PIRITRAMIDE Solution for injection Ref.[9276] Active ingredients: Piritramide

• As with other opioids, patients on piritramide may experience depression of the CNS or respiratory depression including respiratory arrest and respiratory insufficiency.
• An µ-opioid antagonist, e.g. naloxone, should be available at all times. Due to the long duration of action of piritramide repeated administration of the antagonist may be necessary.
• After administering piritramide there may be a fall in blood pressure. This effect may exceed the norm in hypovolaemic patients or in the presence of additionally administered sedatives.
• Piritramide should only be used with special care with: - acute alcohol intoxication, - convulsions, - head injuries and conditions involving increased intracerebral pressure.
• Care is recommended with hypothyroidism, adrenal cortex insufficiency, prostatic hypertrophy and shock or if the patient has taken substances depressing the CNS (e.g. alcohol, barbiturates, hypnotics, certain benzodiazepines etc.).
• Caution is also indicated with elderly patients, patients with impaired liver function, impaired respiratory function or with an impaired general condition (see also Section 4.2).
• As with other opioids, patients can develop a physical and psychological dependence of piritramide (see Section 4.8). The risk of dependence usually increases with the length of use and with increasing doses. Over time, a higher dose may be required to achieve the same analgesic effect (tolerance).
• Discontinuing the drug, substituting a less potent opioid or administering an antagonist may trigger withdrawal symptoms such as balance disorders, tremor, anxiety, vomiting, diarrhoea and/or high blood pressure.
• Like other opioids, piritramide should be used with caution with: biliary disorders, obstructive and inflammatory bowel diseases, pheochromocytoma, pancreatitis and children aged under 1 year.

Intubation and ventilation equipment should be available when administering high doses.

In patients concurrently receiving other central nervous system depressants (e.g. barbiturates, benzodiazepines, phenothiazines, inhalation anaesthetics, other non selective hypnotics or alcohol) the undesirable effects of piritramide can be enhanced, especially respiratory depression.

With the use of monoamine oxidase inhibitors (MAOIs) within 14 days priori to the opioid application life threatening interactions on the central nervous system, respiratory function and circulation with pethidine were observed and can not be excluded for piritramide. Therefore, MAOIs must be stopped at least 10 days prior to the treatment with piritramide.

Pentazocine partly antagonises the effect of piritramide, e.g. the analgesic effect.

Pregnancy

There is no data from the use of piritramide in pregnant women and only insufficient experimental studies in animals (see section 5.3). The potential risk to humans is unknown. Piritramide is therefore not recommended during pregnancy unless clearly necessary.

Lactation

It is not known whether piritramide passes into breast milk. However, it is known that other opioids pass into breast milk. Piritramide should not be used whilst breast-feeding unless absolutely necessary. Breast-feeding should be discontinued during treatment with piritramide and only resume at least 24 hours after the last dose of piritramide.

It cannot be ruled out that chronic use during pregnancy may lead to habituation and to post-partum withdrawal symptoms in the neonate.

Although it varies widely between individuals, the sedative effect of piritramide must be borne in mind. As a precaution the patient should wait for a minimum of 6 to 8 hours after a single dose of 20 mg piritramide and for a minimum of 12 to 24 hours after repeated administration.

The most commonly reported side effects in 7 clinical studies (pooled data) were (in percentage incidence) increased heart rate (15.0%), low blood pressure (13.1%) and stupor (9.9%).

The frequency of undesirable effects is classified into the following categories:

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
Not known cannot be estimated from the available data

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Immune system disorders

Not known: Anaphylaxis, anaphylactic shock

Psychiatric disorders

Uncommon: Dependence

Not known: Withdrawal symptoms

Nervous system disorders

Common: Stupor, vertigo (dizziness), drowsiness

Uncommon: Headache

Not known: Unconsciousness

Eye disorders

Not known: Miosis

Cardiac disorders

Not known: Bradycardia, bradyarrhythmia, cyanosis

Vascular disorders

Uncommon: Hypotension

Respiratory, thoracic and mediastinal disorders

Not known: Respiratory arrest, respiratory insufficiency, status asthmaticus, bronchospasm, dyspnoea

Gastrointestinal disorders

Common: Nausea, vomiting, retching

Skin and subcutaneous tissue disorders

Common: Pallor

Uncommon: Hyperhidrosis

Not known: Allergic dermatitis, pruritus

General disorders and symptoms at the administration site

Not known: Reactions at the administration site

Investigations

Very common: Increased heart rate, low blood pressure

Uncommon: Reduced respiration rate

Withdrawal symptoms can be triggered by stopping the medication after repeated use, replacement with a less potent opioid or application of an opioid antagonist.

A need to counteract the opioid effect was reported in 0.4% of study patients.

As with other opioids, patients who are on piritramide may experience an inhibition of gastrointestinal motility which can lead to constipation.

With other opioids there have also been reports of dry mouth, increased muscle tone in urinary bladder, gall bladder and pancreas and, in rare cases, difficulties in passing water.

Reporting of suspected side effects

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*.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6 to prevent the possibility of precipitation. Precipitations can occur if the pH is above 4.8.