Morphine/ Papaverine/ Codeine

Registered South African indications:

• Pre- and post-operative analgesia
• Severe pain
• Cardiac asthma
• Pulmonary oedema
• Coronary occlusion
• Pulmonary embolism

Contraindications

• Hypersensitivity to the active ingredient or to any of the excipients in this combination product
• Patients with a history of idiosyncratic response to opium alkaloids
• Respiratory depression, obstructive airway disease and in comatose patients
• Severe, acute asthma attack
• Acute alcoholism, convulsive disorders, head injuries and conditions in which intracranial pressure is raised
• Biliary colic
• Heart failure secondary to lung disease
• Phaeochromocytoma
• Risk of paralytic ileus
• Coadministration with monoamine oxidase inhibitors (including moclobemide) or within 14 days of stopping such treatment
• Intravenous administration of morphine/ papaverine/ codeine is contraindicated in patients with complete atrioventricular block

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment
• Elderly
• Glaucoma
• Asthma or decreased respiratory reserve
• Hypothyroidism
• Adrenocortical insufficiency
• Hypotension
• Shock
• Inflammatory bowel disorders
• Biliary disorders
• Risk of paralytic ileus
• Urethral disease or prostatic hypertrophy
• Myasthenia gravis
• Convulsive disorders
• Delirium tremens
• History of substance abuse
• Abuse potential or dependence
• Respiratory depression
• Head injury
• Hypovolaemia
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Pre- and post-operative analgesia
Severe or intractable pain
Cardiac asthma
Pulmonary oedema
Coronary occlusion
Pulmonary embolism

Morphine/ Papaverine/ Codeine
13.44/1.20/1.04 (mg/ml)

• IM/SC: 0.5-1ml, 4hrly

Paed. forms avail. in SA and covered in this monograph: inj

Pre- and post-operative analgesia
Severe or intractable pain

Morphine/ Papaverine/ Codeine
13.44/1.20/1.04 (mg/ml)

• Younger than 1 year: Not established for use
• Between 1-12 years: IM/SC: 0.01-0.015ml/kg, as a single dose
• Older than 12 years: See adult dosage

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• Caution
• This product is not recommended during pregnancy and labour due to the risk of neonatal respiratory depression. Prolonged use of this product during pregnancy can result in neonatal opioid withdrawal syndrome

Breastfeeding

• Contraindicated (Codeine)
• If the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolite of codeine, morphine, may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant, which may be fatal

Fertility

• Effects of morphine exposure on sexual maturation of male rats, their reproductive capacity and the development of their progeny have been examined. Results indicated that exposure during adolescence led to pronounced inhibition of several indices of sexual maturation (e.g. hormone levels, reduced gonad weights), smaller litters and selective gender-specific effects on endocrine function in the offspring
• Animal studies have shown that morphine may reduce fertility
• A disruption in ovulation and amenorrhoea can occur in women given morphine

Renal Impairment

• Caution; dose adjustment recommended (Morphine,Codeine)

Hepatic Impairment

• Contraindicated (Codeine)

Elderly

• Caution; dose adjustment recommended (Morphine)

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Prohibited - In competition

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Morphine
Central Nervous System Disorders

• Confusion
• Insomnia
• Agitation
• Euphoria
• Hallucinations
• Mood altered
• Drug dependence
• Dysphoria
• Thinking disturbances
• Restlessness
• Headache
• Involuntary muscle contractions
• Somnolence
• Dizziness
• Convulsions
• Hypertonia
• Myoclonus
• Paraesthesia
• Syncope
• Raised intracranial pressure
• Coma
• Hyperalgesia
• Hyperaesthesia
• Drug tolerance
• Drug withdrawal syndrome

Cardiovascular Disorders

• Palpitations
• Bradycardia
• Tachycardia
• Facial flushing
• Hypotension
• Circulatory failure
• Hypertension

Respiratory Disorders

• Bronchospasm
• Pulmonary oedema
• Respiratory depression

Gastrointestinal Disorders

• Constipation
• Nausea and vomiting
• Abdominal pain
• Anorexia
• Dry mouth
• Dyspepsia
• Taste perversion
• Narcotic bowel syndrome

Hepatobiliary Disorders

• Increased hepatic enzymes
• Exacerbation of pancreatitis
• Biliary pain

Genitourinary Disorders

• Amenorrhea
• Decreased libido
• Erectile dysfunction
• Urinary retention
• Ureteric spasm
• Dysuria

Endocrine and Metabolic Disorders

• Hypothermia

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Rash
• Urticaria
• Pruritis

Immune, Blood and Lymphatic System Disorders

• Allergic reaction
• Anaphylactic reaction

Sensory Disorders

• Visual disturbance
• Mitosis
• Vertigo

Papavarine
Central Nervous System Disorders

• Headache
• Malaise
• Sedation
• Vertigo

Cardiovascular Disorders

• Arrhythmia
• Flushing
• Hypertension
• Tachycardia

Respiratory Disorders

• Apnoea

Gastrointestinal Disorders

• Abdominal distress
• Anorexia
• Constipation
• Diarrhoea
• Nausea

Hepatobiliary Disorders

• Hepatic cirrhosis

Skin and Subcutaneous Tissue Disorders

• Diaphoresis
• Skin rash
• Hypersensitivity

Codeine
Central Nervous System Disorders

• Hallucinations
• Altered mood
• Restlessness
• Confusion
• Dependance
• Somnolence
• Headache
• Seizures
• Dysphoria
• Euphoria
• Hyperalgesia
• Dizziness

Cardiovascular Disorders

• Bradycardia
• Palpitations
• Tachycardia
• Flushing
• Orthostatic hypotension
• Oedema

Respiratory Disorders

• Respiratory depression

Gastrointestinal Disorders

• Constipation
• Dry mouth
• Nausea and vomiting
• Abdominal pain
• Anorexia
• Pancreatitis

Hepatobiliary Disorders

• Biliary colic

Genitourinary Disorders

• Sexual dysfunction
• Dysuria
• Ureteral spasm
• Urinary retention

Endocrine and Metabolic Disorders

• Amenorrhoea

Musculoskeletal Disorders

• Muscle rigidity
• Muscle fasciculation

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Rash
• Urticaria
• Pruritus

Sensory Disorders

• Miosis
• Vertigo

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Morphine

• Alcohol
• Antiarrhythmics
• Antibacterials
• Antidepressants
• Anxiolytics
• Hypnotic
• Antipsychotics
• Antidiarrhoeal agents
• Antiperistaltic agents
• Antimuscarinics
• Metoclopramide
• Domperidone
• Monoamine oxidase inhibitors
• Cimetidine
• Mixed agonist/antagonist opioid analgesics
• Rifampicin
• Diuretics
• Propranolol

Papavarine

• No information available

Codeine

• Central nervous system depressants
• Nefopam
• Carbamazepine
• Rifampicin
• Quinidine
• Secobarbital

None routine. Specific cases may require

• Vital signs
• Renal function
• Hepatic function
• Respiratory function

Morphine
Morphine is a potent analgesic with competitive agonist actions at opioid receptors, predominantly the mu receptor

Papaverine
Papaverine is a smooth muscle spasmolytic producing generalized smooth muscle relaxation, likely due to the inhibition of cyclic nucleotide phosphodiesterase, which increases cyclic AMP. This results in vasodilatation, gastrointestinal sphincter relaxation, bronchiolar muscle relaxation, and potentially a depressed myocardium

Codeine
Codeine is a centrally acting weak analgesic. Codeine exerts its effects though mu opioid receptors. Its analgesic effect is due to its conversion to morphine

COMBINATION PREPARATIONS

Morphine/ Papaverine/ Codeine

Injection (per ml) 13.44/1.20/1.04mg

• Omnopon-Fresenius (Bodene) originator