Barr Laboratories Inc.

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For Relief of Pain

Dosage should be adjusted according to the severity of the pain and the response of the patient. Meperidine is less effective orally than on parenteral administration. The dose of meperidine hydrochloride should be proportionately reduced (usually by 25 to 50 percent) when administered concomitantly with phenothiazines and many other tranquilizers since they potentiate the action of meperidine HCl.

Adults: The usual dosage is 50 mg to 150 mg orally, every 3 or 4 hours as necessary.

Pediatric Patients: The usual dosage is 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary (see PRECAUTIONS, Pediatric Use).

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To achieve maximum contraceptive effectiveness, Velivet tablets must be taken exactly as directed, at the same time every day, and at intervals not exceeding 24 hours. Velivet tablets may be initiated using either a Sunday start or a Day 1 start.

NOTE: Each cycle pack dispenser is preprinted with the days of the week, starting with Sunday, to facilitate a Sunday start regimen. Six different "day label strips" are provided with each cycle pack dispenser in order to accommodate a Day 1 start regimen. In this case, the patient should place the self-adhesive "day label strip" that corresponds to her starting day over the preprinted days.

During the First Cycle of Use

IMPORTANT: The possibility of ovulation and conception prior to initiation of use of Velivet tablets should be considered. A woman can begin to take Velivet tablets either on the first Sunday after the onset of her menstrual period (Sunday Start) or on the first day of her menstrual period (Day 1 Start). When switching from another oral contraceptive, Velivet tablets should be started on the same day that a new pack of the previous oral contraceptive would have been started.

Sunday Start

When initiating a Sunday start regimen, another method of contraception, such as condoms or spermicide, should be used for the first 7 consecutive days of taking Velivet tablets.

Using a Sunday start, tablets are taken daily without interruption as follows: The first beige tablet should be taken on the first Sunday after menstruation begins (if menstruation begins on Sunday, the first beige tablet is taken on that day). Tablets are then taken sequentially following the arrows marked on the dispenser. One beige tablet is taken daily for 7 days, followed by 1 orange tablet daily for 7 days, 1 pink tablet daily for 7 days, and then 1 white (inactive) tablet daily for 7 days. For all subsequent cycles, the patient then begins a new 28 tablet regimen on the next day (Sunday) after taking the last white (inactive) tablet. [If switching from a Sunday Start oral contraceptive, the first Velivet tablet should be taken on the second Sunday after the last tablet of a 21 day oral contraceptive regimen or should be taken on the first Sunday after the last inactive tablet of a 28 day regimen.]

If a patient misses 1 active tablet in Weeks 1, 2, or 3, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive active tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control (such as condoms or spermicide) if she has intercourse in the 7 days after she restarts her pills. If the patient misses 2 consecutive pink (active) tablets in the third week or misses 3 or more active tablets in a row at any time during the cycle, the patient should keep taking 1 active tablet daily until the next Sunday. On Sunday the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after restarting her pills.

Complete instructions to facilitate patient counseling on proper pill usage can be found in Detailed or Brief Patient Labeling ("HOW TO TAKE THE PILL" section).

Day 1 Start

Counting the first day of menstruation as "Day 1", the first beige tablet should be taken on the first day of menstrual bleeding. Tablets are then taken sequentially without interruption as follows: One beige tablet daily for 7 days, then 1 orange tablet daily for 7 days, followed by 1 pink tablet daily for 7 days and then 1 white (inactive) tablet daily for 7 days. For all subsequent cycles, the patient then begins a new 28-tablet regimen on the next day after taking the last white (inactive) tablet. [If switching directly from another oral contraceptive, the first beige tablet should be taken on the same day that a new pack of the previous oral contraceptive would have been started.]

If a patient misses 1 active tablet in Weeks 1, 2, or 3, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive active tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control (such as condoms or spermicide) if she has intercourse in the 7 days after she restarts her pills. If the patient misses 2 consecutive pink tablets in the third week or misses 3 or more active tablets in a row at any time during the cycle, the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after she restarts her pills.

Complete instructions to facilitate patient counseling on proper pill usage can be found in Detailed or Brief Patient Labeling ("HOW TO TAKE THE PILL" section).

ADDITIONAL INSTRUCTIONS FOR BOTH SUNDAY AND DAY 1 STARTS

If Spotting or Breakthrough Bleeding Occurs

Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, non-functional causes should be considered. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If both pregnancy and pathology have been excluded, time or a change to another preparation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease.

Use of Oral Contraceptives in The Event of a Missed Menstrual Period:

1. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued if pregnancy is confirmed.

2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out. Oral contraceptive use should be discontinued if pregnancy is confirmed.

  Use of Oral Contraceptives Postpartum:

The use of Velivet for contraception may be initiated 4 to 6 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS, Nursing Mothers).

If the patient starts on Velivet postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a beige tablet has been taken daily for 7 consecutive days.

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Dosage should be adjusted according to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effect of opioids. If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. Oxycodone and acetaminophen capsules are given orally.

The usual adult dosage is one capsule every 6 hours as needed for pain. The total daily dose of acetaminophen should not exceed 4 grams.

Cessation of Therapy

In patients treated with oxycodone and acetaminophen capsules for more than a few weeks who no longer require therapy, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

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Adults and Children over 10 years of age: Usual dose is one 100 mg or 200 mg capsule three times a day as needed for cough. If necessary to control cough, up to 600 mg daily in three divided doses may be given. BENZONATATE should be swallowed whole. BENZONATATE Capsules are not to be broken, chewed, dissolved, cut or crushed.

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For patients with sustained VT, no matter what their cardiac status, flecainide, like other antiarrhythmics, should be initiated in-hospital with rhythm monitoring.

Flecainide has a long half-life (12 to 27 hours in patients). Steady-state plasma levels, in patients with normal renal and hepatic function, may not be achieved until the patient has received 3 to 5 days of therapy at a given dose. Therefore, increases in dosage should be made no more frequently than once every four days, since during the first 2 to 3 days of therapy the optimal effect of a given dose may not be achieved.

For patients with PSVT and patients with PAF the recommended starting dose is 50 mg every 12 hours. Flecainide acetate doses may be increased in increments of 50 mg bid every four days until efficacy is achieved. For PAF patients, a substantial increase in efficacy without a substantial increase in discontinuations for adverse experiences may be achieved by increasing the flecainide acetate dose from 50 to 100 mg bid. The maximum recommended dose for patients with paroxysmal supraventricular arrhythmias is 300 mg/day.

For sustained VT the recommended starting dose is 100 mg every 12 hours. This dose may be increased in increments of 50 mg bid every four days until efficacy is achieved. Most patients with sustained VT do not require more than 150 mg every 12 hours (300 mg/day) and the maximum dose recommended is 400 mg/day.

In patients with sustained VT, use of higher initial doses and more rapid dosage adjustments have resulted in an increased incidence of proarrhythmic events and CHF, particularly during the first few days of dosing (see WARNINGS). Therefore, a loading dose is not recommended.

Intravenous lidocaine has been used occasionally with flecainide while awaiting the therapeutic effect of flecainide. No adverse drug interactions were apparent. However, no formal studies have been performed to demonstrate the usefulness of this regimen.

An occasional patient not adequately controlled by (or intolerant to) a dose given at 12 hour intervals may be dosed at eight-hour intervals.

Once adequate control of the arrhythmia has been achieved, it may be possible in some patients to reduce the dose as necessary to minimize side effects or effects on conduction. In such patients, efficacy at the lower dose should be evaluated.

Flecainide should be used cautiously in patients with a history of CHF or myocardial dysfunction (see WARNINGS).

Any use of flecainide in children should be directly supervised by a cardiologist skilled in the treatment of arrhythmias in children. Because of the evolving nature of information in this area, specialized literature should be consulted. Under six months of age, the initial starting dose of flecainide in children is approximately 50 mg/M2 body surface area daily, divided into two or three equally spaced doses. Over six months of age, the initial starting dose may be increased to 100 mg/M2 per day. The maximum recommended dose is 200 mg/M2 per day. This dose should not be exceeded. In some children on higher doses, despite previously low plasma levels, the level has increased rapidly to far above therapeutic values while taking the same dose. Small changes in dose may also lead to disproportionate increases in plasma levels. Plasma trough (less than one hour pre-dose) flecainide levels and electrocardiograms should be obtained at presumed steady state (after at least five doses) either after initiation or change in flecainide dose, whether the dose was increased for lack of effectiveness, or increased growth of the patient. For the first year on therapy, whenever the patient is seen for reasons of clinical follow-up, it is suggested that a 12 lead electrocardiogram and plasma trough flecainide level are obtained. The usual therapeutic level of flecainide in children is 200 to 500 ng/mL. In some cases, levels as high as 800 ng/mL may be required for control.

In patients with severe renal impairment (creatinine clearance of 35 mL/min/1.73 square meters or less), the initial dosage should be 100 mg once daily (or 50 mg bid); when used in such patients, frequent plasma level monitoring is required to guide dosage adjustments (see Plasma Level Monitoring). In patients with less severe renal disease, the initial dosage should be 100 mg every 12 hours; plasma level monitoring may also be useful in these patients during dosage adjustment. In both groups of patients, dosage increases should be made very cautiously when plasma levels have plateaued (after more than four days), observing the patient closely for signs of adverse cardiac effects or other toxicity. It should be borne in mind that in these patients it may take longer than four days before a new steady-state plasma level is reached following a dosage change.

Based on theoretical considerations, rather than experimental data, the following suggestion is made: when transferring patients from another antiarrhythmic drug to flecainide allow at least two to four plasma half-lives to elapse for the drug being discontinued before starting flecainide at the usual dosage. In patients where withdrawal of a previous antiarrhythmic agent is likely to produce life-threatening arrhythmias, the physician should consider hospitalizing the patient.

When flecainide is given in the presence of amiodarone, reduce the usual flecainide dose by 50% and monitor the patient closely for adverse effects. Plasma level monitoring is strongly recommended to guide dosage with such combination therapy (see below).

Plasma Level Monitoring

The large majority of patients successfully treated with flecainide were found to have trough plasma levels between 0.2 and 1 mcg/mL. The probability of adverse experiences, especially cardiac, may increase with higher trough plasma levels, especially when these exceed 1 mcg/mL. Periodic monitoring of trough plasma levels may be useful in patient management. Plasma level monitoring is required in patients with severe renal failure or severe hepatic disease, since elimination of flecainide from plasma may be markedly slower. Monitoring of plasma levels is strongly recommended in patients on concurrent amiodarone therapy and may also be helpful in patients with CHF and in patients with moderate renal disease.

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To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals of 24 hours.

IMPORTANT: If the Sunday start schedule is selected, the patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle. The possibility of ovulation and conception prior to initiation of use should be considered.

Kelnor 1/35 (28 Day Regimen) (ethynodiol diacetate and ethinyl estradiol tablets)

Dosage Schedule

The Kelnor 1/35 (28 Day Regimen) tablet dispenser contains 21 light yellow active tablets arranged in three numbered rows of 7 tablets each, followed by a fourth row of 7 white placebo tablets.

Days of the week are printed above the tablets, starting with Sunday on the left.

28 Day Schedule

For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first tablet (light yellow) is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first tablet (light yellow) is taken on that day. With either a DAY 1 START or SUNDAY START, 1 tablet (light yellow) is taken each day at the same time for 21 days. Then the white tablets are taken for 7 days, whether bleeding has stopped or not. After all 28 tablets have been taken, whether bleeding has stopped or not, the same dosage schedule is repeated beginning on the following day.

Special Notes

Spotting, Breakthrough Bleeding, or Nausea

If spotting (bleeding insufficient to require a pad), breakthrough bleeding (heavier bleeding similar to a menstrual flow), or nausea occurs the patient should continue taking her tablets as directed. The incidence of spotting, breakthrough bleeding or nausea is minimal, most frequently occurring in the first cycle. Ordinarily spotting or breakthrough bleeding will stop within a week. Usually the patient will begin to cycle regularly within two to three courses of tablet-taking. In the event of spotting or breakthrough bleeding organic causes should be borne in mind. (See WARNINGS, No. 11.)

Missed Menstrual Periods

 Withdrawal flow will normally occur 2 or 3 days after the last active tablet is taken. Failure of withdrawal bleeding ordinarily does not mean that the patient is pregnant, providing the dosage schedule has been correctly followed. (See WARNINGS, No. 6.)

If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period, and oral contraceptives should be withheld until pregnancy has been ruled out.

If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

The first intermenstrual interval after discontinuing the tablets is usually prolonged; consequently, a patient for whom a 28 day cycle is usual might not begin to menstruate for 35 days or longer. Ovulation in such prolonged cycles will occur correspondingly later in the cycle. Posttreatment cycles after the first one, however, are usually typical for the individual woman prior to taking tablets. (See WARNINGS, No. 11.)

Missed Tablets

 If a woman misses taking one active tablet, the missed tablet should be taken as soon as it is remembered. In addition, the next tablet should be taken at the usual time. If two consecutive active tablets are missed in week 1 or week 2 of the dispenser, the dosage should be doubled for the next 2 days. The regular schedule should then be resumed, but an additional method of protection must be used as backup for the next 7 days if she has sex during that time or she may become pregnant.

If two consecutive active tablets are missed in week 3 of the dispenser or three consecutive active tablets are missed during any of the first 3 weeks of the dispenser, direct the patient to do one of the following: Day 1 Starters should discard the rest of the dispenser and begin a new dispenser that same day; Sunday Starters should continue to take 1 tablet daily until Sunday, discard the rest of the dispenser and begin a new dispenser that same day. The patient may not have a period this month; however, if she has missed two consecutive periods, pregnancy should be ruled out. An additional method of protection must be used as a backup for the next 7 days after the tablets are missed if she has sex during that time or she may become pregnant.

While there is little likelihood of ovulation if only one active tablet is missed, the possibility of spotting or breakthrough bleeding is increased and should be expected if two or more successive active tablets are missed. However, the possibility of ovulation increases with each successive day that scheduled active tablets are missed.

If one or more placebo tablets of Kelnor are missed, the Kelnor schedule should be resumed on the eighth day after the last light yellow tablet was taken. Omission of placebo tablets in the 28 tablet courses does not increase the possibility of conception provided that this schedule is followed.

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The tablet dispenser has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in either three or four rows of seven tablets each, with the days of the week appearing on the tablet dispenser above the first row of tablets.

Note: Each tablet dispenser has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different days of the week stickers have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day 1 Start regimen. If the patient is using the Day 1 Start regimen, she should place the self-adhesive days of the week sticker that corresponds to her starting day over the preprinted days.

Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen.

The possibility of ovulation and conception prior to initiation of use should be considered.

Dosage and Administration for 21 Day Dosage Regimen

To achieve maximum contraceptive effectiveness, Junel ®21 must be taken exactly as directed and at intervals not exceeding 24 hours.

Junel ®21 provides the patient with a convenient tablet schedule of “3 weeks on --1 week off”. Two dosage regimens are described, one of which may be more convenient or suitable than the other for an individual patient. For the initial cycle of therapy, the patient begins her tablets according to the Day 1 Start or Sunday-Start regimen. With either regimen, the patient takes one tablet daily for 21 consecutive days followed by one week of no tablets.

Sunday Start Regimen: The patient begins taking tablets from the top row on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first tablet is taken on the same day. The last tablet in the dispenser will then be taken on a Saturday, followed by no tablets for a week (7 days). For all subsequent cycles, the patient then begins a new 21-tablet regimen on the eighth day, Sunday, after taking her last tablet. Following this regimen, of 21 days on--7 days off, the patient will start all subsequent cycles on a Sunday. Day 1 Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive days of the week sticker that corresponds to her starting day over the preprinted days on the blister card. She starts taking one tablet daily, beginning with the first tablet in the top row. The patient completes her 21-tablet regimen when she has taken the last tablet in the tablet dispenser. She will then take no tablets for a week (7 days). For all subsequent cycles, the patient begins a new 21-tablet regimen on the eighth day after taking her last tablet, again starting with the first tablet in the top row after placing the appropriate days of the week sticker over the preprinted days on the tablet dispenser. Following this regimen of 21 days on--7 days off, the patient will start all subsequent cycles on the same day of the week as the first course. Likewise, the interval of no tablets will always start on the same day of the week.Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Special Notes on Administration

Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after discontinuing medication. If spotting occurs while on the usual regimen of one tablet daily, the patient should continue medication without interruption.

If a patient forgets to take one or more tablets, the following is suggested:

One tablet is missed

take tablet as soon as remembered take next tablet at the regular time

Two consecutive tablets are missed (week 1 or week 2)

take two tablets as soon as remembered take two tablets the next day use another birth control method for seven days following the missed tablets

Two consecutive tablets are missed (week 3)

Sunday Start Regimen

take one tablet daily until Sunday discard remaining tablets start new pack of tablets immediately (Sunday) use another birth control method for seven days following the missed tablets

Day 1 Start Regimen

discard remaining tablets start new pack of tablets that same day use another birth control method for seven days following the missed tablets

Three (or more) consecutive tablets are missed

Sunday Start Regimen

take one tablet daily until Sunday discard remaining tablets start new pack of tablets immediately (Sunday) use another birth control method for seven days following the missed tablets

Day 1 Start Regimen:

discard remaining tablets start new pack of tablets that same day use another birth control method for seven days following the missed tablets

The possibility of ovulation occurring increases with each successive day that scheduled tablets are missed. While there is little likelihood of ovulation occurring if only one tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive tablets are missed.

In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day 1) depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered.

Dosage and Administration for 28 Day Dosage Regimen

To achieve maximum contraceptive effectiveness, Junel ® Fe 28 must be taken exactly as directed and at intervals not exceeding 24 hours.

Junel ® Fe 28 provides a continuous administration regimen consisting of 21 light yellow or pink tablets of Junel ® and 7 brown nonhormone containing tablets of ferrous fumarate. The ferrous fumarate tablets are present to facilitate ease of drug administration via a 28-day regimen and do not serve any therapeutic purpose. There is no need for the patient to count days between cycles because there are no “off-tablet days.”

Sunday Start Regimen: The patient begins taking the first light yellow or pink tablet from the top row of the dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first light yellow or pink tablet is taken on the same day. The patient takes one light yellow or pink tablet daily for 21 days. The last light yellow or pink tablet in the dispenser will be taken on a Saturday. Upon completion of all 21 light yellow or pink tablets, and without interruption, the patient takes one brown tablet daily for 7 days. Upon completion of this first course of tablets, the patient begins a second course of 28-tablets, without interruption, the next day (Sunday), starting with the Sunday light yellow or pink tablet in the top row. Adhering to this regimen of one light yellow or pink tablet daily for 21 days, followed without interruption by one brown tablet daily for seven days, the patient will start all subsequent cycles on a Sunday. Day 1 Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive days of the week sticker that corresponds to her starting day over the preprinted days on the blister card. She starts taking one light yellow or pink tablet daily, beginning with the first light yellow or pink tablet in the top row. After the last light yellow or pink tablet (at the end of the third row) has been taken, the patient will then take the brown tablets for a week (7 days). For all subsequent cycles, the patient begins a new 28 tablet regimen on the eighth day after taking her last light yellow or pink tablet, again starting with the first tablet in the top row after placing the appropriate days of the week sticker over the preprinted days on the tablet dispenser. Following this regimen of 21 light yellow or pink tablets and 7 brown tablets, the patient will start all subsequent cycles on the same day of the week as the first course.Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Special Notes on Administration

Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after the brown tablets have been started. In any event, the next course of tablets should be started without interruption. If spotting occurs while the patient is taking light yellow or pink tablets, continue medication without interruption.

If a patient forgets to take one or more light yellow or pink tablets, the following is suggested:

One tablet is missed

take tablet as soon as remembered take next tablet at the regular time

Two consecutive tablets are missed (week 1 or week 2)

take two tablets as soon as remembered take two tablets the next day use another birth control method for seven days following the missed tablets

Two consecutive tablets are missed (week 3)

Sunday Start Regimen

take one tablet daily until Sunday discard remaining tablets start new pack of tablets immediately (Sunday) use another birth control method for seven days following the missed tablets

Day 1 Start Regimen

discard remaining tablets start new pack of tablets that same day use another birth control method for seven days following the missed tablets

Three (or more) consecutive tablets are missed

Sunday Start Regimen

take one tablet daily until Sunday discard remaining tablets start new pack of tablets immediately (Sunday) use another birth control method for seven days following the missed tablets

Day 1 Start Regimen

discard remaining tablets start new pack of tablets that same day use another birth control method for seven days following the missed tablets

The possibility of ovulation occurring increases with each successive day that scheduled light yellow or pink tablets are missed. While there is little likelihood of ovulation occurring if only one light yellow or pink tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive light yellow or pink tablets are missed.

If the patient forgets to take any of the seven brown tablets in week four, those brown tablets that were missed are discarded and one brown tablet is taken each day until the pack is empty. A back-up birth control method is not required during this time. A new pack of tablets should be started no later than the eighth day after the last light yellow or pink tablet was taken.

In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day-1), depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered.

Use of Oral Contraceptives in the Event of a Missed Menstrual Period

If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

After several months on treatment, bleeding may be reduced to a point of virtual absence. This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy.

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To achieve maximum contraceptive effectiveness, Camila® must be taken exactly as directed. One tablet is taken every day, at the same time. Administration is continuous, with no interruption between pill packs. See PATIENT LABELING for detailed instructions.

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For symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested: in adults, 50 to 100 mg q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 to 100 mg daily in divided doses.

For use in the management of pruritus due to allergic conditions such as chronic urticaria and atopic and contact dermatoses, and in histamine-mediated pruritus: in adults, 25 mg t.i.d. or q.i.d.; children under 6 years, 50 mg daily in divided doses; and over 6 years, 50 to 100 mg daily in divided doses.

As a sedative when used as a premedication and following general anesthesia: 50 to 100 mg in adults, and 0.6 mg/kg in children.

When treatment is initiated by the intramuscular route of administration, subsequent doses may be administered orally.

As with all medications, the dosage should be adjusted according to the patient’s response to therapy.

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To achieve maximum contraceptive effectiveness, Lessina® (levonorgestrel and ethinyl estradiol tablets USP) must be taken exactly as directed at intervals not exceeding 24-hours.

Lessina Tablets are a monophasic preparation plus 7 inert tablets. The dosage of Lessina Tablets is one tablet daily for 21 consecutive days per menstrual cycle plus 7 white inert tablets according to the prescribed schedule. It is recommended that LessinaTablets be taken at the same time each day, preferably after the evening meal or at bedtime. During the first cycle of medication, the patient should be instructed to take one pink Lessina Tablet daily and then 7 white inert tablets for twenty-eight (28) consecutive days, beginning on day one (1) of her menstrual cycle. (The first day of menstruation is day one.) Withdrawal bleeding usually occurs within 3 days following the last pink tablet. (If LessinaTablets are first taken later than the first day of the first menstrual cycle of medication or postpartum, contraceptive reliance should not be placed on Lessina Tablets until after the first 7 consecutive days of administration. The possibility of ovulation and conception prior to initiation of medication should be considered.)

When switching from another oral contraceptive, Lessina Tablets should be started on the first day of bleeding following the last active tablet taken of the previous oral contraceptive.

The patient begins her next and all subsequent 28-day courses of Lessina Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her pink tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Lessina Tablets is started later than the next day, the patient should be protected by another means of contraception until she has taken a tablet daily for seven consecutive days.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance, however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Lessina Tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more active tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

The risk of pregnancy increases with each active (pink) tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING below. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she is still protected against pregnancy provided she begins taking pink tablets again on the proper day.

In the nonlactating mother, Lessina Tablets may be initiated postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease.) It is to be noted that early resumption of ovulation may occur if bromocriptine mesylate has been used for the prevention of lactation.

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Secondary Amenorrhea

Medroxyprogesterone acetate tablets may be given in dosages of 5 or 10 mg daily for 5 to 10 days. A dose for inducing an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen is 10 mg of medroxyprogesterone acetate daily for 10 days. In cases of secondary amenorrhea, therapy may be started at any time. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing medroxyprogesterone acetate therapy.

Abnormal Uterine Bleeding Due to Hormonal Imbalance in the Absence of Organic Pathology

Beginning on the calculated 16th or 21st day of the menstrual cycle, 5 or 10 mg of medroxyprogesterone acetate may be given daily for 5 to 10 days. To produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen, 10 mg of medroxyprogesterone acetate daily for 10 days beginning on the 16th day of the cycle is suggested. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing therapy with medroxyprogesterone acetate. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with medroxyprogesterone acetate.

Reduction of Endometrial Hyperplasia in Postmenopausal Women Receiving Daily 0.625 mg Conjugated Estrogens

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be re-evaluated periodically as clinically appropriate (for example, 3 to 6 month intervals) to determine if treatment is still necessary (see WARNINGS). For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.

Medroxyprogesterone acetate tablets may be given in dosages of 5 or 10 mg daily for 12 to 14 consecutive days per month, in postmenopausal women receiving daily 0.625 mg conjugated estrogens, either beginning on the 1st day of the cycle or the 16th day of the cycle.

Patients should be started at the lowest dose.

The lowest effective dose of medroxyprogesterone acetate has not been determined.

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To achieve maximum contraceptive effectiveness, Enpresse Tablets (levonorgestrel and ethinyl estradiol tablets USP—triphasic regimen) must be taken exactly as directed and at intervals not exceeding 24 hours.

Enpresse Tablets are a three-phase preparation plus 7 inert tablets. The dosage of Enpresse Tablets is one tablet daily for 28 consecutive days per menstrual cycle in the following order: 6 pink tablets (phase 1), followed by 5 white tablets (phase 2), followed by 10 orange tablets (phase 3), plus 7 light-green inert tablets, according to the prescribed schedule.

It is recommended that Enpresse Tablets be taken at the same time each day, preferably after the evening meal or at bedtime. During the first cycle of medication, the patient should be instructed to take one Enpresse Tablet daily in the order of 6 pink, 5 white, 10 orange tablets, and then 7 light-green inert tablets for twenty-eight (28) consecutive days, beginning on day one (1) of her menstrual cycle. (The first day of menstruation is day one.) Withdrawal bleeding usually occurs within 3 days following the last orange tablet and may not have finished before the next pack is started. (If Enpresse Tablets are first taken later than the first day of the first menstrual cycle of medication or postpartum, contraceptive reliance should not be placed on Enpresse Tablets until after the first 7 consecutive days of administration and a nonhormonal back-up method of birth control should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.)

When switching from another oral contraceptive, Enpresse Tablets should be started on the first day of bleeding following the last active tablet taken of the previous oral contraceptive.

The patient may switch any day from a progestin-only pill and should begin Enpresse the next day. If switching from an implant or injection, the patient should start Enpresse on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection, or implant, the patient should be advised to use a non-hormonal back-up method of birth control for the first 7 days of tablet-taking.

The patient begins her next and all subsequent 28-day courses of Enpresse Tablets on the same day of the week that she began her first course, following the same schedule. She begins taking her pink tablets on the next day after ingestion of the last light-green tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Any time a subsequent cycle of Enpresse Tablets is started later than the next day, the patient should be protected by another means of contraception until she has taken a tablet daily for seven consecutive days.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Enpresse Tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

The risk of pregnancy increases with each active (pink, white, or orange) tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the DETAILED PATIENT LABELING below. If breakthrough bleeding occurs following missed active tablets, it will usually be transient and of no consequence. If the patient misses one or more light-green tablets, she is still protected against pregnancy provided she begins taking pink tablets again on the proper day.

Enpresse Tablets may be initiated no earlier than day 28 postpartum in the non-lactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see “CONTRAINDICATIONS”,“WARNINGS” and “PRECAUTIONS” concerning thromboembolic disease). The patient should be advised to use a nonhormonal back-up method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the start of combined oral contraceptive use or the patient must wait for her first menstrual period. In the case of first-trimester abortion, if the patient starts Enpresse immediately, additional contraceptive measures are not needed. It is to be noted that early resumption of ovulation may occur if Parlodel® (bromocriptine mesylate) has been used for the prevention of lactation.

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2.1 Galantamine Hydrobromide Extended-Release Capsules

Galantamine hydrobromide extended-release capsules should be administered once daily in the morning, preferably with food.

The recommended starting dosage of galantamine hydrobromide extended-release capsules is 8 mg/day. The dosage should be increased to the initial maintenance dose of 16 mg/day after a minimum of 4 weeks. A further increase to 24 mg/day should be attempted after a minimum of 4 weeks at 16 mg/day. Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.

The dosage of galantamine hydrobromide extended-release capsules shown to be effective in a controlled clinical trial is 16 to 24 mg/day.

Patients currently being treated with galantamine tablets can convert to galantamine hydrobromide extended-release capsules by taking their last dose of galantamine tablets in the evening and starting galantamine hydrobromide extended-release capsules once daily treatment the next morning. Converting from galantamine tablets to galantamine hydrobromide extended-release capsules should occur at the same total daily dosage.

2.2 Galantamine Immediate-Release Tablets

The dosage of galantamine tablets shown to be effective in controlled clinical trials is 16 to 32 mg/day given as twice daily dosing. As the dosage of 32 mg/day is less well tolerated than lower dosages and does not provide increased effectiveness, the recommended dosage range is 16 to 24 mg/day given twice daily. The dosage of 24 mg/day did not provide a statistically significant greater clinical benefit than 16 mg/day. It is possible, however, that a daily dosage of 24 mg of galantamine tablets might provide additional benefit for some patients.

The recommended starting dosage of galantamine tablets is 4 mg twice a day (8 mg/day). The dosage should be increased to the initial maintenance dosage of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day).

Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.

Galantamine tablets should be administered twice a day, preferably with morning and evening meals.

Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for more than three days, the patient should be restarted at the lowest dosage and the dosage escalated to the current dose.

The abrupt withdrawal of galantamine hydrobromide extended-release capsules and galantamine tablets in those patients who had been receiving dosages in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same dosages of that drug. The beneficial effects of galantamine hydrobromide extended-release capsules and galantamine tablets are lost, however, when the drug is discontinued.

2.3 Dosage in Patients With Hepatic Impairment

In patients with moderate hepatic impairment (Child-Pugh score of 7 to 9), the dosage should generally not exceed 16 mg/day. The use of galantamine hydrobromide extended-release capsules and galantamine tablets in patients with severe hepatic impairment (Child-Pugh score of 10 to 15) is not recommended [see Clinical Pharmacology (12.3)].

2.4 Dosage in Patients With Renal Impairment

In patients with creatinine clearance of 9 to 59 mL/min, the dosage should generally not exceed 16 mg/day. In patients with creatinine clearance less than 9 mL/min, the use of galantamine hydrobromide extended-release capsules and galantamine tablets is not recommended [see Clinical Pharmacology (12.3)].