Combilipen^® NEO (Solution) Instructions for Use

Marketing Authorization Holder

Pharmstandard-UfaVITA OJSC (Russia)

ATC Code

A11DB (Vitamin B1 in combination with vitamins B6 and/or B12)

Dosage Form

Combilipen® NEO

Solution for intramuscular injection: amp. 2 ml 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intramuscular injection in the form of a transparent, pinkish-red liquid with a characteristic odor.

Excipients: diethanolamine – 5 mg, water for injection – up to 2 ml.

2 ml – ampoules of light-protective glass (5) – contour cell packaging (1) – cardboard packs.
2 ml – ampoules of light-protective glass (5) – contour cell packaging (2) – cardboard packs.

Clinical-Pharmacological Group

B complex vitamins

Pharmacotherapeutic Group

Vitamins; vitamin B1 and its combinations with vitamins B6 and B12; vitamin B1 in combination with vitamins B6 and/or B12

Pharmacological Action

A complex of B vitamins. Thiamine (B₁), pyridoxine (B₆) and Cyanocobalamin (B₁₂) are neurotropic substances and play a special role as coenzymes in the intermediate metabolism occurring in the central and peripheral nervous system.

Like other vitamins, they are essential food components that the body is unable to synthesize on its own.

The therapeutic use of vitamins B₁, B₆ and B₁₂ compensates for the often existing insufficient intake of vitamins from food, which ensures the presence of the necessary amount of coenzymes in the body. The use of B vitamins in the form of a complex increases their therapeutic efficacy, since the efficacy of the combination exceeds the efficacy of individual components.

The therapeutic use of these vitamins in various diseases of the nervous system is aimed, on the one hand, at compensating for an existing deficiency (possibly due to the body’s increased need directly caused by the disease) and, on the other hand, at stimulating natural mechanisms aimed at recovery.

At the same time, the indirect analgesic effect of the B vitamin complex has a beneficial effect on the therapeutic outcome.

Pharmacokinetics

After oral administration, thiamine undergoes dose-dependent transport, the mechanism of which is dual in nature: active absorption at concentrations up to 2 µmol/L and passive diffusion at concentrations above 2 µmol/L. Phosphorylation of thiamine occurs in the liver. T_1/2 is about 4 hours.

The human body contains about 30 mg of thiamine. Given the rapid metabolism, it is eliminated within 4-10 days.

Pyridoxine is absorbed very quickly, mainly in the upper intestine, and is eliminated within a maximum of 2-5 hours. Performing the function of a coenzyme requires phosphorylation of pyridoxine. Pyridoxine in the phosphorylated form (pyridoxal phosphate) is almost 80% bound to plasma proteins.

The human body contains about 40-150 mg. 1.7-3.6 mg is excreted in the urine per day.

Cyanocobalamin is absorbed from the gastrointestinal tract through 2 mechanisms: 1) release under the action of gastric juice and rapid binding to intrinsic factor; 2) passive diffusion through the intestinal epithelium regardless of intrinsic factor.

At doses greater than 1.5 µg, the latter mechanism plays a significant role. In patients with B₁₂-deficiency anemia, reabsorption after oral administration is approximately 1% of 100 µg or more.

Excess cyanocobalamin accumulates in the liver.

Cyanocobalamin is excreted from the liver with bile into the intestine and is largely reabsorbed during enterohepatic circulation. The metabolic rate of Cyanocobalamin per day is 2.5 µg.

Indications

As part of complex therapy for the following neurological diseases: neuritis and neuralgia – trigeminal neuralgia; facial nerve paresis; intercostal neuralgia; pain syndrome caused by spinal diseases (lumboischialgia, plexopathy, radicular syndrome caused by degenerative changes of the spine); herpes zoster; neuropathic pain caused by polyneuropathy including diabetic and alcoholic).

ICD codes

Dosage Regimen

Take orally 1 single dose 3 times/day. The duration of treatment is determined by the doctor and averages 1-1.5 months. Dose adjustment is recommended for therapy lasting more than 4 weeks.

Intramuscularly administer 1 single dose 1 time/day until acute symptoms are relieved. After symptom reduction or in case of moderate severity of the disease, administer 1 single dose 1-3 times a week for 2-3 weeks.

For maintenance therapy, for relapse prevention or continuation of the ongoing course of treatment, oral administration in the appropriate dosage form is recommended. The duration of treatment is determined individually by the doctor.

Adverse Reactions

From the immune system very rarely – hypersensitivity reactions, such as sweating, tachycardia.

Allergic reactions very rarely – itching, urticaria, anaphylactic shock.

From the digestive system: frequency not established – nausea, vomiting, diarrhea, abdominal pain.

From the nervous system frequency not established – long-term use (>6-12 months) of vitamin B₆ at a daily dose >50 mg may cause peripheral sensory neuropathy.

Contraindications

Children under 18 years of age; hypersensitivity to the active substances of the combination.

Use in Pregnancy and Lactation

Use during pregnancy and lactation (breastfeeding) is not recommended due to the high content of vitamins.

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

If signs of peripheral sensory neuropathy (paresthesia) appear, it is necessary to adjust the dose and, if necessary, discontinue the drug.

When administering vitamin B₁₂, the clinical picture, as well as laboratory parameters in funicular myelosis or pernicious anemia, may lose their specificity.

Drug Interactions

When used concomitantly with levodopa, pyridoxine may reduce the antiparkinsonian effect of levodopa.

Concomitant use of pyridoxine antagonists (e.g., isoniazid, hydralazine, penicillamine, or cycloserine) may increase the need for pyridoxine.

Thiamine is inactivated by fluorouracil. Fluorouracil competitively inhibits the phosphorylation of thiamine to thiamine pyrophosphate.

Antacids reduce the absorption of thiamine.

"Loop" diuretics, e.g., furosemide, can block tubular reabsorption, thus enhancing the excretion of thiamine during long-term use, which leads to a decrease in thiamine levels in the blood.

Ingestion of alcohol and black tea leads to reduced absorption of thiamine.

Beverages containing sulfites (e.g., wine) enhance the degradation of thiamine.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.