Tenston Sa 150 mg/10 mg/200 mg/30 mg Capsules, hard.

For the symptomatic relief of mild to moderate pain and fever.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE.
Adults: 1 to 2 capsules four times daily.
Paediatric population: Children 12 years and older: 1 capsule four times daily.
Method of administration: For oral administration.

TENSTON SA CAPSULES are contraindicated in:
u2022 Patients with hypersensitivity to meprobamate, codeine phosphate, opioid analgesics, paracetamol, caffeine or to any excipients in TENSTON SA CAPSULES (see section 6.1).
u2022 Patients who must remain alert.
u2022 Patients who have acute intermittent porphyria or severe kidney or liver dysfunction.
u2022 Patients during an attack of bronchial asthma.
u2022 Patients with respiratory depression especially in the presence of cyanosis and excessive bronchial secretion, after operations on the biliary tract, acute alcoholism, head injuries and conditions in which intracranial pressure is raised.
u2022 Heart failure, secondary to chronic lung disease, a history of cardiac disease, epilepsy and all convulsive states.
u2022 Patients taking monoamine oxidase inhibitors or within 14 days of stopping such treatment.
u2022 Children under the age of 12 years.
u2022 In women who are breastfeeding (see section 4.6).
u2022 During third trimester of pregnancy (see section 4.6).
u2022 Children (0 - 18 years of age) who undergo tonsillectomy or adenoidectomy surgery for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions.

Do not use continuously for more than ten days without consulting your doctor. Consult your doctor if no relief is obtained with the recommended dosage. Paracetamol, as in TENSTON SA CAPSULES TENSTON SA CAPSULES contain 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. Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. Dosages in excess of those recommended may cause severe liver damage. The hazard of overdose is greater in those with noncirrhotic alcoholic liver disease. Paracetamol should be administered only with particular caution under the following circumstances:
u2022 Hepatocellular insufficiency, including Gilbertu2019s Syndrome (familial non-haemolytic jaundice).
u2022 Glucose-6-phosphatase dehydrogenase deficiency which may lead to haemolytic anaemia.
u2022 Severe renal insufficiency (creatinine clearance u2264 30 ml/min).
u2022 Chronic alcoholism, excessive alcohol intake.
u2022 Chronic malnutrition, anorexia, bulimia, cachexia (low reserves of hepatic glutathione).
u2022 Dehydration, hypovolaemia.
u2022 Concomitant treatment with medicinal products affecting hepatic function.
u2022 Glutathione deficiency.
u2022 The elderly, adults and adolescents weighing less than 50 kg.
Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), Drug Reaction with eosinophilia and systemic symptoms (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines. If a patient develops SCAR, treatment with TENSTON SA CAPSULES must immediately be discontinued and appropriate treatment instituted (see section 4.8).

Paracetamol, as in TENSTON SA CAPSULES
Hepatotoxic medicines
Increased risk of hepatotoxicity (see section 4.4).
Enzyme-inducing medicines
Increased risk of hepatotoxicity and possible decrease in therapeutic effects of paracetamol (see section 4.4).
Metoclopramide
Absorption of paracetamol may be accelerated.
Domperidone
Absorption of paracetamol may be accelerated.
Probenecid
Pre-treatment with probenecid can decrease paracetamol clearance and increase its half-life. Although urinary excretion of the sulphate and glucuronide conjugates of paracetamol are reduced, that of paracetamol is unchanged.
Colestyramine
Absorption of paracetamol is reduced if given within one hour of cholestyramine.
Salicylates
Prolonged concurrent use of paracetamol with salicylates increases the risk of adverse renal effects (see section 4.4).
Antibiotics
Chronic use of isoniazid, an antibiotic medicine often prescribed for tuberculosis, may increase the risk of liver damage when combined with paracetamol, even at recommended doses.
Warfarin and anticoagulants
Concurrent, chronic, high-dose administration of paracetamol may increase the anticoagulant effect (see section 4.4). Paracetamol is recommended as the general analgesic and antipyretic of choice in patients on oral anticoagulant therapy. However, caution is needed since, although it has no effect on the gastric mucosa or on platelet function, some studies (with warfarin, anisindione, dicoumarol, or phenprocoumon) and isolated reports have found an increased risk of bleeding in patients taking regular doses of paracetamol while on an oral anticoagulant. An increase in INR has also been reported in controlled studies of the use of paracetamol in patients stabilised on warfarin. Increased monitoring of anticoagulant therapy may be appropriate for those also taking paracetamol regularly.
Antibacterials
The plasma-paracetamol concentrations considered an indication for antidote treatment should be halved in patients receiving enzyme inducing drugs such as rifampicin. Severe hepatotoxicity at therapeutic doses or moderate overdoses of paracetamol has been reported in patients receiving isoniazid, alone or with other medicines for tuberculosis.
Antivirals
Severe hepatotoxicity has occurred after use of paracetamol in a patient taking zidovudine and co-trimoxazole. However, neither short-term nor long-term studies (the latter also in an individual patient) have shown any alteration of zidovudine elimination in patients taking zidovudine and paracetamol.
Interferon alfa
Paracetamol has also been found to enhance the antiviral effect of interferon alfa.
Flucloxacillin
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 risks factors (see section 4.4).
Other medicines
Paracetamol is metabolized in the liver and can therefore interact with other medicines that follow the same pathway or may inhibit or induce this route (e.g. barbiturates, such as phenobarbitone, tricyclic antidepressants, alcohol, carbamazepine, phenytoin, primidone, rifampicin, St Johnu2019s Wort (Hypericum perforatum) or other drugs that induce liver enzymes), causing hepatotoxicity (see section 4.4), particularly in overdose (see section 4.9).
Caffeine, as in TENSTON SA CAPSULES
Caffeine, a CNS stimulant, has an antagonistic effect towards the action of sedatives and tranquilizers. Caffeine may enhance the tachycardia effect of some decongestants.
Codeine, as in TENSTON SA CAPSULES
Metoclopramide and domperidone
Codeine may antagonize the effects of metoclopramide and domperidone on gastrointestinal motility.
Central nervous system medicines
Codeine potentiates the central depressive effects of central nervous system depressants including alcohol, anaesthetics, hypnotics, sedatives, tricyclic antidepressants and phenothiazines.
MAOIs
Opioid analgesics should be given with care to patients receiving monoamine oxidase inhibitors. The effect of CNS depressants (including alcohol) may be potentiated by codeine; these interactions are unlikely to be significant at the dosage involved. MAOIs taken with pethidine have been associated with severe CNS excitation or depression (including hypertension or hypotension). Although this has not been documented with codeine, it is possible that a similar interaction may occur and therefore the use of codeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation. Opiate analgesics may interact with monoamine oxidase inhibitors (MAOI) and result in serotonin syndrome. It is recommended that the product should not be taken concurrently or within two weeks of stopping treatment with a MAOI. Sedative medicines such as benzodiazepines or related drugs: The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increase the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited.

Pregnancy: TENSTON SA CAPSULES should not be used during pregnancy (see section 4.3). This includes maternal use during labour because of the potential for respiratory depression in the neonate. Due to the caffeine content of this product, it should not be used during pregnancy. Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate. The patient should be advised of the risk of neonatal opioid withdrawal syndrome, and it should be ensured that appropriate treatment will be available.
Breastfeeding: Codeine, as in TENSTON SA CAPSULES, should not be used during breastfeeding (see section 4.3), as codeine may be secreted in breast milk and may cause respiratory depression in the infant. At normal therapeutic doses, codeine and its active metabolite may be present in breast milk at very low doses and is unlikely to adversely affect the breast fed infant. However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolite, 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. Although significant caffeine toxicity has not been observed in breastfed infants, caffeine may have a stimulating effect on the infant. Due to the caffeine content of this product, it should not be used during breastfeeding.
Fertility: No information available.

TENSTON SA CAPSULES may cause drowsiness and patients should not drive vehicles or operate machinery where loss of attention could lead to accidents.

Tabulated list of adverse reactions
Paracetamol
System Organ Class Frequency Undesirable effects
Blood and lymphatic system disorders Less frequent Agranulocytosis, thrombocytopenia, leukopenia, pancytopenia, neutropenia, anaemia.
Immune system disorders Frequency not known Drug-induced hypersensitivity syndrome (DIHS)**, hypersensitivity reactions characterised by urticaria, dyspnoea, and hypotension (see Section 4.4).
Metabolism and nutrition disorders Less frequent Pyroglutamic aciduria (5-oxoprolinuria) and high-anion gap metabolic acidosis.
Ear and labyrinth disorders Frequency not known Hearing loss.
Cardiac disorders Frequency not known Possible increase in the risk of hypertension.
Gastrointestinal disorders Less frequent Pancreatitis
Hepatobiliary disorders Less frequent Hepatitis.
Skin and subcutaneous tissue disorders Less frequent Cutaneous hypersensitivity reactions including skin rashes, pruritus, sweating, purpura, urticaria and angioedema, severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Stevensu2013Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS)/ drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruption (FDE) ** (FDE) (see section 4.4).
Renal and urinary disorders Less frequent Renal colic, renal failure and sterile pyuria (cloudy urine).
Caffeine
System Organ Class Frequency Undesirable effects
Psychiatric disorders Frequency not known Nervousness.
Nervous system disorder Frequency not known Headache, insomnia, restlessness, dizziness excitement and muscle tremor.
Eye disorders Frequency not known Scintillating scotoma.
Ear and labyrinth disorders Frequency not known Tinnitus.
Cardiac disorders Frequency not known Tachycardia and extrasystoles.
Gastrointestinal disorder Frequency not known Caffeine increases gastric secretions and may cause gastric ulceration.
Codeine phosphate
System Organ Class Frequency Undesirable effects
Psychiatric disorders Frequency not known Drug dependency can occur after prolonged use of codeine (see section 4.4).
Gastrointestinal disorder Less frequent Acute pancreatitis***. Frequency not known Constipation, nausea, vomiting, dyspepsia, dry mouth.
Nervous system disorder Frequency not known Dizziness, drowsiness, hyperalgesia (see section 4.4).
General disorders and administration site conditions Less frequent Drug withdrawal syndrome.
Renal and urinary disorders Frequency not known Difficulty with micturition.
Skin and subcutaneous tissue disorder Frequency not known Skin rashes, pruritus, sweating
Meprobamate
System Organ Class Frequency Undesirable effects
Blood and lymphatic system disorders Frequency not known Blood disorders including agranulocytosis, eosinophilia, leukopenia, thrombocytopenia, and aplastic anaemia have been reported.
Nervous system disorders Frequent Drowsiness.
Frequency not known Paraesthesia, weakness, headache, excitement, dizziness, ataxia.
Eye disorders Frequency not known Disturbances of vision.
Cardiac disorders Frequency not known Hypotension, tachycardia and cardiac dysrhythmias may occur.
Gastrointestinal disorders Frequency not known Nausea, vomiting, diarrhoea.
Skin and subcutaneous tissue disorders Frequency not known Hypersensitivity reactions such as skin rashes, urticaria and purpura or may be more severe with angioneurotic oedema, bronchospasm, or anuria. Erythema multiforme has been reported.
Post marketing experience
The following less frequent side effects have been reported: **: Fixed drug eruptions (FDE) and drug-induced hypersensitivity syndrome (DIHS) (See section 4.4). *** Increased risk of abdominal pain, including pancreatitis has been reported. 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. For reporting of side effects directly to the HCR, contact +27 11 635 0134 or email [email protected].

In the event of overdosage, consult a doctor 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 control centre.
Codeine: The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic medicines. Patients should be informed of the signs and symptoms of overdose and to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur.
Symptoms: An overdose of codeine is characterised, in the first phase, by nausea and vomiting. An acute depression of the respiratory centre can cause cyanosis, slower breathing, drowsiness, ataxia and, more rarely, pulmonary oedema. Respiratory pauses, miosis, convulsion, collapse and urine retention. Signs of histamine release have been observed as well.
Management: 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 a sustained release preparation has been taken.
Meprobamate: Acute meprobamate overdosage can produce stupor, coma, convulsions, shock, circulatory and respiratory collapse.
Paracetamol: Prompt treatment is essential. In the event of an overdosage, consult a doctor immediately, or take the person directly to a hospital. 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. Susceptibility to paracetamol toxicity is increased in patients who have taken repeated high doses (greater than 5 u2013 10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of drugs that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine.
Symptoms: Symptoms of paracetamol overdosage in the first 24 hours include pallor, nausea, vomiting, anorexia and possibly abdominal pain. Mild symptoms during the first two days of acute poisoning, do not reflect the potential seriousness of the overdosage. Liver damage may become apparent 12 to 48 hours, or later after ingestion, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of the prothrombin time. Liver damage may lead to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Abnormalities of glucose metabolism and metabolic acidosis may occur. Cardiac dysrhythmias have been reported.
After maternal overdosage during pregnancy, foetal metabolism of paracetamol that crosses the placenta can produce hepatotoxic metabolites, causing foetal hepatotoxicity.
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. An initial dose of 150 mg/kg N-acetylcysteine in 200 ml dextrose injection given intravenously over 15 minutes, followed by an infusion of 50 mg/kg in 500 ml dextrose injection over the next four hours, and then 100 mg/kg in 1 000 ml dextrose injection over the next sixteen hours. The volume of intravenous fluid should be modified for children. Although the oral formulation is not the treatment of choice, 140 mg/kg dissolved in water may be administered initially, followed by 70 mg/kg every four hours for seventeen doses. A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours 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 time since ingestion in the nomogram below. A semi-logarithmic plot of plasma-paracetamol concentration against hours after ingestion. Reference: Martindale, The Complete Drug Reference. 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 IV 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. Prothrombin index correlates best with survival. Monitor all patients with significant ingestions for at least ninety-six hours. Hepatic tests must be carried out at the beginning of treatment and repeated every 24 hours. In most cases hepatic transaminases return to normal in one to two weeks with full restitution of the liver function. In very severe cases, however, liver transplantation may be necessary.
Caffeine: Symptoms: Overdose of caffeine may result in epigastric pain, vomiting, diuresis, tachycardia or cardiac dysrhythmia, CNS stimulation (insomnia, restlessness, excitement, agitation, nervousness, jitteriness, tremors and convulsions). It must be noted that for clinically significant symptoms of caffeine overdose to occur with this product, the amount ingested would be associated with serious paracetamol related liver toxicity.
Management: Patients should receive general supportive care (e.g. hydration and maintenance of vital signs). The administration of activated charcoal may be beneficial when performed within one hour of the overdose but can be considered for up to four hours after the overdose. The CNS effects of overdose may be treated with intravenous sedatives.