(isoniazid · DailyMed)
RIFAMPICIN, ISONIAZID, PYRAZINAMIDE & ETHAMBUTOL
rifampicin, isoniazid, pyrazinamide, ethambutol
What it does
Ethambutol is a medication used to treat tuberculosis (TB), a serious lung infection.
Commonly used for: tuberculosis (TB), lung infection
Read more in plain English ↓Plain-language summary for general understanding - not medical advice. Always follow your pharmacist/doctor.
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Sourcing - Kenya onlyRegistration & product details
Source: Botswana Medicines Regulatory Authority · fetched 2026-04-15 20:42:28 · updated 2026-05-12 08:03:05
Drug Interactions
293Pharmacodynamic Warnings
Isoniazid appears in TABLE 1: Drugs that cause hepatotoxicity
Isoniazid appears in TABLE 12: Drugs that cause peripheral neuropathy
Severe (78)
Abemaciclib - decreases exposure
Rifampicin is predicted to markedly decrease the exposure to abemaciclib. Avoid.
Abiraterone - decreases exposure
Rifampicin is predicted to decrease the exposure to anti-androgens (abiraterone). Avoid.
Acalabrutinib - decreases exposure
Rifampicin is predicted to decrease the exposure to acalabrutinib. Avoid.
Anti-Androgens - decreases exposure
Rifampicin is predicted to decrease the exposure to anti-androgens (abiraterone). Avoid.
Antiarrhythmics - decreases exposure
Rifampicin is predicted to decrease the exposure to antiarrhythmics (disopyramide, dronedarone). Avoid.
Moderate (72)
Alprazolam - decreases exposure
Rifampicin is predicted to decrease the exposure to benzodiazepines (alprazolam). Adjust dose.
Amlodipine - decreases exposure
Rifampicin is predicted to decrease the exposure to calcium channel blockers (amlodipine, felodipine, lacidipine, lercanidipine, nicardipine, nimodipine). Monitor and adjust dose.
Antiepileptics - decreases exposure
Rifampicin slightly decreases the exposure to antiepileptics (brivaracetam). Adjust dose.
Antiepileptics - decreases concentration
Rifampicin decreases the concentration of antiepileptics (fosphenytoin, phenytoin). Use with caution and adjust dose.
Antifungals,azoles - decreases exposure
Rifampicin slightly decreases the exposure to antifungals, azoles (fluconazole). Adjust dose.
Unknown (143)
Abrocitinib - decreases exposure
Rifampicinispredictedtodecreasetheexposuretoabrocitinib. Avoid.oStudy
Afatinib - decreases exposure
Rifampicin is predicted to decrease the exposure to afatinib.
Agomelatine - decreases exposure
Rifampicinispredictedtodecreasetheexposureto agomelatine.oTheoretical
Alfentanil - decreases exposure
Rifampicin is predicted to decrease the exposure to opioids (alfentanil, fentanyl).
Aliskiren - decreases exposure
Rifampicin decreases the exposure to aliskiren.
Data from BNF 85 (British National Formulary). This is not a substitute for professional medical advice. Matched via: exact
About ethambutol
Ethambutol is a medication used to treat tuberculosis (TB), a serious lung infection.
What it treats
- tuberculosis (TB)
- lung infection
How it works
Ethambutol helps stop the growth of the bacteria that cause tuberculosis.
Who it's for
It is usually prescribed for people diagnosed with tuberculosis.
AI-assisted summary grounded in BNF data - general information only, not medical advice. Always confirm with your pharmacist or doctor.
About isoniazid
Isoniazid is a medication used to treat tuberculosis, a serious infection that mainly affects the lungs.
What it treats
- tuberculosis (TB)
- pulmonary tuberculosis
How it works
Isoniazid works by stopping the growth of bacteria that cause tuberculosis.
Who it's for
This medicine is for individuals diagnosed with tuberculosis.
Cautions
- • Be cautious if you are taking other medications that can harm the liver.
- • Be careful if you are using drugs that can cause nerve damage.
AI-assisted summary grounded in BNF data - general information only, not medical advice. Always confirm with your pharmacist or doctor.
About pyrazinamide
Pyrazinamide is a medicine used to treat tuberculosis (TB), an infectious disease that primarily affects the lungs.
What it treats
- tuberculosis (TB)
- pulmonary tuberculosis
How it works
It works by stopping the growth of the bacteria that cause TB.
Who it's for
This medicine is for individuals diagnosed with tuberculosis.
AI-assisted summary grounded in BNF data - general information only, not medical advice. Always confirm with your pharmacist or doctor.
About rifampicin
Rifampicin is an antibiotic used to treat bacterial infections, especially tuberculosis.
What it treats
- tuberculosis (TB)
- bacterial infections
How it works
Rifampicin works by stopping the growth of bacteria, helping to clear infections from the body.
Who it's for
Rifampicin is for adults and children who have specific bacterial infections, particularly those with tuberculosis.
AI-assisted summary grounded in BNF data - general information only, not medical advice. Always confirm with your pharmacist or doctor.
Clinical monograph: Pyrazinamide
BNF-referencedPyrazinamide is an antitubercular agent primarily used in the treatment of tuberculosis (TB). It is effective as part of a combination therapy to combat Mycobacterium tuberculosis, particularly in the initial phase of treatment. Pyrazinamide is known for its unique mechanism of action that is most effective in acidic environments, making it a valuable asset in TB treatment regimens.
Indications
- Tuberculosis, in combination with other drugs for the treatment of active tuberculosis
- Treatment of latent tuberculosis infection
Dosage
Children: Children (body-weight up to 50 kg): 50 mg
Adults: Adults (body-weight up to 50 kg): 2 g 3 times a week for 2 months (initial phase). Adults (body-weight 50 kg and above): 2.5 g 3 times a week for 2 months (initial phase).
Mechanism of action
Pyrazinamide diffuses into Mycobacterium tuberculosis where it is converted by the pyrazinamidase enzyme to its active form, pyrazinoic acid. This active form accumulates intracellularly, especially at acidic pH, which is characteristic of the environment in which the bacteria reside. Pyrazinoic acid inhibits fatty acid synthase (FAS) I, disrupting the synthesis of fatty acids necessary for the bacterium's growth and replication. Additionally, pyrazinoic acid may interfere with the bacterial membrane potential and energy production, further inhibiting the survival of M. tuberculosis.
Pharmacodynamics
Pyrazinamide exhibits bactericidal activity against Mycobacterium tuberculosis, effectively killing or inhibiting the growth of the bacteria responsible for tuberculosis. Its efficacy is enhanced in slightly acidic conditions, where it exerts its maximum effect. This drug is specific to M. tuberculosis and is typically utilized in combination with other antitubercular medications to ensure a comprehensive treatment approach.
Pharmacokinetics
Pyrazinamide is well absorbed when administered orally, with peak plasma concentrations reached within 1 to 2 hours after ingestion. It has a half-life of approximately 9 to 10 hours, allowing for convenient dosing schedules. The drug is metabolized primarily in the liver and is excreted through the kidneys, necessitating monitoring of hepatic function and renal function in patients receiving treatment.
Contra-indications
- Acute attack of gout in adults
Adverse effects
- Hepatotoxicity
- Gout
- Nausea
- Vomiting
- Fever
- Malaise
- Jaundice
Interactions
- Allopurinol: Unknown (increases risk of hyperuricaemia)
Precautions
- Hepatic disorders
- Diabetes
- Gout
- Renal impairment
Pregnancy
Manufacturer advises use only if potential benefits outweigh risks.
Breast-feeding
Amount too small to be harmful.
Storage
Store in a cool, dry place away from direct light.
Formulations
- 500 mg tablets
- Oral suspension
- Oral solution
AI-synthesized from BNF references - general information only, not a substitute for professional medical advice or the current BNF. Verify doses with a pharmacist.
Clinical monograph: Rifampicin
BNF-referencedRifampicin is a bactericidal antibiotic that is primarily used to treat infections caused by mycobacteria, particularly tuberculosis. It works by inhibiting RNA synthesis in bacteria, making it effective against both intracellular and extracellular strains of Mycobacterium tuberculosis. It is often used in combination with other antitubercular agents to prevent the development of drug resistance.
Indications
- Tuberculosis, in combination with other drugs
- Prevention of tuberculosis in susceptible close contacts
- Brucellosis in combination with other antibacterials
- Legionnaires disease in combination with other antibacterials
- Serious staphylococcal infections in combination with other antibacterials
- Endocarditis in combination with other drugs
Dosage
Children: For children aged 1–11 years: 10 mg/kg every 12 hours (maximum per dose 600 mg
Adults: 600 mg daily for 6 months, or 600 mg every 12 hours for 2 days in specific conditions such as endocarditis.
Mechanism of action
Rifampicin binds to the beta-subunit of microbial DNA-dependent RNA polymerase, inhibiting the enzyme and impeding RNA synthesis. This action forms a stable drug-enzyme complex that suppresses the initiation of chain formation in RNA synthesis, although it does not affect chain elongation. Importantly, rifampicin has no activity against mammalian RNA polymerase, highlighting its selective antibacterial properties.
Pharmacodynamics
Rifampicin exhibits broad-spectrum antimicrobial activity, particularly against Mycobacterium tuberculosis. It is bactericidal, effective in killing both intracellular and extracellular bacteria. The drug's efficacy is enhanced when used in combination with other antitubercular medications, helping to reduce the risk of developing multi-drug resistant tuberculosis.
Pharmacokinetics
Rifampicin is well absorbed after oral administration, with peak plasma concentrations occurring within 2 to 4 hours. It is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, and has a half-life of approximately 3 to 5 hours. The drug is excreted mainly in bile, with some renal excretion. It also has the potential to induce liver enzymes, which may affect the metabolism of co-administered drugs.
Contra-indications
- Acute porphyrias
- Jaundice
Adverse effects
- Nausea
- Vomiting
- Diarrhoea
- Abdominal discomfort
- Thrombocytopenia
- Leucopenia
- Acute kidney injury
- Adrenal insufficiency
- Agranulocytosis
- Discoloration of soft contact lenses
Interactions
- Severe interaction with atovaquone (increases exposure)
- Severe interaction with abemaciclib (decreases exposure)
- Severe interaction with acalabrutinib (decreases exposure)
- Severe interaction with anti-androgens (decreases exposure)
- Severe interaction with abiraterone (decreases exposure)
- Severe interaction with darolutamide (decreases exposure)
- Severe interaction with antiarrhythmics (decreases exposure)
- Severe interaction with disopyramide (decreases exposure)
- Severe interaction with dronedarone (decreases exposure)
- Severe interaction with isavuconazole (decreases exposure)
Pregnancy
Rifampicin should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breast-feeding
Rifampicin is excreted in breast milk. Caution is advised when administering to nursing mothers.
Storage
Store in a cool, dry place away from direct sunlight. Keep out of reach of children.
Formulations
- Oral capsules
- Oral suspension
- Injectable solution
AI-synthesized from BNF references - general information only, not a substitute for professional medical advice or the current BNF. Verify doses with a pharmacist.
Clinical monograph: Ethambutolhydrochloride
BNF-referencedEthambutol hydrochloride is an antitubercular agent primarily used for the treatment of tuberculosis, particularly in combination with other antitubercular drugs. It is effective against Mycobacterium tuberculosis and is often utilized in multidrug-resistant cases. Its mechanism involves inhibiting the synthesis of the bacterial cell wall, which is crucial for the survival of the bacteria.
Indications
- Tuberculosis, in combination with other drugs (standard treatment)
- Multiple-drug resistant pulmonary tuberculosis, in combination with other drugs
Dosage
Children: Child: 20 mg/kg once daily for 2 months (initial phase) or 30 mg/kg 3 times a week for 2 months (initial phase).
Adults: Adult: 15 mg/kg once daily for 2 months (initial phase) or 100 mg twice daily for 24 weeks, continue appropriate combination therapy after delamanid.
Mechanism of action
Ethambutol inhibits the enzyme arabinosyl transferase, which is involved in the biosynthesis of the mycobacterial cell wall component, arabinogalactan. This inhibition disrupts the integrity of the bacterial cell wall, leading to bacterial cell death.
Pharmacodynamics
Ethambutol exhibits bacteriostatic activity against M. tuberculosis. Its action is concentration-dependent, and effectiveness can be enhanced when used in combination with other antitubercular agents. Resistance can develop through mutations in the gene encoding arabinosyl transferase, leading to decreased drug efficacy.
Pharmacokinetics
Ethambutol is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 4 hours post-administration. The drug has a half-life of approximately 3 to 5 hours and is primarily excreted unchanged in urine. Dose adjustments may be necessary in patients with renal impairment, as the drug's clearance is significantly affected by renal function.
Contra-indications
- Optic neuritis
- Poor vision
Adverse effects
- Anxiety
- Appetite decreased
- Asthenia
- Chest pain
- Cough
- Depression
- Dyslipidaemia
- Dyspnoea
- Ear pain
- Electrolyte imbalance
- Gastrointestinal discomfort
- Haemoptysis
- Headache
- Hyperhidrosis
- Hypertension
- Hypotension
- Malaise
- Muscle weakness
- Nausea
- Oropharyngeal pain
Interactions
- Cycloserine
- Deltyba (Delamanid)
Precautions
- Monitor serum albumin and electrolytes before and during treatment
- Monitor blood-cycloserine concentration if creatinine clearance is less than 50 mL/min
- Use with caution in elderly and young children
- Patients should be able to report symptomatic visual changes accurately
Pregnancy
Manufacturer advises use only if potential benefit outweighs risk, as it crosses the placenta.
Breast-feeding
Present in milk, but amount is too small to be harmful.
Storage
Dispense in original container (contains desiccant).
Formulations
- Capsule
- Tablet
AI-synthesized from BNF references - general information only, not a substitute for professional medical advice or the current BNF. Verify doses with a pharmacist.
Clinical monograph: Isoniazid
BNF-referencedIsoniazid is an antimycobacterial agent used primarily in the treatment and prevention of tuberculosis (TB). It functions as a prodrug that requires activation by bacterial catalase, leading to inhibition of mycolic acid synthesis, an essential component of the mycobacterial cell wall. Isoniazid is effective against actively dividing Mycobacterium tuberculosis and is known for its specificity towards mycobacterial infections.
Indications
- Treatment of active tuberculosis
- Prevention of tuberculosis in susceptible individuals, especially close contacts of infected persons
Dosage
Adults: 10 mg/kg daily (maximum per dose 300 mg) for 3 months, to be taken by mouth or via intramuscular or intravenous
Mechanism of action
Isoniazid is activated by the bacterial catalase-peroxidase KatG, which reduces the ferric form of the enzyme and enables it to react with oxygen to form an oxyferrous enzyme complex. The active form of isoniazid then inhibits the synthesis of mycolic acids by forming a covalent adduct with NAD, inhibiting the enoyl reductase InhA. This inhibition is crucial for the integrity of the mycobacterial cell wall, leading to the bactericidal activity of isoniazid against actively growing Mycobacterium tuberculosis.
Pharmacodynamics
Isoniazid is a bactericidal agent particularly effective against the Mycobacterium genus, including M. tuberculosis, M. bovis, and M. kansasii. It exhibits bactericidal properties during periods of rapid mycobacterial growth and becomes bacteriostatic when the bacteria are in a dormant state. Given its mechanism of action, isoniazid is highly selective, targeting mycobacteria without significant effects on other types of bacteria.
Pharmacokinetics
Isoniazid is well-absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is widely distributed in body tissues and crosses the blood-brain barrier. The drug is metabolized in the liver primarily through acetylation, with variable metabolism rates observed in different populations due to genetic polymorphisms in acetylation. The elimination half-life ranges from 1 to 4 hours, and the drug is excreted in the urine, predominantly as metabolites.
Contra-indications
- History of hypersensitivity to isoniazid
- Acute liver disease
- Severe hepatic impairment
- Previous history of isoniazid-induced liver injury
Adverse effects
- Hepatitis
- Peripheral neuropathy
- Optic neuritis
- Gastrointestinal disturbances
- Rash
- Fever
- Agranulocytosis
- Hematological disorders
- Lupus-like syndrome
Interactions
- Carbamazepine: Increased risk of hepatotoxicity
- Cycloserine: Increased risk of CNS toxicity
- Phenytoin: Increased concentration of phenytoin
- Levodopa: Decreased effects of levodopa
- Lomitapide: Increased exposure
- Antiepileptics: Unknown interactions leading to increased concentrations
Precautions
- Monitor liver function during treatment
- Use with caution in patients with renal impairment
- Patients with diabetes or a history of peripheral neuropathy should be monitored closely
- Ocular monitoring for young children on treatment
Pregnancy
Not known to be harmful; however, prophylactic pyridoxine is recommended.
Breast-feeding
Amount too small to be harmful; monitor infant for possible toxicity.
Storage
Store in a cool, dry place away from direct sunlight. Keep out of reach of children.
Formulations
- Oral tablets
- Oral suspension
- Intramuscular injection
- Intravenous injection
AI-synthesized from BNF references - general information only, not a substitute for professional medical advice or the current BNF. Verify doses with a pharmacist.
Clinical monograph: ethambutol
BNF-referencedEthambutol is an antibiotic used primarily in the treatment of tuberculosis, particularly in conjunction with other anti-tuberculous agents. It acts by inhibiting the synthesis of components crucial for the bacterial cell wall, leading to decreased viability of the Mycobacterium tuberculosis. Ethambutol is classified as a bacteriostatic agent and is particularly effective during the cell division phase of the bacteria.
Indications
- Pulmonary tuberculosis
- Tuberculosis in combination therapy
Dosage
Children: For children, refer to the BNF for Children for appropriate dosing guidance.
Adults: The usual adult dose is 15 mg/kg daily, up to a maximum of 1.6 g per day, in combination with other anti-tuberculosis agents.
Mechanism of action
Ethambutol diffuses into Mycobacterium cells and inhibits the arabinosyltransferases (embA, embB, and embC). This inhibition prevents the formation of arabinogalactan and lipoarabinomannan, which are essential for the integrity of the bacterial cell wall. The resultant decrease in arabinogalactan reduces binding sites for mycolic acid, leading to its accumulation and consequently impairing cell division. Additionally, reduced levels of lipoarabinomannan interfere with the interaction of mycobacteria with host cells. Ethambutol's bacteriostatic action is effective only when the bacteria are actively dividing.
Pharmacodynamics
Ethambutol is indicated for use in combination with other anti-tuberculosis drugs for the treatment of pulmonary tuberculosis. Its long duration of action allows for daily administration, which is beneficial for patient adherence. However, it is important for patients to be informed about potential side effects, including the risk of optic neuritis and hepatic toxicity, which are associated with its use.
Pharmacokinetics
Ethambutol is well absorbed from the gastrointestinal tract, with a peak plasma concentration occurring approximately 2 to 4 hours after administration. It has a volume of distribution that suggests good tissue penetration. The drug is primarily excreted unchanged in the urine, with a half-life of about 3 to 4 hours in individuals with normal renal function. Dosage adjustments may be necessary in patients with renal impairment.
Contra-indications
- Optic neuritis
- Severe renal impairment
Adverse effects
- Optic neuritis
- Visual disturbances
- Nausea
- Vomiting
- Loss of appetite
- Rash
- Hepatic toxicity
Interactions
- Antacids may reduce absorption
- Aluminium-containing antacids may decrease ethambutol serum concentration
Precautions
- Regular monitoring of visual acuity is recommended
- Use with caution in patients with renal impairment
- Periodic liver function tests may be necessary
Pregnancy
Ethambutol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breast-feeding
Ethambutol is excreted in breast milk; caution should be exercised when administered to a nursing mother.
Storage
Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.
Formulations
- Tablets
- Oral suspension
AI-synthesized from BNF references - general information only, not a substitute for professional medical advice or the current BNF. Verify doses with a pharmacist.
Molecular reference: Isoniazid
PubChem CID 3767Molecular formula: C6H7N3O
Mechanism of action
Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular <i>Mycobacterium tuberculosis</i> organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from <i>Mycobacterium tuberculosis</i>, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA. Although the mechanism of action of isoniazid is unknown, several hypotheses have been proposed. These include effects on lipids, nucleic acid biosynthesis, and glycolysis. ... /It has been suggested that/ a primary action of isoniazid /is/ to inhibit the biosynthesis of mycolic acids, important constituents of the mycobacterial cell wall. Because mycolic acids are unique to mycobacteria, this action would explain the high degree of selectivity of the antimicrobial activity of isoniazid. Exposure to isoniazid leads to a loss of acid fastness and a decrease in the quantity of methanol-extractable lipid of the microorganisms. Isoniazid is bacteriostatic for "resting" bacilli but is bactericidal for rapidly dividing microorganisms. The minimal tuberculostatic concentration is 0.025 to 0.05 ug/ml.
Pharmacodynamics
Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically <i>M. tuberculosis</i>, <i>M. bovis</i> and <i>M. kansasii</i>. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal when mycobacteria grow rapidly and bacteriostatic when they grow slowly.
Biological pathways
Source: PubChem (NCBI) · pathways from PathBank, Reactome, WikiPathways & PharmGKB.
Molecular reference: Pyrazinamide
PubChem CID 1046Molecular formula: C5H5N3O
Mechanism of action
Pyrazinamide diffuses into active _M. tuberculosis_ that express pyrazinamidase enzyme that converts pyrazinamide to the active form pyrazinoic acid. Pyrazinoic acid can leak out under acidic conditions to be converted to the protonated conjugate acid, which is readily diffused back into the bacilli and accumulate intracellularly. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted. However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids. This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I. It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria. Pyrazinamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of the infection and the susceptibility of the infecting organism. In vitro and in vivo, the drug is active only at a slightly acidic pH. The exact mechanism of action of pyrazinamide has not been fully elucidated. The antimycobacterial activity of pyrazinamide appears to partly depend on conversion of the drug to pyrazinoic acid. Susceptible strains of Mycobacterium tuberculosis produce pyrazinamidase, an enzyme that deaminates pyrazinamide to pyrazinoic acid, and the in vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity. In vitro studies indicate that pyrazinoic acid has specific antimycobacterial activity against Mycobacterium tuberculosis. In addition, the fact that pyrazinoic acid lowers the pH of the environment below that which is necessary for growth of Mycobacterium tuberculosis appears to contribute to the drug's antimycobacterial activity in vitro. Unknown; pyrazinamide may be bacteriostatic or bactericidal, depending on its concentration and the susceptibility of the organism. It is active in vitro at an acidic pH of 5.6 or less, similar to that found in early, active tubercular inflammatory lesions.
Pharmacodynamics
Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only against <i>Mycobacterium tuberculosis</i>. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication.
Biological pathways
Source: PubChem (NCBI) · pathways from PathBank, Reactome, WikiPathways & PharmGKB.
Molecular reference: Rifampicin
PubChem CID 135398735Molecular formula: C43H58N4O12
Mechanism of action
Rifampin works by binding to the beta-subunit of microbial DNA-dependent RNA polymerase (RNAP), thereby inhibiting the enzyme and impeding RNA synthesis. It reduces the affinity of RNAP for short RNA transcripts. It has no activity against the mammalian RNAP enzyme. Although rifampin is most active during cell multiplication ... /it/ appears to have some effect on resting cells. Electron microscopy has revealed changes in cytoplasm and disappearance of ribosomes in tubercle bacilli exposed to rifampin, indicating inhibition of DNA-dependent RNA polymerase. Rifampin inhibits DNA-dependent RNA polymerase of mycobacteria and other microorganisms by forming a stable drug-enzyme complex, leading to suppression of initiation of chain formation (but not chain elongation) in RNA synthesis. More specifically, the beta subunit of this complex enzyme is the site of action of the drug, although rifampin binds only to the holoenzyme. Nuclear RNA polymerase from a variety of eukaryotic cells does not bind rifampin, and RNA synthesis is correspondingly unaffected. While rifampin can inhibit RNA synthesis in mammalian mitochondria, considerably higher concentrations of the drug are required than for the inhibition of the bacterial enzyme. High concentrations of rifamycin antibiotics also inhibit viral DNA-dependent RNA polymerases and reverse transcriptases. Rifampin is bactericidal for both intracellular and extracellular microorganisms. Developmental expression of CYPlAl, CYPlA2 and CYP3A6 in the rabbit have been studied. Cytochromes P450IAl, P450IA2 and P450IIIA6 exhibited comparable patterns of developmental expression. Present at low level (less than 0.05 mnol/ng) in the new born animal up to week 3, these proteins sharply accumulated between weeks 3 and 4 to reach a maximum by week 4 (P450IAl, 0.2 nmol/mg; P450IA2, 0.8 nmol/ng; P450IIIA6, 0.12 nmol/mg) and decr in the adult (P450IAl, 0.2 nmol/mg; P450IA2, 0.4 mnol/mg; P450IIIA6, 0.09 nmol/mg). Cytochromes P450IAl and P450IA2 were not expressed in the untreated fetus. Onset of CYP3A6 gene expression occurred at day 30 of gestation and both transcription and mRNA accumulation were transplacentally inducible by rifampicin only shortly before birth, i.e. after treatment of the females between days 28 and 30 of gestation. Both long (1.85 kb) and short (1.7 kb) mRNA transcripts were expressed in untreated or rifampicin treated fetuses. CYP3A6 gene expression was also induced by rifampicin in l week old and 2 week old animals. Developmental expression of CYPlAl and CYPlA2 genes was shown to be closely related to the diet change accompanying weaning which occurs at weeks 3-4. In animals subjected to either delayed (week 6) or early (week 2) weaning, sharp accumulation of messages, proteins and related activities were delayed or anticipated accordingly with respect to normal weaning. Artificially scheduled weaning gave similar results when repeated with biological grade lucern (grown in the absence of chemical fertilizers, pesticides) ... the main constituent of commercial rabbit chow. While CYP3A6 gene expression could be brought forward by early weaning at week 2, both message and protein did not exhibit incr accumulation after delayed weaning at week 6, and remained at the low level of the new born animal. Treatment of l week old and 2 week old animals with triiodothyronine or of 3 week old animals with propylthiouracil, an antithyroid factor, did not modify the normal pattern of developmental expression of genes CYPlAl, CYPlA2 and CYP3A6. ...
Pharmacodynamics
Rifampin is an antimicrobial agent with bactericidal effects and a broad-spectrum activity. It is active against intracellular and extracellular _Mycobacterium tuberculosis_.
Biological pathways
Source: PubChem (NCBI) · pathways from PathBank, Reactome, WikiPathways & PharmGKB.
Molecular reference: ethambutol
PubChem CID 14052Molecular formula: C10H24N2O2
Mechanism of action
Ethambutol diffuses into _Mycobacterium_ cells. Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division. Decreased concentrations of arabinogalactan in the cell wall reduces the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate. Lipoarabinomannan is a component of a cell surface molecule involved in the interaction with host cells. Reduced levels of lipoarabinomannan may interfere with mycobacterial interaction with host cells. Ethambutol is bacteriostatic in action. Although the exact mechanism of action has not been fully elucidated, the drug appears to inhibit the synthesis of one or more metabolites in susceptible bacteria resulting in impairment of cellular metabolism, arrest of multiplication, and cell death. Ethambutol is active against susceptible bacteria only when they are undergoing cell division.
Pharmacodynamics
Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis. It has a long duration of action as it is administered daily, and a moderate therapeutic window. Patients should be counselled regarding the risk of optic neuritis and hepatic toxicity.
Source: PubChem (NCBI) · pathways from PathBank, Reactome, WikiPathways & PharmGKB.
This drug in other countries
The same active ingredient registered across other registries we cover - including different brands.
- AKURIT · Nairobi Enterprises
- AKURIT 3 · Nairobi Enterprises
- AKURIT KID · Pharma Specialities
- AKURIT Z KID · Pharma Specialities
- AKURIT4 · Nairobi Enterprises
- AkuriT4 · Lupin Limited
- ETHAMBUTOL TABLETS (Each film-coated tablet contains Ethambutol Hydrochloride 400mg) · Cadila Pharmaceuticals
- Ethambutol Dispersible Tablets (Each film coated tablet contains Ethambutol HCL 100mg) · Macleods Pharmaceutical Ltd
- ISONIAZID DISPERSIBLE TABLETS (Each Dispersible tablet contains Isoniazid 100mg) · Oxalis Labs
- RIFAMPICIN + ISONIAZID TABLETS · Macleods Pharmaceuticals
- RIFAMPICIN ISONIAZID PYRAZINAMIDE TABLETS · Macleods Pharmaceuticals
- RIFAMPIN / ISONIAZID/ PYRIZINAMIDE TABLETS (Each tablet contains Rifampicin/Isoniazid/Pyrizinamide 75mg / 50mg/ 150mg) · Lupin