MITHRACIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MITHRACIN (MITHRACIN).
Binds to DNA and inhibits RNA synthesis; also inhibits osteoclast activity by blocking mRNA transcription.
| Metabolism | Primarily hepatic via unknown enzymes; excreted in bile and urine. |
| Excretion | Renal: ~90% unchanged within 24 hours; biliary/fecal: <10% as metabolites. |
| Half-life | Terminal half-life: 18-36 hours (mean 27 hours); clinically, this supports intermittent dosing every 1-2 weeks to avoid accumulation. |
| Protein binding | Approximately 90% bound to albumin. |
| Volume of Distribution | Vd: 0.3-0.5 L/kg (30-50 L/70 kg), indicating distribution primarily in extracellular fluid. |
| Bioavailability | IV only (100%); oral bioavailability negligible due to GI instability and first-pass metabolism. |
| Onset of Action | IV: Hypocalcemia onset within 6-12 hours; antitumor effect may take several days to weeks. |
| Duration of Action | Hypocalcemic effect lasts 1-3 days; antitumor response duration is variable but typically weeks; cumulative toxicity risk with repeated dosing. |
25 mcg/kg intravenously over 4-6 hours daily for 8-10 days; for hypercalcemia, 25 mcg/kg intravenously once. Maximum cumulative dose due to toxicity: 10-30 mcg/kg per course.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: 75% of standard dose. GFR <10 mL/min: avoid use or reduce to 50% of standard dose with close monitoring. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 25-50%. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Not recommended in children due to severe toxicity; no established weight-based dosing. Use only in life-threatening hypercalcemia with extreme caution: 25 mcg/kg IV once, with monitoring. |
| Geriatric use | Start at 25 mcg/kg IV daily, but due to increased risk of renal and hepatic impairment, consider dose reduction to 15-20 mcg/kg and monitor renal function, electrolytes, and liver enzymes closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MITHRACIN (MITHRACIN).
| Breastfeeding | It is not known whether mithracin is excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants (including bone marrow suppression and carcinogenicity), breastfeeding is contraindicated during therapy and for at least 2 weeks after the last dose. No M/P ratio is available. |
| Teratogenic Risk | Mithracin (plicamycin) is a cytotoxic antibiotic that inhibits RNA synthesis. It is classified as FDA Pregnancy Category X. There is evidence of fetal harm in animal studies and no adequate human studies. First trimester exposure carries a high risk of major malformations. Second and third trimester exposure may cause fetal growth restriction, central nervous system abnormalities, and other adverse effects. Use is contraindicated in pregnancy. |
■ FDA Black Box Warning
May cause severe hepatotoxicity; use with extreme caution in patients with impaired hepatic function.
| Serious Effects |
Hypersensitivity, severe hepatic impairment, pregnancy (category X), lactation.
| Precautions | Hepatotoxicity, nephrotoxicity, myelosuppression, coagulopathy, severe gastrointestinal toxicity, and pulmonary fibrosis. |
Loading safety data…
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests (LFTs), renal function (serum creatinine, BUN), and serum calcium and phosphate levels regularly. Assess for signs of bleeding, infection, hepatotoxicity, and nephrotoxicity. In pregnancy, monitor fetal growth and development via ultrasound; consider amniocentesis for genetic testing if first trimester exposure occurred. |
| Fertility Effects | Mithracin can cause gonadal suppression and infertility in both males and females. It may lead to azoospermia or amenorrhea. Effects may be temporary or permanent depending on dose and duration of therapy. |