METHOCARBAMOL

Methocarbamol injection, USP, a carbamate derivative of guaifenesin, is a central nervous system (CNS) depressant with sedative and musculoskeletal relaxant properties. It is a sterile, pyrogen-free, clear colorless solution, free from visible particles intended for intramuscular or intravenous administration. Each mL contains: Methocarbamol, USP 100 mg, Polyethylene Glycol 300, NF 0.5 mL, Water for Injection, USP q.s. The pH is adjusted, when necessary, with hydrochloric acid and/or sodium hydroxide. The chemical name of methocarbamol is 3-(2-methoxyphenoxy)-1,2-propanediol 1-carbamate and has the molecular formula of C 11 H 15 NO 5 . Its molecular weight is 241.24. The structural formula is shown below: Methocarbamol, USP is a white bulky powder, sparingly soluble in water and chloroform, soluble in alcohol (only with heating) and propylene glycol, and insoluble in benzene and n -hexane. Methocarbamol injection, USP has a pH between 3.5 and 6.0. AFTER MIXING WITH I.V. INFUSION FLUIDS, DO NOT REFRIGERATE. Methocarbamol Chemical Structure

The injectable form of methocarbamol is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Methocarbamol does not directly relax tense skeletal muscles in man.

For Intravenous and Intramuscular Use Only. Total adult dosage should not exceed 30 mL (3 vials) a day for more than 3 consecutive days except in the treatment of tetanus. If the condition persists, a like course may be repeated after a drug-free interval of 48 hours. Dosage and frequency of injection should be based on the severity of the condition being treated and therapeutic response noted. For the relief of symptoms of moderate degree, one dose of 1 gram (one 10 mL vial) may be adequate. Ordinarily this injection need not be repeated, as the administration of the oral form will usually sustain the relief initiated by the injection. For the severest cases or in postoperative conditions in which oral administration is not feasible, additional doses of 1 gram may be repeated every 8 hours up to a maximum of 3 g/day for no more than 3 consecutive days. Directions for Intravenous Use Methocarbamol injection may be administered undiluted directly into the vein at a maximum rate of three mL per minute . It may also be added to an intravenous drip of Sodium Chloride Injection (Sterile Isotonic Sodium Chloride Solution for Parenteral Use) or five percent Dextrose Injection (Sterile 5 percent Dextrose Solution); one vial given as a single-dose should not be diluted to more than 250 mL for I.V. infusion. AFTER MIXING WITH I.V. INFUSION FLUIDS, DO NOT REFRIGERATE . Care should be exercised to avoid vascular extravasation of this hypertonic solution, which may result in thrombophlebitis. It is preferable that the patient be in a recumbent position during and for at least 10 to 15 minutes following the injection. Directions for Intramuscular Use When the intramuscular route is indicated, not more than five mL (one-half vial) should be injected into each gluteal region. The injections may be repeated at eight hour intervals, if necessary. When satisfactory relief of symptoms is achieved, it can usually be maintained with tablets. Not Recommended for Subcutaneous Administration. Special Directions for Use in Tetanus There is clinical evidence which suggests that methocarbamol may have a beneficial effect in the control of the neuromuscular manifestations of tetanus. It does not, however, replace the usual procedure of debridement, tetanus antitoxin, penicillin, tracheotomy, attention to fluid balance, and supportive care. Methocarbamol injection should be added to the regimen as soon as possible. For Adults Inject one or two vials directly into the tubing of the previously inserted indwelling needle. An additional 10 mL or 20 mL may be added to the infusion bottle so that a total of up to 30 mL (three vials) is given as the initial dose (see PRECAUTIONS ). This procedure should be repeated every six hours until conditions allow for the insertion of a nasogastric tube. Crushed methocarbamol tablets suspended in water or saline may then be given through this tube. Total daily oral doses up to 24 grams may be required as judged by patient response. For Pediatric Patients A minimum initial dose of 15 mg/kg or 500 mg/m 2 is recommended. This dosage may be repeated every six hours, if required. The total dose should not exceed 1.8 g/m 2 for 3 consecutive days. The maintenance dosage may be given by injection into tubing or by I.V. infusion with an appropriate quantity of fluid. See directions for I.V. use.

Methocarbamol injection should not be administered to patients with known or suspected renal pathology. This caution is necessary because of the presence of polyethylene glycol 300 in the vehicle. A much larger amount of polyethylene glycol 300 than is present in recommended doses of methocarbamol injection is known to have increased pre-existing acidosis and urea retention in patients with renal impairment. Although the amount present in this preparation is well within the limits of safety, caution dictates this contraindication. Methocarbamol injection is contraindicated in patients hypersensitive to methocarbamol or to any of the injection components.

The following adverse reactions have been reported coincident with the administration of methocarbamol. Some events may have been due to an overly rapid rate of intravenous injection. Body as a Whole Anaphylactic reaction, angioneurotic edema, fever, headache Cardiovascular System Bradycardia, flushing, hypotension, syncope, thrombophlebitis In most cases of syncope there was spontaneous recovery. In others, epinephrine, injectable steroids, and/or injectable antihistamines were employed to hasten recovery. Digestive System Dyspepsia, jaundice (including cholestatic jaundice), nausea and vomiting Hemic and Lymphatic System Leukopenia Immune System Hypersensitivity reactions Nervous System Amnesia, confusion, diplopia, dizziness or light-headedness, drowsiness, insomnia, mild muscular incoordination, nystagmus, sedation, seizures (including grand mal), vertigo The onset of convulsive seizures during intravenous administration of methocarbamol has been reported in patients with seizure disorders. The psychic trauma of the procedure may have been a contributing factor. Although several observers have reported success in terminating epileptiform seizures with methocarbamol injection, its administration to patients with epilepsy is not recommended (see PRECAUTIONS, General ). Skin and Special Senses Blurred vision, conjunctivitis, nasal congestion, metallic taste, pruritus, rash, urticaria Other Pain and sloughing at the site of injection

See WARNINGS and PRECAUTIONS for interaction with CNS drugs and alcohol. Methocarbamol may inhibit the effect of pyridostigmine bromide. Therefore, methocarbamol should be used with caution in patients with myasthenia gravis receiving anticholinesterase agents.