DODEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DODEX (DODEX).

How it works

Hydroxocobalamin is a synthetic form of vitamin B12, which acts as a cofactor for methionine synthase and methylmalonyl-CoA mutase, essential for DNA synthesis, myelin formation, and hematopoiesis.

What the body does with it

Metabolism	Hydroxocobalamin is metabolized in the liver and other tissues by conversion to adenosylcobalamin and methylcobalamin; it is excreted primarily in the bile.
Excretion	Primarily renal: ~50-80% of absorbed dose excreted unchanged in urine via glomerular filtration. Biliary/fecal excretion accounts for <10% as cyanocobalamin.
Half-life	Terminal elimination half-life is approximately 6 days (range 4-10 days) in plasma; however, due to extensive tissue binding and enterohepatic recirculation, the pharmacodynamic half-life for correction of deficiency is about 1 year.
Protein binding	Approximately 90% bound to plasma proteins: mainly transcobalamin II (20-30%) and haptocorrin (60-70%), with a small fraction free.
Volume of Distribution	Vd ~0.2-0.3 L/kg in plasma; however, due to extensive tissue uptake (liver, kidney, bone marrow), total body Vd is much larger (~1.5 L/kg), reflecting high affinity for tissues.
Bioavailability	Oral: ~1-2% (cyanocobalamin) due to dependence on intrinsic factor and carrier-mediated absorption; nasal: ~8-10%; sublingual: similar to oral; IM: 100%.
Onset of Action	Intramuscular injection: reticulocytosis begins within 3-5 days; improvement in neurologic symptoms may take weeks. Oral: similar but delayed due to absorption requiring intrinsic factor.
Duration of Action	Single 1000 mcg IM dose provides adequate stores for 1-3 months in patients with normal absorption; for pernicious anemia, lifelong monthly injections are required. Duration is dose-dependent.

Classification & Brands

Dosing & administration

1 mg intramuscularly once every 7-10 days for maintenance; 1 mg intramuscularly once daily for 7 days for initial treatment.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment; not removed by hemodialysis.
Liver impairment	No dose adjustment required for hepatic impairment; Child-Pugh classification does not alter dosing.
Pediatric use	Newborns: 0.025 mg/kg intramuscularly; Infants/Children: 0.05-0.1 mg intramuscularly once every 7-14 days. Maximum dose: 1 mg per dose.
Geriatric use	No specific dose adjustment; use standard adult dosing. Monitor for potential decreased absorption and increased sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DODEX (DODEX).

Breastfeeding	Cyanocobalamin is excreted in human milk in amounts consistent with maternal dietary intake; M/P ratio not established. Therapeutic doses considered compatible with breastfeeding; no adverse effects reported in nursing infants.
Teratogenic Risk	First trimester: No evidence of structural anomalies in animal studies; limited human data. Second/third trimesters: No known fetal risks; maternal cyanocobalamin deficiency may increase risk of neural tube defects. Overall: FDA pregnancy category C; therapeutic doses not associated with major teratogenicity.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to hydroxocobalamin or any component of the formulation","Leber's hereditary optic neuropathy (relative contraindication)"]

Clinical Precautions

Precautions

["Hypersensitivity reactions including anaphylaxis","Iron and folic acid deficiency may mask response","Hypokalemia may occur during initial therapy","Monitor serum potassium levels","Use with caution in patients with Leber's disease (optic atrophy)"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

DODEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DODEX (DODEX).

How it works

Hydroxocobalamin is a synthetic form of vitamin B12, which acts as a cofactor for methionine synthase and methylmalonyl-CoA mutase, essential for DNA synthesis, myelin formation, and hematopoiesis.

What the body does with it

Metabolism	Hydroxocobalamin is metabolized in the liver and other tissues by conversion to adenosylcobalamin and methylcobalamin; it is excreted primarily in the bile.
Excretion	Primarily renal: ~50-80% of absorbed dose excreted unchanged in urine via glomerular filtration. Biliary/fecal excretion accounts for <10% as cyanocobalamin.
Half-life	Terminal elimination half-life is approximately 6 days (range 4-10 days) in plasma; however, due to extensive tissue binding and enterohepatic recirculation, the pharmacodynamic half-life for correction of deficiency is about 1 year.
Protein binding	Approximately 90% bound to plasma proteins: mainly transcobalamin II (20-30%) and haptocorrin (60-70%), with a small fraction free.
Volume of Distribution	Vd ~0.2-0.3 L/kg in plasma; however, due to extensive tissue uptake (liver, kidney, bone marrow), total body Vd is much larger (~1.5 L/kg), reflecting high affinity for tissues.
Bioavailability	Oral: ~1-2% (cyanocobalamin) due to dependence on intrinsic factor and carrier-mediated absorption; nasal: ~8-10%; sublingual: similar to oral; IM: 100%.
Onset of Action	Intramuscular injection: reticulocytosis begins within 3-5 days; improvement in neurologic symptoms may take weeks. Oral: similar but delayed due to absorption requiring intrinsic factor.
Duration of Action	Single 1000 mcg IM dose provides adequate stores for 1-3 months in patients with normal absorption; for pernicious anemia, lifelong monthly injections are required. Duration is dose-dependent.

Classification & Brands

Dosing & administration

1 mg intramuscularly once every 7-10 days for maintenance; 1 mg intramuscularly once daily for 7 days for initial treatment.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment; not removed by hemodialysis.
Liver impairment	No dose adjustment required for hepatic impairment; Child-Pugh classification does not alter dosing.
Pediatric use	Newborns: 0.025 mg/kg intramuscularly; Infants/Children: 0.05-0.1 mg intramuscularly once every 7-14 days. Maximum dose: 1 mg per dose.
Geriatric use	No specific dose adjustment; use standard adult dosing. Monitor for potential decreased absorption and increased sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DODEX (DODEX).

Breastfeeding	Cyanocobalamin is excreted in human milk in amounts consistent with maternal dietary intake; M/P ratio not established. Therapeutic doses considered compatible with breastfeeding; no adverse effects reported in nursing infants.
Teratogenic Risk	First trimester: No evidence of structural anomalies in animal studies; limited human data. Second/third trimesters: No known fetal risks; maternal cyanocobalamin deficiency may increase risk of neural tube defects. Overall: FDA pregnancy category C; therapeutic doses not associated with major teratogenicity.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to hydroxocobalamin or any component of the formulation","Leber's hereditary optic neuropathy (relative contraindication)"]