Sedofan is indicated for the symptomatic relief of upper respiratory tract disorders which are benefited by a combination of a nasal decongestant and histamine H₁-receptor antagonist, for example allergic rhinitis, vasomoter rhinitis and the common cold and influenza.

Posology

Adults and children over 12 years: One tablet every 4-6 hours up to 4 times a day.

Not more than 4 doses should be given in any 24 hours.

Use in the Elderly

No specific studies have been carried out in the elderly, but triprolidine and pseudoephedrine have been widely used in older people.

Hepatic Dysfunction

Caution should be exercised when administering Pseudoephedrine/Triprolidine tablets to patients with hepatic impairment.

Renal Dysfunction

Caution should be exercised when administering Pseudoephedrine/Triprolidine tablets to patients with moderate to severe renal impairment.

Method of Administration

For oral use.

 This medicine contraindicated in individuals with known hypersensitivity to pseudoephedrine or triprolidine or to any of the excipients listed in section 6.1.  This medicine contraindicated in patients who are taking or have taken monoamine oxidase inhibitors within the preceding 14 days. The concomitant use of pseudoephedrine and this type of product may cause a rise in blood pressure and/or hypertensive crisis (see section 4.5).  Concomitant use of other sympathomimetic decongestants or beta-blockers (see section 4.5).  Cardiovascular disease including hypertension  Diabetes mellitus  Phaeochromocytoma  Hyperthyroidism  Closed angle glaucoma  Severe renal impairment

Pseudoephedrine/Triprolidine tablets may cause drowsiness. This product should not be used to sedate a child.

Triprolidine may enhance the sedative effects of central nervous system depressants including alcohol, sedatives and tranquilisers. While taking pseudoephedrine/triprolidine tablets, patients should be advised to avoid alcoholic beverages and consult a healthcare professional prior to taking with central nervous system depressants.

Use with caution in prostatic hypertrophy, urinary retention or susceptibility to angle closure.

Patients with thyroid disease who are receiving thyroid hormones are advised to consult a physician before using this product.

Use with caution in occlusive vascular disease.

If any of the following occur, this product should be stopped.

-  Hallucinations

-  Restlessness

-  Sleep disturbances

Severe Skin Reactions: Severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) may occur with pseudoephedrine-containing products. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of this medicine should be discontinued, and appropriate measures taken if needed.

Ischaemic colitis: Some cases of ischaemic colitis have been reported with pseudoephedrine. Pseudoephedrine should be discontinued, and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.

Ischaemic optic neuropathy: Cases of ischaemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.

There have been rare cases of posterior reversible encephalopathy syndrome (PRES) / reversible cerebral vasoconstriction syndrome (RCVS) reported with sympathomimetic drugs, including pseudoephedrine. Symptoms reported include sudden onset of severe headache, nausea, vomiting, and visual disturbances. Most cases improved or resolved within a few days following appropriate treatment. Pseudoephedrine should be discontinued, and medical advice sought immediately if signs or symptoms of PRES/RCVS develop.

Patients with the following conditions should not use pseudoephedrine/triprolidine tablets unless directed by a physician: acute or chronic asthma, chronic bronchitis or emphysema.

There have been no specific studies of pseudoephedrine/triprolidine tablets in patients with hepatic and/or renal dysfunction. Caution should be exercised in the presence of hepatic or moderate to severe renal impairment.

This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

MAOIs and/or RIMAs: Pseudoephedrine exerts its vasoconstricting properties by stimulating α-adrenergic receptors and displacing noradrenaline from neuronal storage sites. Since monoamine oxidase inhibitors (MAOIs) impede the metabolism of sympathomimetic amines and increase the store of releasable noradrenaline in adrenergic nerve endings, MAOIs may potentiate the pressor effect of pseudoephedrine. This product should not be given to patients taking monoamine inhibitors or within 14 days of stopping treatment as there is an increased risk of hypertensive crisis (pseudoephedrine) or serotonin syndrome (triprolidine).

Moclobemide: risk of hypertensive crisis

Appetite suppressants and amphetamine-like psychostimulants: Concomitant use of this product with sympathomimetic agents, such as decongestants, tricyclic antidepressants, appetite suppressants and amphetamine-like psychostimulants, may cause a rise in blood pressure.

Antihypertensives: Because of its pseudoephedrine content, this product may partially reverse the hypotensive action of antihypertensive drugs which interfere with sympathetic activity including bretylium, betanidine, guanethidine, debrisoquine, methyldopa, adrenergic neurone blockers and beta blockers.

Cardiac glycosides: increased risk of dysrhythmias

Ergot alkaloids (ergotamine & methysergide): increased risk of ergotism

Oxytocin: risk of hypertension

Anticholinergic drugs: enhances effects of anticholinergic drugs (such as tricyclic antidepressants).

Antimuscarinic drugs: may have an additive muscarinic action with other drugs such as atropine and some antidepressants.

Anaesthetic agents: Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.

CNS depressants: Triprolidine may enhance the sedative effects of CNS depressants including barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives, antipsychotics and alcohol.

This product should not be used during pregnancy or lactation unless the potential benefit of treatment to the mother outweighs the possible risks to the developing foetus or breastfeeding infant.

 

Pregnancy

There are no adequate and well-controlled studies for pseudoephedrine or triprolidine, or for the combination of pseudoephedrine and triprolidine, in pregnant women.

Breast-feeding

Pseudoephedrine is excreted in breast milk in small amounts, but the effect of this on breast-fed infants is not known. It has been estimated that approximately 0.4 to 0.7% of a single 60mg dose of pseudoephedrine ingested by a nursing mother will be excreted in the breast milk over 24 hours. Data from a study of lactating mothers taking 60 mg pseudoephedrine every 6 hours suggests that from 2.2 to 6.7% of the maximum daily dose (240 mg) may be available to the infant from a breastfeeding mother.

Triprolidine is excreted in breast milk, it has been estimated that approximately 0.06 to 0.2% of a single 2.5 mg dose of triprolidine ingested by a nursing mother will be excreted in the breast-milk over 24 hours.

Pseudoephedrine/triprolidine tablets may cause drowsiness and impair performance in tests of auditory vigilance. Patients should not drive or operate machinery until they have determined their own response.

Placebo-controlled studies with sufficient adverse event data are not available for the combination of pseudoephedrine and triprolidine.

Adverse drug reactions identified during clinical trials and post-marketing experience with pseudoephedrine, triprolidine or the combination are listed below by System Organ Class (SOC). The frequencies are defined according to the following convention:

§ Very common ≥1/10

§ Common ≥1/100 and < 1/10

§ Uncommon ≥1/1,000 and <1/100

§ Rare ≥1/10,000 and <1/1,000

§ Very rare <1/10,000

§ Not known (cannot be estimated from the available data)

ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology studies, if available, or 2) when incidence cannot be estimated, frequency category is listed as 'Not known.

System Organ Class (SOC)	Adverse Drug Reaction (Preferred Term)	Frequency
Blood and Lymphatic System Disorders	Blood disorder	Rare
Immune System Disorders	Hypersensitivity – cross-sensitivity may occur with other sympathomimetics	Rare
Psychiatric Disorders	Insomnia	Common
	Nervousness	Common
	Confusional state	Rare
	Depression	Rare
	Sleep disorder	Rare
	Anxiety	Not Known
	Euphoric mood	Not Known
	Excitability	Not Known
	Hallucinations	Not Known
	Irritability	Not Known
	Paranoid delusions	Not Known
	Restlessness	Not Known
Nervous System Disorders	Headache	Very common
	Dizziness	Common
	Paradoxical stimulation	Common
	Psychomotor impairment	Common
	Somnolence	Common
	Extrapyramidal disorder	Rare
	Seizure	Rare
	Tremor	Rare
	Cerebrovascular accident	Not Known
	Paraesthesia	Not Known
	Posterior reversible encephalopathy syndrome (PRES)/reversible cerebral vasoconstriction syndrome (RCVS)	Not Known
	Psychomotor hyperactivity	Not Known
Eye Disorders	Vision blurred	Common
	Ischaemic optic neuropathy	Not Known
Cardiac Disorders	Palpitations	Rare
	Dysrhythmias	Not Known
	Myocardial infarction / myocardial ischaemia	Not Known
	Tachycardia	Not Known
Vascular Disorders	Hypotension	Rare
	Hypertension	Not Known
Respiratory, Thoracic and Mediastinal Disorders	Increased viscosity of bronchial secretion	Common
	Dry throat	Not known
	Epistaxis	Not known
	Nasal dryness	Not known
Gastrointestinal Disorders	Dry mouth	Common
	Gastrointestinal disorder	Common
	Nausea	Common
	Abdominal discomfort	Not Known
	Ischaemic colitis	Not Known
	Vomiting	Not Known
Hepatobiliary Disorders	Liver Disorder	Rare
Skin and Subcutaneous Tissue Disorders	Angioedema	Not known
	Pruritus	Not known
	Rash	Not known
	Severe skin reactions, including acute generalised exanthematous pustulosis (AGEP)	Not known
	Urticaria	Not known
Renal and Urinary Disorders	Urinary Retention (in men whom prostatic enlargement could have been an important predisposing factor)	Common
	Dysuria	Not known
General Disorders and Administration Site Conditions	Fatigue	Not known

 

To report any side effect(s):

§ Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

-     Fax: +966-11-205-7662

-     SFDA Call Centre: 19999

-     E-mail: npc.drug@sfda.gov.sa

-     Website: https://ade.sfda.gov.sa/

§ Other GCC States:

-     Please contact the relevant competent authority.

Symptoms

The effects of acute toxicity from Pseudoephedrine/triprolidine may include drowsiness, lethargy, dizziness, ataxia, weakness, hypotonicity, respiratory depression, dryness of the skin and mucous membranes, tachycardia, hypertension, hyperpyrexia, hyperactivity, irritability, seizures, and difficulty with micturition.

Pseudoephedrine

Overdose may result in hyperglycaemia, hypokalaemia, CNS stimulation, insomnia; irritability, restlessness, anxiety, agitation; confusion, delirium, hallucinations, psychoses, seizures, tremor, intracranial haemorrhage including intracerebral haemorrhage, drowsiness in children, mydriasis, palpitations, tachycardia, reflex bradycardia, supraventricular and ventricular arrhythmias, dysrhythmias, myocardial infarction, hypertension, vomiting, ischaemic bowel infarction, acute renal failure and difficulty in micturition.

Triprolidine

Overdose of an H1 receptor antagonist may result in CNS depression, hyperthermia, anticholinergic syndrome (mydriasis, flushing, fever, dry mouth, urinary retention, decreased bowel sounds), tachycardia, hypotension, hypertension, nausea, vomiting, agitation, confusion, hallucinations, psychosis, seizures, or dysrhythmias. Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, coma, or seizures

Management

Necessary measures should be taken to maintain and support respiration and control convulsions. Catheterisation of the bladder may be necessary. If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.

Pharmacotherapeutic group: Sympathomimetics, pseudoephedrine combinations

ATC code: R01BA52

Triprolidine provides symptomatic relief in conditions believed to depend wholly or partly upon the triggered release of histamine. It is a potent competitive histamine H₁-receptor antagonist of the pyrrolidine class with mild central nervous system depressant properties which may cause drowsiness. Pseudoephedrine has direct and indirect sympathomimetic activity and is an effective upper respiratory tract decongestant. Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation of systolic blood pressure and considerably less potent in causing stimulation of the central nervous system.

After oral administration of a single dose of 2.5mg triprolidine to adults the onset of action, as determined by the ability to antagonise histamine-induced weals and flares in the skin, is within 1 to 2 hours. Peak effects occur at about 3 hours and, although activity declines thereafter, significant inhibition of histamine-induced weals and flares still occurs 8 hours after the dose.

Pseudoephedrine has direct and indirect sympathomimetic activity and is an effective upper respiratory decongestant. Pseudoephedrine is less potent than ephedrine in producing both tachycardia and elevation of systolic blood pressure and is also less potent in causing stimulation of the central nervous system. Pseudoephedrine produces its decongestant effect within 30 minutes, persisting for at least 4 hours.

After the administration of one pseudoephedrine/triprolidine tablet (containing 2.5 mg triprolidine hydrochloride and 60 mg pseudoephedrine hydrochloride) in healthy adult volunteers, the peak plasma concentration (C_max) of triprolidine is approximately 5.5 ng/ml - 6.0 ng/nl, occurring at about 2.0 hours (T_max) after drug administration. The plasma half life of triprolidine is approximately 3.2 hours. The C_max of pseudoephedrine is approximately 180 ng/ml with T_max approximately 2.0 hours after drug administration. The plasma half life of pseudoephedrine is approximately 5.5 hours (urine pH maintained between 5.0-7.0). The plasma half life of pseudoephedrine is markedly decreased by acidification of urine and increased by alkalinisation.

There is insufficient information available to determine whether triprolidine or pseudoephedrine have mutagenic or carcinogenic potential.

Systematic administration of pseudoephedrine in rats, up to 7 times the human daily dosage in females and 35 times the human daily dosage in males, did not impair fertility nor alter foetal morphological development and survival.

No studies have been conducted in animal to determine if triprolidine has the potential to impair fertility.

Systemic administration of triprolidine in rats and rabbits up to 75 times the human dose did not produce teratogenic effects.

Systemic administration of pseudoephedrine, up to 50 times the human daily dosage in rats and up to 35 times the human daily dosage in rabbits, did not produce teratogenic effects.

Inactive Ingredients:

1.     Lactose monohydrate

2.     Polyvinyl pyrrolidone

3.     Magnesium stearate

4.     Maize starch

5.     Purified water* * Evaporated during manufacturing process, does not appear in the final product.

Not applicable.

24 months from the date of manufacturing.

Store below 30ºC, in a dry place, protected from light.

Pack of 30 Tablets: 3x10’s tablets in an Alu-PVC/PVDC blister strip, packed in a printed box along with a leaflet.

No special requirements.

Any unused product or waste material should be disposed of in accordance with local requirements