Online Diazepam

What is the most important information I should know about diazepam? • Use caution when driving, operating machinery, or performing other hazardous activities. Diazepam will cause drowsiness and may cause dizziness. If you experience drowsiness or dizziness, avoid these activities. • Avoid alcohol while taking diazepam. Alcohol may increase drowsiness and dizziness caused by diazepam. Alcohol may also increase the risk of having a seizure if diazepam is being taken for a seizure condition. • Diazepam is habit forming. You can become physically and psychologically dependent on the medication. Do not take more than the prescribed amount of medication or take it for longer than is directed by your doctor. Withdrawal effects may occur if diazepam is stopped suddenly after several weeks of continuous use. Your doctor may recommend a gradual reduction in dose. What is diazepam? • Diazepam is in a class of drugs called benzodiazepines. Diazepam affects chemicals in the brain that may become unbalanced and cause anxiety, seizures, and muscle spasms. • Diazepam is used to relieve anxiety, nervousness, and tension associated with anxiety disorders. It is also used to treat certain types of seizure disorders and muscle spasms. • Diazepam may also be used for purposes other than those listed in this medication guide. What should I discuss with my healthcare provider before taking diazepam? • Do not take diazepam if you have narrow-angle glaucoma. Diazepam may worsen this condition. • Before taking this medication, tell your doctor if you · have kidney disease; · have liver disease; · have asthma, bronchitis, emphysema, or another respiratory disease; or · are depressed or have suicidal thoughts. • You may not be able to take diazepam, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above. • Diazepam is in the FDA pregnancy category D. This means that diazepam is known to harm an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant. • Diazepam passes into breast milk. Do not take diazepam without first talking to your doctor if you are breast-feeding a baby. • If you are over 65 years of age, you may be more likely to experience side effects from diazepam. You may require a lower dose of this medication. How should I take diazepam? • Take diazepam exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you. • Take each oral dose with a full glass of water. • To ensure the correct dose, measure the liquid forms of diazepam with a dose-measuring spoon or cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one. • Your doctor or nurse will give you detailed instructions for administration of the Diastat rectal gel. In general, application of the rectal gel is as follows: · Remove the protective cover from the medication syringe and lubricate the rectal tip with lubricating jelly. · Turn the person on their side facing you. Bend the upper leg forward and separate the buttocks to expose the rectum. · Gently insert the syringe tip into the rectum. The rim should be snug against the rectal opening. Slowly count out loud to three while gently pushing the plunger in until it stops. Slowly count to three before removing the syringe. Slowly count to three and hold the buttocks together to prevent leakage. · Keep the person on their side facing you, note the time the medication was given, and observe the person for signs of seizure, skin color, breathing, or any unusual reaction. • Do not take diazepam more often or in larger doses than is prescribed. • Diazepam is habit forming. You can become physically and psychologically dependent on the medication. Do not take more than the prescribed amount of medication or take it for longer than is directed by your doctor. Withdrawal effects may occur if diazepam is stopped suddenly after several weeks of continuous use. Your doctor may recommend a gradual reduction in dose. • Store diazepam at room temperature away from moisture and heat. What happens if I miss a dose? • Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the dose you missed and take only the next regularly scheduled dose. Do not take a double dose of this medication. A double dose could be dangerous. What happens if I overdose? • Seek emergency medical attention. • Symptoms of a diazepam overdose include sleepiness, dizziness, confusion, a slow heart beat, difficulty breathing, difficulty walking and talking, an appearance of being drunk, and unconsciousness. What should I avoid while taking diazepam? • Use caution when driving, operating machinery, or performing other hazardous activities. Diazepam will cause drowsiness and may cause dizziness. If you experience drowsiness or dizziness, avoid these activities. • Avoid alcohol while taking diazepam. Alcohol may increase drowsiness and dizziness caused by diazepam. Alcohol may also increase the risk of having a seizure if diazepam is being taken for a seizure condition. • Diazepam may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), pain relievers, anxiety medicines, seizure medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any medicine without first talking to your doctor. What are the possible side effects of diazepam? • If you experience any of the following serious side effects, stop taking diazepam and seek emergency medical attention or contact your doctor immediately: · an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, face, or tongue; or hives); · sores in the mouth or throat; · yellowing of the skin or eyes; · a rash; · hallucinations or severe confusion; or · changes in your vision. • Other, less serious side effects may be more likely to occur. Continue to take diazepam and talk to your doctor if you experience · drowsiness, dizziness, or clumsiness; · depression; · nausea, vomiting, diarrhea, or constipation; · difficulty urinating; · vivid dreams; · headache; · dry mouth; · decreased sex drive; or · changes in behavior. • Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. What other drugs will affect diazepam? • Diazepam may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), pain relievers, anxiety medicines, seizure medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any medicine without first talking to your doctor. • Antacids may decrease the effects of diazepam. Separate doses of an antacid and diazepam by several hours whenever possible. • Drugs other than those listed here may also interact with diazepam. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines. Where can I get more information? • Your pharmacist has additional information about diazepam written for health professionals that you may read. -------------------------------------------------------------------------------- • Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. • Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/ or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist. DIAZEPAM Manufacturer: Roche Products The following text is complete prescribing information based on official labeling in effect June 2001. DESCRIPTION Valium (diazepam) is a benzodiazepine derivative. The chemical name of diazepam is 7-chloro-1,3-dihydro-1-methyl -5- phenyl-2H-1,4-benzodiazepin-2-one. It is a colorless crystalline compound, insoluble in water. The empirical formula is C 16 H 13 CIN 2 O and the molecular weight is 284.75. Valium is available for oral administration as tablets containing 2 mg, 5 mg or 10 mg diazepam. In addition to the active ingredient diazepam, each tablet contains the following inactive ingredients: anhydrous lactose, corn starch, pregelatinized starch and calcium stearate with the following dyes: 5-mg tablets contain FD&C Yellow No. 6 and D&C Yellow No. 10; 10-mg tablets contain FD&C Blue No. 1. Valium 2-mg tablets contain no dye. PHARMACOLOGY In animals, Valium appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Valium, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with Valium do have a transient ataxia at higher doses. Valium was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function. Oral LD 50 of diazepam is 720 mg/kg in mice and 1240 mg/kg in rats. Intraperitoneal administration of 400 mg/kg to a monkey resulted in death on the sixth day. Reproduction Studies: A series of rat reproduction studies was performed with diazepam in oral doses of 1, 10, 80 and 100 mg/kg. At 100 mg/kg there was a decrease in the number of pregnancies and surviving offspring in these rats. Neonatal survival of rats at doses lower than 100 mg/kg was within normal limits. Several neonates in these rat reproduction studies showed skeletal or other defects. Further studies in rats at doses up to and including 80 mg/kg/day did not reveal teratological effects on the offspring. In humans, measurable blood levels of Valium were obtained in maternal and cord blood, indicating placental transfer of the drug. INDICATIONS Valium is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. In acute alcohol withdrawal, Valium may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Valium is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; and stiff-man syndrome. Oral Valium may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. The effectiveness of Valium in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient. CONTRAINDICATIONS Valium is contraindicated in patients with a known hypersensitivity to this drug and, because of lack of sufficient clinical experience, in pediatric patients under 6 months of age. It may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in acute narrow angle glaucoma. WARNINGS Valium is not of value in the treatment of psychotic patients and should not be employed in lieu of appropriate treatment. As is true of most preparations containing CNS-acting drugs, patients receiving Valium should be cautioned against engaging in hazardous occupations requiring complete mental alertness such as operating machinery or driving a motor vehicle. As with other agents which have anticonvulsant activity, when Valium is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. Abrupt withdrawal of Valium in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures. Since Valium has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during Valium therapy. Usage in Pregnancy: An increased risk of congenital malformations associated with the use of minor tranquilizers (diazepam, meprobamate and chlordiazepoxide) 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. Management of Overdosage: Manifestations of Valium 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 overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of Levophed® (levarterenol) or Aramine (metaraminol). Dialysis is of limited value. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested. Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation, and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, should be consulted prior to use. Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines. (See DRUG ABUSE AND DEPENDENCE section.) PRECAUTIONS If Valium is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed--particularly with known compounds which may potentiate the action of Valium, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants. The usual precautions are indicated for severely depressed patients or those in whom there is any evidence of latent depression; particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. The usual precautions in treating patients with impaired renal or hepatic function should be observed. In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2 1 / 2 mg once or twice daily, initially, to be increased gradually as needed and tolerated). The clearance of Valium and certain other benzodiazepines can be delayed in association with Tagamet (cimetidine) administration. The clinical significance of this is unclear. Information for Patients: 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. Pediatric Use: Safety and effectiveness in pediatric patients below the age of 6 months have not been established. ADVERSE REACTIONS Side effects most commonly reported were drowsiness, fatigue and ataxia. Infrequently encountered were confusion, constipation, depression, diplopia, dysarthria, headache, hypotension, incontinence, jaundice, changes in libido, nausea, changes in salivation, skin rash, slurred speech, tremor, urinary retention, vertigo and blurred vision. Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances and stimulation have been reported; should these occur, use of the drug should be discontinued. Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy. Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after Valium therapy and are of no known significance. 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 diazepam. 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 (eg, 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 diazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence. DOSAGE AND ADMINISTRATION Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In such cases dosage should be increased cautiously to avoid adverse effects. 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VALIUM® brand of diazepam INJECTION For relief of acute anxiety when rapid action is required In acute alcohol withdrawal As a useful adjunct in • endoscopic procedures • skeletal muscle spasm associated with local pathology, cerebral palsy, athetosis, stiff-man syndrome, tetanus • status epilepticus and severe recurrent convulsive seizures As premedication in patients undergoing • surgical procedures • cardioversion

-------------------------------------------------------------------------------- Warnings Pregnancy: Several studies have suggested an increased risk of congenital malformations associated with the use of diazepam, chlordiazepoxide and meprobamate during the first trimester of pregnancy. Therefore, the administration of diazepam is rarely justified in women of childbearing potential. If the drug is prescribed for a woman of childbearing potential, she should be warned to contact her physician regarding discontinuation of the drug if she intends to become or suspects that she is pregnant. to top -------------------------------------------------------------------------------- Precautions Geriatrics: Elderly and debilitated patients or those with organic brain disorders have been found to be prone to CNS depression following even low doses. For these patients it is recommended that the dosage be limited to the smallest effective amount to preclude development of ataxia, oversedation or other possible adverse effects. Use in emotional disorders: Diazepam is not recommended in the treatment of psychotic or severely depressed patients. Precautions are indicated for severely depressed patients or those who show evidence of impending depression, particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. Since excitement and other paradoxical reactions may result from the use of the drug in psychotic patients, it should not be used in ambulatory patients suspected of having psychotic tendencies. Use in epileptic patients: Since diazepam may exacerbate grand mal seizures in some patients, caution is required when it is used in epileptic patients. An adjustment may be necessary in their anticonvulsive medication. Abrupt withdrawal of diazepam in these patients should also be avoided. Potentiation of drug effects: Patients should be advised to abstain from alcohol and other CNS depressant drugs during treatment with diazepam. Phenothiazines, barbiturates, MAO inhibitors and other psychoactive drugs may potentiate the action of the drug and should not usually be given concurrently. Drug dependence: Abrupt cessation of large doses of diazepam after prolonged periods may precipitate acute withdrawal symptoms and, in these cases, the drug should be discontinued gradually. Caution should be exercised when it is considered necessary to administer diazepam to addiction prone individuals. Occupational Hazards: Patients receiving diazepam should be advised to proceed cautiously whenever mental alertness and physical coordination are required. The usual precautions in treating patients with impaired renal and hepatic functions should be observed. If diazepam is administered for protracted periods, periodic blood counts and liver function tests would be highly advisable. to top -------------------------------------------------------------------------------- Adverse Effects The most common adverse effects reported are drowsiness and ataxia. Other reactions noted less frequently are fatigue, dizziness, nausea, blurred vision, diplopia, vertigo, headache, slurred speech, tremors, hypoactivity, dysarthria, euphoria, impairment of memory, confusion, depression, incontinence or urinary retention, constipation, skin rash, generalized exfoliative dermatitis, hypotension, changes in libido. The more serious adverse reactions occasionally reported are leukopenia, jaundice, hypersensitivity and paradoxical reactions. Paradoxical reactions such as hyperexcited states, anxiety, excitement, hallucinations, increased muscle spasticity, insomnia, rage, as well as sleep disturbances and stimulation, have been reported; should these occur, the drug should be discontinued. Minor changes in EEG patterns have been observed in patients on diazepam therapy. These changes consist of low to moderate voltage fast activity, 20 to 30 cycles/second and are of no known significance. to top -------------------------------------------------------------------------------- Overdose Symptoms: Drowsiness, oversedation and ataxia. When the effects of drug overdosage begin to wear off, the patient exhibits some jitteriness and overstimulation. The cardinal manifestations of overdosage are drowsiness and confusion, reduced reflexes and coma. There are minimum effects on respiration, pulse and blood pressure unless the overdosage is extreme. Treatment: Gastric lavage may be beneficial if performed soon after oral ingestion of diazepam. If necessary, a CNS stimulant such as caffeine or methylphenidate may be administered with caution. Supportive measures should be instituted as indicated, such as, maintenance of an adequate airway, levarterenol for hypotension. Dialysis appears to be of little value. to top -------------------------------------------------------------------------------- Dosage Must be individualized according to diagnosis, severity of symptoms and degree of response. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In the first few days of administration a cumulative effect of the drug may occur, and therefore the dosage should be increased only after stabilization is evident. Adults: Symptomatic relief of anxiety and tension in psychoneurosis and anxiety reactions: 2 to 10 mg, 2 to 4 times daily depending upon severity of symptoms. Symptomatic relief in acute alcohol withdrawal: 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed. Adjunctively for relief of skeletal muscle spasms: 2 to 10 mg, 3 to 4 times daily. Elderly and debilitated patients, or in the presence of debilitating disease: 2 mg, 1 or 2 times daily initially; increase gradually as needed and tolerated. Children (Because of varied responses, initiate therapy with lowest dose and increase as required. Not for use in children under 6 months): 1 to 2.5 mg, 3 or 4 times daily initially; increase gradually as needed and tolerated. Do not prescribe or administer diazepam for periods in excess of 6 weeks, unless a definite need for utilizing this medication has been established by a followup medical examination. Chemistry - A benzodiazepine, diazepam is a white to yellow, practically odorless crystalline powder with a melting point between 131°-135°C and pKa of 3.4. Diazepam is tasteless initially, but a bitter after-taste develops. One gram is soluble in 333 ml of water, 25 ml of alcohol, and it is sparingly soluble in propylene glycol. The pH of the commercially prepared injectable solution is adjusted with benzoic acid/sodium benzoate to 6.2-6.9. It consists of a 5 mg/ml solution with 40% propylene glycol, 10% ethanol, 5% sodium benzoate/benzoic acid buffer, and 1.5% benzyl alcohol as a preservative. Storage/Stability/Compatibility - All diazepam products should be stored at room temperature (15°-30°C). The injection should be kept from freezing and protected from light. The oral dosage forms (tablets/capsules) should be stored in tight containers and protected from light. Because diazepam may adsorb to plastic, it should not be stored drawn up into plastic syringes. The drug may also significantly adsorb to IV solution plastic (PVC) bags and to the infusion tubing. This adsorption appears to be dependent on several factors (temperature, concentration, flow rates, line length, etc.). The manufacturers of injectable diazepam do not recommend the drug be mixed with any other medication or IV diluent. The drug has been successfully diluted to concentrations of 5 mg/50 ml or 5 mg/100 ml in normal saline, lactated Ringer’s and D5W. Differing results have occurred with different manufacturer’s products. Do not administer if a precipitate forms and does not clear. Pharmacology - The subcortical levels (primarily limbic, thalamic, and hypothalamic) of the CNS are depressed by diazepam and other benzodiazepines thus producing the anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects seen. The exact mechanism of action is unknown, but postulated mechanisms include: antagonism of serotonin, increased release of and/or facilitation of gamma-aminobutyric acid (GABA) activity, and diminished release or turnover of acetylcholine in the CNS. Benzodiazepine specific receptors have been located in the mammalian brain, kidney, liver, lung, and heart. In all species studied, receptors are lacking in the white matter. Uses/Indications - Diazepam is used clinically for its anxiolytic, muscle relaxant, hypnotic, appetite stimulant, and anticonvulsant activities. Refer to the dosage section for those and other suggested indications and doses for each species. Pharmacokinetics - Diazepam is rapidly absorbed following oral administration. Peak plasma levels occur within 30 minutes to 2 hours after oral dosing. The drug is slowly (slower than oral) and incompletely absorbed following IM administration. Diazepam is highly lipid soluble and is widely distributed throughout the body. It readily crosses the blood-brain barrier and is fairly highly bound to plasma proteins. In the horse at a serum of concentration of 75 ng/ml, 87% of the drug is bound to plasma proteins. In humans, this value has been reported to be 98-99%. Diazepam is metabolized in the liver to several metabolites, including desmethyldiazepam (nordiazepam), temazepam, and oxazepam, all of which are pharmacologically active. These are eventually conjugated with glucuronide and eliminated primarily in the urine. Because of the active metabolites, serum values of diazepam are not useful in predicting efficacy. Serum half-lives (approximated) have been reported for diazepam and metabolites in dogs, cats, and horses: Dogs Cats Horses Humans Diazepam 2.5 - 3.2 hrs 5.5 hrs 7 - 22 hrs 20 - 50 hrs Nordiazepam 3 hrs 21.3 hrs 30 - 200 hrs Contraindications/Precautions - Slowly inject intravenously. This is particularly true when using a small vein for access or in small animals. Diazepam may cause significant thrombophlebitis. Too rapid of an injection of intravenous diazepam in small animals or neonates, may cause cardiotoxicity secondary to the propylene glycol in the formulation. Intra-carotid artery injections must be avoided. Use cautiously in patients with hepatic or renal disease and in debilitated or geriatric patients. the drug should be administered to patients in coma, shock or with significant respiratory depression very cautiously. It is contraindicated in patients with known hypersensitivity to the drug. Benzodiazepines may impair the abilities of working animals. If administering the drug IV, be prepared to administer cardiovascular or respiratory support. Diazepam has been implicated in causing congenital abnormalities in humans if administered during the first trimester of pregnancy. Infants born of mothers receiving large doses of benzodiazepines shortly before delivery have been reported to suffer from apnea, impaired metabolic response to cold stress, difficulty in feeding, hyperbilirubinemia, hypotonia, etc. Withdrawal symptoms have occurred in infants whose mothers chronically took benzodiazepines during preg­nancy. The veterinary significance of these effects is unclear, but the use of these agents during the first trimester of pregnancy should only occur when the benefits clearly outweigh the risks associated with their use. Benzodiazepines and their metabolites are distributed into milk and may cause CNS effects in nursing neonates. Adverse Effects/Warnings - In horses, diazepam may cause muscle fasiculations, weakness and ataxia at doses sufficient to cause sedation. Doses greater than 0.2 mg/kg may induce recumbency as a result of its muscle relaxant properties and general CNS depressant effects. Cats may exhibit changes in behavior (irritability, depression, aberrant demeanor) after receiving diazepam. There have been recent reports of cats developing hepatic failure after receiving oral diazepam for several days; until this potential adverse effect is confirmed or refuted, use with caution in cats. Dogs may exhibit a contradictory response (CNS excitement) following administration of diazepam. The effects with regard to sedation and tranquilization are extremely variable with each dog. Because of this individual variation, diazepam is not an ideal sedating agent for this species. Overdosage - When administered alone, diazepam overdoses are generally limited to significant CNS depression (confusion, coma, decreased reflexes, etc). Hypotension, respiratory depression, and cardiac arrest have been reported in human patients, but apparently are quite rare. Treatment of acute toxicity consists of standard protocols for removing and/or binding the drug in the gut if taken orally, and supportive systemic measures. The use of analeptic agents (CNS stimulants such as caffeine) are generally not recommended. Drug Interactions - Metabolism of diazepam may be decreased and excessive sedation may occur if given with the following drugs: cimetidine, erythromycin, isoniazid, ketoconazole, propranolol, & valproic acid. If administered with other CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) additive effects may occur. Antacids may slow the rate, but not the extent of oral absorption; administer 2 hours apart to avoid this potential interaction. The pharmacologic effects of digoxin may be increased; monitor serum digoxin levels or symptoms of toxicity. Rifampin may induce hepatic microsomal enzymes and decrease the pharmacologic effects of benzodiazepines. Laboratory Interactions: Patients receiving diazepam, may show false negative urine glucose results if using Diastix® or Clinistix® tests. Doses - Horses: For seizures: a) Foals: 0.05 - 0.4 mg/kg IV; repeat in 30 minutes if necessary; Adults: 25 - 50 mg IV; repeat in 30 minutes if necessary. (Sweeney and Hansen 1987) Treatment of seizures secondary to intraarterial injection of xylazine or other similar agents: a) 0.10 - 0.15 mg/kg IV (Thurmon and Benson 1987) As an appetite stimulant: a) 0.02 mg/kg IV; immediately after dosing offer animal food. Keep loud noises and distractions to a minimum. If effective, usually only 2-3 treatments in a 24-48 hour period is required. (Ralston 1987) Elephants: CAUTION! Sedative and anesthetic drug dosages for African elephants often vary from those for Asian elephants. Do not assume that the recommendations for one species can be applied to the other. Significant variation may also occur between individual elephants. The information provided here should be used as a guideline only. Consultation with experienced colleagues is advised. To control musth: a) A 20 year-old African bull (weight not specified) was placed on the following regimen to reduce signs of musth: 400 mg diazepam in the a.m and 200 mg diazepam in the p.m for 5 days; concentrate feeds reduced by ?; a calming effect was noted; dose was tapered to 400 mg / day over a 5 day period; concentrates gradually increased; dose reduced to 100 mg / day for 10 days; concentrates increased; diazepam discontinued on day 20 and normal diet resumed (Thakuria and Barthakur, 1996). b) To treat extrapyramidal signs associated with overdose of long-acting neuroleptics. Elephant-specific dose not listed (Ebedes et.al. 1995). c) As an anti-convulsant in Asian elephants, 400 - 800 mg diazepam / animal IM (Cheeran et.al. 1995). a) Thakuria,D.B. and Barthakur,T. 1996. Management of musth in a male African elephant by chemical sedatives in the Assam state zoo, Guwahati. Indian Veterinary Journal 73:(3):339-340 Note: This article also discusses a successful regimen using lorazepam. b) Ebedes,H. 1995. The use of long term neuroleptics in the confinement and transport of wild animals. Joint Conf AAZV/WDA/AAWV. Pages: 173-176 c) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1995. Principles and Practice of Fixing Dose of Drugs for Elephants . In: Daniel,J.C. (Editor), A Week with Elephants; Proceedings of the International Seminar on Asian Elephants. Bombay Natural History Society; Oxford University Press, Bombay, India pp. 430-438 Diazepam oral solution 1 mg/ml in 500 ml containers and unit-dose (5 & 10 mg) 5 mg/ml in 30 ml dropper bottle; i.Diazepam Intensol®; (Roxane); Generic (Rx) Diazepam Injection 5 mg/ml in 2 ml amps & syringes & 1, 2, 10 ml vials, 2 ml Tel-E-Ject; Emulsified Injection: 5 mg/ml in 3 ml vials; Valium® (Roche); Zetran® (Hauck);Dizac® (Ohmeda); Generic; (Rx) IMPORTANT NOTE: The following information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that use of the drug is safe, appropriate, or effective for you. Consult your healthcare professional before using this drug. BENZODIAZEPINES - ORAL COMMON BRAND NAME(S): Librium, Serax, Tranxene SD, Valium USES: This medication is used to relieve nervousness and tension or improve sleep disturbances. It is also used to relieve symptoms of alcohol withdrawal such as tremors, or used as an anticonvulsant or skeletal muscle relaxant. HOW TO USE: Take with food or milk if stomach upset occurs. Take exactly as prescribed. Do not increase your dose or take more often than prescribed. Tolerance may develop to this medication making it less effective with prolonged use. For insomnia, take 30 to 60 minutes prior to bedtime. Do not stop taking this medication without your doctor's approval. Your dose may have to be gradually decreased if you have been taking it for some time. SIDE EFFECTS: This medication causes drowsiness and dizziness. Avoid tasks requiring alertness. Other side effects may include: stomach upset, blurred vision, headache, confusion, depression, impaired coordination, change in heart rate, trembling, weakness, memory loss, hangover effect (grogginess), dreaming or nightmares. Notify your doctor if you develop: chest pain, change in heart rate, vision changes, yellowing of the eyes or skin. In the unlikely event you have an allergic reaction to this drug, seek medical attention immediately. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist. PRECAUTIONS: Before using this drug, tell your doctor your medical history, especially of: liver or kidney disease, drug allergies. Alcohol or other sedative-type drugs can lead to extreme drowsiness. Limit alcohol consumption. Elderly persons are usually more sensitive to the effects of this medication. Use cautiously. This medication is not recommended for use during pregnancy. Discuss the risks and benefits with your doctor. Since this medication may appear in breast milk, consult with your doctor before breast-feeding. DRUG INTERACTIONS: Tell your doctor of all prescription and nonprescription drugs you may use, especially of: cimetidine, digoxin, disulfiram, levodopa, seizure medication, sleeping pills, narcotic pain medication (e.g., codeine), medication for depression, barbiturates, tranquilizers, sedatives, certain drowsiness-causing antihistamines (e.g., diphenhydramine), drugs used to treat allergies or colds, alcohol use. Do not eat grapefruit or drink grapefruit juice unless your doctor instructs you otherwise. Smoking can decrease the effectiveness of this drug. Do not start or stop any medicine without doctor or pharmacist approval. OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. Symptoms of overdose may include unconsciousness, reduced reflexes, drowsiness, loss of coordination, or confusion. NOTES: Do not share this medication with others. MISSED DOSE: If you miss a dose, take as soon as remembered; do not take if it is almost time for the next dose. Do not "double-up" the doses. If taking for seizures, take dose if remembered within 1 hour of the missed dose but do not take if remembered after 1 hour has elapsed. STORAGE: Store at room temperature between 59 and 86 degrees F (between 15 and 30 degrees C) away from moisture and sunlight. Do not store in the bathroom. MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA), or 1-800-668-1507 (Canada). -- Please Select -- accolateaccuprilacetaminophenaciphexactonelactosacycloviradderalladipexalbuterolaldactonealdaraallegra-dallopurinolalprazolamaltaceamarylambienamitriptylineamitriptylineamoxicillinamoxilantabuseantivertanusolaphthasolaravaariceptatenololativanavandiaavaprobenicarbiaxinbontrilbusparbuspironebutacaptoprilcardizemcarisoprodolcartiacd qualitycefzilcelebrexcelexacephalexincialisciproclarinexclonazepamclonidinecolchicinecompazinecondyloxcoregcozaarcyclessacyclobenzaprinedepakotedepo-testosteronedetroldiazepamdiclofenacdidrexdiethylpropiondiflucandiltiazemdiovandiproleneditropandovonexdoxazosineffexorelavilelidelenalaprilesgicestraceestradioleunloseevistaevoxacfamvirfioricetflexerilflextra-dsflomaxflonaseflumadinefluoxetinefosamaxfulvicinfurosemidegemfibrozilglipizideglucophageglucotrolgris-peghydocortisonehydrochlorothiazidehydrocodonehydrocodonehydrocodonehydrocodonehydrocodoneibuprofenimitrexionaminisosorbidekenalogkeppraklonopinlamisillasixlevaquinlevitralexaprolipitorlisinoprillorazepamlorcetlortablotensinlunestameclizinemedrolmelanexmembershipmeridiametforminmethylprednisolonemetoprololmetrogelmicrozideminocyclinemiralaxmircettemonoprilmotrinmoviemp3naltrexonenaprosynnaproxennardilnasacortnasonexneurontinnexiumnicotrolnifedipinenizoralnorconordettenortriptylinenorvascortho-evra-patchortho-tri-cyclenovraloxazepampatanolpaxilpenicillinphendimetrazinephendimetrazinephentermineplavixpravacholpremarinpremproprevacidprilosecprinivilproctocortproctocreampromethazinepropeciapropranololprotonixprotopicprovigilprozacrelenzaremeronrenovarestorilretin-asarafemselsunseroquelskelaxinsomasonataspironolactonesumycinsymmetrelsynalarsynthroidtamiflutazoractemazepamtemovatetenuateterazosintetracyclinetiazactoprol-xltramadoltransderm-scoptrazodonetriamcinolonetrimoxtriphasil(28)tussionextylenolultracetultramultravatevaliumvalporicvaltrexvaniqavasotecvermoxviagravicodinvicoprofenvoltarenwellbutrinxanaxxenicalyasminzanaflexzebutalzestoreticzestrilzithromaxzocorzoloftzoviraxzybanzyloprimzyprexazyrtec DIAZEPAM Manufacturer: Roche Products The following text is complete prescribing information based on official labeling in effect June 2001. DESCRIPTION Valium (diazepam) is a benzodiazepine derivative. The chemical name of diazepam is 7-chloro-1,3-dihydro-1-methyl -5- phenyl-2H-1,4-benzodiazepin-2-one. It is a colorless crystalline compound, insoluble in water. The empirical formula is C 16 H 13 CIN 2 O and the molecular weight is 284.75. Valium is available for oral administration as tablets containing 2 mg, 5 mg or 10 mg diazepam. In addition to the active ingredient diazepam, each tablet contains the following inactive ingredients: anhydrous lactose, corn starch, pregelatinized starch and calcium stearate with the following dyes: 5-mg tablets contain FD&C Yellow No. 6 and D&C Yellow No. 10; 10-mg tablets contain FD&C Blue No. 1. Valium 2-mg tablets contain no dye. PHARMACOLOGY In animals, Valium appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Valium, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with Valium do have a transient ataxia at higher doses. Valium was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function. Oral LD 50 of diazepam is 720 mg/kg in mice and 1240 mg/kg in rats. Intraperitoneal administration of 400 mg/kg to a monkey resulted in death on the sixth day. Reproduction Studies: A series of rat reproduction studies was performed with diazepam in oral doses of 1, 10, 80 and 100 mg/kg. At 100 mg/kg there was a decrease in the number of pregnancies and surviving offspring in these rats. Neonatal survival of rats at doses lower than 100 mg/kg was within normal limits. Several neonates in these rat reproduction studies showed skeletal or other defects. Further studies in rats at doses up to and including 80 mg/kg/day did not reveal teratological effects on the offspring. In humans, measurable blood levels of Valium were obtained in maternal and cord blood, indicating placental transfer of the drug. INDICATIONS Valium is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. In acute alcohol withdrawal, Valium may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Valium is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; and stiff-man syndrome. Oral Valium may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. The effectiveness of Valium in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient. CONTRAINDICATIONS Valium is contraindicated in patients with a known hypersensitivity to this drug and, because of lack of sufficient clinical experience, in pediatric patients under 6 months of age. It may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in acute narrow angle glaucoma. WARNINGS Valium is not of value in the treatment of psychotic patients and should not be employed in lieu of appropriate treatment. As is true of most preparations containing CNS-acting drugs, patients receiving Valium should be cautioned against engaging in hazardous occupations requiring complete mental alertness such as operating machinery or driving a motor vehicle. As with other agents which have anticonvulsant activity, when Valium is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. Abrupt withdrawal of Valium in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures. Since Valium has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during Valium therapy. Usage in Pregnancy: An increased risk of congenital malformations associated with the use of minor tranquilizers (diazepam, meprobamate and chlordiazepoxide) 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. Management of Overdosage: Manifestations of Valium 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 overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of Levophed® (levarterenol) or Aramine (metaraminol). Dialysis is of limited value. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested. Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation, and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, should be consulted prior to use. Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines. (See DRUG ABUSE AND DEPENDENCE section.) PRECAUTIONS If Valium is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed--particularly with known compounds which may potentiate the action of Valium, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants. The usual precautions are indicated for severely depressed patients or those in whom there is any evidence of latent depression; particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. The usual precautions in treating patients with impaired renal or hepatic function should be observed. In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2 1 / 2 mg once or twice daily, initially, to be increased gradually as needed and tolerated). The clearance of Valium and certain other benzodiazepines can be delayed in association with Tagamet (cimetidine) administration. The clinical significance of this is unclear. Information for Patients: 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. Pediatric Use: Safety and effectiveness in pediatric patients below the age of 6 months have not been established. ADVERSE REACTIONS Side effects most commonly reported were drowsiness, fatigue and ataxia. Infrequently encountered were confusion, constipation, depression, diplopia, dysarthria, headache, hypotension, incontinence, jaundice, changes in libido, nausea, changes in salivation, skin rash, slurred speech, tremor, urinary retention, vertigo and blurred vision. Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances and stimulation have been reported; should these occur, use of the drug should be discontinued. Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy. Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after Valium therapy and are of no known significance. 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 diazepam. 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 (eg, 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 diazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence. DOSAGE AND ADMINISTRATION Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In such cases dosage should be increased cautiously to avoid adverse effects. Diazepam affects chemicals in the brain that may become unbalanced and cause anxiety, seizures, and muscle spasms. Diazepam is used to relieve anxiety, nervousness, and tension associated with anxiety disorders. Diazepam also used to treat certain types of seizure disorders and muscle spasms. Diazepam may also be used for purposes other than those here. Diazepam is also known as Valium. It comes as tablets, liquid or suppositories. It may be given as an injection in Hospital. Diazepam is pronounced dye-az-ee-pam.

-------------------------------------------------------------------------------- Indications The short-term symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear or aggressiveness, such as may occur in psychoneurosis, anxiety reactions due to stress conditions and anxiety states with somatic expression. In acute alcoholic withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor and impending acute delirium tremens. As an adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology, such as inflammation of the muscle and joints or secondary to trauma; spasticity caused by upper motor neuron disorders, such as cerebral palsy and paraplegia; athetosis and the rare stiff man syndrome. to top -------------------------------------------------------------------------------- Contraindications Myasthenia gravis, known hypersensitivity to benzodiazepines. Not recommended for children under 6 months of age. to top -------------------------------------------------------------------------------- Warnings Pregnancy: Several studies have suggested an increased risk of congenital malformations associated with the use of diazepam, chlordiazepoxide and meprobamate during the first trimester of pregnancy. Therefore, the administration of diazepam is rarely justified in women of childbearing potential. If the drug is prescribed for a woman of childbearing potential, she should be warned to contact her physician regarding discontinuation of the drug if she intends to become or suspects that she is pregnant. to top -------------------------------------------------------------------------------- Precautions Geriatrics: Elderly and debilitated patients or those with organic brain disorders have been found to be prone to CNS depression following even low doses. For these patients it is recommended that the dosage be limited to the smallest effective amount to preclude development of ataxia, oversedation or other possible adverse effects. Use in emotional disorders: Diazepam is not recommended in the treatment of psychotic or severely depressed patients. Precautions are indicated for severely depressed patients or those who show evidence of impending depression, particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. Since excitement and other paradoxical reactions may result from the use of the drug in psychotic patients, it should not be used in ambulatory patients suspected of having psychotic tendencies. Use in epileptic patients: Since diazepam may exacerbate grand mal seizures in some patients, caution is required when it is used in epileptic patients. An adjustment may be necessary in their anticonvulsive medication. Abrupt withdrawal of diazepam in these patients should also be avoided. Potentiation of drug effects: Patients should be advised to abstain from alcohol and other CNS depressant drugs during treatment with diazepam. Phenothiazines, barbiturates, MAO inhibitors and other psychoactive drugs may potentiate the action of the drug and should not usually be given concurrently. Drug dependence: Abrupt cessation of large doses of diazepam after prolonged periods may precipitate acute withdrawal symptoms and, in these cases, the drug should be discontinued gradually. Caution should be exercised when it is considered necessary to administer diazepam to addiction prone individuals. Occupational Hazards: Patients receiving diazepam should be advised to proceed cautiously whenever mental alertness and physical coordination are required. The usual precautions in treating patients with impaired renal and hepatic functions should be observed. If diazepam is administered for protracted periods, periodic blood counts and liver function tests would be highly advisable. to top -------------------------------------------------------------------------------- Adverse Effects The most common adverse effects reported are drowsiness and ataxia. Other reactions noted less frequently are fatigue, dizziness, nausea, blurred vision, diplopia, vertigo, headache, slurred speech, tremors, hypoactivity, dysarthria, euphoria, impairment of memory, confusion, depression, incontinence or urinary retention, constipation, skin rash, generalized exfoliative dermatitis, hypotension, changes in libido. The more serious adverse reactions occasionally reported are leukopenia, jaundice, hypersensitivity and paradoxical reactions. Paradoxical reactions such as hyperexcited states, anxiety, excitement, hallucinations, increased muscle spasticity, insomnia, rage, as well as sleep disturbances and stimulation, have been reported; should these occur, the drug should be discontinued. Minor changes in EEG patterns have been observed in patients on diazepam therapy. These changes consist of low to moderate voltage fast activity, 20 to 30 cycles/second and are of no known significance. to top -------------------------------------------------------------------------------- Overdose Symptoms: Drowsiness, oversedation and ataxia. When the effects of drug overdosage begin to wear off, the patient exhibits some jitteriness and overstimulation. The cardinal manifestations of overdosage are drowsiness and confusion, reduced reflexes and coma. There are minimum effects on respiration, pulse and blood pressure unless the overdosage is extreme. Treatment: Gastric lavage may be beneficial if performed soon after oral ingestion of diazepam. If necessary, a CNS stimulant such as caffeine or methylphenidate may be administered with caution. Supportive measures should be instituted as indicated, such as, maintenance of an adequate airway, levarterenol for hypotension. Dialysis appears to be of little value. to top -------------------------------------------------------------------------------- Dosage Must be individualized according to diagnosis, severity of symptoms and degree of response. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In the first few days of administration a cumulative effect of the drug may occur, and therefore the dosage should be increased only after stabilization is evident. Adults: Symptomatic relief of anxiety and tension in psychoneurosis and anxiety reactions: 2 to 10 mg, 2 to 4 times daily depending upon severity of symptoms. Symptomatic relief in acute alcohol withdrawal: 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed. Adjunctively for relief of skeletal muscle spasms: 2 to 10 mg, 3 to 4 times daily. Elderly and debilitated patients, or in the presence of debilitating disease: 2 mg, 1 or 2 times daily initially; increase gradually as needed and tolerated. Children (Because of varied responses, initiate therapy with lowest dose and increase as required. Not for use in children under 6 months): 1 to 2.5 mg, 3 or 4 times daily initially; increase gradually as needed and tolerated. Do not prescribe or administer diazepam for periods in excess of 6 weeks, unless a definite need for utilizing this medication has been established by a followup medical examination. to top -------------------------------------------------------------------------------- Supplied 2 mg: Each white cylindrical, biplane tablet with edges bevelled, single scored on one side and engraved {ROCHEover2} on unscored side contains: Diazepam 2 mg. Also contains lactose 100 mg. Nonmedicinal ingredients: Cornstarch and magnesium stearate. Energy: 2.8 kJ (0.7 kcal). Gluten-free, paraben-free, sodium-free, sulfite-free and tartrazine-free. Bottles of 100. 5 mg: Each yellow cylindrical, biplane tablet with edges bevelled, single scored on one side engraved ROCHE above and C below the score line and engraved {VALIUMover5} on unscored side contains: Diazepam 5 mg. Nonmedicinal ingredients: Cornstarch, iron oxide, lactose, magnesium stearate and quinoline yellow WS. Energy: 2.8 kJ (0.7 kcal). Gluten-free, paraben-free, sodium-free, sulfite-free and tartrazine-free. Bottles of 100 and 1000. 10 mg: Each light blue cylindrical, biplane tablet with edges bevelled, single scored on one side and engraved {ROCHEover10} on unscored side contains: Diazepam 10 mg. Also contains lactose 100 mg. Nonmedicinal ingredients: Cornstarch, indigotine and magnesium stearate. Energy: 2.8 kJ (0.7 kcal). Gluten-free, paraben-free, sodium-free, sulfite-free and tartrazine-free. Bottles of 100. Diazepam (pronounced da???z?p?m, marketed under brand names Valium, Stesolid, Seduxen, Bosaurin and Apozepam)[1] is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, skeletal muscle relaxant and amnestic properties. This makes it a useful drug for treating anxiety, insomnia, seizures, alcohol withdrawal, and muscle spasms. It is also used before certain medical procedures (such as endoscopies) to reduce tension and anxiety, and in some surgical procedures to induce amnesia.[2][3] Diazepam is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.[4] Diazepam is used to treat a wide range of conditions and is one of the most frequently prescribed benzodiazepines. Diazepam is a benzodiazepine that binds to a specific subunit on the GABAA receptor at a site that is distinct from the endogenous GABA molecule.[5][6]The GABAA receptor is an inhibitory channel which, when activated, decreases neurologic activity. Due to the role of diazepam as a positive allosteric modulator of GABA, when it binds to benzodiazepine receptors it causes inhibitory effects. This arises from the hyperpolarization of the postsynaptic membrane, due to the control exerted over negative chloride ions by GABAA receptors.[5][7] Diazepam appears to act on areas of the limbic system, thalamus and hypothalamus, inducing anxiolytic effects. Its actions are due to the enhancement of GABA activity.[2][5] [edit] History Diazepam was the second benzodiazepine to be invented by Leo Sternbach of Hoffmann-La Roche, and was approved for use in 1963. It is five times more potent than its predecessor, chlordiazepoxide, which it quickly surpassed in terms of sales. After this initial success, other pharmaceutical companies began to introduce other benzodiazepine derivatives.[8] The benzodiazepines gained popularity among medical professionals as an improvement upon barbiturates, which have a comparatively narrow therapeutic index, and are far more sedating at therapeutic doses. The benzodiazepines are also far less dangerous; death rarely results from diazepam overdose, except in cases where it is consumed with large amounts of other depressants (such as alcohol or other sedatives).[9] Diazepam was the top-selling pharmaceutical in the United States from 1969 to 1982, with peak sales in 1978 of 2.3 billion pills.[8] Over the years, physicians, psychiatrists and neurologists have discovered many new off-label uses for diazepam, such as treatment of spastic paresis and palliative treatment of stiff-person syndrome.[10] [edit] Pharmacokinetics Diazepam can be administered orally, intravenously, intramuscularly, or as a suppository.[11] When diazepam is administered orally, it is rapidly absorbed and has a fast onset of action. The onset of action is 1-5 minutes for IV administration and 15-30 minutes for IM administration. The duration of the diazepam's main pharmacological effects is 15 minutes to 1 hour for both routes of administration.[12] Peak plasma levels are achieved 30 minutes to 2 hours after oral administration. When diazepam is administered as an intramuscular injection, absorption is slow, erratic and incomplete.[1][13] Diazepam is highly lipid-soluble, and is widely distributed throughout the body after administration. It easily crosses both the blood-brain barrier and the placenta, and is excreted into breast milk. After absorption, diazepam is redistributed into muscle and adipose tissue. Continual daily doses of diazepam will quickly build up to a high concentration in the body (mainly in adipose tissue), which will be far in excess of the actual dose for any given day.[11][13] Diazepam is metabolised in the liver via the cytochrome P450 enzyme system. It has a biphasic half-life of 1-2 and 2-5 days, and has several pharmacologically active metabolites. The main active metabolite of diazepam is desmethyldiazepam (also known as nordazepam or nordiazepam). Diazepam's other active metabolites include temazepam and oxazepam. These metabolites are conjugated with glucuronide, and are excreted primarily in the urine. Because of these active metabolites, the serum values of diazepam alone are not useful in predicting the effects of the drug.[1][13] Diazepam has a half-life (t1/2?) of 20-50 hours, and desmethyldiazepam has a half-life of 30-200 hours.[13] Most of the drug is metabolised; very little diazepam is excreted unchanged.[11] In humans, the protein binding of diazepam is around 98.5%.[1] [edit] Indications Diazepam is mainly used to treat anxiety, insomnia, and symptoms of acute alcohol or opiate withdrawal. It is also used as a premedication for inducing sedation, anxiolysis or amnesia prior to certain medical procedures (e.g. endoscopy).[1] Diazepam is rarely used as a primary drug for the long-term treatment of epilepsy. This is due to the fact that tolerance to the anticonvulsant effects of diazepam usually develops within 6 to 12 months of treatment, effectively rendering it useless for this purpose.[11] Diazepam has a broad spectrum of indications (most of which are off-label), including: Treatment of anxiety, panic attacks, and states of agitation[1] Treatment of status epilepticus, adjunctive treatment of other forms of epilepsy[1] Treatment of the symptoms of alcohol and opiate withdrawal[1] Short-term treatment of insomnia[1] Treatment of tetanus, together with other measures of intensive-treatment[14] Initial management of mania, together with firstline drugs like lithium, valproate or other antipsychotics[citation needed] Adjunctive treatment (with antidepressants) of depression with symptoms of anxiety[citation needed] Adjunctive treatment (with antipsychotics), in patients who develop early extrapyramidal side-effects[citation needed] Adjunctive treatment of painful muscle conditions[10] Adjunctive treatment of spastic muscular paresis (para-/tetraplegia) caused by cerebral or spinal cord conditions such as stroke, multiple sclerosis, spinal cord injury (long-term treatment is coupled with other rehabilitative measures)[10] Palliative treatment of stiff person syndrome[7] Pre-/postoperative sedation, anxiolysis and/or amnesia (e.g. before endoscopic or surgical procedures)[10] Treatment of overdosage with hallucinogens or CNS stimulants[11] Adjunctive treatment of drug-induced seizures, resulting from exposure to sarin, VX, soman (or other organophosphate poisons), lindane, chloroquine, physostigmine, or pyrethroids[11] Emergency treatment of eclampsia, along with IV magnesium sulfate Prophylactic treatment of oxygen toxicity during hyperbaric oxygen therapy.[15] [edit] Veterinary uses Diazepam is very useful as short term sedative and anxiolytic for cats and dogs. It can also be used for preoperative sedation of cats and dogs and as an anticonvulsive suitable for short-term and long-term treatment, if sedation is tolerated. The anticonvulsant dosage is typically 0.25 milligram/pound administered intervenously or, for emergency treatment, rectally in suppository form.[16] [edit] Dosage Dosages should be determined on an individual basis, depending upon the condition to be treated, the severity of symptoms, the body weight of the patient, and any comorbid conditions the patient may have.[11] Elderly patients and those with liver disorders experience decreased metabolism of diazepam; therefore the dosage for these patients should be reduced. General guidelines for this group of patients: initial doses of 2mg to 2.5mg, 1 or 2 times daily; increase gradually as required/tolerated.[7] [edit] Adult dosage recommendations Insomnia - Up to 30mg orally, as a single dose, at bedtime.[11] Anxiety/panic attacks - Dosage differs depending upon severity of symptoms. For panic attacks, diazepam is taken "as needed". Oral - 2mg to 10mg oral, 2 to 4 times daily.[7] IV/IM - 2mg to 10mg. Repeat in 3 to 4 hours, if necessary.[10] Pre-/postoperative sedation - If other premedications are used, they must be administered separately.[10] Oral - Up to 20mg as a single dose.[11] IV/IM - 2mg to 10mg, repeated at intervals of at least 5 to 10 minutes, until adequate sedation and/or anxiolysis is achieved.[11] Status epilepticus Oral - 2mg to 10mg, 2 to 4 times daily.[7] IV/IM - 5mg to 10mg. May be repeated every 5 to 10 minutes until termination of seizures. Maximum dose of 40mg to 60mg can be used; if this dose is ineffective, other anticonvulsant drug therapy should be instituted.[11] Rectal solution - 10mg as a single dose. May be repeated after 5 minutes, if necessary. The oral solution can also be administered rectally.[11] Painful muscle conditions or muscle spasms Oral - Up to 15mg daily, in divided doses. In severe spasticity associated with cerebral palsy, doses may be increased gradually up to 60mg daily.[11] IV/IM - 5mg to 10mg initially, then 5mg to 10mg in 3 to 4 hours, if necessary.[10] Tetanus - 100 to 300µg/kg intravenously, repeated every 1 to 4 hours.[11] Spastic paresis - Usually starting with 3 times daily 2mg, increasing to up to 3 times 20mg in slow increments, taking care to avoid ataxia.[citation needed] Alcohol/opioid withdrawal - For symptomatic relief of agitation, tremor, delirium tremens and hallucinosis. Oral - 10mg, 3 or 4 times during the first 24 hours. Reduce to 5mg, 3 or 4 times a day, or as needed.[7] IV/IM - 10mg initially, 5mg to 10mg in 3 to 4 hours, if necessary.[10] Initial treatment of mania - 30 to 40mg daily oral or rectal, rarely more.[citation needed] Overdosage with hallucinogens/CNS stimulants - Normally a single intravenous dose of 10 to 20mg is sufficient.[citation needed] Adjunctive treatment of depression - Usually 10 to 30mg daily oral, the greater part of the dose given at bedtime. The doses should be decreased and the medication stopped as soon as the clinical situation allows.[citation needed] Adjunctive treatment of extrapyramidal side-effects - Depends on the individual. Effective dose(s) unknown. Do not administer for more than 4 weeks.[citation needed] Cardioversion - To relieve anxiety/tension and to reduce recall of procedure. 5mg to 15mg IV, 5 to 10 minutes prior to the procedure.[10] Prophylactic treatment of oxygen toxicity during hyperbaric therapy - 5mg to 10mg.[15] [edit] Pediatric dosage recommendations Patients over 6 months of age: Initiate therapy with the lowest effective dose.[7] Oral: Initial dose of 40 to 200µg/kg of bodyweight. Can be repeated as tolerated, up to 4 times daily.[11] Rectal suppository: 40 to 200µg/kg of bodyweight, which can be repeated as tolerated up to 4 times daily.[11] Sedation or muscle relaxation[11] IV/IM - 200µg/kg of bodyweight. Status epilepticus[11] IV/IM - 200 to 300µg/kg of bodyweight. May be repeated after 5 to 10 minutes, if required. Rectal solution - 5mg (for patients 1 to 3 years of age); repeat after 5 to 10 minutes, if necessary. Tetanus[10] Patients 30 days to 5 years of age - 1mg to 2mg IV/IM, slowly; repeat every 3 to 4 hours, as necessary. Patients 5 years of age or older - 5mg to 10mg IV/IM, slowly; repeat every 3 to 4 hours, as necessary. Convulsive disorders[10] Patients 30 days to 5 years of age - 0.2mg to 0.5mg IV/IM, slowly, every 2 to 5 minutes. Maximum dose of 5mg. Patients 5 years of age or older - 1mg IV/IM, slowly, every 2 to 5 minutes. Maximum of dose of 10mg. Repeat in 2 to 4 hours, if necessary. Patients under 6 months of age: Diazepam should not be given to children under 6 months of age.[7] [edit] Availability Diazepam is supplied in the following forms: For oral administration: Tablets - 2mg, 5mg, 10mg[7]. Generic versions available. Capsules, time-release - 15mg (marketed by Roche as Valrelease®)[13] Liquid solution - 1mg/ml in 500ml containers and unit-dose (5mg & 10mg); 5mg/ml in 30 ml dropper bottle (marketed by Roxane as Diazepam Intensol®)[13] For parenteral administration: Solution for IV/IM injection - 5mg/ml. 2ml ampoules and syringes; 1ml, 2ml, 10ml vials; 2 ml Tel-E-Ject; also contains 40% propylene glycol, 10% ethyl alcohol, 5% sodium benzoate and benzoic acid as buffers, and 1.5% benzyl alcohol as a preservative.[17][13] For rectal administration: Solution[11] Suppositories - 5mg and 10mg[18][11] [edit] Side effects Diazepam has a range of side effects which are common to most benzodiazepines. Most common side effects include: Somnolence Suppression of REM sleep or dreaming Impaired motor function Impaired coordination Impaired balance Dizziness Depression Anterograde amnesia (especially pronounced in higher doses) Reflex tachycardia[12] Rare paradoxical side effects can include: nervousness, irritability, insomnia, muscle cramps, and in extreme cases, rage and violence.[citation needed] If these side effects are present, diazepam treatment should be immediately terminated. Up to 30% of individuals treated on a long-term basis develop a form of dependence known as "low-dose-dependence". These patients do not develop a tolerance, and do not need increasingly large doses to experience the euphoric side effects of the drug.[citation needed] Diazepam may impair the ability to drive vehicles or operate machinery. The impairment is worsened by consumption of alcohol, because both act as central nervous system depressants.[7] During the course of therapy, tolerance to the sedative effects usually develops.[citation needed] Patients with severe attacks of apnea during sleep may suffer respiratory depression (hypoventilation) leading to respiratory arrest and death. Organic changes such as leukopenia and liver-damage of the cholostatic type with or without jaundice (icterus) have been observed in a few cases.[citation needed] [edit] Interactions If diazepam is to be administered concomitantly with other drugs, attention should be paid to the possible pharmacological interactions. Particular care should be taken with drugs that enhance the effects of diazepam, such as barbiturates, phenothiazines, narcotics and antidepressants.[7] Diazepam does not increase or decrease hepatic enzyme activity, and does not alter the metabolism of other compounds. There is no evidence which would suggest that diazepam alters its own metabolism with chronic administration.[11] Agents which have an effect on hepatic cytochrome P450 pathways or conjugation can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable.[11] Diazepam increases the central depressive effects of alcohol, other hypnotics/sedatives (e.g. barbiturates), narcotics, and other muscle relaxants. The euphoriant effects of opioids may be increased, leading to increased risk of psychological dependence.[19][20] Cimetidine, omeprazole, ketoconazole, itraconazole, disulfiram, fluvoxamine, isoniazid, erythromycin, probenicid, propranolol, imipramine, ciprofloxacin, fluoxetine and valproic acid prolong the action of diazepam by inhibiting its elimination.[11][13] Oral contraceptives ("the pill") significantly decrease the elimination of desmethyldiazepam, a major metabolite of diazepam.[20] Rifampin, phenytoin, carbamazepine and phenobarbital increase the metabolism of diazepam, thus decreasing drug levels and effects.[11] Nefazodone can cause increased blood levels of benzodiazepines.[20] Cisapride may enhance the absorption, and therefore the sedative activity, of diazepam.[21] Small doses of theophylline may inhibit the action of diazepam.[citation needed] Diazepam may block the action of levodopa (used in the treatment of Parkinson's Disease).[19] Diazepam may alter digoxin serum concentrations.[11] Other drugs that may have interactions with diazepam include: Antipsychotics (e.g. chlorpromazine), MAO inhibitors, ranitidine.[20] Smoking tobacco can enhance the elimination of diazepam and decrease its action.[19] Foods that acidify the urine can lead to faster absorption and elimination of diazepam, reducing drug levels and activity.[19] Foods that alkalinize the urine can lead to slower absorption and elimination of diazepam, increasing drug levels and activity.[11] There are conflicting reports as to whether food in general has any effects on the absorption and activity of orally administered diazepam.[19] [edit] Contraindications Use of diazepam should be avoided, when possible, in individuals with the following conditions: Ataxia Severe hypoventilation Acute narrow-angle glaucoma Severe hepatic deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2) Severe renal deficiencies (e.g. patients on dialysis) Severe sleep apnea Severe depression, particularly when accompanied by suicidal tendencies Acute intoxication with alcohol, narcotics, or other psychoactive substances Myasthenia gravis Hypersensitivity or allergy to any drug in the benzodiazepine class [edit] Special caution needed Pediatric patients Less than 18 years of age - Treatment usually not indicated, except treatment of epilepsy, and pre-/postoperative treatment. The smallest possible effective dose should be used for this group of patients.[20] Under 6 months of age - Safety and effectiveness have not been established; diazepam should not be given to individuals in this age group.[7][20] Elderly and very ill patients - Possibility that apnea and/or cardiac arrest may occur. Concomitant use of other central nervous system depressants increases this risk. The smallest possible effective dose should be used for this group of patients..[7][20][22] I.V. or I.M. injections in hypotensive individuals or those in shock should be administered carefully and vital signs should be monitored.[22] [edit] Patients at a high risk for abuse and dependence Diazepam can lead to physiological tolerance, and psychological and/or physical dependence. At a particularly high risk for diazepam misuse, abuse, and dependence are: Patients with a history of alcohol or drug abuse or dependence[7][23] Emotionally unstable patients[citation needed] Patients with severe personality disorders, such as Borderline Personality Disorder[citation needed] Patients with chronic pain or other physical disorders[citation needed] Patients from the aforementioned groups should be monitored very closely during therapy for signs of abuse and development of dependence. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended.[7][23] The American Society of Addiction Medicine has policy indicating that patients with addictive disease should not be presecribed benzodiazepines such as diazepam. [edit] Withdrawal Administration of therapeutic doses of diazepam for 6 weeks or longer can result in physical dependence, characterized by a withdrawal syndrome when the drug is discontinued. With larger doses, physical dependence develops more rapidly.[11] After continued therapy in excess of a few weeks, diazepam should never be stopped abruptly. The dose should instead be lowered gradually, over a period of 2 to 4 weeks, in order to minimize withdrawal symptoms.[11][23] Withdrawal symptoms are initially minimal, and increase in severity over the first 5 to 9 days after ingestion of the drug is stopped. Diazepam's long half-life and active metabolites delay the onset of such symptoms.[11] The withdrawal symptoms for diazepam are similar to those of other CNS depressants (e.g. alcohol, barbiturates), and can include[11]: Anxiety Dysphoria Irritability Insomnia REM Rebound Confusion Tremors Muscle spasms Abdominal and muscle cramps Anorexia (i.e. lack of appetite) Nausea/vomiting Hyperthermia/sweating Hypotension In severe cases of diazepam withdrawal, symptoms can include: Convulsions (i.e. seizures) Death The more severe side effects usually only develop for patients who were treated with excessive doses for extended periods of time. Usually only the milder symptoms develop in patients terminating therapeutic-level treatment after several months.[7] [edit] Overdose An individual who has consumed too much diazepam will display one or more of the following symptoms[7][24]: Somnolence/difficulty staying awake Mental confusion Hypotension Impaired motor functions Impaired reflexes Impaired coordination Impaired balance Dizziness Coma Although not usually fatal when taken alone, a diazepam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of diazepam (or any other benzodiazepine) is flumazenil (Anexate®). This drug is only used in cases with severe respiratory depression or cardiovascular complications. Because flumazenil is a short-acting drug and the effects of diazepam can last for days, several doses of flumazenil may be necessary. Artificial respiration and stabilization of cardiovascular functions may also be necessary. Although not routinely indicated, activated charcoal can be used for decontamination of the stomach following a diazepam overdose. Emesis is contraindicated. Dialysis is minimally effective. Hypotension may be treated with levarterenol or metaraminol.[11][9][7][24] The oral LD50 (lethal dose in 50% of the population) of diazepam is 720mg/kg in mice and 1240mg/kg in rats.[7] A case where a patient took 300mg resulted only in prolonged sleep and consecutive drowsiness for the next days without serious impairment of cardiac or respiratory functions.[citation needed] Overdoses of diazepam with alcohol and/or other depressants may be fatal.[9] [edit] Recreational use Generally, diazepam is not used as a recreational drug as frequently as alprazolam or flunitrazepam. Diazepam is often found as an adulterant in heroin.[citation needed] This may be because diazepam greatly amplifies the effects of opioids. Sometimes diazepam is used by stimulant abusers to 'come down' and sleep and also by users of LSD and other hallucinogens to help ease their trip without unpleasant after-effects.[citation needed] [edit] Legal status Internationally, diazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[25] [edit] Physical properties Diazepam occurs as solid white or yellow crystals and has a melting point of 131.5 to 134.5°C. It is odorless, and has a slightly bitter taste. The British Pharmacopoeia lists diazepam as being very slightly soluble in water, soluble in alcohol and freely soluble in chloroform. The United States Pharmacopoeia lists diazepam as soluble 1 in 16 of ethyl alcohol, 1 in 2 of chloroform, 1 in 39 of ether, and practically insoluble in water. The pH of diazepam is neutral (i.e. 7). Diazepam has a shelf-life of 5 years for oral tablets and 3 years for IV/IM solution.[11] Diazepam should be stored at room temperature (15°-30°C). The solution for parenteral injection should be protected from light and kept from freezing. The oral forms should be stored in air-tight containers and protected from light.[13] Diazepam can absorb into plastic, and therefore diazepam solution is not stored in plastic bottles or syringes. It can absorb into plastic bags and tubing used for intervenous infusions. Absorption appears to be dependent on several factors such as temperature, concentration, flow rates and tube length. Diazepam should not be administered if a precipitate has formed and will not dissolve.[13] [edit] Trivia Several plants, such as potato and wheat, contain trace amounts of naturally occurring diazepam and other benzodiazepines.[26] Diazepam has had many high-profile users, including Andy Warhol and Elvis Presley.[8] Valium is the subject of "Mother's Little Helper" by The Rolling Stones and "Rowche Rumble" by The Fall. [edit] External links Roche Pharmaceuticals (US) - Valium Product Information Link page to external chemical sources. [edit] References Fachinformationen (German) for Valium, provided by Roche Pharmaceuticals Bandelow, Borwin et al. Handbuch der Arzneimitteltherapie, Bd.1, Psychopharmaka, 2nd edition. Enke, 2004. ISBN 3131130415. Benkert, Otto et al. Kompendium der Psychiatrischen Pharmakotherapie, 5th edition. Springer, 2003. ISBN 3540218939. [edit] Footnotes ^ a b c d e f g h i Wishart, David (2006). Diazepam. DrugBank. Retrieved on 2006-03-10. ^ a b Diazepam. PubChem. National Institute of Health: National Library of Medicine (2006). Retrieved on 2006-03-11. ^ Diazepam. Medical Subject Headings (MeSH). National Library of Medicine (2006). Retrieved on 2006-03-10. ^ WHO Model List of Essential Medicines (PDF). World Health Organization (March 2005). Retrieved on 2006-03-12. ^ a b c ^ Sieghart, W. (January 1994). "Pharmacology of benzodiazepine receptors: an update". Journal of Psychiatry and Neuroscience 19 (1): 24-29. PubMed. Retrieved on 2006-03-10. ^ a b c d e f g h i j k l m n o p q r s Thomson Healthcare (Micromedex) (March 2000). Diazepam. Prescription Drug Information. Drugs.com. Retrieved on 2006-03-11. ^ a b c Sample, Ian. "Leo Sternbach's Obituary", The Guardian (Guardian Unlimited), Monday October 3, 2005. Retrieved on 2006-03-10. ^ a b c Barondes, Samuel H. (2003). Better Than Prozac. New York: Oxford University Press. ISBN 0195151305, 47-59. ^ a b c d e f g h i j k Diazepam: indications. Rxlist.com. RxList Inc. (January 24, 2005). Retrieved on 2006-03-11. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ^ a b Langsam, Yedidyah. DIAZEPAM (VALIUM AND OTHERS). Brooklyn College (Eilat.sci.Brooklyn.CUNY.edu). Retrieved on 2006-03-23. ^ a b c d e f g h i j ^ Okoromah, C. N., F. E. Lesi (2004). "Diazepam for treating tetanus". Cochrane database of systematic reviews (Online) (1). PubMed. ^ a b (1999) Hyperbaric Medicine Practice, Second Edition. Best Publishing Company. ISBN 0941332780. ^ Hines, Ron DVM PhD (January 14, 2006). Epilepsy In Your Dog Or Cat. 2nd Chance Sanctuary Pet Health Center. Retrieved on May 18, 2006. ^ Diazepam: description. Rxlist.com. RxList Inc. (January 24, 2005). Retrieved on 2006-03-10. ^ Kaewnopparat, N., Kaewnopparat, S., Rojanarat, W., Ingkatawornwong, S. (July/August 2004). "Enhanced Release of Diazepam From Hollow-Type Suppositories". International Journal of Pharmaceutical Compounding. Retrieved on 2006-03-10. ^ a b c d e Holt, Gary A. (1998). Food and Drug Interactions: A Guide for Consumers. Chicago: Precept Press. ISBN 0944496598, 90-91. ^ a b c d e f g Diazepam. PDRHealth.com. PDRHealth.com (2006). Retrieved on 2006-03-10. ^ Bateman, D.N. (1986). "The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam.". Eur J Clin Pharmacol. 30 (2): 205-8. PMID 3709647. ^ a b Diazepam: precautions. Rxlist.com. RxList Inc. (January 24, 2005). Retrieved on 2006-03-10. ^ a b c Diazepam: abuse and dependence. Rxlist.com. RxList Inc. (January 24, 2005). Retrieved on 2006-03-10. ^ a b Diazepam: overdose. Rxlist.com. RxList Inc. (January 24, 2005). Retrieved on 2006-03-10. ^ International Narcotics Control Board (2003). List of psychotropic substances under international control. Green list. Retrieved on 2006-03-11. ^ Wildmann J, Vetter W, Ranalder UB, Schmidt K, Maurer R, Mohler H (1988). "Occurrence of pharmacologically active benzodiazepines in trace amounts in wheat and potato". Biochem Pharmacol 37 (19): 3549-59. PubMed. Retrieved on 2006-04-12. Recent updates to the Drugs.com website and database Consumer and prescribing information. Amitiza, Avandaryl, Chantix, Boostrix, Daytrana, Emsam, Eraxis, Exubera, Exjade, Exubera, Hylenex, iPlex, Macugen, Magnevist, Nexavar, Orencia, Ranexa, Relenza, Revlimid, Rotateq, Taclonex, Tamiflu, Vaprisol, Vivaglobin, Vivitrol, Yaz, Zostavax... New Approval: MoviPrep August 8, 2006 - The FDA has granted marketing approval for prescription MoviPrep for bowel cleansing prior to colonoscopy. MoviPrep is the only liquid PEG bowel cleansing agent that incorporates ascorbic acid in its formulation, which contributes to the efficacy and taste. The addition of ascorbic acid provides a novel osmotic cleansing action that enables... New Application: Sparlon August 10, 2006 - Cephalon, Inc. announced today that it has received a letter from the FDA stating that it's supplemental new drug application for Sparlon tablets, a proprietary dosage form of modafinil for the treatment of attention- deficit/hyperactivity disorder (ADHD) in children and adolescents, is not approvable. In consideration of the FDA's decision, the company has... Focus on: Xenical August 10, 2006 - Xenical (orlistat) is used in the management of obesity including weight loss, weight maintenance and prevention of weight regain when used in conjuction with a reduced-calorie diet. Xenical targets the absorption of fat rather than suppressing your appetite. It works by blocking some of the fat that you eat from being absorbed by your body... New Addition: Hoodia gordonii August 10, 2006 - Hoodia gordonii has received a lot of publicity in recent times for its natural appetite suppressant and weight loss properties. The active ingredient in Hoodia gordonii is the appetite-suppressing molecule, P57, which is licensed to the British pharmaceutical company Phytopharm who are researching its potential as an anti-obesity drug... More Resources: Browse by Medical Condition Top 200 drugs by sales New drug applications Pill Identification Illustrated Health Encyclopedia Pharmaceutical Manufacturers Pipeline These days, drugs can be found everywhere, and it may seem like everyone's doing them. Many teens are tempted by the excitement or escape that drugs seem to offer. But learning the facts about drugs can help you see the risks of chasing this excitement or escape. Read on to learn more. The Deal on Substances Thanks to medical and drug research, there are thousands of drugs that help people. Antibiotics and vaccines have revolutionized the treatment of infections. There are medicines to lower blood pressure, treat diabetes, and reduce the body's rejection of new organs. Medicines can cure, slow, or prevent disease, helping us to lead healthier and happier lives. But there are also lots of illegal, harmful drugs that people take to help them feel good or have a good time. How do drugs work? Drugs are chemicals or substances that change the way our bodies work. When you put them into your body (often by swallowing, inhaling, or injecting them), drugs find their way into your bloodstream and are transported to parts of your body, such as your brain. In the brain, drugs may either intensify or dull your senses, alter your sense of alertness, and sometimes decrease physical pain. A drug may be helpful or harmful. The effects of drugs can vary depending upon the kind of drug taken, how much is taken, how often it is used, how quickly it gets to the brain, and what other drugs, food, or substances are taken at the same time. Effects can also vary based on the differences in body size, shape, and chemistry. Although substances can feel good at first, they can ultimately do a lot of harm to the body and brain. Drinking alcohol, smoking tobacco, taking illegal drugs, and sniffing glue can all cause serious damage to the human body. Some drugs severely impair a person's ability to make healthy choices and decisions. Teens who drink, for example, are more likely to get involved in dangerous situations, such as driving under the influence or having unprotected sex. And just as there are many kinds of drugs available, there are as many reasons for trying drugs or starting to use drugs regularly. People take drugs just for the pleasure they believe they can bring. Often it's because someone tried to convince them that drugs would make them feel good or that they'd have a better time if they took them. Some teens believe drugs will help them think better, be more popular, stay more active, or become better athletes. Others are simply curious and figure one try won't hurt. Others want to fit in. A few use drugs to gain attention from their parents. Many teens use drugs because they are depressed or think drugs will help them escape their problems. The truth is, drugs don't solve problems. Drugs simply hide feelings and problems. When a drug wears off, the feelings and problems remain - or become worse. Drugs can ruin every aspect of a person's life. What are some of the more common drugs? Alcohol The oldest and most widely used drug in the world, alcohol is a depressant that alters perceptions, emotions, and senses. How It's Used: Alcohol is a liquid that is drunk. Effects & Dangers: Alcohol first acts as a stimulant, and then it makes people feel relaxed and a bit sleepy. High doses of alcohol seriously affect a person's judgment and coordination. Drinkers may have slurred speech, confusion, depression, short-term memory loss, and slow reaction times. Large volumes of alcohol drunk in a short period of time may cause alcohol poisoning. Addictiveness: Teens who use alcohol can become psychologically dependent upon it to feel good, deal with life, or handle stress. In addition, their bodies may demand more and more to achieve the same kind of high experienced in the beginning. Some teens are also at risk of becoming physically addicted to alcohol. Withdrawal from alcohol can be painful and even life threatening. Symptoms range from shaking, sweating, nausea, anxiety, and depression to hallucinations, fever, and convulsions. Amphetamines Amphetamines are stimulants that accelerate functions in the brain and body. They come in pills or tablets. Prescription diet pills also fall into this category of drugs. Street Names: speed, uppers, dexies, bennies How They're Used: Amphetamines are swallowed, inhaled, or injected. Effects & Dangers: Swallowed or snorted, these drugs hit users with a fast high, making them feel powerful, alert, and energized. Uppers pump up heart rate, breathing, and blood pressure, and they can also cause sweating, shaking, headaches, sleeplessness, and blurred vision. Prolonged use may cause hallucinations and intense paranoia. Addictiveness: Amphetamines are psychologically addictive. Users who stop report that they experience various mood problems such as aggression and anxiety and intense cravings for the drugs. Cocaine and Crack Cocaine is a white crystalline powder made from the dried leaves of the coca plant. Crack, named for its crackle when heated, is made from cocaine. It looks like white or tan pellets. Street Names for Cocaine: coke, snow, blow, nose candy, white, big C Street Names for Crack: freebase, rock How They're Used: Cocaine is inhaled through the nose or injected. Crack is smoked. Effects & Dangers: Cocaine is a stimulant that rocks the central nervous system, giving users a quick, intense feeling of power and energy. Snorting highs last between 15 and 30 minutes; smoking highs last between 5 and 10 minutes. Cocaine also elevates heart rate, breathing rate, blood pressure, and body temperature. Injecting cocaine can give you hepatitis or AIDS if you share needles with other users. Snorting can also put a hole inside the lining of your nose. First-time users - even teens - of both cocaine and crack can stop breathing or have fatal heart attacks. Using either of these drugs even one time can kill you. Addictiveness: These drugs are highly addictive, and as a result, the drug, not the user, calls the shots. Even after one use, cocaine and crack can create both physical and psychological cravings that make it very, very difficult for users to stop. Cough and Cold Medicines (DXM) Several over-the-counter cough and cold medicines contain the ingredient dextromethorphan (also called DXM). If taken in large quantities, these over-the-counter medicines can cause hallucinations, loss of motor control, and "out-of-body" (or disassociative) sensations. Street Names: triple C, candy, C-C-C, dex, DM, drex, red devils, robo, rojo, skittles, tussin, velvet, vitamin D How They're Used: Cough and cold medicines, which come in tablets, capsules, gel caps, and lozenges as well as syrups, are swallowed. DXM is often extracted from cough and cold medicines, put into powder form, and snorted. Effects & Dangers: Small doses help suppress coughing, but larger doses can cause fever, confusion, impaired judgment, blurred vision, dizziness, paranoia, excessive sweating, slurred speech, nausea, vomiting, abdominal pain, irregular heartbeat, high blood pressure, headache, lethargy, numbness of fingers and toes, redness of face, dry and itchy skin, loss of consciousness, seizures, brain damage, and even death. Sometimes users mistakenly take cough syrups that contain other medications in addition to dextromethorphan. High doses of these other medications can cause serious injury or death. Addictiveness: People who use cough and cold medicines and DXM regularly to get high can become psychologically dependent upon them (meaning they like the feeling so much they can't stop, even though they aren't physically addicted). Depressants Depressants, such as tranquilizers and barbiturates, calm nerves and relax muscles. Many are legally available by prescription (such as Valium and Xanax) and are bright-colored capsules or tablets. Street Names: downers, goof balls, barbs, ludes How They're Used: Depressants are swallowed.

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Cialis is a brand new treatment for impotence that works just like Viagra, only it gives you faster results, has a higher success rate, lasts up to 32 hours longer, and causes fewer unpleasant side effects! Tadalafil is also known to: - Increase Sex Drive - Boost Sexual Performance - Cause Fuller & Harder Erections - Increase Stamina & Endurance - Help with Quicker Recharges. How to take This drug is taken by mouth as needed 20 minutes before sexual activity. Take only as directed, usually once each 3 days as needed. Cialis works along with sexual stimulation to help achieve an erection. The usual dose for most people is 10mg (half a pill). Side Effects Headache, flushing, stomach upset, nasal stuffiness, diarrhea and dizziness might occur. If these effects persist or worsen, notify your doctor promptly. Precaution Before using this drug, tell your doctor your medical history, including any allergies (especially drug allergies), any penis conditions such as fibrosis/scarring, history of painful/prolonged erection (priapism), sickle cell anemia, blood system cancers (such as leukemia or myeloma), or Peyronie's disease, eye problems (retina diseases). kidney or liver disease, bleeding disorders or active stomach ulcers, heart diseases, stroke or severe high or low blood pressure. Limit alcohol intake, as it may aggravate side effects of this drug. To avoid dizziness and lightheadedness when rising from a seated or lying position, get up slowly. The elderly may be more sensitive to the side effects of this drug, therefore caution is advised in this group. Drug Interactions Tell your doctor of all nonprescription and prescription medication you may use, especially any nitrate medications (e.g., nitroglycerin, isosorbide dinitrate), nitroprusside (any "nitric oxide donor" medicines), cimetidine, erythromycin, azole antifungals (e.g., itraconazole, ketoconazole), mibefradil, rifamycins (e.g., rifampin) or high blood pressure medicines. Storage Store at room temperature between 59 and 86 degrees F (15-30 degrees C) away from light and moisture. Keep this and all medications out of the reach of children. DESCRIPTION CIALIS® (tadalafil), an oral treatment for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Tadalafil has the empirical formula C 22 H 19 N 3 O 4 representing a molecular weight of 389.41. The structural formula is: The chemical designation is pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-. It is a crystalline solid that is practically insoluble in water and very slightly soluble in ethanol. CIALIS is available as film-coated, almond-shaped tablets for oral administration. Each tablet contains 5, 10, or 20 mg of tadalafil and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, talc, titanium dioxide, and triacetin. CLINICAL PHARMACOLOGY Mechanism of Action Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation. Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas. In vitro studies have shown that the effect of tadalafil is more potent on PDE5 than on other phosphodiesterases. These studies have shown that tadalafil is >10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, tadalafil is 700-fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Tadalafil is >9,000-fold more potent for PDE5 than for PDE8, PDE9, and PDE10 and 14-fold more potent for PDE5 than for PDE11A1, an enzyme found in human skeletal muscle. Tadalafil inhibits human recombinant PDE11A1 activity at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined. Pharmacokinetics Over a dose range of 2.5 to 20 mg, tadalafil exposure (AUC) increases proportionally with dose in healthy subjects. Steady-state plasma concentrations are attained within 5 days of once-daily dosing, and exposure is approximately 1.6-fold greater than after a single dose. Tadalafil is eliminated predominantly by hepatic metabolism, mainly by cytochrome P450 3A4 (CYP3A4). The concomitant use of potent CYP3A4 inhibitors such as ritonavir or ketoconazole resulted in significant increases in tadalafil AUC values ( see PRECAUTIONS and DOSAGE AND ADMINISTRATION ). Mean tadalafil concentrations measured after the administration of a single oral dose of 20 mg to healthy male subjects are depicted in Figure 1. Therefore, CIALIS administration with nitrates is contraindicated. In a patient who has taken CIALIS, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last dose of CIALIS before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring ( see CONTRAINDICATIONS ). Effects on Exercise Stress Testing --The effects of tadalafil on cardiac function, hemodynamics, and exercise tolerance were investigated in a single clinical pharmacology study. In this blinded crossover trial, 23 subjects with stable coronary artery disease and evidence of exercise-induced cardiac ischemia were enrolled. The primary endpoint was time to cardiac ischemia. The mean difference in total exercise time was 3 seconds (tadalafil 10 mg minus placebo), which represented no clinically meaningful difference. Further statistical analysis demonstrated that tadalafil was non-inferior to placebo with respect to time to ischemia. Of note, in this study, in some subjects who received tadalafil followed by sublingual nitroglycerin in the post-exercise period, clinically significant reductions in blood pressure were observed, consistent with the augmentation by tadalafil of the blood-pressure-lowering effects of nitrates. Effects on Vision --Single oral doses of phosphodiesterase inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green), using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. In a study to assess the effects of a single dose of tadalafil 40 mg on vision (N=59), no effects were observed on visual acuity, intraocular pressure, or pupillometry. Across all clinical studies with CIALIS, reports of changes in color vision were rare (<0.1% of patients). Effects on Sperm Characteristics --There were no clinically relevant effects on sperm concentration, sperm count, motility, or morphology in humans in placebo-controlled studies of daily doses of tadalafil 10 mg (N=204) or 20 mg (N=217) for 6 months. In addition, tadalafil had no effect on serum levels of testosterone, luteinizing hormone, or follicle stimulating hormone. Effects on Cardiac Electrophysiology --The effect of a single 100-mg dose of tadalafil on the QT interval was evaluated at the time of peak tadalafil concentration in a randomized, double-blinded, placebo, and active (intravenous ibutilide)-controlled crossover study in 90 healthy males aged 18 to 53 years. The mean change in QT c (Fridericia QT correction) for tadalafil, relative to placebo, was 3.5 milliseconds (two-sided 90% CI=1.9, 5.1). The mean change in QT c (Individual QT correction) for tadalafil, relative to placebo, was 2.8 milliseconds (two-sided 90% CI=1.2, 4.4). A 100-mg dose of tadalafil (5 times the highest recommended dose) was chosen because this dose yields exposures covering those observed upon coadministration of tadalafil with potent CYP3A4 inhibitors or those observed in renal impairment. In this study, the mean increase in heart rate associated with a 100-mg dose of tadalafil compared to placebo was 3.1 beats per minute. Online Buy Cialis, no prior prescription needed. Free online diagnosis. All orders are reviewed by licensed physicians and shipped from US licensed pharmacies. Get overnight delivery. www.kwikmed.com (sponsored listing) Cialis Alternatives Compared Compare Cialis with popular non-prescription impotence treatments and save today. www.impotenceguide.info (sponsored listing) Order Cialis Low As $52.95 10mg x10 pills $99.95 Free FedEx Shipping on All orders. US Pharmacy. US orders only. 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All orders are filled FDA ALERT [07/2005]: A small number of men have lost eyesight in one eye some time after taking Cialis, Viagra, or Levitra. This type of vision loss is called non-arteritic anterior ischemic optic neuropathy (NAION). NAION causes a sudden loss of eyesight because blood flow is blocked to the optic nerve. We do not know at this time if Cialis, Viagra or Levitra causes NAION. NAION also happens in men who do not take these medicines. People who have a higher chance for NAION include those who: have heart disease are over 50 years old have diabetes have high blood pressure have high cholesterol smoke have certain eye problems FDA has approved new labels for Cialis, Viagra, and Levitra to include information on possible eyesight loss (NAION). Stop using Cialis, Viagra, or Levitra if you have a loss in your eyesight. Get medical help right away. Current Information