Interactions between Delavirdine and IsonaRif
2 drug interactions and 26 additional warnings found for the following 2 drugs:
- delavirdine
- IsonaRif (isoniazid/rifampin)
Drug interactions
Major drug interactions
Major:
rifAMPin isoniazid
Applies to: IsonaRif (isoniazid / rifampin) and IsonaRif (isoniazid / rifampin)
Monitor closely
The risk of hepatotoxicity is greater when rifampin and isoniazid (INH) are given concomitantly, than when either drug is given alone. The proposed mechanism is rifampin's induction of isoniazid hydrolase, an enzyme involved in the conversion of INH to isonicotinic acid and hydrazine. Hydrazine is the proposed toxic metabolite of INH, which has been shown in animal studies to cause steatosis, hepatocyte vacuolation and glutathione depletion. Some studies have also shown that slow acetylators have a two-fold increased risk of developing antituberculosis drug-induced hepatotoxicity (ATDH) as compared with fast acetylators due to more available INH for direct hydrolysis to hydrazine. Theoretically, a similar reaction may occur with rifabutin and isoniazid. Additional risk factors for developing hepatotoxicity include patients with advanced age, malnutrition, existing hepatic impairment, daily alcohol consumption, female gender, HIV infection, extra-pulmonary tuberculosis and/or patients who are taking other potent CYP450-inducing agents.
Management
Caution and close monitoring should be considered if isoniazid (INH) is coadministered with rifampin or rifabutin. In cases where coadministration is required, careful monitoring of liver function, especially ALT and AST, should be done at baseline and then every 2 to 4 weeks during therapy, or in accordance with individual product labeling. Some manufacturers of INH recommend strongly considering its discontinuation if serum aminotransferase concentrations (AST or SGOT, ALT or SGPT) exceed 3 to 5 times the upper limit of normal. Product labeling for rifampin also recommends the immediate discontinuation of therapy if hepatic damage is suspected. INH product labeling suggests alternate drugs be used if hepatitis is attributed to INH in patients with tuberculosis. However, if INH must be used, it should only be resumed after the patient's symptoms and laboratory abnormalities have cleared. It should also be restarted in very small, gradually increasing doses and immediately withdrawn if there is any indication of recurrent liver involvement. Patients should be counseled to immediately report signs or symptoms consistent with liver damage and notified that prodromal symptoms usually consist of fatigue, weakness, malaise, anorexia, nausea, and/or vomiting.
References (25)
- O'Brien RJ, Long MW, Cross FS, et al. (1983) "Hepatotoxicity from isoniazid and rifampin among children treated for tuberculosis." Pediatrics, 72, p. 491-9
- Kumar A, Misra PK, Mehotra R, et al. (1991) "Hepatotoxicity of rifampin and isoniazid." Am Rev Respir Dis, 143, p. 1350-2
- Abadie-Kemmerly S, Pankey GA, Dalvisio JR (1988) "Failure of ketoconazole treatment of blastomyces dermatidis due to interaction of isoniazid and rifampin." Ann Intern Med, 109, p. 844-5
- Acocella G, Bonollo L, Garimoldi M, et al. (1972) "Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease." Gut, 13, p. 47-53
- Yamamoto T, Suou T, Hirayama C (1986) "Elevated serum aminotransferase induced by isoniazid in relation to isoniazid acetylator phenotype." Hepatology, 6, p. 295-8
- Steele MA, Burk RF, Des Prez RM (1991) "Toxic hepatitis with isoniazid and rifampin." Chest, 99, p. 465-71
- "Product Information. INH (isoniazid)." Ciba Pharmaceuticals, Summit, NJ.
- Sarma G, Immanuel C, Kailasam S, Narayana AS, Venkatesan P (1986) "Rifampin-induced release of hydrazine from isoniazid." Am Rev Respir Dis, 133, p. 1072-5
- (2001) "Product Information. Mycobutin (rifabutin)." Pharmacia and Upjohn
- (2001) "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel
- Askgaard DS, Wilcke T, Dossing M (1995) "Hepatotoxicity caused by the combined action of isoniazid and rifampicin." Thorax, 50, p. 213-4
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- (2023) "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC.
- (2023) "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd
- (2023) "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB
- Sarma GR, Immanual C, Kailasam S, Narayana AS, Venkatesan P (2024) Rifampin-induced release of hydrazine from isoniazid. A possible cause of hepatitis during treatment of tuberculosis with regimens containing isoniazid and rifampin https://pubmed.ncbi.nlm.nih.gov/3717759/
- Tostmann A, Boeree MJ, Aarnoutse RE, De Lange WCM, Van Der Ven AJAM, Dekhuijzen R (2024) Antituberculosis drug-induced hepatotoxicity: concise up-to-date review https://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2007.05207.x
- (2021) "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc.
- (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
- (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
- (2023) "Product Information. Rifadin (rifampicin)." Sanofi
- (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
- (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.
Major:
rifAMPin delavirdine
Applies to: IsonaRif (isoniazid / rifampin) and delavirdine
Generally avoid
Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of delavirdine, which is primarily metabolized by the isoenzyme. In seven HIV-infected subjects, administration of delavirdine (400 mg three times a day for 30 days) in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily on days 16 thru 30) decreased mean delavirdine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by approximately 92%, 97% and 100%, respectively, compared to administration of delavirdine alone. Oral clearance of delavirdine also increased by nearly 27-fold in the presence of rifampin. When delavirdine (400 mg three times a day for 30 days) was given with rifabutin (300 mg once daily on days 16 thru 30) in seven HIV-positive subjects, mean delavirdine Cmax, AUC and Cmin decreased by about 75%, 84% and 95%, respectively, and oral clearance increased by approximately 5-fold. Likewise, population pharmacokinetic data from efficacy studies showed that delavirdine Cmin was reduced by approximately 90% in patients (n=8) treated with various dosages of phenytoin, phenobarbital, and/or carbamazepine who were given delavirdine 300 to 400 mg three times a day.
Management
Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of delavirdine with potent CYP450 3A4 inducers should generally be avoided.
References (6)
- Borin MT, Chambers JH, Carel BJ, Gagnon S, Freimuth WW (1997) "Pharmacokinetic study of the interaction between rifampin and delavirdine mesylate." Clin Pharmacol Ther, 61, p. 544-53
- (2001) "Product Information. Rescriptor (delavirdine)." Pharmacia and Upjohn
- Borin MT, Chambers JH, Carel BJ, Freimuth WW, Aksentijevich S, Piergies AA (1997) "Pharmacokinetic study of the interaction between rifabutin and delavirdine mesylate in HIV-1 infected patients." Antiviral Res, 35, p. 53-63
- Burman WJ, Jones BE (2001) "Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy." Am J Respir Crit Care Med, 164, p. 7-12
- Tran JQ, Gerber JG, Kerr BM (2001) "Delavirdine: clinical pharmacokinetics and drug interactions." Clin Pharmacokinet, 40, p. 207-26
- (2000) "Notice to readers: updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibiotrs." MMWR Morb Mortal Wkly Rep, 49, p. 185-9
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
rifAMPin Food/Lifestyle
Applies to: IsonaRif (isoniazid / rifampin)
Generally avoid
Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.
Adjust dosing interval
Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.
Management
The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.
References (6)
- (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
- (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
- (2023) "Product Information. Rifadin (rifampicin)." Sanofi
- (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
- Peloquin CA, Namdar R, Singleton MD, Nix DE (2024) Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/
- (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.
Moderate:
isoniazid Food/Lifestyle
Applies to: IsonaRif (isoniazid / rifampin)
Generally avoid
Concurrent use of isoniazid (INH) in patients who ingest alcohol daily may result in an increased incidence of both hepatotoxicity and peripheral neuropathy. The increase in hepatotoxicity may be due to an additive risk as both alcohol and INH are individually associated with this adverse reaction. INH-associated hepatotoxicity is believed to be due to an accumulation of toxic metabolites and may also be partly immune mediated, though the exact mechanisms are not universally agreed upon. INH is metabolized by N-acetyltransferase and CYP450 2E1. The rate of acetylation is genetically determined and generally classified as slow or rapid. Slow acetylators have been identified by some studies as having a higher risk of hepatotoxicity; therefore, this interaction may be more significant for patients who fall into this category. Other studies have postulated that alcohol-mediated CYP450 2E1 induction may play a role, as this isoenzyme is involved in INH metabolism and may be responsible for producing hepatotoxic metabolites. However, available literature is conflicting. The labeling for some INH products lists daily alcohol use or chronic alcoholism as a risk factor for hepatitis, but not all studies have found a significant association between alcohol use and INH-induced hepatotoxicity. Additionally, INH and alcohol are both associated with pyridoxine (B6) deficiency, which may increase the risk of peripheral neuropathy.
Generally avoid
Concomitant administration of isoniazid (INH) with foods containing tyramine and/or histamine may increase the risk of symptoms relating to tyramine- and/or histamine toxicity (e.g., headache, diaphoresis, flushing, palpitations, and hypotension). The proposed mechanism is INH-mediated inhibition of monoamine oxidase (MAO) and diamine oxidase (DAO), enzymes responsible for the metabolism of tyramine and histamine, respectively. Some authors have suggested that the reactions observed are mainly due to INH's effects on DAO instead of MAO or the amounts of histamine instead of tyramine present in the food. A Japanese case report recorded an example in 8 out of 25 patients on the tuberculosis ward who developed an accidental histamine poisoning after ingesting a fish paste (saury). Patients developed allergy-like symptoms, which started between 20 minutes and 2 hours after ingesting the food. A high-level of histamine (32 mg/100 g of fish) was confirmed in the saury paste and all 8 patients were both on INH and had reduced MAO concentrations. The 17 remaining patients were not on INH (n=5) or reported not eating the saury paste (n=12).
Adjust dosing interval
Administration with food significantly reduces oral isoniazid (INH) absorption, increasing the risk of therapeutic failure or resistance. The mechanism is unknown. Pharmacokinetic studies completed in both healthy volunteers (n=14) and tuberculosis patients (n=20 treatment-naive patients during days 1 to 3 of treatment) have resulted in almost doubling the time to reach INH's maximum concentration (tmax) and a reduction in isoniazid's maximum concentration (Cmax) of 42%-51% in patients who consumed high-fat or high-carbohydrate meals prior to INH treatment.
Management
The manufacturer of oral forms of isoniazid (INH) recommends administration on an empty stomach (i.e., 30 minutes before or 2 hours after meals). Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and INH concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with INH. Concomitant pyridoxine (B6) administration is also recommended to reduce the risk of peripheral neuropathy, with some authorities suggesting a dose of at least 10 mg/day. Patients should be advised to avoid foods containing tyramine (e.g., aged cheese, cured meats such as sausages and salami, fava beans, sauerkraut, soy sauce, beer, or red wine) or histamine (e.g., skipjack, tuna, mackerel, salmon) during treatment with isoniazid. Consultation of product labeling for combination products containing isoniazid and/or relevant guidelines may be helpful for more specific recommendations.
References (17)
- Smith CK, Durack DT (1978) "Isoniazid and reaction to cheese." Ann Intern Med, 88, p. 520-1
- Dimartini A (1995) "Isoniazid, tricyclics and the ''cheese reaction''." Int Clin Psychopharmacol, 10, p. 197-8
- Uragoda CG, Kottegoda SR (1977) "Adverse reactions to isoniazid on ingestion of fish with a high histamine content." Tubercle, 58, p. 83-9
- Self TH, Chrisman CR, Baciewicz AM, Bronze MS (1999) "Isoniazid drug and food interactions." Am J Med Sci, 317, p. 304-11
- (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
- (2023) "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC.
- (2023) "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd
- (2023) "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB
- Saukkonen JJ, Cohn DL, Jasmer RM, et al. (2006) "An official ATS statement: hepatotoxicity of antituberculosis therapy." Am J Respir Crit Care Med, 174, p. 935-52
- Bouazzi OE, Hammi S, Bourkadi JE, et al. (2024) First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326068/
- Wang P, Pradhan K, Zhong XB, Ma X (2016) "Isoniazid metabolism and hepatoxicity." Acta Pharm Sin B, 6, p. 384-92
- Saktiawati AM, Sturkenboom MG, Stienstra Y, et al. (2016) "Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment naive TB patients: a randomized cross-over trial." J Antimicrob Chemother, 71, p. 703-10
- Hahn JA, Ngabirano C, Fatch R, et al. (2023) "Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use." AIDS, 37, p. 1535-43
- Huang YS, Chern HD, Su WJ, et al. (2003) "Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis." Hepatology, 37, p. 924-30
- Sousou JM, Griffith EM, Marsalisi C, Reddy P (2024) Pyridoxine deficiency and neurologic dysfunction: an unlikely association. https://www.cureus.com/articles/188310-pyridoxine-deficiency-and-neurologic-dysfunction-an-unlikely-association?score_article=true#!/
- Miki M, Ishikawa T, Okayama H (2005) "An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward." Intern Med, 44, p. 1133-6
- (2021) "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc.
Disease interactions
24 potential interactions Applies to: 19 conditions, including Underactive Thyroid, Peripheral Neuropathy, HIV-1 Infection, Hyperthyroidism, and Diabetes Mellitus.
Achlorhydria
Moderate:
delavirdine
Delavirdine has a moderate potential interaction with Achlorhydria.
Patients with achlorhydria should take delavirdine with an acidic beverage such as orange or cranberry juice, presumably to improve absorption. Although the effects of acidic beverages on delavirdine absorption have not been studied, delavirdine is known to be poorly soluble when pH is greater than 3.
Adrenal Insufficiency
Moderate:
IsonaRif
The rifAMPin in IsonaRif has a moderate potential interaction with Adrenal Insufficiency.
Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.
Alcoholism
Major:
IsonaRif
The isoniazid in IsonaRif has a major potential interaction with Alcoholism.
Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.
Major:
IsonaRif
The isoniazid in IsonaRif has a major potential interaction with Alcoholism.
The use of isoniazid is contraindicated in patients with a history of hepatic injury due to this drug and acute liver disease of any etiology. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. This drug has been associated with severe and sometimes fatal hepatitis, which may occur even after many months of therapy. In a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Epidemiologic studies indicate an increased incidence with increasing age, alcohol use, and female gender. As a precautionary measure, routine monitoring of serum transaminases (SGOT, SGPT) and bilirubin may be considered, although a transient and harmless increase in serum transaminase reportedly occurs in 10% to 20% of patients, usually in the first 3 months of therapy. Patients should be advised to promptly discontinue isoniazid therapy and seek medical attention if they experience signs or symptoms suggestive of liver damage such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Reinstitution of the drug should occur only after symptoms and laboratory abnormalities resolve, with low and gradually increasing dosages.
Major:
IsonaRif
The rifAMPin in IsonaRif has a major potential interaction with Alcoholism.
The use of rifampin has been associated with hepatocellular injury and liver dysfunction. Hepatitis and jaundice resulting in death have occurred, mostly in patients with underlying liver disease and during coadministration with other hepatotoxic agents including other antituberculous drugs such as isoniazid and pyrazinamide. Therapy with rifampin should be administered cautiously and under strict medical supervision in patients with liver disease or a history of alcoholism. Serum transaminases (ALT, AST) and bilirubin should be measured at baseline and every 2 to 4 weeks during therapy, but keeping in mind that elevated levels may occur transiently in 10% to 15% of patients, usually during the early days of treatment. Patients should be instructed to discontinue the drug promptly and seek medical attention if signs and symptoms of hepatic injury develop, including fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.
Bone Marrow Depression/Low Blood Counts
Major:
IsonaRif
The rifAMPin in IsonaRif has a major potential interaction with Bone Marrow Depression/Low Blood Counts.
Rifampin may infrequently cause hematopoietic abnormalities such as thrombocytopenia, leukopenia, decreased hemoglobin, and acute hemolytic anemia. Hemolysis has been described as part of an immune-mediated reaction which generally occurs after gaps in therapy. Thrombocytopenia is observed most frequently in patients receiving high-dose intermittent therapy or after a lapse in therapy, but very rarely during daily administration. It is reversible if rifampin is discontinued as soon as purpura appears. Patients with preexisting bone marrow depression or blood dyscrasias should be monitored closely during rifampin therapy for further decreases in blood counts. Although rifampin-related hematologic effects are often transient, cerebral hemorrhage and fatalities have been reported with the continued administration of rifampin after the appearance of purpura.
Diabetes Mellitus
Major:
IsonaRif
The isoniazid in IsonaRif has a major potential interaction with Diabetes Mellitus.
Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.
Hemodialysis
Moderate:
IsonaRif
The isoniazid in IsonaRif has a moderate potential interaction with Hemodialysis.
Isoniazid is substantially removed by hemodialysis and should be administered after dialysis.
HIV-1 Infection
Moderate:
IsonaRif
The isoniazid in IsonaRif has a moderate potential interaction with HIV-1 Infection.
Caution and close monitoring is advised when using isoniazid in patients with HIV seropositive patients. Patients with pulmonary tuberculosis and HIV infection may have problems with malabsorption. Screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of multi-drug resistant tuberculosis.
Hyperadrenocorticism
Moderate:
IsonaRif
The rifAMPin in IsonaRif has a moderate potential interaction with Hyperadrenocorticism.
Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.
Hyperparathyroidism
Moderate:
IsonaRif
The rifAMPin in IsonaRif has a moderate potential interaction with Hyperparathyroidism.
Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.
Hyperthyroidism
Moderate:
IsonaRif
The rifAMPin in IsonaRif has a moderate potential interaction with Hyperthyroidism.
Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.
Hypoparathyroidism
Moderate:
IsonaRif
The rifAMPin in IsonaRif has a moderate potential interaction with Hypoparathyroidism.
Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.
Liver Disease
Major:
IsonaRif
The rifAMPin in IsonaRif has a major potential interaction with Liver Disease.
The use of rifampin has been associated with hepatocellular injury and liver dysfunction. Hepatitis and jaundice resulting in death have occurred, mostly in patients with underlying liver disease and during coadministration with other hepatotoxic agents including other antituberculous drugs such as isoniazid and pyrazinamide. Therapy with rifampin should be administered cautiously and under strict medical supervision in patients with liver disease or a history of alcoholism. Serum transaminases (ALT, AST) and bilirubin should be measured at baseline and every 2 to 4 weeks during therapy, but keeping in mind that elevated levels may occur transiently in 10% to 15% of patients, usually during the early days of treatment. Patients should be instructed to discontinue the drug promptly and seek medical attention if signs and symptoms of hepatic injury develop, including fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.
Major:
IsonaRif
The rifAMPin in IsonaRif has a major potential interaction with Liver Disease.
Rifampin is primarily metabolized by the liver. Patients with liver disease may be at greater risk for adverse effects from rifampin due to decreased drug clearance. In addition, the accumulation of rifampin may result in hyperbilirubinemia because rifampin competes with bilirubin for uptake by hepatocytes. Dosage adjustments are recommended in patients with liver disease. Withdrawal of rifampin therapy may be required if serum bilirubin is persistently high.
Major:
IsonaRif
The isoniazid in IsonaRif has a major potential interaction with Liver Disease.
The use of isoniazid is contraindicated in patients with a history of hepatic injury due to this drug and acute liver disease of any etiology. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. This drug has been associated with severe and sometimes fatal hepatitis, which may occur even after many months of therapy. In a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Epidemiologic studies indicate an increased incidence with increasing age, alcohol use, and female gender. As a precautionary measure, routine monitoring of serum transaminases (SGOT, SGPT) and bilirubin may be considered, although a transient and harmless increase in serum transaminase reportedly occurs in 10% to 20% of patients, usually in the first 3 months of therapy. Patients should be advised to promptly discontinue isoniazid therapy and seek medical attention if they experience signs or symptoms suggestive of liver damage such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Reinstitution of the drug should occur only after symptoms and laboratory abnormalities resolve, with low and gradually increasing dosages.
Moderate:
delavirdine
Delavirdine has a moderate potential interaction with Liver Disease.
Delavirdine is primarily metabolized by the liver. Patients with liver disease may be at greater risk for toxicities and adverse effects from delavirdine due to decreased drug clearance. Therapy with delavirdine should be administered cautiously in patients with liver disease.
Malnourishment
Major:
IsonaRif
The isoniazid in IsonaRif has a major potential interaction with Malnourishment.
Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.
Noninfectious Colitis
Major:
IsonaRif
The rifAMPin in IsonaRif has a major potential interaction with Noninfectious Colitis.
Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.
Panhypopituitarism
Moderate:
IsonaRif
The rifAMPin in IsonaRif has a moderate potential interaction with Panhypopituitarism.
Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.
Peripheral Neuropathy
Major:
IsonaRif
The isoniazid in IsonaRif has a major potential interaction with Peripheral Neuropathy.
Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.
Porphyria
Major:
IsonaRif
The rifAMPin in IsonaRif has a major potential interaction with Porphyria.
Rifampin may induce the activity of delta amino levulinic acid synthetase, an enzyme involved in the biosynthesis of porphyrins. The use of rifampin has been associated with isolated cases of porphyria exacerbation. Therapy with rifampin should be administered cautiously in patients with a history of porphyria.
Renal Dysfunction
Moderate:
IsonaRif
The isoniazid in IsonaRif has a moderate potential interaction with Renal Dysfunction.
Isoniazid may cause cerebellar syndrome in patients with chronic kidney disease. Patients with end-stage renal disease have been reported to have an increased risk of developing tuberculosis. Careful monitoring is recommended if this drug is used in patients with severe renal dysfunction. Dosage adjustments in renal impairment are generally not necessary except in slow acetylators with a creatinine clearance below 10 mL/min. Approximately 50% of Blacks and Caucasians are slow acetylators, and most Eskimos and Asians are rapid acetylators.
Underactive Thyroid
Moderate:
IsonaRif
The rifAMPin in IsonaRif has a moderate potential interaction with Underactive Thyroid.
Rifampin has enzyme-inducing effects that can enhance the metabolism of many endogenous substrates, including adrenal hormones, thyroid hormones, and vitamin D, the latter of which may affect serum calcium, phosphate and parathyroid hormone levels. Patients with preexisting imbalances of these hormones should be monitored more closely during long-term therapy with rifampin. In patients whose hormonal condition is stabilized on treatment, adjustments may be necessary in their treatment regimen to compensate for these effects.
More resources
delavirdine
A total of 538 drugs are known to interact with delavirdine.
- Delavirdine is in the drug class NNRTIs.
- Delavirdine is used to treat HIV-1 Infection.
IsonaRif
A total of 989 drugs are known to interact with IsonaRif.
- Isonarif is in the drug class antituberculosis combinations.
- Isonarif is used to treat Tuberculosis, Active.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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