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. |
| Molecular Weight | 1097.4 Da |
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 | Contraindicated; teratogenic effects including fetal skeletal anomalies and growth retardation observed in animal studies. |
| 2nd trimester | Contraindicated; risk of fetal hepatotoxicity, renal toxicity, and skeletal abnormalities. |
| 3rd trimester | Contraindicated; may cause fetal toxicity and maternal hepatotoxicity near term. |
Clinical note
Comprehensive clinical and safety monograph for MITHRACIN (MITHRACIN).
| Placental transfer | Crosses placenta; demonstrated in animal studies with distribution to fetal tissues. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants, including hepatotoxicity and immunosuppression. Breastfeeding should be avoided during therapy and for at least 2 weeks after last dose. |
■ FDA Black Box Warning
May cause severe hepatotoxicity; use with extreme caution in patients with impaired hepatic function.
| Serious Effects |
PregnancyBreastfeedingSevere hepatic impairmentSevere renal impairmentHypersensitivity to mithramycin
| Precautions | Hepatotoxicity, nephrotoxicity, myelosuppression, coagulopathy, severe gastrointestinal toxicity, and pulmonary fibrosis. |
| Food/Dietary | No specific food interactions reported. Maintain adequate hydration to reduce renal toxicity. Avoid consumption of grapefruit juice as it may affect hepatic metabolism. |
| Clinical Pearls |
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| Lactation Rating |
| L5 |
| 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. |
| 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. |
| Mithracin (plicamycin) is primarily used for hypercalcemia of malignancy and testicular cancer. It is a potent inhibitor of RNA synthesis, with significant hepatotoxicity and nephrotoxicity. Monitor liver enzymes and creatinine closely. Avoid use in patients with pre-existing hepatic or renal impairment. Pre-medicate with antiemetics due to severe nausea and vomiting. Extravasation causes tissue necrosis; administer via central line. Discontinue at first sign of bleeding diathesis. |
| Patient Advice | This medication can cause liver or kidney damage; you will need regular blood tests. · Report any yellowing of skin/eyes, dark urine, or abdominal pain promptly. · Avoid alcohol and other hepatotoxic drugs. · Nausea and vomiting are common; take prescribed antiemetics as directed. · Tell your doctor if you experience unusual bleeding or bruising. · This drug can cause harm to an unborn baby; use effective contraception during treatment. |