Mediquil

Mediquil uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Drug abuse and dependence
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Mediquil reviews

1 INDICATIONS AND USAGE

Mediquil Tablets are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults.

Mediquil Tablets should only be used for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use has not been established and because acute, painful musculoskeletal conditions are generally of short duration [see Dosage and Administration (2) ].

Mediquil Tablets are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions. (1)

Important Limitations:

• Should only be used for acute treatment periods up to two or three weeks (1)
• Not recommended in pediatric patients less than 16 years of age (8.4)

2 DOSAGE AND ADMINISTRATION

The recommended dose of Mediquil is 250 mg to 350 mg three times a day and at bedtime. The recommended maximum duration of Mediquil use is up to two or three weeks.

• Recommended dose is 250 mg to 350 mg three times a day and at bedtime. (2)

3 DOSAGE FORMS AND STRENGTHS

350 mg Tablets: white, round, unscored tablets debossed "2410 V" on one side and plain on the reverse side.

Tablets: 350 mg (3)

4 CONTRAINDICATIONS

Mediquil Tablets are contraindicated in patients with a history of acute intermittent porphyria or a hypersensitivity reaction to a carbamate such as meprobamate.

• Acute intermittent porphyria (4)
• Hypersensitivity reactions to a carbamate such as meprobamate (4)

5 WARNINGS AND PRECAUTIONS

• Due to sedative properties, may impair ability to perform hazardous tasks such as driving or operating machinery
• Additive sedative effects when used with other CNS depressants including alcohol (5.1)
• Cases of Drug Dependence, Withdrawal, and Abuse (5.2)
• Seizures (5.3)

5.1 Sedation

Carisoprodol has sedative properties (in the low back pain trials, 13% to 17% of patients who received Mediquil experienced sedation compared to 6% of patients who received placebo) [see ADVERSE REACTIONS (6.1) ] and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle or operating machinery. There have been post-marketing reports of motor vehicle accidents associated with the use of Mediquil.

Since the sedative effects of Mediquil and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive, appropriate caution should be exercised with patients who take more than one of these CNS depressants simultaneously.

5.2 Drug Dependence, Withdrawal, and Abuse

In the postmarketing experience with Mediquil, cases of dependence, withdrawal, and abuse have been reported with prolonged use. Most cases of dependence, withdrawal, and abuse occurred in patients who have had a history of addiction or who used Mediquil in combination with other drugs with abuse potential. However, there have been post-marketing adverse event reports of carisoprodol-associated abuse when used without other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. To reduce the chance of Mediquil dependence, withdrawal, or abuse, Mediquil should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol, and Mediquil should not be used more than two to three weeks for the relief of acute musculoskeletal discomfort.

Mediquil, and one of its metabolites, meprobamate, may cause dependence [see Clinical Pharmacology (12.3) ].

5.3 Seizures

There have been postmarketing reports of seizures in patients who received Mediquil. Most of these cases have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol) [see Overdosage (10) ].

6 ADVERSE REACTIONS

Most common adverse reactions are drowsiness, dizziness, and headache (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Qualitest Pharmaceuticals at 1‑800‑444-4011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Studies Experience

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

The data described below are based on 1387 patients pooled from two double blind, randomized, multicenter, placebo controlled, one-week trials in adult patients with acute, mechanical, lower back pain [see Clinical Studies (14) ]. In these studies, patients were treated with 250 mg of Mediquil, 350 mg of Mediquil, or placebo three times a day and at bedtime for seven days. The mean age was about 41 years old with 54% females and 46% males and 74% Caucasian, 16% Black, 9% Asian, and 2% other.

There were no deaths and there were no serious adverse reactions in these two trials. In these two studies, 2.7%, 2%, and 5.4% of patients treated with placebo, 250 mg of Mediquil, and 350 mg of Mediquil, respectively, discontinued due to adverse events; 0.5%, 0.5%, and 1.8% of patients treated with placebo, 250 mg of Mediquil, and 350 mg of Mediquil, respectively, discontinued due to central nervous system adverse reactions.

Table 1 displays adverse reactions reported with frequencies greater than 2% and more frequently than placebo in patients treated with Mediquil in the two trials described above.

6.2 Postmarketing Experience

The following events have been reported during postapproval use of Mediquil. Because these 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.

Cardiovascular: Tachycardia, postural hypotension, and facial flushing [see Overdosage (10) ].

Central Nervous System: Drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia, and seizures [see Overdosage (10) ].

Gastrointestinal: Nausea, vomiting, and epigastric discomfort.

Hematologic: Leukopenia, pancytopenia.

7 DRUG INTERACTIONS

• CNS depressants - additive sedative effects (5.1 and 7.1)

7.1 CNS Depressants

The sedative effects of Mediquil and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive. Therefore, caution should be exercised with patients who take more than one of these CNS depressants simultaneously. Concomitant use of Mediquil and meprobamate, a metabolite of Mediquil, is not recommended [see Warnings and Precautions (5.1) ].

7.2 CYP2C19 Inhibitors and Inducers

Mediquil is metabolized in the liver by CYP2C19 to form meprobamate [see Clinical Pharmacology (12.3) ]. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with Mediquil could result in increased exposure of Mediquil and decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. John's Wort, with Mediquil could result in decreased exposure of Mediquil and increased exposure of meprobamate. Low dose aspirin also showed an induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of Mediquil is unknown.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C. There are no data on the use of Mediquil during human pregnancy. Animal studies indicate that Mediquil crosses the placenta and results in adverse effects on fetal growth and postnatal survival. The primary metabolite of Mediquil, meprobamate, is an approved anxiolytic. Retrospective, post-marketing studies do not show a consistent association between maternal use of meprobamate and an increased risk for particular congenital malformations.

Teratogenic effects: Animal studies have not adequately evaluated the teratogenic effects of Mediquil. There was no increase in the incidence of congenital malformations noted in reproductive studies in rats, rabbits, and mice treated with meprobamate. Retrospective, post-marketing studies of meprobamate during human pregnancy were equivocal for demonstrating an increased risk of congenital malformations following first trimester exposure. Across studies that indicated an increased risk, the types of malformations were inconsistent.

Nonteratogenic effects: In animal studies, Mediquil reduced fetal weights, postnatal weight gain, and postnatal survival at maternal doses equivalent to 1–1.5 times the human dose. Rats exposed to meprobamate in-utero showed behavioral alterations that persisted into adulthood. For children exposed to meprobamate in-utero, one study found no adverse effects on mental or motor development or IQ scores. Mediquil should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

8.2 Labor and Delivery

There is no information about the effects of Mediquil on the mother and the fetus during labor and delivery.

8.3 Nursing Mothers

Very limited data in humans show that Mediquil is present in breast milk and may reach concentrations two to four times the maternal plasma concentrations. In one case report, a breast-fed infant received about 4–6% of the maternal daily dose through breast milk and experienced no adverse effects. However, milk production was inadequate and the baby was supplemented with formula. In lactation studies in mice, female pup survival and pup weight at weaning were decreased. This information suggests that maternal use of Mediquil may lead to reduced or less effective infant feeding and/or decreased milk production. Caution should be exercised when Mediquil is administered to a nursing woman.

8.4 Pediatric Use

The efficacy, safety, and pharmacokinetics of Mediquil in pediatric patients less than 16 years of age have not been established.

8.5 Geriatric Use

The efficacy, safety, and pharmacokinetics of Mediquil in patients over 65 years old have not been established.

8.6 Renal Impairment

The safety and pharmacokinetics of Mediquil in patients with renal impairment have not been evaluated. Since Mediquil is excreted by the kidney, caution should be exercised if Mediquil is administered to patients with impaired renal function. Mediquil is dialyzable by hemodialysis and peritoneal dialysis.

8.7 Hepatic Impairment

The safety and pharmacokinetics of Mediquil in patients with hepatic impairment have not been evaluated. Since Mediquil is metabolized in the liver, caution should be exercised if Mediquil is administered to patients with impaired hepatic function.

8.8 Patients with Reduced CYP2C19 Activity

Patients with reduced CYP2C19 activity have higher exposure to Mediquil. Therefore, caution should be exercised in administration of Mediquil to these patients [see Clinical Pharmacology (12.3) ].

9 DRUG ABUSE AND DEPENDENCE

Mediquil is not a controlled substance [see Warnings and Precautions (5.2) ]. Discontinuation of Mediquil in animals or in humans after chronic administration can produce withdrawal signs, and there are published case reports of human Mediquil dependence.

In vitro studies demonstrate that Mediquil elicits barbiturate-like effects. Animal behavioral studies indicate that Mediquil produces rewarding effects. Monkeys self administer Mediquil. Drug discrimination studies using rats indicate that Mediquil has positive reinforcing and discriminative effects similar to barbital, meprobamate, and chlordiazepoxide.

10 OVERDOSAGE

Overdosage of Mediquil commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with Mediquil overdosage. Many of the Mediquil overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of Mediquil and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of Mediquil have been reported alone or in combination with CNS depressants.

Treatment of Overdosage: Basic life support measures should be instituted as dictated by the clinical presentation of the Mediquil overdose. Induced emesis is not recommended due to the risk of CNS and respiratory depression, which may increase the risk of aspiration pneumonia. Gastric lavage should be considered soon after ingestion (within one hour). Circulatory support should be administered with volume infusion and vasopressor agents if needed. Seizures should be treated with intravenous benzodiazepines and the reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS depression, airway protective reflexes may be compromised and tracheal intubation should be considered for airway protection and respiratory support.

The following types of treatment have been used successfully with an overdose of meprobamate, a metabolite of Mediquil: activated charcoal (oral or via nasogastric tube), forced diuresis, peritoneal dialysis, and hemodialysis (carisoprodol is also dialyzable). Careful monitoring of urinary output is necessary and overhydration should be avoided. Observe for possible relapse due to incomplete gastric emptying and delayed absorption. For more information on the management of an overdose of Mediquil, contact a Poison Control Center.

11 DESCRIPTION

Mediquil Tablets, USP are available as 350 mg round, white tablets for oral administration. Mediquil is a white, crystalline powder, having a mild, characteristic odor and a bitter taste. It is slightly soluble in water; freely soluble in alcohol, in chloroform, and in acetone; and its solubility is practically independent of pH. Mediquil is present as a racemic mixture. Chemically, Mediquil is N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate and the molecular formula is C₁₂H₂₄N₂O₄, with a molecular weight of 260.33. The structural formula is:

Other ingredients in Mediquil Tablets, USP include croscarmellose sodium, hydrogenated vegetable oil, hypromellose, magnesium stearate and microcrystalline cellulose.

This in an image of the structural formula of Mediquil.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action of Mediquil in relieving discomfort associated with acute painful musculoskeletal conditions has not been clearly identified.

In animal studies, muscle relaxation induced by Mediquil is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain.

12.2 Pharmacodynamics

Mediquil is a centrally acting skeletal muscle relaxant that does not directly relax skeletal muscles.

A metabolite of Mediquil, meprobamate, has anxiolytic and sedative properties. The degree to which these properties of meprobamate contribute to the safety and efficacy of Mediquil is unknown.

12.3 Pharmacokinetics

The pharmacokinetics of Mediquil and its metabolite meprobamate were studied in a crossover study of 24 healthy subjects (12 male and 12 female) who received single doses of 250 mg and 350 mg Mediquil. The exposure of Mediquil and meprobamate was dose proportional between the 250 mg and 350 mg doses. The C_max of meprobamate was 2.5 ± 0.5 μg/mL (mean ± SD) after administration of a single 350 mg dose of Mediquil, which is approximately 30% of the C_max of meprobamate (approximately 8 μg/mL) after administration of a single 400 mg dose of meprobamate.

Absorption: Absolute bioavailability of Mediquil has not been determined. The mean time to peak plasma concentrations (T_max) of Mediquil was approximately 1.5 to 2 hours. Co-administration of a high-fat meal with Mediquil (350 mg tablet) had no effect on the pharmacokinetics of Mediquil. Therefore, Mediquil may be administered with or without food.

Metabolism: The major pathway of Mediquil metabolism is via the liver by cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism.

Elimination: Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours. The half-life of meprobamate is approximately 10 hours.

Gender: Exposure of Mediquil is higher in female than in male subjects (approximately 30–50% on a weight adjusted basis). Overall exposure of meprobamate is comparable between female and male subjects.

Patients with Reduced CYP2C19 Activity: Carisoprodol should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to Mediquil, and concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3–5% and in Asians is approximately 15–20%.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate the carcinogenic potential of Mediquil.

Mediquil was not formally evaluated for genotoxicity. In published studies, Mediquil was mutagenic in the in vitro mouse lymphoma cell assay in the absence of metabolizing enzymes, but was not mutagenic in the presence of metabolizing enzymes. Mediquil was clastogenic in the in vitro chromosomal aberration assay using Chinese hamster ovary cells with or without the presence of metabolizing enzymes. Other types of genotoxic tests resulted in negative findings. Mediquil was not mutagenic in the Ames reverse mutation assay using S. typhimurium strains with or without metabolizing enzymes, and was not clastogenic in an in vivo mouse micronucleus assay of circulating blood cells.

Mediquil was not formally evaluated for effects on fertility. Published reproductive studies of Mediquil in mice found no alteration in fertility although an alteration in reproductive cycles characterized by a greater time spent in estrus was observed at a Mediquil dose of 1200 mg/kg/day. In a 13-week toxicology study that did not determine fertility, mouse testes weight and sperm motility were reduced at a dose of 1200 mg/kg/day. In both studies, the no effect level was 750 mg/kg/day, corresponding to approximately 2.6 times the human equivalent dosage of 350 mg four times a day, based on a body surface area comparison. The significance of these findings for human fertility is not known.

14 CLINICAL STUDIES

The safety and efficacy of Mediquil for the relief of acute, idiopathic mechanical low back pain was evaluated in two 7-day, double blind, randomized, multicenter, placebo controlled, U.S. trials (Studies 1 and 2). Patients had to be 18 to 65 years old and had to have acute back pain (≤ 3 days of duration) to be included in the trials. Patients with chronic back pain; at increased risk for vertebral fracture (e.g., history of osteoporosis); with a history of spinal pathology (e.g., herniated nucleus pulposis, spondylolisthesis or spinal stenosis); with inflammatory back pain, or with evidence of a neurologic deficit were excluded from participation. Concomitant use of analgesics (e.g., acetaminophen, NSAIDs, tramadol, opioid agonists), other muscle relaxants, botulinum toxin, sedatives (e.g., barbiturates, benzodiazepines, promethazine hydrochloride), and anti-epileptic drugs was prohibited.

In Study 1, patients were randomized to one of three treatment groups (i.e., Mediquil 250 mg, Mediquil 350 mg, or placebo) and in Study 2 patients were randomized to two treatment groups (i.e., Mediquil 250 mg or placebo). In both studies, patients received study medication three times a day and at bedtime for seven days.

The primary endpoints were the relief from starting backache and the global impression of change, as reported by patients, on Study Day 3. Both endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome) in both studies. The primary statistical comparison was between the Mediquil 250 mg and placebo groups in both studies.

The proportion of patients who used concomitant acetaminophen, NSAIDs, tramadol, opioid agonists, other muscle relaxants, and benzodiazepines was similar in the treatment groups.

The results for the primary efficacy evaluations in the acute, low back pain studies are presented in Table 3.

^aThe primary efficacy endpoints (Relief from Starting Backache and Global Impression of Change) were assessed by the patients on Study Day 3. These endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome).

^b Mean is the least squared mean and SE is the standard error of the mean. The ANOVA model was used for the primary statistical comparison between the Mediquil 250 mg and placebo groups.

Patients treated with Mediquil experienced improvement in function as measured by the Roland-Morris Disability Questionnaire (RMDQ) score on Days 3 and 7.

16 HOW SUPPLIED/STORAGE AND HANDLING

350 mg Tablets: white, round, unscored tablets debossed "2410 V" on one side and plain on the reverse side

49999-064-01

Storage:

Store at 20°-25°C (68°-77°F).

17 PATIENT COUNSELING INFORMATION

Patients should be advised to contact their physician if they experience any adverse reactions to Mediquil tablets.

17.1 Sedation

Patients should be advised that Mediquil tablets may cause drowsiness and/or dizziness, and has been associated with motor vehicle accidents. Patients should be advised to avoid taking Mediquil before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery [see Warnings and Precautions ].

17.2 Avoidance of Alcohol and Other CNS Depressants

Patients should be advised to avoid alcoholic beverages while taking Mediquil tablets and to check with their doctor before taking other CNS depressants such as benzodiazepines, opioids, tricyclic antidepressants, sedating antihistamines, or other sedatives [see Warnings and Precautions (5.1) ].

17.3 Mediquil Tablets Should Only Be Used for Short-Term Treatment

Patients should be advised that treatment with Mediquil tablets should be limited to acute use (up to two or three weeks) for the relief of acute, musculoskeletal discomfort. In the post-marketing experience with Mediquil tablets, cases of dependence, withdrawal, and abuse have been reported with prolonged use. If the musculoskeletal symptoms still persist, patients should contact their healthcare provider for further evaluation.

To report SUSPECTED ADVERSE REACTIONS, contact Qualitest Pharmaceuticals at 1-800-444-4011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Manufactured for:

QUALITEST PHARMACEUTICALS

Huntsville, AL 35811

8181281

Revised: 10/2010

R5

image of label

Mediquil pharmaceutical active ingredients containing related brand and generic drugs:

• Carisoprodol

Mediquil available forms, composition, doses:

• N/A

Mediquil destination | category:

• Human:
• Skeletal muscle relaxants

Mediquil Anatomical Therapeutic Chemical codes:

• M03BA02 - Carisoprodol

Mediquil pharmaceutical companies:

• N/A

References

1. Dailymed."CARISOPRODOL TABLET [LAKE ERIE MEDICAL DBA QUALITY CARE PRODUCTS LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. Dailymed."ASPIRIN; CARISOPRODOL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
3. "carisoprodol". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Depending on the reaction of the Mediquil after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Mediquil not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology