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Rx only
For oral administration, Robaxisal is available as a pink and white laminated tablet containing: methocarbamol, USP 400 mg and aspirin, USP 325 mg. The inactive ingredients present are: corn starch, FD&C Red 3, magnesium stearate, povidone, sodium lauryl sulfate, sodium starch glycolate, and stearic acid.
Methocarbamol has the following structural formula and chemical name:
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3-(2-Methoxyphenoxy)-1,2-propanediol
1-Carbamate
Robaxisal provides a double approach to the management of discomforts associated with musculoskeletal disorders.
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.
Renally impaired
The clearance of methocarbamol in renally-impaired patients on maintenance hemodialysis was reduced about 40% compared to a normal population, although the mean elimination half-life in these two groups was similar (1.2 versus 1.1 hours, respectively).
Hepatically impaired
In patients with cirrhosis secondary to alcohol abuse, the mean total clearance of methocarbamol was reduced approximately 70% compared to a normal population (11.9 L/hr), and the mean elimination half-life was extended to approximately 3.4 hours. The fraction of methocarbamol bound to plasma proteins was decreased to approximately 40 to 45% compared to 46 to 50% in an age- and weight-matched normal population.
Aspirin is a mild analgesic with anti-inflammatory and antipyretic activity. These effects are believed to result from inhibition of the synthesis of certain prostaglandins.
Robaxisal 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.
Robaxisal is contraindicated in patients hypersensitive to methocarbamol, aspirin, or related compounds, or to any of the tablet components.
Since methocarbamol may possess a general CNS depressant effect, patients receiving Robaxisal should be cautioned about combined effects with alcohol and other CNS depressants.
Safe use of Robaxisal has not been established with regard to possible adverse effects upon fetal development. There have been very rare reports of fetal and congenital abnormalities following in utero exposure to methocarbamol. Therefore, Robaxin Injectable 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 ).
Methocarbamol may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. Patients should be cautioned about operating machinery, including automobiles, until they are reasonably certain that methocarbamol therapy does not adversely affect their ability to engage in such activities.
Therapeutic doses of aspirin can cause anaphylactic shock and other severe allergic reactions. It should be determined if the patient is allergic to aspirin, although a specific history of allergy may be lacking.
Products containing aspirin should be administered with caution to patients with gastritis, peptic ulceration, asthma, coagulation abnormalities, hypoprothrombinemia, vitamin K deficiency, or those receiving anticoagulant therapy.
Results from epidemiologic studies in pediatric patients with acute febrile illnesses, such as influenza and varicella, indicate an association between aspirin and Reye' Syndrome.
Caution should be observed when administering salicylates to persons with known allergies. Hypersensitivity to aspirin is particularly likely in patients with nasal polyps, and relatively common in patients with asthma (see also WARNINGS , Aspirin ).
Patients should be cautioned that Robaxisal may cause drowsiness or dizziness, which may impair their ability to operate motor vehicles or machinery.
Because Robaxisal may possess a general CNS depressant effect, patients should be cautioned about combined effects with alcohol and other central-nervous-system-depressants. Patients should be informed that Robaxisal contains aspirin and should not be taken by patients with an aspirin allergy.
Methocarbamol
See WARNINGS and PRECAUTIONS for interaction with CNS drugs and alcohol. Methocarbamol may inhibit the therapeutic effect of pyridostigmine bromide. Therefore, methocarbamol should be used with caution in patients with myasthenia gravis receiving anticholinesterase agents.
Corticosteroids enhance renal clearance of salicylates. In patients receiving concomitant corticosteroids and chronic aspirin therapy, withdrawal of corticosteroids may result in salicylism when renal clearance returns to normal.
Aspirin may enhance the effects of:
Aspirin may diminish the effects of uricosuric agents, such as probenecid and sulfinpyrazone, in the treatment of gout by competing for protein binding sites.
Methocarbamol may cause a color interference in certain screening tests for 5-hydroxyindoleacetic acid (5-HIAA) using nitrosonaphtol reagent and in screening tests for urinary vanillylmandelic acid (VMA) using the Gitlow method.
Aspirin
Aspirin may interfere with the following laboratory determinations in blood: serum amylase, fasting blood glucose, cholesterol, protein, serum glutamic-oxaloacetic transaminase (SGOT), uric acid, prothrombin time, and bleeding time.
Aspirin may interfere with the following laboratory determinations in urine: glucose, 5-hydroxyindoloacetic acid, Gerhardt ketone, vanillylmandelic acid (VMA), uric acid, diacetic acid, and spectrophotometric detection of barbiturates.
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.
Aspirin
Long-term studies conducted in mice and rats with aspirin, alone and in combination with other drugs, found no evidence of carcinogenesis.
Safe use of Robaxisal has not been established with regard to possible adverse effects upon fetal development. There have been very rare reports of fetal and congenital abnormalities following in utero exposure to methocarbamol. Therefore, Robaxisal 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 WARNINGS ).
Teratogenic effects--Pregnancy Category C
Animal reproduction studies have not been conducted with methocarbamol. It is also not known whethermethocarbamol can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
Reproductive studies in rats and mice have shown aspirin to be teratogenic and embryocidal at four to six times the human therapeutic dose. Studies in pregnant women have not shown aspirin to increase the risk of abnormalities when administered during the first trimester of pregnancy. In controlled studies involving 41,337 pregnant women and their offspring, there was no evidence that aspirin taken during pregnancy caused stillbirth, neonatal death or reduced birth weight. In controlled studies of 50,282 pregnant women and their offspring, aspirin administration in moderate and heavy doses during the first four lunar months of pregnancy resulted in no teratogenic effect.
Robaxisal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic effects
Therapeutic doses of aspirin in pregnant women close to term may cause bleeding in the fetus or the neonate.
During the last 6 months of pregnancy, regular use of aspirin in high doses may prolong pregnancy and delivery. Also, ingestion of aspirin prior to delivery may prolong delivery or may lead to bleeding in the mother and/or neonate.
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; however, aspirin is excreted in human milk in moderate amounts. It can produce a bleeding tendency either by interfering with the function of the infants platelets or by decreasing the amount of prothrombin in the blood. The risk is minimal if the mother takes the aspirin just after nursing and if the infant has an adequate store of vitamin K. Because of the potential for serious adverse reactions in nursing infants from Robaxisal, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness of Robaxisal in pediatric patients have not been established.
The following adverse reactions have been reported coincident with the administration of methocarbamol:
Body as a whole: Anaphylactic reaction, fever, headache
Cardiovascular system: Bradycardia, flushing, hypotension, syncope
Digestive system: Dyspepsia, jaundice (including cholestatic jaundice), nausea and vomiting
Hemic and lymphatic system: Leukopenia
Nervous system: Amnesia, confusion, diplopia, dizziness or light-headedness, drowsiness, insomnia, mild muscular incoordination, nystagmus, seizures (including grand mal), vertigo
Skin and special senses: Blurred vision, conjunctivitis with nasal congestion, metallic taste, pruritus, rash, urticaria
Aspirin
Adverse reactions that have been associated with the use of aspirin include: nausea and other gastrointestinal discomfort, gastritis, gastric erosion, vomiting, constipation, diarrhea, angioedema, asthma, rash, pruritus, urticaria.
Gastrointestinal discomfort may be minimized by taking Robaxisal with food.
Methocarbamol
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. One adult survived the deliberate ingestion of 22 to 30 grams of methocarbamol without serious toxicity. Another adult survived a dose of 30 to 50 grams. The principal symptom in both cases was extreme drowsiness. Treatment was symptomatic and recovery was uneventful.
The most severe manifestations of aspirin toxicity result from cardiovascular and respiratory insufficiency secondary to acid-base and electrolyte disturbances, complicated by hyperthermia and dehydration.
Respiratory alkalosis is characteristic of the early phase of aspirin intoxication while hyperventilation is occurring, but is quickly followed by metabolic acidosis in most people with severe intoxication.
Plasma concentrations of aspirin above 30 mg/mL are associated with toxicity. The single lethal dose of aspirin in adults is estimated to be 25 to 30 g.
Management of overdose includes symptomatic and supportive treatment. Supportive measures include maintenance of an adequate airway, monitoring urinary output and vital signs, and administration of intravenous fluids if necessary. The usefulness of hemodialysis in managing overdose is unknown.
If salicylate intoxication occurs, immediate and frequent monitoring of serum acid-base balance and electrolytes is imperative, so therapy with proper intravenous fluids may begin immediately. Hyperpnea may be controlled with sodium bicarbonate, especially in pediatric patients. Bicarbonate infusion may be indicated to correct acidosis and, if possible, to maintain an alkaline diuresis favorable to salicylate excretion. Judicious use of 5% CO 2 with 95% O 2 may be of benefit. Although its utility in methocarbamol toxicity is unknown, hemodialysis effectively removes salicylate from the body.
Two tablets four times daily. Three tablets four times daily may be used in severe conditions for one to three days in patients who are able to tolerate salicylates. These dosage recommendations provide 3.2 and 4.8 grams of methocarbamol, respectively, per day.
Robaxisal® (methocarbamol, USP and aspirin, USP) Tablets are supplied as pink and white laminated, compressed tablets in bottles of 100 (NDC 0031-7469-63).
Store at controlled room temperature, between 20°C and 25°C (68°F and 77°F).
Dispense in well-closed container.
CI 6385-1 Issued May 29, 2001
Manufactured by:
Pharmaceutical Division
A.H. Robins Company
Richmond, VA 23220
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