Respidina 120 Mg 14 Tablets Prolonged Release

Respidina (120 Mg 14 Extended Release Tablets)

Pseudoephedrine hydrochloride

ACTION AND MECHANISM

- [NASUS / PHARYNGEAL DECONGESTANT], [ALPHA-1 ADRENERGIC AGONIST]. Pseudoephedrine, a stereoisomer of ephedrine, behaves as an agonist at alpha-1 receptors, and to a lesser extent at beta receptors. Agonism on alpha-1 receptors leads to vasoconstriction of blood vessels, including those of the nasal mucosa, reducing blood content and swelling of the mucosa, which produces a decongestant effect on the nasal passages. On the other hand, the agonist effect on beta receptors could lead to bronchodilation, reducing resistance to air flow.

On the other hand, pseudoephedrine, like ephedrine, behaves as an indirect agonist, being captured by the sympathetic fiber, displacing norepinephrine from its vesicles and favoring its release. The released norepinephrine could potentiate the sympathomimetic effects of pseudoephedrine by acting on its receptors. However, this mechanism causes a depletion of catecholamine levels in the sympathetic fiber, which would cause tachyphylaxis.

Pseudoephedrine has effects similar to those of ephedrine, although its vasoconstrictor activity and central effects are lower than those of ephedrine.

PHARMACOKINETICS

- Absorption: Pseudoephedrine is rapidly and almost completely absorbed after oral administration. No first pass effect has been observed. After administration of an oral dose of 120 mg of pseudoephedrine, the Cmax of 397-422 ng / ml is obtained after 1.84-1.97 hours, whereas if this same dose is administered in a sustained-release form absorption is delayed until a Tmax of 3.8-6.1 hours.

The effects can last up to 12 hours after administration of 120 mg orally in prolonged-release forms.

Effect of food : Food appears to delay the absorption of pseudoephedrine, but when pseudoephedrine is administered in extended-release forms, food has little effect on absorption.

- Distribution: Its ability to bind to plasma proteins is unknown. It has a Vd between 2.64 and 3.51 l / kg. Pseudoephedrine is capable of crossing the placenta and appears to be excreted in milk, with 0.5% of the oral dose being obtained in milk after 24 hours.

- Metabolism: Pseudoephedrine is metabolized by N-demethylation in the liver, in an incomplete way and less than 1%, giving rise to an inactive metabolite.

- Elimination: Both pseudoephedrine and its hepatic metabolite are eliminated in the urine, with 55-96% of pseudoephedrine unchanged. Elimination of pseudoephedrine is pH dependent, and is accelerated in acidic urine. The elimination half-life is 3-6 hours (pH = 5) or 9-16 hours (pH = 8). The Cl is 7.3-7.6 ml / minute / kg.

Pharmacokinetics in special situations:

- Children: After administering a dose of 30-60 mg of pseudoephedrine in children aged 6-12 years, Cmax values ​​between 244 and 492 ng / ml were obtained after 2.1 and 2.4 hours and Vd of 2 , 6 and 2.4 l / kg respectively. It has an elimination half-life similar to that of adults. Cl is somewhat higher than in adults, with values ​​of 10.3-9.2 ml / minute / kg.

INDICATIONS

- Temporary and symptomatic relief of [NASAL CONGESTION] associated with [RHINITIS], [COMMON COLD] or [FLU].

POSOLOGY

- Adults: 120 mg / 12 hours. Maximum daily dose: 240 mg. Minimum interval between doses: 12 hours.

- Kids:

* Children 12 years or older: 120 mg / 12 hours.

* Children under 12 years of age: Safety and efficacy have not been evaluated.

DOSAGE IN KIDNEY INSUFFICIENCY

Pseudoephedrine is eliminated mainly via the urinary tract, therefore patients with renal insufficiency may require a dose adjustment.

DOSAGE IN LIVER INSUFFICIENCY

- Moderate or severe: Increase in plasma concentrations. Consider reducing the dose.

RULES FOR CORRECT ADMINISTRATION

The capsules / tablets should be swallowed whole, without chewing or crushing, with the help of a glass of water or any other liquid. If it is too big to swallow, it is recommended to mix the contents with jam or jelly, and swallow it without chewing.

If pseudoephedrine is administered at night, it is recommended to do it several hours before bedtime to minimize the possibility of insomnia, especially in patients with difficulty sleeping.

Administration with food : The concomitant taking of this medicine with food or drink does not affect its effectiveness. Do not administer together with bitter orange juice.

CONTRAINDICATIONS

- Hypersensitivity to any component of the drug.

- Severe heart disease or uncontrolled diabetes.

- Patients in treatment with antidepressants of the MAOI type in the 14 days before starting therapy with pseudoephedrine (See Interactions).

- Children under 12 years old.

- [CLOSED ANGLE GLAUCOMA].

- [HYPERTHYROIDISM].

- [URINARY RETENTION].

- History of [BRAIN BLEED] or risk factors for brain haemorrhage.

- Pregnancy and lactation.

PRECAUTIONS

- Patients in whom sympathetic stimulation could worsen their pathologies, such as those with [DIABETES], [GLAUCOMA], [CORONARY INSUFFICIENCY], [ISCHEMIC CARDIOPATIA], [CARDIAC ARRHYTHMIA], [ARTERIAL HYPERTENSION], [HYPERTHROIDISM] PHEOCROMOCYTOMA], [ANEMIA] or [PROSTATIC HYPERPLASIA]. The use of pseudoephedrine or any other sympathomimetic could aggravate the symptoms of these diseases, so its use without a prescription is not recommended. In severe cases, such as decompensated diabetes or severe heart disease, it may be advisable to avoid the administration of pseudoephedrine (See Contraindications).

- Patients with [BOWEL OBSTRUCTION] should not use prolonged-release oral forms without consulting a physician.

- Caution should be exercised in patients who are receiving digitalis or are being treated with ergotamine-type vasoconstrictors.

- The benefit / risk ratio should be carefully evaluated in the following situations: severe [HEPATIC INSUFFICIENCY] or moderate to severe [KIDNEY INSUFFICIENCY], [PROSTATIC HYPERPLASIA], positive anamnesis of [BRONCHIAL SPASM], [PEPTIC ULCER] stenosing, obstruction duodenal pylorus, history of [EPILEPSY].

- As with other CNS stimulants, pseudoephedrine carries a risk of abuse. Its administration in increasing doses can produce long-term toxicity. Its continued use can lead to tolerance, which could lead to an increased risk of overdose. Depression may occur after rapid discontinuation of pseudoephedrine therapy.

- At therapeutic doses, no clinically significant interaction with alcohol has been demonstrated (for a blood alcohol level of 0.5 g / l). However, caution is advised if alcohol is taken concomitantly.

PRECAUTIONS RELATING TO EXCIPIENTS

This medicine may cause stomach upset and diarrhea because it contains hydrogenated castor oil.

ADVICE TO THE PATIENT

- It is recommended not to exceed the recommended daily dose.

- Treatment should be stopped and see a doctor if symptoms persist for more than five days, if they worsen or if high fever, dizziness, insomnia or nervousness, tachycardia or heart palpitations, nausea, vomiting or persistent abdominal pain appears.

- The doctor or pharmacist should be notified if the patient has diabetes, heart disease, hypertension or glaucoma, as well as if he is being treated with any other drug.

- It is recommended to suspend treatment at least 24 hours before surgery.

SPECIAL WARNINGS

- It is recommended to periodically monitor blood pressure in hypertensive patients and blood glucose in diabetic patients.

- It is advisable to distance the taking of MAOIs and pseudoephedrine for at least 14 days.

- It should not be administered in conjunction with other products that contain nasal decongestants.

- The established dose should not be exceeded, the duration of treatment being as short as possible.

INTERACTIONS

- 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 antihypertensive drugs 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

FDA Category C. In animal studies, pseudoephedrine has not produced significant teratogenic effects, although there have been cases of decreased mean weight, length, and skeletal ossification index in the fetus. However, the causal relationship with pseudoephedrine could not be established. However, other sympathomimetic amines have given rise to teratogenic effects in some animal species.

Adequate and well-controlled studies in humans have not been performed. Due to the fact that reproduction studies in animals are not always predictive of the human response, and due to the vasoconstrictive properties of pseudoephedrine, the use of this medicine is contraindicated in pregnancy, and it is only accepted in the absence of safer therapeutic alternatives. , when the benefits outweigh the possible risks.

LACTATION

Pseudoephedrine is excreted in human milk in small amounts, with about 0.5% of the total orally administered dose being detected after 24 hours. Although it is possible that after the administration of repeated doses this amount is somewhat higher, many specialists do not believe that these small amounts make it necessary to stop breastfeeding.

With the use of pseudoephedrine, a decrease in milk production has been described in lactating women. Therefore, this medicine is contraindicated in breastfeeding women.

KIDS

The safety and efficacy of the 120 mg dose of pseudoephedrine in children under 12 years of age have not been evaluated, therefore its use is not recommended.

Children older than that age can be especially sensitive to its adverse effects, so caution is advised.

SENIORS

Patients aged 60 years or older are more susceptible to adverse reactions after the use of sympathomimetics, having reported cases of hallucinations, seizures, nervous depression and even death. These effects can appear even at normal therapeutic doses.

In addition, the elderly can present pathologies that could be worsened by the administration of sympathomimetics, as well as being in treatment with drugs with which this active principle could interact. It is recommended to closely monitor patients over 60 years of age, and discontinue treatment at the slightest indication of significant adverse reactions. A dosage adjustment may be necessary.

ADVERSE REACTIONS

The adverse effects of this medicine are, in general, rare at recommended doses, although they can increase in intensity and severity at higher doses. The most frequent alterations are:

- Digestive. [NAUSEA], [VOMITING], [DYSPEPSIA] and [DRY MOUTH] may appear.

- Neurological / psychological. Nerve stimulation cases are common, especially in sensitive patients. It usually presents with [NERVOSISM], [EXCITABILITY], [INSOMNIA], [DIZZINESS] or [VERTIGO]. More rarely, cases of [ASTENIA], [HEADACHE] and [TREMOR] have been described. In more severe cases, and usually associated with overdose, [ANXIETY], [Drowsiness], [SEIZURES] and [HALLUCINATIONS] may appear.

- Cardiovascular. Pseudoephedrine can lead to [CARDIAC ARRHYTHMIA], with [TACHYCARDIA] and [PALPITATIONS], especially at high doses or in patients predisposed to sympathomimetic effects. Reflex [ARTERIAL HYPERTENSION] and [BRADYCARDIA] may also occur.

- Respiratory. [DYSPNOEA].

- Genitourinary. Occasionally [URINARY RETENTION] may appear in patients with prostatic hypertrophy.

- Ophthalmological. Cases of [BLEPHAROSPASM], with [PHOTOPHOBIA] and [TEARING] have been described.

- Allergic / dermatological. Cases of [HYPERSENSITIVITY REACTIONS] have been described, with [URTICARIA] and [EXANTEMATIC ERUPTIONS]. In the most severe cases, [LEUCOPENIA], [AGRANULOCYTOSIS] and [THROMBOCYTOPENIA] have appeared.

- Generals. [HYPERHYDROSIS], [PALE].

ADVERSE REACTIONS RELATING TO EXCIPIENTS

- Because it contains castor oil, it can cause stomach discomfort and [DIARRHEA].

OVERDOSE

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 lead to a reduction in the penalty as long as the athlete can demonstrate that the use of the specific substance in question was not intended to increase your athletic performance.

Package Leaflet Respidin 120 Mg 14 Tablets Prolonged Release