Source: Health Products Regulatory Authority (ZA) Publisher: PHARMACARE LIMITED, Healthcare Park, Woodlands Drive, Woodmead 2191
STILPANE is contraindicated in:
COMPOSITION).
STILPANE contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or Poison Centre must be contacted immediately.
Codeine phosphate: Exceeding the prescribed dose together with the prolonged continuous use of STILPANE may lead to dependency and addiction (see DOSAGE AND DIRECTIONS FOR USE).
STILPANE should not be used for periods longer than 5 days.
Patients receiving meprobamate as contained in STILPANE should be warned that their tolerance to ingested alcohol and other depressants of the central nervous system may be lowered with consequent impairment of judgment and co-ordination.
STILPANE should be avoided in elderly and debilitated patients and in those with mental depression. STILPANE should be used with caution in patients with impaired hepatic or renal function, and as with all sedatives, in patients with impaired respiratory functions. Symptoms of porphyria may be exacerbated (see CONTRAINDICATIONS).
There is a serious dependence risk with a typical withdrawal syndrome.
Meprobamate may induce the hepatic microsomal enzymes involved in medicine metabolism: the metabolism of agents such as oral contraceptives, corticosteroids, phenytoin, phenothiazines, and tricyclic antidepressants may be enhanced if given concurrently (see INTERACTIONS and CONTRAINDICATIONS).
Codeine should be given with caution to patients with hypothyroidism, adrenocortical insufficiency, asthma, impaired liver function, prostatic hypertrophy, hypotension or shock. It should be used with caution in patients with inflammatory or obstructive bowel disorders, and myasthenia gravis.
Administration of STILPANE during labour may cause respiratory depression in the new-born infant.
The depressant effects of codeine are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics and sedatives, and phenothiazines (see INTERACTIONS).
The prolonged use of high doses of codeine has produced dependence of the morphine type.
Depending on the genetic variability of CYP2D6, the individual metabolizing capacity for codeine may vary. Even therapeutic doses can lead to increased formation of the active metabolite morphine resulting in clinical signs of morphine intoxication (see KNOWN SYMPTOMS OF OVERDOSAGE and SIDE EFFECTS of Codeine).
Paracetamol dosages in excess of those recommended may cause severe liver damage. Prolonged excessive use can cause irreversible kidney damage.
Dosages in excess of those recommended may cause severe liver damage. Patients suffering from liver or kidney disease should take STILPANE under medical supervision. Consult your doctor if no relief is obtained from the recommended dosage. STILPANE should be given with care to patients taking other medicines that affect the liver, e.g. barbiturates (see KNOWN SYMPTOMS OF OVERDOSAGE).
Caffeine should be given with caution to patients with peptic ulceration, hyperthyroidism, hypertension, epilepsy, cardiac dysrhythmias, or other cardiovascular disease as these conditions may be exacerbated. Caffeine should also be given with caution to patients with heart failure, hepatic dysfunction, chronic alcoholism, acute febrile illness, neonates and elderly, since in all of these circumstances the clearance may be decreased resulting in increases in serum concentrations of caffeine and serum half-life.
Severe overdosage or idiosyncrasy due to caffeine may lead to agitation, diuresis, repeated vomiting with extreme thirst, delirium, hyperthermia, cardiac dysrhythmias including tachycardia, electrolyte disturbances, convulsions and death.
Caffeine undergoes extensive metabolism by hepatic microsomal cytochrome P450 isoenzyme CYP1A2, and is subject to interactions with other medicines which enhance or reduce its metabolic clearance.
Alcohol: Caffeine and alcohol causes a synergistic interaction which further increases reaction time.
Antidysrhythmics: Mexiletine reduces the elimination of caffeine. Lidocaine, flecainide and tocainide have no effect on caffeine elimination.
Antibacterials: Caffeine elimination half-life increases and the clearance decreases when given with ciprofloxacin, enoxacin and pipemidic acid, whereas lomefloxacin, norfloxacin and ofloxacin have little or no effect on these parameters.
Antidepressants: Fluvoxamine reduces the clearance and prolongs the elimination half-life of caffeine.
Antiepileptics: The mean clearance of caffeine increases and its half-life decreases in epileptic patients taking phenytoin. Treatment with carbamazepine or valproic acid have no effect.
Gastrointestinal medicines: Cimetidine reduces the systemic clearance of caffeine and prolongs its elimination half-life.
Lithium: Lithium concentrations increase when caffeine is eliminated from the diet. Toxicity may occur in patients maintained at higher concentrations.
Methoxsalen: Methoxsalen reduces the clearance of caffeine in patients with psoriasis.
Sex hormones: Oral contraceptives reduce the clearance and increases the elimination half-life of caffeine.
Sympathomimetics: The use of caffeine with phenylpropanolamine produces greater plasmacaffeine concentrations, greater increases in blood pressure and more reports of physical adverse effects than either medicine alone. Giving caffeine with ephedrine produce cardiovascular, metabolic and hormonal responses, increased systolic blood pressure and heart rate, as well as raised fasting glucose and insulin.
The sedative effects of meprobamate are enhanced by CNS depressants including alcohol. Meprobamate is capable of inducing hepatic microsomal enzyme systems involved in medicine metabolism: the metabolism of other medicines may be enhanced if given concurrently.
Paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic medicines or medicines that induce liver microsomal enzymes. The absorption of paracetamol may be accelerated by medicines such as metoclopramide. Excretion may be affected and plasma concentrations altered when given with probenecid. Cholestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol.
Antibacterials: Severe hepatotoxicity at therapeutic doses or moderate overdose of paracetamol has been reported in patients receiving isoniazid, alone or with other medicines for tuberculosis.
Anticoagulants: STILPANE has no effect on the gastric mucosa or on platelet function, caution should be observed, since an increased risk of bleeding in patients taking regular doses of paracetamol while on an oral anticoagulant have been observed. An increase in INR has also been reported, therefore increased monitoring may be appropriate.
Antiepileptics: Enzyme inducing medicines such as carbamazepine, phenobarbital, phenytoin or primidone increases paracetamol metabolism (glucuronidation and oxidation) and clearance from the body. This could result in an increased production of the hepatotoxic metabolite of paracetamol. If this toxic metabolite then exceeds the normal glutathione binding capacity, liver damage may occur. Therefore, the plasma-paracetamol concentrations should be halved in patients receiving enzyme-inducing medicines. Paracetamol reduces the area under the plasma concentration-time curve for lamotrigine, and its half-life, and increased the percentage of lamotrigine recovered in the urine.
Antivirals: Paracetamol enhances the antiviral effect of Inteferon Alfa. Severe hepatotoxicity has occurred after the use of paracetamol in patients taking zidovudine and co-trimoxazole.
Probenecid: Pretreatment with probenecid can decrease paracetamol clearance and increase its plasma half-life.
The depressant effects may be exaggerated and prolonged by phenothiazines, monoamine oxidase (MAO) inhibitors, and tricyclic antidepressants (see CONTRAINDICATIONS).
Codeine also increases the degree of sedation and the hypotensive effects of phenothiazines. Phenothiazines seem to be antianalgesic and increases the amount of opioid required to produce satisfactory relief from pain.
A number of antihistamines e.g. hydroxyzine enhance the analgesic effects of low doses of opioids.
The safety of STILPANE in pregnancy and lactation has not been established.
STILPANE should not be used during pregnancy and lactation (see CONTRAINDICATIONS).
The use of STILPANE may lead to drowsiness and impaired concentration that may be aggravated by the simultaneous intake of alcohol or central nervous system depressants.
Affected patients should not drive or operate machinery (see SIDE EFFECTS).
Frequency unknown: Neutropenia, pancytopenia, leucopenia, thrombocytopenia and agranulocytosis
Less frequent: Sensitivity reactions resulting in reversible skin rash, usually erythematous or urticarial
Frequency unknown: Sensitivity reactions accompanied by medicine fever and mucosal lesions
Frequent: Drowsiness
Less frequent: Confusion, euphoria, mood changes, restlessness, miosis, hallucinations, sedation, dizziness, faintness. Large doses of codeine can cause excitement and convulsions
Frequency unknown: Deepening coma, vertigo, hypothermia, raised intracranial pressure
Less frequent: Bradycardia, palpitations, orthostatic hypotension, facial flushing
Frequent: Constipation
Less frequent: Dry mouth, nausea, vomiting
Less frequent: Pruritus, urticaria, sweating
Frequency unknown: Contact dermatitis, itching of the nose and idiosyncrasy
Less frequent: Muscle rigidity following high doses
Less frequent: Difficulty in micturition
Frequent: Insomnia, headache, anxiety, restlessness
Frequency unknown: Vertigo, palpitations, tremor and hypotension
Frequent: Nausea, vomiting, abdominal pain
Less frequent: Gastrointestinal bleeding
Frequency unknown: Agranulocytosis, eosinophilia, leucopenia, thrombocytopenia, and aplastic anaemia
Frequent: Drowsiness, ataxia
Less frequent: Weakness, headache, disturbances of vision, excitement, dizziness
Frequency unknown: Paraesthesia
Less frequent: Tachycardia and cardiac dysrhythmias
Frequency unknown: Hypotension
Less frequent: Nausea, vomiting, diarrhoea
Less frequent: Skin rashes, urticaria
Frequency unknown: Purpura, angio oedema, bronchospasm, anuria, erythema multiforme
Treatment should be discontinued as soon as these hypersensitivity reactions occur.
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