The State Food and Drug Administration revised the drug inserts for tramadol suppositories and compound preparations

On April 13, the State Construction and Drug Administration issued an announcement on the revision of the drug inserts for tramadol suppositories and compound preparations (No.

attachment1

Tramadol suppository (tramadol hydrochloride suppository) instructions

Amendment requirements

1.

1.

2.

2.

The following adverse reactions/event reports of tramadol preparations were found in post-marketing surveillance:

Digestive system damage: nausea, vomiting, stomach upset, abdominal pain, diarrhea, bloating, abdominal discomfort, dry mouth, hiccups, constipation, abnormal liver function.

Nervous and mental disorders: dizziness, dizziness, headache, convulsions, tremors, numbness, drowsiness, insomnia, abnormal appetite (such as loss of appetite, etc.

Damage to the skin and its accessories: itching, rash (such as erythema, urticaria, maculopapular rash, etc.

Systemic damage: fatigue, chills, fever (high fever), angioedema, severe cases can cause syncope.

Urinary system damage: dysuria, urinary retention, frequent urination.

Cardiovascular system damage: palpitations, tachycardia, bradycardia, lower blood pressure (such as orthostatic hypotension), increased blood pressure, cyanosis, flushing.

Immune dysfunction and infection: allergic-like reactions, allergic reactions, anaphylactic shock.

Respiratory system damage: chest tightness, shortness of breath, dyspnea, respiratory depression.

Others: abnormal vision, muscle weakness, tinnitus, hypoglycemia.

3.

1.

2.
Children under 12 years old.

3.
Those with severe respiratory depression, severe brain injury, confusion, acute or severe bronchial asthma (without resuscitation equipment or monitoring).

4.
Known or suspected gastrointestinal obstruction, including paralytic intestinal obstruction.

5.
For patients with acute poisoning by alcohol, sleeping pills, anesthetics, central analgesics, opioids or psychotropic drugs, this product can aggravate the depression of the central and respiratory systems of these patients.

6.
Patients who have used MAOIs in combination with monoamine oxidase inhibitors (MAOIs) or have used MAOIs in the past 14 days.

Four, [Notes] should include but not limited to the following

1.
For patients with liver and kidney dysfunction, reduce the dosage or extend the interval of administration as appropriate.

2.
Long-term use cannot rule out the possibility of drug resistance or drug dependence.
It is forbidden to be used as a substitute for patients who are dependent on opioids because it cannot suppress the withdrawal symptoms of morphine.

3.
Sudden withdrawal of the drug may cause withdrawal symptoms (such as: anxiety, sweating, insomnia, chills, pain, nausea, tremor, diarrhea, upper respiratory symptoms, hairs, hallucinations, etc.
), it is recommended to slowly reduce the drug.

4.
When taking central nervous system depressants (such as alcohol, opioids, anesthetics, phenothiazines, tranquilizers or sedative hypnotic drugs) at the same time, the treatment must be cautious, because in these cases, respiratory depression and occurrence cannot be ruled out.
The possibility of increased respiratory depression.

5.
Children under 18 years of age undergoing tonsillectomy and/or adenoidectomy and 12-18 years of age have other factors that may increase the sensitivity of tramadol to respiratory depression (obesity, obstructive sleep apnea syndrome or severe lung Diseases): It should be used in medical institutions with rescue conditions.
Closely monitor symptoms related to breathing problems such as slow or superficial breathing, difficulty or noisy breathing, lethargy or weakness, and strengthen monitoring.

If adverse reactions are found, the drug should be stopped in time.

6.
This product may affect the patient's driving and mechanical operation ability, especially when taken at the same time with alcohol.

5.
[Medication for pregnant women and breastfeeding women] item, should include but not limited to the following content

There is no sufficient evidence for the safety of tramadol in pregnant humans.
There are reports showing that long-term use of tramadol preparations during pregnancy may cause neonatal withdrawal syndrome and neonatal seizures.
It is not recommended for pregnant women to use this product.

The use of this product during lactation may lead to the risk of serious adverse reactions in breastfed infants, including excessive sleepiness, difficulty in breastfeeding, or may cause severe breathing problems or even death.
This product is not recommended for breastfeeding women.

6.
[Children's Medications] item, should include but not limited to the following content

1.
This product is forbidden for children under 12 years old.

2.
Children under 18 years of age undergoing tonsillectomy and/or adenoidectomy and 12-18 years of age have other factors that may increase the sensitivity of tramadol to respiratory depression (obesity, obstructive sleep apnea syndrome or severe lung Diseases): It should be used in medical institutions with rescue conditions.
Closely monitor symptoms related to breathing problems such as slow or superficial breathing, difficulty or noisy breathing, lethargy or weakness, and strengthen monitoring.
If adverse reactions are found, the drug should be stopped in time.

7.
[Medications for the Elderly], which should include but not limited to the following

Elderly patients (over 75 years of age) may have a longer drug clearance time, so the dosing interval should be extended according to individual needs.

8.
[Drug Interactions] item should include but is not limited to the following

1.
Combination of this product with ethanol, sedatives, analgesics or other psychotropic drugs can cause acute poisoning.
When combined with central nervous system inhibitors (such as Valium), this product has enhanced sedative and analgesic effects, especially enhanced respiratory depression The effect should be reduced appropriately, and the combined use of barbiturates can prolong the anesthesia time.
In combination with nerve blockers, convulsions have been reported in individual cases.

2.
Carbamazepine is a CYP3A4 inducer, which can reduce the analgesic effect of this product and the effective time of the drug, and increase the risk of seizures related to this product.
Therefore, it is not recommended to use carbamazepine in combination with this product.

3.
It is not recommended to use partial agonists or mixed agonists/antagonists (such as buprenorphine, nalbuphine, pentazocine, butorphanol) in combination with this product, which may reduce the analgesic effect of this product , And/or trigger withdrawal symptoms.

4.
Combined with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), antipsychotics and other drugs that lower the seizure threshold: very rare seizures.

5.
Taking together with selective serotonin reuptake inhibitors (SSRIs) can cause

Increased serotonin activation (serotonin syndrome).

6.
There are individual reports: the interaction with the coumarin anticoagulant leads to an increase in the international normalized ratio (INR).
Therefore, when patients start to take tramadol therapy, anticoagulants should be used with caution.

(Note: In principle, the manual cannot be deleted.
If the safety content of the original approved manual is more comprehensive or stricter than the requirements of this revision, the original approved content should be retained.
If the other contents of the manual are inconsistent with the above revised requirements, they should be included.
Make revisions.
)

Annex 2

Revised requirements for the instructions of tramadol compound preparations

1.
Add warnings

1.
Patients who use tramadol may have the risk of addiction, abuse and misuse.
In severe cases, it can cause overdose and death.
Physicians should carefully evaluate before prescribing this product and regularly monitor the above conditions.

2.
The use of tramadol may cause severe, life-threatening or fatal respiratory depression.
In the initial stage of taking this product or when the dose is increased, adverse reactions such as respiratory depression should be closely monitored.

2.
[Adverse Reaction] item, should include but not limited to the following

The following adverse reactions/event reports were found in this product during post-marketing surveillance:

Digestive system damage: nausea, vomiting, stomach upset, abdominal pain, diarrhea, bloating, abdominal discomfort, dry mouth, hiccups, constipation, abnormal liver function.

Nervous and mental disorders: dizziness, dizziness, headache, tremor, numbness, drowsiness, insomnia, abnormal appetite (such as loss of appetite, etc.
), hallucinations, delirium, irritability, convulsions, drug dependence.

Damage to the skin and its accessories: itching, rash, hyperhidrosis.

Systemic damage: fatigue, chills, fever, severe cases can cause syncope.

Urinary system damage: dysuria, urinary retention, frequent urination.

Cardiovascular system damage: palpitations, tachycardia, decreased blood pressure (such as orthostatic hypotension), increased blood pressure, flushing.

Immune dysfunction and infection: allergic-like reactions, allergic reactions, anaphylactic shock.

Respiratory system damage: chest tightness, shortness of breath, difficulty breathing.

Others: visual impairment, muscle weakness, tinnitus, hypoglycemia.

3.
[Taboo] item, should include but not limited to the following content

1.
Those who are allergic to tramadol or other ingredients in this product or opioids.

2.
Children under 12 years old.

3.
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6.
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2.
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4.
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5.
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6.
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