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DICONAL 10 MG + 30 MG TABLETS

Active substance(s): CYCLIZINE HYDROCHLORIDE / DIPIPANONE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS
1.

NAME OF THE MEDICINAL PRODUCT
Diconal 10 mg + 30 mg Tablets.
Dipipanone/Cyclizine 10 mg/30 mg Tablets.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 10 mg of Dipipanone Hydrochloride and 30 mg of Cyclizine
Hydrochloride
Excipient with known effect:
Lactose: 91.666 mg
For the full list of excipients, see section 6.1.
3.

PHARMACEUTICAL FORM
Tablet coloured deep pink, scored and coded 'F3A'
The scoreline is only to facilitate breaking for ease of swallowing and not to divide into
equal doses

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications
Diconal Tablets are indicated for the management of moderate to severe pain in medical
and surgical conditions in which morphine may be indicated.
Cyclizine is effective in preventing nausea and vomiting associated with the
administration of narcotic analgesics.

4.2

Posology and method of administration
Posology:
Adults:
The initial dose in all conditions is one tablet every 6 hours. It is unwise to exceed this
dose in view of the difficulty in accurately predicting the initial central effects of
dipipanone.
Should this dose fail to provide adequate analgesia, as in severe intractable pain or when
other potent opioids have been used, it may be increased by half a tablet every six hours.

It is seldom necessary to exceed a dose of 30 mg dipipanone given 6-hourly (i.e. 12
tablets in 24 hours).
Older people:
There is no specific information on the use of Diconal in elderly patients. In common
with opioid drugs, Diconal may be expected to cause confusion in this age group, and
careful monitoring is advised (see section 4.4).
Paediatric population:
There is no specific information on the use of Diconal in children. Diconal is very rarely
indicated in children and dosage guidelines cannot be stated.
Method of administration:
Oral
4.3

Contraindications
Diconal is contraindicated in:
Individuals who are hypersensitive to dipipanone or cyclizine or to any of the
excipients listed in section 6.1.
Patients with respiratory depression, especially in the presence of cyanosis and excessive
bronchial secretions.
Patients with obstructive airway disease, during an attack of bronchial asthma or in heart
failure secondary to chronic lung disease.
Head injury and raised intracranial pressure.
Acute alcohol intoxication. The anti-emetic properties of cyclizine may increase the
toxicity of alcohol.
Individuals receiving monoamine oxidase inhibitors, or within 14 days of stopping such
treatment.
Patients with ulcerative colitis since in common with other narcotic analgesics it may
precipitate toxic dilatation or spasm of the colon.
Patients with paralytic ileus and delayed gastric emptying.
Patients with spasm of the biliary or renal tract, particularly immediately after
operative interventions on the biliary tract.
Pre-operative period or during the first 24 hours post operatively.

Patients with severe hepatic impairment as it may precipitate hepatic encephalopathy or
coma.
Severe renal impairment. Diconal, in common with all narcotic analgesics, may
precipitate coma or severe and prolonged respiratory depression.
4.4

Special warnings and precautions for use
Concomitant use of alcohol and Diconal tablets may increase the undesirable effects of
Diconal tablets and should be avoided.
The repeated use of Diconal may lead to tolerance and physical dependence as well as to
psychological dependence on the product. Abrupt cessation of therapy after prolonged
use may result in withdrawal symptoms.
Misuse of Diconal has been reported, particularly by young addicts who have previously
been dependent on, or have misused other agents both opiate and non-opiate. Extreme
caution is warranted when prescribing Diconal to this group of patients.
Diconal should be used with caution in the debilitated since they may be more sensitive
to the respiratory depressant effects.
Diconal should be used with caution (including consideration of dose administered) in the
presence of the following:
Convulsive disorders
Delirium tremens
Hypothyroidism
Adrenocortical insufficiency
Hypopituitarism;
Prostatic hypertrophy
Shock
Diabetes mellitus
Myasthenia gravis
Hypotension and hypovolaemia
Pancreatitis
Obstructive bowel disorders
Inflammatory bowel disorders
Diseases of the biliary tract (see section 4.3)
Impaired respiratory function (see section 4.3)
Urinary retention
Diconal should not be used where there is a possibility of paralytic ileus occurring (see
section 4.3). Should paralytic ileus be suspected to occur during use, treatment should be
discontinued immediately.

Diconal is metabolised in the liver and excreted along with its metabolites in the urine.
Where not contraindicated in patients with impaired hepatic and/or renal function,
Diconal should be given at less than the usual recommended dose, and the patient's
response used as a guide to further dosage requirements.
Cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean
arterial pressure and pulmonary wedge pressure. Diconal should therefore be used with
caution in patients with severe heart failure.
Cyclizine should be avoided in patients with porphyria. Therefore use of Diconal should
also be avoided in these patients.
Because cyclizine has anticholinergic activity it may precipitate incipient glaucoma. It
should be used with caution and appropriate monitoring in patients with glaucoma.
Extreme caution should be exercised when administering Diconal to patients with
phaeochromocytoma, since hypertension has been reported in association with other
potent opioids.
Diconal tablets contain lactose
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction
The central nervous system depressant effects of Diconal may be increased by
phenothiazine drugs, alcohol, sedatives, gabapentin, antihypertensives, barbiturates,
hypnotics, neuroleptics, muscle relaxants and tricyclic antidepressants. Concurrent
administration of some phenothiazines increases the respiratory depressant effects of
narcotic analgesics and also produces hypotension.
Cyclizine enhances the soporific effect of pethidine.
The action of opioids may in turn affect the activities of other compounds, for example its
gastrointestinal effects may delay absorption as with mexiletine or may be counteractive
as with metoclopramide.
Monoamine oxidase inhibitors (MAOIs) may prolong and enhance the respiratory
depressant effects of opioids. Opioids and MAOIs used together may cause fatal
hypotension and coma (see section 4.3 ).
Cimetidine inhibits the metabolism of opioids.
Because of its anticholinergic activity, cyclizine may enhance the side effects of other
anticholinergic agents.

Cyclizine may mask the warning signs of damage caused by ototoxic drugs such as
aminoglycoside antibacterials.
Analgesic effects of opioid drugs tend to be enhanced by co-administration of
dexamphetamine and hydroxyzine
Opioids may reduce the efficacy of diuretics by inducing the release of antidiuretic
hormone.
Propranolol has been reported to enhance the lethality of toxic doses of opioids in
animals, although the significance of this finding is not known for man. Caution should
be exercised when these drugs are administered concurrently.
In vitro data suggest that St. John’s Wort (Hypericum perforatum) may induce
cytochrome P450 3A4. There is a theoretical possibility therefore, that plasma levels of
opioids may be decreased during concomitant administration and increased upon
withdrawal of St. John’s Wort.
Although there are no pharmacokinetic data available for concomitant use of ritonavir
with opioids, ritonavir induces the hepatic enzymes responsible for the glucuronidation of
opioids, and may possibly decrease plasma concentrations of opioids.
Interference with laboratory tests
Opioids can react with Folin-Ciocalteau reagent in the Lowry method of protein
estimation.
Opioids can also interfere with the determination of urinary 17-ketosteroids due to
chemical structure effects in the Zimmerman procedure.
4.6.

Fertility, pregnancy and lactation
Pregnancy
There is no evidence on the safety of the combination in human pregnancy nor is there
evidence from animal work that the constituents are free from hazard. However, limited
data from epidemiological studies of cyclizine and morphine in human pregnancies have
found no evidence of teratogenicity. In the absence of definitive human data with the
combination, the use of Diconal in pregnancy is not advised.
It may be anticipated that if given in the last trimester, Diconal would cause withdrawal
symptoms in the neonate.
Diconal is not recommended for use in labour because of its potential to cause respiratory
depression in the neonate.
Breast-feeding:

Cyclizine is excreted in human milk, however, the amount has not been quantified.
Opioids can significantly suppress lactation. Opioids are excreted in human milk, but the
amount is generally considered to be less than 1% of any dose.
Fertility:
Effects of opioid exposure on sexual maturation of male rats, their reproductive capacity
and the development of their progeny have been examined. Results indicated that
exposure during adolescence led to pronounced inhibition of several indices of sexual
maturation (e.g. hormone levels, reduced gonad weights), smaller litters and selective
gender specific effects on endocrine function in the offspring.
A disruption in ovulation and amenorrhoea can occur in women given morphine.

4.7

Effects on ability to drive and use machines
In common with other opioids, dipipanone may produce orthostatic hypotension and
drowsiness in ambulatory patients. Sedation of short duration has been reported in
patients receiving intravenous cyclizine. The CNS depressant effects of Diconal may be
enhanced by combination with other centrally acting agents (see Interaction with other
medicaments and other forms of interactions).
This medicine can impair cognitive function and can affect a patient’s ability to drive
safely. This class of medicine is in the list of drugs included in regulations under 5a of the
Road Traffic Act 1988. When prescribing this medicine, patients should be told:


The medicine is likely to affect your ability to drive



Do not drive until you know how the medicine affects you



It is an offence to drive while under the influence of this medicine

However, you would not be committing an offence (called ‘statutory defence’) if:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the
information provided with the medicine and
o It was not affecting your ability to drive safely

4.8

Undesirable effects

As Diconal contains dipipanone and cyclizine, the type of adverse effects associated with
such compounds may be expected.
Adverse reactions attributable to dipipanone include:

Undesirable effect SOC

Undesirable effect

Immune system disorders

Allergic reaction, anaphylactic reaction,
anaphylactoid reaction.
Metabolism and nutrition disorders Decreased appetite
Psychiatric disorders
Confusion, mood changes, euphoria,
dysphoria, psychosis, restlessness,
insomnia, agitation, hallucinations, drug
dependence, decreased libido.
Ear and labyrinth disorders
Vertigo
Nervous system disorders
Somnolence, sedation, raised intracranial
pressure, involuntary muscle contractions,
dizziness, convulsions, hypertonia,
paraesthesia, syncope, coma, headache,
myoclonus, taste perversion.
Eye disorders
Miosis, visual disturbance.
Cardiac disorders
Tachycardia, bradycardia, palpitations.
Vascular disorders
Facial flushing, hypotension, hypertension,
circulatory failure, orthostatic hypotension
Respiratory, thoracic and
Respiratory depression, respiratory failure,
mediastinal disorders
bronchospasm, pulmonary oedema, cough
decreased.
Gastrointestinal disorders
Constipation, nausea, vomiting, abdominal
pain, ileus, dyspepsia, dry mouth,
exacerbation of pancreatitis.
Hepatobiliary disorders
Biliary pain, biliary spasm.
Skin and subcutaneous tissue
Hyperhidrosis, urticaria, rash, pruritis.
disorders
Renal and urinary disorders
Ureteric spasm, urinary retention, dysuria.
Reproductive system and breast
Amenorrhea, erectile dysfunction.
disorders
General disorders and
Asthenia, drug withdrawal syndrome,
administration site conditions
malaise, peripheral oedema, drug tolerance,
hypothermia.
Investigations
Increased hepatic enzymes.

Adverse reactions attributable to cyclizine include:
Undesirable effect SOC

Undesirable effect

Blood and lymphatic system
disorders

Agranulocytosis, leucopenia, haemolytic
anaemia, thrombocytopenia.

Immune system disorders
Metabolism and nutrition
disorders
Psychiatric disorders

Ear and labyrinth disorders
Nervous system disorders

Eye disorders
Cardiac disorders
Vascular disorders
Respiratory, thoracic and
mediastinal disorders
Gastrointestinal disorders

Hepatobiliary disorders

Skin and subcutaneous tissue
disorders
Musculoskeletal and connective
tissue disorders
Renal and urinary disorders
General disorders and
administration site conditions

Hypersensitivity reactions, including
anaphylaxis has occurred.
Decreased appetite
Disorientation, restlessness or agitation,
nervousness, euphoria, insomnia and
auditory and visual hallucinations have
been reported, particularly when dosage
recommendations have been exceeded.
Tinnitus
Effects on the central nervous system have
been reported with cyclizine these include:
somnolence, headache,
dystonia, decreased consciousness,
dyskinesia, extrapyramidal motor
disturbances, tremor, convulsions,
dizziness, decreased consciousness,
transient speech disorders, paraesthesia,
generalised chorea, drowsiness,
incoordination.
There have been rare case reports of
patients experiencing depressed levels of
consciousness/loss of consciousness.
Blurred vision, oculogyration.
Tachycardia, palpitations, arrhythmias.
Hypertension, hypotension.
Bronchospasm, apnoea, nasal dryness, dry
throat.
Dryness of the mouth, nose and throat.
Constipation, increased gastric reflux,
nausea, vomiting, diarrhoea, stomach pain.
Hepatic dysfunction, including hepatitis
due to hypersensitivity.
Cholestatic jaundice, cholestatic hepatitis
Urticaria, drug rash, angioedema
allergic skin reactions, fixed drug eruption,
photosensitivity.
Twitching, muscle spasms.
Urinary retention.
Asthenia, malaise

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked t o report any suspected adverse reactions via
Yellow Card Scheme (Website: www.mhra.gov.uk/yellowcard).
4.9

Overdose
Symptoms:
The signs of overdosage with Diconal are those pathognomic of opioid poisoning i.e.
respiratory depression, bradycardia, pin point pupils, hypotension, circulatory failure and
deepening coma. Mydriasis may replace miosis as asphyxia intervenes. Opioid overdose
can result in death.
Drowsiness, floppiness, miosis and apnoea are signs of opioid overdosage in children as
are convulsions.
Rhabdomyolysis progressing to renal failure has been reported in opioid overdosage.
Signs and symptoms of acute toxicity from cyclizine arise from peripheral anticholinergic
effects and effects on the central nervous system.
Peripheral anticholinergic symptoms include, dry mouth, nose and throat, blurred vision,
tachycardia and urinary retention.
Central nervous system effects include drowsiness, dizziness, incoordination, ataxia,
weakness, hyperexcitability, disorientation, impaired judgement, hallucinations,
hyperkinesia, extrapyramidal motor disturbances, convulsions, hyperpyrexia and
respiratory depression.
Management:
It is imperative to maintain and support respiration and circulation.
The specific opioid antagonist naloxone is the treatment of choice for the reversal of
coma and restoration of spontaneous respiration. The literature should be consulted for
details of appropriate dosage.
The use of a specific opioid antagonist in patients tolerant to dipipanone may produce
withdrawal symptoms.
Convulsions should be controlled with parenteral anticonvulsant therapy.
Patients should be monitored closely for at least 48 hours in case of relapse.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Piperazine derivatives.
ATC code:R06AE
Mechanism of action:
The onset of analgesic action of dipipanone is approximately one hour and lasts for 4 to 6
hours.
Cyclizine is a histamine H1 receptor antagonist of the piperazine class which is
characterised by a low incidence of drowsiness. It possesses anticholinergic and
antiemetic properties. The exact mechanism by which cyclizine can prevent or suppress
both nausea and vomiting from various causes is unknown. Cyclizine increases lower
oesophageal sphincter tone and reduces the sensitivity of the labyrinthine apparatus. It
may inhibit the part of the midbrain known collectively as the emetic centre. Cyclizine
produces its anti-emetic effect within 2 hours and lasts for approximately 4 hours.
5.2

Pharmacokinetic properties
Absorption:
Dipipanone is absorbed from the gastrointestinal tract.
In healthy adult volunteers, the administration of a single oral dose of 50 mg cyclizine
resulted in a peak plasma concentration of approximately 70 nanogram/ml occurring
approximately 2 hours after drug administration.
Biotransformation:
Dipipanone is metabolised in the liver.

Elimination:
Dipipanone excreted in the urine and faeces, although data on the proportions of parent
compound and metabolites so excreted are lacking.
The plasma elimination half-life was approximately 20 hours.
The N-demethylated derivative, norcyclizine, has been identified as a metabolite of
cyclizine. Norcyclizine has little antihistaminic (H1) activity compared with cyclizine
and has a plasma elimination half life of approximately 20 hours. After a single oral dose
of 50 mg cyclizine given to a single adult male volunteer, urine collected over the
following 24 hours contained less than 1% of the total dose administered.

5.3

Preclinical safety data
A. Mutagenicity
Cyclizine was not mutagenic in an Ames test (at a dose level of 100 µg/plate), with or
without metabolic activation.

No bacterial mutagenicity studies with dipipanone have been reported. A review of the
literature with regards to opioids has indicated that morphine was negative in gene
mutation assays in Drosophila melanogaster, but was positive in a mammalian
spermatocyte test. The results of another study by the same authors has indicated that
morphine causes chromosomal aberrations, in germ cells of male mice when given at
dose levels of 10, 20, 40 or 60 mg/kg bodyweight for 3 consecutive days.
B. Carcinogenicity
No long term studies have been conducted in animals to determine whether cyclizine or
dipipanone are potentially carcinogenic.
C. Teratogenicity
Some animal studies indicate that cyclizine may be teratogenic at dose levels up to 25
times the clinical dose level. In another study, cyclizine was negative at oral dose levels
up to 65 mg/kg in rats and 75 mg/kg in rabbits. The relevance of these studies to the
human situation is not known.
There is no data of relevance for dipipanone, however, morphine was shown not to be
teratogenic in rats when dosed for up to 15 days at 70 mg/kg/day. Morphine given
subcutaneously to mice at very high doses (200, 300 or 400 mg/kg/day) on days 8 or 9 of
gestation, resulted in a few cases of exencephaly and axial skeletal fusions. The hypoxic
effects of such high doses could account for the defects seen.
Lower doses of morphine (40, 4.0 or 0.4 mg/ml) given to mice as a continuous i.v.
infusion (at a dose volume of 0.3 ml/kg) between days 7 and 10 of gestation, caused soft
tissue and skeletal malformations as shown in previous studies.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

6.2

Lactose, starches, dye (FD and C Red No. 3), gelatin, magnesium stearate.
Incompatibilities

6.3

Not applicable.
Shelf life

6.4

5 years
Special precautions for storage

6.5

Store below 25°C. Protect from light. Keep dry.
Nature and contents of container
PVC/aluminium foil blister packs containing 50 tablets.

6.6

Special precautions for disposal

No special requirements.
7.

MARKETING AUTHORISATION HOLDER
Amdipharm UK Limited
Capital House,
85 King William Street,
London EC4N 7BL,
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 20072/0009

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
Date of first authorisation:15th September 2003

10

DATE OF REVISION OF THE TEXT
29/03/2016

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Source: Medicines and Healthcare Products Regulatory Agency

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