Stilpane Capsules 150 mg/8 mg/320 mg Capsules

STILPANE CAPSULES are indicated for short term use (no longer than 10 days) in mild to moderate pain and fever, and pain associated with anxiety or tension.

Adults and children over 12 years
Take two capsules three or four times a day as required. DO NOT EXCEED THE RECOMMENDED DOSE. For short term use only. Do not use STILPANE CAPSULES continuously for longer than 10 days without consulting your doctor.

Paediatric population
Not recommended for children under 12 years of age (see section 4.3).

Method of administration
For oral administration.

STILPANE CAPSULES is contraindicated in:

• Patients with hypersensitivity to meprobamate, codeine phosphate, paracetamol or any of the excipients of STILPANE CAPSULES (see section 6.1).
• Patients with hypersensitivity to other opioid analgesics.
• Patients with severe liver or kidney complications.
• Patients with pulmonary insufficiency.
• Patients with acute intermittent porphyria or porphyria variegate.
• Patients with a history of epilepsy as STILPANE CAPSULES may induce convulsions.
• Patients with obstructive airways disease, respiratory depression, especially in the presence of cyanosis and excessive bronchial secretion.
• After operations on the biliary tract.
• Acute alcoholism.
• Convulsions, head injuries and conditions in which intracranial pressure is raised.
• Comatose patients.
• During an attack of bronchial asthma or in heart failure secondary to lung disease.
• Patients taking monoamine oxidase inhibitors or within fourteen days of stopping such treatment (see section 4.5).
• Pregnancy and lactation (see section 4.6).
• Patients for whom it is known that they are CYP2D6 ultra-rapid metabolisers.
• Children under 12 years of age (see section 4.2).
• Codeine phosphate, as contained in STILPANE CAPSULES, is also contraindicated in conditions where inhibition of peristalsis is to be avoided, where there is a risk of paralytic ileus, where abdominal distension develops, or in acute diarrhoeal conditions such as acute ulcerative colitis or antibiotic associated colitis (e.g. pseudomembranous colitis) or diarrhoea caused by poisoning.
• All paediatric patients who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see section 4.4).

STILPANE CAPSULES 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 continuous use of STILPANE CAPSULES may lead to dependency and addiction (see section 4.2). Consult your doctor if no relief is obtained with the recommended dosage. The lowest effective dose should be used, and the duration of treatment should be as short as possible.

Meprobamate
STILPANE CAPSULES should not be used for more than 10 days (see section 4.2).

Elderly, debilitated and patients with mental depression
STILPANE CAPSULES should be avoided in elderly and debilitated patients and in those with mental depression.

History of epilepsy
STILPANE CAPSULES may induce convulsions in patients with a history of epilepsy (see section 4.3).

Impaired hepatic, renal or respiratory function
STILPANE CAPSULES should be used with caution in patients with impaired hepatic or renal function. STILPANE CAPSULES should not be used in patients with impaired respiratory function (see section 4.3).

Concomitant use with alcohol and CNS depressants
Patients receiving STILPANE CAPSULES 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.

Dependence and withdrawal
There is a high risk of dependency with a typical withdrawal syndrome. STILPANE CAPSULES should not be used for the stress of daily living.

Porphyria
Symptoms of porphyria may be exacerbated (see section 4.3).

Paracetamol
Liver and kidney disease
Paracetamol, as contained in STILPANE CAPSULES, dosages in excess of those recommended may cause severe liver damage. Prolonged excessive use can cause irreversible kidney damage (see section 4.3). Patients suffering from liver or kidney disease should take STILPANE CAPSULES under medical supervision (see section 4.3).

Myasthenia gravis
Use with caution in patients with myasthenia gravis.

Glutathione depleted states
Caution should be exercised in patients with glutathione depleted states, as the use of paracetamol, as contained in STILPANE CAPSULES, may increase the risk of metabolic acidosis. Use with caution in patients with glutathione depletion due to metabolic deficiencies.

Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), eosinophilia and systemic (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines, as contained in STILPANE. If a patient develops SCAR, treatment with STILPANE must immediately be discontinued and appropriate treatment instituted.

Flucloxacillin
Caution is advised if paracetamol, as contained in STILPANE CAPSULES, is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as those using maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.

Codeine phosphate
CYP2D6 metabolism
Depending on the genetic variability of CYP2D6, the individual metabolising capacity for codeine phosphate, as contained in STILPANE CAPSULES, may vary. Even therapeutic doses can lead to increased formation of the active compound morphine resulting in clinical signs of morphine intoxication (see sections 4.8 and 4.9). STILPANE CAPSULES should be given with caution to patients with hypothyroidism, adrenocortical insufficiency, impaired liver function, prostatic hypertrophy, hypotension or shock. STILPANE CAPSULES should be used with caution in patients with inflammatory or obstructive bowel disorders.

Labour
STILPANE CAPSULES administration during labour may cause respiratory depression in the newborn infant (see section 4.6).

Concomitant alcohol and CNS depressant use
The depressant effects of codeine phosphate as contained in STILPANE CAPSULES, are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics and sedatives, and phenothiazines (see section 4.5).

Dependence, tolerance, and potential for abuse
The prolonged use of high doses of codeine phosphate as in STILPANE CAPSULES has produced dependence of the morphine type. STILPANE CAPSULES should be used with caution in patients with a history of substance abuse. The risks are increased in individuals with current or history or family history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression). Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced or supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.

Discontinuation should be carried out gradually in patients who may have developed physical dependence, to avoid precipitating withdrawal symptoms.

Withdrawal syndrome
Withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months. The opioid withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

Opioid-Induced Hyperalgesia and Allodynia
Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily nonpainful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behaviour. Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation (safety switching the patient to a different opioid moiety).

Post-operative use in children
There have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see section 4.3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

Children with compromised respiratory function
Codeine, as contained in STILPANE CAPSULES, is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures (see section 4.3). These factors may worsen symptoms of morphine toxicity.

Paediatric population
STILPANE CAPSULES should not be used in children below the age of 12 years because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see section 4.3).

Meprobamate
Central nervous system (CNS) depressants and alcohol
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 (see section 4.4).

Paracetamol
Hepatotoxic medicines
Paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic medicines or medicines that induce liver microsomal enzymes.

Metoclopramide and domperidone
The absorption of paracetamol may be accelerated by medicines such as metoclopramide and domperidone.

Probenecid
Excretion may be affected and plasma concentrations altered when given with probenecid. Pretreatment with probenecid can decrease paracetamol clearance and increase its plasma half-life.

Colestyramine
Colestyramine 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.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risk factors (see section 4.4).

Anticoagulants
STILPANE CAPSULES 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 Interferon Alfa. Severe hepatotoxicity has occurred after the use of STILPANE CAPSULES in patients taking zidovudine and co-trimoxazole.

Coumarins (e.g. warfarin)
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding.

Codeine phosphate
Phenothiazines
Codeine phosphate, as contained in STILPANE CAPSULES, also increases the degree of sedation and the hypotensive effects of phenothiazines. Phenothiazines seem to be anti-analgesic and increases the amount of opioid required to produce satisfactory relief from pain.

Antihistamines
A number of antihistamines e.g.hydroxyzine, enhance the analgesic effects of low doses of opioids. Concomitant administration of codeine and antihistamines with sedative properties may cause increased CNS depression and/or respiratory depression and/or hypotension.

Alcohol
The hypotensive, sedative and respiratory depressive effects of alcohol may be enhanced.

Anaesthetics
Concomitant administration of codeine phosphate and anaesthetics may cause increased CNS depression and/or respiratory depression and/or hypotension.

Anti-dysrhythmics
Codeine phosphate delays the absorption of mexiletine. The analgesic activity of codeine phosphate is likely to be significantly impaired by quinidine which impairs codeine phosphate metabolism.

Antidepressants
The depressant effects of opioid analgesics such as STILPANE CAPSULES may be enhanced by tricyclic antidepressants.

Monoamine oxidase (MAO) inhibitors
The depressant effects may be exaggerated and prolonged. The use of STILPANE CAPSULES and MAOs is contraindicated (see section 4.3).

Antipsychotics
Enhanced sedative and hypotensive effect.

Anxiolytics and hypnotics
Enhanced sedative effect.

Domperidone, metoclopramide and cisapride
Codeine phosphate antagonises the effect of cisapride, metoclopramide and domperidone on gastrointestinal activity.

Sodium oxybate
Concomitant administration of codeine and sodium oxybate may cause increased CNS depression and/or respiratory depression and/or hypotension.

Ulcer-healing medicines
Cimetidine may inhibit the metabolism of codeine phosphate resulting in increased plasma concentrations.

Interference with laboratory tests
Opioids such as codeine phosphate may interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure. Sedative medicines such as benzodiazepines or related medicines the concomitant use of opioids such as codeine phosphate with sedative medicines such as benzodiazepines or related medicines increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect.

STILPANE CAPSULES should not be used in pregnancy and lactation as safety has not been established (see section 4.3).

Pregnancy
Codeine phosphate
A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine, as contained in STILPANE CAPSULES. Regular use during pregnancy may cause dependence in the foetus, leading to withdrawal symptoms in the neonate. Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available (see section 4.4). Opioid analgesics may cause gastric stasis during labour, increasing the risk of inhalation pneumonia in the mother.

Breastfeeding
Codeine phosphate
Administration to nursing women is not recommended as codeine phosphate, as contained in STILPANE CAPSULES, may be secreted in breast milk and may cause respiratory depression in the infant.

Fertility
No data available

STILPANE CAPSULES has major influence on the ability to drive or operate machinery. The use of STILPANE CAPSULES 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 section 4.8).

a) Summary of the safety profile
Adverse effects of paracetamol as contained in STILPANE CAPSULES are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Other side effects may include constipation, nausea, dizziness and drowsiness. Regular prolonged use of codeine phosphate as contained in STILPANE CAPSULES is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped. Prolonged use of a painkiller for headaches can make them worse.

b) Tabulated list of adverse reactions
Paracetamol
System organ class
Frequent
Less frequent
Frequency unknown (cannot be estimated from the available data)
Blood and the lymphatic system disorders
Neutropenia, pancytopenia, leucopenia, thrombocytopenia, anaemia, agranulocytosis
Immune system disorders
Anaphylaxis
Cutaneous hypersensitivity reactions including, among others, skin rashes and angioedema. Very rare cases of serious skin reactions have been reported.
Respiratory, thoracic and mediastinal disorders
Bronchospasm*
Hepatobiliary disorders
Hepatitis
Pancreatitis
Hepatic dysfunction
Skin and subcutaneous tissue disorders
Skin rashes, usually erythematous or urticarial, dermatitis
Other allergic reactions accompanied by medicine fever and mucosal lesions, risk of fixed drug eruptions (FDE) and Drug-induced hypersensitivity syndrome (DIHS)
Renal and urinary disorders
Renal colic, renal failure and sterile pyuria
* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

Codeine phosphate
System organ class
Frequent
Less frequent
Frequency unknown (cannot be estimated from the available data)
Immune system disorders
Maculopapular rash has been seen as part of a hypersensitivity syndrome associated with oral codeine phosphate; fever, splenomegaly and lymphadenopathy also occurred.
Endocrine disorders
Hyperglycaemia
Metabolism and nutrition disorders
Anorexia
Psychiatric disorders
mood changes, hallucinations
Euphoria, dysphoria, nightmares, mental depression, drug dependence (see section 4.4), mood changes, hallucinations
Nervous system disorders
Drowsiness
Confusion, restlessness, sedation, dizziness, faintness. Large doses of codeine can cause excitement and convulsions
Vertigo, hypothermia, raised intracranial pressure, headache.
Eye disorders
Miosis, blurred or double vision or other changes in vision
Cardiac disorders
Bradycardia, palpitations
Tachycardia
Vascular disorders
Orthostatic hypotension, facial flushing
Respiratory, thoracic and mediastinal disorders
Dyspnoea. Large doses produce respiratory depression
Gastrointestinal disorders
Constipation
Dry mouth, nausea, vomiting
Stomach cramps, risk of acute pancreatitis
Hepatobiliary disorders
Biliary spasm (may be associated with altered liver enzyme values).
Skin and subcutaneous tissue disorders
Pruritus, urticaria, sweating, Contact dermatitis, itching of the nose and idiosyncrasy, allergic reactions such as skin rashes and facial oedema
Musculoskeletal and connective tissue disorders
Muscle rigidity following high doses
Uncontrolled muscle movements.
Renal and urinary disorders
Difficulty in micturition
Urinary retention, ureteric spasm, dysuria. An antidiuretic effect may also occur with codeine.
Reproductive system and breast disorders
Sexual dysfunction, erectile dysfunction, decreased potency, decreased libido.
General disorders and administrative site conditions
Drug withdrawal syndrome
Malaise, tiredness
These effects occur more commonly in ambulant patients than in those at rest in bed.

Meprobamate
System organ class
Frequent
Less frequent
Frequency unknown (cannot be estimated from the available data)
Blood and the lymphatic system disorders
Agranulocytosis, eosinophilia, leucopenia, thrombocytopenia, and aplastic anaemia
Nervous system disorders
Drowsiness, ataxia
Weakness, headache, disturbances of vision, excitement, dizziness
Paraesthesia
Eye disorders
Disturbances of vision
Cardiac disorders
Tachycardia and cardiac dysrhythmias
Vascular disorders
Hypotension
Respiratory, thoracic and mediastinal disorders
Bronchospasm
Gastrointestinal disorders
Nausea, vomiting, diarrhoea
Hepatobiliary disorders
Skin and subcutaneous tissue disorders
Skin rashes, urticaria
Purpura, angioedema, erythema multiforme
Renal and urinary disorders
Anuria

c) Description of selected adverse reactions
Sensitivity reactions resulting in reversible skin rash or blood disorders may occur. Treatment should be discontinued as soon as these hypersensitivity reactions occur. Post marketing data for paracetamol, as contained in STILPANE CAPSULES, has reported Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), eosinophilia and systemic (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) as an undesirable effect with unknown frequency (see section 4.4). Pyroglutamic aciduria (5-oxoprolinuria) and high-anion gap metabolic acidosis have also been reported as undesirable effects with unknown frequency (see section 4.4). Post marketing data for codeine phosphate, as contained in STILPANE CAPSULES, has reported increased risk of abdominal pain, including pancreatitis as an undesirable effect with unknown frequency.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Aspen Pharmacare: E-mail: [email protected] Tel: 0800 118 088/+27 (0)11 239-6200

Symptoms
In the event of an overdosage, consult a doctor immediately, or take the patient to the nearest hospital immediately. Specialised treatment is essential as soon as possible. The latest information regarding the treatment of overdosage can be obtained from the nearest poison centre. The consequences can be extremely serious because of the narrow margin between therapeutic and toxic doses.

Liver damage, which may be fatal, may only appear after a few days. Kidney failure has been described following acute intoxication.

Paracetamol:
Prompt treatment is essential. A delay in starting treatment may mean that antidote is given too late to be effective. Evidence of liver damage, is often delayed until after the time for effective treatment has lapsed. Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and possibly abdominal pain. Abnormalities of glucose metabolism and metabolic acidosis may occur. Mild symptoms during the first two days of acute poisoning, do not reflect the potential seriousness of overdosage. Liver damage may become apparent 12 to 48 hours after ingestion, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of the prothrombin time. The liver damage may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of liver damage. Cardiac dysrhythmias have been reported. Central oedema and non-specific myocardial depression have also occurred.

Treatment for paracetamol overdosage:
N-acetylcysteine should be administered to all cases of suspected overdose as soon as possible preferably within eight hours of overdosage, although treatment up to 36 hours after ingestion may still be of benefit, especially if more than 150 mg/kg of paracetamol was taken. IV: An initial dose of 150 mg/kg N-acetylcysteine in 200 ml glucose injection, given intravenously over 15 minutes, followed by an intravenous infusion of 50 mg/kg in 500 ml glucose injection over the next 4 hours, and then 100 mg/kg in 1 000 ml over the next 16 hours. The volume of intravenous fluid should be modified for children. Orally: Although oral treatment is not the treatment of choice, 140 mg/kg as a 5 % solution initially, followed by 70 mg/kg every 4 hours for 17 doses may be administered. N-acetylcysteine is effective if administered preferably within 8 hours of overdosage. A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours, unless high, may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine, can be identified according to their 4-hour plasma paracetamol level. The plasma paracetamol level can be plotted against the time since ingestion in the nomogram below. The nomogram should be used only in relation to a single acute ingestion. Those whose plasma paracetamol levels are above the u201cNormal treatment lineu201d, should continue N-acetylcysteine treatment with 100 mg/kg over sixteen hours repeatedly until recovery. Patients with increased susceptibility to liver damage as identified above, should continue treatment if concentrations are above the u201cHigh - risk treatment lineu201d. INR correlates best with survival.

Codeine phosphate:
Respiratory depression is the most important feature of overdosage with codeine and it occurs with circulatory failure and deepening coma. Pinpoint pupils, hypotension and hypothermia, excitement and convulsions and non-cardiogenic pulmonary oedema occur.

Treatment
This should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg. Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion or eight hours if sustained release preparation has been taken. Naloxone may be given according to the following dose regimens: Intravenous Injection: 0,8 to 2 mg repeated at intervals of 2 to 3 minutes to a maximum of 10 mg. Child: 10 u03bcg/kg and, if no response, subsequent doses of 100 u03bcg/kg. Subcutaneous or Intramuscular Injection: As for intravenous injection but only if the i.v. route is not feasible. The onset of action is slower with s.c. or i.m. injection. Continuous intravenous infusion: 2 mg diluted in 500 ml of intravenous infusion solution at a rate adjusted according to the patient's response.

Meprobamate
Symptoms of overdosage with meprobamate are those of central nervous system depression. Included are severe or even fatal hypotension, respiratory depression, shock, heart failure and ultimately death. Acute meprobamate overdosage can produce stupor, coma, convulsions, circulatory and respiratory collapse.