TENSTON SA Capsules, hard Ref.[115607] Active ingredients: Caffeine Codeine Meprobamate Paracetamol

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:

• Hepatocellular insufficiency, including Gilbert’s Syndrome (familial non-haemolytic jaundice).
• Glucose-6-phosphatase dehydrogenase deficiency which may lead haemolytic anaemia.
• Severe renal insufficiency (creatinine clearance ≤30 ml/min).
• Chronic alcoholism, excessive alcohol intake.
• Chronic malnutrition, anorexia, bulimia, cachexia (low reserves of hepatic glutathione).
• Dehydration, hypovolaemia.
• Concomitant treatment with medicinal products affecting hepatic function.
• Glutathione deficiency.
• The elderly, adults and adolescents weighing less than 50 kg.

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), 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).

Flucloxacillin

Caution is advised if paracetamol 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 (see section 4.5).

Salicylates

Salicylates in prolonged treatments together with paracetamol significantly increased the risk of analgesic nephropathy, renal papillary necrosis, end-stage renal diseases, and cancer of the urinary bladder. Do not exceed the recommended individual dosages for salicylates and paracetamol, as in TENSTON SA CAPSULES (see section 4.5).

Anticoagulants

The anticoagulant effect could be increased when high doses of paracetamol is used together with anticoagulants, such as warfarin (see section 4.5).

Hepatotoxic medicines

The risk of paracetamol toxicity may be increased in patients receiving potentially hepatotoxic medicines or medicines that induce liver microsomal enzymes (see section 4.5).

Codeine, as in TENSTON SA CAPSULES

Exceeding the prescribed dose, together with prolonged and continuous use of this medication, may lead to dependency and addiction.

Codeine should be given with caution to patients with hypothyroidism, adrenocortical insufficiency, impaired liver function, prostatic hypertrophy or shock. It should be used with caution in patients with inflammatory or obstructive bowel disorders. The dosage should be reduced in elderly and debilitated patients.

The depressant effects of codeine are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics, sedatives, and phenothiazines.

The prolonged use of high doses of codeine has produced dependence of the morphine type.

Patients with a history of cholecystectomy should consult a doctor before using TENSTON SA CAPSULES as it may cause acute pancreatitis in some patients.

Patients taking, or who have taken, monoamine oxidase inhibitors (MAOIs) within the preceding two weeks should not take TENSTON SA CAPSULES (see section 4.3 and 4.5).

Drug dependence, tolerance and potential for abuse

Tolerance, physical and psychological dependence and opioid use disorder (OUD) may develop upon repeated administration of opioids such as codeine. Abuse or intentional misuse of TENSTON SA CAPSULES may result in overdose and/or death. Patients should be informed about the risks and signs of OUD as well as serious clinical outcomes. If these signs occur, patients should be advised to contact their doctor.

Withdrawal symptoms, such as restlessness and irritability may occur once the medicine is stopped.

Codeine, as in TENSTON SA CAPSULES should be used with caution in patients with personal or family history of substance abuse or mental health disorders because the risk of addiction is increased.

Drug withdrawal syndrome

Addiction can cause drug withdrawal syndrome upon abrupt cessation of therapy or dose reduction. The opioid drug 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 (OIH) and Allodynia

Opioid pain medicines have been associated with opioid-induced hyperalgesia (OIH), a condition where opioids cause an increase in pain (called hyperalgesia) or an increased sensitivity to pain (called allodynia). Increases in pain typically occur following a dose increase and resolve quickly following proper diagnosis and management of the condition. 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 non-painful stimuli (allodynia).

Caffeine, as in TENSTON SA CAPSULES

Caffeine should be given with care to patients with a history of peptic ulceration.

Excessive intake of caffeine (e.g. coffee, tea and some canned drinks) should be avoided while taking TENSTON SA CAPSULES (see section 4.9).

Meprobamate, as in TENSTON SA CAPSULES

Patients receiving meprobamate should be warned that their tolerance to ingested alcohol and other depressants of the central nervous system may be lowered with consequent impairment of judgement and co-ordination. Symptoms of porphyria may be exacerbated (see section 4.3).

Prolonged use of meprobamate may lead to the development of dependence of the barbiturate-alcohol type. Meprobamate may induce the hepatic microsomal enzymes involved in drug metabolism.

TENSTON SA CAPSULES contains sodium

TENSTON SA CAPSULES contains less than 1 mmol sodium (23 mg) per table, that is to say essentially ‘sodium-free’.

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 cotrimoxazole. 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 John’s 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:

Caffeine:

Codeine phosphate:

Meprobamate:

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 Adcock.aereports@adcock.com.

Not applicable.