Difflam Anti-Inflammatory Loz (with cough suppressant)

Difflam Anti-Inflammatory Loz (with cough suppressant)

Manufacturer:

iNova

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Benzydamine hydrochloride, cetylpyridinium chloride, pholcodine.
Description
Actives: Benzydamine Hydrochloride 1.5 mg, Cetylpyridinium Chloride 1.33 mg, Pholcodine 5.5 mg per lozenge. Also contains isomalt and saccharin sodium.
Benzydamine is 1-Benzyl-3-(3-dimethylaminopropoxy)-1H-indazole.
Benzydamine hydrochloride is a white, odourless, crystalline powder with a bitter taste, soluble in water, ethanol, methanol and chloroform.
It is sparingly soluble in ether and petroleum ether.
Pholcodine is 3-0-(2-Morpholinoethyl) morphine monohydrate.
Pholcodine is colourless crystals or a white or almost white crystalline powder. Freely soluble in alcohol and acetone but less soluble in water.
Cetylpyridinium chloride is 1-Hexadecylpyridinium chloride monohydrate. Cetylpyridinium chloride is a white unctuous powder with a slight characteristic odour, very soluble in alcohol and chloroform; very slightly soluble in ether.
Action
Pharmacology: Benzydamine is an anti-inflammatory analgesic agent structurally unrelated to the steroid group. Benzydamine differs chemically from other non-steroidal anti-inflammatory agents in that it is a base rather than an acid.
Animal models show that when administered systemically, benzydamine is effective against pain and oedema due to inflammatory conditions. It also inhibits granuloma formation.
At concentrations used for topical treatment, benzydamine possesses local anaesthetic action. Benzydamine does not cause erosion of the gastric mucosa when given orally to rats at doses of up to 100 mg/kg.
The analgesic activity of benzydamine was more pronounced in models involving an experimental inflammation rather than in non-inflammatory pain. In common with the aspirin-like drugs, benzydamine possesses an antipyretic activity. Peripheral reflexes were transiently inhibited after intravenous administration to cats.
Pholcodine is an opioid chemically related to morphine. Pholcodine is a cough suppressant and has a mild sedative effect which relieves local irritation of the respiratory tract.
Pholcodine has little or no analgesic action. Unlike, morphine, codeine and dihydrocodeine therapeutic doses of pholcodine to not cause depression of respiration, CNS excitation, constipation or other side effects associated with narcotics.
Pholcodine is not euphorigenic therefore psychological dependence is unlikely to be a problem. There is no evidence of physical dependence after prolonged administration of pholcodine so it is not likely to be habit forming.
Isomalt is a sugar-substitute. It is a disaccharide alcohol and is an approximately equimolar mixture of glucose-mannitol and glucose-sorbitol. Isomalt produces no measurable changes in blood glucose levels.
Pharmacodynamics: The mechanism of anti-inflammatory action of benzydamine is not related to stimulation of the pituitary-adrenal axis. Like other non-steroidal anti-inflammatory agents, benzydamine inhibits the biosynthesis of prostaglandins under certain conditions, but its properties in this respect have not been fully elucidated. The stabilising effect on cellular membranes may also be involved in the mechanism of action.
Pholcodine acts primarily on the CNS causing depression of the cough reflex which is due to partly to the direct effect on the cough centre in the medulla. Pholcodine has a selective effect on the cough centre without affecting the respiratory centre.
Pharmacokinetics: Absorption: Benzydamine is well absorbed following oral administration. Following topical administration of benzydamine hydrochloride in solution form, benzydamine is well absorbed into the inflamed oral mucosa where it exerts anti-inflammatory and local anaesthetic actions. Plasma benzydamine levels following use of benzydamine solutions are low and parallel the amount actually ingested.
Pholcodine is readily absorbed from the gastrointestinal tract and does cross the blood-brain barrier.
Excretion: Benzydamine and its metabolites are excreted largely in the urine.
Metabolism is largely by oxidative pathways, although dealkylation can be shown.
Benzydamine has been detected in blood and urine following gargling with Difflam solutions. Most of the absorbed dose was eliminated in the first 24 hours. Repeated administration for 7 days did not result in accumulation of benzydamine in plasma.
Pholcodine is metabolised in the liver and its action may be prolonged in hepatic insufficiency. Pholcodine is not metabolised to morphine in man, a fact which may contribute to its more favourable toxicity profile. The low metabolism of the rather lipophilic pholcodine is the reason for its very slow elimination.
Indications/Uses
For temporary relief of painful conditions of the mouth and throat: to suppress unproductive coughs.
Dosage/Direction for Use
Difflam Anti-inflammatory Lozenges with Cough Suppressant should not be chewed. They should be slowly dissolved in the mouth. Slowly dissolve two lozenges in the mouth one at a time. Use two additional lozenges every 3 hours as required, up to a maximum of 12 lozenges per day. For children 6 to 12 years one lozenge should be sucked slowly every 3 hours as required, up to a maximum of 8 per day. Uninterrupted treatment should not exceed seven days.
With Impaired Renal Function: Since absorbed benzydamine and its metabolites are excreted in the urine, the possibility of systemic effects should be considered in patients with severe renal impairment.
With Impaired Liver Function: Since absorbed benzydamine is highly metabolised in the liver the possibility of systemic effects should be considered in patients with severe hepatic impairment. Pholcodine is metabolised in the liver and its action may be prolonged in hepatic insufficiency.
Overdosage
There are no known cases of overdosage with Difflam lozenges.
Adverse CNS effects have been reported following overdosage with high doses of benzydamine hydrochloride in solution form. There is no specific antidote for benzydamine and should excessive quantities be ingested the treatment should be symptomatic. Excess consumption of products containing isomalt may have a laxative effect.
Contraindications
Patients with known hypersensitivity to benzydamine, cetylpyridinium chloride or pholcodine or to any of the components of the vehicle.
Special Precautions
If a sore throat is either caused or complicated by a bacterial infection, appropriate antibacterial therapy should be considered in addition to the use of Difflam Anti-Inflammatory Lozenges with Cough Suppressant.
For use in patients with hepatic or renal impairment see Dosage & Administration.
Excess consumption of products containing isomalt may have a laxative effect.
Risks from Concomitant Use with Benzodiazepines: Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Difflam Anti-inflammatory Lozenges with Cough Suppressant with benzodiazepines. Observational studies have demonstrated that concomitant use of opioids and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
If the decision is made to newly prescribe a benzodiazepine and an opioid together, prescribe the lowest effective dosages and minimum durations of concomitant use.
If the decision is made to newly prescribe a benzodiazepine in a patient already receiving an opioid, prescribe a lower initial dose of the benzodiazepine than indicated in the absence of an opioid, and titrate based on clinical response.
If the decision is made to prescribe an opioid in a patient already taking a benzodiazepine, prescribe a lower initial dose of the opioid, and titrate based on clinical response.
Follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when Difflam Anti-inflammatory Lozenges with Cough Suppressant is used with benzodiazepines. Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warm them of the risk for overdose and death associated with the use of benzodiazepines (see Interactions).
Serotonin Syndrome with Concomitant Use of Serotonergic Drugs: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concurrent use of Difflam Anti-inflammatory Lozenges with Cough Suppressant with serotonergic drugs (See Interactions). This may occur within the recommended dosage range.
Serotonin syndrome symptoms may include mental-status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) and can be fatal (See Interactions). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue Difflam Anti-inflammatory Lozenges with Cough Suppressant if serotonin syndrome is suspected.
Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, decreased appetite, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement dosing of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tired as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioid as being more likely to be associated with adrenal insufficiency.
Sexual Function/ Reproduction: Long term use of opioids may be associated with decreased sex hormones levels and symptoms such as low libido, erectile dysfunction, or infertility (see Postmarketing Experience under Adverse Reactions).
Use in Pregnancy: Benzydamine: Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of foetal damage.
The safety of benzydamine hydrochloride has not been established in pregnant patients. Risk to benefit ratio should be established if Difflam Anti-Inflammatory Lozenges with Cough Suppressant are to be used in these patients.
Pholcodine: Pholcodine has been taken by a large number of pregnant women and women of child bearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
Use in Lactation: Pholcodine: No information is available as to whether pholcodine is excreted in breast milk nor whether it has a harmful effect on the newborn. Therefore it is not recommended for nursing mothers unless the expected benefit to the mother outweighs any potential risks to the infant.
Use in Children: Because of the lack of sufficient clinical experience Difflam Anti-Inflammatory Lozenges with Cough Suppressant are not recommended in children under 6 years of age.
Use In Pregnancy & Lactation
Use in Pregnancy: Benzydamine: Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of foetal damage.
The safety of benzydamine hydrochloride has not been established in pregnant patients. Risk to benefit ratio should be established if Difflam Anti-Inflammatory Lozenges with Cough Suppressant are to be used in these patients.
Pholcodine: Pholcodine has been taken by a large number of pregnant women and women of child bearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
Use in Lactation: Pholcodine: No information is available as to whether pholcodine is excreted in breast milk nor whether it has a harmful effect on the newborn. Therefore it is not recommended for nursing mothers unless the expected benefit to the mother outweighs any potential risks to the infant.
Adverse Reactions
Difflam in topical oral preparations is generally well tolerated and side effects are minor.
Benzydamine: The following adverse reactions have been reported after use of benzydamine hydrochloride in solution form.
Local Adverse Reactions: The most commonly reported reaction is oral numbness (2.6%). Occasional burning or stinging may occur and has been reported in 1.4% of treated cases. Other local adverse effects were less common and included dryness or thirst (0.2%), tingling (0.2%), warm feeling in mouth and altered sense of taste (<0.1%).
Systemic Adverse Reactions: These were very uncommon and never of a serious nature. They consisted mainly of nausea, vomiting, retching, gastro-intestinal disorders (0.4%), dizziness (0.1%), headache and drowsiness (<0.1%). Hypersensitivity reactions occur very rarely but may be associated with pruritus, rash, urticaria, photodermatitis and occasionally laryngospasm or bronchospasm.
Pholcodine: Pholcodine may occasionally cause nausea and vomiting. After large doses, drowsiness, restlessness, excitement, ataxia and respiratory depression may occur.
Postmarketing Experience: Serotonin syndrome: (See Precautions).
Adrenal insufficiency: (See Precautions).
Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids. Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and physiological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.
Infertility: Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.
Drug Interactions
There are no known drug interactions with benzydamine. Pholcodine may enhance the effects of CNS depressants.
Benzodiazepines: Due to additive pharmacologic effect, the concomitant use of opioids with benzodiazepines increases the risk of respiratory depression, profound sedation, coma and death.
The concomitant use of opioids and benzodiazepines increases the risk of respiratory depression because of actions at different receptor sites in the central nervous system that control respiration. Opioids interact primarily at μ-receptors, and benzodiazepines interact at GABAA sites. When opioids and benzodiazepines are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.
Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate (see Precautions).
Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation.
Serotonergic Drugs: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Difflam Anti-inflammatory Lozenges with Cough Suppressant if serotonin syndrome is suspected. Examples of serotonergic drugs are selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g. mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (See Precautions).
Storage
Store below 30°C.
Shelf-Life: 2 years.
ATC Classification
R05DA20 - combinations ; Belongs to the class of opium alkaloids and derivatives. Used as cough suppressant.
Presentation/Packing
Loz (round, flat bevelled, 19mm diameter, firm, smooth surfaces, pink to lilac in colour with blackcurrant and sweet flavour) 16's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in