Termalgin Cold 10 Sachets Powder Oral Solution

Termalgin Cold (10 Sachets Powder Oral Solution)

ACTION AND MECHANISM
Combination of paracetamol and pseudoephedrine.

Paracetamol has analgesic and anti-inflammatory activity, mainly mediated by its inhibition of prostaglandin synthesis in the central nervous system.

Pseudoephedrine is a sympathomimetic agent with alpha-agonist activity. It is the dextroisomer of ephedrine, both agents are equally effective as nasal decongestants. They stimulate the alpha-adrenergic receptors of the vascular smooth muscles, constricting the dilated arterioles of the nasal mucosa and reducing blood flow to the congested area.

INDICATIONS
- [FLU SYMPTOMS] and [COMMON COLD]: Relief of symptoms of catarrhal and flu-like processes that occur with pain, [FEVER] and [NASAL CONGESTION] / sinus.

DOSAGE
- Adults, the elderly and adolescents> / = 15 years: 1 envelope / 4-6 h, as needed.

Maximum dose: 4 sachets in 24 hours.

Each sachet contains: 500 mg of paracetamol and 30 mg of pseudoephedrine.

- Children and adolescents <15 years: not recommended.

Duration of treatment: if symptoms persist for more than 3 days or worsen, the clinical situation should be evaluated.

DOSAGE IN LIVER INSUFFICIENCY
The dose should be reduced or the dosing interval prolonged.

RULES FOR CORRECT ADMINISTRATION
- Dissolve the content of 1 sachet in a cup of hot water (approximately 250 ml) (not boiling). Drink when cool to an acceptable temperature.

- After dissolving the powder in hot water, the liquid is a cloudy yellow solution with the smell of berries.

CONTRAINDICATIONS
- Hypersensitivity to paracetamol, pseudoephedrine, menthol or any other component of the drug. Also, do not use in case of allergy to peanuts or soy (as it contains soy lecithin).

- [ARTERIAL HYPERTENSION], heart disease, and cardiovascular disease.

- [HYPERTHYROIDISM]

- [CLOSED ANGLE GLAUCOMA]

- [URINARY RETENTION]

- [PHEOCROMOCYTOMA]

- Patients who are taking or have taken monoamine oxidase inhibitors (MAOIs) during the last two weeks. Patients receiving tricyclic antidepressants (see Interactions).

- Patients in treatment with beta-blocking drugs (see Interactions).

- Patients being treated with other sympathomimetic drugs such as decongestants, appetite suppressants and amphetamine psychostimulants (see Interactions).

- First trimester of pregnancy (see Pregnancy).

PRECAUTIONS
- Patients should not take any other medicines containing paracetamol concomitantly due to the risk of serious liver damage in case of overdose.

- Other sympathomimetic drugs (ocular or nasal decongestants) should not be administered concomitantly.

- [KIDNEY FAILURE] severe and moderate. Caution is advised in the administration of paracetamol.

- [HEPATOPATIA], [HEPATIC INSUFFICIENCY]. Caution is advised in the administration of paracetamol to patients with mild to moderate hepatocellular impairment (including Gilbert's syndrome), severe hepatic impairment (Child-Pugh> 9), [ACUTE HEPATITIS], concomitant treatment with medications that affect liver function, [GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY], [HEMOLYTIC ANEMIA], [DEHYDRATION], alcohol abuse and chronic [MALNUTRITION].

- [CHRONIC ALCOHOLISM]. Paracetamol should be administered with caution in patients with alcohol dependence (see Interactions). Alcoholic beverages should be avoided while taking this medicine. The risk of overdose is greater in those with non-cirrhotic alcoholic liver disease.

- Evaluate the benefit-risk ratio in patients with:

* cardiovascular disease,

* [DIABETES],

* [PROSTATIC HYPERPLASIA], since they can be susceptible to urinary retention and dysuria,

* vascular occlusive disease (eg [RAYNAUD'S DISEASE]),

* [PSYCHOSIS],

* chronic cold, [ASTHMA] or [PULMONARY EMPHYSEMA].

- In case of [SURGERY], it is advisable to interrupt the treatment a few days before. The risk of hypertensive crisis is increased if halogenated anesthetics are used (see Interactions).

- After administration for long periods of time, high doses or incorrect use of analgesics, headaches may occur that should not be treated using higher doses of analgesics.

- In general, the habitual consumption of painkillers, particularly a combination of several analgesic substances, can cause permanent kidney damage with the risk of kidney failure.

- Abrupt discontinuation after long periods of time, high doses, or incorrect use of pain relievers can lead to headache, fatigue, muscle pain, nervousness, and autonomic symptoms. These withdrawal symptoms resolve within a few days. Until that time, the use of pain relievers should be avoided and should not be restarted without medical advice.

- Its use is not recommended during the second and third trimesters of pregnancy (contraindicated in the first).

PRECAUTIONS RELATING TO EXCIPIENTS
- This medicinal product contains sodium salts. To know the exact sodium content, it is recommended to review the composition. Oral and parenteral dosage forms with sodium amounts greater than 1 mmol (23 mg) / maximum daily dose should be used with caution in patients with [KIDNEY FAILURE] or on low sodium diets.

- This medicine contains orange yellow S as an excipient. May cause allergic-type reactions including [ASTHMA], especially in patients with [SALICYLATE ALLERGY].

- This medicine contains aspartame as an excipient, so it should be taken into account by people affected by [PHENYLKETONURIA]. 100 mg of aspartame correspond to 56.13 mg of phenylalanine.

- This medicine contains sucrose. Patients with hereditary [FRUCTOSE INTOLERANCE], glucose or galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine.

- This medicine contains sucrose. The administration of amounts greater than 5 g daily should be taken into account in patients with [DIABETES].

ADVICE TO THE PATIENT
- This medicine contains paracetamol. No other medicines containing paracetamol should be taken due to the risk of overdose.

- The doctor and / or pharmacist must be informed if you are using other medications such as nasal or ocular decongestants.

- Administer only when symptoms (pain and / or fever, congestion) are present. It should only be used for a few days. Consult a doctor if symptoms worsen or persist for more than 3 days.

- In case of surgery, it is advisable to interrupt the treatment a few days before.

- The consumption of alcoholic beverages should be avoided while taking this medicine.

SPECIAL WARNINGS
- Patients should not take any other medicines containing paracetamol concomitantly due to the risk of serious liver damage in case of overdose.

- Other sympathomimetic drugs (such as ocular or nasal decongestants) should not be administered concomitantly.

- Administer only when symptoms, pain and / or fever, congestion are present. It should only be used for a few days. Patients should seek medical advice if symptoms worsen and persist for more than 3 days.

- In general, the habitual consumption of painkillers, particularly a combination of several analgesic substances, can cause permanent kidney damage with the risk of kidney failure.

- The consumption of alcoholic beverages should be avoided while taking this medicine. Paracetamol should be administered with caution in patients with alcohol dependence.

- In case of surgery, it is advisable to interrupt the treatment a few days before. The risk of hypertensive crisis is increased if halogenated anesthetics are used (see Interactions).

- Abrupt discontinuation after long periods of time, high doses, or incorrect use of pain relievers can lead to headache, fatigue, muscle pain, nervousness, and autonomic symptoms. These withdrawal symptoms resolve within a few days. Until that time, the use of pain relievers should be avoided and should not be restarted without medical advice.

INTERACTIONS
In general, interactions with paracetamol are not expected to be serious, due to its occasional use. Only in those patients treated with high doses, especially if there are other risk factors for hepatotoxicity, or in long-term treatment, it is expected that the interactions have clinical significance.

- NSAIDs. Paracetamol is usually used in combination with other analgesics, such as ibuprofen, for the treatment of febrile processes in children.However, it must be taken into account that its administration together with NSAIDs or salicylates at high doses and for prolonged periods of time could increase the risk of kidney damage. It is therefore recommended not to exceed the recommended doses and limit joint treatment to the bare minimum.

- Oral anticoagulants. Unlike NSAIDs and acetylsalicylic acid, paracetamol does not have antiplatelet activity nor does it affect blood clotting per se, which is why it is used as the analgesic drug of choice in patients treated with oral anticoagulants.

However, in the case of prolonged and high-dose treatments, but without entering into toxic doses, a slight hepatotoxic effect could occur, characterized by the decrease in the production of hepatic coagulation factors, so the INR of these patients could be increased. , with risk of hemorrhage.

Therefore, it is recommended to monitor this parameter in these patients treated with high doses. The risk seems insignificant in the case of specific treatments or in prolonged treatments with doses <2 g / 24 h.

- Busulfan. Risk of toxicity due to busulfan, as paracetamol reduces the levels of glutathione, a substance with which busulfan is conjugated in its elimination. It is recommended to avoid the administration of paracetamol, or limit exposure if this is not possible, within 72 hours before and during treatment with busulfan.

- Chloramphenicol. Paracetamol could favor the accumulation of chloramphenicol by reducing its hepatic metabolism, with the risk of hematological toxicity. It is advisable to monitor the patient.

- Drugs that delay gastric emptying, such as anticholinergics or exenatide. This delay could slow down the absorption of paracetamol and the onset of the effect, rather than its intensity.

- Hepatotoxic drugs. Paracetamol at high doses exerts a hepatotoxic effect. It is recommended to avoid its joint administration with other hepatotoxic drugs, as well as with alcohol.

- Enzyme inducers (estrogenic oral contraceptives, barbiturates, carbamazepine, phenytoin, rifampicin). Paracetamol is partially metabolized by cytochrome P450, so its plasma levels and therapeutic effects could be reduced in case of administration together with a potent inducer drug of the hepatic microsomal system. On the other hand, in case of paracetamol overdose, the inducer could increase liver toxicity as a consequence of a higher production of toxic metabolites generated by this enzymatic system.

- Enzyme inhibitors (imatinib, isoniazid, propranolol). Increases in paracetamol plasma levels have been reported by drugs with inhibitory activity on its metabolism.

- Reverse transcriptase inhibitors (didanosine, zidovudine). Paracetamol could potentiate the hematological toxicity of zidovudine. On the other hand, both didanosine and zidovudine could promote hepatotoxicity due to paracetamol.

- Lamotrigine. Paracetamol could increase the metabolism of lamotrigine, reducing its therapeutic effects.

- Ion exchange resins (cholestyramine, colestipol). Possible decreased absorption of paracetamol. Distance the administration one hour.

Studies have shown the absence of significant pharmacokinetic interaction with adefovir, amantadine, h3 antihistamines or proton pump inhibitors, argatroban, chloroquine, erythromycin, lithium, methotrexate, oseltamivir, sucralfate, telmisartan or zolmitriptan. There has also been no interaction of any kind with alpha-1 adrenergic blockers (doxazosin, terazosin), furosemide, letrozole or zanamivir.

Paracetamol slightly reduces urinary excretion of diazepam, although plasma levels remain unchanged.

Paracetamol does not affect the immunogenicity of influenza vaccines, and could reduce the symptoms of their adverse reactions.

Because it contains pseudoephedrine, the following interactions could be expected:

- Urinary acidifiers (ammonium chloride). The administration of ammonium chloride or any other acidifying drug could favor the elimination of pseudoephedrine, since this drug is a basic amine. A decrease in pharmacological activity could occur.

- Urinary alkalinizers (sodium bicarbonate). Cases of patients have been described in which the elimination half-life of pseudoephedrine increased by 71-100% after administration of a urinary alkalinizer. This effect could be due to the lower solubility of pseudoephedrine in basic urine, as it is a weak base.

- Inhalation anesthetics. Administration of pseudoephedrine before or shortly after anesthesia with these anesthetics could increase the risk of serious ventricular arrhythmias, especially in patients with pre-existing heart disease, since anesthetics greatly sensitize the myocardium to the effects of sympathomimetics. In the event that the patient is to undergo a scheduled surgical intervention, it is recommended to suspend the administration of this medicine at least 24 hours before the operation.

- Tricyclic antidepressants. Tricyclic antidepressants could potentiate the vasopressor effects of sympathomimetic amines, leading to hypertensive crisis. It is recommended to avoid association.

- Antihypertensive. Co-administration of pseudoephedrine together with antihypertensives such as beta-blockers, methyldopa or diuretics could reduce the antihypertensive activity, due to the vasopressor effects of pseudoephedrine. In addition, beta-blockers have led to cases of hypertensive crisis when administered with pseudoephedrine, due to beta blockade, which favors the greater binding of pseudoephedrine to alpha-adrenergic receptors. Regular monitoring of heart function and blood pressure is recommended.

- Digoxin. Simultaneous administration of digoxin with pseudoephedrine could increase the risk of cardiac arrhythmias.

- Nerve stimulants (amphetamines, cocaine, xanthines). Co-administration could enhance nerve stimulation, leading to intense excitability. It is recommended to avoid association. Cocaine could also increase cardiovascular side effects.

- Guanethidine. Pseudoephedrine opposes the sympatholytic effects of guanethidine, both by stimulating the release of norepinephrine and by binding to alpha-1 receptors. There is a risk of losing the therapeutic effects of guanethidine, appearing hypertension. It is recommended to avoid association.

- Thyroid hormones. There could be a potentiation of the effects of both drugs, with a risk of arterial hypertension and coronary insufficiency.

- MAOI (including linezolid). MAOIs have led to potentiation of the effects of pseudoephedrine due to the inhibition of norepinephrine metabolism, intensifying and prolonging the vasopressor and cardiac stimulant effects, and leading to headache, cardiac arrhythmias, vomiting or hypertensive and / or hyperpyretic crisis sudden and intense. Pseudoephedrine should not be administered during treatment with MAOIs or for 14 days after treatment with these drugs.

- Levodopa. The administration of levodopa together with sympathomimetics increases the risk of cardiac arrhythmias, so a decrease in the dose of the adrenergic agonist might be necessary.

- Nitrates. Pseudoephedrine acts as a vasoconstrictor, so it could antagonize the antianginal effects of nitrates. It is recommended to avoid association.

- Reserpine. Administration of reserpine may lead to a reduction in the effects of indirect sympathomimetics such as pseudoephedrine, probably due to depletion of noradrenergic vesicles by reserpine. It is recommended to avoid association.

- Sympathomimetics. There could be a potentiation of the cardiovascular and neurological effects of both drugs. It is recommended to avoid association.

PREGNANCY
The effects of this medicine during pregnancy have not been specifically investigated.

Paracetamol: epidemiological studies in pregnant women have shown that there are no harmful effects due to paracetamol used at the recommended doses, but patients should follow the advice of their doctor regarding its use.

Pseudoephedrine: There are limited data on the use of pseudoephedrine in pregnant women. The vasoconstriction of the uterine vessels and the reduction in uterine blood flow associated with the use of pseudoephedrine can lead to fetal hypoxia. The use of pseudoephedrine is contraindicated during the first trimester of pregnancy and is not recommended for the rest of the pregnancy.

Therefore, based on currently available data, the drug is contraindicated during the first trimester of pregnancy and its use is not recommended for the rest of pregnancy.

Effects on Fertility: No specific studies have been performed in humans. Preclinical studies with paracetamol do not indicate a special risk of fertility at therapeutically relevant doses. There are no adequate reproductive toxicity studies with pseudoephedrine.

BREASTFEEDING
Paracetamol and pseudoephedrine pass into breast milk in small amounts. Since there are no data available on the combination of the two substances, this medicine should be avoided during breastfeeding.

CHILDREN
This medicine should not be given to children under 15 years of age.

ELDERLY
Elderly patients may be particularly sensitive to the central nervous system effects of pseudoephedrine.

EFFECTS ON DRIVING
No studies on the effects on the ability to drive and use machines have been performed. If the patient experiences a feeling of dizziness, he should be advised not to drive or operate machinery.

ADVERSE REACTIONS
Adverse reactions from clinical trials are rare adverse reactions and are derived from trials in which there is limited patient exposure.

The post-marketing adverse effects found at the therapeutic dose and according to the established dosage that can be considered attributable are described below. Due to the limited number of clinical data, the frequency of adverse effects is considered unknown (cannot be estimated from the available data), but post-marketing experience indicates that adverse reactions due to paracetamol are rare ( 0.01-0.1%) and serious adverse reactions are very rare (<0.01%).

- Digestive: Paracetamol: Abdominal discomfort, [DIARRHEA], [NAUSEAS] and [VOMITING].

- Hepatic: Paracetamol: Hepatic dysfunction ([INCREASE IN TRANSAMINASES], [INCREASE IN ALKALINE PHOSPHATASE], [HYPERBILIRUBINEMIA]).

- Cardiovascular: Pseudoephedrine: Cardiac effects (eg [TACHYCARDIA]), Increased blood pressure ([ARTERIAL HYPERTENSION]), although not in controlled hypertension

- Neurological / psychological: Pseudoephedrine: Central nervous system stimulation (eg [INSOMNIA], rarely [HALLUCINATIONS]).

- Genitourinary: Pseudoephedrine: [URINARY RETENTION], particularly in patients with prostate hypertrophy.

- Dermatological: Pseudoephedrine: [EXANTEMATIC ERUPTIONS], [PRURITO], [ERYTHEMA], [URTICARIA], [DERMATITIS] allergic.

- Allergic: Paracetamol: [HYPERSENSITIVITY REACTIONS], including [ANAPHYLAXIA], [ANGIOEDEMA], [STEVENS-JOHNSON SYNDROME] and [BRONCHIAL SPASM] (there have been cases of bronchospasm with paracetamol, but they are more likely in asthmatics sensitive to aspirin or other NSAIDs).

- Hematological: There is not necessarily a causality related to paracetamol: [THROMBOCYTOPENIA], [AGRANULOCITOSIS], [PANCITOPENIA], [LEUCOPENIA], [NEUTROPENIA].

ADVERSE REACTIONS RELATED TO EXCIPIENTS
- Containing yellow-orange (E-110) may cause [HYPERSENSITIVITY REACTIONS].

OVERDOSE
Regarding paracetamol:

Symptoms: Paracetamol can lead to very serious and life-threatening poisoning. Toxicity can begin to be experienced from single doses of 6 g in adults or 100 mg / kg in children. Doses greater than 20-25 g are potentially fatal. Chronic doses greater than 4 g / 24 h can lead to transient hepatotoxicity. However, patients treated with other hepatotoxic drugs, enzyme inducers or with chronic alcoholism could be more susceptible to its toxic effects, requiring a lower dose to produce toxicity.

Hepatotoxicity can appear at paracetamol Cp greater than 120 mcg / ml at 4 h and 30 mcg / ml at 12 h. Levels of 300 mcg / ml 4 h after overdose have been associated with hepatotoxicity phenomena in 90% of patients.

Paracetamol overdose follows four characteristic clinical stages:

- Phase I: appears a few hours after overdosing, and up to the first 24 hours. It presents with general malaise, nausea and vomiting, abdominal pain, paleness, excessive sweating and anorexia. Liver function and liver parameters are normal.

- Phase II: occurs within 24-36 h after overdose. Symptoms of liver damage begin to appear, such as abdominal pain in the right upper quadrant and increased levels of transaminases and bilirubin, and prothrombin time.

- Phase III: occurs 72-96 h after overdose, and coincides with the peak of hepatotoxicity, with transaminase elevations of up to 10,000 U / le and even higher, increases in bilirubin, glucose, lactate and phosphate, as well as elevated prothrombin time. The patient may have encephalopathy and coma. Similarly, renal tubular necrosis and myocardial involvement have occasionally been reported. Death can occur from fulminant liver failure with liver necrosis.

- Phase IV: occurs 7-8 days after overdose. Recovery of those patients who have survived the previous stage.

The risk of severe paracetamol poisoning depends on the route of administration as well as the conditions of use of the drug. In this way, it is not expected that serious poisonings will occur in case of overdose with suppositories (yes by ingestion of the same, although this is not frequent), or in case of injectables (due to their hospital use, with sanitary control , despite the fact that serious poisoning has occurred due to confusion of the dose in the amount of paracetamol or volume of the injectable solution). However, in no case can it be ruled out.

Treatment: in case of oral overdose, and preferably within 4 hours after ingestion, gastric aspiration and lavage will be carried out, along with administration of activated charcoal, reducing the absorption of paracetamol.

N-acetylcysteine ​​is the specific antidote for paracetamol overdose. N-acetylcysteine ​​can be used orally in adults and parenterally in adults and children.

- IV route: the dose to be administered is 300 mg / kg, over a period of 20 h and 15 minutes, according to the following guideline:

* Adults: initially 150 mg / kg (equivalent to 0.75 ml / kg of 20% aqueous solution, with pH 6.5) by slow iv or diluted in 200 ml of 5% glucose serum, for 15 min.

Then 50 mg / kg (0.25 ml / kg of 20% aqueous solution, pH 6.5) diluted in 500 ml of 5% glucose serum as an iv infusion for 4 h.

Finally 100 mg / kg (0.50 ml / kg of 20% aqueous solution, with pH 6.5) diluted in 1,000 ml of 5% glucose serum as an iv infusion for 16 h.

* Children: the same schedule will be administered, although the volume of the infusion solutions will be adjusted to the age and weight of the child to avoid pulmonary vascular congestion.

The efficacy of parenteral treatment with N-acetylcysteine ​​is greatest when administered within 8 hours after overdose, gradually reducing thereafter until being ineffective at 15 hours.

The administration of N-acetylcysteine ​​can be suspended when paracetamol plasma levels are below 200 mcg / ml.

- Oral route (for adults only): initially 140 mg / kg, followed by 17 doses of 70 mg / kg / 4 h. The dose should be diluted in water, cola drinks or orange or grape juice to a final concentration of 5%, as it has an unpleasant taste and can lead to irritation or sclerosing. If the dose is vomited within 1 h, its administration will be repeated.

If necessary, it will be administered diluted in water through a duodenal tube.

If the patient experiences symptoms of hepatotoxicity, liver function should be monitored every 24 hours.

Regarding pseudoephedrine:

Symptoms: In case of overdose, adrenergic symptoms associated with cardiac and nerve stimulation usually appear. Other symptoms may include excitability, nervousness, restlessness, hallucinations, tachycardia with continuous and irregular heartbeat, high blood pressure, tachypnea, and dyspnea. Bradycardia and rebound hypotension have occasionally been described. In the most severe cases, hypokalaemia, psychosis, seizures, coma and hypertensive crisis may appear.

Treatment: The recommended treatment consists of the administration of emetics and subsequent gastric lavage within 4 hours of the overdose. Adsorbent charcoal is only useful if administered within the first hour, unless it is administered in controlled-release forms. Forced diuresis in conjunction with a urinary acidifier will increase the elimination of pseudoephedrine as long as kidney function is adequate. However, diuresis is not recommended in severe overdose.

If absorption has already occurred, the individual should be monitored. It is recommended to monitor cardiac status and measure serum electrolyte levels. If there are signs of cardiac toxicity, intravenous propranolol may be indicated. Hypokalaemia can be treated with slow infusion of a dilute potassium chloride solution, monitoring the serum potassium concentration during administration and for several hours thereafter. For delirium or seizures, diazepam can be given intravenously.

DOPING
Pseudoephedrine is a prohibited substance during competition.

It is prohibited when its administration results in a urine concentration greater than 150 mcg / ml.

The detection in a sample during the competition of any quantity of pseudoephedrine in combination with a diuretic or a masking agent, will be considered an adverse analytical result, unless the athlete has obtained an approved therapeutic use authorization (TUE) for ephedrine, in addition than that granted for the diuretic or masking agent.

It is considered a “specific substance” and, therefore, a violation of the rule in which this substance is involved may cause a reduction in the penalty as long as the athlete can demonstrate that the use of the specific substance in question was not with the intention of increase your athletic performance.

See leaflet Termalgin Cold 10 Sachets Powder Oral Solution

See Technical Data Sheet Termalgin Cold 10 Envelopes Powder Oral Solution