Consumer medicine information

1. Why am I taking CADIVAST?

CADIVAST contains the active ingredient amlodipine besilate and atorvastatin calcium trihydrate. It is used to treat high blood pressure and high cholesterol (fat in the blood) and angina (a certain type of chest pain). CADIVAST is also used to help reduce the risk of having a heart attack or stroke in people who have high blood pressure and coronary heart disease (CHD) or who are at risk of CHD (for example, if they have diabetes, a history of stroke, or small blood vessel disease). For more information, see Section 1. Why am I taking CADIVAST? in the full CMI.

2. What should I know before I take CADIVAST?

Do not use if you have ever had an allergic reaction to CADIVAST or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I take CADIVAST? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with CADIVAST and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take CADIVAST?

CADIVAST is taken once a day. Your doctor will decide which strength is suitable for you. More instructions can be found in Section 4. How do I take CADIVAST? in the full CMI.

5. What should I know while taking CADIVAST?

6. Are there any side effects?

Speak to your doctor if you have any of these: headache; flushing; dizziness; tiredness or weakness; drowsiness or sleepiness; stomach pain or nausea (feeling sick); constipation, diarrhoea, wind; heartburn, indigestion; urine infection; stuffy or runny nose; nose bleeds; rash. Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you have any of these: symptoms of allergy such as skin rash, itching, swelling of the face, lips, mouth, throat or neck which may cause difficulty in swallowing and breathing; shortness of breath; unexpected muscle pain, tenderness or weakness not caused by exercise (particularly if you also feel unwell or have a fever); changes in heart beat either fast, slow or irregular; chest pain; sudden severe headache which may be accompanied by nausea, vomiting, loss of sensation, tingling in any part of the body or ringing in the ears; severe blisters and bleeding of the lips, eyes, mouth, nose or genitals; severe upper stomach pain often with nausea and vomiting. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Amlodipine (as besilate) and atorvastatin (as calcium trihydrate).

2 Qualitative and Quantitative Composition

The Cadivast tablets contain 5 or 10 mg amlodipine (as amlodipine besilate) and 10, 20, 40, or 80 mg atorvastatin (as atorvastatin calcium trihydrate).
Excipients with known effect. Soya bean products.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Cadivast 5/10 tablets. A white to off-white, film-coated, oval, biconvex tablet debossed with "AA 4" on one side of the tablet and "M" on the other side.
Cadivast 5/20 tablets. A white to off-white, film-coated, round, biconvex tablet debossed with "AA 5" on one side of the tablet and "M" on the other side.
Cadivast 5/40 tablets. A white to off-white, film-coated, capsule shaped, biconvex tablet debossed with "AA 6" on one side of the tablet and "M" on the other side.
Cadivast 5/80 tablets. A white to off-white, film-coated, oval, biconvex tablet debossed with "AA 7" on one side of the tablet and "M" on the other side.
Cadivast 10/10 tablets. A blue, film-coated, barrel shaped, biconvex tablet debossed with "AA 8" on one side of the tablet and "M" on the other side.
Cadivast 10/20 tablets. A blue, film-coated, oval, biconvex tablet debossed with "AA 9" on one side of the tablet and "M" on the other side.
Cadivast 10/40 tablets. A blue, film-coated, round, biconvex tablet debossed with "AA 10" on one side of the tablet and "M" on the other side.
Cadivast 10/80 tablets. A blue, film-coated, capsule shaped, biconvex tablet debossed with "AA 11" on one side of the tablet and "M" on the other side.

4 Clinical Particulars

4.9 Overdose

Symptoms. There is no information on overdoses with amlodipine besilate and atorvastatin calcium trihydrate tablet.
Available data suggest that amlodipine besilate and atorvastatin calcium trihydrate tablet overdose, due to its CCB component, might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. Dysrhythmias may occur following overdose with any calcium antagonist. Hypotension and bradycardia are usually seen within 1 to 5 hours following amlodipine overdose. Hypotension can persist for longer than 24 hours despite treatment. Cardiac rhythm disturbances have been noted to persist for up to 7 days. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.
Treatment. If massive amlodipine besilate and atorvastatin calcium trihydrate tablet overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support, including elevation of the extremities, and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors should be considered with attention to circulating volume and urine output. Intravenous calcium may help to reverse the effects of calcium entry blockade. In symptomatic patients, monitor serum creatinine, BUN, creatinine kinase, urine myoglobin for indications of renal impairment secondary to rhabdomyolysis and liver function tests.
If there has been significant ingestion, consider administration of activated charcoal. Administration of activated charcoal to healthy volunteers immediately or up to 2 hours after ingestion of amlodipine 10 mg has been shown to significantly decrease amlodipine absorption. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected. Ipecac emesis is not recommended since haemodynamic instability and CNS depression may rapidly develop. As both amlodipine and atorvastatin are highly protein bound, dialysis is not likely to be of benefit. For atorvastatin induced rhabdomyolysis, administer sufficient 0.9% saline to maintain urine output of 2 to 3 mL/kg/hr. Diuretics may be necessary to maintain urine output. Urinary alkalinisation is not routinely recommended.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. There are no genotoxicity or carcinogenicity studies with the amlodipine/atorvastatin combination.
Amlodipine. Amlodipine did not induce gene mutation in bacteria and mouse lymphoma cells; nor did it induce chromosome aberrations in human lymphocytes or Chinese hamster V79 fibroblast cells (in vitro) and in mouse bone marrow cells (in vivo).
Atorvastatin. Atorvastatin did not demonstrate mutagenic or clastogenic potential in an appropriate battery of assays. It was negative in the Ames test with Salmonella typhimurium and Escherichia coli, and in the in vitro hypoxanthine-guanine phosphoribosyltransferase (HGPRT) forward mutation assay in Chinese hamster lung cells. Atorvastatin did not produce significant increases in chromosomal aberrations in the in vitro Chinese hamster lung cell assay and was negative in the in vivo mouse micronucleus test.
Carcinogenicity. There are no carcinogenicity studies with amlodipine/ atorvastatin combination.
Amlodipine. The carcinogenic potential of amlodipine has not been fully elucidated. Amlodipine did not induce any tumours when tested in mice or rats at oral doses up to 2.5 mg/kg. This dose gave rise to plasma levels that are similar to or below those achieved clinically.
Atorvastatin. In a 2-year study in rats given 10 mg/kg/day, 30 mg/kg/day or 100 mg/kg/day, the incidence of hepatocellular adenoma was marginally, although not significantly, increased in females at 100 mg/kg/day. The maximum dose used was 11 times higher than the highest human dose (80 mg/day) based on AUC (0-24) values. In a 2 year study in mice given 100 mg/kg, 200 mg/kg or 400 mg/kg, incidences of hepatocellular adenoma in males and hepatocellular carcinoma in females were increased at 400 mg/kg/day. The maximum dose used was 14 times higher than the highest human dose (80 mg/day) based on AUC (0-24) values. Other HMG-CoA reductase inhibitors have been reported to induce hepatocellular tumours in mice and rats.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Amlodipine.
Chemical structure. Structural formula:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSAMBESI.gif Chemical name: 3-ethyl, 5-methyl (4RS)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate benzene sulfonate.
Molecular formula: C₂₀H₂₅ClN₂O₅.C₆H₆O₃S.
Molecular weight: 567.1.
CAS number. CAS registry no.: 111470-99-6.
Atorvastatin calcium trihydrate.
Chemical structure. Structural formula:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSATOCAT.gif Chemical name: (3R, 5R)-7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate calcium trihydrate.
Molecular formula: C₆₆H₆₈CaF₂N₄O₁₀.3H₂O.
Molecular weight: 1209.39.
CAS number. CAS registry no.: 344423-98-9.
Amlodipine besilate is white or almost white powder. Atorvastatin calcium trihydrate is white or almost white powder. Amlodipine besilate is slightly soluble in water, freely soluble in methanol, sparingly soluble in anhydrous ethanol and slightly soluble in 2-propanol. Atorvastatin calcium trihydrate slightly soluble in water, slightly soluble in ethanol (96%), and practically insoluble in methylene chloride.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/CADIVAST.gif