Generic Name
Ipratropium bromide / Salbutamol sulfate
Brand Name
Ipratrex-S®
Dosage Form
Metered-dose inhaler
Strength
20 mcg/dose Ipratropium bromide – 100 mcg/dose Salbutamol sulfate
Indication
This product is used to treat and prevent symptoms (wheezing and shortness of breath) caused by ongoing lung disease (chronic obstructive pulmonary disease-COPD which includes bronchitis and emphysema). This product contains 2 medications: ipratropium and albuterol (also known as salbutamol). Both drugs work by relaxing the muscles around the airways so that they open up and you can breathe more easily. Controlling symptoms of breathing problems can decrease time lost from work or school.
Recommended Dose:
Dosage of any medicine is determined by your physician.
The recommended dosage of this medicine is as follows:
· Adults and children 12 years or older; 2 doses, four times a day.
· Children less than 12 years old; this medicine is not recommended.
· The maximum dose per day is 12 puffs.
Missed Dose
If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at the regular time. Do not double the dose to catch up.
Route of Elimination
About 80-100% of the administered dose of ipratropium is excreted in the urine leaving less than 20% of the dose to be eliminated through the feces. From the urine eliminated portion, almost all the drug is found unchanged.
However, when ipratropium is orally administered, due to its low absorption, most of the dose is recovered in the feces with a very minimal amount found in the urine.
Salbutamol after oral administration, 58-78% of the dose is excreted in the urine in 24 hours, approximately 60% as metabolites. A small fraction is excreted in the feces.
Half- life
Ipratropium presents a short half-life of about 1.6 hours.
The elimination half-life of inhaled or oral salbutamol has been recorded as being between 2.7 and 5 hours while the apparent terminal plasma half-life of albuterol has been documented as being approximately 4.6 hours.
Clearance
The average clearance rate of ipratropium is of 2.3 L/min with a renal clearance of 0.9 L/min.
The renal clearance of salbutamol has been documented as 272 +/- 38 ml/min after oral administration and 291 +/- 70 ml/min after intravenous administration. Furthermore, the renal clearance of the predominant sulfate conjugate metabolite was recorded as 98.5 +/- 23.5 ml/min following oral administration.
Toxicity
The reported LD50 in mice after oral administration of ipratropium is 1500 mg/kg. However, overdosage is not very likely due to the poor absorption of ipratropium.
Ipratropium was not shown to present carcinogenesis, teratogenesis not mutagenesis potential and it did not present effects on fertility. The only effect after high administration of ipratropium was a reduction in the conception rate.
The expected signs and symptoms with overdosage of albuterol are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms of beta-adrenergic stimulation (e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, metabolic acidosis). In particular, the signs of salbutamol overdosage are significant tachycardia and/or significant muscle tremor.
Hypokalaemia may occur following overdosage with salbutamol. Serum potassium levels should be monitored.
Lactic acidosis has been reported in association with high therapeutic doses as well as overdoses of short-acting beta-agonist therapy, therefore monitoring for elevated serum lactate and consequent metabolic acidosis (particularly if there is persistence or worsening of tachypnea despite resolution of other signs of bronchospasm such as wheezing) may be indicated in the setting of overdose.
Pregnancy and Lactation
-There is no data on use in pregnant women to know this drugs risks, including the risk of fetal harm or reproductive effects.
-Ipratropium has negligible systemic absorption after inhalation, so fetal exposure is not expected with maternal use.
-Published literature, including cohort and case control studies and case series over several decades have not identified a risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with ipratropium use.
-Available data from epidemiological studies and postmarketing reports of fetal outcomes after albuterol use do not consistently demonstrate a risk of major birth defects or miscarriage.
-Labor and delivery: Because of the potential for beta-agonist interference with uterine contractility, this drug during labor should be used only if the benefits clearly outweigh the risk.
-Serious adverse reactions (including pulmonary edema) have occurred during or following treatment of premature labor with beta-2 agonists including albuterol.
Ipratropium bromide: Animal oral reproduction studies demonstrated no evidence of teratogenic effects. Embryotoxicity was observed as increased resorption in rats at oral large doses, however, this effect is not considered relevant to human use.
Salbutamol: It has been shown to be teratogenic in mice and rabbits. A reproduction study in CD-1 mice given salbutamol subcutaneously showed cleft palate formation at approximately 14 times the maximum recommended human daily inhalation dose (MRHDID) in adults. None was observed at less than MRHDID in adults. A reproductive study with oral salbutamol in Stride Dutch rabbits revealed cranioschisis at approximately 1,100 times the MRHDID in adults. A study with radiolabeled salbutamol sulfate demonstrated that drug-related material is transferred from the maternal circulation to the fetus.
There are no adequate and well-controlled studies of the use of this combination drug or its single components in pregnant women. The background birth defect and miscarriage risk for the indicated population is not known. In the US general population, the estimated major birth defect risk is 2 to 4% and the miscarriage risk is 15 to 20%.
-There is no information regarding this drug on the presence in human milk, the effects on a breastfed infant, or effects on milk production.
-Although lipid-insoluble quaternary cations enter breast milk, plasma levels after inhalation of therapeutic doses of ipratropium are low, as are albuterol concentrations; concentrations in human breast milk are expected to be correspondingly low.
-Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for this medication as well as any potential adverse effects from this drug or the underlying maternal condition.
Interactions with medicines
Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
Precautions
Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood pressure, heart disease (such as chest pain, heart attack, irregular heartbeat), personal or family history of glaucoma (angle-closure type), difficulty urinating (for example, due to enlarged prostate), seizure, overactive thyroid (hyperthyroidism), diabetes.
This drug may make you dizzy or blur your vision or cause vision changes. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).
Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).
Older adults may be more sensitive to the side effects of this drug, especially problems urinating or constipation.
During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.
It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.
Side effects
Headache, dizziness, nausea, dry mouth, shaking (tremors), nervousness, or constipation may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.
Rarely, this medication may cause severe sudden worsening of breathing problems right after use. If you have sudden worsening of breathing, get medical help right away.
Tell your doctor right away if you have any serious side effects, including: difficult/painful urination, muscle cramps.
Get medical help right away if you have any serious side effects, including: chest pain, fast/pounding/irregular heartbeat, rapid breathing, confusion, eye pain/swelling/redness, vision changes (such as seeing rainbows around lights at night, blurred vision).
A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
Contraindications
Previous severe allergic reaction symptoms upon the use of ipratropium or atropine and its other derivatives, such as angioedema, urticaria, severe shortness of breath, oropharyngeal edema, and ultimately anaphylaxis is a contraindication to ipratropium use.
Salbutamol sulphate is contraindicated in patients with hypersensitivity (allergy) to any of the active substances or the excipients. Salbutamol and non-selective beta-blocking drugs, such as propranolol, should not usually be prescribed together. Caution is also advised in patients using cardiac glycosides.
Storage
Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.