Substitol Uses

• Substitol indications
• Uses of Substitol in details
• Substitol description
• Substitol dosage
• Substitol interactions
• Substitol side effects
• Substitol contraindications

What is Substitol?

Substitol is an opioid pain medication. An opioid is sometimes called a narcotic.

Substitol is used to treat moderate to severe pain. Short-acting Substitol is taken as needed for pain.

The extended-release form of this medicine is for around-the-clock treatment of pain. This form of Substitol is not for use on an as-needed basis for pain.

Substitol is not for treating short-term pain just after surgery unless you were already taking Substitol before the surgery.

Substitol may also be used for purposes not listed in this medication guide.

Substitol indications

Substitol is indicated for the relief of severe pain. It is used preoperatively to sedate the patient and allay apprehension, facilitate anesthesia induction and reduce anesthetic dosage. It is likewise effective in the control of postoperative pain.

The use of Substitol for the relief of pain should be reserved for the more severe manifestations of pain, as in myocardial infarction, severe injuries, or in severe chronic pain associated with terminal cancer after all non-narcotic analgesics have failed.

Effective analgesic therapy of severe chronic pain associated with terminal cancer continues to be a difficult problem. Intermittent administration of intramuscular Substitol may be effective; however, the mode of therapy has significant limitations. Substitol has a short plasma half-life of 2.5 to 3.0 hours; therefore, frequent administration (every 1 to 2 hours) often becomes necessary to control severe pain associated with cancer. Tolerance develops to the analgesic effects and increasingly higher doses of Substitol are required to produce analgesia. The higher Substitol doses produce significant and often lifethreatening side effects. The peak and trough effects produced by intermittent administration cause fluctuations in pain control. Repeated IM injections are frequently unacceptable due to the lack of muscle mass in the debilitated patient, the tendency for bruising and bleeding at the injection site, and the anxiety and pain associated with the injection.

Continuous IV infusion of Substitol has been employed as an alternative to traditional modes of administration. Lower doses of Substitol produce uniform pain control because a steady Substitol concentration is maintained. Titration of the dosage to the patient’s needs is easily achieved by adjusting the infusion rate. The lag time between the patient’s request for pain medication and administration of the dose and the amount of nursing time necessary for preparation and administration of frequent doses are reduced. The degree of respiratory depression and sedation may be decreased, and the anxiety experienced by the patient in anticipation of IM administration is avoided. Some Investigators feel that tolerance to the analgesic effects may develop more slowly with continuous IV infusion.

In addition to analgesia, the drug may relieve anxiety and reduce left ventricular work by reducing preload pressure. Substitol is also used in the therapy of dyspnea associated with acute left ventricular and pulmonary edema. Care must be taken to avoid inducing respiratory depression in such patients.

For open-heart surgery, especially in high risk patients with cardiac disease, some anesthesiologists use Substitol to produce anesthesia.

How should I use Substitol?

Use Substitol extended-release capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Substitol extended-release capsules by mouth with or without food.
• Swallow Substitol extended-release capsules whole. Do not crush, chew, or dissolve Substitol extended-release capsules before swallowing. If you cannot swallow the capsule whole, you may open it and sprinkle the contents over a spoonful of applesauce. Mix the medicine with the applesauce and swallow the mixture right away, followed by a glass of water. Do not crush or chew the medicine before swallowing. Do not store the mixture for future use.
• Take Substitol extended-release capsules on a regular schedule to get the most benefit from it. Do not take doses of Substitol extended-release capsules closer than 12 hours apart.
• Continue to take Substitol extended-release capsules even if you feel well. Do not miss any doses.
• Do not suddenly stop taking Substitol extended-release capsules. You may have an increased risk of withdrawal symptoms (eg, anxiety, stomach cramps). If you need to stop Substitol extended-release capsules or add a new medicine, your doctor will gradually lower your dose.
• If Substitol extended-release capsules is no longer needed, dispose of it as soon as possible. Ask your doctor or pharmacist how to dispose of Substitol extended-release capsules properly.
• If you miss a dose of Substitol extended-release capsules, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Substitol extended-release capsules.

Uses of Substitol in details

This medication is used to help relieve severe ongoing pain (such as due to cancer). Substitol belongs to a class of drugs known as opioid (narcotic) analgesics. It works in the brain to change how your body feels and responds to pain.

The higher strengths of this drug (100 milligrams per capsule and higher) should be used only if you have been regularly taking moderate to large amounts of an opioid pain medication. These strengths may cause overdose (even death) if taken by a person who has not been regularly taking opioids.

Do not use the sustained-action form of Substitol to relieve pain that is mild or that will go away in a few days. This medication is not for occasional ("as needed") use.

How to use Substitol

Read the Medication Guide provided by your pharmacist before you start using Substitol and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication on a regular schedule as directed by your doctor, not as needed for sudden (breakthrough) pain. Take this drug with or without food, usually once or twice daily (every 12 or 24 hours). If you have nausea, it may help to take this drug with food. Ask your doctor or pharmacist about other ways to decrease nausea (such as lying down for 1 to 2 hours with as little head movement as possible).

Swallow the capsules whole. Adults who have trouble swallowing the capsule may open the capsule and carefully sprinkle its contents on a spoonful of soft, cool applesauce. Swallow all of the drug/food mixture right away without chewing. Then rinse your mouth and swallow the rinse liquid to make sure that you have swallowed all of the dose. Do not chew the mixture or prepare a supply in advance. Do not give this medication to a child this way, since they might chew the mixture and overdose. For children who have trouble swallowing the capsule, ask the doctor about using a different form of Substitol instead.

The dosage is based on your medical condition and response to treatment. Do not increase your dose, take the medication more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.

If you are giving this medication through a certain tube into the stomach (gastric tube), ask your health care professional for detailed instructions on how to give it.

Before you start taking this medication, ask your doctor or pharmacist if you should stop or change how you use your other opioid medication(s). Other pain relievers (such as acetaminophen, ibuprofen) may also be prescribed. Ask your doctor or pharmacist about using Substitol safely with other drugs.

This medication may cause withdrawal reactions, especially if it has been used regularly for a long time or in high doses. In such cases, withdrawal symptoms (such as restlessness, watering eyes, runny nose, nausea, sweating, muscle aches) may occur if you suddenly stop using this medication. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Ask your doctor or pharmacist for more details, and report any withdrawal reactions right away.

When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.

Along with its benefits, this medication may rarely cause abnormal drug-seeking behavior (addiction). This risk may be increased if you have abused alcohol or drugs in the past. Take this medication exactly as prescribed to lessen the risk of addiction.

Tell your doctor if your pain persists or worsens.

Substitol description

The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Substitol Extra-Forte has widespread effects in the central nervous system and on smooth muscle.

Substitol dosage

Substitol tablets should be used twice daily, at 12-hrly intervals. The dosage is dependent upon the severity of the pain, the patient's age and previous history of analgesic requirements.

A patient presenting with severe pain should normally be started on a dosage of 1 or 2 Substitol tablets 10 mg twice daily.

Persisting or increasing severity of pain will require increased dosage of Substitol tablets using 10-mg, 30-mg and 60-mg tablets alone or in combination to achieve the desired pain relief. Increases of the dosage should be made in 25-50% increments.

A patient transferred from immediate-release oral Substitol preparations should normally receive the same total 24-hr Substitol dosage divided between morning and evening administration.

Patients receiving Substitol tablets in place of parenteral Substitol should be given a sufficiently increased dosage to compensate for any reduction in analgesic effects associated with oral administration. Usually such increased requirement is of the order of 50-100%. In such patients, individual dose adjustments are required.

Postoperative Pain: Substitol tablets are not recommended in the first 24 hrs postoperatively; thereafter it is suggested that the following dosage schedule be observed at the physician's discretion: a) Substitol tablets 20 mg 12-hrly to patients <70 kg. b) Substitol tablets 30 mg 12-hrly to patients >70 kg.

Supplemental parenteral Substitol may be given if required but with careful attention to the total dosage of Substitol and bearing in mind the prolonged effects of Substitol in the Substitol formulation.

As with oral Substitol preparations, Substitol tablets should be used with caution postoperatively and particularly in "acute abdomen" and following abdominal surgery.

Transferability: It is not possible to ensure bioequivalence between different prolonged-release Substitol products. Therefore, it should be emphasized that patients, once titrated to an effective dose, should not be changed from Substitol tablet to other slow, sustained-release or prolonged-release Substitol preparations without re-titration and clinical assessment.

Administration: Substitol tablets must be swallowed whole and not chewed.

Substitol interactions

See also:
What other drugs will affect Substitol?

Substitol sulphate potentiates the effects of tranquilizers, general anesthetics, phenothiazines, other CNS depressant including hypnotics or sedatives, alcohol, muscle relaxants, antihypertensives and gabapentin. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these drugs are taken in combination with the usual doses of Substitol sulphate.

Substitol sulphate should not be co-administered with monoamine oxidase inhibitors (MAOIs) or within 2 weeks of such therapy.

Medicinal products that block the action of acetylcholine ie, antihistamines, anti-parkinsons and anti-emetics, may interact with Substitol sulphate to potentiate anticholinergic adverse events.

Cimetidine inhibits the metabolism of Substitol sulphate.

Plasma concentrations of Substitol sulphate may be reduced by rifampicin.

Although there are no pharmacokinetic data available for concomitant use of ritonavir with Substitol sulphate, ritonavir induces the hepatic enzymes responsible for glucuronidation of Substitol sulphate, and may possibly decrease plasma concentrations of Substitol sulphate.

Substitol side effects

See also:
What are the possible side effects of Substitol?

The most serious adverse experience encountered during administration of Substitol (Substitol injection) is respiratory depression and/or respiratory arrest. This depression and/or respiratory arrest may be severe and could require intervention. Because of delay in maximum CNS effect with intravenously administered drug (30 min), rapid administration may result in overdosing. Single-dose neuraxial administration may result in acute or delayed respiratory depression for periods at least as long as 24 hours.

Tolerance and Myoclonus

While low doses of intravenously administered Substitol have little effect on cardiovascular stability, high doses are excitatory, resulting from sympathetic hyperactivity and increase in circulating catecholamines. Excitation of the central nervous system, resulting in convulsions, may accompany high doses of Substitol given intravenously. Dysphoric reactions may occur after any size dose and toxic psychoses have been reported.

Pruritus

Single-dose epidural or intrathecal administration is accompanied by a high incidence of pruritus that is dose-related but not confined to the site of administration. Pruritus, following continuous infusion of epidural or intrathecal Substitol, is occasionally reported in the literature; these reactions are poorly understood as to their cause.

Urinary Retention

Urinary retention, which may persist 10 to 20 hours following single epidural or intrathecal administration, is a frequent side effect and must be anticipated primarily in male patients, with a somewhat lower incidence in females. Also frequently reported in the literature is the occurrence of urinary retention during the first several days of hospitalization for the initiation of continuous intrathecal or epidural Substitol therapy. Patients who develop urinary retention have responded to cholinomimetic treatment and/or judicious use of catheters.

Constipation

Constipation is frequently encountered during continuous infusion of Substitol; this can usually be managed by conventional therapy.

Headache

Lumbar puncture-type headache is encountered in a significant minority of cases for several days following intrathecal catheter implantation; this, generally, responds to bed rest and/or other conventional therapy.

Other

Other adverse experiences reported following Substitol therapy include—Dizziness, euphoria, anxiety, hypotension, confusion, reduced male potency, decreased libido in men and women, and menstrual irregularities including amenorrhea, depression of cough reflex, interference with thermal regulation and oliguria. Evidence of histamine release such as urticaria, wheals and/or local tissue irritation may occur. Nausea and vomiting are frequently seen in patients following Substitol administration.

Pruritus, nausea/vomiting and urinary retention, if associated with continuous infusion therapy, may respond to intravenous administration of a low dose of naloxone (0.2 mg). The risks of using narcotic antagonists in patients chronically receiving narcotic therapy should be considered.

In general, side effects are amenable to reversal by narcotic antagonists.

Drug Abuse And Dependence

Controlled Substance

Substitol is a Schedule II narcotic under the United States Controlled Substance Act (21 U.S.C. 801-886).

Substitol is the most commonly cited prototype for narcotic substances that possess an addiction-forming or addiction-sustaining liability. A patient may be at risk for developing a dependence to Substitol if used improperly or for overly long periods of time. As with all potent opioids which are µ-agonists, tolerance as well as psychological and physical dependence to Substitol may develop irrespective of the route of administration (intravenous, intramuscular, intrathecal, epidural or oral). Individuals with a prior history of opioid or other substance abuse or dependence, being more apt to respond to the euphorogenic and reinforcing properties of Substitol, would be considered to be at greater risk.

Care must be taken to avert withdrawal in patients who have been maintained on parenteral/oral narcotics when epidural or intrathecal administration is considered. Withdrawal symptoms may occur when Substitol is discontinued abruptly or upon administration of a narcotic antagonist.

Substitol contraindications

See also:
What is the most important information I should know about Substitol?

Respiratory depression, head injury, paralytic ileus, biliary colic, delayed gastric emptying, obstructive airways disease, cardiac arrhythmias, known Substitol sensitivity, acute hepatic disease, concurrent administration of monoamine oxidase inhibitors (MAOIs) or within 2 weeks of discontinuation of their use.

Should paralytic ileus be suspected or occur during use, Substitol tablets should be discontinued immediately.

Substitol tablets are not recommended for paediatric use or in pregnancy.

Preoperative administration of Substitol tablets is not recommended and is not an approved indication.

Not recommended for preoperative use or for the first 24 hrs postoperatively.

Use in pregnancy & lactation: Use of Substitol should be avoided during pregnancy and labour due to risk of neonatal respiratory depression. Administration to nursing mothers is not recommended as Substitol is excreted in breast milk.

Withdrawal symptoms may be observed in the newborn of mothers undergoing chronic treatment.

Active ingredient matches for Substitol:

Morphine in Bulgaria, Slovenia.

Estradiol in Austria.

Morphine Sulfate

References

1. DailyMed. "MORPHINE SULFATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. DailyMed. "ESTRADIOL HEMIHYDRATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
3. PubChem. "estradiol". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).

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Information checked by Dr. Sachin Kumar, MD Pharmacology