Tamsulosin Sandoz may be available in the countries listed below.
Tamsulosin hydrochloride (a derivative of Tamsulosin) is reported as an ingredient of Tamsulosin Sandoz in the following countries:
International Drug Name Search
Besnoline may be available in the countries listed below.
Tolperisone hydrochloride (a derivative of Tolperisone) is reported as an ingredient of Besnoline in the following countries:
International Drug Name Search
Bob Martin Totaal Ontwormer may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Mebendazole is reported as an ingredient of Bob Martin Totaal Ontwormer in the following countries:
International Drug Name Search
Bestatin may be available in the countries listed below.
Ubenimex is reported as an ingredient of Bestatin in the following countries:
International Drug Name Search
Idofer may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Iron Dextran is reported as an ingredient of Idofer in the following countries:
International Drug Name Search
Bromocorn may be available in the countries listed below.
Bromocriptine mesilate (a derivative of Bromocriptine) is reported as an ingredient of Bromocorn in the following countries:
International Drug Name Search
Besilato de Atracurio may be available in the countries listed below.
Atracurium Besilate is reported as an ingredient of Besilato de Atracurio in the following countries:
International Drug Name Search
Generic Name: dextromethorphan (Oral route)
dex-troe-meth-OR-fan
In the U.S.
Available Dosage Forms:
Therapeutic Class: Antitussive
Dextromethorphan is used to relieve coughs due to colds or influenza (flu). It should not be used for chronic cough that occurs with smoking, asthma, or emphysema or when there is an unusually large amount of mucus or phlegm (flem) with the cough.
Dextromethorphan relieves cough by acting directly on the cough center in the brain.
This medicine is available without a prescription.
Do not give any over-the-counter (OTC) cough and cold medicine to a baby or child under 4 years of age. Using these medicines in very young children might cause serious or possibly life-threatening side effects .
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Although there is no specific information comparing use of dextromethorphan in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children 4 years of age and older than it does in adults.
Do not give any over-the-counter (OTC) cough and cold medicine to a baby or child under 4 years of age. Using these medicines in very young children might cause serious or possibly life-threatening side effects .
Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of dextromethorphan in the elderly with use in other age groups.
Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain dextromethorphan. It may not be specific to Simply Cough. Please read with care.
Make certain your health care professional knows if you are on a low-sodium, low-sugar, or any other special diet. Most medicines contain more than their active ingredient, and many liquid medicines contain alcohol.
Use this medicine only as directed by your doctor or the directions on the label. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor or the label says. Although this effect has happened only rarely, dextromethorphan has become habit-forming (causing mental or physical dependence) in some persons who used too much for a long time.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
If your cough has not improved after 7 days, if sore throat has not improved after 2 days, if you have a high fever, skin rash, or continuing headache with the cough, or if asthma or high blood pressure is present, check with your doctor. These signs may mean that you have other medical problems.
Dissolve lozenges in the mouth with caution, to lessen the risk of choking.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor as soon as possible if any of the following side effects occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
See also: Simply Cough side effects (in more detail)
The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
A.P.L. may be available in the countries listed below.
Chorionic Gonadotrophin is reported as an ingredient of A.P.L. in the following countries:
International Drug Name Search
SPMC Phenoxymethylpenicillin may be available in the countries listed below.
Phenoxymethylpenicillin is reported as an ingredient of SPMC Phenoxymethylpenicillin in the following countries:
International Drug Name Search
Gestofam may be available in the countries listed below.
Famotidine is reported as an ingredient of Gestofam in the following countries:
International Drug Name Search
Pirodeine may be available in the countries listed below.
Pirenzepine dihydrochloride (a derivative of Pirenzepine) is reported as an ingredient of Pirodeine in the following countries:
International Drug Name Search
Staxyn™ is indicated for the treatment of erectile dysfunction.
Staxyn is available in 10 mg orally disintegrating tablets. Staxyn is not interchangeable with vardenafil 10 mg film-coated tablets (LEVITRA). Staxyn provides higher systemic exposure compared to vardenafil 10 mg film-coated tablets (LEVITRA). [See Clinical Pharmacology (12.3).]
Staxyn should be taken orally, as needed, approximately 60 minutes before sexual activity. The maximum dosing frequency is one Staxyn tablet per day. Sexual stimulation is required for a response to treatment.
Staxyn should be placed on the tongue where it will disintegrate. The tablet should be taken without liquid. It should be taken immediately upon removal from the blister.
Those patients who require a lower or higher dose of vardenafil need to be prescribed vardenafil film-coated tablets [see Patient Counseling Information (17.11)].
Staxyn can be taken with or without food.
Hepatic Impairment: Do not use Staxyn in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment [see Warnings and Precautions (5.8) and Clinical Pharmacology (12.3)].
Renal Impairment: Do not use Staxyn in patients on renal dialysis [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.3)].
Nitrates: Concomitant use with nitrates in any form is contraindicated [see Contraindications (4.1)].
CYP3A4 Inhibitors: Do not use Staxyn with potent or moderate CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, atazanavir, clarithromycin and erythromycin [see Warnings and Precautions (5.2) and Drug Interactions (7.2)].
Alpha-Blockers: In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest recommended starting dose. In patients taking alpha-blockers, do not initiate vardenafil therapy with Staxyn. Lower doses of vardenafil film-coated tablets should be used as initial therapy in these patients. [see Dosage and Administration (2.4)]. Patients taking alpha-blockers who have previously used vardenafil film-coated tablets may change to Staxyn at the advice of their healthcare provider. [See Warnings and Precautions (5.6) and Drug Interactions (7.1).]
Staxyn is available in 10 mg white, round, orally disintegrating tablets (not scored), no debossing.
Administration of Staxyn with nitrates (either regularly and/or intermittently) and nitric oxide donors is contraindicated [see Clinical Pharmacology (12.2)]. Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors, including Staxyn, may potentiate the hypotensive effects of nitrates. A suitable time interval following Staxyn dosing for the safe administration of nitrates or nitric oxide donors has not been determined.
The evaluation of erectile dysfunction should include a medical assessment, a determination of potential underlying causes and the identification of appropriate treatment.
Before prescribing Staxyn, it is important to note the following:
Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatment for erectile dysfunction, including Staxyn, should not be used in men for whom sexual activity is not recommended because of their underlying cardiovascular status.
There are no controlled clinical data on the safety or efficacy of vardenafil in the following patients; and therefore its use is not recommended until further information is available: unstable angina; hypotension (resting systolic blood pressure of <90 mmHg); uncontrolled hypertension (>170/110 mmHg); recent history of stroke, life-threatening arrhythmia, or myocardial infarction (within the last 6 months); severe cardiac failure.
Patients with left ventricular outflow obstruction (for example, aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators including PDE5 inhibitors.
Vardenafil has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 7 mmHg systolic and 8 mmHg diastolic) [see Clinical Pharmacology (12.2)]. While this normally would be expected to be of little consequence in most patients, prior to prescribing Staxyn, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects.
Concomitant administration with potent CYP3A4 inhibitors (such as ritonavir, indinavir, ketoconazole) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. Do not use Staxyn in patients taking potent or moderate CYP3A4 inhibitors. [See Dosage and Administration (2.4), Drug Interactions (7.2) and Patient Counseling Information (17.11).]
There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds, including vardenafil. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.
Staxyn should be used with caution by patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease) or by patients who have conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
Physicians should advise patients to stop use of all PDE5 inhibitors, including Staxyn, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. It is not possible to determine whether these events were related directly to the use of PDE5 inhibitors or to other factors. Physicians should also discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators such as PDE5 inhibitors [see Adverse Reactions (6.2)].
Staxyn has not been evaluated in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, therefore its use is not recommended until further information is available in those patients.
Physicians should advise patients to stop taking all PDE5 inhibitors, including Staxyn, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including vardenafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.2)].
In patients taking alpha-blockers, do not initiate vardenafil therapy with Staxyn. Patients treated with alpha-blockers who have previously used vardenafil film-coated tablets may be changed to Staxyn at the advice of their healthcare provider. Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including Staxyn, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)] leading to symptomatic hypotension (for example, fainting). Consideration should be given to the following:
In a study of the effect of vardenafil on QT interval in 59 healthy males [see Clinical Pharmacology (12.2)], therapeutic (10 mg film-coated tablets) and supratherapeutic (80 mg) doses of vardenafil and the active control moxifloxacin (400 mg) produced similar increases in QTc interval. A postmarketing study evaluating the effect of combining vardenafil with another drug of comparable QT effect showed an additive QT effect when compared with either drug alone [see Clinical Pharmacology (12.2)]. These observations should be considered in clinical decisions when prescribing vardenafil to patients with known history of QT prolongation or patients who are taking medications known to prolong the QT interval.
Patients taking Class 1A (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic medications or those with congenital QT prolongation, should avoid using Staxyn .
Do not use Staxyn in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment [see Dosage and Administration (2.3) Clinical Pharmacology (12.3)] and Use in Specific Populations (8.6)].
Do not use Staxyn in patients on renal dialysis, as vardenafil has not been evaluated in this population [see Dosage and Administration (2.3) and Use in Specific Populations (8.7)].
The safety and efficacy of Staxyn used in combination with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.
In humans, vardenafil film-coated tablet alone in doses up to 20 mg does not prolong the bleeding time. There is no clinical evidence of any additive prolongation of the bleeding time when vardenafil is administered with aspirin. Staxyn has not been administered to patients with bleeding disorders or significant active peptic ulceration. Therefore Staxyn should be administered to these patients after careful benefit-risk assessment.
Staxyn contains aspartame, a source of phenylalanine which may be harmful for people with phenylketonuria.
Phenylketonurics: Each Staxyn tablet contains 1.01 mg phenylalanine per tablet.
Staxyn contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take Staxyn.
The use of Staxyn offers no protection against sexually transmitted diseases. Counseling of patients about protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), should be considered.
The following serious adverse reactions with the use of Staxyn (vardenafil) are discussed elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Staxyn: Safety of Staxyn was evaluated in two identical multi-national, randomized, double-blind, placebo-controlled trials. In both pivotal studies, enrollment was stratified so that approximately 50% of patients were ≥65 years old. Approximately 8% (n=29) were ≥75 years old. An integrated analysis of both studies included a total of 355 subjects that received Staxyn compared to 340 subjects that received placebo (mean age was 61.7, range 21.0 to 88.0; 68% White, 5% Black, 6% Asian, 11% Hispanic and 11% Other). The discontinuation rates due to adverse reactions were 1.4% for Staxyn compared to 0.6% for placebo. Table 1 below details the most frequently reported adverse reactions.
| Adverse Drug Reaction | Staxyn (n=355) | Placebo (n=340) |
| Headache | 14.4% | 1.8% |
| Flushing | 7.6% | 0.6% |
| Nasal Congestion | 3.1% | 0.3% |
| Dyspepsia | 2.8% | 0% |
| Dizziness | 2.3% | 0% |
| Back Pain | 2% | 0.3% |
Adverse drug reactions reported in the Staxyn placebo controlled trials were comparable to the adverse drug reactions reported in earlier vardenafil film-coated tablets placebo controlled trials.
All Vardenafil Studies: Vardenafil film-coated tablets and Staxyn has been administered to over 17,000 men (mean age 54.5, range 18–89 years; 70% White, 5% Black, 13% Asian, 4% Hispanic and 8% Other) during controlled and uncontrolled clinical trials worldwide. The number of patients treated for 6 months or longer was 3357, and 1350 patients were treated for at least 1 year.
In the placebo-controlled clinical trials for vardenafil film-coated tablets and Staxyn, the discontinuation rate due to adverse events was 1.9% for vardenafil compared to 0.8% for placebo.
Placebo-controlled trials suggested a dose effect in the incidence of some adverse reactions (for example, dizziness, headache, flushing, dyspepsia, nausea, nasal congestion) over the 5 mg, 10 mg, and 20 mg doses of vardenafil film-coated tablets.
The following section identifies additional, less frequent adverse reactions (<2%) reported during the clinical development of vardenafil film-coated tablets and Staxyn. Excluded from this list are those adverse reactions that are infrequent and minor, those events that may be commonly observed in the absence of drug therapy, and those events that are not reasonably associated with the drug:
Body as a whole: allergic edema and angioedema, feeling unwell, allergic reactions, chest pain
Auditory: tinnitus, vertigo
Cardiovascular: palpitation, tachycardia, angina pectoris, myocardial infarction, ventricular tachyarrhythmias, hypotension
Digestive: nausea, gastrointestinal and abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increase in transaminases
Musculoskeletal: increase in creatine phosphokinase (CPK), increased muscle tone and cramping, myalgia
Nervous: paresthesia and dysesthesia, somnolence, sleep disorder, syncope, amnesia, seizure
Respiratory: dyspnea, sinus congestion
Skin and appendages: erythema, rash
Ophthalmologic: visual disturbance, ocular hyperemia, visual color distortions, eye pain and eye discomfort, photophobia, increase in intraocular pressure, conjunctivitis
Urogenital: increase in erection, priapism
The following adverse reactions have been identified during post approval use of vardenafil in the film-coated tablet formulation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.
Ophthalmologic: Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient’s underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors [see Warnings and Precautions (5.4) and Patient Counseling Information (17.8)].
Visual disturbances including vision loss (temporary or permanent), such as visual field defect, retinal vein occlusion, and reduced visual acuity, have also been reported rarely in postmarketing experience. It is not possible to determine whether these events are related directly to the use of vardenafil.
Neurologic: Seizure, seizure recurrence and transient global amnesia have been reported postmarketing in temporal association with vardenafil.
Otologic: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. In some cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of vardenafil, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Patient Counseling Information (17.9)].
The drug interaction studies described below were conducted using vardenafil film-coated tablets.
Nitrates: Concomitant use of Staxyn and nitrates is contraindicated. The blood pressure lowering effects of sublingual nitrates (0.4 mg) taken 1 and 4 hours after vardenafil and increases in heart rate when taken at 1, 4 and 8 hours after vardenafil were potentiated by a 20 mg dose of vardenafil in healthy middle-aged subjects. These effects were not observed when vardenafil 20 mg was taken 24 hours before the nitroglycerin (NTG). Potentiation of the hypotensive effects of nitrates for patients with ischemic heart disease has not been evaluated, and concomitant use of Staxyn and nitrates is contraindicated [see Contraindications (4.1) and Clinical Pharmacology (12.2)].
Alpha-Blockers: Patients taking alpha-blockers should not initiate vardenafil therapy with Staxyn. Patients treated with alpha-blockers who have previously used vardenafil film-coated tablets may be switched to Staxyn at the advice of their healthcare provider. Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including Staxyn and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. Clinical pharmacology studies have been conducted with co-administration of vardenafil with terazosin or tamsulosin. [See Dosage and Administration (2.4), Warnings and Precautions (5.6), and Clinical Pharmacology (12.2).]
Antihypertensives: Staxyn may add to the blood pressure lowering effect of antihypertensive agents. In a clinical pharmacology study of patients with erectile dysfunction, single doses of 20 mg vardenafil caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1.
Alcohol: Vardenafil 20 mg did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers when administered with alcohol (0.5 g/kg body weight: approximately 40 mL of absolute alcohol in a 70 kg person). Alcohol and vardenafil plasma levels were not altered when dosed simultaneously.
Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)].
Do not use Staxyn with moderate and potent CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration (2.4)].
Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil area under the curve (AUC) and a 4-fold increase in maximum concentration (Cmax) when co-administered with vardenafil 5 mg in healthy volunteers. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]
Indinavir (800 mg t.i.d.) co-administered with vardenafil 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil Cmax and a 2-fold increase in vardenafil half-life. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]
Ritonavir (600 mg b.i.d.) co-administered with vardenafil 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil Cmax. The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9. [See Dosage and Administration (2.4) and Warnings and Precautions (5).]
Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in vardenafil Cmax when co-administered with vardenafil 5 mg in healthy volunteers [see Dosage and Administration (2) and Warnings and Precautions (5)].
No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters.
Cimetidine (400 mg b.i.d.) had no effect on AUC and Cmax of vardenafil when co-administered with 20 mg vardenafil in healthy volunteers.
Vardenafil and its metabolites had no effect on CYP1A2, 2A6, and 2E1 (Ki >100 micromolar). Weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4) were found, but Ki values were in excess of plasma concentrations achieved following dosing. The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 Cmax values after an 80 mg vardenafil dose.
Nifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the relative AUC or Cmax of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil when taken in combination. In these patients whose hypertension was controlled with nifedipine, vardenafil 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo.
Ritonavir and Indinavir: Upon concomitant administration of 5 mg vardenafil with 600 mg b.i.d. ritonavir, the Cmax and AUC of ritonavir were reduced by approximately 20%. Upon administration of 10 mg of vardenafil (film-coated tablets) with 800 mg t.i.d. indinavir, the Cmax and AUC of indinavir were reduced by 40% and 30%, respectively.
Aspirin: Vardenafil 10 mg and 20 mg did not potentiate the increase in bleeding time caused by aspirin (two 81 mg tablets).
Other Interactions: Vardenafil had no effect on the pharmacodynamics of glyburide (glucose and insulin concentrations) and warfarin (prothrombin time or other pharmacodynamic parameters).
Pregnancy Category B: Staxyn is not indicated for use in women. There are no studies of Staxyn use in pregnant women.
No evidence of specific potential for teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits that received vardenafil at up to 18 mg/kg/day during organogenesis. This dose is approximately 100 fold (rat) and 29 fold (rabbit) greater than the AUC values for unbound vardenafil and its major metabolite in humans given the maximum recommended human dose (MRHD) of 20 mg.
In the rat pre-and postnatal development study, the NOAEL (no observed adverse effect level) for maternal toxicity was 8 mg/kg/day. Retarded physical development of pups in the absence of maternal effects was observed following maternal exposure to 1 and 8 mg/kg possibly due to vasodilatation and/or secretion of the drug into milk. The number of living pups born to rats exposed pre- and postnatally was reduced at 60 mg/kg/day. Based on the results of the pre- and postnatal study, the developmental NOAEL is less than 1 mg/kg/day. Based on plasma exposures in the rat developmental toxicity study, 1 mg/kg/day in the pregnant rat is estimated to produce total AUC values for unbound vardenafil and its major metabolite comparable to the human AUC at the MRHD of 20 mg. There are no adequate and well-controlled trials of vardenafil in pregnant women.
Staxyn is not indicated for use in women. It is not known if vardenafil is excreted in human breast milk.
Vardenafil was secreted into the milk of lactating rats at concentrations approximately 10-fold greater than found in the plasma. Following a single oral dose of 3 mg/kg, 3.3% of the administered dose was excreted into the milk within 24 hours.
Staxyn is not indicated for use in pediatric patients. Safety and efficacy in children has not been established.
Vardenafil AUC and Cmax in elderly patients (65 years or older) taking Staxyn were increased by 39% and 21%, respectively, in comparison to patients aged 45 years and below. No overall differences in safety or effectiveness were observed between patients ≥65 years old and those < 65 years old in placebo-controlled clinical trials [see Clinical Pharmacology (12.3)].
Do not use Staxyn in patients with moderate or severe hepatic impairment.
In volunteers with mild hepatic impairment (Child-Pugh A), the Cmax and AUC following a 10 mg vardenafil (film-coated tablets) dose were increased by 22% and 17%, respectively, compared to healthy control subjects. Staxyn can be used in patients with mild hepatic impairment. In volunteers with moderate hepatic impairment (Child-Pugh B), the Cmax and AUC following a 10 mg vardenafil (film-coated tablets) dose were increased by 130% and 160%, respectively, compared to healthy control subjects. Vardenafil has not been evaluated in patients with severe (Child-Pugh C) hepatic impairment. Do not use Staxyn in patients with moderate to severe hepatic impairment. [See Warnings and Precautions (5.8) and Dosage and Administration (2).]
Do not use Staxyn in patients on renal dialysis.
In volunteers with mild renal impairment (CLcr = 50–80 mL/min), the pharmacokinetics of vardenafil 20 mg film-coated tablets were similar to those observed in a control group with normal renal function. In the moderate (CLcr = 30–50 mL/min) or severe (CLcr <30 mL/min) renal impairment groups, the AUC of vardenafil was 20–30% higher compared to that observed in a control group with normal renal function (CLcr >80 mL/min). Staxyn can be used in patients with mild, moderate or severe renal impairment. Do not use Staxyn in patients on renal dialysis as vardenafil has not been evaluated in such patients [see Dosage and Administration (2.3) and Warnings and Precautions (5.9)].
The maximum dose of vardenafil for which human data are available is a single 120 mg dose of the film–coated tablets administered to eight healthy male volunteers. The majority of these subjects experienced reversible back pain/myalgia and/or “abnormal vision.”
In cases of overdose, standard supportive measures should be taken as required. Renal dialysis is not expected to accelerate clearance because vardenafil is highly bound to plasma proteins and is not significantly eliminated in the urine.
Staxyn is an oral therapy for the treatment of erectile dysfunction. This monohydrochloride salt of vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific PDE5.
Vardenafil HCl is designated chemically as piperazine, 1 - [[3 - (1,4 - dihydro - 5 - methyl - 4 - oxo - 7 - propylimidazo[5,1 - f][1,2,4]triazin - 2 - yl) - 4 - ethoxyphenyl]sulfonyl] - 4 - ethyl - , monohydrochloride and has the following structural formula:
Vardenafil HCl is a nearly colorless, solid substance with a molecular weight of 579.1 g/mol and a solubility of 0.11 mg/mL in water.
Staxyn is formulated as white round orally disintegrating tablets with no debossing. Each tablet contains 11.85 mg vardenafil hydrochloride, which corresponds to 10 mg vardenafil, and the following inactive ingredients: aspartame, peppermint flavor, magnesium stearate, and Pharmaburst™ B2 (crospovidone, mannitol, silica colloidal hydrated, and sorbitol).
Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMP-specific PDE5; therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has no effect in the absence of sexual stimulation.
In vitro studies have shown that vardenafil is a selective inhibitor of PDE5. The inhibitory effect of vardenafil is more selective on PDE5 than for other known phosphodiesterases (>15-fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1,000-fold relative to PDE2, 3, 4, 7, 8, 9, and 10).
The pharmacodynamic studies described below were conducted using vardenafil film-coated tablets.
In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg film-coated tablets caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1. Vardenafil may add to the blood pressure lowering effects of antihypertensive agents [see Drug Interactions (7)].
A study was conducted in which the blood pressure and heart rate response to 0.4 mg nitroglycerin (NTG) sublingually was evaluated in 18 healthy subjects following pretreatment with vardenafil 20 mg film-coated tablets at various times before NTG administration. Vardenafil 20 mg caused an additional time-related reduction in blood pressure and increase in heart rate in association with NTG administration. The blood pressure effects were observed when vardenafil 20 mg was dosed 1 or 4 hours before NTG and the heart rate effects were observed when 20 mg was dosed 1, 4, or 8 hours before NTG. Additional blood pressure and heart rate changes were not detected when vardenafil 20 mg film-coated tablet was dosed 24 hours before NTG (see Figure 1).
Figure 1: Placebo-subtracted point estimates (with 90% CI) of mean maximal blood pressure and heart rate effects of pre-dosing with vardenafil 20 mg at 24, 8, 4, and 1 hour before 0.4 mg NTG sublingually
Because the disease state of patients requiring nitrate therapy is anticipated to increase the likelihood of hypotension, the use of vardenafil by patients on nitrate therapy or on nitric oxide donors is contraindicated [see Contraindications (4.1)].
Two clinical pharmacology studies were conducted in patients with benign prostatic hyperplasia (BPH) on stable-dose alpha-blocker treatment for at least four weeks.
Study 1: This study was designed to evaluate the effect of 5 mg vardenafil film-coated tablets compared to placebo when administered to BPH patients on chronic alpha-blocker therapy in two separate cohorts: tamsulosin 0.4 mg daily (cohort 1, n=21) and terazosin 5 or 10 mg daily (cohort 2, n=21). The design was a randomized, double blind, cross-over study with four treatments: vardenafil 5 mg or placebo administered simultaneously with the alpha-blocker and vardenafil 5 mg or placebo administered 6 hours after the alpha-blocker. Blood pressure and pulse were evaluated over the 6-hour interval after vardenafil dosing. For blood pressure (BP) results, see Table 2. One patient, after simultaneous treatment with 5 mg vardenafil and 10 mg terazosin, exhibited symptomatic hypotension with standing blood pressure of 80/60 mmHg occurring one hour after administration and subsequent mild dizziness and moderate lightheadedness lasting for 6 hours. For vardenafil and placebo, five and two patients, respectively, experienced a decrease in standing systolic blood pressure (SBP) of >30 mmHg following simultaneous administration of terazosin. Hypotension was not observed when vardenafil 5 mg and terazosin were administered 6 hours apart. Following simultaneous administration of vardenafil 5 mg and tamsulosin, two patients had a standing SBP of <85 mmHg; two and one patient (vardenafil and placebo, respectively) had a decrease in standing SBP of >30 mmHg. When tamsulosin and vardenafil 5 mg were separated by 6 hours, two patients had a standing SBP <85 mmHg and one patient had a decrease in SBP of >30 mmHg. There were no severe adverse events related to hypotension reported during the study. There were no cases of syncope.
| Alpha-Blocker | Simultaneous dosing of Vardenafil 5 mg and Alpha-Blocker, Placebo-Subtracted | Dosing of Vardenafil 5 mg and Alpha-Blocker Separated by 6 Hours, Placebo-Subtracted | |
| Terazosin 5 or 10 mg daily | Standing SBP | -3 (-6.7, 0.1) | -4 (-7.4, -0.5) |
| Supine SBP | -4 (-6.7, -0.5) | -4 (-7.1, -0.7) | |
| Tamsulosin 0.4 mg daily | Standing SBP | -6 (-9.9, -2.1) | -4 (-8.3, -0.5) |
| Supine SBP | -4 (-7, -0.8) | -5 (-7.9, -1.7) |
Blood pressure effects (standing SBP) in normotensive men on stable dose tamsulosin 0.4 mg following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours are shown in Figure 2. Blood pressure effects (standing SBP) in normotensive men on stable dose terazosin (5 or 10 mg) following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours, are shown in Figure 3.
Figure 2: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (study 1)
Figure 3: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose terazosin (5 or 10 mg) in normotensive BPH patients (study 1)
Study 2: This study was designed to evaluate the effect of 10 mg vardenafil (film-coated tablets) (stage 1) and 20 mg vardenafil (film-coated tablets) (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=23) on stable therapy with tamsulosin 0.4 mg or 0.8 mg daily for at least four weeks. The design was a randomized, double blind, two-period, cross-over study. Vardenafil or placebo was given simultaneously with tamsulosin. Blood pressure and pulse were evaluated over the 6-hour interval after vardenafil dosing. For BP results see Table 3. One patient experienced a decrease from baseline in standing SBP of >30 mmHg following vardenafil 10 mg. There were no other instances of outlier blood pressure values (standing SBP <85 mmHg or decrease from baseline in standing SBP of >30 mmHg). Three patients reported dizziness following vardenafil 20 mg. There were no cases of syncope.
| Vardenafil 10 mg Placebo-subtracted | Vardenafil 20 mg Placebo-subtracted | |
| Standing SBP | -4 (-6.8, -0.3) | -4 (-6.8, -1.4) |
| Supine SBP |
Bestflan may be available in the countries listed below.
Betamethasone 17α-valerate (a derivative of Betamethasone) is reported as an ingredient of Bestflan in the following countries:
Neomycin sulfate (a derivative of Neomycin) is reported as an ingredient of Bestflan in the following countries:
International Drug Name Search
Nandrolona Decanoato may be available in the countries listed below.
Nandrolone 17ß-decanoate (a derivative of Nandrolone) is reported as an ingredient of Nandrolona Decanoato in the following countries:
International Drug Name Search
Berlinsulin H Normal may be available in the countries listed below.
Insulin Injection, Soluble human (a derivative of Insulin Injection, Soluble) is reported as an ingredient of Berlinsulin H Normal in the following countries:
International Drug Name Search
Brexine may be available in the countries listed below.
Piroxicam ß-cyclodextrine (a derivative of Piroxicam) is reported as an ingredient of Brexine in the following countries:
International Drug Name Search
Setlers Floroflatine may be available in the countries listed below.
Dimeticone is reported as an ingredient of Setlers Floroflatine in the following countries:
International Drug Name Search
Class: Hydantoins
VA Class: CN400
Chemical Name: 5,5-Diphenyl-3-[(phosphonooxy)methyl]-2,4-imidazoleidinedione disodium salt
Molecular Formula: C16H13N2Na2O6P
CAS Number: 92134-98-0
Brands: Cerebyx
Hydantoin-derivative anticonvulsant; prodrug of phenytoin.1 2 4 6
Short-term (up to 5 days) parenteral therapy when the usual means of phenytoin administration is unavailable, inappropriate, or deemed less advantageous.1 Used for the treatment of generalized convulsive status epilepticus,1 4 5 6 10 19 for the prevention and treatment of seizures occurring during neurosurgery, and as a short-term parenteral replacement for oral phenytoin.1 7 27
IV fosphenytoin sodium is associated with fewer infusion site reactions (e.g., erythema, pain, burning, swelling, pruritus, soft tissue damage, phlebitis, necrosis) and less frequent need for infusion rate reduction, interruption, and/or changes of infusion sites than IV phenytoin sodium,1 2 4 6 9 10 14 15 18 19 22 but with a higher incidence of paresthesia and pruritus.1 2 6 7 9 10 14 22
Use fosphenytoin rather than phenytoin for IM administration.1 2 6 9 10 27
Not indicated for the treatment of absence seizures or seizures associated with hypoglycemia or other metabolic causes.1
When administering IV loading doses, continuous ECG, BP, and respiratory monitoring is essential during the period of maximal plasma phenytoin concentrations (about 10–20 minutes postinfusion).1 24
Administer by IV infusion1 2 4 5 6 9 10 19 27 or by IM injection.1 2 6 9 10 23 27 30
Dilute in 5% dextrose injection or 0.9% sodium chloride injection to provide a solution containing 1.5–25 mg PE/mL.1
Infuse loading dose for status epilepticus at rate of 100–150 mg PE/minute.1
Administered once daily in 1 or 2 injection sites in clinical studies.1 Some patients may require more frequent IM dosing.1
IM administration is not recommended for initial treatment of status epilepticus.1 If IV access is impossible, loading doses of fosphenytoin sodium have been given IM for other indications.1
Available as fosphenytoin sodium; dosage expressed in terms of phenytoin sodium equivalents (PE).1 Always prescribe and dispense in terms of PE.1
Each mmol of fosphenytoin is converted into 1 mmol of phenytoin; however, because of differences in molecular weight, each 75 mg of fosphenytoin sodium is equivalent to only 50 mg of phenytoin sodium.1 2
IV and IM dosages (in terms of PE) are the same; 24 25 total daily doses of parenteral fosphenytoin sodium (in terms of PE) generally are equivalent to those of oral phenytoin sodium.1
15–20 mg PE/kg, followed by maintenance doses of fosphenytoin sodium or parenteral or oral doses of phenytoin.1 Concomitant therapy with an IV benzodiazepine usually is necessary for initial control of status epilepticus.1 4
Initiation of anticonvulsant therapy: 10–20 mg PE/kg.1
Initial maintenance dosage: 4–6 mg PE/kg daily.1
Same total daily dose (in terms of PE) as oral phenytoin sodium.1 However, plasma phenytoin concentrations may be slightly higher with parenteral fosphenytoin sodium than with oral phenytoin sodium (Dilantin) capsules due to different bioavailabilities (90 and 100%, respectively, in terms of phenytoin concentrations).1
Do not infuse loading dose at a rate >150 mg PE/minute.1
Safety and efficacy for >5 days have not been systematically evaluated.1
Reduced or less frequent doses may be necessary.1
Known hypersensitivity to fosphenytoin or any ingredient in the formulation, phenytoin, or other hydantoins.1
Sinus bradycardia, sinoatrial block, second- or third-degree AV block, Adams-Stokes syndrome.1
Always express dosage of fosphenytoin sodium in terms of PE;1 therefore, do not adjust recommended dosage when switching from phenytoin sodium to fosphenytoin sodium or vice versa.1
Administration of the recommended IV dose generally takes 5–7 minutes; administration of equimolar doses of phenytoin sodium takes 15–20 minutes.1
IV route is preferred if the primary goal is rapid achievement of therapeutic phenytoin concentrations.1
Do not discontinue abruptly; reduce dosage, discontinue drug, or make drug substitution gradually.1 However, if an allergic or hypersensitivity reaction occurs, rapid substitution with an anticonvulsant that is structurally unrelated to hydantoins may be necessary.1
Potential for hypotension, especially after IV administration of high doses or rapid IV infusions.1 Careful cardiac monitoring is needed when administering IV loading doses.1 If hypotension occurs, may need to reduce the administration rate or discontinue the drug.1
Use with caution in patients with hypotension or severe heart failure.1
Contraindicated in patients with some cardiac conduction disorders. (See Contraindications under Cautions.)1
Acute hepatotoxicity, including infrequent cases of acute hepatic failure, reported with phenytoin.1 If acute hepatotoxicity occurs, discontinue fosphenytoin immediately and do not resume.1
Adverse hematologic effects (e.g., thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia with or without bone marrow suppression), sometimes fatal, reported with phenytoin.1
Development of local or generalized lymphadenopathy (e.g., benign lymph node hyperplasia, pseudolymphoma, lymphoma, Hodgkin’s disease) associated with phenytoin.1 If lymphadenopathy develops, observe patient closely for an extended period; if possible, use alternative anticonvulsant.1
Fosphenytoin is embryotoxic and teratogenic in animals.1 Phenytoin may cause fetal harm (e.g., congenital malformations, adverse developmental outcomes) in pregnant women.1
Life-threatening bleeding disorders secondary to decreased concentrations of vitamin K-dependent clotting factors may occur in neonates exposed to phenytoin in utero; administration of vitamin K to the mother prior to delivery and to the neonate after birth prevents these disorders.1
Possible increased risk of developing toxic epidermal necrolysis or Stevens-Johnson syndrome with phenytoin in individuals of Asian ancestry who carry the human leukocyte antigen (HLA)-B*1502 allele.32 33 34 Precaution relating to presence of the HLA-B*1502 allele applies to fosphenytoin because fosphenytoin is converted to phenytoin.32 FDA is evaluating the relationship between use of phenytoin and serious dermatologic reactions in individuals with the HLA-B*1502 allele.32 Screening for presence of HLA-B*1502 allele before initiating fosphenytoin or phenytoin therapy not recommended at this time.32 Fosphenytoin or phenytoin should not be used as an alternative to carbamazepine in HLA-B*1502-positive patients.32
If rash occurs, discontinue fosphenytoin.1
Do not resume fosphenytoin if the rash is exfoliative, purpuric, or bullous or if lupus erythematosus, Stevens-Johnson syndrome, or toxic necrolysis is suspected; consider alternative anticonvulsant therapy.1
If the rash is a milder type (measles-like or scarlatiniform), may restart fosphenytoin after the rash has completely disappeared; however, if rash recurs when fosphenytoin is restarted, further fosphenytoin or phenytoin therapy is contraindicated.1
Exercise caution when using structurally similar compounds (e.g., barbiturates, succinimides, oxazolidinediones) in patients who have experienced phenytoin hypersensitivity.1
Severe burning, pruritus, and/or paresthesia (mainly in groin) reported with IV administration; symptoms generally persist for up to 14 or 24 hours for severe or mild reactions, respectively.1 2
Patients receiving doses of 20 mg PE/kg at a rate of 150 mg PE/minute are likely to experience some discomfort; reducing or temporarily stopping the infusion may decrease the incidence and intensity.1
Each mg PE provides 0.0037 mmol of phosphate; consider the phosphate content in patients who require phosphate restriction (e.g., patients with severe renal impairment).1
Hyperglycemia reported with phenytoin.1
Plasma phenytoin concentrations sustained above the optimal range may produce confusional states (e.g., delirium, psychosis, encephalopathy); rarely, irreversible cerebellar dysfunction may develop.1
Determine plasma phenytoin concentrations at the first sign of acute toxicity.1 If concentrations are excessive, reduce the fosphenytoin dosage; if symptoms persist, discontinue the drug.1
Phenytoin may reduce serum folate concentrations.1
Dosage of fosphenytoin (in PE) usually is selected to achieve total plasma phenytoin concentrations of 10–20 mcg/mL (unbound phenytoin concentrations of 1–2 mcg/mL).1
Do not monitor plasma phenytoin concentrations until conversion of fosphenytoin to phenytoin is essentially complete (about 2 hours after conclusion of an IV infusion or 4 hours after an IM injection).1 2 6
Unbound phenytoin fraction may be increased in patients with renal or hepatic impairment or hypoalbuminemia.1 Interpret total plasma phenytoin concentrations with caution in these patients; consider monitoring unbound plasma phenytoin concentrations.1
Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Potential for increased seizure frequency during pregnancy due to alteration of phenytoin pharmacokinetics.1 Monitor plasma phenytoin concentrations and adjust dosage accordingly; restoration of the patient’s usual dosage will probably be necessary postpartum.1
Not known whether fosphenytoin is distributed into milk.1 Phenytoin is distributed into milk; nursing is not recommended in women receiving fosphenytoin.1
Safety1 and efficacy24 not established in children.1 24
Limited pharmacokinetic data in children 5–10 years of age with status epilepticus indicate that plasma fosphenytoin, total phenytoin, and unbound phenytoin concentration-time profiles following IV loading doses are similar to those achieved in adult patients with status epilepticus receiving comparable doses.1 8
Not systematically evaluated in geriatric adults.1
Use with caution.1 Following IV administration, conversion of fosphenytoin to phenytoin may be increased without a similar increase in phenytoin clearance; the increases in plasma phenytoin concentrations may be associated with an increased incidence and severity of adverse effects.1
Interpret total plasma phenytoin concentrations with caution.1 (See Monitoring Plasma Phenytoin Concentrations under Cautions.)
Phenytoin may exacerbate porphyria; use with caution in patients with this disease.1
Use with caution.1 Following IV administration, conversion of fosphenytoin to phenytoin may be increased without a similar increase in phenytoin clearance; the increases in plasma phenytoin concentrations may be associated with an increased incidence and severity of adverse effects.1
Interpret total plasma phenytoin concentrations with caution.1 (See Monitoring Plasma Phenytoin Concentrations under Cautions.)
Nystagmus, dizziness, pruritus, paresthesia, headache, somnolence, ataxia.1 2 6 7
Phenytoin is metabolized by CYP isoenzymes.1 Phenytoin induces hepatic enzymes.1
No drugs are known to interfere with conversion of fosphenytoin to phenytoin.1
Drug interactions that occur with phenytoin expected to occur with fosphenytoin.1
Potential for fosphenytoin or phenytoin to displace or to be displaced by other protein-bound drugs.1 Use with caution.1
CYP inhibitors: Potential for increased plasma phenytoin concentrations.1
Drug | Interaction | Comments |
|---|---|---|
Alcohol, acute intake | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Alcohol, chronic intake | Possible decreased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Amiodarone | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Anticoagulants | Efficacy of anticoagulants, including warfarin, impaired1 Possible increased plasma phenytoin concentrations when administered with dicumarol (no longer commercially available in US)1 | Monitor plasma phenytoin concentration if pharmacokinetic interaction suspected1 |
Antidepressants, tricyclic | Increased risk of seizures1 | Adjust fosphenytoin dosage as necessary1 |
Carbamazepine | Possible decreased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Chloramphenicol | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Chlordiazepoxide | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Corticosteroids | Efficacy of corticosteroids impaired1 | |
Diazepam | Pharmacokinetic (including protein binding) interaction unlikely1 | |
Disulfiram | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Doxycycline | Efficacy of doxycycline impaired1 | |
Estrogens | Possible increased plasma phenytoin concentrations1 Efficacy of estrogens impaired1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Ethosuximide | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Fluoxetine | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Furosemide | Efficacy of furosemide impaired1 | |
Histamine H2-receptor antagonists (cimetidine) | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Halothane | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Isoniazid | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Methylphenidate | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Oral contraceptives | Efficacy of oral contraceptives impaired1 | |
Phenobarbital | Possible increased or decreased plasma phenytoin or phenobarbital concentrations1 | Monitor plasma concentrations if interaction suspected1 |
Phenothiazines | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Rifampin | Efficacy of rifampin impaired1 | |
Quinidine | Efficacy of quinidine impaired1 | |
Salicylates | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Succinimides | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Sulfonamides | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Theophylline | Efficacy of theophylline impaired1 | |
Tolbutamide | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Trazodone | Possible increased plasma phenytoin concentrations1 | Monitor plasma phenytoin concentration if interaction suspected1 |
Valproic acid and Valproate sodium | Possible increased or decreased plasma concentrations of phenytoin or valproic acid1 | Monitor plasma concentrations if interaction suspected1 |
Completely converted to phenytoin following IV or IM administration; conversion half-life is 15 minutes.1 2
Completely bioavailable following IM administration.1 Peak plasma phenytoin concentrations are achieved in about 3 hours.1 Concentrations are similar to those achieved with oral phenytoin sodium.1
IV loading doses of 15–20 mg PE/kg infused at maximally tolerated rates (100–150 mg PE/minute) result in therapeutic plasma concentrations of unbound phenytoin (about 1–2 mcg/mL) within about 10 minutes.1 2 4 6 7 19 25 26
Onset of action in controlling status epilepticus is similar to that of IV phenytoin sodium.4 26
Fosphenytoin: 95–99%.1
Phenytoin: 88%.1
Fosphenytoin displaces phenytoin from binding sites.1 In the presence of fosphenytoin, the fraction of unbound phenytoin increases; 70% of phenytoin is bound during the period required for conversion of fosphenytoin to phenytoin (0.5–1 hour postinfusion).1
In patients with renal or hepatic impairment or hypoalbuminemia, fraction of unbound phenytoin is increased.1
Fosphenytoin is rapidly metabolized to phenytoin by blood and tissue phosphatases.2 Each mmol of fosphenytoin is metabolized to one mmol of phenytoin.1
Phenytoin is metabolized by hepatic CYP isoenzymes (saturable process).1 A small percentage of individuals metabolize phenytoin slowly.1
Phenytoin is excreted in urine principally as metabolites.1
Phenytoin: 12–28.9 hours.1
Following IV administration in patients with renal and/or hepatic impairment or hypoalbuminemia, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance.1
In geriatric patients, phenytoin clearance may be decreased.1
2–8°C.1 Do not store at room temperature for >48 hours.1
For information on systemic interactions resulting from concomitant use, see Interactions.
Compatible |
|---|
Amino acid injection 10% |
Dextrose 5% in Ringer’s injection, lactated |
Dextrose 5% in sodium chloride 0.45% |
Dextrose 5 or 10% in water |
Hetastarch 6% in sodium chloride 0.9% |
Mannitol 20% |
Plasma-Lyte A, pH 7.4 |
Ringer’s injection, lactated |
Sodium chloride 0.9% |
Compatible |
|---|
Potassium chloride |
Compatible |
|---|
Lorazepam |
Phenobarbital sodium |
Incompatible |
Fenoldopam mesylate |
Midazolam HCl |
Prodrug of phenytoin.1 2 4 6 Pharmacologic effects include those of phenytoin.1 2 6
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection | 75 mg (equivalent to 50 mg phenytoin sodium [PE]) per mL* | Cerebyx | Pfizer |
Fosphenytoin Sodium |
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Parke-Davis. Cerebyx (fosphenytoin sodium) injection prescribing information. New York, NY; 2002 Feb.
2. Browne TR, Kugler AR, Eldon MA. Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996; 46(Suppl 1):S3-7. [IDIS 368224] [PubMed 8649612]
3. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2001 Aug 21. From FDA web site.
4. Lowenstein DH, Alldredge BK. Status Epilepticus. N Engl J Med. 1998; 14:970-6.
5. Allen FH Jr, Runge JW, Legarda S et al. Safety, tolerance, and pharmacokinetics of intravenous fosphenytoin (Cerebyx) in status epilepticus. Epilepsia. 1995; 36(Suppl 4):90.
6. Boucher BA. Fosphenytoin: a novel phenytoin prodrug. Pharmacotherapy. 1996; 16:777-91. [IDIS 374567] [PubMed 8888074]
7. Meek PD, Davis SN, Collins M et al. Guidelines for the nonemergency use of parenteral phenytoin products: proceedings of an expert panel consensus process. Arch Intern Med. 1999; 159:2639-44. [IDIS 440708] [PubMed 10597754]
8. Pellock JM. Fosphenytoin use in children. Neurology. 1996; 46(Suppl 1):S14-6.
9. Fierro LS Savulich DH, Benezra DA. Safety of fosphenytoin sodium. Am J Health-Syst Pharm. 1996; 53:2707-12. [IDIS 375372] [PubMed 8931812]
10. DeToledo JC, Ramsay RE. Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. Drug Safety. 2000; 22:459-66. [PubMed 10877039]
11. Labiner DM. Data vs opinion, phenytoin vs fosphenytoin: the saga continues. Arch Intern Med. 1999; 159:2631-2. [IDIS 440706] [PubMed 10597752]
12. Nightingale SL. Cerebyx labels changed. JAMA. 1999, 281:786.
13. Sigmund W II. Dear health care professional letter regarding revisions to the Cerebyx (fosphenytoin sodium) prescribing information concerning inadvertent overdosage of fosphenytoin sodium because the manufacturer’s label on the vial was misread. Morris Plains, NJ: Parke Davis; 1999 Jan 28.
14. Paloucek FP. Fosphenytoin safety and economics. Am J Health-Syst Pharm. 1996; 53:2702. [IDIS 375371] [PubMed 8931811]
15. Holliday SM, Benfield P, Plosker GL. Fosphenytoin: pharmacoeconomic implications of therapy. Pharmacoeconomics. 1998; 14:685-90. [PubMed 10346419]
16. Touchette DR, Rhoney DH. Cost-minimization analysis of phenytoin and fosphenytoin in the emergency department. Pharmacotherapy. 2000; 20:908-16. [IDIS 450897] [PubMed 10939551]
17. Marchetti A, Magar R, Fischer J et al. A pharmacoeconomic evaluation of intravenous fosphenytoin (Cerebyx) versus intravenous phenytoin (Dilantin) in hospital emergency departments. Clin Ther. 1996. 18:953-66. (IDIS 376632)
18. Armstrong EP, Sauer KA, Downey MJ. Phenytoin and fosphenytoin: a model of cost and clinical outcomes. Pharmacotherapy. 1999; 19:844-53. [IDIS 429096] [PubMed 10417033]
19. Bleck TP. Management approaches to prolonged seizures and status epilepticus. Epilepsia. 1999; 40(Suppl 1):S59-63. [IDIS 431654] [PubMed 10421562]
20. Matheson C. Reactions to fosphenytoin editorial and review article. Am J Health-Syst Pharm. 1997; 54:441-2. [IDIS 379822] [PubMed 9043571]
21. Cohen MR. Flawed dispensing practice and Cerebyx label confusion result in child’s death. Hosp Pharm. 1998; 33:828,831.
22. Sangha K, Privitera M. Fosphenytoin restrictions at the Health Alliance of Greater Cincinnati. Hosp Pharm. 1997;32:1293-4. (IDIS 396163)
23. Pryor FM, Gidal B, Ramsay RE et al. Fosphenytoin: phramacokinetics and tolerance of intramuscular doses. Epilepsia. 2001; 42:245-50. [IDIS 460662] [PubMed 11240597]
24. Pfizer, Morris Plains, NJ: Personal communication.
25. Reviewers’ comments (personal observations).
26. Kugler AR, Knapp LE, Eldon MA. Rapid attainment of therapeutic phenytoin concentrations following administration of loading doses of fosphenytoin: a metaanalysis. Neurology. 1996; 46(Suppl):A176. [IDIS 368224] [PubMed 8649612]
27. Boucher BA, Feler CA, Dean JC et al. The safety, tolerability, and pharmacokinetics of fosphenytoin: intramuscular and intravenous administration in neurosurgery. Pharmacotherapy. 1996; 16:638-45. [IDIS 370972] [PubMed 8840370]
28. Jamerson BD, Donn KH, Dukes GE et al. Absolute bioavailability of phenytoin after 3-phosphoryloxymethyl phenytoin disodium (ACC-9653) administration to humans. Epilepsia. 1990; 31:592-7. [IDIS 273305] [PubMed 2401249]
29. Leppik IE, Boucher BA, Wilder BJ et al. Pharmacokinetics and safety of a phenytoin prodrug given i.v. or i.m. in patients. Neurology. 1990; 40(3 Part 1):456-60. [IDIS 285422] [PubMed 2314588]
30. Uthman BM, Wilder BJ, Ramsay RE. Intramuscular use of fosphenytoin: an overview. Neurology. 1996; 46(Suppl 1):S24-28.
31. Sharpe R. Monsanto, FDA are trying to overcome confusion over name of arthritis drug. Wall St J. 1999 Apr 15.
32. Food and Drug Administration. Information for healthcare professionals phenytoin (marketed as Dilantin, Phenytek and generics) and Fosphenytoin (marketed as Cerebyx and generics). 2008 Nov 24. From FDA website. Accessed 2008 Nov 25.
33. Locharernkul C, Loplumlert J, Limotai C et al. Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008; 49:2087-91. [PubMed 18637831]
34. Man CBL, Kwan P, Baum L et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007: 48:1015-8.
HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:754-6.
