Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
AZATHIOPRINE vs OFIRMEV
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Azathioprine is a purine analog that inhibits purine nucleotide synthesis, thereby suppressing DNA replication and cell proliferation. It is converted to 6-mercaptopurine, which acts as a purine antagonist, inhibiting de novo purine synthesis and interfering with RNA and DNA synthesis, particularly in rapidly dividing cells such as T-lymphocytes.
OFIRMEV (acetaminophen) is a para-aminophenol derivative with analgesic and antipyretic activity. Its mechanism of action is not fully understood, but it is thought to involve inhibition of cyclooxygenase (COX) enzymes in the central nervous system, with minimal peripheral COX inhibition. It may also act on serotonergic pathways and cannabinoid receptors.
Renal transplant rejection prophylaxis (FDA),Rheumatoid arthritis (FDA),Off-label: autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease (Crohn's disease, ulcerative colitis), pemphigus, myasthenia gravis, dermatomyositis/polymyositis,Off-label: myelodysplastic syndrome, refractory immune thrombocytopenic purpura, atopic dermatitis, Behçet's syndrome
Management of mild to moderate pain,Management of moderate to severe pain with adjunctive opioid analgesics,Reduction of fever
1.5 to 2.5 mg/kg orally once daily; typical adult dose 50-150 mg/day orally. Intravenous dose is 3-5 mg/kg/day as a slow infusion over 30-60 minutes.
IV: 1000 mg every 6 hours or 650 mg every 4 hours; maximum single dose: 1000 mg; minimum dosing interval: 4 hours; maximum daily dose: 4000 mg.
Terminal elimination half-life of azathioprine is approximately 2–5 hours; its active metabolite 6-mercaptopurine has a half-life of 1–2 hours, but 6-thioguanine nucleotides accumulate in red blood cells with a half-life of several days, correlating with myelosuppression.
Terminal elimination half-life is 2-3 hours in adults (2.5-3 hours in children). Clinically, dosing every 4-6 hours is needed to maintain therapeutic levels.
Azathioprine is metabolized by xanthine oxidase (XO) and thiopurine methyltransferase (TPMT) to active (6-mercaptopurine) and inactive metabolites. 6-Mercaptopurine is further metabolized by XO to 6-thiouric acid and by TPMT to 6-methylmercaptopurine. Genetic deficiency of TPMT increases risk of toxicity.
Acetaminophen is primarily metabolized in the liver via conjugation with glucuronide (50-60%) and sulfate (20-30%). A minor amount is oxidized by cytochrome P450 (CYP2E1, CYP1A2, CYP3A4) to a toxic reactive metabolite (NAPQI), which is normally detoxified by glutathione. At toxic doses, glutathione is depleted, leading to NAPQI accumulation and hepatotoxicity.
Renal (approximately 2% as unchanged drug, 30% as 6-thiouric acid and other metabolites); biliary/fecal (minor, <10% as metabolites).
Primarily renal (85% as sulfate and glucuronide conjugates, 10% as unchanged drug). Less than 5% fecal/biliary.
Approximately 30% bound, primarily to albumin.
10-25% bound to albumin at therapeutic concentrations.
0.8–1.0 L/kg, indicating distribution into total body water; extensive distribution into tissues including liver and erythrocytes.
0.8-1.0 L/kg. Indicates distribution into total body water.
Oral bioavailability of azathioprine is 60–80% (mean 70%) with interindividual variability; absorption may be reduced by food.
100% (intravenous); not applicable for other routes as OFIRMEV is IV only.
GFR >50 m L/min: no adjustment. GFR 10-50 m L/min: administer 75% of normal dose. GFR <10 m L/min: administer 50% of normal dose. Hemodialysis: administer 50% of normal dose after dialysis.
No dose adjustment required for GFR ≥30 m L/min. For GFR <30 m L/min, extend dosing interval to every 8 hours; maximum daily dose 3000 mg.
Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 25-50%. Child-Pugh Class C: contraindicated or use with extreme caution; reduce dose by at least 50%.
Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce total daily dose by 50% (max 2000 mg/day). Child-Pugh Class C: Contraindicated or use with extreme caution; reduce dose to 50% of standard and extend interval to every 8 hours; maximum 2000 mg/day.
1.5 to 2.5 mg/kg orally once daily; maximum 150 mg/day. For inflammatory bowel disease: 2-3 mg/kg/day. Intravenous: 3-5 mg/kg/day as a slow infusion.
Weight-based: <10 kg: 7.5 mg/kg/dose every 6 hours; 10-50 kg: 15 mg/kg/dose every 6 hours; >50 kg: 1000 mg every 6 hours or 650 mg every 4 hours. Maximum single dose: 15 mg/kg (up to 1000 mg); maximum daily dose: 75 mg/kg (up to 4000 mg).
Initiate at lower end of dosing range (1.5 mg/kg/day) due to potential for decreased renal and hepatic function; monitor renal function and hematologic parameters closely.
No specific dose adjustment; consider reduced renal function. For Cr Cl <30 m L/min, extend interval to every 8 hours. Maximum daily dose: 3000 mg in frail elderly or with comorbidities.
Malignancy: Patients receiving immunosuppressive therapy including azathioprine have an increased risk of developing lymphoma and other malignancies, particularly skin cancers. The risk is related to the duration and intensity of immunosuppression. Hematologic toxicity: Severe leukopenia, thrombocytopenia, and anemia, which may be dose-related, can occur. Regular monitoring of blood counts is required. Hepatotoxicity: Hepatotoxicity, including fatal liver injury, has been reported, particularly at high doses.
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 mg per day, and often involve more than one acetaminophen-containing product.
Hematologic monitoring: regular CBCs; Increased risk of infection; Hepatotoxicity; Pancreatitis; Carcinogenicity (lymphoma, skin cancer); TPMT deficiency increases myelotoxicity; Vaccination (live vaccines contraindicated); Renal and hepatic impairment; Drug interactions: allopurinol (reduce dose by 75%), ACE inhibitors (anemia), warfarin (anticoagulant effect decreased).
Risk of serious hepatotoxicity, especially with doses >4000 mg/day or in patients with underlying liver disease,Risk of severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis) – discontinue at first sign of rash,Risk of hypersensitivity reactions including anaphylaxis,Use caution in patients with severe hepatic impairment, active hepatic disease, or alcoholism,Avoid concurrent use of other acetaminophen-containing products
Hypersensitivity to azathioprine or 6-mercaptopurine; Pregnancy (unless benefit outweighs risk) - Category D; Lactation; Patients with TPMT deficiency (increased risk of severe myelotoxicity); Severely depressed bone marrow function; Active infections; Concurrent use of live vaccines; Pre-existing malignancy (except in organ transplantation context).
Known hypersensitivity to acetaminophen or any component of the formulation,Severe hepatic impairment or active liver disease (relative contraindication without black box)
No known significant food interactions. Avoid grapefruit juice? (No interaction reported). Maintain consistent diet; no specific restrictions. Limit alcohol due to hepatotoxicity risk.
No known food interactions. However, avoid excessive alcohol consumption as it may increase the risk of liver damage.
Azathioprine is pregnancy category D. First trimester: increased risk of congenital anomalies including ventricular septal defects, limb defects, and esophageal atresia. Second and third trimesters: risk of intrauterine growth restriction, preterm birth, and neonatal immunosuppression (leukopenia, thrombocytopenia). Use only if benefit outweighs risk.
Acetaminophen (OFIRMEV) is generally considered low risk across all trimesters. No increased risk of major congenital anomalies has been consistently demonstrated. Chronic high-dose use in third trimester may be associated with preterm birth or low birth weight. Avoid prolonged use above recommended doses.
Azathioprine is excreted into breast milk in low concentrations. M/P ratio is approximately 0.7. Nursing infants of mothers on azathioprine have not shown adverse effects; however, theoretical risk of immunosuppression exists. Caution is advised; monitor infant for increased infections.
Acetaminophen is excreted in breast milk in low concentrations (M/P ratio approximately 0.9-1.0). Considered compatible with breastfeeding; peak milk levels occur 1-2 hours after maternal dosing. Use lowest effective dose for shortest duration.
Pharmacokinetic changes in pregnancy include increased clearance and decreased absorption. Dose may need adjustment to maintain therapeutic efficacy. Close monitoring of disease activity and drug levels (6-thioguanine nucleotide levels) is recommended. No standard dose adjustment; individualization required.
No dose adjustment required during pregnancy. Pharmacokinetic changes in pregnancy (increased volume of distribution, clearance) may lead to lower peak concentrations but standard dosing remains effective. Maximum single dose: 1 g; maximum daily dose: 4 g.
Monitor CBC and LFTs weekly for first month, then biweekly for 2 months, then monthly. TPMT genotype testing before initiation. Avoid concurrent allopurinol unless dose reduced to 25% of original. Use with caution in renal impairment. May cause hepatotoxicity, pancreatitis, or lymphoproliferative disorders.
OFIRMEV (acetaminophen) injection is an IV formulation of acetaminophen used for pain and fever management. It is a prodrug that requires no hepatic conversion, providing rapid onset of action. Monitor for hepatotoxicity; maximum daily dose is 4 grams in adults but lower in patients with hepatic impairment or malnutrition. Do not exceed 1 gram per dose. Hypotension and anaphylaxis have been reported. Not interchangeable with oral acetaminophen due to dose equivalency. Use with caution in patients with alcohol use disorder.
Take exactly as prescribed; do not double dose if missed.,Avoid live vaccines during treatment and for 3 months after stopping.,Report any signs of infection, unexplained bruising/bleeding, or jaundice immediately.,Limit sun exposure and use sunscreen due to increased skin cancer risk.,Do not take allopurinol or other new medications without consulting doctor.,Maintain adequate hydration to reduce risk of hepatotoxicity.,Regular blood tests are required to monitor for side effects.
OFIRMEV is given intravenously for pain or fever.,Do not take additional acetaminophen-containing medications while receiving OFIRMEV.,Report any signs of allergic reaction (rash, itching, swelling, trouble breathing).,Seek immediate medical attention if you experience severe abdominal pain, yellowing of skin or eyes, or dark urine.,Inform your healthcare provider about all medications you are taking, especially blood thinners.
"Azathioprine may reduce the therapeutic efficacy and cardiotoxic effects of digitoxin by accelerating its metabolism through induction of cytochrome P450 enzymes, particularly CYP3A4. This interaction can lead to decreased digitoxin serum concentrations, potentially resulting in loss of heart rate control in patients with atrial fibrillation or heart failure. Conversely, the cardiotoxic risk of digitoxin is diminished, but the therapeutic goal may be compromised."
"Azathioprine and fingolimod both suppress lymphocyte function, leading to additive or synergistic immunosuppression. This combination increases the risk of severe infections, including opportunistic infections, due to profound immune system suppression. Clinically, patients may present with prolonged lymphopenia, increased susceptibility to infections, and potential reactivation of latent viruses such as JC virus (causing progressive multifocal leukoencephalopathy) or cytomegalovirus."
"Azathioprine, an immunosuppressant that acts as a prodrug for 6-mercaptopurine, can increase the myelosuppressive effects of benazepril, an ACE inhibitor. This interaction is likely due to additive bone marrow suppression, leading to an elevated risk of leukopenia, anemia, and thrombocytopenia, especially in patients with renal impairment or concomitant use of other myelosuppressive agents."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about AZATHIOPRINE vs OFIRMEV, answered by our medical review team.
AZATHIOPRINE is a Immunosuppressant that works by Azathioprine is a purine analog that inhibits purine nucleotide synthesis, thereby suppressing DNA replication and cell proliferation. It is converted to 6-mercaptopurine, which acts as a purine antagonist, inhibiting de novo purine synthesis and interfering with RNA and DNA synthesis, particularly in rapidly dividing cells such as T-lymphocytes.. OFIRMEV is a Non-opioid Analgesic that works by OFIRMEV (acetaminophen) is a para-aminophenol derivative with analgesic and antipyretic activity. Its mechanism of action is not fully understood, but it is thought to involve inhibition of cyclooxygenase (COX) enzymes in the central nervous system, with minimal peripheral COX inhibition. It may also act on serotonergic pathways and cannabinoid receptors.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between AZATHIOPRINE and OFIRMEV depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of AZATHIOPRINE is: 1.5 to 2.5 mg/kg orally once daily; typical adult dose 50-150 mg/day orally. Intravenous dose is 3-5 mg/kg/day as a slow infusion over 30-60 minutes.. The standard adult dose of OFIRMEV is: IV: 1000 mg every 6 hours or 650 mg every 4 hours; maximum single dose: 1000 mg; minimum dosing interval: 4 hours; maximum daily dose: 4000 mg.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between AZATHIOPRINE and OFIRMEV in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. AZATHIOPRINE is classified as Category D/X. Azathioprine is pregnancy category D. First trimester: increased risk of congenital anomalies including ventricular septal defects, limb defects, and esophageal atresia. Second and. OFIRMEV is classified as Category C. Acetaminophen (OFIRMEV) is generally considered low risk across all trimesters. No increased risk of major congenital anomalies has been consistently demonstrated. Chronic high-dos. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.