(eye soe NYE a zid)
- Isonicotinic Acid Hydrazide
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Generic: 100 mg/mL (10 mL)
Generic: 50 mg/5 mL (473 mL)
Generic: 100 mg, 300 mg
- Antitubercular Agent
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 Mycobacterium tuberculosis organisms.
Oral, IM: Rapid and complete; food reduces rate and extent of absorption
All body tissues and fluids including CSF
Hepatic to acetylisoniazid with decay rate determined genetically by acetylation phenotype; undergoes further hydrolysis to isonicotinic acid and acetylhydrazine
Urine (75% to 95% as unchanged drug and metabolites); small amounts excreted in feces and saliva
Time to Peak
Serum: 1 to 2 hours
May be prolonged in patients with impaired hepatic function or severe renal impairment
Fast acetylators: 30 to 100 minutes; Slow acetylators: 2 to 5 hours
10% to 15%
Use: Labeled Indications
Active tuberculosis infections: Treatment of susceptible active tuberculosis (eg, Mycobacterium tuberculosis) infections.
Latent tuberculosis infection (LTBI): Treatment of LTBI caused by Mycobacterium tuberculosis (also referred to as prophylaxis or preventive therapy). Note: To identify candidates for LTBI treatment, refer to CDC guidelines (http://www.cdc.gov/tb/publications/ltbi/pdf/TargetedLTBI.pdf) for current recommendations.
Off Label Uses
Treatment of nontuberculous mycobacterium (eg. M. kansasii)
Based on the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) Diagnosis, Treatment and Prevention of Nontuberculous Mycobacterial Diseases guidelines, isoniazid given as combination therapy for the treatment of nontuberculous mycobacterium (eg. M. kansasii) is effective and recommended in the management of this condition.
Hypersensitivity to isoniazid or any component of the formulation, including drug-induced hepatitis; acute liver disease; previous history of hepatic injury during isoniazid therapy; previous severe adverse reaction (drug fever, chills, arthritis) to isoniazid
Tuberculosis, active (drug susceptible): Oral, IM: Note: Always administer in combination with other antitubercular drugs. Concomitant pyridoxine is also recommended in any patient at risk for neuropathy (eg, patients with HIV infection, diabetes, alcoholism, nutritional deficiency, chronic renal failure, advanced age) (Nahid 2016).
ATS/CDC/IDSA Drug-susceptible tuberculosis guideline recommendations (Nahid 2016):
Once-daily therapy: 5 mg/kg/dose (usual dose: 300 mg) once daily Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days per week administration by directly observed therapy (DOT) is an acceptable alternative.
Three-times-weekly DOT: 15 mg/kg/dose (usual dose: 900 mg) administered 3 times weekly
Twice-weekly DOT: 15 mg/kg/dose (usual dose: 900 mg) administered twice weekly
Once-weekly DOT: 15 mg/kg/dose (usual dose: 900 mg) administered once weekly
Regimens: Treatment regimens for pulmonary tuberculosis and tuberculous meningitis consist of an initial 2-month phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of isoniazid and rifampin for pulmonary tuberculosis and a continuation phase of an additional 7 to 10 months of isoniazid and rifampin for tuberculous meningitis (optimal duration is not defined although continuation phase must continue for a minimum of 7 additional months). Adjunctive corticosteroid therapy (eg, dexamethasone, prednisolone) tapered over 6 to 8 weeks is also recommended for tuberculous meningitis. Isoniazid frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive TB guidelines (Nahid 2016).
Tuberculosis, latent infection (LTBI): Oral, IM: Note: Concomitant administration of pyridoxine 10 to 50 mg daily is recommended in malnourished patients or those prone to neuropathy (eg, patients with HIV-infection, diabetes or chronic alcohol abusers).
CDC recommendations (CDC 2013):
Non-HIV exposed/infected: 5 mg/kg (maximum: 300 mg per dose) once daily for 6 or 9 months or 15 mg/kg (maximum: 900 mg per dose) twice weekly for 6 or 9 months. Note: 9 months is optimal; 6 months may be considered to reduce costs of therapy and improve adherence.
HIV-exposed/-infected patients who are receiving antiretroviral therapy: 5 mg/kg (maximum: 300 mg per dose) once daily for 9 months or 15 mg/kg (maximum: 900 mg per dose) twice weekly for 9 months. Note: LTBI treatment is recommended in HIV-infected patients testing positive for LTBI (but have no evidence of TB disease and no history of treatment for active or LTBI) or in HIV-infected close contacts of anyone who has infectious TB (regardless of screening tests for LTBI). LTBI treatment is not associated with clinical benefit or recommended in HIV infected patients who are anergic and who have not had recent contact with anyone with infectious TB (HHS [OI adult 2015])
Alternate regimen: 15 mg/kg/dose (maximum 900 mg) once weekly in combination with rifapentine for 12 weeks. Note: The rifapentine-containing regimen may only be used in patients who are not pregnant and/or not expecting to become pregnant; if used in HIV-infected patients, it may only be used in otherwise healthy HIV-infected patients not receiving antiretroviral therapy (ART) (high risk of drug-drug interactions with rifapentine) (CDC 2013; HHS [adult] 2015).
Nontuberculous mycobacterium (M. kansasii) (off-label use): 5 mg/kg/day (maximum: 300 mg daily) for duration to include 12 months of culture-negative sputum; typically used in combination with ethambutol and rifampin (Griffith 2007).
Refer to adult dosing.
Tuberculosis, active (drug-susceptible) (excludes meningitis): Oral, IM: Use as part of a multidrug regimen:
ATS/CDC/IDSA Drug-susceptible tuberculosis guideline recommendations (Nahid 2016):
Once-daily therapy: Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days-per-week administration by directly observed therapy (DOT) is an acceptable alternative.
Infants, Children and Adolescents <15 years and ≤40 kg: 10 to 15 mg/kg/dose once daily; maximum dose: 300 mg/dose
Children and Adolescents <15 years and >40 kg and Adolescents ≥15 years: 5 mg/kg/dose once daily (typical dose: 300 mg)
Three-times-weekly DOT: Note: Although suggested dosing based on experience with twice-weekly regimen; experts suggest 3-times-weekly regimens are more effective than twice-weekly DOT regimens; 3-times-weekly DOT may be used as part of an intensive phase and/or continuation phase dosing regimen; consult guidelines for specific information.
Infants, Children and Adolescents <15 years, weighing ≤40 kg: 20 to 30 mg/kg/dose 3 times weekly; maximum dose: 900 mg/dose; in adolescents, some experts would use 15 mg/kg/dose (maximum dose: 900 mg/dose)
Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: 15 mg/kg/dose 3 times weekly (typical dose: 900 mg)
Regimens: Treatment regimens for pulmonary tuberculosis consist of an initial 2-month phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of isoniazid and rifampin. Isoniazid frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive TB guidelines (Nahid 2016).
Tuberculosis, latent infection (LTBI):
Infants and Children <12 years: Oral, IM:
CDC recommendation (CDC 2013): 10 to 20 mg/kg/day once daily (maximum: 300 mg per dose)(preferred regimen) or 20 to 40 mg/kg (maximum: 900 mg per dose) twice weekly for 9 months.
Note: Once weekly regimen of isoniazid and rifapentine may also be considered in children ≥2 or <12 years if completion of 9 month regimen (preferred) is unlikely and the hazard of tuberculosis is great (CDC 2013). Refer to Children ≥ 12 years and Adolescents dosing.
Alternate recommendations (Red Book [AAP 2012]): 10 to 15 mg/kg/day once daily (maximum: 300 mg per dose) for 9 months.
Children ≥12 years and Adolescents: Oral, IM:
CDC recommendations (CDC 2013): 10 to 20 mg/kg/day once daily (maximum: 300 mg per dose) (preferred regimen) or 20 to 40 mg/kg (maximum: 900 mg per dose) twice weekly for 9 months (CDC 2013), or 15 mg/kg/dose (maximum: 900 mg per dose) once weekly in combination with rifapentine for 12 weeks (CDC 2013). Note: The rifapentine-containing regimen may be used in otherwise healthy HIV-infected patients, but only in patents not receiving antiretroviral therapy (ART) (CDC 2013; HHS [adult] 2015).
Alternate recommendation (Red Book [AAP 2012]): 10 to 15 mg/kg/day once daily (maximum: 300 mg per dose) for 9 months
Dosing: Renal Impairment
Manufacturer’s labeling: There are no dosage adjustments provided in the manufacturer's labeling; use with caution in severe impairment.
Alternate recommendations: Adults:
CrCl <30 mL/minute: Treatment of drug-susceptible TB: 300 mg once daily or 900 mg administered 3 times weekly (Nahid 2016)
ESRD receiving intermittent hemodialysis (IHD):
Administer dose postdialysis (Aronoff 2007; Nahid 2016); Dialyzable (50% to 100%);
Treatment of drug-susceptible TB: 300 mg once daily or 900 mg administered 3 times weekly (Nahid 2016)
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling; however, use with caution, may accumulate and additional liver damage may occur in patients with preexisting liver disease. Contraindicated in patients with acute liver disease or previous isoniazid-associated hepatic injury. For ALT or AST >3 times the ULN: discontinue or temporarily withhold treatment. Treatment with isoniazid for latent tuberculosis infection should be deferred in patients with acute hepatic diseases.
Note: Commercial oral solution is available (50 mg/5 mL)
A 10 mg/mL oral suspension may be made with tablets, purified water, and sorbitol. Crush ten 100 mg tablets in a mortar and reduce to a fine powder. Add 10 mL of purified water and mix to a uniform paste. Mix while adding sorbitol in incremental proportions to almost 100 mL; transfer to a graduated cylinder, rinse mortar with sorbitol, and add quantity of sorbitol sufficient to make 100 mL (do not use sugar-based solutions). Label "shake well" and "refrigerate". Stable for 21 days refrigerated.Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Oral: Do not administer with food (bioavailability is decreased).
Intramuscular: IM injection may be used for patients who are unable to either take or absorb oral therapy. Inject deep IM into a large muscle mass.
Do not take with food; avoid tyramine- and/or histamine-containing foods. Increase dietary intake of folate, niacin, magnesium.
Tablet: Store at 20°C to 25°C (68°F to 77°F). Protect from moisture and light.
Oral solution: Store at 15°C to 30°C (59°F to 86°F). Protect from light.
Injection: Store at 20°C to 25°C (68°F to 77°F). Protect from light. Isoniazid injection may crystallize at low temperatures. If this occurs, warm the vial to room temperature before use to redissolve the crystals.
Acetaminophen: Isoniazid may enhance the adverse/toxic effect of Acetaminophen. Monitor therapy
Antacids: May decrease the absorption of Isoniazid. Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Artesunate: CYP2A6 Inhibitors may decrease serum concentrations of the active metabolite(s) of Artesunate. CYP2A6 Inhibitors may increase the serum concentration of Artesunate. Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
CarBAMazepine: May enhance the hepatotoxic effect of Isoniazid. Isoniazid may increase the serum concentration of CarBAMazepine. Monitor therapy
Chlorzoxazone: Isoniazid may increase the serum concentration of Chlorzoxazone. Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy
Corticosteroids (Systemic): May decrease the serum concentration of Isoniazid. Monitor therapy
CycloSERINE: Isoniazid may enhance the adverse/toxic effect of CycloSERINE. Specifically, CNS toxicity may be enhanced. Monitor therapy
CYP2A6 Substrates: CYP2A6 Inhibitors (Moderate) may decrease the metabolism of CYP2A6 Substrates. Monitor therapy
CYP2E1 Substrates: CYP2E1 Inhibitors (Moderate) may decrease the metabolism of CYP2E1 Substrates. Monitor therapy
Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Monitor therapy
Disulfiram: May enhance the adverse/toxic effect of Isoniazid. Disulfiram may increase the serum concentration of Isoniazid. Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
Ethionamide: May increase the serum concentration of Isoniazid. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Fosphenytoin: Isoniazid may increase the serum concentration of Fosphenytoin. Management: Consider alternatives. If concomitant therapy cannot be avoided, monitor for increased phenytoin concentrations/effects with isoniazid initiation/dose increase, or decreased concentrations/effects with isoniazid discontinuation/dose decrease. Consider therapy modification
HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy
Itraconazole: Isoniazid may decrease the serum concentration of Itraconazole. Monitor therapy
Ketoconazole (Systemic): Isoniazid may decrease the serum concentration of Ketoconazole (Systemic). Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Levodopa: Isoniazid may diminish the therapeutic effect of Levodopa. Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Phenytoin: Isoniazid may increase the serum concentration of Phenytoin. Management: Consider alternatives. If concomitant therapy cannot be avoided, monitor for increased phenytoin concentrations/effects with isoniazid initiation/dose increase, or decreased concentrations/effects with isoniazid discontinuation/dose decrease. Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Propacetamol: Isoniazid may enhance the hepatotoxic effect of Propacetamol. Monitor therapy
Prothionamide: Isoniazid may increase the serum concentration of Prothionamide. Prothionamide may increase the serum concentration of Isoniazid. Management: Consider a prothionamide dose reduction and do not exceed 500 mg per day if combined with isoniazid. Additionally, monitor for increased isoniazid toxicities and ensure pyridoxine supplementation is provided if these drugs are combined. Consider therapy modification
Rifamycin Derivatives: May enhance the hepatotoxic effect of Isoniazid. Even so, this is a frequently employed combination regimen. Monitor therapy
Safinamide: May enhance the adverse/toxic effect of Isoniazid. Specifically, there is an increased risk for hypertension. Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Tegafur: CYP2A6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tegafur. Specifically, CYP2A6 inhibitors may inhibit the conversion of tegafur into its active metabolite, 5-fluorouracil. Avoid combination
Theophylline Derivatives: Isoniazid may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
False-positive urinary glucose with Clinitest®
>10%: Hepatic: Increased serum transaminases (mild and transient 10% to 20%)
Frequency not defined.
Central nervous system: Brain disease, memory impairment, paresthesia, peripheral neuropathy, psychosis, seizure
Dermatologic: Skin rash (morbilliform, maculopapular, pruritic, or exfoliative), toxic epidermal necrolysis
Endocrine & metabolic: Gynecomastia, hyperglycemia, metabolic acidosis, pellagra, pyridoxine deficiency
Gastrointestinal: Epigastric distress, nausea, pancreatitis, vomiting
Hematologic & oncologic: Agranulocytosis, anemia (sideroblastic, hemolytic, or aplastic), eosinophilia, lymphadenopathy, thrombocytopenia
Hepatic: Hepatitis (risk increases with age; 2% in patients ≥50 years), hyperbilirubinemia, jaundice
Immunologic: DRESS syndrome
Neuromuscular & skeletal: Lupus-like syndrome, rheumatic disease
Ophthalmic: Optic atrophy, optic neuritis
<1% (Limited to important or life-threatening): Hepatotoxicity (idiosyncratic) (Chalasani 2014)
Concerns related to adverse effects:
• Hepatitis: [US Boxed Warning]: Severe and sometimes fatal hepatitis may occur; usually occurs within the first 3 months of treatment, although may develop even after many months of treatment. The risk of developing hepatitis is age-related, although isoniazid-induced hepatotoxicity has been reported in children; daily ethanol consumption, chronic liver disease, or injection drug use may also increase the risk. Patients given isoniazid must be monitored carefully and interviewed at monthly intervals. Fatal hepatitis associated with isoniazid may be increased in women (particularly black and Hispanic and in any woman in the postpartum period). Closer monitoring may be considered in these groups. Patients ≥35 years should also have AST and ALT measured at baseline and periodically throughout treatment. Patients must report any prodromal symptoms of hepatitis, such as fatigue, paresthesias of hands and feet, weakness, dark urine, rash, anorexia, nausea, fever >3 days’ duration, and/or abdominal pain (especially right upper quadrant discomfort), icterus, or vomiting. Patients should be instructed to immediately hold therapy if any of these symptoms occur, and contact their prescriber. If abnormalities of liver function exceed 3 to 5 times the upper limit of normal (ULN), strongly consider discontinuation of isoniazid. If isoniazid must be reinstituted, wait for symptoms and laboratory abnormalities to resolve and use very small and gradual increasing doses, withdrawing therapy immediately if an indication of recurrent hepatic involvement.
• Peripheral neuropathies: Pyridoxine supplementation is recommended in individuals at risk for development of peripheral neuropathies (eg, HIV infection, nutritional deficiency, diabetes, alcoholism, chronic renal failure, advanced age) (Nahid 2016).
• Hepatic impairment: Use with caution in patients with hepatic impairment; contraindicated in patients with acute liver disease or previous isoniazid-associated hepatic injury. Treatment with isoniazid for latent tuberculosis infection (LTBI) should be deferred in patients with acute hepatic diseases.
• Renal impairment: Use with caution in patients with severe renal impairment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Appropriate use: Multidrug regimens should be utilized for the treatment of active tuberculosis to prevent the emergence of drug resistance.
• Monitoring: Use should be carefully monitored in the following groups: Daily users of alcohol, active chronic liver disease, severe renal dysfunction, age >35 years, concurrent use of any chronically administered drug, history of previous isoniazid discontinuation, existence of or conditions predisposing to peripheral neuropathy, pregnancy, injection drug use, women in minority groups (particularly postpartum), HIV seropositive patients.
Baseline and periodic (more frequently in patients with higher risk for hepatitis) liver function tests (ALT and AST); sputum cultures monthly (until 2 consecutive negative cultures reported); monitoring for prodromal signs of hepatitis
LTBI therapy: American Thoracic Society/Centers for Disease Control (ATS/CDC) recommendations: Monthly clinical evaluation, including brief physical exam for adverse events. Use should be carefully monitored in the following groups: daily users of alcohol, active chronic liver disease, severe renal dysfunction, age > 35 years, concurrent use of any chronically administered drug, history of previous isoniazid discontinuation, existence of or conditions predisposing to peripheral neuropathy, pregnancy, injection drug use, women in minority groups (particularly postpartum), HIV seropositive patients. AST and ALT should be obtained at baseline and at least monthly during LTBI use. Discontinue temporarily or permanently if liver function tests > 3 to 5 times ULN. Routine, periodic monitoring is recommended for any patient with an abnormal baseline or at increased risk for hepatotoxicity.
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Isoniazid crosses the human placenta. Due to the risk of tuberculosis to the fetus, treatment is recommended when the probability of maternal disease is moderate to high. Drug-susceptible TB guidelines recommend isoniazid as part of the initial treatment regimen. Isoniazid is also recommended for the treatment of TB in pregnant women with HIV-coinfection. Pyridoxine supplementation is recommended (Nahid 2016). Due to biologic changes during pregnancy and early postpartum, pregnant women may have increased susceptibility to tuberculosis infection or reactivation of latent disease (Mathad 2012).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, vomiting, or injection site irritation. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), signs of acidosis (confusion, fast breathing, tachycardia, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), burning or numbness feeling, vision changes, chills, joint pain, joint edema, memory impairment, enlarged breasts, mood changes, seizures, confusion, bruising, bleeding, severe loss of strength and energy, or confusion (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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