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Ethex Corporation Drugs

Hydromorphone Hydrochlo...

Hydromorphone Hydrochloride

Hydromorphone hydrochloride tablets (2 mg, 4 mg, 8 mg): The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on lower starting dose (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism).
Hydrocodone Bitartrate ...

Hydrocodone Bitartrate And Acetaminophen

Dosage should be adjusted according to severity of pain and response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

The usual adult dosage is one tablespoonful every 4 to 6 hours as needed for pain. The total daily dosage should not exceed 6 tablespoonfuls.

The usual dosages for children are given by the table below, and are to be given every 4 to 6 hours as needed for pain. These dosages correspond to an average individual dose of 0.27 mL/kg of hydrocodone bitartrate and acetaminophen oral solution (providing 0.135 mg/kg of hydrocodone bitartrate and 9 mg/kg of acetaminophen). Dosing should be based on weight whenever possible.
BODY WEIGHT APPROXIMATEAGE DOSEevery 4to 6 hours MAXIMUMTOTALDAILY DOSE(6 dosesper day) 12 to 15 kg27 to 34 lbs. 2 to 3 years ¾ teaspoonful= 3.75 mL 4½ teaspoonfuls= 22.5 mL 16 to 22kg35 to 50 lbs. 4 to 6 years 1 teaspoonful= 5 mL 6 teaspoonfuls= 30 mL 23 to 31 kg51 to 69 lbs. 7 to 9 years 1½ teaspoonfuls= 7.5 mL 9 teaspoonfuls= 45 mL 32 to 45 kg70 lbs. to 100 lbs. 10 to 13 years 2 teaspoonfuls= 10 mL 12 teaspoonfuls= 60 mL 46 kg and up101 lbs. and up 14 years to adult 1 Tablespoonful= 15 mL 6 Tablespoonfuls= 90 mL
The total daily dosage for children should not exceed 6 doses per day. It is of utmost importance that the dose of hydrocodone bitartrate and acetaminophen oral solution be administered accurately. A household teaspoon or tablespoon is not an adequate measuring device, especially when one-half or three-fourths of a teaspoonful is to be measured. Given the inexactitude of the household spoon measure and the possibility of using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that caregivers obtain and use a calibrated measuring device. Healthcare providers should recommend a dropper that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage.
Dextroamphetamine Sulfa...

Dextroamphetamine Sulfate

Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia.

Narcolepsy:Usual dose is 5 mg to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in pediatric pateints under 12 years of age; however, when it does, dextroamphetamine sulfate tablets may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until an optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening: additional doses (1 or 2) at intervals of 4 to 6 hours.

Attention Deficit Disorder with Hyperactivity:Not recommended for pediatric patients under 3 years of age.

In pediatric patients from 3 to 5 years of age, start with 2.5 mg daily, by tablet; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In pediatric patients 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day.

Give first dose on awakening: additional doses (1 or 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.
Benzonatate

Benzonatate

Adults and children over 10: Usual dose is one 100 mg or 200 mg capsule t.i.d. as required. If necessary, up to 600 mg daily may be given.
Oxycodone Hydrochloride...

Oxycodone Hydrochloride

General Principles

OXYCODONE HCl CONTROLLED-RELEASE TABLETS ARE AN OPIOID AGONIST AND A SCHEDULE II CONTROLLED SUBSTANCE WITH AN ABUSE LIABILITY SIMILAR TO MORPHINE. OXYCODONE, LIKE MORPHINE AND OTHER OPIOIDS USED IN ANALGESIA, CAN BE ABUSED AND IS SUBJECT TO CRIMINAL DIVERSION.

OXYCODONE HCl CONTROLLED-RELEASE TABLETS ARE TO BE SWALLOWED WHOLE AND ARE NOT TO BE BROKEN, CHEWED, OR CRUSHED. TAKING BROKEN, CHEWED, OR CRUSHED OXYCODONE HCl CONTROLLED-RELEASE TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF OXYCODONE.

One Oxycodone HCl controlled-release 160 mg tablet is comparable to two 80 mg tablets when taken on an empty stomach. With a high-fat meal, however, there is a 25% greater peak plasma concentration following one 160 mg tablet. Dietary caution should be taken when patients are initially titrated to 160 mg tablets (see DOSAGE AND ADMINISTRATION).

Patients who are not currently taking opioid analgesics should generally be started on the lowest appropriate dose (see DOSAGE AND ADMINISTRATION; Initiation of Therapy).

In treating pain it is vital to assess the patient regularly and systematically. Therapy should also be regularly reviewed and adjusted based upon the patient's own reports of pain and side effects and the health professional's clinical judgment.

Oxycodone HCl Controlled-Release Tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time. The controlled-release nature of the formulation allows Oxycodone HCl Controlled-Release Tablets to be effectively administered every 12 hours (see CLINICAL PHARMACOLOGY; PHARMACOKINETICS AND METABOLISM). While symmetric (same dose AM and PM), around-the-clock, q12h dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern. It is usually appropriate to treat a patient with only one opioid for around-the-clock therapy.

Physicians should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines. Healthcare professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring (see BOXED WARNING).

Initiation of Therapy

It is critical to initiate the dosing regimen for each patient individually, taking into account the patient's prior opioid and non-opioid analgesic treatment. Attention should be given to:
(1) the general condition and medical status of the patient; (2) the daily dose, potency, and kind of the analgesic(s) the patient has been taking; (3) the reliability of the conversion estimate used to calculate the dose of oxycodone; (4) the patient's opioid exposure and opioid tolerance (if any); (5) the Special Instructions for Oxycodone HCl Controlled-Release 80 mg and 160 mg Tablets , or a Single Dose Greater Than 40 mg; and (6) the balance between pain control and adverse experiences.
Care should be taken to use low initial doses of Oxycodone HCl Controlled-Release Tablets in patients who are not already opioid-tolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS active medications (see PRECAUTIONS: Drug-Drug Interactions).

For initiation of Oxycodone HCl Controlled-Release Tablets therapy for patients previously taking opioids, the conversion ratios from Foley, KM. [NEJM, 1985; 313:84-95], found below, are a reasonable starting point, although not verified in well-controlled, multiple-dose trials.

Experience indicates a reasonable starting dose of Oxycodone HCl Controlled-Release Tablets for patients who are taking non-opioid analgesics and require continuous around-the-clock therapy for an extended period of time is 10 mg q12h. If a non-opioid analgesic is being provided, it may be continued. Oxycodone HCl Controlled-Release Tablets should be individually titrated to a dose that provides adequate analgesia and minimizes side effects.
Using standard conversion ratio estimates (see Table 4 below), multiply the mg/day of the previous opioids by the appropriate multiplication factors to obtain the equivalent total daily dose of oral oxycodone. When converting from oxycodone, divide the 24-hour oxycodone dose in half to obtain the twice a day (q12h) dose of Oxycodone HCl Controlled-Release Tablets. Round down to a dose which is appropriate for the tablet strengths available (10 mg, 20 mg, 40 mg, and 80 mg tablets). Discontinue all other around-the-clock opioid drugs when Oxycodone HCl Controlled-Release Tablet therapy is initiated. No fixed conversion ratio is likely to be satisfactory in all patients, especially patients receiving large opioid doses. The recommended doses shown in Table 4 are only a starting point, and close observation and frequent titration are indicated until patients are stable on the new therapy. TABLE 4. Multiplication Factors for Converting the Daily Dose of Prior Opioids to the Daily Dose of Oral Oxycodone*
* To be used only for conversion to oral oxycodone. For patients receiving high-dose parenteral opioids, a more conservative conversion is warranted. For example, for high-dose parenteral morphine, use 1.5 instead of 3 as a multiplication factor.
(Mg/Day Prior Opioid x Factor = Mg/Day Oral Oxycodone) Oral Prior Opioid Parenteral Prior Opioid Oxycodone 1 -- Codeine 0.15 -- Hydrocodone 0.9 -- Hydromorphone 4 20 Levorphanol 7.5 15 Meperidine 0.1 0.4 Methadone 1.5 3 Morphine 0.5 3
In all cases, supplemental analgesia should be made available in the form of a suitable short-acting analgesic.

Oxycodone HCl Controlled-Release Tablets can be safely used concomitantly with usual doses of non-opioid analgesics and analgesic adjuvants, provided care is taken to select a proper initial dose (see PRECAUTIONS).

Conversion from Transdermal Fentanyl to Oxycodone HCl Controlled-Release Tablets

Eighteen hours following the removal of the transdermal fentanyl patch, Oxycodone HCl Controlled-Release Tablet treatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg q12h of Oxycodone HCl Controlled-Release Tablets, should be initially substituted for each 25-μg/hr fentanyl transdermal patch. The patient should be followed closely for early titration, as there is very limited clinical experience with this conversion.

Managing Expected Opioid Adverse Experiences

Most patients receiving opioids, especially those who are opioid-naive, will experience side effects. Frequently the side effects from Oxycodone HCl Controlled-Release Tablets are transient, but may require evaluation and management. Adverse events such as constipation should be anticipated and treated aggressively and prophylactically with a stimulant laxative and/or stool softener. Patients do not usually become tolerant to the constipating effects of opioids.

Other opioid-related side effects such as sedation and nausea are usually self-limited and often do not persist beyond the first few days. If nausea persists and is unacceptable to the patient, treatment with antiemetics or other modalities may relieve these symptoms and should be considered.

Patients receiving Oxycodone HCl Controlled-Release Tablets may pass an intact matrix “ghost” in the stool or via colostomy. These ghosts contain little or no residual oxycodone and are of no clinical consequence.

Individualization of Dosage

Once therapy is initiated, pain relief and other opioid effects should be frequently assessed. Patients should be titrated to adequate effect (generally mild or no pain with the regular use of no more than two doses of supplemental analgesia per 24 hours). Patients who experience breakthrough pain may require dosage adjustment or rescue medication. Because steady-state plasma concentrations are approximated within 24 to 36 hours, dosage adjustment may be carried out every 1 to 2 days. It is most appropriate to increase the q12h dose, not the dosing frequency. There is no clinical information on dosing intervals shorter than q12h. As a guideline, except for the increase from 10 mg to 20 mg q12h, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose at each increase.

If signs of excessive opioid-related adverse experiences are observed, the next dose may be reduced. If this adjustment leads to inadequate analgesia, a supplemental dose of immediate-release oxycodone may be given. Alternatively, non-opioid analgesic adjuvants may be employed. Dose adjustments should be made to obtain an appropriate balance between pain relief and opioid-related adverse experiences.

If significant adverse events occur before the therapeutic goal of mild or no pain is achieved, the events should be treated aggressively. Once adverse events are under control, upward titration should continue to an acceptable level of pain control.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient and the caregiver/family.

Special Instructions for Oxycodone HCl Controlled-Release 80 mg Tablets, or a single dose greater than 40 mg (for use in opioid-tolerant patients only.)

Oxycodone HCl Controlled-Release 80 mg Tablets, or a single dose greater than 40 mg, are for use only in opioid-tolerant patients only. A single daily dose greater than 40 mg, or total daily doses greater than 80 mg, may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids. Patients should be instructed against use by individuals other than the patient for whom it was prescribed, as such inappropriate use may have severe medical consequences, including death.

One Oxycodone HCl Controlled-Release 160 mg tablet is comparable to two 80 mg tablets when taken on an empty stomach. With a high-fat meal, however, there is a 25% greater peak plasma concentration following one 160 mg tablet. Dietary caution should be taken when patients are initially titrated to 160 mg tablets.

Supplemental Analgesia

Most patients given around-the-clock therapy with controlled-release opioids may need to have immediate-release medication available for exacerbations of pain or to prevent pain that occurs predictably during certain patient activities (incident pain).

Maintenance of Therapy

The intent of the titration period is to establish a patient-specific q12h dose that will maintain adequate analgesia with acceptable side effects for as long as pain relief is necessary. Should pain recur then the dose can be incrementally increased to re-establish pain control. The method of therapy adjustment outlined above should be employed to re-establish pain control.

During chronic therapy, especially for non-cancer pain syndromes, the continued need for around-the-clock opioid therapy should be reassessed periodically (e.g., every 6 to 12 months) as appropriate.

Cessation of Therapy

When the patient no longer requires therapy with Oxycodone HCl Controlled-Release Tablets, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

Conversion from Oxycodone HCl Controlled-Release Tablets to Parenteral Opioids

To avoid overdose, conservative dose conversion ratios should be followed.
Metoprolol Succinate

Metoprolol Succinate

Metoprolol succinate extended-release tablets are intended for once daily administration. For treatment of hypertension and angina, when switching from immediate-release metoprolol to metoprolol succinate extended-release tablets, the same total daily dose of metoprolol succinate extended-release tablets should be used. Dosages of metoprolol succinate extended-release tablets should be individualized and titration may be needed in some patients.

Metoprolol succinate extended-release tablets are scored and can be divided; however, the whole or half tablet should be swallowed whole and not chewed or crushed.

Hypertension

The usual initial dosage is 25 to 100 mg daily in a single dose, whether used alone or added to a diuretic. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. Dosages above 400 mg per day have not been studied.

Due to AstraZeneca's marketing exclusivity rights, this generic drug product is not labeled for pediatric use. Dosage and administration information in pediatric patients 6 years and older is approved for AstraZeneca's metoprolol succinate extended-release tablets.

Angina Pectoris

The dosage of metoprolol succinate extended-release tablets should be individualized. The usual initial dosage is 100 mg daily, given in a single dose. The dosage may be gradually increased at weekly intervals until optimum clinical response has been obtained or there is a pronounced slowing of the heart rate. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, the dosage should be reduced gradually over a period of 1 to 2 weeks (see WARNINGS).

Heart Failure

Dosage must be individualized and closely monitored during up-titration. Prior to initiation of metoprolol succinate extended-release tablets, the dosing of diuretics, ACE inhibitors, and digitalis (if used) should be stabilized. The recommended starting dose of metoprolol succinate extended-release tablets is 25 mg once daily for two weeks in patients with NYHA Class II heart failure and 12.5 mg once daily in patients with more severe heart failure. The dose should then be doubled every two weeks to the highest dosage level tolerated by the patient or up to 200 mg of metoprolol succinate extended-release tablets. If transient worsening of heart failure occurs, it may be treated with increased doses of diuretics, and it may also be necessary to lower the dose of metoprolol succinate extended-release tablets or temporarily discontinue it. The dose of metoprolol succinate extended-release tablets should not be increased until symptoms of worsening heart failure have been stabilized. Initial difficulty with titration should not preclude later attempts to introduce metoprolol succinate extended-release tablets. If heart failure patients experience symptomatic bradycardia, the dose of metoprolol succinate extended-release tablets should be reduced.
Metoprolol Succinate

Metoprolol Succinate

Metoprolol succinate extended-release tablets are intended for once daily administration. For treatment of hypertension and angina, when switching from immediate-release metoprolol to metoprolol succinate extended-release tablets, the same total daily dose of metoprolol succinate extended-release tablets should be used. Dosages of metoprolol succinate extended-release tablets should be individualized and titration may be needed in some patients.

Metoprolol succinate extended-release tablets are scored and can be divided; however, the whole or half tablet should be swallowed whole and not chewed or crushed.

Hypertension

The usual initial dosage is 25 to 100 mg daily in a single dose, whether used alone or added to a diuretic. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. Dosages above 400 mg per day have not been studied.

Due to AstraZeneca's marketing exclusivity rights, this generic drug product is not labeled for pediatric use. Dosage and administration information in pediatric patients 6 years and older is approved for AstraZeneca's metoprolol succinate extended-release tablets.

Angina Pectoris

The dosage of metoprolol succinate extended-release tablets should be individualized. The usual initial dosage is 100 mg daily, given in a single dose. The dosage may be gradually increased at weekly intervals until optimum clinical response has been obtained or there is a pronounced slowing of the heart rate. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, the dosage should be reduced gradually over a period of 1 to 2 weeks (see WARNINGS).

Heart Failure

Dosage must be individualized and closely monitored during up-titration. Prior to initiation of metoprolol succinate extended-release tablets, the dosing of diuretics, ACE inhibitors, and digitalis (if used) should be stabilized. The recommended starting dose of metoprolol succinate extended-release tablets is 25 mg once daily for two weeks in patients with NYHA Class II heart failure and 12.5 mg once daily in patients with more severe heart failure. The dose should then be doubled every two weeks to the highest dosage level tolerated by the patient or up to 200 mg of metoprolol succinate extended-release tablets. If transient worsening of heart failure occurs, it may be treated with increased doses of diuretics, and it may also be necessary to lower the dose of metoprolol succinate extended-release tablets or temporarily discontinue it. The dose of metoprolol succinate extended-release tablets should not be increased until symptoms of worsening heart failure have been stabilized. Initial difficulty with titration should not preclude later attempts to introduce metoprolol succinate extended-release tablets. If heart failure patients experience symptomatic bradycardia, the dose of metoprolol succinate extended-release tablets should be reduced.
Prednisolone Syrup

Prednisolone Syrup

Dosage of prednisolone syrup should be individualized according to the severity of the disease and the response of the patient. For infants and children, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight.

Hormone therapy is an adjunct to and not a replacement for conventional therapy. Dosage should be decreased or discontinued gradually when the drug has been administered for more than a few days.

The severity, prognosis, expected duration of the disease, and the reaction of the patient to medication are primary factors in determining dosage. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued.

Blood pressure, body weight, routine laboratory studies, including two-hour postprandial blood glucose and serum potassium, and a chest X-ray should be obtained at regular intervals during prolonged therapy. Upper GI X-rays are desirable in patients with known or suspected peptic ulcer disease.

The initial dosage of prednisolone syrup 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, prednisolone syrup 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 decrements 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 prednisolone syrup for a period of time consistent with the patient’s condition. If after longterm therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
Morphine Sulfate

Morphine Sulfate

(See also CLINICAL PHARMACOLOGY, WARNINGS, and PRECAUTIONS sections)

MORPHINE SULFATE EXTENDED-RELEASE TABLETS ARE AN OPIOID AGONIST AND A SCHEDULE II CONTROLLED SUBSTANCE WITH AN ABUSE LIABILITY SIMILAR TO OTHER OPIOID AGONISTS. MORPHINE AND OTHER OPIOIDS USED IN ANALGESIA CAN BE ABUSED AND ARE SUBJECT TO CRIMINAL DIVERSION.

MORPHINE SULFATE EXTENDED-RELEASE TABLETS ARE TO BE SWALLOWED WHOLE, AND ARE NOT TO BE BROKEN, CHEWED, DISSOLVED, OR CRUSHED. TAKING BROKEN, CHEWED, DISSOLVED, OR CRUSHED MORPHINE SULFATE EXTENDED-RELEASE TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE.

Physicians should individualize treatment in every case, initiating therapy at the appropriate point along a progression from non-opioid analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen to opioids in a plan of pain management such as those outlined by the World Health Organization, the Federation of State Medical Boards Model Guidelines, or the American Pain Society. Healthcare professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring (see BOXED WARNING).

Morphine sulfate extended-release tablets are a controlled-release oral formulation of morphine sulfate indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time. The controlled-release nature of the formulation allows it to be administered on a more convenient schedule than conventional immediate-release oral morphine products (see CLINICAL PHARMACOLOGY;Pharmacokinetics and Metabolism). However, morphine sulfate extended-release tablets do not release morphine continuously over the course of a dosing interval. The administration of single doses of morphine sulfate extended-release tablets on a q12h dosing schedule will result in higher peak and lower trough plasma levels than those that occur when an identical daily dose of morphine is administered using conventional oral formulations on a q4h regimen. The clinical significance of greater fluctuations in morphine plasma level has not been systematically evaluated.

As with any potent opioid drug product, it is critical to adjust the dosing regimen for each patient individually, taking into account the patient’s prior opioid and non-opioid analgesic treatment experience. Although it is clearly impossible to enumerate every consideration that is important to the selection of initial dose and dosing interval of morphine sulfate extended-release tablets, attention should be given to 1) the daily dose, potency, and precise characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist/antagonist), 2) the reliability of the relative potency estimate used to calculate the dose of morphine needed [N.B. potency estimates may vary with the route of administration], 3) the degree of opioid tolerance, if any, and 4) the general condition and medical status of the patient.

The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions in the management of the pain of an individual patient.

During periods of changing analgesic requirements including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family.

Conversion from Immediate-Release Oral Morphine to Morphine Sulfate Extended-Release Tablets

A patient’s daily morphine requirement is established using immediate-release oral morphine (dosing every 4 to 6 hours). The patient is then converted to morphine sulfate extended-release tablets in either of two ways: 1) by administering one-half of the patient’s 24-hour requirement as morphine sulfate extended-release tablets on an every 12-hour schedule; or, 2) by administering one-third of the patient’s daily requirement as morphine sulfate extended-release tablets on an every eight hour schedule. With either method, dose and dosing interval is then adjusted as needed (see discussion below). The 15 mg tablet should be used for initial conversion for patients whose total daily requirement is expected to be less than 60 mg. The 30 mg tablet strength is recommended for patients with a daily morphine requirement of 60 mg to 120 mg. When the total daily dose is expected to be greater than 120 mg, the appropriate combination of tablet strengths should be employed.

Conversion from Parenteral Morphine or Other Opioids (Parenteral or Oral) to Morphine Sulfate Extended-Release Tablets

Morphine sulfate extended-release tablets can be administered as the initial oral morphine drug product; in this case, however, particular care must be exercised in the conversion process. Because of uncertainty about, and intersubject variation in, relative estimates of opioid potency and cross tolerance, initial dosing regimens should be conservative. It is better to underestimate the 24-hour oral morphine requirement than to overestimate. To this end, initial individual doses of morphine sulfate extended-release tablets should be estimated conservatively. In patients whose daily morphine requirements are expected to be less than or equal to 120 mg per day, the 30 mg tablet strength is recommended for the initial titration period. Once a stable dose regimen is reached, the patient can be converted to the 60 mg or 100 mg tablet strength, or an appropriate combination of tablet strengths, if desired.

Estimates of the relative potency of opioids are only approximate and are influenced by route of administration, individual patient differences, and possibly, by an individual’s medical condition. Consequently, it is difficult to recommend any fixed rule for converting a patient to morphine sulfate extended-release tablets directly. The following general points should be considered, however.
Parenteral to Oral Morphine Ratio: Estimates of the oral to parenteral potency of morphine vary. Some authorities suggest that a dose of oral morphine only three times the daily parenteral morphine requirement may be sufficient in chronic use settings. Other Parenteral or Oral Opioids to Oral Morphine: Because there is lack of systematic evidence bearing on these types of analgesic substitutions, specific recommendations are not possible.
Physicians are advised to refer to published relative potency data, keeping in mind that such ratios are only approximate. In general, it is safer to underestimate the daily dose of morphine sulfate extended-release tablets required and rely upon ad hoc supplementation to deal with inadequate analgesia (see discussion which follows).

Use of Morphine Sulfate Extended-Release Tablets as the First Opioid Analgesic

There has been no systematic evaluation of morphine sulfate extended-release tablets as an initial opioid analgesic in the management of pain. Because it may be more difficult to titrate a patient using a controlled-release morphine, it is ordinarily advisable to begin treatment using an immediate-release formulation (see Special Instructions for Morphine Sulfate Extended-Release 100 mg and 200 mg Tablets).

Considerations in the Adjustment of Dosing Regimens

Whatever the approach, if signs of excessive opioid effects are observed early in a dosing interval, the next dose should be reduced. If this adjustment leads to inadequate analgesia, that is, “breakthrough” pain occurs late in the dosing interval, the dosing interval may be shortened. Alternatively, a supplemental dose of a short-acting analgesic may be given. As experience is gained, adjustments can be made to obtain an appropriate balance between pain relief, opioid side effects, and the convenience of the dosing schedule.

In adjusting dosing requirements, it is recommended that the dosing interval never be extended beyond 12 hours because the administration of very large single doses may lead to acute overdose. (N.B. Morphine sulfate extended-release tablets are a controlled-release formulation; it does not release morphine continuously over the dosing interval.)

For patients with low daily morphine requirements, the 15 mg tablet should be used.

Special Instructions for Morphine Sulfate Extended-Release 100 mg and 200 mg Tablets

(For use in opioid-tolerant patients only.)

Morphine sulfate extended-release 100 mg and 200 mg tablets are for use only in opioid-tolerant patients requiring daily morphine equivalent dosages of 200 mg or more for the 100 mg tablet and 400 mg or more for the 200 mg tablet. It is recommended that these strengths be reserved for patients that have already been titrated to a stable analgesic regimen using lower strengths of morphine sulfate extended-release tablets or other opioids.

Supplemental Analgesia

Most patients given around-the-clock therapy with controlled-release opioids may need to have immediate-release medication available for exacerbations of pain or to prevent pain that occurs predictably during certain patient activities (including incident pain).

Continuation of Therapy

The intent of the titration period is to establish a patient-specific daily dose that will provide adequate analgesia with acceptable side effects and minimal rescue doses (2 or less) for as long as pain relief is necessary. Should pain recur, the dose can be increased to re-establish pain control as outlined above. During chronic, around-the-clock opioid therapy, especially for non-cancer pain syndromes, the continued need for around-the-clock opioid therapy should be reassessed periodically (e.g., every 6 to 12 months) as appropriate.

Cessation of Therapy

When the patient no longer requires therapy with morphine sulfate extended-release tablets, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

Conversion from Morphine Sulfate Extended-Release Tablets to Parenteral Opioids

When converting a patient from morphine sulfate extended-release tablets to parenteral opioids, it is best to assume that the parenteral to oral potency is high. NOTE THAT THIS IS THE CONVERSE OF THE STRATEGY USED WHEN THE DIRECTION OF CONVERSION IS FROM THE PARENTERAL TO ORAL FORMULATIONS. IN BOTH CASES, HOWEVER, THE AIM IS TO ESTIMATE THE NEW DOSE CONSERVATIVELY. For example, to estimate the required 24-hour dose of morphine for IM use, one could employ a conversion of 1 mg of morphine IM for every 6 mg of morphine as morphine sulfate extended-release tablets. The IM 24-hour dose would have to be divided by six and administered on a q4h regimen. This approach is recommended because it is least likely to cause overdose.

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Ethex Corporation Drugs