Artridol

Betamethasone:

• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Artridol (Betamethasone) reviews

Artridol (Betamethasone) Spray is indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older.

Artridol (Betamethasone) Spray is a corticosteroid indicated for the treatment of mild to moderate plaque psoriasis in patients 18 years of age or older. (1)

2 DOSAGE AND ADMINISTRATION

Shake well before use.

Apply Artridol (Betamethasone) Spray to the affected skin areas twice daily and rub in gently.

Use Artridol (Betamethasone) Spray for up to 4 weeks of treatment. Treatment beyond 4 weeks is not recommended.

Discontinue Artridol (Betamethasone) Spray when control is achieved.

Do not use if atrophy is present at the treatment site.

Do not bandage, cover, or wrap the treated skin area unless directed by a physician.

Avoid use on the face, scalp, axilla, groin, or other intertriginous areas.

Artridol (Betamethasone) Spray is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

• Apply to the affected skin areas twice daily. Rub in gently. (2)
• Use Artridol (Betamethasone) Spray for up to 4 weeks and not beyond. (2)
• Discontinue treatment when control is achieved. (2)
• Do not use if atrophy is present at the treatment site. (2)
• Do not use with occlusive dressings unless directed by a physician. (2)
• Avoid use on the face, scalp, axilla, groin, or other intertriginous areas. (2)
• Not for oral, ophthalmic, or intravaginal use. (2)

3 DOSAGE FORMS AND STRENGTHS

Spray, 0.05% for topical use. Each gram of Artridol (Betamethasone) Spray contains 0.643 mg Artridol (Betamethasone) dipropionate USP (equivalent to 0.5 mg Artridol (Betamethasone)) in a slightly thickened, white to off-white oil-in-water emulsion.

Spray: 0.05% (equivalent to 0.5 mg betamethasone/g) (3)

4 CONTRAINDICATIONS

None.

• None. (4)

5 WARNINGS AND PRECAUTIONS

• Artridol Spray can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency during or after treatment. (5.1)
• Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can result from systemic absorption of topical corticosteroids. (5.1)
• Use of topical corticosteroids may require periodic evaluation for HPA axis suppression. (5.1)
• Modify use if HPA axis suppression develops. (5.1)
• High potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure and young age may predispose patients to HPA axis suppression. (5.1)
• Pediatric patients may be more susceptible to systemic toxicity when treated with topical corticosteroids. (5.1, 8.4)

5.1 Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression and Other Unwanted Systemic Glucocorticoid Effects

Artridol (Betamethasone) Spray can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during or after withdrawal of treatment. Factors that predispose to HPA axis suppression include the use of high-potency corticosteroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age.

Evaluation for HPA axis suppression may be done by using the adrenocorticotropic hormone (ACTH) stimulation test.

In a study including 48 evaluable subjects 18 years of age or older with moderate to severe plaque psoriasis, abnormal ACTH stimulation test results suggestive of adrenal suppression were identified in 5 out of 24 (20.8%) subjects after treatment with Artridol (Betamethasone) Spray twice daily for 15 days. No subject (0 out of 24) had abnormal ACTH stimulation test results after treatment with Artridol (Betamethasone) Spray twice daily for 29 days .

If HPA axis suppression is documented, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. If signs and symptoms of steroid withdrawal occur, supplemental systemic corticosteroids may be required.

Systemic effects of topical corticosteroids may also manifest as Cushing’s syndrome, hyperglycemia, and glucosuria. These events are rare and generally occur after prolonged exposure to larger than recommended doses, particularly with high-potency topical corticosteroids.

Minimize the unwanted risks from endocrine effects by mitigating the risk factors favoring increased systemic bioavailability and by using the product as recommended .

Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratios. Use of Artridol (Betamethasone) Spray is not recommended in pediatric patients .

5.2 Allergic Contact Dermatitis

Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Corroborate such an observation with appropriate diagnostic patch testing. If irritation develops, discontinue the topical corticosteroid and institute appropriate therapy.

6 ADVERSE REACTIONS

The most common adverse reactions are application site reactions, including pruritus, burning and/or stinging, pain, and atrophy. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Promius Pharma, LLC. at 1-888-966-8766 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In two randomized, multicenter, prospective vehicle-controlled clinical trials, subjects with moderate plaque psoriasis of the body applied Artridol (Betamethasone) Spray or vehicle spray twice daily for 4 weeks. A total of 352 subjects applied Artridol (Betamethasone) Spray and 180 subjects applied vehicle spray.

Adverse reactions that occurred in at least 1% of subjects treated with Artridol (Betamethasone) Spray for up to 28 days are presented in Table 1.

Less common adverse reactions (with occurrence lower than 1% but higher than 0.1%) in subjects treated with Artridol (Betamethasone) spray were application site reactions including telangiectasia, dermatitis, discoloration, folliculitis and skin rash, in addition to dysgeusia and hyperglycemia. These adverse reactions were not observed in subjects treated with vehicle.

6.2 Postmarketing Experience

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Postmarketing reports for local adverse reactions to topical corticosteroids have also included striae, irritation, dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, and miliaria.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Artridol Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Artridol (Betamethasone) dipropionate has been shown to be teratogenic in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. The abnormalities observed included umbilical hernias, cephalocele, and cleft palate.

8.3 Nursing Mothers

Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids can result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Artridol (Betamethasone) Spray is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Artridol Spray in patients younger than 18 years of age have not been studied; therefore use in pediatric patients is not recommended. Because of a higher ratio of skin surface area to body mass, pediatric patients are at greater risk of systemic toxicity, including HPA axis suppression and adrenal insufficiency, when treated with topical drugs. [see Warnings and Precautions (5.1)]

Rare systemic effects such as Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high potency topical corticosteroids.

Local adverse reactions including skin atrophy have also been reported with use of topical corticosteroids in pediatric patients.

8.5 Geriatric Use

Clinical studies of Artridol (Betamethasone) Spray did not include sufficient numbers of subjects who were 65 years of age or older to determine whether they respond differently from younger subjects.

11 DESCRIPTION

Artridol (Betamethasone) Spray contains 0.0643% Artridol (Betamethasone) dipropionate (equivalent to 0.05% Artridol (Betamethasone)), a synthetic, fluorinated corticosteroid.

The chemical name for Artridol (Betamethasone) dipropionate is 9-fluoro-11(β), 17, 21-trihydroxy-16(β)-methylpregna-1,4-diene-3,20-dione-17,21-dipropionate. The empirical formula is C₂₈H₃₇FO₇ and the molecular weight is 504.6. The structural formula is shown below.

Each gram of Artridol (Betamethasone) Spray contains 0.643 mg of Artridol (Betamethasone) dipropionate USP (equivalent to 0.5 mg Artridol (Betamethasone)) in a slightly thickened, white to off-white, oil-in-water, non-sterile emulsion with the following inactive ingredients:, butylated hydroxytoluene, cetostearyl alcohol, hydroxyethyl cellulose, methylparaben, mineral oil, oleyl alcohol, polyoxyl 20 cetostearyl ether, propylparaben, purified water, and sorbitan monostearate. Artridol (Betamethasone) Spray is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing to patients.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of Artridol Spray in psoriasis is unknown.

12.2 Pharmacodynamics

Vasoconstrictor studies performed with Artridol (Betamethasone) Spray in healthy subjects indicate that it is in the mid-range of potency as compared with other topical corticosteroids; however, similar blanching scores do not necessarily imply therapeutic equivalence.

The potential for HPA axis suppression by Artridol (Betamethasone) Spray was evaluated in a study randomizing 52 adult subjects with moderate to severe plaque psoriasis. Artridol (Betamethasone) Spray was applied twice daily for 15 or 29 days, in subjects with psoriasis involving a mean of 29.0% and 26.5% body surface area at baseline across the 2 treatment duration arms, respectively. Forty-eight (48) subjects were evaluated for HPA axis suppression at the end of treatment. The proportion of subjects demonstrating HPA axis suppression was 20.8% (5 out of 24) in subjects treated with Artridol (Betamethasone) Spray for 15 days. No subjects (0 out of 24) treated with Artridol (Betamethasone) Spray for 29 days had HPA axis suppression. In this study HPA axis suppression was defined as serum cortisol level ≤18 mcg/dL 30-minutes post-cosyntropin stimulation. In the 4 subjects with available follow-up values, all subjects had normal ACTH stimulation tests at follow-up.

12.3 Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.

Topical corticosteroids are absorbed through normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Plasma concentrations of Artridol (Betamethasone) dipropionate, betamethasone-17-propionate, and Artridol (Betamethasone) were measured at baseline, and before and after the last dose (1, 3, and 6 hours) in the HPA axis suppression trial in subjects with psoriasis [see Clinical Pharmacology (12.2)]. The majority of subjects had no measurable plasma concentration (<5.00 pg/mL) of Artridol (Betamethasone) dipropionate, while the metabolites, betamethasone-17-propionate and Artridol (Betamethasone), were detected in the majority of subjects (Table 2). There was high variability in the data but there was a trend toward higher systemic exposure at Day 15 and lower systemic exposure at Day 29.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Artridol (Betamethasone) dipropionate.

In a 90-day repeat-dose toxicity study in rats, topical administration of Artridol (Betamethasone) dipropionate spray formulation at dose concentrations of 0.05% and 0.1% (providing dose levels up to 0.5 mg/kg/day in males and 0.25 mg/kg/day in females) resulted in a toxicity profile consistent with long-term exposure to corticosteroids including reduced body weight gain, adrenal atrophy, and histological changes in bone marrow, thymus and spleen indicative of severe immune suppression. A no observable adverse effect level (NOAEL) could not be determined in this study. Although the clinical relevance of the findings in animals to humans is not clear, sustained glucocorticoid-related immune suppression may increase the risk of infection and possibly the risk of carcinogenesis.

Artridol (Betamethasone) was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in vitro human lymphocyte chromosome aberration assay, and equivocal in the in vivo mouse bone marrow micronucleus assay.

Studies in rabbits, mice, and rats using intramuscular doses up to 1, 33, and 2 mg/kg, respectively, resulted in dose-related increases in fetal resorptions in rabbits and mice.

14 CLINICAL STUDIES

Two multi-center, randomized, double-blind, vehicle-controlled clinical trials were conducted in subjects aged 18 years and older with moderate plaque psoriasis. In both trials, randomized subjects applied Artridol (Betamethasone) Spray or vehicle spray to the affected areas twice daily for 28 days. Enrolled subjects had body surface area of involvement between 10% to 20%, and an Investigator Global Assessment (IGA) score of 3 (moderate).

Efficacy was assessed as the proportion of subjects who were considered a treatment success (defined as having an IGA score of 0 or 1 [clear or almost clear] and at least a 2-grade reduction from baseline). Table 3 presents the efficacy results at Day 15 and Day 29.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied/Storage

Artridol Spray is a slightly thickened, white to off-white, non-sterile emulsion supplied in high density polyethylene bottles with a heat induction seal lined polypropylene cap. The drug is supplied in the following volumes:

• 60 mL (NDC 67857-808-17)
• 120 mL (NDC 67857-808-04)

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) .

Each unit is co-packaged with a manual spray pump for installation by the pharmacist prior to dispensing.

16.2 Handling/Instructions for the Pharmacist

• Remove the spray pump from the wrapper.
• Remove and discard the cap from the bottle.
• Keeping the bottle upright, insert the spray pump into the bottle and turn clockwise until it is closed tightly.
• Dispense the bottle with the spray pump inserted.
• Include the date dispensed in the space provided on the carton.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Inform patients of the following:

• Discontinue therapy when control is achieved, unless directed otherwise by the physician.
• Do not use for longer than 4 consecutive weeks.
• Avoid contact with the eyes.
• Avoid use of Artridol (Betamethasone) Spray on the face, scalp, underarms, groin or other intertriginous areas, unless directed by the physician.
• Do not occlude the treatment area with bandage or other covering, unless directed by the physician.
• Local reactions and skin atrophy are more likely to occur with occlusive use, prolonged use, or use of higher potency corticosteroids.

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Distributed by: Promius Pharma, LLC., Princeton, NJ 08540

Artridol (Betamethasone) is a trademark of Promius Pharma, LLC.

Issued: 02/2016

007465

140728

Instructions for Use

Artridol (Betamethasone) (ser-ne-vo)

(betamethasone dipropionate)

Spray, 0.05%

Important: Artridol (Betamethasone) Spray is for use on the skin only. Do not get Artridol (Betamethasone) Spray near or in your eyes, mouth, or vagina.

Read this “Instructions for Use” before you start using Artridol (Betamethasone) Spray and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

Parts of the Artridol (Betamethasone) Spray bottle.

Figure A

How to apply Artridol (Betamethasone) Spray:

Step 1: Shake the Artridol (Betamethasone) Spray bottle well. Remove the cap from the pump top.

Step 2: Hold the bottle in an upright position while pointing the opening of the pump top in the direction of the affected area. To spray, push down on the pump top. Apply Artridol (Betamethasone) Spray to the affected area as instructed by your doctor. (See Figure B )

Figure B

Step 3: Spray only enough Artridol (Betamethasone) Spray to cover the affected area, for example, the elbow (See Figure C ). Rub in Artridol (Betamethasone) Spray gently.

Figure C

Repeat Steps 2 and 3 to apply Artridol (Betamethasone) Spray to other affected areas as instructed by your doctor.

Step 4: After applying Artridol (Betamethasone) Spray, place the cap back onto the pump top. (See Figure D )

Figure D

How should I store Artridol (Betamethasone) Spray?

• Store Artridol (Betamethasone) Spray at room temperature between 68°F to 77°F (20°C to 25°C).
• Throw away (discard) any unused Artridol (Betamethasone) Spray after 28 days.

Keep Artridol (Betamethasone) Spray and all medicines out of the reach of children.

This “Instructions for Use” has been approved by the U.S. Food and Drug Administration.

Manufactured by: DPT Laboratories, Ltd., San Antonio, TX 78215

Distributed by: Promius Pharma, LLC., Princeton, NJ 08540

Artridol (Betamethasone) is a trademark of Promius Pharma, LLC.

Issued: 02/2016

007528

140693

Indometacin:

• Artridol information
• Artridol indications
• Artridol warnings
• Artridol intake guidelines
• Artridol dosage
• Artridol overdose
• Artridol missed dose
• Artridol side effects
• Artridol drug reactions
• Artridol (Indometacin) reviews

Artridol information

Artridol (Indometacin) is a non-steroidal anti-inflammatory drug, typically prescribed in order to manage symptoms such as pain, fever, swelling and stiffness. This medication acts as an inhibitor of prostaglandin production - prostaglandins are the agents that are known to induce these symptoms.

Artridol indications

There are several medical conditions for which Artridol (Indometacin) may be prescribed, including rheumatoid arthritis, ankylosing spondylitis, arthritic gout, juvenile arthritis, osteoarthritis and psoriatic arthritis. Apart from these, this drug has shown positive results when prescribed for the treatment of Reiter's syndrome, Bartter syndrome and Paget's disease. Artridol (Indometacin) may also be prescribed for patients that are suffering from pseudogout, pericarditis, dysmenorrheal, bursitis or tendonitis. This drug is also effective for the management of such affections as nephrogenic diabetes insipidus, hemicrania continua, paroxysmal hemicrania and migraine, but it may also be used in the management of symptoms such as pain and fever associated with malignancies (bony metastases, tumors or lymphogranulomatosis). There may be other uses for this medication as well.

Artridol warnings

The intake of Artridol (Indometacin) is not suitable in the case of patients that are suffering from an allergy to this drug, to any of its components, to Aspirin or to other non-steroidal anti-inflammatory medications. Also, this drug should not be employed in the treatment of patients with concurrent peptic ulcers or with severe preexisting liver or kidney damage. In the case of neonates with patent ductus arteriosus, Artridol (Indometacin) should not be employed in the treatment of children of less than 2 years of age.

Caution should be employed in the treatment of patients suffering from Parkinson's disease, psychotic disorders or epilepsy as Artridol (Indometacin) may worsen the symptoms of these conditions. Therapy with this medication may require special consideration when employed in the treatment of patients suffering from bleeding tendencies as Artridol (Indometacin) may inhibit the aggregation of platelets. Frequent blood cell counts clinical evaluations are recommended in the case of patients with preexisting bone marrow damage.

Artridol intake guidelines

It is highly recommended that the patient closely follows the Artridol (Indometacin) intake guidelines that he or she has been given by the prescribing doctor. In many cases, regular physical examination of the patient may be required, in order to detect early signs of oedema or any possible side effects affecting the central nervous system. Blood pressure should be measured in order to check for hypertension. As part of the regular testing, blood cell counts, serum electrolyte measurements of the sodium, chloride and potassium and assessment of renal and liver functions should be performed, especially in the case of patients that are being administered Artridol (Indometacin) in combination with a potassium-sparing diuretic or an ACE inhibitor; this is useful in order to detect or prevent development of kidney failure or hyperkalemia.

Artridol dosage

The exact Artridol (Indometacin) dosage depends on the medical condition that the individual is being treated for. Apart from that, the examining health care professional will decide the appropriate dosage based on several factors such as the patient's medical history, his or her age as well as general health condition. The Artridol (Indometacin) dosage may vary greatly from one patient to another, so it is highly recommended that you use the exact dosage that has been prescribed in your case.

Artridol overdose

Artridol (Indometacin) has a high factor of acute toxicity in humans, and in some cases an overdose with this drug resulted in the death of the patient. As such, it is highly advised to take the medication dosage that has been prescribed for your case, and never take a higher dose.

Typical symptoms of a Artridol (Indometacin) overdose include dizziness, drowsiness, mental confusion, severe headache, paraesthesia, nausea, vomiting and numbness of limbs. In some cases, severe gastrointestinal bleeding as well as cardiac arrest or cerebral oedema are possible.

Artridol missed dose

It is highly advised that you set up a regular intake schedule in order to lower the risks of missing a dose of your medication. In the case of Artridol (Indometacin), if you happen to miss a dose it is advised to take it as soon as you remember, unless it is almost time for another dose of the medication. If this is the case, you should completely skip the missed dose and continue with your regular intake schedule; you should bring the matter to the attention of your personal health care provider as soon as possible. He or she will assess the situation and decide on the appropriate course of action to take, if needed.

Artridol side effects

There are several side effects associated with a Artridol (Indometacin) treatment. Treatment with this drug may lead to the appearance of peptic ulcers or other less severe gastrointestinal disturbances such as mild diarrhea, dyspepsia or heartburn. Due to the retention of lithium, patients following a treatment with Artridol (Indometacin) have a higher risk of lithium toxicity. Hypertension, hyperkalemia and hypernatremia as well as oedema are also possible side effects of a therapy with this drug. In up to 20% of the cases, the patients may experience headaches, sometimes together with tinnitus, vertigo, dizziness, hearing loss or blurred vision. Photosensitivity and skin reactions have been reported. In rare cases, Artridol (Indometacin) may cause severe damage to the bone marrow, severe or even lethal hepatitis or potentially fatal shock.

Artridol drug reactions

At this time, there is no exact information regarding the possible interactions between Artridol (Indometacin) and other medications. It is advised that you consult with your personal health care professional and inform him or her about any other medication you are currently taking before starting a treatment with this drug.

Methocarbamol:

• Description:
• Clinical pharmacology:
• Indications and usage:
• Contraindications:
• Warnings:
• Precautions:
• Adverse reactions
• Overdosage
• Dosage and administration:
• How supplied:
• Artridol (Methocarbamol) reviews

Artridol (Methocarbamol) TABLETS, USP

Rev. 03/11

Rx Only

DESCRIPTION:

Artridol (Methocarbamol) Tablets, USP, a carbamate derivative of guaifenesin, are a central nervous system (CNS) depressant with sedative and musculoskeletal relaxant properties. The structural formula is:

The chemical name for Artridol (Methocarbamol) is 3-(2-Methoxyphenoxy)-1,2-propanediol 1-carbamate and has the empirical formula C₁₁H₁₅NO₅. Its molecular weight is 241.24.

Artridol (Methocarbamol) is a white powder, sparingly soluble in water and chloroform, soluble in alcohol (only with heating) and propylene glycol, and insoluble in benzene and n-hexane.

Each tablet, for oral administration, contains 500 mg or 750 mg of Artridol (Methocarbamol), USP. In addition each tablet contains the following inactive ingredients: Colloidal Silicon Dioxide, Lactose Monohydrate, Magnesium Stearate, Methylcellulose, Microcrystalline Cellulose, Pregelatinized Starch and Sodium Starch Glycolate.

Artridol (Methocarbamol) structural formula

CLINICAL

Pharmacology:

The mechanism of action of Artridol 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.

Pharmacokinetics :

In healthy volunteers, the plasma clearance of Artridol (Methocarbamol) ranges between 0.20 and 0.80 L/h/kg, the mean plasma elimination half-life ranges between 1 and 2 hours, and the plasma protein binding ranges between 46% and 50%.

Artridol (Methocarbamol) is metabolized via dealkylation and hydroxylation. Conjugation of Artridol (Methocarbamol) also is likely. Essentially all Artridol (Methocarbamol) metabolites are eliminated in the urine. Small amounts of unchanged Artridol (Methocarbamol) also are excreted in the urine.

Special Populations :

Elderly

The mean elimination half-life of Artridol (Methocarbamol) in elderly healthy volunteers (mean (± SD) age, 69 (± 4) years) was slightly prolonged compared to a 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 Artridol (Methocarbamol) was slightly decreased in the elderly versus younger volunteers (41 to 43% versus 46 to 50%, respectively).

Renally Impaired

The clearance of Artridol (Methocarbamol) in 8 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 Impaired

In 8 patients with cirrhosis secondary to alcohol abuse, the mean total clearance of Artridol (Methocarbamol) was reduced approximately 70% compared to that obtained in 8 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 Artridol (Methocarbamol) bound to plasma proteins was decreased to approximately 40 to 45% compared to 46 to 50% in the normal subjects.

INDICATIONS AND USAGE:

Artridol (Methocarbamol) Tablets are 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 Artridol (Methocarbamol) has not been clearly identified, but may be related to its sedative properties. Artridol (Methocarbamol) does not directly relax tense skeletal muscles in man.

CONTRAINDICATIONS:

Methocarbamol Tablets are contraindicated in patients hypersensitive to Artridol (Methocarbamol) or to any of the tablet components.

WARNINGS:

Since Artridol may possess a general CNS depressant effect, patients receiving Artridol (Methocarbamol) Tablets should be cautioned about combined effects with alcohol and other CNS depressants.

Safe use of Artridol (Methocarbamol) Tablets 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 Artridol (Methocarbamol). Therefore, Artridol (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 ).

Use in Activities Requiring Mental Alertness :

Artridol (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 Artridol (Methocarbamol) therapy does not adversely affect their ability to engage in such activities.

PRECAUTIONS:

Information for Patients:

Patients should be cautioned that Artridol may cause drowsiness or dizziness, which may impair their ability to operate motor vehicles or machinery.

Because Artridol (Methocarbamol) may possess a general CNS-depressant effect, patients should be cautioned about combined effects with alcohol and other CNS depressants.

Drug Interactions:

See WARNINGS and PRECAUTIONS for interaction with CNS drugs and alcohol.

Artridol (Methocarbamol) may inhibit the effect of pyridostigmine bromide. Therefore, Artridol (Methocarbamol) should be used with caution in patients with myasthenia gravis receiving anticholinesterase agents.

Drug /Laboratory Test Interactions:

Artridol may cause a 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility :

Long-term studies to evaluate the carcinogenic potential of Artridol (Methocarbamol) have not been performed. No studies have been conducted to assess the effect of Artridol (Methocarbamol) on mutagenesis or its potential to impair fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with Artridol. It is also not known whether Artridol (Methocarbamol) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Methocarbamol Tablets should be given to a pregnant woman only if clearly needed.

Safe use of Artridol (Methocarbamol) Tablets has not been established with regard to possible adverse effects upon fetal development. There have been reports of fetal and congential abnormalities following in utero exposure to Artridol (Methocarbamol). Therefore, Artridol (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 WARNINGS ).

Nursing Mothers

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

Pediatric Use

Safety and effectiveness of Artridol (Methocarbamol) Tablets in pediatric patients below the age of 16 have not been established.

ADVERSE REACTIONS

Adverse reactions reported coincident with the administration of Artridol (Methocarbamol) include:

Body as a Whole : Anaphylactic reaction, angioneurotic edema, fever, headache

Car d iovascular System : Bradycardia, flushing, hypotension, syncope, thrombophlebitis

Digestive System : Dyspepsia, jaundice (including cholestatic jaundice), nausea and vomiting

Hemic and Lymphatic S ystem : Leukopenia

Immune System : Hypersensitivity reactions

Nervous System : Amnesia, confusion, diplopia, dizziness or lightheadedness, drowsiness, insomnia, mild muscular incoordination, nystagmus, sedation, seizures (including grand mal), vertigo

Skin and Special Senses : Blurred vision, conjunctivitis, nasal congestion, metallic taste, pruritus, rash, urticaria

To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

Limited information is available on the acute toxicity of Artridol. Overdose of Artridol (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 Artridol (Methocarbamol) alone or in the presence of other CNS depressants, alcohol or psychotropic drugs.

Treatment:

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.

DOSAGE AND ADMINISTRATION:

500 mg – Adults: Initial dosage, 3 tablets q.i.d.; maintenance dosage, 2 tablets q.i.d.

750 mg – Adults: Initial dosage, 2 tablets q.i.d.; maintenance dosage, 1 tablet q.4h. or 2 tablets t.i.d.

Six grams a day are recommended for the first 48 to 72 hours of treatment. (For severe conditions 8 grams a day may be administered.) Thereafter, the dosage can usually be reduced to approximately 4 grams a day.

HOW SUPPLIED:

Artridol (Methocarbamol) Tablets 500 mg: White, Round Tablets; Debossed “West-ward 290” on one side and Scored on the other side.

Bottles of 100 tablets

Bottles of 500 tablets

Bottles of 1000 tablets

Unit Dose Box of 100 tablets

Artridol (Methocarbamol) Tablets 750 mg: White, Capsule Shaped Tablets; Debossed “WEST-WARD 292” on one side and Scored on the other side.

Bottles of 100 tablets

Bottles of 500 tablets

Bottles of 1000 tablets

Unit Dose Box of 100 tablets

Store at 20-25^oC (68-77^oF). Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Manufactured by:

West-ward Pharmaceutical Corp.

Eatontown, NJ 07724

Revised March 2011