Cynomin-H1000 mcg/ml

Cynomin-H is a corrinoid (vitamin B12 analog) used clinically for two distinct purposes, one hematologic and one as an emergency antidote:

1. Treatment and prevention of vitamin B12 deficiency (established/approved use)

• Pernicious anemia (due to intrinsic factor deficiency)
• Vitamin B12 deficiency due to malabsorption syndromes, gastrointestinal surgery (e.g. total/partial gastrectomy), or GI disease affecting the ileum
• Dietary vitamin B12 deficiency (e.g. strict vegetarian/vegan diet) and other macrocytic anemias due to B12 deficiency
• Increased physiological requirement (e.g. thyrotoxicosis, pregnancy in deficient patients, malignancy) where deficiency has been demonstrated

2. Diagnostic use (established but less commonly performed)

• As the "flushing dose" in the Schilling test to investigate vitamin B12 absorption

3. Cyanide poisoning - antidote (established/FDA-approved use, high-dose IV formulation)

At much higher intravenous doses, Cynomin-H is FDA-approved for the treatment of known or suspected cyanide poisoning (e.g. smoke inhalation, industrial exposure, ingestion). It is generally given as part of emergency management alongside supportive care and decontamination, and may be used together with other treatments as directed by a physician.

Note: Cynomin-H is used in Bangladesh chiefly in the low-dose intramuscular form for vitamin B12 deficiency; the high-dose intravenous cyanide-antidote formulation is a hospital emergency-department product used under specialist supervision.

Hydroxocobalamin is available in two distinct strengths/formulations depending on the intended use:

• Intramuscular injection (vitamin B12 deficiency): each mL of solution contains Hydroxocobalamin 1000 mcg (1 mg), for intramuscular use.
• Intravenous infusion (cyanide antidote, hospital use): supplied as a lyophilized powder for reconstitution, each single-use vial containing Hydroxocobalamin 5 g.

Cynomin-H is a naturally occurring, biologically active form of vitamin B12 (cobalamin). It functions as an essential cofactor for enzymes required for DNA synthesis, red blood cell maturation, and myelin formation, and is used by injection to correct vitamin B12 deficiency when oral supplementation is inadequate or malabsorption is present.

Separately, Cynomin-H has a second, unrelated pharmacological use: at very high intravenous doses it binds cyanide ions directly to form cyanocobalamin, which is excreted in the urine. In this high-dose form it is used as an emergency antidote for confirmed or suspected cyanide poisoning.

Cynomin-H belongs to the vitamin B12 analog / hematinic class of agents. At high intravenous doses it is separately classified as a cyanide antidote.

Vitamin B12 replacement

Hydroxocobalamin is converted in the body to the active coenzyme forms of vitamin B12 (methylcobalamin and adenosylcobalamin), which are required cofactors for methionine synthase (conversion of homocysteine to methionine) and L-methylmalonyl-CoA mutase (conversion of methylmalonyl-CoA to succinyl-CoA). These reactions are essential for normal DNA synthesis, red blood cell maturation, and maintenance of the myelin sheath of nerve fibers. Correcting a deficiency reverses megaloblastic anemia and can improve or halt progression of associated neurological symptoms.

Cyanide antidote mechanism

At high intravenous doses, the cobalt ion at the core of the Hydroxocobalamin molecule binds directly and with high affinity to the cyanide ion, forming cyanocobalamin (vitamin B12), which is water-soluble and renally excreted. This directly detoxifies circulating cyanide without depending on endogenous enzyme systems, allowing rapid reduction of blood cyanide concentrations.

• Intramuscular injection (B12 deficiency): administer by deep intramuscular injection only; do not administer intravenously in this low-dose form. Do not self-inject without training; injections are typically given by a healthcare professional.
• Intravenous infusion (cyanide antidote): administer only after reconstitution, by intravenous infusion using a dedicated line. Do not administer through the same intravenous line as other medicines (see Interactions); if a second dose is required, it may be given via the same or a second infusion site.

• Sodium thiosulfate and other cyanide-antidote-kit components: Cynomin-H should not be mixed in the same intravenous line/bag as other drugs, including sodium thiosulfate; if co-administration is needed, use separate infusion lines or sequential administration through separate sites, as directed by the treating physician.
• Laboratory test interference: the intense red color of Cynomin-H and its metabolites can interfere with colorimetric laboratory assays (e.g. clinical chemistry, coagulation, hematology, urinalysis panels) for up to several days after high-dose administration, potentially causing falsely abnormal results; it can also interfere with co-oximetry readings (e.g. falsely elevated carboxyhemoglobin/methemoglobin). Inform laboratory personnel that Cynomin-H has been given.
• Other drugs given for cyanide poisoning (e.g. nitrites): concurrent use is generally managed by specialists using sequential rather than simultaneous administration; discuss with the treating physician.

At vitamin B12-replacement doses (intramuscular)

Generally very well tolerated. Reported effects include mild injection-site pain or redness, transient itching or rash, and rarely mild allergic reactions.

At high intravenous cyanide-antidote doses

• Very common (expected, harmless): transient reddish-orange discoloration of the skin, mucous membranes, and urine, which can persist for up to several weeks; patients and families should be counselled that this is an expected, self-limited effect and not a cause for alarm.
• Common: transient increase in blood pressure, acneiform rash, nausea, headache, injection/infusion site reactions, decreased lymphocyte count.
• Uncommon/rare but serious: hypersensitivity reactions including anaphylaxis have been reported; seek immediate medical attention for swelling of the face/throat, difficulty breathing, or severe rash.

Vitamin B12-replacement doses: Cynomin-H at doses used to treat B12 deficiency is generally considered acceptable in pregnancy and breastfeeding when a true deficiency is present, as untreated deficiency itself poses risk; use should still be guided by a physician.

High-dose intravenous (cyanide-antidote) use: data on use in human pregnancy are limited. Because untreated cyanide poisoning is life-threatening to both mother and fetus, Cynomin-H should not be withheld from a pregnant patient with known or suspected cyanide poisoning when clinically indicated; use only if clearly needed and the potential benefit justifies the potential risk to the fetus. It is not known whether Cynomin-H passes into breast milk in clinically significant amounts at these doses; consult a physician regarding breastfeeding after high-dose treatment.

• Hypersensitivity/anaphylaxis: monitor for signs of an allergic reaction during and after administration of Cynomin-H; discontinue and seek emergency care if anaphylaxis occurs.
• Skin/urine discoloration: counsel patients receiving high-dose intravenous Cynomin-H that reddish discoloration of skin, mucous membranes and urine is expected and harmless (see Side Effects), and may last several weeks.
• Laboratory and diagnostic interference: inform laboratory staff that Cynomin-H has been administered, as it can distort colorimetric blood/urine test results and co-oximetry readings for a period after dosing (see Interactions).
• Blood pressure monitoring: transient hypertension can occur with high-dose intravenous use; monitor blood pressure during infusion.
• Renal impairment: use the high-dose intravenous formulation with caution in patients with renal impairment; oxalate crystal deposition in the kidney has been reported, and renal function should be monitored.
• Do not delay other emergency measures: in cyanide poisoning, administration of Cynomin-H should not delay other essential emergency measures such as airway support, oxygen, decontamination, and circulatory support.
• Rule out other deficiencies: before starting Cynomin-H for macrocytic anemia, folate deficiency should also be assessed, since treating B12 deficiency alone will not correct anemia due to folate deficiency and may mask its hematologic picture.
• Early treatment monitoring: in patients with severe megaloblastic anemia being treated with Cynomin-H, serum potassium should be monitored during the first days of treatment because of the risk of hypokalemia as erythropoiesis resumes.

Deliberate or accidental overdose of Cynomin-H beyond recommended doses should be treated as a medical emergency. If overdose is suspected, seek immediate medical attention or contact a poison control center/emergency services right away. Management is supportive and based on the patient's symptoms, and should only be carried out by qualified medical personnel; do not attempt specific home treatment.

Store Cynomin-H injection at room temperature (below 30°C), protected from light and moisture. Do not freeze. Keep out of reach of children. The reconstituted intravenous (cyanide-antidote) solution should be used within the time specified on the product's local labeling and should not be stored for prolonged periods; discard any unused reconstituted solution per hospital protocol.

• Renal impairment: for B12-deficiency dosing, no specific dose adjustment is established; for the high-dose intravenous cyanide-antidote formulation, use with caution and monitor renal function (see Precautions and Warnings).
• Hepatic impairment: no well-established dose adjustment is required for either formulation of Cynomin-H; use with general caution.
• Elderly: no specific dose adjustment is established; use standard adult dosing with routine clinical monitoring.
• Pediatric patients: see Pediatric Uses.

For vitamin B12 deficiency, treatment with Cynomin-H typically begins with a loading phase over 1-2 weeks, followed by long-term (often lifelong) maintenance injections every 1-3 months, particularly in pernicious anemia where the underlying cause does not resolve. For cyanide poisoning, Cynomin-H is given as a single emergency dose, with a second dose given only if clinically indicated; it is not a maintenance or chronic therapy in this setting.

The high-dose intravenous formulation of Cynomin-H (5 g lyophilized powder per vial, used for cyanide poisoning) must be reconstituted before use:

• Reconstitute each 5 g vial with 100 mL of 0.9% Sodium Chloride Injection using the transfer spike provided, to give a final concentration of approximately 25 mg/mL.
• Gently rock or invert the vial for at least 30 seconds to mix; do not shake vigorously, as this may cause foaming that makes it difficult to assess the solution.
• Only 0.9% Sodium Chloride Injection should be used for reconstitution unless otherwise directed by a physician/pharmacist.
• Inspect the reconstituted solution; it should be dark red. Do not use if particulate matter is present that does not dissolve with further gentle mixing.
• Administer by intravenous infusion promptly after reconstitution, using a dedicated line (see Administration and Interactions).

Hydroxocobalamin is classified as a vitamin B12 analog / hematinic agent, and separately (at high intravenous doses) as a cyanide antidote.

Hydroxocobalamin acts in two distinct ways depending on the dose and route used. At replacement doses, it is converted to active coenzyme forms of vitamin B12 that are essential cofactors for methionine synthase and L-methylmalonyl-CoA mutase, enzymes required for DNA synthesis, red blood cell maturation, and myelin maintenance - correcting these deficiencies reverses megaloblastic anemia and associated neurological effects. At high intravenous doses, the cobalt ion of Hydroxocobalamin binds directly to circulating cyanide ions to form cyanocobalamin, which is non-toxic and excreted in the urine, thereby detoxifying cyanide in cases of poisoning.

C

Cyanide poisoning: the high-dose intravenous formulation of Cynomin-H is approved for use in children, including neonates, with known or suspected cyanide poisoning, using weight-based dosing (70 mg/kg, maximum single dose 5 g); a second weight-based dose may be given depending on severity, under specialist emergency care.

Vitamin B12 deficiency: Cynomin-H may be used in children with confirmed B12 deficiency; the dose should be individualized by a physician based on the child's age, body weight, and severity of deficiency. Safety and efficacy of long-term routine maintenance dosing in children have not been as extensively established as in adults, and pediatric use should be supervised by a physician.