Morphine

Introduction

Morphine is a strong painkiller. It's used to treat severe pain, for example, after an operation or a serious injury, or pain from cancer or a heart attack. It's also used for other types of long-standing pain when weaker painkillers no longer work. Morphine is available only on prescription.

Composition

One ml solution for injection contains 20.00 mg anhydrous morphine hydrochloride corresponding to 23.3530 mg morphine hydrochloride trihydrate and excipients: disodium monocalcic edetate, hydrochloric acid, water for injections.

Pharmacotherapeutic group: analgesics, natural opium alkaloids, morphine derivatives.

Morphine

Therapeutic indications

• Treatment of acute pain:
• post-operative pain.
• Acute pulmonary edema.
• Myocardial infarction (with caution): relative indication (hemodynamic effects are favorable, but hypotensive effects may be harmful).
• Rib fractures, tension pneumothorax, pulmonary infarction, aortic aneurysm: cases in which analgesic and antitussive action are necessary.

Treatment of chronic pain (especially neoplastic).

It is used especially in adults and in children (3 to 15 years old), in cases of extreme necessity.

Contraindications

• Hypersensitivity to morphine, to morphine derivatives, or any of the excipients.
• Asthma, bronchial stasis with bronchitis (antitussive effect and inhibition of ciliary motility make it difficult to eliminate expectoration).
• Decompensated respiratory failure (in the absence of assisted breathing). Severe hepatocellular insufficiency (with encephalopathy).
• Acute abdomen, pancreatitis, paralytic ileus.
• Ulcerohemorrhagic rectocolitis (may cause toxic dilation of the colon). Subocclusion and intestinal obstruction.
• Acute head injury with intracranial hypertension in the absence of assisted breathing. Therapeutic uncontrolled epilepsy.
• Concomitant treatment with buprenorphine, nalbuphine, and pentazocine. Hypotension due to hypovolemia, spinal cord injury, or endotoxin shock. Renal insufficiency.
• Prostate hypertrophy. Children under 3 years old.

Precautions

In the context of treating pain, increasing doses, even those that are already high, most often do not reveal an addictive process.

The patient's condition should be reassessed frequently for early detection of addictive behavior. This most often shows a real need for analgesia, which should not be confused with addictive behavior.

Morphine is a drug that can be addictive and used in the treatment of pain for purposes other than therapy: physical and mental addiction can also be observed, so tolerance (addiction) can develop with repeated administration. A history of drug addiction does not contraindicate the drug when necessary.

Depending on the duration of the treatment, the dose administered, and the evolution of the pain, the discontinuation of the morphine treatment should be done progressively to avoid the withdrawal syndrome. It consists of: anxiety, irritability, insomnia, yawning, chills, mydriasis, feeling hot, sweating, tearing, rhinorrhea, nausea, vomiting, anorexia, abdominal cramps, diarrhea, myalgia, arthralgia. It is recommended to monitor the intensity of pain, attention, and respiratory function during treatment. Drowsiness is a sign of respiratory decompensation.

Athletes should be aware that morphine may cause doping tests to be positive.

Morphine

Interaction

Agonists - morphine antagonists (buprenorphine, pentazocine, nalbuphine): the combination with morphine is contraindicated because it decreases the analgesic effect by competitively blocking the receptor's risk of withdrawal syndrome.

Alcohol: increases the sedative effects of morphine analgesics. Therefore, it is recommended to avoid consuming ethyl alcohol or medicines containing ethyl alcohol.

Rifampicin: Decreases plasma concentrations of morphine decreases the effectiveness of morphine and its active metabolite. Clinical supervision and, possibly, dose adjustment of morphine during rifampicin treatment and after discontinuation is recommended.

Trovafloxacin: Decreased bioavailability of trovafloxacin co-administered with morphine. Remote administration of morphine is recommended with trovafloxacin (preferably 2 hours later).

Other central nervous system depressants (morphine derivatives - analgesics and antitussives - sedative antidepressants, H1 sedative antihistamines, barbiturates or other hypnotics, benzodiazepines, and anxiolytics benzodiazepines, neuroleptics, clonidine, and derivatives): increases the depressant and central depressant effect.

Special warnings

Morphine should be used with caution in the following situations:

acute myocardial infarction (hemodynamic effects are favorable, but hypotensive effects can be harmful).

Hypovolemia: morphine can cause circulatory collapse. It is recommended to correct hypovolemia before treatment with morphine.

Renal failure: renal elimination of morphine, in the form of an active metabolite, requires the initiation of treatment with a low dose, adjusted during treatment. Doses and frequency of administration depend on the patient's clinical condition.

Etiological treatment: because the etiology of the pain is treated concomitantly, the doses of morphine must be adjusted according to the results of the applied treatment.

Respiratory failure: respiratory rate should be monitored frequently. Drowsiness is an alarm signal (respiratory decompensation). If other painkillers are associated with central action, the risk of sudden respiratory failure increases.

Hepatic impairment: caution is advised when administering morphine and clinical surveillance.

Elderly patients: their particular sensitivity to analgesic effects, but also to adverse reactions of a central type (confusion) or of a digestive nature, to which are frequently added alterations in renal function, urethro-prostatic pathology (risk of urinary retention), concomitant administration of antidepressants requires increased caution and dose reduction (especially halving the initial dose).

Constipation: this should be investigated and differentiated from an occlusive syndrome before and during treatment with morphine.

Intracranial hypertension: morphine in chronic painful conditions should be done with caution.

Boys

In general, children are poorly tolerant of morphine. Morphine can cause idiosyncratic reactions in some children at low doses, with paralysis of the respiratory centers.

Pregnancy and breastfeeding

Preclinical studies in pregnant women have shown that morphine use may be associated with malformative effects.

The available data did not reveal any malformative or fetotoxic effects of morphine in humans. However, when taking high doses even in short-term treatment at the end of pregnancy, respiratory depression may occur in the newborn. Naloxone can be used to treat possible respiratory depression in newborns.

Chronic use of morphine by the mother in the last 3 months of pregnancy can lead to a withdrawal syndrome in the newborn, manifested by irritability, vomiting, seizures, and death. Consequently, the use of morphine during pregnancy is recommended only in the absence of a therapeutic alternative and after evaluating the maternal therapeutic benefit / potential fetal risk ratio.

Because morphine is excreted in human milk, breastfeeding is not recommended during treatment.

Ability to drive or use machines

Impaired alertness, especially at the beginning of treatment and other central nervous system depressants, is contraindicated when driving or using machines during treatment with morphine.

Doses and method of administration

The dose-efficacy-tolerance ratio varies greatly from patient to patient. Therefore, it is very important to evaluate the efficacy and tolerance frequently and to adjust the dose progressively according to the patient's needs. The maximum dose should not be used to control side effects.

Treatment of acute pain:

Adults: the recommended dose is 0.25 - 0.5 ml solution for injection (5 - 10 mg morphine) every 4 to 6 hours, administered subcutaneously.

Children: the recommended dose is 0.1 - 0.2 mg morphine / Kg every 4 hours, not to exceed 0.75 ml solution for injection (15 mg morphine per dose).

Treatment of chronic pain:

By weight, the doses given to adults and children are equivalent. In patients who do not require oral treatment with morphine orally, the recommended starting dose is 0.5 mg morphine/kg/day (the usual adult dose is 30 mg morphine per day, given in 4 to 6 hours). In patients requiring pre-treatment with oral morphine, the initial daily dose for solution for injection should be half the oral dose.

Morphine

Dose adjustment:

• Frequency of evaluation (degree of pain relief, presence of side effects): do not insist on an ineffective dose. Therefore, the patient should be closely monitored, especially at the beginning of treatment, until the pain is no longer controlled.
• Increase the dose: if the pain is no longer controlled, the daily dose of morphine should be increased by about 30-50%. The maximum dose should not be reached to control side effects during dose adjustment.

Side effects

The most common side effects are drowsiness, nausea, vomiting, constipation, and dizziness at the recommended doses. In the case of chronic administration, constipation does not regress spontaneously and requires treatment. In contrast, drowsiness, nausea, and vomiting are generally transient, and their persistence requires investigation of an associated cause.

Other side effects:

• Addiction is the primary adverse reaction to the use of opioids. Includes: mental dependence, tolerance, physical dependence (appearance of withdrawal syndrome), phytotoxicity.
• Confusion, sedation, excitement, nightmares, especially in the elderly, with possible hallucinatory phenomena.
• Respiratory depression up to apnea.
• Increase in intracranial pressure.
• Dysuria and urinary retention are mainly due to prostate adenoma or urethral stenosis.
• Itching and redness at the site of administration.
• Withdrawal syndrome upon abrupt discontinuation of medication: nausea, anxiety, irritability, insomnia, chills, mydriasis, heat, hyperhidrosis, tearing, rhinorrhea, nausea, vomiting, anorexia, abdominal cramps, diarrhea, myalgia, arthralgia.
• Tachycardia, hypotension, vertigo, headache, the tendency to lipothymia.
• Very rarely, leukopenia thrombocytopenia may occur.
• Libido disorders.

Overdose Symptoms :

• Respiratory depression can be very severe by decreased respiratory volume, bronchospasm, and decreased respiratory rate; respiratory rhythm may become irregular (Cheyne-Stokes rhythm); bradypnea worsens to the point of stopping breathing. Drowsiness is an early sign of respiratory depression.
• Hypotension, bradycardia, and atrioventricular conduction depression.
• Depression of the thermoregulation center, with a tendency to hypothermia.
• Miosis, agitation, confusion, hallucinations, delusions, cardio-respiratory arrest.

Treatment :

Emergency treatment involves assisting with respiratory and cardiac function. Specific treatment consists of intravenous infusion of naloxone; The severity of the symptoms determines the dose of naloxone.

Storage

Please do not use it after the expiry date stated on the pack. Store below 25 ° C in the original package. Keep out of reach of children.

Packaging

Box of 5 clear glass ampoules with a 1 ml rupture solution for injection. Box of 10 clear glass ampoules with a 1 ml rupture solution for injection.