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helps prevent recurrence of flaking and itching assocaited with dandruff
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Dandruff Manufacturers
- Dza Brands, Llc
- Meijer Distribution, Inc
- Supervalu Inc
- Supervalu Inc
- Supervalue Inc.
- Supervalu Inc.
- Target Corporation
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- Nash Finch Company
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- Your Military Exchanges
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Dandruff | Remedyrepack Inc.
WARNING: This is a potent drug; it must be diluted before administration to the patient.
Dopamine Hydrochloride Injection, USP is administered (only after dilution) by intravenous infusion.
Suggested Dilution – For the 40 mg/mL preparation, transfer by aseptic technique the contents containing either 5 mL, 200 mg or 10 mL, 400 mg of Dopamine Hydrochloride to either a 250 mL or 500 mL bottle of one of the sterile I.V. solutions listed below. For the 80 mg/mL preparation, transfer by aseptic technique the contents containing 10 mL, 800 mg of Dopamine Hydrochloride to a 250 mL, 500 mL or 1000 mL bottle of one of the following sterile I.V. solutions:
0.9% Sodium Chloride Injection, USP
5% Dextrose Injection, USP
5% Dextrose and 0.9% Sodium Chloride Injection, USP
5% Dextrose and 0.45% Sodium Chloride Injection, USP
5% Dextrose and Lactated Ringer’s Injection
Sodium Lactate Injection, USP 1/6 Molar
Lactated Ringer’s Injection, USP
The resultant dilutions are summarized in the following chart:
Concentration of
Dopamine Hydrochloride
40 mg/mL
80 mg/mL
Volume of Dopamine
Hydrochloride Injection, USP
5 mL
10 mL
10 mL
250 mL Bottle of I.V. Solution
800 mcg/mL
1600 mcg/mL
3200 mcg/mL
500 mL Bottle of I.V. Solution
400 mcg/mL
800 mcg/mL
1600 mcg/mL
1000 mL Bottle of I.V. Solution
200 mcg/mL
400 mcg/mL
800 mcg/mL
Dopamine Hydrochloride Injection, USP has been found to be stable for a minimum of 24 hours after dilution in the foregoing I.V. solutions. However, as with all I.V. admixtures, dilution should be made just prior to administration.
Do NOT add Dopamine Hydrochloride to Sodium Bicarbonate Injection, USP or other alkaline I.V. solutions, since the drug is inactivated in alkaline solution.
Rate of Administration – Dopamine Hydrochloride Injection, USP after dilution, is administered intravenously by infusion via a suitable I.V. catheter or needle. When administering Dopamine Hydrochloride (or any potent medication) by continuous intravenous infusion, it is advisable to use a precision volume control I.V. set. Each patient must be individually titrated to the desired hemodynamic or renal response to dopamine.
In titrating to the desired increase in systolic blood pressure, the optimum dosage rate for renal response may be exceeded, thus necessitating a reduction in rate after the hemodynamic condition is stabilized.
Administration at rates greater than 50 mcg/kg/min have safely been used in advanced circulatory decompensation states. If unnecessary fluid expansion is of concern, adjustment of drug concentration may be preferred over increasing the flow rate of a less concentrated dilution.
Suggested Regimen:
1. When appropriate, increase blood volume with whole blood or plasma until central venous pressure is 10 to 15 cm H2O or pulmonary wedge pressure is 14 to 18 mm Hg.
2. Begin infusion of diluted solution at doses of 2 – 5 mcg/kg/min of Dopamine Hydrochloride in patients who are likely to respond to modest increments of heart force and renal perfusion.
In more seriously ill patients, begin infusion of diluted solution at doses of 5 mcg/kg/min of Dopamine Hydrochloride and increase gradually using 5 to 10 mcg/kg/min increments up to a rate of 20 to 50 mcg/kg/min as needed. If doses in excess of 50 mcg/kg/min are required, it is advisable to check urine output frequently. Should urinary flow begin to decrease in the absence of hypotension, reduction of dopamine dosage should be considered. Multiclinic trials have shown that more than 50 percent of patients have been satisfactorily maintained on doses less than 20 mcg/kg/min.
In patients who do not respond to these doses with adequate arterial pressures or urine flow, additional increments of dopamine may be given in an effort to produce an appropriate arterial pressure and central perfusion.
3. Treatment of all patients requires constant evaluation of therapy in terms of blood volume, augmentation of cardiac contractility, and distribution of peripheral perfusion.
Dosage of dopamine should be adjusted according to the patient’s response, with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indices for decreasing or temporarily suspending the dosage.
4. As with all potent intravenously administered drugs, care should be taken to control the rate of administration to avoid inadvertent administration of a bolus of the drug.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
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Dandruff | Aurobindo Pharma Limited
2.1 Important Administration Instructions Cefuroxime axetil tablets and cefuroxime axetil for oral suspension are not bioequivalent and are therefore not substitutable on a milligram-per-milligram basis [see Clinical Pharmacology (12.3)]. Administer cefuroxime axetil tablets as described in the appropriate dosage guidelines [see Dosage and Administration (2.2)]. Administer cefuroxime axetil tablets with or without food. Pediatric patients (aged 13 years and older) who cannot swallow the cefuroxime axetil tablets whole should receive cefuroxime axetil for oral suspension because the tablet has a strong, persistent bitter taste when crushed [see Dosage and Administration (2.2)]. 2.2 Dosage for Cefuroxime Axetil TabletsAdminister cefuroxime axetil tablets as described in the dosage guidelines table below with or without food.
Table 1. Adult Patients and Pediatric Patients Dosage Guidelines for Cefuroxime Axetil Tablets a The safety and effectiveness of cefuroxime axetil tablets administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established.
b When crushed, the tablet has a strong, persistent bitter taste. Therefore, patients who cannot swallow the tablet whole should receive the oral suspension.
Infection
Dosage
Duration
(Days)
Adults and Adolescents (13 years and older)
Pharyngitis/tonsillitis (mild to moderate)
250 mg every 12 hours
10
Acute bacterial maxillary sinusitis (mild to moderate)
250 mg every 12 hours
10
Acute bacterial exacerbations of chronic bronchitis (mild to moderate)
250 mg or 500 mg every
12 hours
10a
Secondary bacterial infections of acute bronchitis
250 mg or 500 mg every
12 hours
5 to 10
Uncomplicated skin and skin-structure infections
250 mg or 500 mg every
12 hours
10
Uncomplicated urinary tract infections
250 mg every 12 hours
7 to 10
Uncomplicated gonorrhea
1,000 mg
single dose
Early Lyme disease
500 mg every 12 hours
20
Pediatric Patients younger than 13 years (who can swallow tablets whole)b
Acute bacterial otitis media
250 mg every 12 hours
10
Acute bacterial maxillary sinusitis
250 mg every 12 hours
10
2.5 Dosage in Patients with Impaired Renal FunctionA dosage interval adjustment is required for patients whose creatinine clearance is <30 mL/min, as listed in Table 4 below, because cefuroxime is eliminated primarily by the kidney [see Clinical Pharmacology (12.3)].
Table 4. Dosing in Adults with Renal Impairment Creatinine Clearance (mL/min)
Recommended Dosage
≥30
No dosage adjustment
10 to <30
Standard individual dose given every 24 hours
<10 (without hemodialysis)
Standard individual dose given every 48 hours
Hemodialysis
A single additional standard dose should be given at the end of each dialysis - Demoulas Super Markets, Inc
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Dandruff | Valeant Pharmaceuticals North America Llc
As noted under CLINICAL PHARMACOLOGY, multiple-dose studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for Isordil Titradose tablets must provide a daily dose-free interval to minimize the development of this tolerance. With immediate-release ISDN, it appears that one daily dose-free interval must be at least 14 hours long.
As also noted under CLINICAL PHARMACOLOGY, the effects of the second and later doses have been smaller and shorter-lasting than the effects of the first.
Large controlled studies with other nitrates suggest that no dosing regimen with Isordil Titradose tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
As with all titratable drugs, it is important to administer the minimum dose which produces the desired clinical effect. The usual starting dose of Isordil Titradose is 5 mg to 20 mg, two or three times daily. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. Some patients may require higher doses. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen.
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Dandruff | Bayer Healthcare Pharmaceuticals Inc.
Mirena contains 52 mg of levonorgestrel (LNG). Initially, LNG is released at a rate of approximately 20 mcg/day. This rate decreases progressively to half that value after 5 years.
Mirena must be removed by the end of the fifth year and can be replaced at the time of removal with a new Mirena if continued contraceptive protection is desired.
Mirena is supplied within an inserter in a sterile package (see Figure 1Figure 1) that must not be opened until required for insertion [see Description (11.2)]. Do not use if the seal of the sterile package is broken or appears compromised. Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions (5.3)].
2.1. Insertion Instructions • A complete medical and social history should be obtained to determine conditions that might influence the selection of a levonorgestrel-releasing intrauterine system (LNG IUS) for contraception. If indicated, perform a physical examination, and appropriate tests for any forms of genital or other sexually transmitted infections. [See Contraindications ( 4) and Warnings and Precautions ( 5.10).] • Follow the insertion instructions exactly as described in order to ensure proper placement and avoid premature release of Mirena from the inserter. Once released, Mirena cannot be re-loaded. • Mirena should be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the insertion instructions before attempting insertion of Mirena. • Insertion may be associated with some pain and/or bleeding or vasovagal reactions (for example, syncope, bradycardia), or with seizure in an epileptic patient, especially in patients with a predisposition to these symptoms. Consider administering analgesics prior to insertion. Timing of InsertionInsert Mirena into the uterine cavity during the first seven days of the menstrual cycle or immediately after a first trimester abortion. Back up contraception is not needed when Mirena is inserted as directed.
Postpone postpartum insertion and insertions following second trimester abortions a minimum of six weeks or until the uterus is fully involuted. If involution is delayed, wait until involution is complete before insertion [see Warnings and Precautions (5.6, 5.7)].
Tools for Insertion Preparation • Gloves • Speculum • Sterile uterine sound • Sterile tenaculum • Antiseptic solution, applicator Procedure • Sterile gloves • Mirena with inserter in sealed package • Instruments and anesthesia for paracervical block, if anticipated • Consider having an unopened backup Mirena available • Sterile, sharp curved scissors Preparation for insertion • Exclude pregnancy and confirm that there are no other contraindications to the use of Mirena. • Ensure that the patient understands the contents of the Patient Information Booklet and obtain the signed patient informed consent located on the last page of the Patient Information Booklet. With the patient comfortably in lithotomy position, do a bimanual exam to establish the size, shape and position of the uterus. • Gently insert a speculum to visualize the cervix. • Thoroughly cleanse the cervix and vagina with a suitable antiseptic solution. • Prepare to sound the uterine cavity. Grasp the upper lip of the cervix with a tenaculum forceps and gently apply traction to stabilize and align the cervical canal with the uterine cavity. Perform a paracervical block if needed. If the uterus is retroverted, it may be more appropriate to grasp the lower lip of the cervix. The tenaculum should remain in position and gentle traction on the cervix should be maintained throughout the insertion procedure. • Gently insert a uterine sound to check the patency of the cervix, measure the depth of the uterine cavity in centimeters, confirm cavity direction, and detect the presence of any uterine anomaly. If you encounter difficulty or cervical stenosis, use dilatation, and not force, to overcome resistance. If cervical dilatation is required, consider using a paracervical block. • The uterus should sound to a depth of 6 to 10 cm. Insertion of Mirena into a uterine cavity less than 6 cm by sounding may increase the incidence of expulsion, bleeding, pain, perforation, and possibly pregnancy. Insertion ProcedureProceed with insertion only after completing the above steps and ascertaining that the patient is appropriate for Mirena. Ensure use of aseptic technique throughout the entire procedure.
Step 1–Opening of the package • Open the package ( Figure 1Figure 1). The contents of the package are sterile.Figure 1 Opening the Mirena Package
• Using sterile gloves lift the handle of the sterile inserter and remove from the sterile package. Step 2–Load Mirena into the insertion tube • Push the slider forward as far as possible in the direction of the arrow thereby moving the insertion tube over the Mirena T-body to load Mirena into the insertion tube ( Figure 2Figure 2). The tips of the arms will meet to form a rounded end that extends slightly beyond the insertion tube.Figure 2 Move slider all the way to the forward position to load Mirena
• Maintain forward pressure with your thumb or forefinger on the slider. DO NOT move the slider downward at this time as this may prematurely release the threads of Mirena. Once the slider is moved below the mark, Mirena cannot be re-loaded. Step 3–Setting the flange • Holding the slider in this forward position, set the upper edge of the flange to correspond to the uterine depth (in centimeters) measured during sounding ( Figure 3Figure 3).Figure 3 Setting the flange
Step 4–Mirena is now ready to be inserted • Continue holding the slider in this forward position. Advance the inserter through the cervix until the flange is approximately 1.5–2 cm from the cervix and then pause ( Figure 4Figure 4).Figure 4 Advancing insertion tube until flange is 1.5 to 2 cm from the cervix
Do not force the inserter. If necessary, dilate the cervical canal.
Step 5–Open the armsWhile holding the inserter steady, move the slider down to the mark to release the arms of Mirena (Figure 5Figure 5). Wait 10 seconds for the horizontal arms to open completely.
Figure 5 Move the slider back to the mark to release and open the arms
Step 6–Advance to fundal position • Advance the inserter gently towards the fundus of the uterus until the flange touches the cervix. If you encounter fundal resistance do not continue to advance. Mirena is now in the fundal position ( Figure 6Figure 6). Fundal positioning of Mirena is important to prevent expulsion.Figure 6 Move Mirena into the fundal position
Step 7–Release Mirena and withdraw the inserter • Holding the entire inserter firmly in place, release Mirena by moving the slider all the way down ( Figure 7Figure 7).Figure 7 Move the slider all the way down to release Mirena from the insertion tube
• Continue to hold the slider all the way down while you slowly and gently withdraw the inserter from the uterus. • Using a sharp, curved scissor, cut the threads perpendicular, leaving about 3 cm visible outside of the cervix [cutting threads at an angle may leave sharp ends ( Figure 8Figure 8)]. Do not apply tension or pull on the threads when cutting to prevent displacing Mirena.Figure 8 Cutting the threads
Mirena insertion is now complete. Prescribe analgesics, if indicated. Keep a copy of the Consent Form with lot number for your records.
Important information to consider during or after insertion • If you suspect that Mirena is not in the correct position, check placement (for example, using transvaginal ultrasound). Remove Mirena if it is not positioned completely within the uterus. A removed Mirena must not be re-inserted. • If there is clinical concern, exceptional pain or bleeding during or after insertion, appropriate steps (such as physical examination and ultrasound) should be taken immediately to exclude perforation. 2.2 Patient Follow-up • Reexamine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated. 2.3 Removal of Mirena Timing of Removal • Mirena should not remain in the uterus after 5 years. • If pregnancy is not desired, the removal should be carried out during menstruation, provided the woman is still experiencing regular menses. If removal will occur at other times during the cycle, consider starting a new contraceptive method a week prior to removal. If removal occurs at other times during the cycle and the woman has had intercourse in the week prior to removal, she is at risk of pregnancy. [See Dosage and Administration ( 2.4) .] Tools for Removal Preparation • Gloves • Speculum Procedure • Sterile forceps Removal Procedure • Remove Mirena by applying gentle traction on the threads with forceps. ( Figure 9Figure 9).Figure 9 Removal of Mirena
• If the threads are not visible, determine location of Mirena by ultrasound [see Warnings and Precautions ( 5.10)]. • If Mirena is found to be in the uterine cavity on ultrasound exam, it may be removed using a narrow forceps, such as an alligator forceps. This may require dilation of the cervical canal. After removal of Mirena, examine the system to ensure that it is intact. • Removal may be associated with some pain and/or bleeding or vasovagal reactions (for example, syncope, or a seizure in an epileptic patient). 2.4 Continuation of Contraception after Removal • If pregnancy is not desired and if a woman wishes to continue using Mirena, a new system can be inserted immediately after removal any time during the cycle. • If a patient with regular cycles wants to start a different birth control method, time removal and initiation of new method to ensure continuous contraception. Either remove Mirena during the first 7 days of the menstrual cycle and start the new method immediately thereafter or start the new method at least 7 days prior to removing Mirena if removal is to occur at other times during the cycle. • If a patient with irregular cycles or amenorrhea wants to start a different birth control method, start the new method at least 7 days before removal. - American Sales Company
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Dandruff | Camber Pharmaceuticals Inc.
2.1 Dosage for Postherpetic NeuralgiaIn adults with postherpetic neuralgia, gabapentin may be initiated on Day 1 as a single 300 mg dose, on Day 2 as 600 mg/day (300 mg two times a day), and on Day 3 as 900 mg/day (300 mg three times a day). The dose can subsequently be titrated up as needed for pain relief to a dose of 1800 mg/day (600 mg three times a day). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range; however, in these clinical studies, the additional benefit of using doses greater than 1800 mg/day was not demonstrated.
2.2 Dosage for Epilepsy with Partial Onset SeizuresPatients 12 years of age and above
The starting dose is 300 mg three times a day. The recommended maintenance dose of gabapentin Capsules is 300 mg to 600 mg three times a day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. Administer gabapentin capsules three times a day using 300 mg or 400 mg capsules. The maximum time between doses should not exceed 12 hours.
Pediatric Patients Age 3 to 11 years
The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the recommended maintenance dose reached by upward titration over a period of approximately 3 days. The recommended maintenance dose of gabapentin in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses. The recommended maintenance dose of gabapentin in patients 5 to 11 years of age is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Gabapentin may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.
2.3 Dosage Adjustment in Patients with Renal ImpairmentDosage adjustment in patients 12 years of age and older with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication).
2.4 Dosage in ElderlyBecause elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.
2.5 Administration InformationAdminister gabapentin orally with or without food.
Gabapentin capsules should be swallowed whole with water.
If the gabapentin dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).
- Cvs
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Dandruff | Meijer Distribution
shake well for maximum dandruff control, use every time you shampoo wet hair,massage onto scalp, rinse, repeat if desired for best results use at least twice a week or as directed by a doctor if used on bleached, gray, tinted or permed hair, rinse for at least 5 minutes - Publix
- Wakefern Food Corp
- Wal-mart Stores, Inc.
Dandruff | Mylan Institutional Inc.
The optimum daily dosage of carbidopa and levodopa tablets must be determined by careful titration in each patient. Carbidopa and levodopa tablets are available in a 1:4 ratio of carbidopa to levodopa (carbidopa and levodopa tablets 25 mg/100 mg) as well as 1:10 ratio (carbidopa and levodopa tablets 25 mg/250 mg and carbidopa and levodopa tablets 10 mg/100 mg). Tablets of the two ratios may be given separately or combined as needed to provide the optimum dosage.
Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 mg to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.
Usual Initial DosageDosage is best initiated with one tablet of carbidopa and levodopa 25 mg/100 mg 3 times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of carbidopa and levodopa 25 mg/100 mg a day is reached.
If carbidopa and levodopa 10 mg/100 mg is used, dosage may be initiated with one tablet 3 or 4 times a day. However, this will not provide an adequate amount of carbidopa for many patients. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (two tablets q.i.d.) is reached.
How to Transfer Patients from LevodopaLevodopa must be discontinued at least 12 hours before starting carbidopa and levodopa tablets. A daily dosage of carbidopa and levodopa should be chosen that will provide approximately 25% of the previous levodopa dosage. Patients who are taking less than 1500 mg of levodopa a day should be started on one tablet of carbidopa and levodopa 25 mg/100 mg 3 or 4 times a day. The suggested starting dosage for most patients taking more than 1500 mg of levodopa is one tablet of carbidopa and levodopa 25 mg/250 mg 3 or 4 times a day.
MaintenanceTherapy should be individualized and adjusted according to the desired therapeutic response. At least 70 mg to 100 mg of carbidopa per day should be provided. When a greater proportion of carbidopa is required, one tablet of carbidopa and levodopa 25 mg/100 mg may be substituted for each tablet of carbidopa and levodopa 10 mg/100 mg. When more levodopa is required, carbidopa and levodopa 25 mg/250 mg should be substituted for carbidopa and levodopa 25 mg/100 mg or carbidopa and levodopa 10 mg/100 mg. If necessary, the dosage of carbidopa and levodopa 25 mg/250 mg may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.
Because both therapeutic and adverse responses occur more rapidly with carbidopa and levodopa than with levodopa alone, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly with carbidopa and levodopa than with levodopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.
Addition of Other Antiparkinsonian MedicationsStandard drugs for Parkinson's disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa tablets are being administered, although dosage adjustments may be required.
Interruption of TherapySporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa and levodopa. Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa and levodopa is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)
If general anesthesia is required, carbidopa and levodopa tablets may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS and the usual daily dosage may be administered as soon as the patient is able to take oral medication.
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Dandruff | Proficient Rx Lp
Gastric irritation may be reduced if taken before, during, or immediately after meals or with food or milk.
The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity (am) for single dose administration. Therefore, it is recommended that prednisone be administered in the morning prior to 9 am and when large doses are given, administration of antacids between meals to help prevent peptic ulcers. Multiple dose therapy should be evenly distributed in evenly spaced intervals throughout the day.
Dietary salt restriction may be advisable in patients.
Do not stop taking this medicine without first talking to your doctor. Avoid abrupt withdraw of therapy.
The initial dosage of prednisone may vary from 5 mg to 60 mg per day, depending on the specific disease entity being treated. In situations of less severity lower doses will generally suffice, while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, prednisone should be discontinued and the patient transferred to other appropriate therapy. IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small increments at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation, it may be necessary to increase the dosage of prednisone for a period of time consistent with the patient’s condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
Multiple SclerosisIn the treatment of acute exacerbations of multiple sclerosis daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective. (Dosage range is the same for prednisone and prednisolone.)
Alternate Day TherapyAlternate day therapy is a corticosteroid dosing regimen in which twice the usual daily dose of corticoid is administered every other morning. The purpose of this mode of therapy is to provide the patient requiring long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the cushingoid state, corticoid withdrawal symptoms, and growth suppression in children.
The rationale for this treatment schedule is based on two major premises: (a) the anti-inflammatory or therapeutic effect of corticoids persists longer than their physical presence and metabolic effects and (b) administration of the corticosteroid every other morning allows for re-establishment of more nearly normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day.
A brief review of the HPA physiology may be helpful in understanding this rationale. Acting primarily through the hypothalamus a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally the HPA system is characterized by diurnal (circadian) rhythm. Serum levels of ACTH rise from a low point about 10 pm to a peak level about 6 am. Increasing levels of ACTH stimulate adrenocortical activity resulting in a rise in plasma cortisol with maximal levels occurring between 2 am and 8 am. This rise in cortisol dampens ACTH production and in turn adrenocortical activity. There is a gradual fall in plasma corticoids during the day with lowest levels occurring about midnight.
The diurnal rhythm of the HPA axis is lost in Cushing’s disease, a syndrome of adrenocortical hyperfunction characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc. The same clinical findings of hyperadrenocorticism may be noted during long-term pharmacologic dose corticoid therapy administered in conventional daily divided doses. It would appear, then, that a disturbance in the diurnal cycle with maintenance of elevated corticoid values during the night may play a significant role in the development of undesirable corticoid effects. Escape from these constantly elevated plasma levels for even short periods of time may be instrumental in protecting against undesirable pharmacologic effects.
During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of treatment. During this time the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every 6 hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenocortical suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenocortical suppression for 1 1/4 to 1 1/2 days following a single dose) and thus are recommended for alternate day therapy.
The following should be kept in mind when considering alternate day therapy:
1. Basic principles and indications for corticosteroid therapy should apply. The benefits of alternate day therapy should not encourage the indiscriminate use of steroids.
2. Alternate day therapy is a therapeutic technique primarily designed for patients in whom long-term pharmacologic corticoid therapy is anticipated.
3. In less severe disease processes in which corticoid therapy is indicated, it may be possible to initiate treatment with alternate day therapy. More severe disease states usually will require daily divided high dose therapy for initial control of the disease process. The initial suppressive dose level should be continued until satisfactory clinical response is obtained, usually four to ten days in the case of many allergic and collagen diseases. It is important to keep the period of initial suppressive dose as brief as possible particularly when subsequent use of alternate day therapy is intended. Once control has been established, two courses are available: (a) change to alternate day therapy and then gradually reduce the amount of corticoid given every other day or (b) following control of the disease process reduce the daily dose of corticoid to the lowest effective level as rapidly as possible and then change over to an alternate day schedule. Theoretically, course (a) may be preferable.
4. Because of the advantages of alternate day therapy, it may be desirable to try patients on this form of therapy who have been on daily corticoids for long periods of time (e.g., patients with rheumatoid arthritis). Since these patients may already have a suppressed HPA axis, establishing them on alternate day therapy may be difficult and not always successful. However, it is recommended that regular attempts be made to change them over. It may be helpful to triple or even quadruple the daily maintenance dose and administer this every other day rather than just doubling the daily dose if difficulty is encountered. Once the patient is again controlled, an attempt should be made to reduce this dose to a minimum.
5. As indicated above, certain corticosteroids, because of their prolonged suppressive effect on adrenal activity, are not recommended for alternate day therapy (e.g., dexamethasone and betamethasone).
6. The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocortical activity the least, when given at the time of maximal activity (am).
7. In using alternate day therapy it is important, as in all therapeutic situations to individualize and tailor the therapy to each patient. Complete control of symptoms will not be possible in all patients. An explanation of the benefits of alternate day therapy will help the patient to understand and tolerate the possible flare-up in symptoms which may occur in the latter part of the off-steroid day. Other symptomatic therapy may be added or increased at this time if needed.
8. In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive daily divided corticoid dose for control. Once control is again established alternate day therapy may be re-instituted.
9. Although many of the undesirable features of corticosteroid therapy can be minimized by alternate day therapy, as in any therapeutic situation, the physician must carefully weigh the benefit-risk ratio for each patient in whom corticoid therapy is being considered.
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