MANGANESE CHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MANGANESE CHLORIDE (MANGANESE CHLORIDE).
Manganese is an essential trace element that acts as a cofactor for numerous enzymes, including arginase, glutamine synthetase, superoxide dismutase (Mn-SOD), and various kinases and transferases. It is critical for amino acid, lipid, and carbohydrate metabolism, as well as bone development and wound healing.
| Metabolism | Manganese is not significantly metabolized; it is eliminated primarily via biliary excretion into feces. Enterohepatic circulation occurs. Small amounts are excreted in urine and pancreatic secretions. The liver plays a major role in regulating manganese homeostasis via biliary secretion. |
| Excretion | Primarily fecal (biliary) elimination (~80-90%); renal excretion accounts for ~10-20% of total manganese elimination. |
| Half-life | Terminal elimination half-life ranges from 2 to 4 weeks (mean ~20 days) for total manganese; reflects slow turnover in tissues, particularly bone and brain. |
| Protein binding | Approximately 80-90% bound, primarily to albumin and α2-macroglobulin; also binds to transferrin and β1-globulin. |
| Volume of Distribution | Volume of distribution is approximately 0.6-1.0 L/kg, indicating wide distribution into tissues, with high concentrations in liver, kidney, and bone. |
| Bioavailability | Bioavailability is not defined for intravenous administration; oral bioavailability of manganese chloride is low (~3-5%) due to extensive first-pass hepatic extraction and biliary excretion. |
| Onset of Action | Not applicable; manganese chloride is administered as a trace element supplement in parenteral nutrition, with effects on enzyme function occurring over hours to days as manganese is incorporated into metalloenzymes. |
| Duration of Action | Duration extends days to weeks after discontinuation due to slow tissue release; clinical effects (e.g., repletion of deficiency) persist until body stores are replenished. |
0.1-0.2 mg/kg manganese as manganese chloride intravenously daily as a component of parenteral nutrition, typically added to total parenteral nutrition (TPN) solutions; usual adult dose: 0.5-1 mg elemental manganese per day.
| Dosage form | INJECTABLE |
| Renal impairment | Contraindicated in severe renal impairment (GFR <30 mL/min) due to risk of accumulation and neurotoxicity; in moderate impairment (GFR 30-59 mL/min), reduce dose by 50% and monitor plasma manganese levels. |
| Liver impairment | In cirrhosis (Child-Pugh B or C), avoid use or reduce dose by 50-75% due to impaired biliary excretion; monitor plasma manganese levels to avoid neurotoxicity. |
| Pediatric use | Neonates and infants: 0.1-0.2 mg/kg/day elemental manganese intravenously as part of TPN; maximum daily dose: 1 mg in children <40 kg; adjust based on plasma levels (maintain 0.4-0.85 mcg/L). |
| Geriatric use | Start at lower end of dosing range (0.5 mg elemental manganese/day) due to age-related decline in renal function; monitor serum manganese levels and neurological status; avoid in patients with baseline renal impairment (CrCl <30 mL/min). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MANGANESE CHLORIDE (MANGANESE CHLORIDE).
| Breastfeeding | Manganese is excreted into breast milk and is a normal constituent. M/P ratio is approximately 0.4-0.7. Supplementation at recommended dietary allowances (RDA) is considered safe; high doses should be avoided. Monitor infant for potential neurological effects. |
| Teratogenic Risk | Manganese chloride is an essential trace element; deficiency is associated with skeletal abnormalities and impaired growth. High doses may be teratogenic in animal studies, but human data are insufficient to establish a clear risk. Caution is advised in all trimesters. Avoid excessive supplementation. |
■ FDA Black Box Warning
None
| Serious Effects |
Absolute: Hypersensitivity to manganese chloride or any component of the formulation. Relative: Pre-existing neurological disorder (e.g., Parkinson's disease), hepatic failure or biliary tract obstruction (increased risk of toxicity), or hypermanganesemia.
| Precautions | WARNING: Manganese accumulation can cause neurotoxicity (manganism) with symptoms resembling Parkinson's disease, especially in patients with liver dysfunction or cholestasis. Monitor plasma manganese levels in patients on long-term parenteral nutrition. Use with caution in patients with hepatic impairment, as impaired biliary excretion increases risk of toxicity. Avoid excessive or prolonged use without monitoring. |
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| Fetal Monitoring | Monitor serum manganese levels to avoid toxicity. Assess liver and neurological function in the mother. For the fetus, consider ultrasound for skeletal development if high exposure is suspected. No specific fetal monitoring is routinely required with normal dietary intake. |
| Fertility Effects | No adverse effects on fertility at physiological levels. High-dose exposure may impair spermatogenesis in males and alter ovarian function in animal studies. Relevance to humans is unknown. |