SUMMARY OF PRODUCT CHARACTERISTICS

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1. NAME OF THE MEDICINAL PRODUCT

DIMENHYDRINAT ROTEXMEDICA 50 mg/mL solution for injection (IM)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One 1 mL ampoule contains 50 mg of Dimenhydrinate.

One 2 mL ampoule contains 100 mg of Dimenhydrinate.

Excipient with known effects: Benzyl alcohol (52.5 mg/ml)

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection (IM)

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

For prophylaxis and symptomatic treatment of:

- nausea and vomiting of various aetiology
- motion sickness

Note:
Dimenhydrinate is not appropriate as a sole agent for treatment of chemotherapy induced nausea and
vomiting.

4.2 Posology and method of administration

Posology

In general, the dosage is:

For adults and adolescents over 14 years:

100-300 mg dimenhydrinate (equivalent to 2-6 ml) per day. A maximum daily dose of 400 mg should
not be exceeded.

For children aged 6 to 14 years:

25-50 mg dimenhydrinate 1-3 times daily. A maximum daily dose of 150 mg should not be exceeded.

For children from 6 kg body weight:

1.25 mg dimenhydrinate/kg body weight, 1-3 times daily.

Overdosing dimenhydrinate can be life threatening, particularly in children below the age of
three years and must therefore be absolutely avoided. See section 4.9.

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Method of administration

For prophylaxis of motion sickness, the initial dose is given approximately ½ - 1 hour prior to
departure.

For the treatment of nausea and vomiting, the doses are spread throughout the day at regular intervals.

For intramuscular administration, Dimenhydrinate solution for injection (IM) must be given as a
deep intragluteal injection.

Dimenhydrinate solution for injection (IM) is, unless otherwise prescribed by a physician, only
intended for short-term use. If symptoms persist, a physician should therefore be consulted. No later
than after 2 weeks of treatment, it should be reviewed whether treatment with Dimenhydrinate solution
for injection (IM) is still necessary.

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
- Porphyria
- Acute asthma attack
- Narrow-angle glaucoma
- Phaeochromocytoma
- Prostatic hyperplasia with residual urine formation,
- Seizure disorders (epilepsy, eclampsia)

Due to the presence of benzyl alcohol, this medicinal product must not be used in newborn infants,
especially those with signs of immaturity.

4.4 Special warnings and precautions for use

Dimenhydrinate solution for injection (IM) may only be used with particular caution in cases of:

− impaired hepatic function,

− cardiac arrhythmias,
− hypokalaemia, hypomagnesaemia,
− bradycardia,
− congenital long QT syndrome or other clinically significant cardiac disorders (especially
coronary heart disease, conduction disturbances, arrhythmias),
− concomitant use of medicinal products that also prolong the QT interval (e.g. class IA or III
antiarrhythmics, antibiotics, antimalarials, antihistamines, antipsychotics) or lead to
hypokalaemia,
− chronic respiratory symptoms and asthma,
− pyloric stenosis.

Dimenhydrinate solution for injection (IM) solution for injection contains 52.5 mg benzyl alcohol per
ml and 520 mg propylene glycol per ml.

Benzyl alcohol may cause anaphylactoid reactions and toxic reactions in infants and children up to 3
years old.

Propylene glycol can cause symptoms such as after drinking alcohol.

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4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use of dimenhydrinate with other CNS depressants (psychotropic agents, hypnotics,
sedatives, analgesics, narcotics) may lead to mutual potentiation of the effects.

During treatment with dimenhydrinate, no alcohol should be consumed, as alcohol can alter and
enhance the effect of dimenhydrinate in an unpredictable manner. The ability to drive and use
machines is further impaired.

The anticholinergic effect of dimenhydrinate may be potentiated by the concomitant administration of

other substances with anticholinergic effects (e.g. atropine, biperiden or tricyclic antidepressants).

During concomitant administration of dimenhydrinate with MAO inhibitors, life-threatening intestinal

paralysis, urinary retention or an increase in intraocular pressure may develop. Furthermore, there may
be a decrease in blood pressure and increased central nervous system and respiratory dysfunction.
Dimenhydrinate must therefore not be administered concomitantly with monoamine oxidase
inhibitors. .

Concomitant use of medicinal products that also prolong the QT interval (e.g. class IA and III
antiarrhythmics, antibiotics, antimalarials, antipsychotics) or lead to hypokalaemia (e.g. certain
diuretics) must be avoided.

The use of dimenhydrinate together with antihypertensive agents can lead to increased fatigue or an
enhanced hypotensive effect.

Dimenhydrinate may possibly lead to false-negative test results in scheduled allergy tests.

Furthermore, it should be noted that ototoxic effects that may possibly occur during aminoglycoside
antibiotic therapy may sometimes be masked by dimenhydrinate.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are inconsistent reports about the safe use of dimenhydrinate during pregnancy. A prospective
study on pregnant women did not reveal any evidence for a relationship between dimenhydrinate
treatment and malformations. Another study described an association between cardiovascular defects
or inguinal hernia with dimenhydrinate exposition during pregnancy.
A case-control study included 38,151 new-borns without congenital malformations and 22,843 with
congenital malformations of whom a total of 2,640 children were exposed to dimenhydrinate.
Dimenhydrinate showed no evidence of teratogenic potential. There are no indications that
dimenhydrinate application leads to a higher abortion rate during the first trimester of pregnancy.
Dimenhydrinate can stimulate preterm uterine contractions and increases the risk for premature labour.
Animal studies with dimenhydrinate are insufficient with respect to reproductive toxicity (see section
5.3).

Dimenhydrinate should only be used during pregnancy if a therapy without medication or a treatment
with other, safe medicinal products were not effective. Dimenhydrinate should not be used during the
third trimester because it can trigger preterm uterine contractions.

Breastfeeding
Dimenhydrinate is excreted into human breast milk. There are no data about the use of dimenhydrinate
during breast feeding. Because undesirable effects on a nursing infant such as increased irritability
cannot be excluded, either [Dimenhydrinate] treatment should be discontinued or breast feeding
should be discontinued.

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Fertility
No data are available (see section 5.3).

4.7 Effects on ability to drive and use machines

Drowsiness, impaired memory and reduced powers of concentration may adversely affect the ability to
drive or use machines. In particular, this applies after an insufficient duration of sleep, at the start of
treatment and when switching medications or in combination with alcohol (see section 4.5).

4.8 Undesirable effects

The following frequencies are used for the evaluation of undesirable effects:
Very common: ≥ 1/10
Common: ≥ 1/100 to < 1/10
Uncommon: ≥ 1/1,000 to < 1/100
Rare: ≥ 1/10,000 to < 1/1,000
Very rare: < 1/10,000
Frequency not known: cannot be estimated from the available data

Especially at the beginning of the treatment undesirable effects such as somnolence, drowsiness,
dizziness, and muscle weakness may occur depending on the individual susceptibility and dose. These
side effects can last into the following day.

System organ class Frequency

Blood and lymphatic system disorders
Psychiatric disorders
Nervous system disorders
Not known: In exceptional cases blood cell damages can
occur.
Common: mood swings.
Not known: drug dependence
Very common: somnolence, drowsiness, dizziness
Common: restlessness, agitation, insomnia, anxiety or
tremor.

Eye disorders Common: visual disturbances (accommodation

weakness, photophobia, impaired night vision,
stereoscopic vision). Increased intraocular pressure.
Cardiac disorders Common: tachycardia.
.
Gastrointestinal disorders Common: constipation, diarrhoea, nausea, vomiting,
epigastric pain.
.
Hepatobiliary disorders Not known: hepatic dysfunction (cholestatic jaundice).
Skin and subcutaneous tissue disorders Common: dry oral and nasal mucosa, blocked nose.
Not known: allergic skin reactions. Skin photosensitivity
(avoid direct sunlight exposure).
Musculoskeletal and connective tissue Very Common: muscle weakness
disorders
Renal and urinary disorders Common: urinary dysfunction.

Sudden discontinuation after long-term daily treatment can temporarily cause insomnia. Therefore,
treatment should be discontinued by gradually decreasing the dose in these cases.

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As with other medicinal products with a hypnotic effect, development of drug dependence cannot be
ruled out after long-term therapy. Therefore, the indication for a treatment longer than only short-term
should be carefully checked.

Paediatric population

Particularly in children, there is the possibility of paradoxical reactions such as restlessness, excitation,
insomnia, anxiety and shaking (tremor).

Dimenhydrinate solution for injection (IM):

Anaphylactoid reactions and toxic reactions may occur as a result of benzyl alcohol in infants and
children up to 3 years old.

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 to report any suspected adverse reactions via the national reporting system
listed in Appendix V.

4.9 Overdose

Intoxication with dimenhydrinate, the active substance of Dimenhydrinate solution for injection (IM),
can be life-threatening. Children are particularly at risk.

In the event of an overdose or poisoning with Dimenhydrinate, a doctor should always be consulted
immediately.

The signs of overdose with Dimenhydrinate solution for injection (IM) are mainly characterised by
different stages of impaired consciousness, ranging from strong drowsiness to coma - depending on
the applied dose. Apart from this, signs of the anticholinergic syndrome are observed: mydriasis,
vision disturbances, tachycardia, hyperthermia, hot, reddened skin and dry mucosal membranes,
constipation, CNS caused restlessness, anxiety, agitation, increased muscle reflexes, and
hallucinations. Furthermore, tonic-clonic seizures and respiratory depression may occur that after high
doses can lead to respiratory paralysis and cardiac arrest. In addition, cardiac dysrhythmias like
prolonged QT intervals (whereas torsades de pointes cannot be ruled out) are possible.

In case of overdose vomiting should not be induced independently from the pharmaceutical form the
patient received.

Further treatment should be based on the respective symptoms: in case of spasm diazepam can be
given, fever-reducing treatment if necessary, artificial respiration in case of potential respiratory
paralysis. Physostigmine salicylate is recommended as an antidote for anticholinergic symptoms (after
performing a physostigmine test).

Due to high degree of plasma protein binding and a high distribution volume forced diuresis or
haemodialysis are not effective in case of intoxications with dimenhydrinate as a sole agent.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiemetics and antinauseants, antihistamines

ATC code: A04AB02

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Dimenhydrinate is the salt of diphenhydramine and 8-chlortheophylline. The pharmacological effects
are caused by diphenhydramine.
Diphenhydramine is an ethanolamine derivate with H1 antihistaminic, anticholinergic and pronounced
CNS sedating properties. In addition, dimenhydrinate has antiemetic and local anaesthetic effects.

5.2 Pharmacokinetic properties

Dimenhydrinate is well absorbed after oral and rectal administration. It dissociates in the blood into
diphenhydramine and 8-chlorotheophylline. Diphenhydramine undergoes extensive first-pass
metabolism in the liver (about 50%).

The duration of action is generally 3 - 6 hours.

Diphenhydramine is well distributed within the body, including the central nervous system. There is
rapid redistribution of diphenhydramine from the blood into tissue. The relative volume of distribution
is 3 to 4 L/kg. Dimenhydrinate is highly bound to plasma proteins, crosses the placental barrier and
passes into breast milk.

Diphenhydramine is metabolised in the liver and primarily excreted via the kidneys, largely in
metabolised form. Excretion is usually complete within 24 hours.

5.3 Preclinical safety data

Limited experience from animal studies with single and repeated dose application reveal no additional
specific hazards to humans, beyond those already mentioned in other parts of the SmPC.

In electrophysiological in vitro tests with concentrations that exceeded the therapeutically effective
dose by a factor of approximately 40, diphenhydramine blocked the rapid delayed rectifier K+ channel
and extended the duration of the action potential. Therefore, diphenhydramine has the potential to
induce torsade de pointes arrhythmias, if there are additional auxiliary factors. This is supported by
single case reports of diphenhydramine.

Dimenhydrinate was tested in vitro for mutagenic effects. The tests did not show any relevant
indications for mutagenic effects.

There are no data from long-term carcinogenicity studies with dimenhydrinate. Carcinogenicity
studies with diphenhydramine did not provide any indication of a tumour-inducing potential in
humans.

Reproductive toxicity
Dimenhydrinate is only insufficiently investigated for reproductive toxicity. Animal studies on
embryo- and foetal- toxicity of dimenhydrinate were negative, but the amount of data was insufficient.
Animal studies have not been performed to assess the risk of impairment of fertility.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Benzyl alcohol (52.5 mg/ml), Propylene glycol (520.0 mg/ml), Hydrochloric acid (pH adjustment),
Water for injection .

6.2 Incompatibilities

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This medicinal product must not be mixed with other medicinal products except those mentioned in
section 6.6.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store in the original package in order to protect from light.

6.5 Nature and contents of container

Clear and colourless solution in 1 mL or 2 mL colourless glass ampoules.

Boxes of 5 or 50 ampoules of 1 mL.
Boxes of 5 or 50 ampoules of 2 mL.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

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

7. MARKETING AUTHORISATION HOLDER

PANPHARMA
ZI du Clairay
35133 Luitré
France

8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: [To be completed nationally]

10. DATE OF REVISION OF THE TEXT

[To be completed nationally]