Drug Interactions between efavirenz and isoniazid / rifampin
This report displays the potential drug interactions for the following 2 drugs:
- efavirenz
- isoniazid/rifampin
Interactions between your drugs
rifAMPin isoniazid
Applies to: isoniazid / rifampin and 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 It should also be restarted in very small, gradually increasing doses and immediately withdrawn if there is any indication of recurrent liver involvement.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
- 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.
rifAMPin efavirenz
Applies to: isoniazid / rifampin and efavirenz
ADJUST DOSE: Coadministration with rifampin may decrease the plasma concentrations of efavirenz. The mechanism is rifampin induction of efavirenz metabolism via CYP450 3A4. In 8 HIV-infected subjects, administration of antiretroviral treatment including efavirenz (600 mg once daily) in combination with an antituberculosis regimen containing rifampin (480 to 720 mg/day based on body weight) for 7 days resulted in decreased mean efavirenz peak plasma concentration (Cmax), systemic exposure (AUC) and trough concentration (Cmin) by 24%, and 22% and 25%, respectively, compared to administration with nonrifampin antituberculosis agents. These differences were not statistically significant, and given the large interpatient variability in the pharmacokinetics of efavirenz observed in the study, the clinical relevance of these modest changes is unknown. Differences in bodyweight appeared to cause further variations in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing less than 50 kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis, whereas plasma concentrations in patients weighing 50 kg or more were almost halved compared to those observed in the lighter patients. In the same study, it was demonstrated in another eight subjects that plasma concentrations of efavirenz 800 mg/day in the presence of rifampin were similar to those of efavirenz 600 mg/day without rifampin. Efavirenz had no significant effect on the pharmacokinetics of rifampin. Likewise, the manufacturer reports that when efavirenz 600 mg/day was coadministered with rifampin 600 mg/day for seven days in 12 subjects, efavirenz Cmax, AUC and Cmin decreased by 20%, 26% and 32%, respectively. In another study consisting of 84 HIV-infected Thai patients (mean body weight approximately 50 kg) receiving at least one month of rifampin for active tuberculosis, the median plasma concentration of efavirenz was similar in patients treated with efavirenz 600 mg/day compared to patients treated with efavirenz 800 mg/day as part of their antiretroviral regimen. There was no significant difference in the time to virologic success (HIV RNA below 50 copies/mL). A follow-up study at 48 weeks also found no significant difference in the virological and immunological outcomes between the two groups. Whether these results are applicable to other ethnic populations with greater body weights is unknown. Interestingly, one group of investigators found an increased incidence of toxicity in patients receiving efavirenz 800 mg/day in combination with antituberculous therapy containing rifampin. In this population, 7 of 9 patients developed clinical toxicity (e.g., anxiety, depression, hepatitis) in association with significantly elevated efavirenz trough levels beyond the therapeutic range. Six of the seven patients who developed toxicity were of African descent.
MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity such as rifampin may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.
MANAGEMENT: Some authorities (US manufacturer of Rifadin) recommend avoiding concomitant use of rifampin and efavirenz. If concomitant use is unavoidable, clinicians should be aware that the optimal dosage of efavirenz in combination with rifampin is unknown. Limited data suggest that the usual dosage of 600 mg once daily may be adequate and appropriate in settings of limited resources or where cost is otherwise a concern. Some experts, as well as the efavirenz manufacturer, recommend increasing the dosage of efavirenz to 800 mg once daily when it is coadministered with rifampin in patients weighing 50 kg or more. Because toxicity may be increased with the higher dosage, therapeutic drug monitoring is also recommended. Rifampin can be used with efavirenz without dosage modification. However, interactions with other antiretroviral agents in the regimen (e.g., protease inhibitors) may preclude the use of rifampin or necessitate modification of the existing antiretroviral regimen. In general, treatment of tuberculosis (TB) in the context of antiretroviral therapy is complex and requires an individualized approach. Experts in the treatment of HIV-related TB should be consulted, and TB and HIV care providers should work in close coordination throughout treatment. Due to the potential for additive risk of hepatic injury, patients receiving both efavirenz and rifampin should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, light-colored stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.
References
- (2001) "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel
- (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
- Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T (2001) "Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients." Aids, 15, p. 71-5
- 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
- (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
- Lopez-Cortes LF, Ruiz-Valderas R, Viciana P, et al. (2002) "Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis." Clin Pharmacokinet, 41, p. 681-90
- American Thoracic Society, CDC, Infectious Diseases Society of America (2003) "Treatment of tuberculosis." MMWR Morb Mortal Wkly Rep, 52(RR-11), p. 1-77
- Brennan-Benson P, Lyus R, Harrison T, Pakianathan M, Macallan D (2005) "Pharmacokinetic interactions between efavirenz and rifampicin in the treatment of HIV and tuberculosis: one size does not fit all." AIDS, 19, p. 1541-1543
- Manosuthi W, Sungkanuparph S, Thakkinstian A, et al. (2005) "Efavirenz levels and 24-week efficacy in HIV-infected patients with tuberculosis receiving highly active antiretroviral therapy and rifampicin." AIDS, 19, p. 1481-6
- Manosuthi W, Kiertiburanakul S, Sungkanuparph S, et al. (2006) "Efavirenz 600 mg/day versus efavirenz 800 mg/day in HIV-infected patients with tuberculosis receiving rifampicin: 48 weeks results." AIDS, 20, p. 131-132
isoniazid efavirenz
Applies to: isoniazid / rifampin and efavirenz
MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.
MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.
References
- (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
- Elsharkawy AM, Schwab U, McCarron B, et al. (2013) "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol, 58, p. 331-3
Drug and food interactions
rifAMPin food
Applies to: 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
- (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.
isoniazid food
Applies to: 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
- 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.
efavirenz food
Applies to: efavirenz
ADJUST DOSING INTERVAL: Administration with food increases the plasma concentrations of efavirenz and may increase the frequency of adverse reactions. According to the product labeling, administration of efavirenz capsules (600 mg single dose) with a high-fat/high-caloric meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced-fat/normal-caloric meal (440 kcal, 2 g fat, 4% calories from fat) was associated with mean increases of 39% and 51% in efavirenz peak plasma concentration (Cmax) and 22% and 17% in systemic exposure (AUC), respectively, compared to administration under fasted conditions. For efavirenz tablets, administration of a single 600 mg dose with a high-fat/high-caloric meal (approximately 1000 kcal, 500-600 kcal from fat) resulted in a 79% increase in mean Cmax and a 28% increase in mean AUC of efavirenz relative to administration under fasted conditions.
MANAGEMENT: Efavirenz should be taken on an empty stomach, preferably at bedtime. Dosing at bedtime may improve the tolerability of nervous system symptoms such as dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations, although they often resolve on their own after the first 2 to 4 weeks of therapy . Patients should be advised of the potential for additive central nervous system effects when efavirenz is used concomitantly with alcohol or psychoactive drugs, and to avoid driving or operating hazardous machinery until they know how the medication affects them.
References
- (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
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. |
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