Amiodaron HCl Merck may be available in the countries listed below.
Amiodarone hydrochloride (a derivative of Amiodarone) is reported as an ingredient of Amiodaron HCl Merck in the following countries:
International Drug Name Search
Lemsip Max All in One Lemon
Powder for Oral Solution
Each sachet (4.8g) of this product contains:
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For full list of excipients, see Section 6.1.
Powder for oral solution
Pale yellow powder.
For the relief of symptoms of colds and influenza, including the relief of aches and pains, sore throat, headache, nasal congestion, lowering of temperature and chesty coughs.
Oral administration after dissolution in water.
Adults and adolescents 12 years and over: One sachet dissolved by stirring in hot water and sweetened to taste.
Dose may be repeated in 4-6 hours. No more than four doses should be taken in 24 hours.
Not to be given in children under 12 without medical advice.
Hypersensitivity to any of the ingredients.
Severe coronary heart disease.
Hypertension.
Concurrent use of monoamine oxidase inhibitors (MAOI).
Paracetamol
Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.
Phenylephrine
Use with caution in patients with Raynaud's phenomenon or diabetes mellitus
Phenylephrine should be used with care in patients with hyperthyroidism, cardiovascular disease, diabetes mellitus, closed angle glaucoma, prostatic enlargement and hypertension.
Sucrose
This product also contains 1973.3mg sucrose per dose (total sugars 2g). Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Sodium
This product contains 129.0mg (5.6mmol) sodium per dose – to be taken into consideration for patients on a controlled sodium diet.
The following warnings will appear on the package label and/or leaflet:
• Contains a source of phenylalanine. May be harmful for people with phenylketonuria.
• Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.
• DO NOT EXCEED THE STATED DOSE.
• CONTAINS PARACETAMOL. Do not take with any other paracetamol-containing products. Immediate medical advice should be sought in the event of an overdose, even if you feel well.
• Keep out of the reach and sight of children.
• If symptoms persist, consult your doctor.
• DO NOT TAKE IF: allergic to any of the ingredients, if you have heart disease or high blood pressure.
• Do not store above 25oC.
• Store in the original package.
• This medicinal product contains 129.0mg sodium per dose. To be taken into consideration by patients on a controlled sodium diet.
• If you are pregnant or are being prescribed medicine by your doctor, seek his advice before taking this product.
• Also contains aspartame, sucrose and sodium.
The rate of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
Phenylephrine may adversely interact with other sympathomimetics, vasodilators and beta-blockers. Drugs, which induce hepatic microsomal enzymes, such as alcohol, barbiturates, monoamine oxidase inhibitors and tricyclic antidepressants, may increase the hepatotoxicity of paracetamol, particularly after overdosage. Not recommended for patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors.
Guaifenesin may increase the rate of absorption of paracetamol. Guaifenesin may interfere with diagnostic measurements of urinary 5-hydroxyindoleactic acid or vanillylmandelic acid.
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use. Paracetamol is excreted in breast milk, but not in a clinically significant amount. Available published data do not contraindicate breast-feeding.
Phenylephrine hydrochloride: Due to the vasoconstrictive properties of phenylephrine, the product should be used with caution in patients with a history of pre-eclampsia. Phenylephrine may reduce placental perfusion and the product should be used in pregnancy only if the benefits outweigh this risk. There is no information on use in lactation.
Guaifenesin: Has been linked with an increased risk of neural tube defects in a small number of women with febrile illness in the first trimester of pregnancy. The product should be used in pregnancy only if the benefits outweigh this risk. There is no information on use in lactation.
Lemsip Max Cold & Flu Breathe Easy has no or negligible influence on ability to drive or use machinery.
Adverse effects of paracetamol are rare, but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
Phenylephrine hydrochloride: High blood pressure with headache, vomiting and rarely, palpitations. Also, rare reports of allergic reactions.
Guaifenesin has occasionally been reported to cause gastro-intestinal discomfort, nausea and vomiting, particularly in very high doses.
Paracetamol: Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).
Risk Factors
If the patient:
(a) Is on long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes, or
(b) Regularly consumes ethanol in excess of recommended amounts, or
(c) Is likely to be glutathione deplete, e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Management
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be discussed with the NPIS or a liver unit.
Phenylephrine hydrochloride: Features of severe overdosage of phenylephrine include haemodynamic changes and cardiovascular collapse with respiratory depression. Treatment includes early gastric lavage and symptomatic and supportive measures. Hypertensive effects may be treated with an i.v. alpha-receptor-blocking agent.
Guaifenesin: Very large doses may cause nausea and vomiting. The drug is, however, rapidly metabolised and excreted in the urine. Patients should be kept under observation and treated symptomatically.
ATC Code: N02B E51.
Paracetamol: Paracetamol has both analgesic and antipyretic activity, which is believed to be mediated principally through its inhibition of prostaglandin synthesis within the central nervous system.
Phenylephrine hydrochloride: Phenylephrine is a post-synaptic alpha-receptor agonist with low cardioselective beta-receptor affinity and minimal central stimulant activity. It is a recognised decongestant and acts by vasoconstriction to reduce oedema and nasal swelling.
Guaifenesin: Guaifenesin is an expectorant which reduces the viscosity of tenacious sputum.
The active ingredients are not known to cause sedation.
Paracetamol: Paracetamol is absorbed rapidly and completely from the small intestine, producing peak plasma levels after 15-20 minutes following oral dosing. The systemic availability is subject to first-pass metabolism and varies with dose between 70% and 90%. The drug is rapidly and widely distributed throughout the body and is eliminated from plasma with a T½ of approximately 2 hours. The major metabolites are glucuronide and sulphate conjugates (>80%) which are excreted in urine.
Phenylephrine hydrochloride: Phenylephrine is absorbed from the gastrointestinal tract, but has reduced bioavailability by the oral route due to first-pass metabolism. It retains activity as a nasal decongestant when given orally, the drug distributing through the systemic circulation to the vascular bed of the nasal mucosa. When taken by mouth as a nasal decongestant phenylephrine is usually given at intervals of 4-6 hours.
Guaifenesin: Guaifenesin is absorbed from the gastrointestinal tract. It is rapidly metabolised by oxidation to ί-(2 methoxy-phenoxy) lactic acid; which is excreted in the urine.
There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.
Ascorbic acid
Sucrose
Citric acid
Sodium citrate
Lemon flavour no. 1
Aspartame (E951)
Saccharin sodium
Curcumin WD
None known.
Two years
Do not store above 25°C. Store in the original package.
Heat-sealed sachet of paper/polyethylene / aluminium foil/polyethylene laminate in an outer cardboard carton.
Carton of 16 sachets.
Not applicable.
Reckitt Benckiser Healthcare (UK) Limited, Dansom Lane, Hull, HU8 7DS, East Yorkshire, UK.
PL 00063/0537
13/10/2009
26/04/2011
Cytropil may be available in the countries listed below.
Piracetam is reported as an ingredient of Cytropil in the following countries:
International Drug Name Search
Treating disorders associated with high levels of the hormone prolactin, either due to tumors in the pituitary gland or to unknown causes. It may also be used for other conditions as determined by your doctor.
Cabergoline is a dopamine receptor agonist. It works by blocking prolactin secretion from the pituitary gland.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Cabergoline. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Cabergoline. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Cabergoline may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Cabergoline as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Cabergoline.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Constipation; dizziness; headache; indigestion; mild stomach pain; nausea; tiredness or weakness; vomiting.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); back pain; behavior changes (eg, aggression, increased gambling or sexual urges); burning, numbness, or tingling; chest pain; confusion; decreased urination; fainting; hallucinations; irregular heartbeat; mood or mental changes (eg, depression); persistent cough; severe or persistent dizziness or light-headedness; severe stomach pain or tenderness; shortness of breath; sudden, unexplained weight gain; swelling of hands, ankles, legs, or feet; vision changes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Cabergoline side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fainting; hallucinations; nasal congestion.
Store Cabergoline at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Cabergoline out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Cabergoline. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Relieving congestion, sneezing, and watery eyes due to colds, flu, or hay fever.
Carboxine 12D Suspension is an antihistamine and decongestant combination. It works by blocking the action of histamine and reducing the symptoms of an allergic reaction. It also relieves nasal congestion by causing vasoconstriction and shrinkage of the nasal mucous membranes and promoting drainage.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Carboxine 12D Suspension. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Carboxine 12D Suspension. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Carboxine 12D Suspension may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Carboxine 12D Suspension as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Carboxine 12D Suspension.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome: Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Appetite loss; diarrhea; dizziness; drowsiness; dry mouth, throat, or nose; headache; heartburn; nausea; nervousness; trouble sleeping; vomiting.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; difficulty urinating; double vision or other vision problems; fast or irregular heartbeat; frequent or painful urination; hallucinations; seizures; severe headache and dizziness; severe nervousness; tremor; weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Carboxine2D side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include decreased mental alertness; fast or irregular heartbeat; fever; hallucinations; nausea; seizures; sleeplessness; sweating; trouble breathing; unusual drowsiness or dizziness; tremors; vomiting.
Store Carboxine 12D Suspension at room temperature between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Keep Carboxine 12D Suspension out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Carboxine 12D Suspension. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Generic Name: colistimethate (koe LIS ti METH ate)
Brand Names: Coly Mycin M
Colistimethate is an antibiotic that fights bacteria in the body.
Colistimethate is used to treat infections caused by bacteria.
Colistimethate may also be used for purposes not listed in this medication guide.
Before using colistimethate, tell your doctor if you are allergic to any drugs, or if you have kidney disease. You may need a dose adjustment or special tests during treatment.
Colistimethate is given as an injection into a muscle or through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection. You may be shown how to inject your medicine at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.
Keep using colistimethate for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Colistimethate will not treat a viral infection such as the common cold or flu.
Before using colistimethate, tell your doctor if you are allergic to any drugs, or if you have kidney disease. You may need dose adjustments or special tests during treatment.
Your doctor will tell you if any of your medication doses need to be changed.
Colistimethate is given as an injection into a muscle or through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection. You may be shown how to inject your medicine at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.
The colistimethate injection is sometimes given every 12 hours. The medication can also be mixed with a liquid in an IV bag and given as a slow infusion over a 24-hour period.
Use each disposable needle and syringe only one time. Throw away used needles and syringes in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.
Use this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.
Keep using colistimethate for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Colistimethate will not treat a viral infection such as the common cold or flu.
Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.
Overdose symptoms may include confusion, dizziness, loss of balance or coordination, blurred vision, slurred speech, severe numbness or tingling, or trouble breathing.
Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or has blood in it, call your doctor. Do not use any medicine to stop the diarrhea unless your doctor has told you to.
diarrhea that is watery or bloody;
fever;
urinating less than usual or not at all;
muscle weakness; or
trouble breathing.
Less serious side effects may include:
mild numbness or tingling in your hands or feet;
dizziness, spinning feeling;
itching, mild skin rash; or
upset stomach.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Usual Adult Dose for Gram Negative Infection:
Parenteral: 2.5 to 5 mg/kg/day IM or IV in 2 to 4 divided doses
Inhalation: 50 to 75 mg in normal saline (3 to 4 mL total volume) via nebulizer 2 to 3 times a day has been suggested
Usual Pediatric Dose for Gram Negative Infection:
Parenteral: 2.5 to 5 mg/kg/day IM or IV in 2 to 4 divided doses
Inhalation:
Neonates: 4 mg/kg/dose every 12 hours has been used to treat ventilator-associated pneumonia
Infants, children, adolescents: 50 to 75 mg in normal saline (3 to 4 mL total volume) via nebulizer 2 to 3 times a day has been suggested
The following antibiotics can interact with colistimethate. Tell your doctor if you are using any of these:
amikacin (Amikin);
gentamicin (Garamycin);
kanamycin (Kantrex);
neomycin (Mycifradin, Neo-Fradin, Neo-Tab);
netilmicin (Netromycin);
polymyxin;
streptomycin; or
tobramycin (Nebcin, Tobi).
This list is not complete and there may be other drugs that can interact with colistimethate. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.
See also: colistimethate side effects (in more detail)
Generic Name: estradiol and norethindrone (topical patches) (ess tra DYE all and nor ETH in drone)
Brand Names: Combipatch
Estradiol is a form of estrogen. Estrogen is a female sex hormone that is involved in the development and maintenance of the female reproductive system.
Norethindrone is a form of progesterone. Progesterone is a female hormone important for the regulation of ovulation and menstruation.
Together, estradiol and norethindrone are used to treat the symptoms of menopause such as feelings of warmth in the face, neck and chest, or sudden intense spells of heat and sweating ("hot flashes" or "hot flushes"); to treat vulvar and vaginal changes (itching, burning, dryness in or around the vagina, difficulty or burning with urination) caused by menopause; and to replace estrogen in conditions such as hypogonadism, removal of the ovaries, or primary ovarian failure that result in a lack of estrogen.
Estradiol and norethindrone may also be used for purposes other than those listed in this medication guide.
Estradiol increases the risk of developing endometrial hyperplasia, a condition that may lead to cancer of the lining of the uterus. Using a progestin, such as norethindrone, with estradiol lowers the risk of developing this condition. Visit your doctor regularly and report any unusual vaginal bleeding right away.
Treatment with estrogens long-term may increase the risk of heart attack, stroke, breast cancer, and blood clots in the lungs or legs. Because of these risks, you should contact your doctor or healthcare provider to discuss your individual risks and benefits before using estradiol and norethindrone long-term. You should also talk to your doctor or healthcare provider on a regular basis (for example, every 3-6 months) about whether you should continue this treatment.
Have yearly physical exams and examine your breasts for lumps on a monthly basis while using estradiol and norethindrone.
a circulation, bleeding, or blood-clotting disorder;
undiagnosed, abnormal vaginal bleeding; or
any type of breast, uterine, or hormone-dependent cancer. or
Using estradiol and norethindrone may be dangerous in some cases if you have any of the conditions listed above.
Before using estradiol and norethindrone, tell your doctor if you have
high blood pressure, angina, or heart disease;
high levels of cholesterol or triglycerides in your blood;
asthma;
epilepsy;
migraines;
depression;
diabetes;
gallbladder disease;
uterine fibroids; or
had a hysterectomy (uterus removed).
You may not be able to use estradiol and norethindrone, or you may need a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.
Use estradiol and norethindrone exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.
To use estradiol and norethindrone patches:
Apply each patch to a smooth (fold free), clean, dry area on your lower abdomen. The area should not be oily, damaged, or irritated.
After opening a pouch, remove one side of the protective liner, taking care not to touch the adhesive part with your fingers. Immediately apply the patch. Remove the second side of the protective liner and press the patch firmly in place with your hand for at least 10 seconds, making sure there is good contact, especially around the edges.
Replace the patch on the same two days each week (every 3 to 4 days) as directed by your doctor. Only one patch should be worn at any time.
Allow at least 1 week to pass between applications of the patch to a given area.
Take care so the patch does not come off during bathing or other activities. If a patch falls off for any reason, reapply it to another site on your lower abdomen. If it will not stick, apply a new patch to a new site. Continue changing the patch on your regular schedule.
Removal of the patch should be done carefully and slowly to avoid irritation of the skin. If any adhesive remains on the skin, allow it to dry for 15 minutes. Then gently rub the area with an oil-based cream or lotion.
Your doctor may prescribe two different patches for you. In this treatment regimen, use the estrogen-only patch for the first 14 days of a 28-day cycle, according to the product directions. Then, use the estradiol and norethindrone patches for the remaining 14 days, according to the product directions. Follow your doctor's instructions or ask your pharmacist for help if you do not remember. Monthly withdrawal bleeding often occurs with this regimen.
Have yearly physical exams and examine your breasts for lumps on a monthly basis while using estradiol and norethindrone.
Apply the next patch as soon as you remember. Continue to follow your regular schedule for changing the patch. Do not use two patches simultaneously unless your doctor directs otherwise.
If a patch falls off for any reason, reapply it to another site on your lower abdomen. If it will not stick, apply a new patch to a new site. Continue changing the patch on your regular schedule.
Symptoms of a estradiol and norethindrone overdose may include nausea, vomiting, and withdrawal bleeding may occur in females.
There are no restrictions on food, beverages, or activity while using estradiol and norethindrone unless your doctor directs otherwise.
Treatment with estrogens long-term may increase the risk of heart attack, stroke, breast cancer, and blood clots in the lungs or legs. Because of these risks, you should contact your doctor or healthcare provider to discuss your individual risks and benefits before using estradiol and norethindrone long-term. You should also talk to your doctor or healthcare provider on a regular basis (for example, every 3-6 months) about whether you should continue this treatment.
an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);
sharp chest pain, coughing of blood or shortness of breath (possible blood clot in the lung );
pain in the calf (possible blood clot in the leg);
crushing chest pain or heaviness in the chest (possible heart attack);
sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (possible stroke);
partial or complete loss of vision (possible clot in the eye);
stomach pain or tenderness, yellowing of the skin or eyes, fever, fatigue, loss of appetite, dark-colored urine, or light-colored stools (possible liver problems); or
new or changing breast lumps.
Other, less serious side effects may be more likely to occur. Continue to use estradiol and norethindrone and talk to your doctor if you experience
nausea and vomiting;
tenderness or enlargement of the breasts;
weakness;
swelling of the hands or feet;
spotty darkening of the skin, particularly on the face;
difficulty in wearing contact lenses;
vaginal irritation or discomfort;
a rash or reaction at the patch application site; or
changes in menstrual cycle, painful menstruation, or breakthrough bleeding.
Estradiol increases the risk of developing endometrial hyperplasia, a condition that may lead to cancer of the lining of the uterus. Using a progestin, such as norethindrone, with estradiol lowers the risk of developing this condition. Visit your doctor regularly and report any unusual vaginal bleeding right away.
Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.
Before using estradiol and norethindrone, tell your doctor if you are taking an anticoagulant (blood thinner) such as warfarin (Coumadin). You may not be able to use estradiol and norethindrone, or you may require a dosage adjustment or special monitoring during treatment if you are taking warfarin (Coumadin).
Drugs other than those listed here may also interact with estradiol and norethindrone. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.
See also: Combipatch side effects (in more detail)
Testosterone Undecanoate may be available in the countries listed below.
Testosterone Undecanoate (BANM, USAN) is known as Testosterone in the US.
International Drug Name Search
Glossary
| BANM | British Approved Name (Modified) |
| USAN | United States Adopted Name |
Pravastatine Qalimed may be available in the countries listed below.
Pravastatin sodium salt (a derivative of Pravastatin) is reported as an ingredient of Pravastatine Qalimed in the following countries:
International Drug Name Search
Panhodiel may be available in the countries listed below.
Sodium Picosulfate monohydrate (a derivative of Sodium Picosulfate) is reported as an ingredient of Panhodiel in the following countries:
International Drug Name Search
Xipagamma may be available in the countries listed below.
Xipamide is reported as an ingredient of Xipagamma in the following countries:
International Drug Name Search
Calan SR (verapamil hydrochloride) is a calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist). Calan SR is available for oral administration as light green, capsule-shaped, scored, film-coated tablets (caplets) containing 240 mg of verapamil hydrochloride; as light pink, oval, scored, film-coated tablets (caplets) containing 180 mg of verapamil hydrochloride; and as light violet, oval, film-coated tablets (caplets) containing 120 mg of verapamil hydrochloride. The caplets are designed for sustained release of the drug in the gastrointestinal tract; sustained-release characteristics are not altered when the caplet is divided in half.
The structural formula of verapamil HCl is:
Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl) hydrochloride
Verapamil HCl is an almost white, crystalline powder, practically free of odor, with a bitter taste. It is soluble in water, chloroform, and methanol. Verapamil HCl is not chemically related to other cardioactive drugs.
Inactive ingredients include alginate, carnauba wax, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl pyrrolidone, talc, titanium dioxide, and coloring agents: 240 mg—D&C Yellow No. 10 Lake and FD&C Blue No. 2 Lake; 120 and 180 mg—iron oxide.
CALAN (verapamil HCl) is a calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist) that exerts its pharmacologic effects by modulating the influx of ionic calcium across the cell membrane of the arterial smooth muscle as well as in conductile and contractile myocardial cells.
Verapamil exerts antihypertensive effects by decreasing systemic vascular resistance, usually without orthostatic decreases in blood pressure or reflex tachycardia; bradycardia (rate less than 50 beats/min) is uncommon (1.4%). During isometric or dynamic exercise, CALAN does not alter systolic cardiac function in patients with normal ventricular function.
CALAN does not alter total serum calcium levels. However, one report suggested that calcium levels above the normal range may alter the therapeutic effect of CALAN.
CALAN dilates the main coronary arteries and coronary arterioles, both in normal and ischemic regions, and is a potent inhibitor of coronary artery spasm, whether spontaneous or ergonovine-induced. This property increases myocardial oxygen delivery in patients with coronary artery spasm and is responsible for the effectiveness of CALAN in vasospastic (Prinzmetal's or variant) as well as unstable angina at rest. Whether this effect plays any role in classical effort angina is not clear, but studies of exercise tolerance have not shown an increase in the maximum exercise rate–pressure product, a widely accepted measure of oxygen utilization. This suggests that, in general, relief of spasm or dilation of coronary arteries is not an important factor in classical angina.
CALAN regularly reduces the total systemic resistance (afterload) against which the heart works both at rest and at a given level of exercise by dilating peripheral arterioles.
Electrical activity through the AV node depends, to a significant degree, upon calcium influx through the slow channel. By decreasing the influx of calcium, CALAN prolongs the effective refractory period within the AV node and slows AV conduction in a rate-related manner.
Normal sinus rhythm is usually not affected, but in patients with sick sinus syndrome, CALAN may interfere with sinus-node impulse generation and may induce sinus arrest or sinoatrial block. Atrioventricular block can occur in patients without preexisting conduction defects (see WARNINGS).
CALAN does not alter the normal atrial action potential or intraventricular conduction time, but depresses amplitude, velocity of depolarization, and conduction in depressed atrial fibers. CALAN may shorten the antegrade effective refractory period of the accessory bypass tract. Acceleration of ventricular rate and/or ventricular fibrillation has been reported in patients with atrial flutter or atrial fibrillation and a coexisting accessory AV pathway following administration of verapamil (see WARNINGS).
CALAN has a local anesthetic action that is 1.6 times that of procaine on an equimolar basis. It is not known whether this action is important at the doses used in man.
With the immediate-release formulation, more than 90% of the orally administered dose of CALAN is absorbed. Because of rapid biotransformation of verapamil during its first pass through the portal circulation, bioavailability ranges from 20% to 35%. Peak plasma concentrations are reached between 1 and 2 hours after oral administration. Chronic oral administration of 120 mg of verapamil HCl every 6 hours resulted in plasma levels of verapamil ranging from 125 to 400 ng/mL, with higher values reported occasionally. A nonlinear correlation between the verapamil dose administered and verapamil plasma level does exist. In early dose titration with verapamil, a relationship exists between verapamil plasma concentration and prolongation of the PR interval. However, during chronic administration this relationship may disappear. The mean elimination half-life in single-dose studies ranged from 2.8 to 7.4 hours. In these same studies, after repetitive dosing, the half-life increased to a range from 4.5 to 12.0 hours (after less than 10 consecutive doses given 6 hours apart). Half-life of verapamil may increase during titration. No relationship has been established between the plasma concentration of verapamil and a reduction in blood pressure.
Aging may affect the pharmacokinetics of verapamil. Elimination half-life may be prolonged in the elderly. In multiple-dose studies under fasting conditions, the bioavailability, measured by AUC, of Calan SR was similar to CALAN (immediate release); rates of absorption were of course different.
In a randomized, single-dose, crossover study using healthy volunteers, administration of 240 mg Calan SR with food produced peak plasma verapamil concentrations of 79 ng/mL; time to peak plasma verapamil concentration of 7.71 hours; and AUC (0–24 hr) of 841 ng∙hr/mL. When Calan SR was administered to fasting subjects, peak plasma verapamil concentration was 164 ng/mL; time to peak plasma verapamil concentration was 5.21 hours; and AUC (0–24 hr) was 1,478 ng∙hr/mL. Similar results were demonstrated for plasma norverapamil. Food thus produces decreased bioavailability (AUC) but a narrower peak-to-trough ratio. Good correlation of dose and response is not available, but controlled studies of Calan SR have shown effectiveness of doses similar to the effective doses of CALAN (immediate release).
In healthy men, orally administered CALAN undergoes extensive metabolism in the liver. Twelve metabolites have been identified in plasma; all except norverapamil are present in trace amounts only. Norverapamil can reach steady-state plasma concentrations approximately equal to those of verapamil itself. The cardiovascular activity of norverapamil appears to be approximately 20% that of verapamil. Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days. About 3% to 4% is excreted in the urine as unchanged drug. Approximately 90% is bound to plasma proteins. In patients with hepatic insufficiency, metabolism of immediate-release verapamil is delayed and elimination half-life prolonged up to 14 to 16 hours (see PRECAUTIONS); the volume of distribution is increased and plasma clearance reduced to about 30% of normal. Verapamil clearance values suggest that patients with liver dysfunction may attain therapeutic verapamil plasma concentrations with one third of the oral daily dose required for patients with normal liver function.
After four weeks of oral dosing (120 mg q.i.d.), verapamil and norverapamil levels were noted in the cerebrospinal fluid with estimated partition coefficient of 0.06 for verapamil and 0.04 for norverapamil.
In ten healthy males, administration of oral verapamil (80 mg every 8 hours for 6 days) and a single oral dose of ethanol (0.8 g/kg) resulted in a 17% increase in mean peak ethanol concentrations (106.45 ± 21.40 to 124.23 ± 24.74 mg∙hr/dL) compared to placebo. The area under the blood ethanol concentration versus time curve (AUC over 12 hours) increased by 30% (365.67 ± 93.52 to 475.07 ± 97.24 mg∙hr/dL). Verapamil AUCs were positively correlated (r=0.71) to increased ethanol blood AUC values (see PRECAUTIONS, Drug interactions).
CALAN reduces afterload and myocardial contractility. Improved left ventricular diastolic function in patients with Idiopathic Hypertrophic Subaortic Stenosis (IHSS) and those with coronary heart disease has also been observed with CALAN. In most patients, including those with organic cardiac disease, the negative inotropic action of CALAN is countered by reduction of afterload, and cardiac index is usually not reduced. However, in patients with severe left ventricular dysfunction (eg, pulmonary wedge pressure above 20 mm Hg or ejection fraction less than 30%), or in patients taking beta-adrenergic blocking agents or other cardiodepressant drugs, deterioration of ventricular function may occur (see PRECAUTIONS, Drug interactions).
CALAN does not induce bronchoconstriction and, hence, does not impair ventilatory function.
Calan SR is indicated for the management of essential hypertension.
Verapamil HCl caplets are contraindicated in:
Verapamil has a negative inotropic effect, which in most patients is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema.
Verapamil should be avoided in patients with severe left ventricular dysfunction (eg, ejection fraction less than 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker (see PRECAUTIONS, Drug interactions). Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment. (Note interactions with digoxin under PRECAUTIONS)
Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels, which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt-table testing (60 degrees) was not able to induce orthostatic hypotension.
Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear even in the face of continued verapamil treatment. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge; half of these had clinical symptoms (malaise, fever, and/or right upper quadrant pain) in addition to elevation of SGOT, SGPT, and alkaline phosphatase. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent.
Some patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated (see CONTRAINDICATIONS). Treatment is usually DC-cardioversion. Cardioversion has been used safely and effectively after oral CALAN.
The effect of verapamil on AV conduction and the SA node may cause asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR-interval prolongation is correlated with verapamil plasma concentrations, especially during the early titration phase of therapy. Higher degrees of AV block, however, were infrequently (0.8%) observed. Marked first-degree block or progressive development to second- or third-degree AV block, requires a reduction in dosage or, in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy, depending upon the clinical situation.
In 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (greater than 20 mm Hg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see PRECAUTIONS, Drug interactions) preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second-degree AV block in 4%, and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction, and only rarely did verapamil use have to be discontinued.
Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of immediate-release verapamil to about 14 to 16 hours; hence, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects (see OVERDOSAGE) should be carried out.
It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne's muscular dystrophy, and that verapamil prolongs recovery from the neuromuscular blocking agent vecuronium. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission.
About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Verapamil is not removed by hemodialysis. Until further data are available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage (see OVERDOSAGE).
Concomitant therapy with beta-adrenergic blockers and verapamil may result in additive negative effects on heart rate, atrioventricular conduction and/or cardiac contractility. The combination of sustained-release verapamil and beta-adrenergic blocking agents has not been studied. However, there have been reports of excessive bradycardia and AV block, including complete heart block, when the combination has been used for the treatment of hypertension. For hypertensive patients, the risks of combined therapy may outweigh the potential benefits. The combination should be used only with caution and close monitoring.
Asymptomatic bradycardia (36 beats/min) with a wandering atrial pacemaker has been observed in a patient receiving concomitant timolol (a beta-adrenergic blocker) eyedrops and oral verapamil.
A decrease in metoprolol and propranolol clearance has been observed when either drug is administered concomitantly with verapamil. A variable effect has been seen when verapamil and atenolol were given together.
Clinical use of verapamil in digitalized patients has shown the combination to be well tolerated if digoxin doses are properly adjusted. However, chronic verapamil treatment can increase serum digoxin levels by 50% to 75% during the first week of therapy, and this can result in digitalis toxicity. In patients with hepatic cirrhosis the influence of verapamil on digoxin kinetics is magnified. Verapamil may reduce total body clearance and extrarenal clearance of digitoxin by 27% and 29%, respectively. Maintenance and digitalization doses should be reduced when verapamil is administered, and the patient should be carefully monitored to avoid over- or under-digitalization. Whenever over-digitalization is suspected, the daily dose of digitalis should be reduced or temporarily discontinued. On discontinuation of CALAN use, the patient should be reassessed to avoid under-digitalization.
Verapamil administered concomitantly with oral antihypertensive agents (eg, vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta-blockers) will usually have an additive effect on lowering blood pressure. Patients receiving these combinations should be appropriately monitored. Concomitant use of agents that attenuate alpha-adrenergic function with verapamil may result in a reduction in blood pressure that is excessive in some patients. Such an effect was observed in one study following the concomitant administration of verapamil and prazosin.
Until data on possible interactions between verapamil and disopyramide phosphate are obtained, disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.
A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. Concomitant therapy with flecainide and verapamil may result in additive negative inotropic effect and prolongation of atrioventricular conduction.
In a small number of patients with hypertrophic cardiomyopathy (IHSS), concomitant use of verapamil and quinidine resulted in significant hypotension. Until further data are obtained, combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy should probably be avoided.
The electrophysiologic effects of quinidine and verapamil on AV conduction were studied in 8 patients. Verapamil significantly counteracted the effects of quinidine on AV conduction. There has been a report of increased quinidine levels during verapamil therapy.
Verapamil has been found to inhibit ethanol elimination significantly, resulting in elevated blood ethanol concentrations that may prolong the intoxicating effects of alcohol (see CLINICAL PHARMACOLOGY, Pharmacokinetics and metabolism).
Verapamil has been given concomitantly with short- and long-acting nitrates without any undesirable drug interactions. The pharmacologic profile of both drugs and the clinical experience suggest beneficial interactions.
The interaction between cimetidine and chronically administered verapamil has not been studied. Variable results on clearance have been obtained in acute studies of healthy volunteers; clearance of verapamil was either reduced or unchanged.
Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant verapamil-lithium therapy; lithium levels have been observed sometimes to increase, sometimes to decrease, and sometimes to be unchanged. Patients receiving both drugs must be monitored carefully.
Verapamil therapy may increase carbamazepine concentrations during combined therapy. This may produce carbamazepine side effects such as diplopia, headache, ataxia, or dizziness.
Therapy with rifampin may markedly reduce oral verapamil bioavailability.
Phenobarbital therapy may increase verapamil clearance.
Verapamil therapy may increase serum levels of cyclosporin.
Verapamil may inhibit the clearance and increase the plasma levels of theophylline.
Animal experiments have shown that inhalation anesthetics depress cardiovascular activity by decreasing the inward movement of calcium ions. When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, should each be titrated carefully to avoid excessive cardiovascular depression.
Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). It may be necessary to decrease the dose of verapamil and/or the dose of the neuromuscular blocking agent when the drugs are used concomitantly.
Hypotension and bradyarrhythmias have been observed in patients receiving concurrent telithromycin, an antibiotic in the ketolide class.
Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.
An 18-month toxicity study in rats, at a low multiple (6-fold) of the maximum recommended human dose, and not the maximum tolerated dose, did not suggest a tumorigenic potential. There was no evidence of a carcinogenic potential of verapamil administered in the diet of rats for two years at doses of 10, 35, and 120 mg/kg/day or approximately 1, 3.5, and 12 times, respectively, the maximum recommended human daily dose (480 mg/day or 9.6 mg/kg/day).
Verapamil was not mutagenic in the Ames test in 5 test strains at 3 mg per plate with or without metabolic activation.
Studies in female rats at daily dietary doses up to 5.5 times (55 mg/kg/day) the maximum recommended human dose did not show impaired fertility. Effects on male fertility have not been determined.
Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the human oral daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.
It is not known whether the use of verapamil during labor or delivery has immediate or delayed adverse effects on the fetus, or whether it prolongs the duration of labor or increases the need for forceps delivery or other obstetric intervention. Such adverse experiences have not been reported in the literature, despite a long history of use of verapamil in Europe in the treatment of cardiac side effects of beta-adrenergic agonist agents used to treat premature labor.
Verapamil is excreted in human milk. Because of the potential for adverse reactions in nursing infants from verapamil, nursing should be discontinued while verapamil is administered.
Safety and efficacy of Calan SR in pediatric patients below the age of 18 years have not been established.
In chronic animal toxicology studies, verapamil caused lenticular and/or suture line changes at 30 mg/kg/day or greater, and frank cataracts at 62.5 mg/kg/day or greater in the beagle dog but not in the rat. Development of cataracts due to verapamil has not been reported in man.
Serious adverse reactions are uncommon when verapamil therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. The following reactions to orally administered verapamil occurred at rates greater than 1.0% or occurred at lower rates but appeared clearly drug-related in clinical trials in 4,954 patients:
| Constipation | 7.3% | Dyspnea | 1.4% |
| Dizziness | 3.3% | Bradycardia | |
| Nausea | 2.7% | (HR <50/min) | 1.4% |
| Hypotension | 2.5% | AV block | |
| Headache | 2.2% | (total 1°, 2°, 3°) | 1.2% |
| Edema | 1.9% | (2° and 3°) | 0.8% |
| CHF, Pulmonary | Rash | 1.2% | |
| edema | 1.8% | Flushing | 0.6% |
| Fatigue | 1.7% |
Elevated liver enzymes (see WARNINGS)
In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or flutter, ventricular rates below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients.
The following reactions, reported in 1% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:
Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope.
Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia.
Hemic and lymphatic: ecchymosis or bruising.
Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence.
Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme.
Special senses: blurred vision, tinnitus.
Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
The frequency of cardiovascular adverse reactions that require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately; eg, intravenously administered norepinephrine bitartrate, atropine sulfate, isoproterenol HCl (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl) should be used to maintain blood pressure, and isoproterenol and norepinephrine should be avoided. If further support is necessary, dopamine HCl or dobutamine HCl may be administered. Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
Overdose with verapamil may lead to pronounced hypotension, bradycardia, and conduction system abnormalities (eg, junctional rhythm with AV dissociation and high degree AV block, including asystole). Other symptoms secondary to hypoperfusion (eg, metabolic acidosis, hyperglycemia, hyperkalemia, renal dysfunction, and convulsions) may be evident.
Treat all verapamil overdoses as serious and maintain observation for at least 48 hours (especially Calan SR), preferably under continuous hospital care. Delayed pharmacodynamic consequences may occur with the sustained-release formulation. Verapamil is known to decrease gastrointestinal transit time.
In overdose, caplets of Calan SR have occasionally been reported to form concretions within the stomach or intestines. These concretions have not been visible on plain radiographs of the abdomen, and no medical means of gastrointestinal emptying is of proven efficacy in removing them. Endoscopy might reasonably be considered in cases of massive overdose when symptoms are unusually prolonged.
Treatment of overdosage should be supportive. Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel and have been used effectively in treatment of deliberate overdosage with verapamil. Continued treatment with large doses of calcium may produce a response. In a few reported cases, overdose with calcium channel blockers that was initially refractory to atropine became more responsive to this treatment when the patients received large doses (close to 1 g/hr for more than 24 hr) of calcium chloride. Verapamil cannot be removed by hemodialysis. Clinically significant hypotensive reactions or high degree AV block should be treated with vasopressor agents or cardiac pacing, respectively. Asystole should be handled by the usual measures including cardiopulmonary resuscitation.
The dose of Calan SR should be individualized by titration and the drug should be administered with food. Initiate therapy with 180 mg of sustained-release verapamil HCl, Calan SR, given in the morning. Lower initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (eg, the elderly or small people). Upward titration should be based on therapeutic efficacy and safety evaluated weekly and approximately 24 hours after the previous dose. The antihypertensive effects of Calan SR are evident within the first week of therapy.
If adequate response is not obtained with 180 mg of Calan SR, the dose may be titrated upward in the following manner:
When switching from immediate-release CALAN to Calan SR, the total daily dose in milligrams may remain the same.
Calan SR 120 mg caplets are light violet, oval, film coated, with CALAN debossed on one side and SR 120 on the other, supplied as:
| NDC Number | Size |
|---|---|
| 0025-1901-31 | bottle of 100 |
Calan SR 180 mg caplets are light pink, oval, scored, film coated, with CALAN debossed on one side and SR 180 on the other, supplied as:
| NDC Number | Size |
|---|---|
| 0025-1911-31 | bottle of 100 |
Calan SR 240 mg caplets are light green, capsule shaped, scored, film coated, with CALAN debossed on one side and SR 240 on the other, supplied as:
| NDC Number | Size |
|---|---|
| 0025-1891-31 | bottle of 100 |
| 0025-1891-51 | bottle of 500 |
| 0025-1891-34 | carton of 100 unit dose |
Store at 59° to 77°F (15° to 25°C) and protect from light and moisture. Dispense in tight, light-resistant containers.
Rx only
Manufactured for:
G.D. Searle LLC
Division of Pfizer, Inc
NY, NY 10017
by: (120 mg and 180 mg caplets)
Abbott Laboratories
North Chicago, IL 60064
Pfizer, Inc
Caguas, PR 00725
(240 mg caplets)
Abbott GmbH & Co. KG
Ludwigshafen, Germany
LAB-0268-5.0
October 2009
NDC 0025-1901-31
100 Caplets
Rx only
Calan® SR
(verapamil hydrochloride)
SUSTAINED-RELEASE
120 mg
Pfizer
Distributed by
G.D. Searle LLC
Division of Pfizer Inc, NY, NY 10017
NDC 0025-1911-31
100 Caplets
Rx only
Calan® SR
(verapamil hydrochloride)
SUSTAINED-RELEASE
180 mg
Pfizer
Distributed by
G.D. Searle LLC
Division of Pfizer Inc, NY, NY 10017
NDC 0025-1891-31
100 Caplets
Rx only
Calan® SR
(verapamil hydrochloride)
SUSTAINED-RELEASE
240 mg
Pfizer
Distributed by
G.D. Searle LLC
Division of Pfizer Inc, NY, NY 10017
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NDA | NDA019152 | 03/06/1991 | |
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NDA | NDA019152 | 12/15/1989 | |
| Calan SR verapamil hydrochloride tablet, film coated, extended release | ||||||||||||
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