OVERDOSAGE SECTION.

OVERDOSAGE. Limited information is available on the acute toxicity of methocarbamol. Overdose of methocarbamol is frequently in conjunction with alcohol or other CNS depressants and includes the following symptoms: nausea, drowsiness, blurred vision, hypotension, seizures, and coma.In post-marketing experience, deaths have been reported with an overdose of methocarbamol alone or in the presence of other CNS depressants, alcohol or psychotropic drugs.

PHARMACOKINETICS SECTION.

Pharmacokinetics. In healthy volunteers, the plasma clearance of methocarbamol ranges between 0.20 and 0.80 L/h/kg, the mean plasma elimination half-life ranges between and hours, and the plasma protein binding ranges between 46% and 50%.Methocarbamol is metabolized via dealkylation and hydroxylation. Conjugation of methocarbamol also is likely. Essentially all methocarbamol metabolites are eliminated in the urine. Small amounts of unchanged methocarbamol also are excreted in the urine.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. Adverse reactions reported coincident with the administration of methocarbamol include:Body as whole: Anaphylactic reaction, angioneurotic edema, fever, headacheCardiovascular system: Bradycardia, flushing, hypotension, syncope, thrombophlebitisDigestive system: Dyspepsia, jaundice (including cholestatic jaundice), nausea and vomitingHemic and lymphatic system: LeukopeniaImmune system: Hypersensitivity reactionsNervous system: Amnesia, confusion, diplopia, dizziness or lightheadedness, drowsiness, insomnia, mild muscular incoordination, nystagmus, sedation, seizures (including grand mal), vertigoSkin and special senses: Blurred vision, conjunctivitis, nasal congestion, metallic taste, pruritus, rash, urticariaTo report SUSPECTED ADVERSE REACTIONS, contact Misemer Pharmaceutical, Inc. at 1-662-993-9625 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term studies to evaluate the carcinogenic potential of methocarbamol have not been performed. No studies have been conducted to assess the effect of methocarbamol on mutagenesis or its potential to impair fertility.

CLINICAL PHARMACOLOGY SECTION.

Clinical Pharmacology. The mechanism of action of methocarbamol in humans has not been established, but may be due to general central nervous system (CNS) depression. It has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber.

DESCRIPTION SECTION.

DESCRIPTION. Methocarbamol Tablets USP,1000 mg, carbamate derivative of gualfenesin, is central nervous system (CNS) depressant with sedative and musculoskeletal relaxant properties.The chemical name of methocarbamol is 3-(2 methoxyphenoxy)-1,2-propanediol 1-carbamate and has the empirical formula C11H15NO5. Its molecular weight is 241.24. The structural formula is shown below.Methocarbamol is white powder, sparingly soluble in water and chloroform, soluble in alcohol (only with heating) and propylene glycol, and insoluble in benzene and n-hexane.Methocarbamol tablet, 1000 mg is available as an orange, film coated, oblong-shaped tablet containing 1000 mg of methocarbamol, USP for oral administration. The inactive ingredients present are microcrystalline cellulose, croscarmellose sodium, FD&C Yellow aluminum lake, hydroxypropyl cellulose, hypromellose, magnesium stearate, lactose monohydrate, polyethylene glycol, triacetin, titanium dioxide. Methocarbamol Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. Methocarbamol, 1000 mg Adults: Initial dosage: 1/2 tablets time daily Maintenance dosage: tablet times daily Six grams day are recommended for the first 48 to 72 hours of treatment. (For severe conditions grams day may be administered). Thereafter, the dosage can usually be reduced to approximately grams day.

DRUG & OR LABORATORY TEST INTERACTIONS SECTION.

Drug/Laboratory Test Interactions. Methocarbamol may cause color interference in certain screening tests for 5-hydroxyindoleacetic acid (5-HIAA) using nitrosonaphthol reagent and in screening tests for urinary vanillylmandelic acid (VMA) using the Gitlow method.

DRUG INTERACTIONS SECTION.

Drug Interactions. 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.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Methocarbamol Tablets USP, 1000 mg Orange, film coated, oblong-shaped tablets, one side debossed AP349, the other side bisected. They are supplied as follows: Bottles of 100, NDC 0276-0510-10 Store at controlled room temperature, between 20C and 25C (68F and 77F). Dispense in tight container. Manufactured by: AustarPharma, LLC 18 Mayfield Ave, Edison, NJ 08837, USA Manufactured for: Misemer Pharmaceutical, Inc Ripley, MS 38663 LBL426 REV032022 Revised: March 2022.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. 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 methocarbamol has not been clearly identified, but may be related to its sedative properties. Methocarbamol does not directly relax tense skeletal muscles in man.

NURSING MOTHERS SECTION.

Nursing Mothers. Methocarbamol and/or its metabolites are excreted in the milk of dogs; however, it is not known whether methocarbamol or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when methocarbamol is administered to nursing woman.

SPL UNCLASSIFIED SECTION.

Special populations. ElderlyThe mean (+- SD) elimination half-life of methocarbamol in elderly healthy volunteers (mean (+- SD) age, 69 (+- 4) years) was slightly prolonged compared to younger (mean (+- SD) age, 53.3 (+- 8.8) years), healthy population (1.5 (+- 0.4) hours versus 1.1 (+- 0.27) hours, respectively). The fraction of bound methocarbamol was slightly decreased in the elderly versus younger volunteers (41 to 43% versus 46 to 50%, respectively).Preclinical studies (in male rats) show that alendronate transiently distributes to soft tissues following mg/kg IV administration but is then rapidly redistributed to bone or excreted in the urine. The mean steady-state volume of distribution, exclusive of bone, is at least 28 in humans. Concentrations of drug in plasma following therapeutic oral doses are too low (less than ng/mL) for analytical detection. Protein binding in human plasma is approximately 78%.Renally impairedThe clearance of methocarbamol in renally-impaired patients on maintenance hemodialysis was reduced about 40% compared to 17 normal subjects, although the mean (+- SD) elimination half-life in these two groups was similar: 1.2 (+- 0.6) versus 1.1 (+- 0.3) hours, respectively.Hepatically impairedIn patients with cirrhosis secondary to alcohol abuse, the mean total clearance of methocarbamol was reduced approximately 70% compared to that obtained in age- and weight-matched normal subjects. The mean (+- SD) elimination half-life in the cirrhotic patients and the normal subjects was 3.38 (+- 1.62) hours and 1.11 (+- 0.27) hours, respectively. The percent of methocarbamol bound to plasma proteins was decreased to approximately 40 to 45% compared to 46 to 50% in the normal subjects.

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects -- Pregnancy Category C. Animal reproduction studies have not been conducted with methocarbamol. It is also not known whether methocarbamol can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. Methocarbamol should be given to pregnant woman only if clearly needed.Safe use of methocarbamol has not been established with regard to possible adverse effects upon fetal development. There have been reports of fetal and congenital abnormalities following in utero exposure to methocarbamol. Therefore, methocarbamol should not be used in women who are or may become pregnant and particularly during early pregnancy unless in the judgment of the physician the potential benefits outweigh the possible hazards (seeWARNINGS).

WARNINGS SECTION.

WARNINGS. Since methocarbamol may possess general CNS depressant effect, patients receiving methocarbamol tablets should be cautioned about combined effects with alcohol and other CNS depressants.Safe use of methocarbamol has not been established with regard to possible adverse effects upon fetal development. There have been reports of fetal and congenital abnormalities following in utero exposure to methocarbamol. Therefore, methocarbamol tablets should not be used in women who are or may become pregnant and particularly during early pregnancy unless in the judgment of the physician the potential benefits outweigh the possible hazards (see PRECAUTIONS, Pregnancy).