Sanmag Tablets

Chlordiazepoxide Hydrochloride:

• Warning: risks from concomitant use with opioids
• Description
• Animal pharmacology
• Indications and usage
• Contraindications
• Warnings
• Overdosage
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Dosage and administration
• How supplied
• Medication guide
• Sanmag Tablets (Chlordiazepoxide Hydrochloride) reviews

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

• Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.

DESCRIPTION

Sanmag Tablets (Chlordiazepoxide Hydrochloride) combines in a single capsule formulation the antianxiety action of Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride and the anticholinergic/spasmolytic effects of clidinium bromide.

Each Sanmag Tablets (Chlordiazepoxide Hydrochloride) capsule contains the active ingredients 5 mg Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride and 2.5 mg clidinium bromide. Each capsule also contains the inactive ingredients corn starch, lactose monohydrate, talc, methylparaben, propylparaben, potassium sorbate, D&C Yellow No. 10, FD&C Green No. 3, titanium dioxide, and gelatin.

Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride is a versatile, therapeutic agent of proven value for the relief of anxiety and tension. It is indicated when anxiety, tension or apprehension are significant components of the clinical profile. It is among the safer of the effective psychopharmacologic compounds.

Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride is 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide hydrochloride. A colorless, crystalline substance, it is soluble in water. It is unstable in solution and the powder must be protected from light. The molecular weight is 336.22. The structural formula of Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride is as follows:

Clidinium bromide is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Structurally clidinium bromide is:

Chemical Structure Chemical Structure

ANIMAL PHARMACOLOGY

Sanmag Tablets hydrochloride has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses. Hostile monkeys were made tame by oral drug doses, which did not cause sedation. Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride revealed a "taming-action with the elimination of fear and aggression”. The taming effect of Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.

The oral LD₅₀ of single doses of Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride, calculated according to the method of Miller and Tainter, is 720 ± 51 mg/kg as determined in mice observed over a period of 5 days following dosage.

Clidinium bromide is an effective anticholinergic agent with activity approximating that of atropine sulfate against acetylcholine-induced spasms in isolated intestinal strips. On oral administration in mice, it proved an effective antisialagogue in preventing pilocarpine-induced salivation. Spontaneous intestinal motility in both rats and dogs is reduced following oral dosing with 0.1 to 0.25 mg/kg. Potent cholinergic ganglionic blocking effects (vagal) were produced with intravenous usage in anesthetized dogs.

Oral doses of 2.5 mg/kg to dogs produced signs of nasal dryness and slight pupillary dilation. In two other species, monkeys and rabbits, doses of 5 mg/kg, po, given three times daily for 5 days did not produce apparent secretory or visual changes.

The oral LD₅₀ of single doses of clidinium bromide is 860 ± 57 mg/kg as determined in mice observed over a period of 5 days following dosage; the calculations were made according to the method of Miller and Tainter.

Effects on Reproduction

Reproduction studies in rats fed Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride, 10, 20 and 80 mg/kg daily, and bred through one or two matings showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. However, in another study at 100 mg/kg daily there was noted a significant decrease in the fertilization rate and a marked decrease in the viability and body weight of offspring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened maternal nursing and care of the young. One neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. Further studies are in progress to determine the significance of these findings.

Two series of reproduction experiments with clidinium bromide were carried out in rats, employing dosages of 2.5 and 10 mg/kg daily in each experiment. In the first experiment, clidinium bromide was administered for a 9-week interval prior to mating; no untoward effect on fertilization or gestation was noted. The offspring were taken by caesarean section and did not show a significant incidence of congenital anomalies when compared to control animals. In the second experiment, adult animals were given clidinium bromide for 10 days prior to and through two mating cycles. No significant effects were observed on fertility, gestation, viability of offspring or lactation, as compared to control animals, nor was there a significant incidence of congenital anomalies in the offspring derived from these experiments.

A reproduction study of Sanmag Tablets (Chlordiazepoxide Hydrochloride) was carried out in rats through two successive matings. Oral daily doses were administered in two concentrations: 2.5 mg/kg Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride with 12.5 mg/kg clidinium bromide. In the first mating, no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. As with all anticholinergic drugs, an inhibiting effect on lactation may occur. In the second mating, similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups. Additional animal reproduction studies are in progress.

INDICATIONS AND USAGE

Sanmag Tablets (Chlordiazepoxide Hydrochloride) is indicated to control emotional and somatic factors in gastrointestinal disorders. Sanmag Tablets (Chlordiazepoxide Hydrochloride) may also be used as adjunctive therapy in the treatment of peptic ulcer and in the treatment of the irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis.

CONTRAINDICATIONS

Sanmag Tablets (Chlordiazepoxide Hydrochloride) is contraindicated in the presence of glaucoma (since the anticholinergic component may produce some degree of mydriasis) and in patients with prostatic hypertrophy and benign bladder neck obstruction. It is contraindicated in patients with known hypersensitivity to Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride and/or clidinium bromide.

WARNINGS

Concomitant use of benzodiazepines, including Sanmag Tablets, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe Sanmag Tablets (Chlordiazepoxide Hydrochloride) concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when Sanmag Tablets (Chlordiazepoxide Hydrochloride) is used with opioids (see PRECAUTIONS ).

As in the case of other preparations containing CNS-acting drugs, patients receiving Sanmag Tablets (Chlordiazepoxide Hydrochloride) should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.

Usage In Pregnancy

An increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam and meprobamate) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.

As with all anticholinergic drugs, an inhibiting effect on lactation may occur.

OVERDOSAGE

Manifestations of Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride overdosage include somnolence, confusion, coma and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride overdosage.

While the signs and symptoms of Sanmag Tablets (Chlordiazepoxide Hydrochloride) overdosage may be produced by either of its components, usually such symptoms will be overshadowed by the anticholinergic actions of clidinium bromide. The symptoms of overdosage of clidinium bromide are excessive dryness of mouth, blurring of vision, urinary hesitancy and constipation.

General supportive measures should be employed, along with immediate gastric lavage. Administer physostigmine 0.5 to 2 mg at a rate of no more than 1 mg per minute. This may be repeated in 1 to 4 mg doses if arrhythmias, convulsions or deep coma recur. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of levarterenol or metaraminol. Methylphenidate or caffeine and sodium benzoate may be given to combat CNS-depressive effects. Dialysis is of limited value. Should excitation occur, barbiturates should not be used. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.

Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines.

PRECAUTIONS

In debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion capsules per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of Sanmag Tablets (Chlordiazepoxide Hydrochloride) and other psychotropic agents is not recommended. If such combination therapy seems indicated, careful consideration should be given to the pharmacology of the agents to be employed - particularly when the known potentiating compounds such as the MAO inhibitors and phenothiazines are to be used. The usual precautions in treating patients with impaired renal or hepatic function should be observed.

Paradoxical reactions to Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and should be watched for during Sanmag Tablets (Chlordiazepoxide Hydrochloride) therapy. The usual precautions are indicated when Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride is used in the treatment of anxiety states where there is any evidence of impending depression; it should be borne in mind that suicidal tendencies may be present and protective measures may be necessary. Although clinical studies have not established a cause and effect relationship, physicians should be aware that variable effects on blood coagulation have been reported very rarely in patients receiving oral anticoagulants and Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride.

Information for Patients

Inform patients and caregivers that potentially fatal additive effects may occur if Sanmag Tablets (Chlordiazepoxide Hydrochloride) is used with opioids or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider (see WARNINGS and PRECAUTIONS ).

To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.

Drug Interactions

The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Geriatric subjects may be particularly prone to experiencing drowsiness, ataxia and confusion while receiving Sanmag Tablets (Chlordiazepoxide Hydrochloride). These effects can usually be avoided with proper dosage adjustment, although they have occasionally been observed even at the lower dosage ranges. Dosing in geriatric subjects should be initiated cautiously (no more than 2 capsules per day) and increased gradually if needed and tolerated. Sanmag Tablets (Chlordiazepoxide Hydrochloride) is contraindicated in the presence of glaucoma, prostatic hypertrophy and benign bladder neck obstruction.

ADVERSE REACTIONS

No side effects or manifestations not seen with either compound alone have been reported with the administration of Sanmag Tablets (Chlordiazepoxide Hydrochloride). However, since Sanmag Tablets (Chlordiazepoxide Hydrochloride) contains Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride and clidinium bromide, the possibility of untoward effects which may be seen with either of these two compounds cannot be excluded.

When Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride has been used alone the necessity of discontinuing therapy because of undesirable effects has been rare. Drowsiness, ataxia and confusion have been reported in some patients - particularly the elderly and debilitated. While these effects can be avoided in almost all instances by proper dosage adjustment, they have occasionally been observed at the lower dosage ranges. In a few instances syncope has been reported.

Other adverse reactions reported during therapy with Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride include isolated instances of skin eruptions, edema, minor menstrual irregularities, nausea and constipation, extrapyramidal symptoms, as well as increased and decreased libido. Such side effects have been infrequent and are generally controlled with reduction of dosage. Changes in EEG patterns (low-voltage fast activity) have been observed in patients during and after Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride treatment.

Blood dyscrasias, including agranulocytosis, jaundice and hepatic dysfunction have occasionally been reported during therapy with Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride. When Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride treatment is protracted, periodic blood counts and liver function tests are advisable.

Adverse effects reported with use of Sanmag Tablets (Chlordiazepoxide Hydrochloride) are those typical of anticholinergic agents, i.e., dryness of the mouth, blurring of vision, urinary hesitancy and constipation. Constipation has occurred most often when Sanmag Tablets (Chlordiazepoxide Hydrochloride) therapy has been combined with other spasmolytic agents and/or a low residue diet.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG ABUSE AND DEPENDENCE

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuance of Sanmag Tablets (Chlordiazepoxide Hydrochloride). The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving Sanmag Tablets (Chlordiazepoxide Hydrochloride) or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

DOSAGE AND ADMINISTRATION

Because of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of Sanmag Tablets varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects. The usual maintenance dose is 1 or 2 capsules, 3 or 4 times a day administered before meals and at bedtime.

Geriatric Dosing

Dosage should be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion. The initial dose should not exceed 2 Sanmag Tablets (Chlordiazepoxide Hydrochloride) capsules per day, to be increased gradually as needed and tolerated.

HOW SUPPLIED

Sanmag Tablets (Chlordiazepoxide Hydrochloride) is available in light green opaque capsules, each containing 5 mg Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride and 2.5 mg clidinium bromide - bottles of 100 (NDC 0187-4100-10), with Sanmag Tablets (Chlordiazepoxide Hydrochloride) imprinted on the body of the capsule.

Store at 25°C (77°F); excursions permitted to 15°C - 30°C (59°F - 86°F).

Keep out of reach of children. Dispense in tight, light-resistant container as defined in USP/NF.

Manufactured by:

Valeant Pharmaceuticals International, Inc.

Steinbach, MB R5G 1Z7 Canada

Manufactured for:

Valeant Pharmaceuticals North America LLC

Bridgewater, NJ 08807 USA

Sanmag Tablets (Chlordiazepoxide Hydrochloride) is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.

©Valeant Pharmaceuticals North America LLC

9548900-20001220

Revised: 01/2017

Medication Guide

Sanmag Tablets (Chlordiazepoxide Hydrochloride) (lee braks)

(chlordiazepoxide HCl and clidinium bromide) capsules

What is the most important information I should know about Sanmag Tablets (Chlordiazepoxide Hydrochloride)?

• Do not stop taking Sanmag Tablets (Chlordiazepoxide Hydrochloride) without first talking to your healthcare provider. Stopping Sanmag Tablets (Chlordiazepoxide Hydrochloride) suddenly can cause serious side effects.
• Taking Sanmag Tablets (Chlordiazepoxide Hydrochloride) with opioid medicines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death.
• Do not drive, operate heavy machinery, or do other dangerous activities until you know how Sanmag Tablets (Chlordiazepoxide Hydrochloride) affects you.
• Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking Sanmag Tablets (Chlordiazepoxide Hydrochloride) without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, Sanmag Tablets (Chlordiazepoxide Hydrochloride) may make your sleepiness or dizziness much worse.
• Sanmag Tablets (Chlordiazepoxide Hydrochloride) can cause abuse and dependence.
• Do not stop taking Sanmag Tablets (Chlordiazepoxide Hydrochloride) all of a sudden. Stopping Sanmag Tablets (Chlordiazepoxide Hydrochloride) suddenly can cause seizures, shaking, stomach and muscle cramps, vomiting and sweating.
• Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction.

What is Sanmag Tablets (Chlordiazepoxide Hydrochloride)?

• Sanmag Tablets (Chlordiazepoxide Hydrochloride) is a prescription medicine that is used with other therapies for the treatment of:
• stomach (peptic) ulcers
• irritable bowel syndrome (IBS)
• inflammation of the colon called acute enterocolitis
• Sanmag Tablets (Chlordiazepoxide Hydrochloride) contains the medicines Sanmag Tablets (Chlordiazepoxide Hydrochloride) HCl and clidinium bromide.
• Sanmag Tablets (Chlordiazepoxide Hydrochloride) can be abused or lead to dependence. Keep Sanmag Tablets (Chlordiazepoxide Hydrochloride) in a safe place to prevent misuse and abuse. Selling or giving away Sanmag Tablets (Chlordiazepoxide Hydrochloride) may harm others. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription medicines or street drugs.
• It is not known if Sanmag Tablets (Chlordiazepoxide Hydrochloride) is safe and effective in children.

Do not take Sanmag Tablets (Chlordiazepoxide Hydrochloride) if you:

• have glaucoma
• have an enlarged prostate
• have a blockage of your bladder that causes problems with urination
• are allergic to Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride or clidinium bromide

Before you take Sanmag Tablets (Chlordiazepoxide Hydrochloride), tell your healthcare provider about all of your medical conditions, including if you:

• have eye problems
• have problems urinating or emptying your bladder
• have coordination problems
• have kidney or liver problems
• have a history of depression, mental illness, or suicidal thoughts
• have a history of drug or alcohol abuse or addiction
• have bleeding problems
• are pregnant or plan to become pregnant. Sanmag Tablets (Chlordiazepoxide Hydrochloride) may harm your unborn baby. Avoid taking Sanmag Tablets (Chlordiazepoxide Hydrochloride) during the first trimester of pregnancy. Tell your healthcare provider right away if you become pregnant during treatment with Sanmag Tablets (Chlordiazepoxide Hydrochloride).
• are breastfeeding or plan to breastfeed. Sanmag Tablets (Chlordiazepoxide Hydrochloride) may pass through your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take Sanmag Tablets (Chlordiazepoxide Hydrochloride). Sanmag Tablets (Chlordiazepoxide Hydrochloride) may decrease the amount of breast milk your body makes.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking Sanmag Tablets (Chlordiazepoxide Hydrochloride) with certain other medicines can cause side effects or affect how well Sanmag Tablets (Chlordiazepoxide Hydrochloride) or the other medicines work.

Do not start or stop other medicines without talking to your healthcare provider.

Especially tell your healthcare provider if you:

• take a monoamine oxidase inhibitor (MAOI) medicine or an anti-psychotic medicine called phenothiazine.

How should I take Sanmag Tablets (Chlordiazepoxide Hydrochloride)?

• Take Sanmag Tablets (Chlordiazepoxide Hydrochloride) exactly as your healthcare provider tells you to take it.
• Your healthcare provider may change your dose of Sanmag Tablets (Chlordiazepoxide Hydrochloride) if needed. Do not change your dose of Sanmag Tablets (Chlordiazepoxide Hydrochloride) or suddenly stop taking Sanmag Tablets (Chlordiazepoxide Hydrochloride) without talking with your healthcare provider.
• If you take too much Sanmag Tablets (Chlordiazepoxide Hydrochloride), call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of Sanmag Tablets (Chlordiazepoxide Hydrochloride)?

Sanmag Tablets (Chlordiazepoxide Hydrochloride) may cause serious side effects, including: See “What is the most important information I should know about Sanmag Tablets (Chlordiazepoxide Hydrochloride)?”

The most common side effects of Sanmag Tablets (Chlordiazepoxide Hydrochloride) include:

• dry mouth
• blurred vision
• nausea
• constipation
• skin problems
• swelling
• irregular menstrual (periods) cycles
• increase and decreased desire for sex (libido)
• problems starting to urinate
• drowsiness, coordination problems, and confusion may happen, especially in people who are elderly or weak

These are not all the possible side effects of Sanmag Tablets (Chlordiazepoxide Hydrochloride).

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Sanmag Tablets (Chlordiazepoxide Hydrochloride)?

• Store Sanmag Tablets (Chlordiazepoxide Hydrochloride) at room temperature 77°F (25°C).
• Keep Sanmag Tablets (Chlordiazepoxide Hydrochloride) and all medicines out of the reach of children.

General information about the safe and effective use of Sanmag Tablets (Chlordiazepoxide Hydrochloride).

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Sanmag Tablets (Chlordiazepoxide Hydrochloride) for a condition for which it was not prescribed. Do not give Sanmag Tablets (Chlordiazepoxide Hydrochloride) to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Sanmag Tablets (Chlordiazepoxide Hydrochloride) that is written for health professionals.

What are the ingredients in Sanmag Tablets (Chlordiazepoxide Hydrochloride)?

Active ingredient: Sanmag Tablets (Chlordiazepoxide Hydrochloride) hydrochloride and clidinium bromide

Inactive ingredients: corn starch, lactose and talc. Gelatin capsule shells may contain methyl and propyl parabens and potassium sorbate, with the following dye systems: D&C Yellow No. 10 and either FD&C Blue No.1 or FD&C Green No. 3.

Manufactured in Canada by: Valeant Pharmaceuticals International, Inc. Steinbach, MB R5G 1Z7 Canada

Manufactured for: Valeant Pharmaceuticals North America LLC Bridgewater, NJ 08807 USA

Sanmag Tablets (Chlordiazepoxide Hydrochloride) is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.

©Valeant Pharmaceuticals North America LLC

For more information, go to www.valeant.com or contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576

This Medication Guide has been approved by the U.S. Food and Drug Administration

Issued: 01/2017

NDC 0187-4100-10

Rx Only

Sanmag Tablets (Chlordiazepoxide Hydrochloride)^®

(chlordiazepoxide HCl)

(clidinium bromide)

Each capsule

contains 5 mg

Sanmag Tablets (Chlordiazepoxide Hydrochloride)

HCl and 2.5 mg

clidinium bromide.

VALEANT

100 Capsules

Papaverine Hydrochloride:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Sanmag Tablets (Papaverine Hydrochloride) reviews

Rx Only

This product is to be used by or under the direction of a physician.

Each vial contains a sufficient amount to permit withdrawal and administration of the volume specified on the label.

DESCRIPTION

Sanmag Tablets (Papaverine Hydrochloride), USP, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. It does not contain a phenanthrene group as do morphine and codeine.

Sanmag Tablets (Papaverine Hydrochloride), USP, is 6,7-dimethoxy-1- veratrylisoquinoline hydrochloride and contains, on the dried basis, not less than 98.5% of C₂₀H₂₁NO₄-HCI. The molecular weight is 375.85. The structural formula is as shown.

Sanmag Tablets (Papaverine Hydrochloride) occurs as white crystals or white crystalline powder. One gram dissolves in about 30 mL of water and in 120 mL of alcohol. It is soluble in chloroform and practically insoluble in ether.

Sanmag Tablets (Papaverine Hydrochloride) Injection, USP, is a clear, colorless to pale-yellow solution.

Sanmag Tablets (Papaverine Hydrochloride), for parenteral administration, is a smooth-muscle relaxant that is available in vials containing 30 mg/mL. Each vial also contains edetate disodium 0.005%. The 10 mL vials also contain chlorobutanol 0.5% as a preservative. pH may be adjusted with sodium citrate and/or citric acid.

Adobe Systems

CLINICAL PHARMACOLOGY

The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted. Sanmag Tablets (Papaverine Hydrochloride) apparently acts directly on the muscle itself. This relaxation is noted in the vascular system and bronchial musculature and in the gastrointestinal, biliary and urinary tracts.

The main actions of papaverine are exerted on cardiac and smooth muscle. Papaverine relaxes various smooth muscles, especially those of larger arteries; this relaxation may be prominent if spasm exists. The antispasmodic effect is a direct one and unrelated to muscle innervation, and the muscle still responds to drugs and other stimuli causing contraction. Papaverine has minimal actions on the central nervous system, although very large doses tend to produce some sedation and sleepiness in some patients. In certain circumstances, mild respiratory stimulation can be observed, but this is therapeutically inconsequential. Papaverine stimulates respiration by acting on carotid and aortic body chemoreceptors.

Papaverine relaxes the smooth musculature of the larger blood vessels, including the coronary, cerebral, peripheral, and pulmonary arteries. This action is particularly evident when such vessels are in spasm, induced reflexly or by drugs, and it provides the basis for the clinical use of papaverine in peripheral or pulmonary arterial embolism.

Experimentally in dogs, the alkaloid has been shown to cause fairly marked and long-lasting coronary vasodilatation and an increase in coronary blood flow. However, it also appears to have a direct inotropic effect and, when increased mechanical activity coincides with decreased systemic pressure, increases in coronary blood flow may not be sufficient to prevent brief periods of hypoxic myocardial depression.

Papaverine is effective by all routes of administration. A considerable fraction of the drug localizes in fat deposits and in the liver, with the remainder being distributed throughout the body. It is metabolized in the liver. About 90% of the drug is bound to plasma protein. Although estimates of its biologic half-life vary widely, reasonably constant plasma levels can be maintained with oral administration at 6 hour intervals. The drug is excreted in the urine in an inactive form.

INDICATIONS AND USAGE

Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such as vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease in which there is a vasospastic element, or certain cerebral angiospastic states; and visceral spasm, as in ureteral, biliary, or gastrointestinal colic.

CONTRAINDICATIONS

Intravenous injection of papaverine is contraindicated in the presence of complete atrioventricular heart block. When conduction is depressed, the drug may produce transient ectopic rhythms of ventricular origin, either premature beats or paroxysmal tachycardia.

Sanmag Tablets (Papaverine Hydrochloride) is not indicated for the treatment of impotence by intracorporeal injection. The intracorporeal injection of Sanmag Tablets (Papaverine Hydrochloride) has been reported to have resulted in persistent priapism requiring medical and surgical intervention.

PRECAUTIONS

General

Sanmag Tablets Injection, USP, should not be added to Lactated Ringer’s Injection, because precipitation would result.

Sanmag Tablets (Papaverine Hydrochloride) should be used with caution in patients with glaucoma. The medication should be discontinued if hepatic hypersensitivity with gastrointestinal symptoms, jaundice, or eosinophilia becomes evident or if liver function test values become altered.

Pregnancy

Pregnancy Category C - No teratogenic effects were observed in rats when Sanmag Tablets (Papaverine Hydrochloride) was administered subcutaneously as a single agent. It is not known whether papaverine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sanmag Tablets (Papaverine Hydrochloride) should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Sanmag Tablets is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children have not been established.

ADVERSE REACTIONS

The following side effects have been reported: general discomfort, nausea, abdominal discomfort, anorexia, constipation or diarrhea, skin rash, malaise, vertigo, headache, intensive flushing of the face, perspiration, increase in the depth of respiration, increase in heart rate, a slight rise in blood pressure, and excessive sedation.

Hepatitis, probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to cirrhosis.

DRUG ABUSE AND DEPENDENCE

Drug dependence resulting from the abuse of many of the selective depressants, including Sanmag Tablets (Papaverine Hydrochloride), has been reported.

OVERDOSAGE

Signs and Symptoms –

The symptoms of toxicity from Sanmag Tablets often result from vasomotor instability and include nausea, vomiting, weakness, central nervous system depression, nystagmus, diplopia, diaphoresis, flushing, dizziness, and sinus tachycardia. In large overdoses, papaverine is a potent inhibitor of cellular respiration and a weak calcium antagonist. Following an oral overdose of 15 g, metabolic acidosis with hyperventilation, hyperglycemia, and hypokalemia have been reported. No information on toxic serum concentrations is available.

Following intravenous overdosing in animals, seizures, tachyarrhythmias, and ventricular fibrillation have been reported. The oral median lethal dose in rats is 360 mg/kg.

Treatment –

To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physician’s Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor vital signs, blood gases, blood chemistry values, and other variables.

If convulsions occur, consider diazepam, phenytoin, or phenobarbital. If the seizures are refractory, general anesthesia with thiopental or halothane and paralysis with a neuromuscular blocking agent may be necessary.

For hypotension, consider intravenous fluids, elevation of the legs, and an inotropic vasopressor, such as dopamine or norepinephrine (levarterenol). Theoretically, calcium gluconate may be helpful in treating some of the toxic cardiovascular effects of papaverine; monitor the ECG and plasma calcium concentrations.

Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of Sanmag Tablets (Papaverine Hydrochloride).

DOSAGE AND ADMINISTRATION

Sanmag Tablets (Papaverine Hydrochloride) may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects.

Parenteral administration of Sanmag Tablets (Papaverine Hydrochloride) in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of cardiac extrasystoles, 2 doses may be given 10 minutes apart.

HOW SUPPLIED

Sanmag Tablets (Papaverine Hydrochloride) Injection, USP, 30 mg/mL

0517-4002-25 2 mL Vial packaged in boxes of 25

0517-4010-01 10 mL Multiple Dose Vial* packaged individually

*The 10 mL Multiple Dose Vial contains chlorobutanol 0.5% as a preservative.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

PROTECT FROM LIGHT. RETAIN IN CARTON UNTIL TIME OF USE.

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

IN4002

Rev. 1/09

Vitamin B12:

• Pharmacological action
• Pharmacokinetics
• Why is Sanmag Tablets prescribed?
• Dosage and administration
• Sanmag Tablets (Vitamin B12) side effects, adverse reactions
• Sanmag Tablets contraindications
• Sanmag Tablets using during pregnancy and breastfeeding
• Special instructions
• Sanmag Tablets (Vitamin B12) drug interactions
• Sanmag Tablets (Vitamin B12) reviews

Pharmacological action

Sanmag Tablets refers to a group of water-soluble vitamins. It has high biological activity. Sanmag Tablets (Vitamin B12) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.

Pharmacokinetics

After oral administration Sanmag Tablets (Vitamin B12) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.

Why is Sanmag Tablets prescribed?

Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of Sanmag Tablets (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Sanmag Tablets is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Sanmag Tablets (Vitamin B12) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.

In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with Sanmag Tablets (Vitamin B12) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.

When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.

Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.

When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.

In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.

When deficiency of Sanmag Tablets (Vitamin B12) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.

Sanmag Tablets (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

Cardiovascular system: rarely - pain in the heart, tachycardia.

Allergic reactions: rarely - urticaria.

Sanmag Tablets contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Sanmag Tablets using during pregnancy and breastfeeding

Cyanocobalamin can be used in pregnancy according to prescriptions.

Special instructions

When stenocardia should be used with caution in a single dose of Sanmag Tablets 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.

Sanmag Tablets (Vitamin B12) drug interactions

In an application of Sanmag Tablets (Vitamin B12) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.

In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.

In an Sanmag Tablets (Vitamin B12) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.

Pharmaceutical incompatibility

Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.