the serum and increase the serum uric acid level. When used with anti-gout drugs such as allopurinol, colchicine, and probenecid, the dose of the above drugs should be adjusted.
2. Enhance the neuromuscular blocking effect of succincholine, resulting in prolonged apnea.
3. It can inhibit cholinesterase activity, prolong the anesthetic effect of cocaine, and increase toxicity.
4. With the simultaneous use of large doses of barbiturates (sedatives of the central nervous system) and corticosteroids, the acute toxicity of cyclophosphamide increases (affects the metabolism of cyclophosphamide).
(2) Metal complexes
- Representative drug: cisplatin
Indications: For palliative care of non-seminal germ cell carcinoma, advanced refractory ovarian carcinoma, advanced refractory bladder cancer, refractory head and neck squamous cell carcinoma. Can be used as a stand-alone or combined application.
Adverse drug interactions
Nephrotoxic or ototoxic drugs such as aminoglycoside antibiotics and renal climb diuretics can enhance the nephrotoxicity and ototoxicity of cisplatin.
Compatibility contraindications: cisplatin can interact with aluminum to form a black precipitate. When preparing or using cisplatin, aluminum-containing needles, syringes, cannulas or intravenous injection devices should not be used. Sulfites, hyposulfites, sodium carbonates and fluorouracil can affect the stability of cisplatin.
- Representative drug: carboplatin
Indications: Mainly used for solid tumors such as small cell lung cancer, ovarian cancer, testicular tumor, head and neck cancer and malignant lymphoma have a good effect. Other tumors such as cervical cancer, bladder cancer and non-small cell lung cancer may also be tried.
Adverse drug interactions:
1. Carboplatin can change kidney function. There is no literature to prove that the use of aminoglycosides and other nephrotoxic drugs will aggravate nephrotoxicity, but it is recommended not to use it in combination with the above drugs.
2. Combined with various bone marrow inhibitors or radiotherapy, it can aggravate bone marrow suppression, and carboplatin should be adjusted in dose.
3. Combined with other anti-cancer drugs, attention should be paid to the increase in toxicity.
4. Patients with cisplatin causing hearing damage, after treatment with carboplatin, ototoxicity will continue or worsen.
5. Patients who have been treated with cisplatin, treatment with carboplatin, will increase the incidence and intensity of neurotoxicity.
- Representative drug: oxaliplatin (third generation platinum antineoplastic drugs)
Indications: Chemotherapy for gastrointestinal tumors, colorectal cancer and hepatocellular carcinoma. Patients with metastases of colon and rectal cancer after failed treatment with 5-fluorouracil may be used alone or in combination with 5-fluorouracil (with a synergistic effect).
Adverse drug interactions:
1. Between sodium chloride and alkaline solutions (especially 5-fluorouracil), there are compatibility contraindications, do not mix with the above preparations or administer simultaneously through the same infusion channel.
2. In vitro tests, the following drugs can not replace platinum on plasma proteins: erythromycin, salicylate, sodium valproate, granisetron and paclitaxel.
3. In vitro studies, oxaliplatin is not metabolized by the cytochrome P450 isoenzyme or in turn inhibits P450, so there will be no P450-mediated drug-drug interactions in the patient.
4. Platinum-containing varieties are mainly eliminated by the kidneys, and the combination of compounds with potential renal toxicity may reduce the clearance of platinum drugs.
5. With cardiotoxicity, caution should be exercised when combined with other drugs that can cause the QT interval to be prolonged, and the QT interval should be closely monitored.
6. Use with other drugs that can cause rhabdomyolysis should be cautious.
(3) Topoisomerase inhibitors: The role of topoisomerases is to open the DNA superhelix and participate in dna replication, recombination, repair and transcription processes. Topoisomerase inhibitors can block DNA replication, repair, and lead to DNA break destruction. Such drugs include hydroxycamptothecin, irinotecan, doxorubicin, daunorubicin, and etoposide.
Representative medicine: doxorubicin
Indications: For patients with low CD4 (<200CD4 lymphocytes/mm^3) and AIDS-associated Kaposi's sarcoma (AIDS-KS) with extensive diseases of the mucocutaneous viscera. Used as a first-line systemic chemotherapy agent, or as a second-line chemotherapy agent for AIDS-KS with progressive disease, and also in patients who cannot tolerate a combination of two or more drugs: vincristine, bleomycin, and doxorubicin (or other anthracycline antibiotics).
Adverse drug interactions:
Doxorubicin hydrochloride has been reported to worsen hemorrhagic cystitis caused by cyclophosphamide and enhance the hepatotoxicity of mercaptopurine. Concomitant use with other cytotoxic drugs, especially myelotoxic drugs, requires caution.
(4) Mitomycin
Indications: Relieves the self-conscious signs and symptoms of the following diseases: stomach cancer, colon and rectal cancer, lung cancer, pancreatic cancer, liver cancer, cervical cancer, uterine cancer, breast cancer, head and neck tumors, bladder tumors.
Adverse drug interactions:
1. Simultaneous application with doxorubicin can increase cardiotoxicity, it is recommended that the total amount of doxorubicin is limited to less than 450mg/m^2 by body surface area.
2. Combined with other anti-tumor drugs, sometimes enhance bone marrow suppression.
3. Combined with vinblastine drugs (vinblastine, vincristine, vinpocetaxine), sometimes causing shortness of breath and bronchospasm.
Fourth, drugs that interfere with protein synthesis
(1) Vinblastine: Vinblastine, Vincristine, Vinblastine
Representative drug: Vincristine
Indications: Used for the treatment of acute leukemia, Hodgkin's disease, malignant lymphoma, but also for breast cancer, bronchopulmonary cancer, soft tissue sarcoma, neuroblastoma, etc.
Adverse drug interactions:
1. Pyrrole series of antifungal agents (itraconazole), increases side effects of the muscular nervous system. If side effects are found, appropriate treatment such as dose reduction, suspension or discontinuation should be carried out. Itraconazole has the effect of hindering hepatocytope P-450 3A, vincristine is metabolized by hepatocytope P-450 3A, and the combination can inhibit vincristine metabolism.
2. Combined with phenytoin sodium, reduce the absorption of phenytoin sodium, or make hypermetabolism.
3. Combined with platinum-containing anti-sub-sub- and malignant tumor agents, it may enhance the 8th pair of cranial nerve disorders.
4. Combined with L-asparaginase, it may enhance the disorders of the nervous system and blood system. To minimize toxicity, vincristine sulfate can be used 12 to 24 hours before L-asparaginase administration.
5. This product can prevent methotrexate from oozing from within the cell, improve the intracellular concentration of the latter, so it is often injected with this product first, and then methotrexate is used.
6. Combined with isoniazid and spinal cord radiation therapy can aggravate neurotoxicity.
(2) Taxanes: paclitaxel, docetaxel
Representative drug: paclitaxel
Indications: Can be used for first-line chemotherapy for ovarian cancer and later for the treatment of metastatic ovarian cancer, as first-line chemotherapy, and can also be used in combination with cisplatin. It can be used for follow-up treatment or for patients with recurrence in breast cancer who have previously used standard chemotherapy containing doxorubicin. It can be combined with cisplatin for first-line chemotherapy in patients with non-small cell lung cancer who cannot be operated on or treated with radiotherapy.
Adverse drug interactions:
1. Pharmacokinetic data prove that after the use of cisplatin is administered to this product, the clearance of this product is reduced by about 30%. Bone marrow toxicity is more severe.
2. Simultaneous application of ketoconazole affects the metabolism of this product.
5. Other cytotoxic drugs
Representative drug: asparaginase (L-Asp)
Anti-cancer mechanism: The proliferation of tumor cells is inseparable from asparagine. But they cannot synthesize on their own and are therefore strongly dependent on asparagine in the plasma of the host (patient). The injection of asparaginase drugs can hydrolyze the asparagine in the host plasma into aspartic acid and ammonia, so that tumor cells lack asparagine, thereby inhibiting their division and growth.
Adverse drug interactions:
1. Methotrexate: asparaginase can reduce the efficacy of methotrexate. Concomitant application or application of asparaginase after methotrexate should be avoided.
2. Glucocorticoids: can aggravate hyperglycemia, blood glucose should be monitored during medication.
3. Vincristine: increases the incidence and extent of virality in the nervous system. Asparaginase should be applied after vincristine.
02
Antitumor drugs that regulate hormone balance in the body
(1) Estrogen regulators: tamoxifen, torrimifen, raloxifene
Representative drug: tamoxifen
Indications: for estrogen-dependent breast cancer.
Adverse drug interactions:
1. When combined with warfarin or any other aromatic legumin anticoagulant, a significant increase in anticoagulant effect may occur, and close monitoring of the patient is recommended.
2. When combined with cytotoxic drugs, the risk of thromboembolism increases.
3. In patients with bone metastases, at the beginning of treatment with tamoxifen, combined with drugs that can reduce the excretion of calcium in the kidneys, for example, thiazide diuretics, may increase the risk of hypercalcemia.
(2) Androgen regulators
Representative drug: flutamide
Indications: for prostate cancer in patients with initial or re-treatment.
Adverse drug interactions
1. When with the new double coumarin, it can be seen that the prothrombin time is prolonged. Prothrombin time should be monitored to determine the first dose and to maintain the amount of anticoagulant.
2. It has been reported that there will be an increase in the plasma concentration of theophylline when combined with theophylline. CYP 1A2 is the main metabolic enzyme of theophylline and the main metabolic enzyme for the conversion of flutamide into the active substance 2-hydroxyfluorotamide.
03
Biological reaction regulator
Tumors are suppressed mainly through the body's immune function.
- Interferon (IFN)
Indications: tumors of the lymphatic or hematopoietic system: trichomecytic leukemia; Multiple myeloma; Low-grade malignant non-Hodgkin's lymphoma; Cutaneous T-cell lymphoma; Chronic myeloid leukemia; Thrombocytosis associated with myeloproliferative disorders.
Solid tumors: AIDS-associated Kapozi's sarcoma in patients without a history of opportunistic infection; Recurrent or metastatic renal cell carcinoma; Metastatic malignant melanoma.
Viral diseases: adult chronic active hepatitis B with viral replication markers such as HBV-DNA, DNA polymerase positive or HBeAg positive; Adult chronic hepatitis C with positive HCV antibodies and elevated alanine transaminases (ALT), but not with hepatic decompensation. Genital warts.
Adverse drug interactions:
1. For drugs that cause bone marrow suppression, or drugs metabolized by the cytochrome P-450 pathway, caution should be exercised when using recombinant integrated interferon α injection, which may affect the oxidative metabolic process by reducing the activity of intrahepatic microsomal cytochrome enzyme P450. Treatment and/or toxicity levels of the accompanying agent should be closely monitored.
2. The clearance of theophylline in the body is reduced.
3. Neurotoxicity, hematotoxicity and cardiotoxicity caused by the use of drugs taken will increase the toxicity due to the use of interferon.
4. Interactions occur when combined with drugs with central effects.
- Interleukin-2 (IL-2)
Indications: Immunomodulators for the biological treatment of tumors, especially for the treatment of kidney cancer, malignant melanoma and cancerous chest and abdominal effusions, and also for the comprehensive treatment of other malignant tumors and immunocompromised patients. Adjunctive for the treatment of refractory tuberculosis caused by drug-resistant strains of tuberculosis.
Adverse drug interactions:
1. Affect the function of the central nervous system, and after use with psychotropic drugs, interactions may occur (such as anesthetics, analgesics, antiemetics, sedatives, tranquilizers).
2. When administered in parallel with drugs that are harmful to the kidneys (such as glucosamine, analgesic and anti-inflammatory drugs), drugs that are toxic to bone marrow (such as chemotherapy of cytotoxins), drugs that are toxic to the heart (such as doxorubicin) or hepatotoxic drugs (such as methotrexate, asparaginase), the toxic effect on these organ systems will be enhanced.
3. The decline in liver and kidney function caused by the use of this product will delay the elimination of concomitant drugs, thereby increasing the risk of adverse reactions of these drugs. It has been reported that continuous, high doses of combined antineoplastic agents trigger allergic reactions, particularly those such as methamine, cisplatin, and α-interferon. These reactions include erythema, pruritus, and hypotension, and occur within hours of chemotherapy, and some patients require treatment.
4. Combined treatment with α-interferon will increase myocardial damage, including myocardial infarction, myocarditis, ventricular motor dysfunction and severe rhabdomyomas. When treated with α-interferon and this product in parallel administration, it was observed that the patient had worsened or caused some autoimmune and inflammatory diseases, including crescent IgA vascular nephritis, eyelid myasthenia gravis, inflammatory arthritis, thyroiditis, and bullous pemphigoid.
5. Although glucocorticoids can alleviate the adverse reactions caused by this product, including fever, renal insufficiency, hyperbilirubinemia and dyspnea, the use with such drugs will weaken the anti-tumor efficacy of this product, so avoid use.
6. When used with β-blockers and other hypertensive drugs, it may cause hypotension.
- Thymic peptide preparations: thymus peptide, thymic pentapeptide, thymic peptide α1 (thymic macron)
Representative drug: Thymus peptide
Indications: patients with chronic hepatitis B over 18 years of age; various primary or secondary T-cell deficiencies (eg, congenital immunodeficiency disorders in children); Certain autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.); Various diseases with low cellular immune function; Adjuvant therapy for tumors.
Drug Interactions:
1. Combined with many commonly used drugs, including interferons, anti-inflammatory drugs, antibiotics, hormones, analgesics, antihypertensive drugs, diuretics, drugs for the treatment of cardiovascular diseases, central nervous system drugs, contraceptives, there is no interference phenomenon.
2. Combined with interferon, it has a synergistic effect on improving immune function.
3. Combined with antibiotics, it can enhance the antibacterial effect.
4. Combined with chemotherapy drugs, it can reduce the toxic side effects of chemotherapy.
04
Molecularly targeted therapy drugs
Commonly used therapeutic targets for tumor molecular targeted therapy are: cell receptors, signaling and anti-angiogenesis.
There are two main categories, monoclonal antibodies to macromolecules and small molecule compounds
Macromolecular monoclonal antibody-oriented drugs
- Trastuzumab for injection (Herceptin)
Indications: Metastatic breast cancer, early breast cancer, metastatic gastric cancer
Adverse drug interactions
1. Benzyl alcohol
Benzyl alcohol, used as a preservative in sterile water for injection in the 440 mg specification, causes toxic reactions in newborns and children under 3 years of age. Patients with known allergy to benzyl alcohol should be re-dissolved with water for injection when administered to trastuzumab, with trastuzumab administered only once per bottle. Discard unused parts.
2. Paclitaxel
Reduce the clearance of trastuzumab by 1/2. Compared with trastuzumab combined with anthracyclines and cyclophosphamides, the average blood concentration of trastuzumab increased by about 1.5 times.
- Bevacizumab injection
Indications: metastatic colorectal cancer; Advanced, metastatic or recurrent non-small cell lung cancer; Recurrent glioblastoma;
Hepatocellular carcinoma; Epithelial ovarian, fallopian tube or primary peritoneal cancer; Cervical cancer.
Adverse drug interactions
Bevacizumab is used in combination with sunitinib malate
In two clinical studies of metastatic renal cell carcinoma, 7 of the 19 patients treated with bevacizumab (10 mg/kg every 2 weeks) in combination with sunitinib malate (50 mg per day) reported developing microvascular hemolytic anemia (MAHA).
MAHA is a hemolytic disorder manifested by erythrocyte disruption, anemia, and thrombocytopenia. In addition, hypertension (including hypertensive crisis), elevated creatinine, and neurologic symptoms have been observed in some patients. All of these findings, which recover with the discontinuation of bevacizumab and sunitinib, are reversible.
- Rituximab injection (merova)
Indications:
Non-Hodgkin lymphoma:
Patients with previously untreated CD20-positive stage III-IV follicular non-Hodgkin lymphoma should be used in combination with chemotherapy. Patients with follicular lymphoma who are initially treated are treated with monotherapy with complete or partial remission after melovar combined chemotherapy. Follicular lymphoma with relapsed or chemotherapy resistance.
CD20-positive diffuse large B-cell non-Hodgkin lymphoma (DLBCL) should be combined with 8 cycles of standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone).
Chronic lymphocytic leukemia:
Treatment in combination with fludarabine and cyclophosphamide (FC) in patients with previously untreated or recurrent/refractory chronic lymphocytic leukemia (CLL).
Adverse drug interactions
Patients with human anti-murine antibody (HAMA) or human anti-chimeric antibody (HACA) titer may develop anaphylactic or hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.
Small molecule targeted drugs
- Bcr-Abl protein kinase inhibitor: imatinib
Indications: treatment of the chronic, accelerated or blast phases of Philadelphia chromosome-positive chronic myeloid leukemia (Ph + CML); Adult patients with malignant gastrointestinal stromal tumors (GIST) that cannot be resected and / or develop metastatic; combination chemotherapy in the treatment of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); Adult patients with relapsed refractory Ph + ALL.
Drug Interactions:
The drugs that can change the plasma concentration of imatinib are as follows:
1. CYP3A4 inhibitors: After healthy subjects took a single dose of ketoconazole (CYP3A4 inhibitor) at the same time, the drug exposure of imatinib increased significantly. There is no experience of concomitant use with other CYP3A4 inhibitors such as itraconazole, erythromycin, and clarithromycin.
2. CYP3A4 inducer: after simultaneous administration of phenytoin drugs, resulting in a decrease in the plasma concentration of imatinib, the efficacy is reduced, and imatinib should be avoided from taking it at the same time as CYP3A4 inducers (including dexamethasone, cataimidine, phenobarbital, etc.).
3. In patients taking enzyme-induced antiepileptic drugs (EIAEDs), such as carbamazepine, oxcarbazepine, phenytoin, phosphophenytoin, phenobarbital and deoxyphenepite, while receiving malignant glioma treatment with this product, the plasma concentration of imatinib is reduced, and the efficacy is reduced.
4. When combined with preparations containing St. John's wort, it can cause a 30% to 32% decrease in AUC.
The following drugs can be used to change plasma concentrations:
1. Imatinib increases the mean Cmax and AUC of simvatatin (CYP3A4 substrate) by 2 and 3.5 times, respectively. Plasma concentrations of other drugs metabolized by CYP3A4 (e.g., benzodiazepines, dihydropyridine, calcium channel antagonists, and other HMG-CoA reductase inhibitors) can also be increased. Therefore, it is prudent to use imatinib and CYP3A4 substrates with narrowing of the treatment window (eg, cyclosporine, pimozide).
2. Imatinib can inhibit the activity of CYP2D6 in vitro, so when used simultaneously, the system's exposure to CYP2D6 substrate may increase, it is recommended to use with caution.
3. Imatinib can also inhibit the activity of CYP2C9 and CYP2C19 in vitro, and the prothrombin time can be seen after taking warfarin. At the beginning and end of imatinib therapy or when changing the dose, the prothrombin time should be monitored for a short time with dicoumarin.
4. In vitro experiments have shown that imatinib inhibits O-glucuronidation of paracetamol (Ki is 58.5 μM).
Simultaneous use of imatinib (400 mg / day, 8 days of use) and acetaminophen / paracetamol (1000 mg single dose on day 8) in CML patients did not change the pharmacokinetics of acetaminophen / paracetamol. In the case of a single administration of acetaminophen / paracetamol, the pharmacokinetics of imatinib did not change. Patients who have previously treated fever with acetaminophen die from acute liver failure, the exact cause of death is unknown, but patients should be warned to avoid the simultaneous use of over-the-counter and prescription drugs containing acetaminophen.
Note: AUC refers to the area under the curve under the plasma concentration of the drug, represents the relative cumulative amount of the drug in the blood plasma over a period of time, and is the most important pharmacokinetic parameter reflecting drug exposure.
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor: gefitinib
Indications: Monotherapy is indicated for treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with sensitive mutations in the epidermal growth factor receptor (EGFR) gene.
Adverse drug interactions:
In vitro tests confirmed that gefitinib is metabolized primarily by CYP3A4 in the hepatocellular pigment P-450 system and may interact with drugs that induce, inhibit, or metabolize for the same liver enzyme. Gefitinib can inhibit CYP2D6 to a limited extent. Animal studies have shown that gefitinib has little enzyme-inducing effect.
1. Drugs that inhibit CYP3A4
Gefitinib was combined with itraconazole ( a CYP3A4 inhibitor ) in healthy volunteers, and the average AUC of gefitinib increased by 80%. Studies of interaction with other CYP3A4 inhibitors have not been conducted, but this class of drugs such as ketoconazole, clotrimazole, and Ritonovir may also inhibit the metabolism of gefitinib.
2. Drugs that raise the pH of the stomach
Combined with ranitidine, which can significantly and continuously increase the gastric pH to ≥5, can reduce the average AUC of gefitinib by 47%, reducing the efficacy of gefitinib.
3. Rifampicin (antibiotic)
Administered simultaneously with rifampicin (known strong CYP3A4 inducer) in healthy volunteers, gefitinib's average AUC was 83% lower than when used alone.
4. Substances that induce CYP3A4 activity can increase the metabolism of gefitinib and reduce its plasma concentration. Combination with CYP3A4 inducers such as phenytoin, carbamazepine, barbiturates, or St. John's wort may reduce efficacy.
5. Drugs metabolized by CYP2D6
Gefitinib taken with other drugs metabolized by CYP2D6 may increase blood levels in the latter.
6. Warfarin
Although no drug interaction studies have been conducted, some patients taking warfarin have reported increased INR (International Normalized Ratio) and/or bleeding events. Patients taking warfarin should regularly monitor their prothrombin time or INR.
7. Changchun Ruibin
Phase II clinical studies have shown that concomitant administration with vinorebine may exacerbate the neutral leukopenia effects caused by vinorelbine.
Warm tips: Popular science articles do not provide professional diagnosis and treatment opinions, and the specific diagnosis and treatment should be carried out under the guidance of professional doctors
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