Special populations Renal and hepatic impairment
Caution is required in patients with renal or hepatic impairment and dosage adjustment may be necessary .
Contraindications
Known hypersensitivity to pizotifen or to any of the excipients . Mosegor should not be given to children under 2 years of age .
Warnings and precautions
Hepatic injury has been reported , ranging from transaminase elevations to severe hepatitis . Pizotifen treatment should be discontinued if there is any clinical evidence of hepatic dysfunction during treatment and until the cause of the liver abnormality is determined . In view of the slight anticholinergic effect of pizotifen , caution is required in patients with narrowängle glaucoma ( except those successfully treated by surgery ) or urinary retention . ( e.g. in prostatic enlargement ) Seizures as undesirable effects have been observed more frequently in patients with epilepsy . Pizotifen should be used with caution in patients with epilepsy .
Withdrawal symptoms like depression , tremor , nausea , anxiety , malaise , dizziness , sleep disceder and weight decreased have been reported following abrupt cessation of pizottion , therefore gradual withdraw is recommended .
Driving and using machines
Pizotifen may cause sedation , somnolence , dizziness other CNS effects . Therefore , caution should be exercised when driving or using machines , Patients being treated with Mosegor and presenting with sedation and / or somnolence episodes must be instructed to refrain from driving or engaging in activities where impaired alertness , may put themselves or others at risk .
Adverse drug reactions
The most common side effects are appetite stimulating effect , increase in body weight and sedation ( including somnolence and fatigue ) . Adverse reactions are ranked under headings of frequency , the most frequent first , using the following convention : Very common ( > 1/10 ) ; common ( > 1/100 , < 1/10 ) , uncommon ( > 1/1000 , < 1/100 ) ; rare ( > 1 / 10,000 , < 1/1000 ) ; very rare ( < 1 / 10,000 ) , including isolated reports
Adverse drug reactions
Immune system disorders
Rare : Hypersensitivity reactions, face oedems
Metabolism and nutrition disorders
Very common : increased appetite, weight increased
Psychiatric disorders
Rare : Depression, CNS Stimulation (e.g. aggression, agitation ),
Hallucination, insomnia, anxiety
Nervous system disorders
Common : Sedation ( including somnolence ), dizziness
Rare : Paraesthesa
Very rare : Seizures
Gastrointestinal disorders
Common : Nausen , dry mouth Constipation
Uncommon : Constipation
Skin and subcutaneous tissue disorders
Rare : Urticaria , rash
Musculoskeletal and connective tissue disorders
Rare : Myalgin
General disorders and administration site conditions
Common : Fatigue
Adverse drug reactions from post - marketing spontaneous reports
The following additional adverse drug reactions have been identified with pizotifen based on post marketing spontaneous reports . Because these reactions are reported voluntarily from a population of uncertain size , it is not always possible to reliably estimate their frequency .
Hepatobiliary disorders
Unknown : Hepatic enzyme increased , jaundice , hepatitis
Musculoskeletal and connective tissue disorders
Unknown : Muscle cramps
Withdrawal symptoms
Withdrawal reactions have been reported following abrupt cessation of pizotifen , therefore gradual withdrawal is recommended ( see section Warnings and precautions ) . Withdrawal symptoms may include : depression , tremor , nausea , anxiety , malaise , dizziness , sleep disorder and weight decreased
Interactions
The following drugs may exhibit drug interactions with pizotifen upon concomitant administration
Anticipated drug Interactions to be considered
Pizotifen is extensively metabolized in the liver , primarily by N - glucuronidation Incrisased plasma
concentration of pizotifen upon concomitant administration of drugs which exclusively undergo glucuronidation can not be excluded .
Cluapride
Concomitant administration of pizotifen with cisapride may lead to reduced efficacy of cisapride .
Central nervous system agente
Central effects of sedatives , hypnotics , antihistamines ( including certain common cold preparations ) and alcohol may be enhanced .
Pregnancy and breast - feeding Pregnancy
As clinical data for pizotifen in pregnancy are very limited , Sandomigran , Mosegor should be administered in pregnancy only in compelling circumstances .
Breast - feeding
Although the concentrations of pizotifen measured in the milk of treated mothers are not likely to affect the infant , the use of Sandomigran , Mosegor in nursing mothers is not recommanded .
Overdosage Symptoms :
drowsiness , nausea , dry mouth , tachycardia , pyrexia , hypotension , dizziness , excitatory star states ( in children ) , respiratory depression , convulsion ( particularly in children ) , coma .
Treatment :
Administration of activated charcoal is recommended ; in case of very recent intake , gastric lavage may be considered . If necessary , symptomatic treatment should be given including monitoring of the cardiovascular and respiratory symptoms . For excitatory states or convulsions , benzodiazepinos may be used
Interaction with other medicinal products and other forms of Interaction
Central effects of sedatives , hypnotics , antihistamines ( including certain common cold preparations ) and alcohol may be enhanced .
Pregnancy and lactation Pregnancy
As clinical data for pizotifen in pregnancy are very limited , Mosegor should be administered in pregnancy only in compelling circumstances .
Lactation
Although the concentrations of pizotilen measured in the milk of treated mothers are not likely to affect the infant , the use of Mosegor in nursing mothers is not recommended .
Pharmacology Mechanism of action ( MOA )
Pizotifen is characterized by its polyvalent inhibitory effect on biogenic amines , such as serotonin , histamine and tryptamine .
Pharmacodynamic properties
Pharmacotherapeutic group : antimigraine drug , ATC code : N02C X01 Pizotifen is suitable for the prophylactic treatment of migraine , reducing the frequency of attacks Pizoten also possesses appetite - stimulating properties ,
Pharmacokinetic properties Absorption
Following oral administration , the drug is rapidly and almost completely absorbed from the gastrointestinal tract . The mean absolute bioavailability after oral administration is about 80 % .
Distribution
Pizotifen is extensively and rapidly distributed throughout the body with the mean distribution volume of 833 L and 70 L for the parent drug and its metabolite N - glucuronide , respectively . Approximately . 91 % of the drug is bound to plasma proteins .
Metabolism
Pizotifen is extensively metabolized in the liver primarily by glucuronidation . The main metabolite is the N - glucuronide - conjugate and accounts for at least 50 % of the plasma exposure .
Elimination
About one - third of an orally administered dose is excreted via the billary route . A significant proportion of the parent drug , corresponding to about 18 % of the administered dose , is found in the face . Theremaining fraction of the administered doso ( about 58 % ) is primarily oncoinated in the forms of metabolis In the urine . Less than 1 % of the administered dose of pizotifen is excreted unchanged through the kidneys . Pizotifen and ita major metabolite , N - glucuronido conjugate , is eliminated with a half - life.of approximately 23 hours
Special patient groups
In patients with kidney insufficiency dosage adjustment may be necessary Special population Renal impairment No specific pharmacokinetic studies were conducted in patients with ronal impairment . Although pizotifen is primarily eliminated in the form of metabolites in the urine , the possibility of accumulation of inactive metabolites subsequently leading to the accumulation of the parent drug can not be ruled out . Caution is required in patients with renal impairment and dosage adjustment may be necessary . Hepatic impairment Although no specific pharmacokinetic studies were conducted in patients with hepatic impairment , pizotifen is extensively metabolized in liver and primarily eliminated in the form of glucuronides in the urine . Caution is required in patients with hepatic impairment and dosage adjustment may be necessary .
Clinical studies
Mosegor an established product . There are no recent clinical data regarding the approved indications for Mosegor .
Non - clinical safety data Repeat - dose toxicity
Repeat - dose toxicity studies were performed in rats and dogs of up to 2 years duration . Target organs . based on histopathological findings , were liver , kidney and possibly thyroid in rats and liver , thyroid and spleen in dogs . The no - observed - affect level ( NOELY in both rats and dogs was 3 mg / kg which is over 30 - fold greater than the maximum recommended human daily dose .
Reproductive toxicity
Pizotifen hydrogen malate was evaluated in multiple reproductive and developmental toxicity studies for its effects on fertility and its embryotoxic , fetotoxic , teratogenic and developmental toxic potential . There were no specific reproductive or developmental effects observed in mice , rats or rabbits up to the highest tested doses of 30 mg / kg . This dose level is greater than 300 times the daily maximum recommended adult human dose of 0.09 mg / kg .
Mutagenicity
In vitro and in vivo mutagenicity tests were performed and did not reveal any mutagenic activity of pizotifen hydrogen malate .
Carcinogenicity
A 2 - year rat toxicity study did not reveal any gross lesions or masses attributable to pizotifen hydrogen malate administration at dose levels of up to 27 mg / kg which is 300 fold greater than the maximum recommended human daily dose on a mg / kg basis .
Special precautions for storage
Tablet : Protect from heat , light and moisture . Syrup : Protect from heat and light . Mosegor must be kept out of the reach and sight of children ,
Nature and contents of container
Mosegor Tablets = Pack of 30's Mosegor Syrup = Bottle of 60 ml and 120 ml .
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